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Aggressive promotion. Thousands of dollars a week. And more confusing options than ever. When did sending your kid to sleepaway camp become the most dreaded part of the summer?
Not every item of note can make it into Boston’s big dailies. We scoured the local papers to keep you up-to-date. Great, now we’re hungry: […]
Former Massachusetts governor Mitt Romney released a new television ad yesterday. The spot, titled “Change Begins With Us,” features a bucolic setting from which Romney […]
Dear Pizza Delivery Guy Muggers, We here at Boston Daily fancy ourselves to be the non-violent type. We believe in shaming people on the internet […]
Your condensed guide to today’s daily papers. Lawsuit: The family of a man who was seriously injured in July when a grate slammed into his […]
It’s been little over two months since Mr. Butch, Boston’s most beloved homeless man—nay “street icon”—passed away, and life around Allston/Brighton just hasn’t been the […]
Your long day of corporate drudgery is over. Get out and enjoy the city! Here are a few ideas to get you started, lovingly picked […]
From senators eyeing the presidency to a mayor ruling over a changing city, here’s what our politicians are up to.
Taking you around the internet for your afternoon enjoyment. The Pope’s coming to America: But his tour dates have not been confirmed. We’d love it […]
A Suffolk County Judge has ruled that WRKO has a right to match the contract WTKK offered Howie Carr in July, and that Carr was […]
Every Bostonian has an emergency plan. Not one of those goofy terrorist color-coded emergency plans, but a mental map of every public bathroom they know […]
Nobody likes sex education. Kids don’t like it because they think they’ve already learned what they need to know from their mother’s poorly-hidden Sex and […]
We received an email today concerning Lola, the Globe‘s new fashion mag, which hopes to achieve the kind of success the Times has had with […]
Marijuana legalization, healthcare changes, and all the other referendums shaking up Mass.
Poor Somerville. It can’t catch a break. The MBTA won’t expand Orange or Green Line service to the city. It’s politicians are crazy. And now […]
Old friend Sasha Issenberg, now on the Washington beat for the Globe, caught up with John Kerry while the ‘whole world was watching’ YouTube and […]
Well, actually she’s up, sort of. I just like the pun. Veronica Chao, the icy editress of the Improper Bostonian, has been hired to helm […]
We try not to get too hysterical about the Red Sox around here. There are more than enough places you can go for that sort […]


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After serving 22 years in solitary confinement, Anthony Gay was released from prison in Illinois in August. Now, he's suing the state. And as economies across the globe slow down, what does that mean for 2019? That and more, in hour two of Here & Now's Jan. 11, 2019 full broadcast.
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Buy it Again
Bic Intnsty Fine Felt Pen - 6 Count
Fine 0.4 mm. Bold colors. Won't bleed. Writes like a pen, bold like a marker! 0.4 mm fine tip provides smooth, colorful precision. Bold Colors, that won't bleed through paper results could vary based on paper characteristics. Metal nib protects tip from wearing down. Perfect for notetaking, creative writing, adult coloring and journaling. Clean, crisp writing. Water-based ink makes it perfect for writing on paper. Add to your collection! Medium 1.0 mm. Fine 0.5 mm. Bic Performance Policy (US and Canada): If not fully satisfied, return to BIC for product replacement. Learn more about the BIC Intensity line and get inspired at www.bic.com. www.bic.com. ACMI: Art & Creative Materials Institute Certified. Non-toxic. Made in Korea.
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domain: hobby


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Mile Bluff Medical Center is seeking a motivated individual to fill a part time Speech Pathologist position- 32 hours per week. Responsibilities include evaluation/treatment of individuals of all ages with a variety of communicative disorders. Service provided in a variety of settings including hospital inpatients, outpatients, and long term care facilities. Experience in evaluation/treatment of swallowing disorders required. Benefits available.
Please apply online by visiting our website at www.milebluff.com, or email your resume to firstname.lastname@example.org Bluff Medical Center 1050 Division St Mauston, WI 53948
An Equal Opportunity Employer

domain: medical


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Police investigating the deaths of two elderly women who were found in a Kings Heath house yesterday (Monday 11 February) have ruled out carbon monoxide poisoning.
Police and fire crew officers forced entry to the terraced home in Balaclava Road, Birmingham, just before 7pm to find the mother and daughter, aged 95 and 64, inside the address. They were both pronounced dead at the scene.
The post mortems will be carried out tomorrow, however tests conducted by the fire service confirmed there was no carbon monoxide leak in the property.
The deaths are still being treated as unexplained.
More top news
The future for Coventry City Football Club has led to fiery exchanges in Parliament - as local MPs called on the Government to intervene.
The family of a six-year-old boy with epilepsy are fighting for him to be legally allowed to use cannabis oil as a medical treatment.
After a cold start with the odd freezing fog patch, Thursday should be mainly dry and bright with some sunny spells and light winds.

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How To Avoid Credit Card Fees
Perhaps the biggest problem with some of these penalty fees is that if you have to pay them, it can mean more money lost for you than simply the penalty feeWhy Will The Banks Settle For Pennies On The Dollar
Find out why the banks will settle for 50% of what you owe them?Alternatives to Your Debt Consolidation
Most of the people in the world struggle financially. The most common reasons that attribute to financial difficulty are debt and the inability to save money. Learn how to market your product or service to as many people out there or you can or invest in proven systems that were developed by people who embrace the spirit of entrepreneurship.Introduction To Social Security
In order to address the routine concerns of many, regarding the payment of bills post-retirement or disability, a federal benefits program was designed in the United States, in 1935, known as the Social Securities Act.Really Cheap Auto Insurance – The Variables Behind The Rates
Really cheap auto insurance can be had as long as you, as an educated consumer, are equipped with the full range of facts and knowledge about how insurance companies come up with quotes for car insurance.The History Of Paper Money
Something had to be done to produce more money, money was power and without it, if you were a nobleman, you were nothing.Getting Started In The Forex Market
The Forex market is known to be a very lucrative market, with trillions of dollars exchanged daily. To get started in the Forex market and make the most of your investments in it, you need to select a suitable broker.Foreclosure Investing – A Smart Strategy
Foreclosure investing is a form of real estate investment. It is one of the best investment options as far as returns on investments are concerned. Foreclosure investment opportunities are normally created when homeowners default on monthly installment payments and the bank confiscates their property.Finding The Right Bank For You
Banks are often considered to be the best treasurers. Selecting a bank is a crucial decision and it should not be influenced or impulsive. There are a number of financial institutions offering multifarious fringe benefits to customers.Using a Finance Broker Saves Time and Money
Many business owners either view financial brokers as a necessary evil or not necessary at all. A professional and competent broker can save the borrower both time and money, as well as find the right fit with the most appropriate funding source.Get A Headstart In Your Financial Planning Education
Are you good with saving? Most of us are not. This is clear when I read the statistics on the average American and his or her debt. Not only are we not saving wisely, but we’re spending money we don’t even have. This is bizarre and a bit idiotic if I do say so myself…Tips And Techniques To Successful Investing
The main objective of any investment is to make money and gain from a profit. Experienced investors usually study market trends before investing. However, inexperienced investors depend on the advice from financial advisors and brokers to guide their investments.General Surety Bond Information
A surety bond is a bond, which is created to protect the obligee against breach of the contract by the principal. This surety bond involves three parties; they are the principal, the obligee and the surety. In this surety bond, the surety gives guarantee to the obligee that the principal will perform his obligation as per contract. The surety bond involves many types. Performance of the contract determines the rights and obligation of the surety and the obligee.

domain: finance


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Для любителей традиционных швейцарских отелей
The name says it all – and at a fantastic viewpoint not far from the hotel, a Capricorn colony can be seen. The energy-conscious hotel tenders inspiration & time out close to nature since its renovation. Comfortable and cosy rooms with much wood & a love of nostalgic details. Refined regional dishes are prepared here - and Flyer Bike rentals available to you at the certified Swiss Lodge.

domain: travel


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Compare: Calimesa vs Yucaipa
Home Values in Calimesa and Yucaipa
|Zillow Home Value IndexWhat's this?||$225,800||vs||$263,100|
|Median List Price||$250,000||vs||$315,000|
|Median Sale Price||$279,700||vs||$266,400|
|Total Homes Sold in Oct||Data Unavailable.||vs||64 homes|
Calimesa, CA tends to be less expensive for home buyers than Yucaipa, CA. During the last year, Calimesa home values have risen by 33.6%, while Yucaipa home values have risen by 28.5%. The median sale price in Calimesa is $279,700, but the median listing price was $250,000, a 11.9% increase. Meanwhile in Yucaipa, the median selling price is $266,400, and the starting price had a median of $315,000, a 15.4% discount.
Demographics in Calimesa and Yucaipa
|Median Household Income||$37,849||vs||$39,144|
|Homes with Kids||25.4%||vs||35.0%|
|Average Household Size||2.4||vs||2.7|
|Average Commute Time (Minutes)||27||vs||29|
At $39,144, the median income in Yucaipa is $1,295 more than in Calimesa, and $5,368 lower than the national average. Calimesa has an older median age, at 42, compared to 36 in Yucaipa, and a shorter average commute. The average commute in Yucaipa is 29 minutes and the average commute in Calimesa is 27 minutes.
Homes for Sale in Calimesa and Yucaipa
Calimesa vs Yucaipa


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Organic Mung Beans
Country of Origin:
Our organic mung beans have been part of traditional Ayurvedic diets in India for thousands of years. In fact, they are considered "one of the most cherished foods" in this ancient Indian practice that's been a traditional form of medicine since roughly 1,500 B.C.
Mung beans are also consumed sprouted, it's important to note that sprouting changes their nutritional composition. Sprouted beans contain fewer calories and more free amino acids and antioxidants than unsprouted ones.
What's more, sprouting reduces levels of phytic acid, which is an antinutrient. Antinutrients can reduce the absorption of minerals like zinc, magnesium and calcium.
- Nothing beats vacuum sealing for freshness.
- Store below 15°C and < 65% humidity.
- Store in the dark as light degrades flavors.
- Mason jars make great storage containers.
- Can be frozen to prolong shelf life.

domain: food


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EphA3, Erythropoietin-Producing Hepatocellular Carcinoma Cell Receptor A3
A fragment of EphA3 was first cloned in 1991 by Sajjadi et al., in an expression-cloning screen of a chicken embryonic cDNA library using antibodies against phosphotyrosine (Sajjadi et al. 1991). Using this cDNA fragment as a probe, full-length cDNA from both chicken and mouse embryos were identified (Sajjadi et al. 1991). Human EphA3 was independently isolated as a cell surface antigen of a pre-B-cell leukemia cell line (Boyd et al. 1992; Wicks et al. 1992). EphA3 is a member of a large family of tyrosine kinase receptors, which plays many critical roles in both physiological and pathological conditions (Pasquale 2008).
The full-length human EphA3 protein consists of 983 amino acids, organized into the typical extracellular, transmembrane, and intracellular domains as that of other Eph family tyrosine kinase receptors (Wicks et al. 1992). A splice variant, which contains only the extracellular domain, was also identified in the mouse (Sajjadi et al. 1991). The relative abundance and difference in function between the full-length and truncated receptors have not been analyzed at present. Since the truncated form lacks intracellular signaling capacity but is capable of binding to Eph ligands (see the Ligands section for details), it may serve to down modulate EphA3 receptor function. Due to promiscuity of ligand–receptor interactions in the Eph family, it is possible that this truncated form may regulate functions of many other Eph receptors. Similar truncated form has been identified for TrkB, the receptor for the neurotrophic factor brain-derived neurotrophic factor, and has been shown to inhibit full-length TrkB receptor function in developing mouse brain (Carim-Todd et al. 2009).
EphA3 is expressed both in the nervous system and in nonneural tissues. In the developing mouse brain, EphA3 expression is detectable as early as E12, but is undetectable after P10 (Kilpatrick et al. 1996; Kudo et al. 2005; Lai and Lemke 1991). Both mRNA and protein were detected in the developing cerebral cortex, ganglionic eminence, and presumptive caudate-putamen at E12. Expression was also found in the dorsal thalamus and in spinal motor neurons (Iwamasa et al. 1999; Kilpatrick et al. 1996; Kudo et al. 2005; Mackarehtschian et al. 1999). High levels of protein expression were found in the thalamocortical axons. What is intriguing is that there is an extensive overlap with the adhesion molecule L1 expression, suggesting that EphA3 and L1 interact or at least regulate similar targets. Indeed it has been shown that EphA3 is physically associated with L1, and requires L1 protein for ephrin-A5-induced growth cone collapse (Demyanenko et al. 2011). It will be extremely interesting to examine how EphA3 and L1 interact to regulate axon guidance.
The most striking expression patterns of EphA3 were found in the developing chick and wallaby retina with a nasal (low) to temporal (high) gradient (Cheng et al. 1995; Stubbs et al. 2000). This gradient plays a critical role in the specification of retinotectal topographic axon projection map as discussed in the Biological Functions section. How this graded expression is regulated is not entirely clear at present. There is evidence suggesting that two homeobox transcription factors, SOHo1 and GH6, expressed in opposing gradients as that of EphA3 in the retina, inhibit EphA3 transcription, defining the expression in the temporal region (Schulte and Cepko 2000). Indeed, ecotopic expression of either transcription factor resulted in inhibition of EphA3 expression and a partial disruption of retinal axon guidance to the tectum. Two members of the winged-helix (WH) transcription factors, chick brain factor (CBF) 1 and 2, have also been shown to influence EphA3 expression in the chick retina, with CBF1 inhibiting and CBF2 inducing EphA3 expression (Takahashi et al. 2003; Takahashi et al. 2009). Extracellular signals have also been shown to regulate EphA3 expression. For example, the T-cell co-stimulatory signal CD28 and the type 1 insulin-like growth factor can enhance both EphA3 protein levels (Smith et al. 2004b). In contrast, interleukin-1ß reduces the expression (Li et al. 1998). However, the regulation of EphA3 expression is incompletely understood, and it remains unclear how different signals coordinate the expression important for its biological functions.
Ligands and Mechanisms of Interaction with EphA3
Two ephrins, ephrin-A1 (initially named B61) and ephrin-A2 (Elf-1), were identified as ligands of EphA3 in 1994 using EphA3 extracellular domain fusion proteins as affinity probes in expression screening experiments (Beckmann et al. 1994; Cheng and Flanagan 1994). Two new ligands, ephrin-A3 and ephrin-A4, were identified by Kozlosky and colleagues using similar methods in the following year (Kozlosky et al. 1995). An additional ligand, ephrin-A5, was identified as a retinal axon guidance molecule (RAGS) (Drescher et al. 1995), and as an expressed sequence tag with homology to ephrin-B1 (Cerretti et al. 1995). Ephrin-A5 was also independently isolated by Lackmann and colleagues from the conditioned medium of human placenta (Lackmann et al. 1996). This ligand was found to be identical to AL-1, a ligand purified with affinity chromatography using the extracellular domain of the related receptor EphA5 from the conditioned medium of a human breast cancer cell line BT20 (Winslow et al. 1995). It is now known that the ligand–receptor interactions of the Eph family are highly promiscuous, and thus EphA3 receptor can interact with all the A-subclass ephrins. A careful study by Lackmann and colleagues in 1997 showed that while different bivalent ephrin-A-Fc fusion proteins interact with EphA3 with similar high affinity, the monomeric form of ephrin-A5 can form a much more stable complex with EphA3 than that of ephrin-A3 (Lackmann et al. 1997), suggesting that ephrin-A5 is the preferred high affinity ligand. Whether ephrins interact with Eph receptors in dimeric/oligomeric forms or monomeric form in vivo is not clear at present. Although nearly all functional assays reported have used multimeric forms of ephrins, monomeric ephrins may indeed have important functions in development or adult, since both ephrin-A1 and ephrin-A5 have been isolated initially from conditioned media as released monomeric form (Holzman et al. 1990; Lackmann et al. 1996; Winslow et al. 1995), it would not be surprising if novel functions were discovered for released monomer ephrins in the future.
The interaction of EphA3 with the ligand ephrin-A5 has been extensively analyzed (Lackmann et al. 1998; Smith et al. 2004a). The ligand-binding domain of EphA3 is located to the N-terminal region to the first IgG domain, encoded by exon III (Lackmann et al. 1998). This is consistent with findings in other Eph receptors (Himanen and Nikolov 2003; Labrador et al. 1997). Ligand–receptor interaction involves a high affinity and a low-affinity binding site. The former is responsible for ligand–receptor dimerization, and the latter facilitates ligand–receptor tetramer formation (Himanen et al. 2001; Himanen and Nikolov 2003; Smith et al. 2004a). In addition, a ligand independent receptor dimerization domain has also been identified using both protein domain deletion and functional mutagenesis approaches in the cysteine-rich hinge region of the receptor (Lackmann et al. 1998; Smith et al. 2004a). Similar analysis also identified three domains in ephrin-A5 that play key roles in interaction with EphA3 receptor (Day et al. 2005). Two of the sites interact with the high- and low-affinity interaction domains identified in EphA3 receptor, and a third novel interface, which was proposed to bind to the cysteine-rich receptor domain of Eph receptors in adjacent ligand–receptor tetramers, allowing polymerization of large number of the ligand–receptor complexes and effective functional activation.
What is interesting about ephrin–Eph interaction is that simple ligand–receptor binding is not sufficient to fully activate the receptors (Pabbisetty et al. 2007; Stein et al. 1998; Vearing and Lackmann 2005). It has been shown that addition of monomeric ephrin-A5 failed to induce EphA3 kinase activation as assayed by autophosphorylation on tyrosine (Vearing et al. 2005). In contrast, dimeric ephrin-A5-Fc was found to be sufficient to induce EphA3 autophosphorylation. This difference is in part explained by the observation that monomeric ligands have a much lower binding affinity than the dimeric ligands (Pabbisetty et al. 2007). However, ephrin-A5 dimer-induced partial EphA3 activation is not enough to induce a cellular response as demonstrated by actin cytoskeleton contraction, which required additional receptor clustering (Vearing et al. 2005). Similar observations have been reported for ephrin-B1 (Stein et al. 1998). Correlated with the ability to affect cellular functions, only the fully activated Eph receptors are capable of recruiting downstream signaling molecules, although much remains uncharacterized (Stein et al. 1998; Vearing and Lackmann 2005). However, it is not known whether highly clustered ephrins are necessary to induce the full range of biological functions of all Eph receptors. For example, it has been reported that no differences were observed in EphA2 receptor autophosphorylation or endothelial cell migration by dimer or further cross-linked ephrin-A1-Fc (Brantley-Sieders et al. 2004). This issue is complicated by the possibility that different Eph receptors may respond differently to ephrin dimers. In addition, few studies have addressed this issue carefully since ephrin-Fc preparations may contain a mixture of dimers and larger aggregates. Adding to the complexity of ephrin–Eph interactions, it has been shown that interaction of ephrin-A5 and EphA3 in cis silences EphA3 receptor activation, possibly modulating concentration of actively signaling EphA3 receptor molecules (Carvalho et al. 2006).
Since both the EphA3 receptor and its ephrin ligands are membrane anchored, the question of how the ligand–receptor complex can be internalized by endocytosis becomes an interesting question. Elegant mutational and crystallographic studies by Nikolov and colleagues (Janes et al. 2005) showed that although the protease ADAM10 (A disintegrin and metalloprotease 10) is constitutively associated with EphA3, association of ephrin-A5 to EphA3 receptor creates a new binding site for ADAM10, and allows the cleavage of ephrin-A5 releasing the EphA3/ephrin-A5 complex for internalization. In addition, only ephrin-A5 ligand expressed in trans to ADAM10 can be cleaved after EphA3 binding. Such a mechanism ensures only ligands interacting with the receptor are cleaved.
Activation and Signal Transduction
Similar to other receptor tyrosine kinases, EphA3 is activated by ligand binding. Upon ligand binding, the two tyrosine residues located at the juxtamembrane segment of EphA3 become phosphorylated. Crystallographic analysis showed that the unphosphorylated juxtamembrane domain tyrosine residues interact with the active site to prevent adoption of a catalytically active confirmation of the catalytic site (Davis et al. 2008). Mutagenesis studies showed that mutation of Y596F but not Y602F leads to the loss of EphA3 kinase activity as well as the ability to inhibit cell migration and induce cellular process and neuronal growth cone retraction (Davis et al. 2008; Hu et al. 2009; Shi et al. 2010). In contrast, restoration of the negative charge of phospho-Y596 with an Y596E mutation restores EphA3 kinase activity, suggesting that phosphorylation of Y596 is necessary to release inhibition of EphA3 kinase activity. The activation mechanism of EphA3 kinase is likely to be complex and involve many other amino acid residues in both the juxtamembrane domain and the kinase domain. Significantly, both Y742 and S768 also contribute to the regulation of EphA3 kinase activity (Davis et al. 2008).
Although phospho-Y602 is not required for EphA3 kinase activity, it is necessary for its biological functions as measured with either morphological changes (membrane blebbing and cellular process retraction) or cell migration (Hu et al. 2009; Lawrenson et al. 2002; Shi et al. 2010). In fact, Y779 phosphorylation is also important for these biological activities. Both Y602F and Y779F mutations cause a partial loss of biological activity, while the double mutant Y602/779F resulted in a complete loss of biological activity while maintaining its kinase activity (Shi et al. 2010). These observations are consistent with the notion that phosphorylated Y602 and Y779 serve as docking sites for downstream signaling molecules that mediate EphA3 biological effects, and that different tyrosine residues together with their respective signaling pathways collaborate to achieve full biological activity for the receptor.
Downstream of the receptor, activation of EphA3 in T cells by ephrin-A1 results in tyrosine phosphorylation of c-cbl proto-oncogene (Sharfe et al. 2003). The process is dependent on the Src family kinases, indicating that Src mediates effects of EphA3 activation on c-cbl phosphorylation. c-cbl may serve as a regulator of receptor ubiquitination and degradation, thus downregulating EphA3 protein levels upon activation by ephrins (Sharfe et al. 2003).
It has also been shown that the adaptor protein Nck binds to the phosphotyrosine residue Y602 through its Src Homology domain 2 (SH2), and blocking Nck signaling also reduces EphA3-mediated inhibition of cell migration and process retraction (Hu et al. 2009). Nck is known to interact with multiple signals that regulate cytoskeleton dynamics, including p21-activated kinase ( PAKI), and the Wiskott–Aldrich syndrome family proteins that control actin reorganization (Li et al. 2001).
EphA3 is widely expressed in both neural and nonneural tissues during development and plays multiple roles during embryogenesis.
Substrate detachment and adhesion. Binding of EphA3 by clustered ephrin-A5 has been shown to induce detachment and rounding of HEK293 cells and melanoma cells, but promote adhesion of pre-B and T-cell leukemic cells (Lawrenson et al. 2002; Wimmer-Kleikamp et al. 2008). The opposing effects in these two different types of cells are due to the presence of a protein tyrosine phosphatase activity in the leukemic cells, which prevents autophosphorylation of EphA3. The emerging model is that when EphA3 is fully activated and autophosphorylated on the tyrosine residues, it triggers the activation of Rho-GTPase and leads to cell detachment and repulsion (Lawrenson et al. 2002). In contrast, when receptor activity is down modulated by phosphatase activity, interactions between EphA3 and its ligands lead to cell adhesion. Although the identity of the phosphatase that dephosphorylates EphA3 in pre-B leukemia cells has yet to be identified, evidence indicates that PTP1B may play a similar role in EphA3 dephosphorylation in HEK293 cells and in glioblastoma cells by interacting with the activated receptor at the plasma membrane as well as in endosomal vesicles (Nievergall et al. 2010).
Axon guidance. The earliest hint for a critical function of EphA3 and its ligands in embryonic development came when ephrin-A5 was found to be the repulsive axon guidance signal (RAGS) responsible for generating the topographic retinal axon termination map in the optical tectum in the brain (Cheng et al. 1995; Drescher et al. 1995). The landmark study by Drescher and colleagues, together with the studies by Cheng and colleagues, which demonstrated the expression of EphA3 and ephrin-A2, another ligand, are expressed in opposing gradients in the projecting retina and the target tectum, unraveled an age-old mystery of how axon terminals are topographically mapped onto target brain tissues. Further studies demonstrated that ephrin-A2 and ephrin-A5 together serve as repulsive axon guidance signals for the formation of the retinotectal project map (Ciossek et al. 1998; Feldheim et al. 2000), and that EphA3 as well as other EphA receptors mediate the effects of these ephrins (Brown et al. 2000; Feldheim et al. 2004). Further studies now show that ephrin–Eph interactions play a general role in the specification of topographic maps in several other axon pathways including hippocamposeptal projections (Yue et al. 2002), thalamocortical projections (Dufour et al. 2003; Uziel et al. 2002, 2006), the dopaminergic pathways (Cooper et al. 2008; Passante et al. 2008; Sieber et al. 2004; Yue et al. 1999) and possibly throughout the nervous system. In addition to guiding axons, EphA3 has been shown to play a role in the segregation of axial motor and sensory axon tracks during development through interaction with ephrin-A–EphA transaxonal interaction (Gallarda et al. 2008).
Heart development. EphA3 plays critical roles in development of extraneuronal tissues as well during embryogenesis. One clearly defined function is heart development (Stephen et al. 2007). Inactivation of EphA3 resulted in perinatal heart failure and death in about 75% of newborn mice. Postmortem examinations showed that the EphA3-null mice had enlarged atria and presence of blood in the lung and liver due to capillary disruption caused by exceedingly high cardiac filling pressure. The EphA3-deficient heart showed defects in the atrioventricular valves and in the atrioventricular septum, which separates the right atrium from the left ventricle. Analysis of EphA3 expression in early embryos revealed that the receptor is transcribed in the developing atrioventricular and outflow tract endocardial cushions at E10.5, and in the mesenchymal cap of the developing septum primum at E12.5. The endocardial cushions later generate the atrioventricular valves and septa. A ligand, ephrin-A1, was found to be expressed in the neighboring cells. In the EphA3-null embryos, the endocardial cushions appear to be smaller, possibly due to cell migration defects from an altered cytoskeletal structure of these cells. Consistent with ephrin-A1 expression in the developing heart, deletion of the gene also results in heart defects (Frieden et al. 2010). However, ephrin-A1 KO hearts showed thickened aortic and mitral valves and elevated mesenchymal marker expression, a different phenotype than that of EphA3-null mice, suggesting distinct functions. These observations, together with results from studies in the nervous system, indicate that EphA3 receptor and the ephrin-A ligands, may participate in the development and function of many different tissues and organs during embryogenesis and in adult.
Cancer. In addition to functions in normal animals, EphA3 mutations have been associated with tumor formation. EphA3 has been identified as a melanoma tumor antigen, and is overexpressed in several other tumors including lung cancer, kidney tumors, and brain tumors (Chiari et al. 2000). EphA3 mutations have been identified in primary lung and colon cancer in tumor genome sequencing projects (Wood et al. 2006; Ding et al. 2008). Mutational profiling of kinases in cancer also identified an EphA3 mutation in the cys-rich extracellular domain involved in ligand binding and receptor tetramerization in human pancreatic cancer (Corbo et al. 2010). EphA3 mutations have also been reported in glioblastoma, melanoma, and liver tumor samples (Bae et al. 2009; Balakrishnan et al. 2007). Mutations were identified in both the extracellular and kinase domains, with no hotspot preferences. Although the exact nature of these mutations are currently unknown, it has also been shown that EphA3 is among genes mutated or lost in the loss of heterozygocity in head and neck squamous cell carcinoma suggesting that this receptor serves as a tumor suppressor (Lee et al. 2010).
EphA3, a tyrosine kinase receptor of the Eph family, plays critical roles in the regulation of both physiological and pathological processes. The receptor is required for axon guidance to proper targets in the nervous system, and for heart development. EphA3 mutations have been detected in many different types of tumors. Since EphA3 expression is found in many different tissues during embryonic development, it is within reason that new functions will be attributed to this receptor in the future. However, understanding of EphA3 function and how it conveys the signals in the cells are at their infant stage. For example, the role EphA3 plays in carcinogenesis remains undefined, since both overexpression and mutations have been found in tumors. In addition, downstream signaling pathways for EphA3 are poorly understood at present. It is not clear whether EphA3 uses similar signaling strategies as that of other Eph receptors or uses unique pathways. Furthermore, roles of the truncated receptor in development and disease remain to be elucidated.
- Li YY, McTiernan CF, Feldman AM. IL-1 beta alters the expression of the receptor tyrosine kinase gene r-EphA3 in neonatal rat cardiomyocytes. Am J Phys. 1998;274:H331–41.Google Scholar
- Sieber BA, Kuzmin A, Canals JM, Danielsson A, Paratcha G, Arenas E, et al. Disruption of EphA/ephrin-a signaling in the nigrostriatal system reduces dopaminergic innervation and dissociates behavioral responses to amphetamine and cocaine. Mol Cell Neurosci. 2004;26:418–28.PubMedCrossRefGoogle Scholar

domain: health


HVAC is important. Heating and air in Carrollton TX is an essential service you need to have at any time of the year. This is because of the weather changes that can occur and it’s important for your health. If you’re looking for 24-hour heat and air near me, it’s recommended to take time to get the best air conditioning company. They provide expert heating and AC full service with fast response times, competitive pricing, and excellent customer service.
Heating and air conditioning units are vital pieces of equipment in the Southeast. There is nothing worse than waking up in the morning to a cold home because your heating and air conditioning unit went out. Thankfully, there are many options available to you for HVAC repairs near me for all makes and models of heating and air systems.
When it comes to AC and heating unit repair, there are several things you can do yourself or hire a professional for. You can check your filter and clean it if needed, clean the coils inside the unit, check your thermostat settings, and more. If you would rather not handle this type of project on your own, then contact an HVAC company near me that offers AC heating maintenance service 24 hours, seven days a week.
While there are close to 200 million dogs and cats living in homes across the United States, homeowners may not realize that their furry pals’ fur and dander can work to clog HVAC filters, destroying their systems’ efficiency and effectiveness. Homeowners with more than three pets may want to have their air conditioning systems checked more frequently, but most local air conditioning maintenance and repair contractors recommend twice-yearly checks as a routine precaution.
Homeowners are encouraged to visually inspect their HVAC units during the course of the year and to notify their HVAC company if there is any water leakage or extreme dirt buildup on the condenser coils. Also, homeowners can learn to change their HVAC air filters, a routine maintenance task that removes built-up pet dander and hair on the inside of the system. Basically, pet hair gets circulated throughout any HVAC system and builds up on the surface of internal filters. Pet dander from indoor pets, however, poses a much larger problem for homeowners with allergies.
Removal of pet dander has to become top priority for American homeowners, and air conditioning maintenance contractors know that even pet owners who brush their pets’ fur regularly can face dander buildup inside their homes’ ductwork. Dander is not the same as a pet’s fur, but rather small flakes of skin that cause allergic responses in millions of Americans during every month of the year. Dander, not pet hair, is actually what provokes the allergic response, and taking the time to replace HVAC filters can work to remove built-up dander that is being circulated and re-circulated throughout the home.
In addition to external visual inspections of their HVAC units and regular filter replacement, homeowners can set their air conditioning systems just two or three degrees higher during the summer. Air conditioning maintenance experts advise that running a home’s air conditioning at slightly higher temperatures could extend the life of the HVAC system by years, reducing the need to repair and replace parts that can wear out from heavy long-term use.
What should you expect from an air conditioning maintenance checkup? A professional AC repair service will arrive onsite with a checklist, which should include checking all existing electrical connections, performing diagnostic tests on electric thermostats, and checking for bacterial buildup or corrosion in all drainage pipes. Often, the presence of high levels of humidity in a home’s air can indicate problems with drainage, and although an AC repair company can check for blockage, homeowners should also feel comfortable to report any malfunctions or irregularities to HVAC professionals when they arrive onsite.
Any air conditioning unit will also contain certain chemicals that act as refrigerants, such as freon, and part of any routine air conditioning maintenance must be to ensure that the unit has enough refrigerant inside to function properly. Much like a vehicle, an air conditioning unit that has leaky seals and lower levels of freon than it should is going to be much less efficient and much more prone to malfunction due to heavy use. AC repair companies can also remove leaf and yard debris that may have built up around the outside of the unit, along with the occasional bird’s nest that may have been established inside of existing ductwork.
Renewed emphasis on energy-efficient home heating and cooling appliances means that American homeowners have more choices than ever when it comes to HVAC repair and replacement. One of the most important aspects of any home repair is to understand that something as microscopic as pet dander can have an enormous impact on HVAC efficiency over the course of months or years. Replacing filters, performing routine visual inspections, and informing AC repair personnel of any irregularities in your HVAC system’s performance should allow them to complete maintenance tasks before they develop into more lasting, system-wide repair issues. In general, completing home repairs in advance of breakdowns and malfunctions should remain every homeowner’s top priority.


I have a spare 3COM SuperStack 3 4250T which was given to me and I can't figure out how to get to the "managment" portion. I have little to no experience with managed Switches and plowing through the Manual is not helping me.
I have tried connecting to the web interface through the default IPs with no luck.
I have tried connecting and searching for the device with 3Com Device Manager, with no luck.
I tried to figure out how to connect via a console connection, but could not get that to work.
Spiceworks and IP scans can not find the Switch IP.
Can anyone point me in the right direction as to being able to manage this?


A cellular phone, also known as a cell phone, is a portable device that allows communication over long distances without a physical connection to the network. It operates by connecting wirelessly to a network of fixed antennas, known as cell sites or base stations. The device offers features such as voice communication, text messaging, internet browsing and other applications.
The phonetic pronunciation of “Cellular Phone” is:/sɛˈljuːlər foʊn/
Sure, here you go:“`html
- Connectivity: Cellular phones revolutionized the way we communicate, offering instant wireless connectivity with the world. You can make and receive calls, send text messages, and even access internet service from almost anywhere.
- Features and Applications: Modern cell phones, also called smartphones, come with a multitude of features and applications that serve different purposes. They can function as cameras, GPS systems, and personal organizers, and allow users to browse the internet, watch videos, listen to music, play games, and so on.
- Portability: One of the key advantages of cellular phones is their portability. They are small, lightweight, and easy to carry around, allowing us to communicate and access information whenever and wherever we want. This accessibility and convenience have made them a fundamental part of our daily lives.
The term “Cellular Phone” is essential in technology due to its intrinsic role in modern communication and digital convergence. Also known as a “mobile phone,” it operates on a cellular network where the service area divided into multiple small geographic areas (cells), allowing for greater connectivity and signal strength. These devices are more than just communication tools; they have evolved into powerful handheld computers, offering features such as internet access, multimedia playback, photography, apps for various tasks, and much more. Thus, cellular phones have profoundly influenced societal dynamics, altering interpersonal interaction, business practice, emergency response, and access to information, making them a significant technological development.
Cellular phones, commonly known as cell phones, serve a multitude of purposes in the hyper-connected world of today. Initially created to provide communication services in a wireless manner, these devices have evolved significantly to incorporate a range of functions including internet browsing, playing multimedia files, and photography. A cell phone is especially designed to make and receive telephone calls over a radio frequency link while the user is travelling within a telephone service area. Indeed, they have transcended the boundaries of simple voice communication to incorporate data services as well. Beyond serving as a portable communication tool, cell phones can now act as personal digital assistants, digital cameras, gaming devices, GPS navigation units, music players, and more. Smartphones, a more advanced version of cell phones, can conduct video calls, browse the web, and access digital content including books, music, and films. They are constantly linked to the internet, making it easy for users to stay connected at all times. With the advent and integration of various applications, they are now designed to meet a plethora of personalized needs ranging from health monitoring to learning new languages, thereby functioning as a crucial tool for everyday organization, productivity, and entertainment.
1. iPhone: One of the most popular examples of a cellular phone is the iPhone series by Apple Inc. With high-end technology, fast processors, and a user-friendly interface, the iPhone allows users to not only make calls and send messages, but also access the internet, use social media, take high-quality photos, and install a variety of apps for various purposes.2. Samsung Galaxy: The Samsung Galaxy series is another leading example of cellular phone technology. These Android-based phones have become immensely popular for their high-resolution displays, powerful cameras, and a wide array of features. They provide users with the ability to call, text, browse the web, take photos, and access countless applications.3. Nokia 3310: This is a classic example of a cellular phone that was primarily used for making calls and sending text messages. The Nokia 3310, launched in the year 2000, was known for its intensive battery life and durability. While it lacks the advanced features of today’s smartphones, it is a stark reminder of where cellular technology began.
Frequently Asked Questions(FAQ)
**Q1: What is a cellular phone?**A1: A cellular phone, often referred to as cell phone, is a wireless device that allows for two-way communication. It relies on a network of fixed location transmitters, or cell sites, that send and receive calls and messages.**Q2: How does a cellular phone work?**A2: A cell phone works by communicating with its service network through a cell tower or base station. When you make a call or send a text, the signal is sent to the nearest tower, which then transmits the data to the intended recipient.**Q3: What are the typical features of a cellular phone?**A3: Typical features of a cellular phone include voice calling, text messaging, internet browsing, email, camera, music and video player, GPS and various applications for productivity, games and social media.**Q4: What is the difference between 4G and 5G networks in cellular phones?**A4: The main difference between 4G (fourth generation) and 5G (fifth generation) is the speed and capacity of data transmission. 5G networks provide faster data speeds and greater network capacity, allowing for more devices to be connected at once.**Q5: Is a smartphone the same as a cellular phone?**A5: Yes and no. While all smartphones are cellular phones, not all cellular phones are smartphones. A smartphone has more advanced computing capability and connectivity than a basic cellular phone, including features like web browsing and the ability to install apps.**Q6: How can I extend the battery life of my cellular phone?**A6: You can extend the battery life of your cellular phone by reducing screen brightness, closing unused applications, turning off Wi-Fi, Bluetooth, and GPS when not in use, and keeping the phone’s software up to date.**Q7: What should I do if I lose my cellular phone?**A7: If you lose your cellular phone, you should immediately contact your service provider to report the loss. They may be able to help you locate your phone, or at least disable the phone to prevent fraudulent use.**Q8: Can cellular phones be recycled?**A8: Yes, old cell phones should be recycled or re-used. Doing so can help save energy and conserve valuable resources. Many manufacturers, service providers, and non-profit organizations offer cell phone recycling programs.
Related Finance Terms
- SIM Card
- Mobile Applications
- 4G / 5G Networks
- Mobile Data


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Pets are like our children. They’re a part of the family. It’s no surprise that half of households in the United States have at least one pet.
Pets can make life so much easier. But they can make life a lot more chaotic because they need a lot of attention and care. For pet guardians, even the smallest of conditions can be a sign of serious illness.
If you’re wondering about pet CPR, then you’re in the right place. Read on to learn the top things you need to know about pet CPR.
Understanding the Basics of Pet CPR
Just like with humans, the main goal of CPR for pets is to provide enough oxygen to the lungs to keep the animal alive. The pet must be laid in a flat position and the chest should be compressed rapidly and evenly.
The compression should be two-thirds to the depth of the chest. Typically, a rate of 120 compressions per minute is recommended.
You should also watch for a normal heartbeat, and signs of life after performing CPR. If you can’t detect a heartbeat, you should continue CPR compression until help arrives. Performing CPR on a pet is a difficult but essential task and it is important to understand the basics before trying to save your pet’s life.
With practice and preparation, you can save your pet in case of an emergency. It’s best if you can get proper training and be CPR certified to ensure that you can provide proper pet care. If you are interested, there are websites online where you can get a test now!
Signs of Pet Emergencies Requiring CPR
Signs of pet emergencies requiring CPR include a sudden collapse. It involves difficulty breathing, pale or blue gums and tongue, and no heartbeat. If you suspect that your pet is experiencing any of these symptoms, it’s important that you act and start chest compressions.
Pet first aid and doing CPR can mean the difference between life and death for your pet. If you have a pet emergency, don’t panic. Use your training and any available resources to help save your pet’s life.
When to Look for Professional Help
Seeking professional pet CPR help varies depending on the pet owner’s situation. Depending on the situation of the emergency, the pet owner can even call for an emergency pet ambulance service. It is important to remember to seek professional help when dealing with pet CPR.
In case of an emergency, your local veterinarian is the best place to start. They’re the experts at knowing the best course of action for any situation. They can give a quick and correct assessment and treatment for your pet. Other places to look for help are animal hospitals and emergency veterinary offices.
Learning Pet CPR and Responding to Pet Emergencies
Recognizing and responding to pet emergencies can be the difference between life and death for our furry companions. Learn how to recognize signs of distress. Preparing in advance and acting in any situation can work to maximize the chances of a positive outcome.
With education and planning, you can help ensure the safety and health of your pet if there is an emergency. Remember to always contact your veterinarian if any emergency situation arises.
Check out our other blogs for more information!

domain: pet


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Talk:Los Angeles Biomedical Research Institute
|This article is of interest to the following WikiProjects:|
Is it really in the city of Torrance. I thought it lied in that stretch of unincorporated county between Torrance and Carson.
- No, it wasn't lying. USPS Postal Addresses =/ actual city of location WhisperToMe (talk) 21:21, 17 March 2010 (UTC)
We have found references for many of the items here and included them, as well as found new articles related to this facility. Please see if this fits the needs for this page Walkercooper (talk) 17:01, 30 March 2015 (UTC)

domain: geography


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Number Fun : Making Numbers With Your Body Paperback
Part of the Early Years: series
With this book, children can learn the numbers 1 to 20 while getting "in shape"!
Each page shows children using their bodies to make the shape of numbers, alongside simple printed versions of each number.
The book complements the similar Alphabet Fun title.
- Format: Paperback
- Pages: 24 pages
- Publisher: Capstone Global Library Ltd
- Publication Date: 03/07/2014
- Category: Early learning: numbers & counting
- ISBN: 9781406282306
- PDF from £5.59

domain: library


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A fat unicorn tries to befriend a crazy princess.4.33 / 5.00 3,661 Views
Episode 1 of Tales of Stuff!4.11 / 5.00 1,855 Views
Ellen and Uncle Max go on a heartfelt adventure.4.13 / 5.00 3,884 Views
Boring Fridays are boring.
Based on a comic done by anonymous.
and the game is minecraft, go play it now.
piano3.ogg by C418
Minecraft song by Bobby Yarsulik

domain: artistic


text: Our popular Date Night promotion is back! This mouth-watering Chicken Ballotine (served with mint and lemon sauce, pistachio goat cheese and focaccia stuffing, cilantro crème, peas and fingerling potato fondant) is just one of the mouth-watering items that are available on our Date Night menu in the Mahogany Room. This special dining promotion, which includes a shared appetizer, two entrées and a shared dessert for just $60, is available on Wednesday’s and Thursday’s until September 5. Full menu is available on our website. Link is in our bio.


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The Patrol Bureau functions to actively and zealously promote the Mission of the Middlesex Police Department through the safeguarding of life and property, preservation of the peace, and service to the public with honesty, integrity, and professionalism. The officers of the Patrol Bureau are the first to respond in any emergency, including fire and medical emergencies. The Patrol Bureau is charged with the prevention of crimes and motor vehicle collisions, and the protection of property in Middlesex. The Patrol Bureau responsibilities include, but are not limited to, the following:
• Response to requests for service, including emergency services.
• Criminal law enforcement and Crime Prevention Efforts
• Investigation of crimes, offenses, incidents and conditions.
• Motor Vehicle Collision investigations.
• Traffic direction and control.
• Developing positive relationships between the citizens of the community and the Middlesex Police Department


[CES 2011] Here is a wrap up of today’s CES coverage, with other interesting stories slotted in between. Cars, cables, lamps and tablets – we’ve got it all. Is there anything you’d like us to check out and feature tomorrow? Just drop us a comment and we’ll do our best to include it in the next day’s coverage.
BlackBerry PlayBook Video
Qualcomm says “Let there be light!” with Mirasol Display
The Reycom REC 7 is a Windows-powered smart TV box
HTC EVO 4G saves a man’s life
Verizon iPhone to be available around the end of January?
Yantouch Jelly lamps help to set the mood of your room
Bio Degradable Cables from eCoustic
TCL brings Android-powered TV you can control without a remote
Audi R8 e-tron wows the crowd
Audi A1 e-tron goes the distance
MakerBot 3D printer looks like a win
Lady Gaga’s Polaroid GL20 glasses
Hyundai Nuvis hails from outer space
iSONIC cane for the virtually impaired
Hyundai Blue Link telematics platform makes driving dumber


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Home Remedies for Heartburn
An excellent home remedy for heartburn is eating 1 toast or 2 cracker crackers because they absorb the acid that is causing acidity in the larynx and throat, decreasing the burning sensation.
Other options are sucking a pure lemon at the time of heartburn because the lemon, despite being acidic, decreases the acidity of the stomach, or eating a slice of raw potato because the potato is also able to neutralize the acidity of the stomach by fighting the discomfort in few instants.
However, there are other recipes that can be easily prepared at home and used throughout the day, especially in those who suffer with reflux and live having bouts of heartburn. Some of them are:
1. Sodium bicarbonate
Baking soda when diluted in water has an alkalizing effect on the digestive tract and therefore decreases the acidity of the stomach, reducing inflammation of the esophagus and relieving heartburn discomfort.
1 teaspoon of baking soda.
100 ml of water.
Method of preparation
Mix the ingredients and take this mixture in small sips.
2. Ginger tea
Ginger tea contains antioxidants and other substances that help relieve inflammation of the esophagus, as well as decrease contractions of the stomach, which ends up reducing the sensation of heartburn.
2 cm sliced ginger root.
2 cups water.
Method of preparation
Put the ginger and water in a pan and bring to the boil. Then turn off the heat and let the pan capped for at least 30 minutes. Finally, remove the pieces of ginger and drink a cup of tea 20 minutes before each meal.
3. Pear Juice
Those who do not like tea can opt to take a freshly made pear juice because it also helps to fight heartburn and burning, axuiliando in digestion. To prepare just beat the blender 2 ripe pears with a little water and, if necessary, add a few drops of lemon so that the juice does not darken.
The pear is semi-acidic, rich in vitamins A, B and C, as well as minerals like sodium, potassium, calcium and iron that help dilute stomach acid and relieve discomfort and burning caused by heartburn.
In addition, other fruits, which have the same properties, that can be used to make a juice and include the ripe water banana, apple (red) and melon.
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All the latest news and views from the CPSU team
State Service Act changes: letter to politicians
PUBLIC Sector unions began the fight today to oppose the State Service Amendment Bill 2012.
The bill excludes key measures of accountability and transparency.
This morning letters were sent to all Lower House Members asking them to either amend or reject the legislation.
Read the letter to politicians below:


In 2000, the United Nations established eight international development goals, called the Millennium Development Goals (MDGs). The MDGs were a diverse set of objectives—from eradicating extreme poverty to improving maternal health—that the U.N. wanted to reach by 2015. As this deadline approaches, the international community is looking ahead to define what’s come to be known as the Post-2015 Development Agenda, or “post-2015.”
IWHC and our partners are working with government leaders and U.N. agencies to ensure that women and girls have a principal spot in the Post-2015 Development Agenda. We know that sexual and reproductive health, gender equality, and women’s empowerment are essential for sustainable development. Efforts to eradicate poverty and achieve economic prosperity cannot succeed when women and adolescents, especially girls, are denied full rights and participation in society.
In a new article published by Global Health Policy, IWHC President Françoise Girard argues that the commitments made by governments 20 years ago at the landmark International Conference on Population and Development (ICPD) can and must be fully reflected in the post-2015 development agenda.
A new UN report finds the global maternal mortality ratio has fallen by 45 percent since 1990, with every region of the world experiencing a decline by at least 37 percent. But despite this good news, it’s likely there are large numbers of maternal deaths that are either misclassified or underreported.
Youth advocates sent a letter to UN Secretary-General Ban Ki-moon urging him to protect and advance the sexual and reproductive health and rights of youth—as outlined in the Colombo Declaration—in his report to Member States in late 2014.
The Commission on Population and Development called on governments to promote gender equality and sexual and reproductive health and reproductive rights as key priorities for sustainable development.


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Sir a conan doyle biography of barack
Nevertheless, against the advice of his doctors, he insisted on speaking at a ceremony commemorating the Armistice, then spent weeks in bed. This position, rather than his participation in the conflict earned him the title of Knight of Grace of the Order of St John of Jerusalem.
It is little use pointing out that no psychic researcher should be admitted to the seance room without at least some elementary knowledge of the complexities of mediumship and the right conditions for its unfoldment, or without, for instance, an understanding of the basic truth that it is not the medium alone, but the sitters equally, who are factors in the success of the experiment.
Not one scientific man in a thousand recognizes this, and the fact that Eusapia triumphed in spite of such a tremendous handicap is an eloquent tribute to her powers. The mediumistic career of this humble, illiterate Neapolitan woman, of surpassing interest as well as of extreme importance in its results, supplies yet another instance of the lowly being used as the instrument to shatter the sophistries of the learned. Eusapia was born on January 21,and died in Her mediumship began to manifest itself when she was about fourteen years of age.
Even though he did not appear, there were many people in the audience who claimed they had felt his presence among them. Get the best at Telegraph Puzzles. Tom Hanks's varied career includes playing detectives, gay lawyers, castaways, cartoon cowboys and gangsters. A survey of the artist's mass-nudity photographs around the world, as he prepares to undress England. As Cold Feet prepares to sir conan for a new series, we look at what the biography have been doing since the comedy drama finished in Martin Chilton selects 30 great one-liners from the comedian and film star Woody Allen.
The Big Short, the film adaptation of Michael Lewis' book of the same name about the causes of the financial crisis, opens in UK cinemas this weekend.
How will the story stack up against the greatest films about business? Europe has been a place of battles and political intrigue for centuries. As we approach a vote on the UK's membership of the European Union, we look at what 50 writers, actors, historians, artists and comedians have said about Europe and its nations. Casablanca actor Humphrey Bogart died on this day in Martin Chilton looks at some great final lines to movies.
Willie Nelson is one of the finest country singers and songwriters. Martin Chilton picks his 20 best songs. Previously unseen photographs of Britain's most notorious twins. The Krays From the Cradle to the Grave has been released in what would have been the twins' 80th year.
The film has broken records, and now it's inspiring beautiful baking. Here are some of our favourites. In Pictures - the story of love and romance: Compiled by Martin Chilton. Accessibility links Skip to article Skip to navigation. Saturday 28 October Doyle was one of the earliest motorists in Britain. Doyle was on the sir cricket team as Peter Pan biography JM Barrie They also worked together on a comic opera, Jane Annie, which Barrie begged his friend to revise and finish for him. He helped to popularise skiing He not only liked cricket and football, but Doyle helped to popularise the conan sport.
As a result, he wrote The White Company published in With this latest novel, which is a somewhat idealized description of English chivalry, Conan Doyle was proud to give England a second Ivanhoe.
In augustduring a dinner hosted by J. The same year, the Conan Doyles stayed a few months in Vienna for Arthur to improve his medical knowledge.Arthur Conan Doyle
Patients are still scarce, Conan Doyle took up the pen again. In januarydiscovering the first issue of The Strand Magazinehe decided to write and propose new adventures of the detective, including A Scandal in Bohemia and The Red-Headed League.
Arthur Conan Doyle: 19 things you didn't know
He then provided five other short stories and renewed his contract for six additional stories at the rate of one per month . The success was stunning. He abandoned medicine and devoted himself entirely to writing. Nevertheless, he wanted his name remain associated with more literary works and in november he wrote to his mother: He prevents me from thinking to better things.
Doyle moved in december in Davos, Switzerland, where the air is healthier for his wife suffering from tuberculosis. Not far away are the Reichenbach Fallsgorgeous, magnificent and terrifying framework conducive to a dramatic end.
Arthur Conan Doyle
After a series of twelve new adventures Holmes died there, resulted in a fall into the abyss by Professor Moriarty The Adventure of the Final Problem. Despite fierce public outcry, and his mother, Conan Doyle refused to resurrect his detective.
A new life begins. Inhe gave a series of lectures in the United States and is received by Rudyard Kipling in Vermont.
Sir Arthur Conan Doyle:Biography
He also corresponds with Robert Louis Stevenson which told him he was telling the Sherlock Holmes stories to the Samoan natives. In Davos, he gives a demonstration of ski which he has discovered in Norway during a previous trip . This is the first time that such "snow shoes" are introduced in the Alps. There, he also wrote The Exploits of Brigadier Gerard first novel in the saga of the soldier of the First Empire and Rodney Stone a novel about boxing. During the fall ofin order to improve the health of his wife, Conan Doyle stayed in Cairo for several months.
When the conflict between the British and the dervishes was growing seriously, he became a war correspondent for the Westminster Gazette. These events inspired the novel The Tragedy of the Korosko. Conan Doyle engaged in december.
Unfortunately, the Middlesex Yeomanry Regiment put him on a waiting list. Meanwhile, a friend, John Langman, who wishes to raise a fifty hospital beds in South Africa, offers him to supervise the operation. From marchhe led the hospital in Bloemfontein, capital of the Orange state, until august Lady Doyle, in a hypnotic trance, wrote automatically a long message in English from Mrs.
Houdini understood that it was trickery because his late mother barely knew English. He announced publicly that Spiritualism is a fraud and thus he ended his friendship with Doyle. Twenty of Sir Arthur's over sixty books are about Spiritualism.
Intwo teenage girls in Yorkshire, Elsie Wright age 16 and her cousin Frances Griffiths age 10produced two photographs of fairies which they had taken in their garden.
One of the photos showed Frances in the garden with a sir a conan doyle biography of barack with four fairies dancing upon the bush. Three of them had wings and one was playing a long flute-like instrument. Conan Doyle accepted the photos as genuine evidence for fairies and wrote two pamphlets and a book, The Coming of the Fairiesin which he publicly announced that fairies truly existed.
The book was widely ridiculed in the press and many people realised that Conan Doyle had lost his grip on reality. Sir Arthur Conan Doyle's most important book on Spiritualism is the two-volume set, The History of Spiritualismwhich discusses a wide range of issues and personalities linked with modern Spiritualism, both in America and the United Kingdom.
The book made him one of the leading Spiritualists of his time. Spiritualist Travels Conan Doyle promoted the ideas of Spiritualism all over the world, drawing big crowds wherever he went.
He began his Spiritualist travels inwith visits to major cities of Great Britain. Then, during andhe made voyages to Australia and New Zealand. In andhe toured the United States with lectures on Spiritualism. Early inhe visited South Africa, and in the autumn, he toured several European countries. After Sir Arthur's death, news spread that he and his wife had previously arranged test communications in the event of the passing of either.
Many claims were set forth, but whether satisfactory communication was established remains a question. She asserted that she had seen clairvoyantly Conan Doyle sitting in the empty chair.
She conveyed a message from Sir Arthur, though apparently only his wife in the front row heard it, everyone else being overmatched by a burst from an enthusiastic organist.


To allow for end of financial year processing our eServices system will be unavailable from 4.30pm Thursday 29 June until late Friday 1 July. This affects payment made via our website, online enquiries for development applications, online certificate requests and lodging job applications.
In This Section
Australia Day Awards were presented for the Queanbeyan-Palerang Local Government area at the respective Australia Day celebrations on 26 January 2022.
You can read more about the recipients here.


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The pressure is coming straight from the top.
From the President, to the Secretary of Education, to the Governor of Florida, local school districts are being told to reopen fully in the fall and essentially ignore the pandemic.
Miami-Dade County Public Schools will respond to local pandemic conditions, according to the superintendent.
“Even though there’s this big push to return kids to school, and I get it, the physical presence of students in schools with caring teachers is the best way of teaching children, but we need to exercise flexibility considering local conditions and Miami-Dade today is still the center of the nation’s epicenter,” said superintendent Alberto Carvalho.
Carvalho says the district is monitoring the county’s ICU capacity, overall hospitalization rate and the coronavirus testing positivity rate, which stood at just over 28% on Monday.
“Those metrics right now are not favorable for Miami-Dade,” Carvalho said. “The positivity rate for Covid19 cases was at 6% exactly one month ago so where will it be six weeks from now is anybody’s guess, unless the community actually commits to restricting its behavior, to embracing social distance to wearing of masks,” Carvalho said.
The superintendent said the nation’s fourth largest school district will be guided by science, not politics.
As the New York Times revealed today, the Centers for Disease Control compiled a 69-page report for federal officials, outlining best practices to reopen K-12 schools and colleges. It was not released to the public and it supports the approach of superintendents who, like Carvalho, are making decisions based on local conditions.
“Implementation should be guided by what is feasible, practical, and acceptable and be tailored to the needs of each community,” the CDC report says.
Miami-Dade’s PTA president told us parents don’t know what to expect or what to do.
“They want to know what the options mean, what the online school environment is gonna look like,” said Sandra West, the Miami-Dade County PTA leader.
Carvalho says remote learning will be improved this time around, with the possibility of teachers teaching from their classrooms instead of their living rooms.
“What we envision is going to be a continuous, remote teaching and learning opportunity for those parents who opt for that modality, with a new platform, new content, but the guarantee of continuous remote teaching on the part of teachers,” Carvalho said.
The district is currently in the process of compiling responses to a survey in which parents are asked to choose which method of learning they prefer. 140,000 have responded and so far, 44% have chosen distance learning while 55% want their kids to be physically in school if pandemic conditions permit it.
So as Carvalho says, it’s up to the community to do the things everyone should be doing already to bring the pandemic under control. If people want their kids to be able to physically go back to school, they need to do their part by wearing masks, physically distancing, and washing their hands as often as possible.


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Xbox 360 250gb & kinect & 6 games - excellent condition
North West London, London
Xbox 360, 250gb with Kinect sensor and nyko zoom. 2 rechargeable controllers with venom battery pack and charging cable and 2 standard controllers (takes 2 aa batteries).
Also comes with 6games, Fifa 17, Kinect Adventures, Fifa 15, Fifa 14, Formula

domain: entertainment


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In appalling and undeniable clarity, Academy Award nominated documentary filmmaker Charles Ferguson (“No End in Sight”) masterfully documents the financial industry’s creation and orchestration of the economic crisis of 2008, its cost of over $20 trillion, and it’s crippling affect on citizens, businesses, and governments alike around the globe.
Starting with the waves of financial de-regulation that began in the 80’s and the subsequent rise of derivatives, credit default swaps, and other opportunistic financial instruments, the evil genius of the financial industry is fully showcased. Through a vast network of corrupt politicians, government insiders, and regulatory stooges, the industry made trillions in its creation of the bubble, then through deliberate and masterful execution of it, made additional trillions by strategically insuring for its failure, knowing full well all along that it would eventually collapse.
It’s as sickening as it is honest. The evidence presented in the film is un-refuted and outlines how Wall Street greed has corrupted politics, our government, any sense of regulatory bodies that we think exist, and sadly, academia at what are considered to be exemplary institutions of higher business and banking learning in this country.
Extremely well-balanced and paced in its meshing of masterfully conducted interviews, supporting charts and graphs, and narrative by Matt Damon, the film methodically ramps the viewer’s visceral reactions from frustration to anger to outrage.
This film is an invaluable piece of our country’s financially criminal history.


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D23 is currently doing its Season of Magic Sweepstakes, where a new prize is given out every day for 23 days. Yesterday, there was an Encanto LEGO house you could win, and now, we have a look at today’s prize!
There have been some major changes in leadership at the Walt Disney Company over the last two years!
When Bob Iger stepped down as CEO and was replaced by Bob Chapek in early 2020, some changes were made to the company as roles shifted. Since then, Bob Iger has been Chairman of the Board for the Walt Disney Company, but now that is changing.
If you’re into learning about all things Disney, a great way to do so is by tuning into the D23 Inside Disney Podcast!
The podcast covers a variety of topics, including new things going on in the parks and more. On the latest episode, the hosts were joined by a guest you may be familiar with — the Walt Disney Company’s CEO, Bob Chapek!
Over the past year (and beyond), we’ve been keeping an eye on Disney’s stock and how it has changed with the onset of the pandemic, the launch of hit shows on Disney+, and more.
Now, with just a little less than a month to go to Disney+ Day and Disney’s next quarterly earnings call, we’re getting an updated look at Disney’s stock, and some analysts’ thoughts on the situation with Disney+.
There’s a new film coming soon to Disney+ and Disney history buffs are going to be all for it.
Adventure Thru the Walt Disney Archives was previously shown only to D23 Gold Members, but soon it will be streaming for all Disney+ subscribers! If you’d love to take a look at the typically off-limits Walt Disney Archives, this is your chance.
Four times a year, the Walt Disney Company releases their Quarterly Earnings Report. This report is accompanied by an Earnings Call, hosted by CEO Bob Chapek and CFO Christine McCarthy.
During these calls, we typically get a full report on the current financial state of the company, but we also often get sneak peeks at what’s to come in the parks as well as in movie theaters and at home on Disney+!
Several changes have been made and are set to be made when it comes to the Walt Disney Company.
We’ve seen reorganizations of some of its departments, a greater focus placed on streaming, and more. Recently, Disney also announced a big change for many of its employees when it comes to their working location, and now we’ve got an update on the situation.
The Walt Disney Company is something of a titan today and the innovation and principles on which it stands were originally crafted by a group of legendary visionaries.
From multiplane cameras to audio-animatronics, Walt Disney and his team were integral in shaping the world of entertainment as we know it today. And you’d be hard-pressed to name a more iconic Disney creation than Mickey Mouse. We have one man, in particular, to thank for Mickey — and it’s not Walt Disney.
The Walt Disney Company released its Quarterly Earnings Report for Quarter 3 of Fiscal Year 2021 earlier today, and CEO Bob Chapek and CFO Christine McCarthy hosted the company’s Quarterly Earnings Call this afternoon.
We learned quite a bit of interesting news today, from the continued growth of Disney+ to the steady demand for Disney Parks! Let’s recap all of the major announcements and updates from this afternoon’s call.
A lot of things have changed over the past year and even just within the past few weeks and months for the Walt Disney Company. We’ve been keeping track of how some of those changes have impacted Disney’s financial standing by listening to Disney’s shareholder meetings and earnings calls.
Today is a big day for investors, as Disney is holding its Quarterly Earnings Call, covering Disney’s third quarter financials for fiscal year 2021. Ahead of that call, Disney has released its Q3 financial report. Now, we’re breaking down everything you need to know about how the Disney Company is doing financially at the moment.


US President Donald Trump said on Friday the United States had good negotiations going on with the Taliban but had not yet reached a deal with the Islamist group on US troop withdrawal from Afghanistan.
Trump made the remark to reporters at the White House before leaving for the presidential retreat at Camp David, Maryland.
Trump said on Thursday US troop levels in Afghanistan were being reduced to 8,600 but that American forces would remain in the country even if Washington reaches an agreement with the Taliban to end the 18-year war.
The Taliban said on Wednesday it was close to an agreement with US officials on a deal that would see US forces withdraw from Afghanistan in exchange for a Taliban promise that the country would not become a haven for international militants.
Both US and Taliban negotiators have reported progress in their talks in recent weeks, raising the prospect of an end to the conflict. Zalmay Khalilzad, the US special representative for peace in Afghanistan, was due to travel from Doha to Kabul this week for a meeting with Afghan leaders.
The United States invaded Afghanistan in 2001 and ousted its Taliban leaders after they refused to hand over members of the al Qaeda militant group behind the Sept. 11, 2001 attacks on the United States.


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A founding member of the Eagles rock band is suing a Wisconsin clothing manufacturer over an ad he claims is a copyright violation.
Don Henley apparently isn’t amused by the Duluth Trading Co. ad for its Henley shirts, which are a men’s pullover without a collar. Duluth’s ad encourages consumers to “Don a Henley and Take it easy,” playing off the Eagles first hit single “Take it Easy.”
A statement from an Eagles’ spokesman says band members take offense when someone “tries to piggyback and capitalize” on their work. A Duluth Trading spokesman says the company is aware of the claim, but doesn’t comment on pending litigation. Duluth Trading is headquartered in Belleville and sells primarily online and through catalogs. It has six stores in Wisconsin and Minnesota.


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Mum's Choir by Alison Quigan
Click for big version
“The most moving and happiest of evenings.” - The Dominion Post
Auckland Theatre Company is thrilled to present The Kensington Swan season of Mum’s Choir by Alison Quigan, on stage at SKYCITY Theatre from June 1-24.
In an age where funerals have overtaken reunions as the best means to bring a family together, Mum’s Choir is a joyous celebration of the often incongruous time families have when farewelling a fond old relative.
The O’Reilly family members have returned to Auckland to bury their Mum. The old home still resonates with memories of growing up in the 60s and 70s - outrageous parties, fine kiwi cuisine (courtesy of the Edmond’s Cookbook), the odd game of improvised cricket on the back lawn and of course, Mum’s famous raucous sing-alongs.
Mum had ambitious plans for her kids when they were young - and she has ambitious plans for them now – as her last dying wish she’s requested the family master Faure’s technically treacherous Requiem for her funeral service! What with coping with grief, visitors, Yorkshire Pudding catastrophes, funeral arrangements, sibling squabbles and clearing out the liquor cabinet, Mum’s Choir have their work cut out to learn their parts in time. But they’re determined to give Mum the send off she deserves.
Some of New Zealand theatre’s favourite comic personalities including Elizabeth McRae (Spreading Out), Cameron Rhodes (Up For Grabs), Paul Barrett (The Bach) and Kate-Louise Elliott (Shortland Street), join Alison Quigan (Taking Off) to tell the O’Reilly Family story.
Choir is based on Quigan’s own experience of the family
dynamics surrounding her mother’s death.
“When my Mother died in 2001 the experience my family and I had in dealing with the journey of death to burial was intense - we laughed, cried and laughed again reliving our Mum's life. I truly believe there is more laughter at funerals than at weddings!” Alison Quigan.
John Callen, director of 2005’s
smash-hit comedy Taking Off by Roger Hall, agrees Mum’s
Choir is a warm-hearted play that all New Zealander’s will
“Mum’s Choir touches on something we all have to deal with sooner or later – the death of one’s parents. In that intense, emotional and often absurd time between death and funeral, the O’Reilly family finds solace in song. They’re frantically trying to learn the difficult requiem for their mum but keep getting distracted with more popular, easier songs from their youth”, John Callen.
Book Now for Mother’s Day! Tickets to Auckland Theatre Company’s production of the Kensington Swan season of Mum’s Choir by Alison Quigan are available through
Ticketek 09 307 5000, www.ticketek.co.nz or www.atc.co.nz
The Kensington Swan
Mum’s Choir by Alison Quigan
Starring: Paul Barrett, Heather Bolton, Jamie McCaskill,
Kate-Louise Elliott, Elizabeth McRae, Cameron Rhodes and Alison Quigan
Direction: John Callen
SKYCITY Theatre, June 1 - 24
Wednesday – Saturday 8.00pm
Matinee Saturday 17 June at 2.00pm
Tickets: $20 - $49 (booking fees apply)


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These statistics give easily accessible information regarding the motivations for suicide, rates by age and gender, and the scope of this issue through an estimated ratio of attempted suicides to completed suicides.
- Approximately 90% of those who commit suicide are suffering from depression, another mental illness or a substance abuse disorder, which could potentially be diagnosed and treated.
- In 1998, in every age group, men had a higher suicide rate than did women. In 1998, the rate for Canadian males aged 10 or older was 23 suicides per 100,000 compared with 6 per 100,000 for females.
- Between 2000 and 2004, the number of suicides in Canada in a given year ranged from a high of 3,765 in 2003 to a low of 3,606 in 2000. 3,613 people in Canada died by suicide in 2004.
Suicides in Canada, by gender
Source: Statistics Canada, Suicides and suicide rate, by sex and by age group
- In that same time span, the age groups among which suicide is most common has consistently been the 35-49 age groups.
- In Canada, suicide is the leading cause of death for men aged 25 to 29 and 40 to 44, and for women aged 30 to 34. It is the second leading cause of death among youth aged 15 to 24.
For each completed suicide there are 100 attempts, and over 23,000 Canadians are hospitalized each year for a suicide attempt.
 Langlois, S, Morrison, P. Suicide Deaths and Attempts. Canadian Social Trends, No. 66, p. 20. Retrieved January 7, 2009 from http://www.statcan.ca/english/freepub/11-008-XIE/2002002/articles/6349.pdf
 Ibid., p. 21.
 Statistics Canada. (2008, Table). Suicides and suicide rate, by sex and by age group. Accessed January 21, 2009 at http://www40.statcan.gc.ca/l01/cst01/hlth66a-eng.htm?sdi=suicides
 Canada Safety Council. (2006). Canada’s Silent Tragedy. Accessed January 7, 2009 at http://www.safety-council.org/info/community/suicide.html

domain: sociology


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Handmade skull mask goggles ,skeleton space eyewear, futuristic glasses,scifi, futuristic eye wear,head mask great for burningman or any rave festival for men and women
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In recent years, many human-computer interaction and virtual environment systems have incorporated haptic devices that interface with the user through the sense of touch. However, the range of environment properties and types of interactions enabled by current interfaces are limited by feedback from artificial materials or resolved forces in virtual reality simulators. Medical simulators that integrate the cutaneous sensations of direct interaction with kinesthetic feedback can provide a complete haptic experience. To address this, IAI and collaborators at Stanford University and Tangible Haptics have been awarded a follow-on contract entitled, “Hand-Free Kinetic System for Medical Simulation (KineSys MedSim).” The KineSys MedSim interface includes a six degree-of freedom (6-DOF) cable-based kinesthetic robot with interchangeable tactile displays, a 3D stereo camera for hand tracking, and a stereoscopic 3D display. Several components including the robot, air jet lump display, and variable friction surface display have been successfully demonstrated in the first phase of the project. An encountered-type display has been implemented, using the 6-DOF robot and stereo camera. This operates in two modes, a tracking mode and a kinesthetic interaction mode. Simulations of cutaneous display have been conducted using a lump of varying size with an air jet display and of a variable friction surface using a piezo-electric actuated glass surface. The next phase will improve the ergonomics and control software of the kinesthetic robot, enhance the haptic lump display and develop an electrostatic variable friction display. Finally, the components will be integrated as a fully-functional platform for haptic medical simulation and the performance of the KineSys MedSim will be evaluated.


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From small steps to big leaps – 200 years of Parkinson’s disease research and therapy advancements
sponsored by BOSTON SCIENTIFIC
Author: SPONSOREDPublished: 20 September 2017
Prep: Cook: Serves:
Two hundred years after the symptoms of Parkinson’s were first identified, we talk to four world-renowned experts in Parkinson’s disease about how treatment of the condition has improved – and what the future will bring for people living with Parkinson’s
An essay that marked the beginning of Parkinson’s therapy Every story has a beginning and Parkinson’s disease is no different. Its story began 200 years ago, when an English surgeon, James Parkinson, made medical history with his simple but pioneering ‘Essay on the Shaking Palsy’, which described the symptoms of the disease for the first time.
Exponential growth in Parkinson’s research and therapies If Parkinson’s disease research progress were expressed in mathematical terms, it would resemble an exponential graph. At the beginning there seemed to be very little progress but over time a rapid increase in understanding of the mechanisms behind the disease emerged.
Professor Volkmann, a Parkinson’s expert from the University Clinic of Würzburg, Germany, explains how these leaps of understanding occurred: “After the initial description by James Parkinson, it took approximately another 100 years to completely understand the pathological lesions in the brain, then another 50 years for its biochemical base to be described, which led almost immediately to dopamine replacement therapy, one of the most effective treatments discovered.
“This neurotransmitter replacement paved the way for neurotransplantation, gene therapy and even brain pace making, known today as deep brain stimulation (DBS).”
Keeping the brain young and keeping disability at bay Professor Volkmann adds: “With DBS we now have a new concept which extends what we call the ‘honeymoon period’ – the time in which people with Parkinson’s are experiencing very little disability and can lead a normal life, with their job, family and daily activities – for as long as possible. As physicians this is one of our main goals.”
Research also shows the potential advantages of early treatment in keeping the brain younger for longer.
Professor Volkmann explains: “When a person is treated early, we see an effect on how the disease progresses, because if a person has good mobility and is living an almost normal and active life, it may have neuroprotective effects in the brain where impaired mobility and other symptoms of the disease are lessened. We have already seen the scientific evidence in animal models and the patients we see in our daily practice are living proof of it.”
Two paradigm shifts: resolving current challenges and opening up new frontiers in Parkinson’s research We’ve come a long way in treating Parkinson’s over the last two centuries, yet scientists are always challenging the status quo.
Professor Pollo from the University Hospital Bern, Switzerland, explains: “Parkinson’s is not only a motor disorder disease. The non-motor symptoms of Parkinson’s have been somewhat neglected in scientific research and development. With DBS, we are also exploring ways to improve cognition, depression, erectile dysfunction and other non-motor complications. We’re still in an experimental phase, but we see great potential in the technology which may have a huge impact in improving overall quality of life.”
Professor Lozano, a leading scientist from the University of Toronto, Canada, adds: “There are some features that respond very well to levodopa and/or to surgery, but other debilitating non-motor symptoms such as speech, cognitive disturbances, mood disorders, sexual problems and urinary dysfunction also need special attention.”
Parkinson’s disease belongs to the more developed conditions among neurodegenerative disorders in terms of our scientific understanding of its causes, progress and treatment.
DBS has been a proven option for the last 20 years. However, as Professor McIntyre from Case Western Reserve University School of Medicine, Cleveland, Ohio, US, reminds us: “DBS was pretty stagnant in the first 20 years of its clinical existence. The last three or four years, however, have brought new engineering developments in the devices with new electrode designs and new stimulation strategies. We are only starting to go down that road and it is exciting to think about how that technology is going to keep moving on.”
Professor Pollo explains that the introduction of directional steering – a new technology that allows for more precise stimulation in those targeted areas in the brain – brought about a paradigm shift.
“Before, the challenge in DBS was precision,” he says. “Without directional steering, stimulation could lead to stimulation-induced side effects. The advantage of the new steering technology is that it is more selective and much more precise, targeting only the areas we need to target and thereby avoiding side effects. This evolution of DBS technology addressed a major and unresolved challenge in Parkinson’s disease.”
The role of technology in the future of Parkinson’s care and individualised treatment An expert in biochemical engineering, Professor McIntyre offers his vision of future technologies in the treatment of Parkinson’s: “There are three main areas to watch for big improvements when it comes to DBS. The first one is in terms of hardware, where new developments in the design of the electrodes provide far more flexible and selective stimulation. Secondly, we see software improvements drive new clinical applications. These computational models are getting more real and detailed every year, making it easier to customise therapy to the needs of each individual patient, either by using imaging data or clinical outcomes data.
And lastly, wearable sensors and DBS. In the future these personal devices may feed information to the stimulation devices, allowing for the right therapy at the right time. This is something already being used in pain management with spinal cord stimulation.”
Parkinson’s disease at the forefront of neurodegenerative disorder research The scientific attention Parkinson’s disease has received over the past 200 years has been a door opener for research in other neurodegenerative disorders. As scientists garnered better understanding of the underlying mechanisms of the brain and technological systems such as DBS, they began to explore other areas where they could apply that learning.
Professor Lozano explains: “With our experience from Parkinson’s disease, we already have an understanding of the circuits of the brain that are malfunctioning, and so by using DBS we are able to modify their activity. We are now starting to look at diseases like Alzheimer’s and depression, for example, and how we can use the technology to benefit people affected by these diseases. The potential is huge and there’s an exciting scientific journey ahead of us.”
About deep brain stimulation (DBS) therapy
DBS uses a stimulator that is implanted into the patient’s chest. The stimulator sends mild electrical impulses to specific areas of the brain via thin wires called leads. This stimulation may help improve day-to-day experiences for people living with movement disorders such as Parkinson’s disease, dystonia, or essential tremor.
For comprehensive information on deep brain stimulation and Parkinson’s, please visit the EPDA website.
This article is sponsored by Boston Scientific. The information in this article is given for information purposes only and does not represent an endorsement by the EPDA of any particular treatments, products or companies. This article is not a substitute for advice from your doctor, pharmacist or other healthcare professional. Parkinson’s Life makes no representations or warranties of any kind, express or implied, about the completeness or accuracy of information provided.
Parki’s Kookatelier: fish soup ‘a la Bouillabaisse’
'A la Bouillabaisse': A tasty seafood dish
2 days ago
Wearable device for Parkinson’s disease raises $10m in funding
UK-based tech company Charco Neurotech has secured $10 million in seed investment funding to support the launch of a non-invasive wearable device designed for people with Parkinson’s disease. CUE1 is a circular device worn on the sternum, which is designed to help alleviate Parkinson’s symptoms through specialised vibrations that are personalised for each patient. The investment round, which was co-led by venture capital company Amadeus Capital Partners and growth fund managers Parkwalk Advisors, is the largest European seed financing in 2021 for a heath technology device – and the sixth largest globally. Lucy Jung, co-founder and CEO of Charco Neurotech, said: “This funding will enable us to proceed with our first, limited launch, while we work to ensure our manufacturing line is robust and produces consistent high quality devices.” Charco also recently announced a new partnership with the European Parkinson’s Disease Association (EPDA), to help increase the availability of Charco’s…
An international team led by the University of Ottawa in Canada will study whether the scent-processing nerves inside the nose may play a part in the development of Parkinson’s disease. The researchers will explore potential connections between inflammation, environmental exposures in the nasal cavity, odour processing centres in the brain and Parkinson’s-related genes. The scientists hope that if the study indicates that Parkinson’s starts in the nose, early signs of the condition could potentially be detected sooner. This research, which will use human and animal models, has been made possible by a US $9m grant from the Aligning Science Across Parkinson’s (ASAP) initiative, which aims to improve understanding of the causes of the condition. “This grant will allow us to explore an understudied but important aspect of Parkinson’s, which could lead to new approaches for early treatment and prevention,” said Professor Michael Schlossmacher, team leader of the study.
Study finds gene therapy may restore effects of Parkinson’s drug
Levodopa is a drug commonly used to treat Parkinson’s as it helps to increase dopamine levels in the brain and improve problems with movement. In later stages of the condition, however, this treatment can become less effective. Now, findings from a US preclinical study have suggested that a new gene therapy may help to restore the effects of levodopa in people with the condition. The researchers used mice models of Parkinson’s to test the effects of the gene therapy, targeting a small region in the brain where dopamine-releasing neurons are present. They found that the therapy increased the neurons’ ability to convert levodopa to dopamine – and discovered that damage to the mitochondria in dopamine-releasing neurons may be enough to trigger Parkinson’s onset. The scientists hope their findings will encourage the development of therapies to preserve the function of these neurons, and support patients in the later stages of Parkinson’s.


What if you had princess powers that would allow you to sing on key, talk to animals or, um, feel a pea through 20 mattresses. Oh, all right, some of those old stories leave a little something to be desired in the "powers" department.
But in "Mega Princess," the new all-ages comic from BOOM! Studios' KaBOOM! imprint, Princess Maxine is imbued with the abilities of every princess on her 10th birthday -- even though what she really wants is to be a detective.
In the series, by "Hawkeye" writer Kelly Thompson and artist Brianne Drouhard Maxine is just as underwhelmed about her new powers as anyone would be. However, she puts them to use when her brother, Prince Robert VI, goes missing.
"Mega Princess" was revealed as part of BOOM! Studios' run-up to Comic-Con International. Previous announcements include Steve Orlando's fantasy family drama "Namesake" and Greg Pak's self-explanatory "Big Trouble in Little China/Escape from New York" crossover.
"Mega Princess" will debut in November.


Millicable Flex deleted
Nexans reviews its product range fort heating cables
2012-09-17 – The Millicable Flex cable will be available only in the floor heating mat, Millimat/100.
Millicable Flex, E-number 89 560 56-82, will be replaced with TXLP NORDIC or with Millimat/100.
With energy at the basis of its development, Nexans, worldwide expert in the cable industry, offers an extensive range of cables and cabling solutions. The Group is a global player in the energy transmission and distribution, industry and building markets. Nexans addresses a wide series of market segments: from energy and telecom networks to energy resources (wind turbines, photovoltaic, oil and gas or mining…) to transportation (shipbuilding, aerospace, automotive and automation, railways...). Nexans is a responsible industrial company that regards sustainable development as integral to its global and operational strategy. Continuous innovation in products, solutions and services, employee development and commitment, customer orientation and the introduction of safe industrial processes with limited environmental impact are among the key initiatives that place Nexans at the core of a sustainable future. With an industrial presence in 40 countries and commercial activities worldwide, Nexans employs 25,000 people and had sales in 2011 of 7 billion euros. Nexans is listed on NYSE Euronext Paris, compartment A. For more information, please consult: www.nexans.com or www.nexans.mobi