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Purpose The Children’s Oncology Group (COG) renal tumor study (AREN03B2) requires real-time central review of radiology pathology and the surgical procedure to determine appropriate risk-based therapy. using the Fleiss’ Kappa statistic two-sided hypothesis assessments (Kappa p-value). Results Local tumor stage correlated in all 3 reviews except in one case (Kappa = 0.9775 p < 0.001). Similarly overall disease stage had excellent correlation (0.9422 p < 0.001). There was strong correlation for type of renal procedure (0.8357 p < 0.001) presence of tumor rupture (0.6858 p < 0.001) intraoperative tumor spill (0.6493 p < 0.001) and blood vessel involvement (0.6470 p < 0.001). Variables that had lower correlation were determination of the presence of peritoneal implants (0.2753 p < 0.001) and interpretation of residual disease status (0.5310 p < 0.001). Conclusion The inter-rater reliability of the surgical review is usually high based on the great consistency in the 3 indie review outcomes. This evaluation provides validation and establishes precedent for real-time central operative review to find out treatment project within a risk-based stratagem for multimodal cancers therapy. Birinapant (TL32711) Keywords: Wilms Tumor Quality guarantee Surgery Final results Multi-modality treatment for a child with Wilms Tumor (WT) is based on risk classification which includes age tumor excess weight histology stage and molecular characteristics . This requires interpretation of surgical radiological pathological and oncological Birinapant (TL32711) data. Staging for WT is usually complicated as both local and disease groups must be established. Briefly Stage I tumors are completely excised. Tumor was not ruptured or biopsied prior to removal blood vessels of the renal sinus are not involved. Note: for any tumor to qualify for certain therapeutic protocols as stage I lymph nodes must be examined microscopically and unfavorable for disease. Stage II tumors penetrated the renal capsule but were completely excised. Tumors that lengthen beyond the kidney as evidenced by: penetration of the renal capsule or considerable invasion of the renal sinus; blood vessels within the nephrectomy specimen outside the renal parenchyma including those of the renal sinus contain tumor. Notice: rupture or spillage confined to the flank including biopsy is no longer considered stage II and is now considered stage III. Residual non-hematogenous tumor present following surgery and Birinapant (TL32711) confined to the stomach is considered stage III. Additional Birinapant (TL32711) stage III criteria include: positive regional lymph node metastases penetration to the peritoneal surface or implants gross or microscopic tumor remains postoperatively local infiltration into essential buildings tumor spillage before or during medical procedures the tumor is certainly treated with preoperative chemotherapy before therapy regardless of type of biopsy tumor is usually removed in greater than one piece (e.g. tumor thrombus in renal vein removed separately from nephrectomy specimen. Stage IV is usually hematogenous metastases (lung liver etc) or lymph nodes outside the stomach. Stage V is usually bilateral renal involvement . Prior research has shown a high discordance and protocol violation rates when staging was carried out by an individual institution compared to a central group of Birinapant (TL32711) experts [2 3 Misclassification is likely to adversely impact delivery of appropriate therapy. Under staging a child can result in less therapy and an increased risk of recurrence. Conversely over staging can result in treatment of increased intensity with an unnecessary higher risk of both short and long-term toxicity. Quality assurance (QA) is essential to maintain data reliability validity and integrity and is mandated by the National Cancer Institute for any clinical trial . Most of the QA evaluate has been performed retrospectively. However since 2006 treatment on any therapeutic Children’s Oncology Group (COG) renal tumor protocol has required enrollment in the Renal Birinapant Rabbit Polyclonal to Synaptotagmin (phospho-Thr202). (TL32711) Tumor Classification Biology and Banking Study (AREN03B2) . Risk assignment is determined by real-time central review of clinical and molecular factors of known predictive value. Central reviewers add a united group of surgeons pathologists radiologists and oncologists. By executing the central review in real-time (data are shipped and assimilated instantly as collected time zero may be the time of medical procedure) every individual kid is normally assured the very best risk project before the initiation of therapy. The radiological operative and pathology testimonials.
Background Little is known about the result of methylphenidate (MPH) in interest in Alzheimer’s disease (Advertisement). and apathy using the Apathy Evaluation Size GSK-3787 (AES). A blended results linear regression approximated the difference in differ from baseline between treatment groupings thought as δ [MPH (DS week 6-DS baseline)] – [placebo (DS week 6-DS baseline)]. LEADS TO 60 sufferers (37 females age group=76±8 Mini-Mental Condition Test [MMSE]=20±5 NPI Apathy=7±2) the modification in DS forwards (δ=0.87 (95% CI: 0.06-1.68) p=0.03) and GSK-3787 DS total (δ=1.01 (95% CI: 0.09-1.93) p=0.03) favoured MPH more than placebo. Of 57 completers 17 sufferers got improved apathy (≥3.3 points in the AES from baseline to get rid of point) and 40 didn’t. There have been no significant organizations between AES and NPI Apathy with DS modification ratings in the MPH placebo AES responder or nonresponder groupings. DS ratings didn’t predict response to MPH treatment apathy. Bottom line These total outcomes suggest MPH may improve interest and apathy in Advertisement; the consequences appear independent within this population however. ClinicalTrials.gov Identifier NCT01117181 (2008) discovered that increased inattention carrying out a one dosage of dextro-amphetamine predicted better improvements in apathy (ρ = ?0.69 p = 0.02) in Advertisement patients getting treated with methylphenidate. The writers proposed that insufficient attention could be a predictor of treatment response to MPH which is certainly in keeping with books in normal handles suggesting that Rabbit Polyclonal to OR10A4. the consequences of MPH vary based on baseline dopamine amounts (Cools (2008) didn’t assess interest as an outcome. While interest is a definite cognitive area it might be connected with apathy also. Links between apathy and interest are rational due to the fact DAergic neurons make projections to interest networks in the mind and attention-associated areas present decreased activity in apathetic sufferers (Lanct?t et GSK-3787 al. 2007 Inspiration identified as among the crucial deficits in apathy is certainly regarded as closely connected with attentional elements in reward handling (Ivanov et al. 2012 Nieoullon and Coquerel 2003 Despite a theoretical common neurobiology small is well known about the partnership between apathy and interest in AD. A recently available randomized placebo-controlled trial (ADMET) recommended that MPH was well tolerated and got results on apathy using a craze for boosts in global cognition (Rosenberg et al. 2013 Within this supplementary analysis we looked into the result of MPH on interest in sufferers with apathy aswell as the partnership between interest and apathy adjustments following MPH treatment. Strategies Study Sample Sufferers signed up for ADMET (Rosenberg et al.) in Sunnybrook Wellness Sciences Center Johns Hopkins College or university as well as the Medical College or university of SC had been found in this pre-planned supplementary analysis. All scholarly research sites received acceptance off their specific analysis ethics panel. ADMET was a stage II GSK-3787 randomized double-blind placebo-controlled research investigating the protection and efficiency of MPH (10mg PO double daily) versus placebo for 6 weeks GSK-3787 for the treating apathy in Advertisement patients. Patients had been recruited from outpatient treatment centers assisted living services associated with the treatment centers referrals from regional doctors and advertisements in regional media. Procedures The analysis methods have already been referred to somewhere else (Drye et al. 2013 Informed consent was supplied by research individuals or a legitimately authorized representative prior to the start of trial. Eligible sufferers with mild-to-moderate Advertisement (Mini-Mental Status Evaluation MMSE 10-26 inclusive) and medically significant apathy (Neuropsychiatric Inventory NPI Apathy ≥ 4) had been randomized using a 1:1 project proportion to either MPH or placebo for 6 weeks. ADMET allowed usage of steady dosages of cognitive enhancers selective-serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors aswell as trazodone for rest however not treatment with various other psychotropic medications. Research medications (either MPH or placebo) had been initiated at 5 mg PO double daily for 3 times. This was elevated to the mark dosage of 10 mg PO double daily (total of 20 mg each day) for the rest from the trial. Assessments had been performed every 14 days (baseline week 2 week 4 and week 6). Sufferers finished the Wechsler Adult Cleverness.
The (pro)renin receptor ((P)RR) is expressed in a number of tissues including kidney heart and human brain and is considered to regulate the tissue renin-angiotensin program (RAS) through the non-proteolytic activation of prorenin. within a prior research.24 power analysis with all this worth suggested that at least 98 sufferers must determine the correlation using a power of 80% between serum s(P)RR and eGFR inside our sufferers. Multiple regression analyses had been used to recognize feasible determinants. Non-paired Student’s =56) and feminine (19.2 ± 5.2 =66) individuals or between individuals without medication (19.0 ± 4.6 =52) AVL-292 benzenesulfonate and the ones with treated with calcium mineral route blocker (17.8 ± 4.3 =70). In normotensive topics the common serum s(P)RR amounts had been 20.3 ± 4.0 ng ml?1 and these beliefs weren’t different weighed against those of necessary hypertensive sufferers significantly. There have been no factor between guys (20.1 ± 2.1 ng ml?1 =12) and women (20.4 ± 4.2 ng ml?1 =20) in the values of serum (P)RR. Interactions between background elements and RAS elements In sufferers with EH age group was significantly favorably correlated with the serum degree of s(P)RR (Desk 2 and Body 1a) but had not been considerably correlated with serum prorenin amounts (=0.113 =0.291). Age group was significantly adversely correlated with PRA (= ?0.298 = ?0.332 = ?0.051 =0.611) PRA (= ?0.072 =0.902) or PAC (=0.133 =0.432). Body 3 Scattergrams displaying romantic relationship between approximated glomerular filtration price (eGFR) and serum soluble (pro)renin receptor (s(P)RR) level. Open up circles sufferers with important hypertension; closed circles normotensive subjects. It is well known that age BP and glucose metabolism affect renal function. AVL-292 benzenesulfonate To determine if the relationship between eGFR and serum s(P)RR levels is independent of these factors multiple regression analysis testing age systolic BP HbA1c and serum s(P)RR levels as independent variables was performed. Serum s(P)RR levels in addition to age were negatively correlated with eGFR (Table 3). Table 3 Multiple regression analysis with eGFR There was a significant positive relationship between eGFR and serum s(P)RR levels in normotensive subjects as well (= ?0.576 =22 =0.419 power analyses revealed that the power (1-β) was high enough for age (0.802) and eGFR (0.970) but not for HDL-cholesterol (0.792) triglyceride (0.598) or CAVI (0.688). ARF6 Large-scale studies are needed to clarify the mechanisms underlying the role of serum s(P)RR levels in hypertension. AVL-292 benzenesulfonate Third our findings are basically based on the relationships between serum s(P)RR levels and background factors. Longitudinal studies may reveal the impacts of serum s(P)RR levels on the progression of organ damages AVL-292 benzenesulfonate and prognosis of the patients. CONCLUSIONS In conclusion there is a AVL-292 benzenesulfonate significant relationship between serum s(P)RR levels in patients with EH and renal function that is independent of age BP and glucose metabolism. An increase in the intrarenal RAS status is thought to underlie the progression of kidney damage. Serum s(P)RR could therefore serve as a useful biomarker reflecting the tissue RAS status in clinical settings. Furthermore there may be associations between age or lipid metabolism dysfunction and serum s(P)RR levels. Future studies including investigations to determine the source of serum s(P)RR in various pathological conditions are needed for serum s(P)RR to be validated a useful biomarker for tissue RAS. Footnotes CONFLICT OF INTEREST The authors declare no conflict of.
Cardiovascular diseases remain the best factors behind mortality and morbidity in the formulated world. induced pluripotent stem cell produced cardiac cells. Once we continue steadily to make improvement in induced pluripotent stem cell and cardiac differentiation technology we can be closer to software of cardiac regenerative medication. transiently contaminated mouse hepatocytes with adenoviruses expressing the four elements c-Myc Klf4 Oct4 and Sox2 and acquired iPSCs with low effectiveness (0.0001% to 0.001%)9. This technique takes Mouse monoclonal to ENO2 benefit of the unlikelihood of adenoviruses to integrate in to the sponsor genome and writers record that their iPSCs maintained pluripotency actually after viral APR-246 vectors have already been diluted to undetectable amounts in the cells9. Plasmid vectors could possibly be utilized to create transgene-free iPSCs alternatively. Researchers describe an episomal-based technique concerning oriP/EBNA1 plasmid vectors produced from Epstein-Barr pathogen10. The episomal vectors indicated many mixtures of reprogramming elements to induce iPSC APR-246 era in human being foreskin fibroblasts. Writers demonstrated through PCR that plasmid vectors didn’t integrate in to the sponsor genome also demonstrating through RT-PCR that iPSC lines didn’t communicate the transgenes10. Another group reported improved reprogramming effectiveness (~0.005%) in human adipose stem cells utilizing a minicircle vector expressing an individual reprogramming cassette containing OCT4 SOX2 LIN28 and NANOG. Writers obtained human being iPSC colonies by times 14-16 and Southern blot verified insufficient genomic integration from the minicircle vector in choose colonies11. Desk 1 Breakthroughs in iPSC era technology Other ways of generate transgene-free iPSCs involve transient manifestation of reprogramming elements accompanied by faithful removal (excision) APR-246 APR-246 from the transgenes. One particular method employs Cre/loxP excision technology. reported utilizing a solitary built lentiviral “stem cell cassette (STEMCCA)” vector expressing the four reprogramming genes (Oct4 Klf4 Sox2 and c-Myc) flanked by loxP sites to induce pluripotency in mouse tail-tip fibroblasts12. The writers chosen clones with an individual integration of STEMCCA using Southern blot after that utilized an adenoviral vector to transiently express Cre-recombinase in these clones to excise the STEMCCA eventually confirming 96% excision effectiveness as confirmed by genomic PCR. Writers even record improved differentiation potential (both and created a transgene-free strategy for producing iPSCs utilizing a vector predicated on the Sendai pathogen a non-integrating RNA pathogen14. Producing iPSCs utilizing the non-integrating Sendai pathogen vectors is actually a even more useful and safer option for reprogramming15 16 The Sendai pathogen approach in addition has been used to create iPSCs from circulating T cells gathered from the peripheral blood which could serve as an even more clinically relevant approach for practically generating patient-specific iPSCs15. Researchers have also developed protein-based transgene free methods to create iPSCs. used to express recombinant forms of the four reprogramming proteins (Oct4 Sox2 Klf4 c-Myc) each with a poly-arginine (11R) domain name at the C terminus17. Proponents of protein-based reprogramming methods state that the lack of genetic manipulation and DNA transfection potentially enhances the safety of iPSCs for use in regenerative therapy17. New and latest function in iPSCs strives to create them with high performance to provide the large numbers of cells necessary for cell-based regenerative therapy. devised some mRNA adjustments including treatment with phosphatase and substitution with changed nucelobases to diminish web host interferon signaling to be able to reduce the web host cell’s immune system response to international mRNA18. Writers created man made mRNA for Oct4 Sox2 Klf4 LIN28 and c-Myc with adjustments using transcription. The customized mRNAs from the reprogramming elements were repeatedly sent to many individual somatic cell types and iPSC colonies made an appearance as soon as two weeks. Like this authors report a higher induction performance of 4.4% in low-oxygen.
Common quorum-sensing (QS) enables bacteria to communicate and takes on a critical part Gefitinib (Iressa) in controlling bacterial virulence. state transitions and host-circuit relationships. A mathematical model that integrates the circuit��s nonlinearity stochasticity and host-circuit relationships was developed and its predictions of conditions for trimodality were verified experimentally. Combining synthetic biology and mathematical modeling this work sheds light within the complex behaviors growing from QS crosstalk which could become exploited for therapeutics and biotechnology. Intro Quorum-sensing (QS) is really a widespread mechanism bacterias use to modify gene appearance and coordinate inhabitants behavior predicated on regional cell thickness (Ng and Bassler 2009 It really is achieved with the binding of QS regulators making use of their cognate indication molecules (autoinducers) to modify Gefitinib (Iressa) downstream QS pathways. Autoinducers are produced in the diffuse and cell into and away from bacterial cells. As a result an autoinducer��s intracellular focus correlates with regional cell thickness (Ng and Bassler 2009 You can find diverse QS systems enabling bacterial conversation: gram-positive bacterias generally make use of two-component systems mediated by peptides while gram-negative bacterias primarily make use of LuxR/LuxI-type systems mediated by acylated homoserine lactones (AHL) (Miller and Bassler 2001 Ng and Bassler 2009 Many bacterial actions are managed or governed by QS such as for Gefitinib (Iressa) example antibiotic creation biofilm advancement bioluminescence colonization sporulation symbiosis and virulence (Jayaraman and Timber 2008 LaSarre and Federle 2013 Miller and Bassler 2001 Ng and Bassler 2009 Solano et al. 2014 With well-defined and characterized natural properties many QS regulators and matching autoinducers are also used for artificial gene networks. For instance LuxR/LuxI and/or LasR/LasI pairs had been used to create designed patterns (Basu et al. 2005 Payne et al. 2013 cause biofilm development (Hong et al. 2012 Kobayashi et al. 2004 develop artificial ecosystems and plan inhabitants dynamics (Balagadde et al. 2008 Brenner et al. 2007 and build synchronized oscillators (Danino et al. 2010 Prindle et al. 2012 advantage detectors (Tabor et al. 2009 and pulse generators (Basu et al. 2004 RhlR/RhlI in addition has been found in the analysis of generic systems of organic selection (Chuang et al. 2009 Gefitinib (Iressa) in addition to for carrying away natural computations as chemical substance ��cables�� (Tamsir et al. 2011 Nevertheless ramifications of QS crosstalk useful connections between QS elements that aren’t normally Ctnnd1 paired stay unexplored. For instance trusted LuxR-family regulators talk about comprehensive homologies and structural commonalities within their corresponding autoinducers. LuxR binds its organic ligand 3-oxo-C6-HSL (3OC6HSL hereafter denoted as C6) to Gefitinib (Iressa) activate the pLux promoter while LasR bind 3-oxo-C12-HSL (3OC12HSL hereafter denoted as C12) to activate pLas (Desk S1) Gefitinib (Iressa) (Fuqua et al. 1996 Meighen 1994 Bassler and Miller 2001 Ng and Bassler 2009 Schuster et al. 2004 Stevens and Greenberg 1997 Nevertheless the LuxR proteins may also bind various other HSLs such as for example C7HSL and 3OC8HSL (Canton et al. 2008 When binding C12 LasR can activate pLux as well as the normally matched pLas promoter (Balagadde et al. 2008 Implications of such crosstalk on gene cell and regulation response remain largely unknown. Here we make use of rationally designed gene systems to probe crosstalk between your LuxR/I and LasR/I systems and investigate their elicited bistable behaviors from positive reviews topologies. With a artificial biology strategy all combinations of autoinducer regulator and promoter had been tested showing that QS crosstalk could be dissected into indication crosstalk and promoter crosstalk. When examined in the framework of a man made positive reviews gene network our outcomes indicate that QS crosstalk results in distinct dynamic manners: indication crosstalk significantly lowers the circuit��s induction range for bistability but promoter crosstalk causes transposon insertions in to the regulator gene and produces trimodal responses because of a combined mix of mutagenesis and sound induced condition transitions. To totally understand why complicated response we created and experimentally confirmed a numerical model that considers many of these elements to simulate and anticipate.
Disruption of NOTCH1 signaling was recently discovered in head and neck tumor. in OSCC indicating an important part of these clonal events in the progression of early neoplasms. We then compared all known mutations recognized in Chinese OSCC individuals with those reported in Caucasians to date. Although we found obvious overlaps in essential regulatory domains alterations and recognized specific mutations shared by both organizations possible gain-of-function mutations were predominantly seen in Chinese human population. Our findings demonstrate that pre-malignant lesions display mutations at an early stage and are therefore drivers of OSCC progression. Moreover our results reveal that NOTCH1 promotes unique tumorigenic mechanisms in individuals from different ethnical populations. and (13-15). is particularly noteworthy. In Caucasians potentially inactivating mutations occurred in 11%-15% of tumors and as such is the second most frequently mutated gene in HNSCC after (13-15). Recently Song et al. showed that in Chinese OSCC individuals Rabbit Polyclonal to ME3. the mutation rate of recurrence was greater than 40% and strongly associated with poor prognosis and shorter survival (16). While these data show that disruption of NOTCH1 signaling is definitely involved in oral tumorigenesis of both Asian/Chinese and Caucasian populations this study was performed with standard PCR to by hand amplify through hundreds of individual reactions and the part of NOTCH1 in malignant transformation of oral leukoplakia was not addressed. Using fresh enrichment technology and NGS we assessed mutation-status at different phases of OSCC progression in Chinese individuals. The mutation rate of recurrence was 54% for OSCC and 60% for pre-neoplastic lesions. Importantly most leukoplakia individuals with mutated carried mutations that were also recognized in OSCC indicating an important part of these events in the progression of early neoplasms. Moreover we compared all known mutations in Chinese OSCC individuals with those reported in Caucasians to date. Although we found obvious overlaps in essential regulatory domains alterations and recognized mutations shared by both cohorts possible gain-of-function mutations were predominantly seen in the Asian human population. Materials and Methods Samples 144 cells samples were collected in the Ninth People’s Hospital Shanghai China. 49 samples were normal oral mucosa from individuals undergoing oral surgery treatment and 45 displayed oral leukoplakia biopsies. Fifty OSCC samples were acquired during resection. Among them 22 paired normal tissues were gained from your adjacent areas at least 1cm away from cancer. Samples were promptly freezing at ?80��C TTP-22 after initial pathological exam. Frozen tissue were cut into 5��m sections stained with H&E and examined by light microscopy. Lesions with a low neoplastic cellularity (<70%) were additionally microdissected to remove contaminating normal cells before DNA extraction. OSCC individuals had not been treated with chemotherapy or radiation before their tumor biopsy so the spectrum of changes we observed mainly displays those of tumors in their naturally occurring state. The histopathological analysis was made by pathologist on duty according TTP-22 to World Health Organization criteria (17) (18). Clinical characteristics are demonstrated in Supp. Table 1 2 3 and 4. This study was authorized by the Human being Study Ethics Committee of Shanghai Jiaotong University or college and the Administration Office of the Chinese Human Genetic Resources. Informed written consent was from all individuals before sampling. DNA isolation Genomic DNA was isolated from new frozen samples by QIAamp DNA kit (Qiagen) and quantified with Nanodrop system (Thermo Scientific). Notch1 amplification 108 primers pairs were designed by Fluidigm (San Francisco USA) to protect all 34 exons of the and exon-intron boundaries (Supp. Table 5). PCR amplification was performed using a Fluidigm Access-Array microfluidic TTP-22 chip according to the manufacturer’s instructions. Each sample was combined with primer pairs inside a microfluidic chip and thermal cycling on a Fluidigm FC1 Cycler was performed. PCR products were then collected using the IFC TTP-22 controller and transferred to a 96-well plate. In a separate PCR Illumina sequence-specific adaptors and barcodes were attached. Sequencing Pooled and indexed PCR products were sequenced within the Illumina MiSeq instrument following standard protocols with the following modifications: Illumina-specific sequencing primers were substituted with a mixture of two Fluidigm-specific primers pairs (FL1 and FL2). The.
Control of just one 1 2 and 1 4 of substituted phenols to allylic oxides is attained by intercepting palladium π-allyl complexes. liberates the stereogenic hydroxyl and is key to carbasugar planning via AORR (vide infra; Structure 2). Structure 2 AORR kinetic and thermodynamic palladium allyl distribution and ensuing diastereomers. Desk 1 Regiochemical control of enantioinduction. Just like Trost’s stereoinduction of allylic acetates and carbonates 2 the C2-symmetric ligand blocks among the two sites from the π-allyl diverting each oxide to another constitutional isomer of just one Amlodipine besylate 1 2 or 1 4 The suggested model suits the noticed enantioenriched oxide data and a predictive basis for fresh studies of complicated allylic oxides altogether synthesis.10 When oxide (+)-1 can be used the π-allyl from the ester is generated inside the complex leading to attack in Amlodipine besylate the pro- (ligand predicts a 1 2 with a rise to 99:1 er and a loss of the 1 4 product to 67:33. The noticed 1 2 item fits a 98:2 er having a 1 4 item er of 68:32. The (?)-oxide (90:10 er) using the ligand predicts a 1:99 er of just one 1 4 items and a 40:60 er for the 1 2 The noticed 1 4 is at error in 4:96 as well as the 24:76 from the 1 2 is definitely fair. The predictive model was after that put on carbasugar frameworks that include additional functionality inside the cyclohexenoate. Applying the AORR solution to common synthon 812 was expected to offer syn-1 2 (11) and syn-1 4 (12) items from the kinetic palladium π-allyl complicated 10 (Structure 2). The steric needs from the substituted dioxolane may destabilize kinetic π-allyl complicated 9 leading to conversion towards the thermodynamic π-allyl complicated 13 via an exogenous Pd0 complicated as noticed by B?ckvall.13 Addition from the nucleophile to Amlodipine besylate complicated 14 leads to two forms: anti-1 2 (15) and anti-1 4 (16). Earlier attempts by Hudlicky and co-workers14 established that anti-1 2 of malonates to acetonide allylic oxides can be done but happens in low produces or as mixtures of diastereomers. Common synthon 8 will be demonstrative from the kinetic to thermodynamic isomerization and would offer usage of four classes of carbasugars. We found that three from the four feasible regioisomers were shaped from synthon 8 using the response proceeding to complete conversion (Structure 3a). Anti-1 2 item 19 was isolated in 13% produce (93:7 er) and syn-1 4 item 20 in 12% produce (88:12 er). The high stereoselectivity albeit with low produce for every isomer reflects the excess constraints the dioxolane imposes for the palladium π-allyl program. The syn-1 2 item (21) was isolated in 24% produce (91:9 er) using the anti-1 4 item (22) undetected. The improved yield from the syn-1 2 item (21) was anticipated provided the sterically encumbered anti-1 4 setting under these circumstances. The regioisomeric products were carried forward to three natural basic products then. Structure 3 Applying the AORR strategy for the full total NT5E synthesis of streptol cyathiformine B type MK7607 and a fresh cyclitol. The anti-1 2 item (19) comprises the stereoarray of streptol (23) a powerful plant development inhibitor.15 The conversion to streptol 23 was attained by reducing the ester and safeguarding the transient acyl accompanied by cerium ammonium nitrate (CAN) oxidative cleavage from the anisole. Removing the dioxolane using acetyl chloride and catalytic zinc chloride accompanied by global Amlodipine besylate acyl cleavage demonstrated uneventful. The syn-1 4 item (22) fits the uncommon fungal metabolite cyathiformine B (25) a chorismic acidity derivative.16 The cyathiformine framework poses potential complications because of its sensitive enol pyruvate that could complicate the oxidative cleavage from the anisole and Lewis-acid mediated dioxolane removal. Proceeding ahead installing the diazophosphonate using rhodium acetate was accompanied by May oxidation with remarkably small degradation. Horner-Wadsworth-Emmons olefination using gaseous formaldehyde offered cyathiformine B type 24. The dioxolane demonstrated difficult to eliminate with varying degrees of achievement (not demonstrated). The syn-1 2 item (21) mapped to MK760717 (25) and was targeted following. Following a identical method of streptol we ready MK7607 in five measures. The lacking isomer anti-1 4 (22) had not been seen in the regio-resolution of oxide 8. To handle all feasible additions towards the allylic oxide we.
Background Exhaustion is a multidimensional build which has significant implications for physical function in chronic non-cancer discomfort populations but remains relatively understudied. and accounted for the entirety of the initial statistical romantic relationship between sleep disruption and both physical function and pain-related disturbance. Conclusions Fatigue can be a complex create with human relationships to both physical and mental factors which has significant implications for physical working in chronic non-cancer discomfort. The current outcomes identify potential focuses on for potential treatment of exhaustion in chronic discomfort and may offer directions for potential medical and ABT theoretical study in the region of chronic non-cancer discomfort. Perspective Fatigue can be an essential physical and mental variable that elements prominently in the deleterious outcomes of discomfort intensity sleep disruption and melancholy for physical function in chronic non-cancer discomfort. route) as well as the mediator-outcome route (the road). However mainly because we could not really establish proof for the temporal purchasing of the factors inside our mediation model it really is more appropriate to hire the word “intervening adjustable” to spell it out the mediator in these versions following the suggestions of MacKinnon and co-workers.30 With this ABT caution at heart nevertheless the analytic approach will become known as mediation analyses henceforth. Evaluation email address details are reported using both standardized and unstandardized route coefficients. Addition of standardized route coefficient versions was deemed to become necessary to ABT be able to give a common dimension metric against that your size of every route could be likened. As Mplus will not offer significance ideals for standardized route coefficient models nevertheless we also opted to add unstandardized route coefficient models to be able to offer estimations of statistical significance for every examined route. As the analyzed models were almost recursive and would therefore yield only match indices recommending near-perfect match of the info we opted never to consist of these measures inside our manuscript. Discomfort intensity melancholy and sleep disruption scores had been freed to co-vary predicated on a theoretical probability of distributed variance between these factors. Covariates representing age group gender Rabbit Polyclonal to ELAV2/4. and discomfort diagnosis connected with preliminary clinic visits had been contained in the estimation of most pathways. As an exploratory stage variations in each route had been computed using Wald chi-square difference testing between each one of the 5 largest discomfort diagnosis groups inside our sample. This task was used purchase to articulate a number of the potential variations in interrelationships between research factors. Significant Wald chi-square difference ideals suggest a big change between two factors and are mentioned appropriately in the Outcomes section. As mentioned previously because of the chance for sex-based variations in our factors we have selected to record our study factors individually by gender (discover Desk 1). Desk 1 Regular and Means Deviations of Research Factors by Gender. Results Descriptive figures are available in Desk 1 and the full total percentage of variance of every outcome adjustable (exhaustion physical function and discomfort disturbance) accounted for by the entire model are available in Desk 2. Unstandardized route coefficients and ABT their connected significance ideals are reported in Shape 1 and standardized route coefficients had been reported for simple interpretation and representation from the comparative size of every statistical route reported in Shape 2. Our outcomes indicated that rankings of average discomfort intensity sleep disruption and depression got exclusive and statistically significant efforts to fatigue rankings over once period. Based on the standardized route coefficients in Shape 2 depression ratings demonstrated the biggest effect on exhaustion followed by the consequences of sleep disruption and discomfort intensity. Shape 1 Route model representing indirect ramifications of discomfort sleep disruption and melancholy on actions of discomfort disturbance and physical function through exhaustion with unstandardized route coefficients and significance ideals. Figure 2 Route model representing indirect ramifications of discomfort sleep disruption and melancholy on actions of discomfort disturbance and physical function through exhaustion with standardized route coefficients Desk 2 Quantity of Variance Accounted for in each Endogenous.
A way is described to generate and validate antibodies based on mapping the linear epitopes of a polyclonal antibody followed by sequential epitope-specific capture using synthetic peptides. a path forward to use the mapped binding sites of polyclonal antibodies to generate epitope-specific antibodies providing an attractive approach for large-scale efforts to characterize the human proteome by antibodies. = 15 0 of the human protein-encoding genes. The availability of well-validated antibodies provides a useful resource for functional studies of the corresponding proteins and facilitates the systematic identification of protein profiles including subcellular locations and tissue-specificity. Today more than 70% of the antibodies in FLJ34766 Antibodypedia and 80% of the antibodies in the Human Protein Atlas are polyclonal antibodies. These antibodies have the advantageous characteristic of being directed to several binding sites (epitopes) of the target proteins but this also means that binding to multiple epitopes can raise the threat of cross-specificity towards various other Mogroside IV protein. Furthermore polyclonal antibodies display limitations in relation to renewability because of the limited quantities obtained from one immunizations as well as the batch-to-batch variants Mogroside IV obtained when many immunizations are performed to create larger levels of antibodies.8 This stresses the necessity for the introduction of solo epitope-specific antibodies with defined binding sites of the mark proteins. This may be achieved using the era of monoclonal antibodies or recombinant affinity reagents but an alternative solution may be to utilize the multiple binding sites of polyclonal antibodies to create one or many epitope-specific antibodies instead of monoclonal antibodies. This way the currently existing thousands of polyclonal antibodies could possibly be used to make a precious reference of epitope-specific antibodies. Right here we explain such a technique predicated on epitope mapping using peptide bead arrays and affinity purification using artificial peptides. Four proteins implicated as potential biomarkers for several individual cancers including breasts colorectal lung and prostate cancers were selected as goals for the strategy. In all situations monospecific antibodies had been generated and eventually employed for the evaluation across many immunological systems including Traditional western blot immunohistochemistry immunofluorescence and sandwich immunoassays. Outcomes The concept for era of monospecific antibodies A strategy to generate epitope-specific antibodies predicated on sequential affinity purification of polyclonal sera continues to be developed as specified schematically in Amount 1. The linear epitopes from the polyclonal antibody depends upon overlapping synthetic peptides as pioneered already in 1987 Mogroside IV by Geysen synthesized peptides on planar microarrays for the mapping effort to limit the synthesis of individual peptides to the epitopes recognized by high-density peptide arrays. Recently we have acquired high-quality reproducible results from such an approach with synthetic peptides of the space 10-20 amino acids produced by photo-activated chemical substance synthesis on the microarray with an increase of than 100 0 Mogroside IV obtainable areas (Rockberg Schaffer and Uhlen unpublished). Additionally additionally it is possible to employ a bacterial screen method 20 where the epitopes are mapped using cell sorting and sequencing from the inserts of bacterial cells exhibiting various fragments from the antigen on the top. Together these procedures provide a effective toolbox for mapping the binding sites of Mogroside IV antibodies to allow the era of monospecific antibodies as defined in this specific article. It really is noteworthy that the technique described here offers a strategy to generate monoclonal antibodies within a organized manner predicated on the info generated by preceding evaluation from the functionality of the polyclonal antibody. Many monospecific antibodies produced from an individual polyclonal antibody could be examined in relevant application-specific assays and antibodies to the epitopes showing great efficiency across these assays can eventually be used being a business lead of peptide selection to create monoclonal antibodies. Right here the outcomes from the monospecific antibodies had been used to steer the era from the monoclonal antibodies towards individual RBM3. Synthetic peptides related to the epitopes shown to give practical monospecific antibodies were utilized for the immunization to generate hybridoma cells but on the other hand one could also use the unique antigen for the immunization and then use the peptide as.
The adhesion protein junctional adhesion molecule-A (JAM-A) regulates epithelial cell morphology and migration and its over-expression has recently been linked with increased risk of metastasis in breast cancer patients. we performed immunoprecipitations in MCF7 cells and primary breast cells to determine the binding partners connecting JAM-A to Rap1 activation. Results JAM-A knockdown in MCF7 breast cancer cells reduced adhesion to and migration through the β1-integrin substrate fibronectin. This was accompanied by reduced protein expression of β1-integrin and its binding partners αV- and α5-integrin. Rap1 activity was reduced in response to JAM-A knockdown or inhibition and pharmacological inhibition of Rap1 reduced MCF7 cell migration. No additive anti-migratory effect was observed in response to simultaneous inhibition of JAM-A Rap1 and β1-integrin suggesting that they lie in a linear migratory pathway. Finally in an attempt to elucidate the binding partners putatively linking JAM-A to Rap1 activation we have demonstrated the formation of a complex between JAM-A AF-6 and the Rap1 activator PDZ-GEF2 in MCF7 cells and in primary cultures from breast cancer patients. Conclusions Our findings AM 580 provide compelling evidence of a novel role for JAM-A in driving breast cancer cell migration via activation AM 580 of Rap1 GTPase and β1-integrin. We speculate that JAM-A over-expression in some breast cancer patients may represent a novel therapeutic target to reduce the likelihood of metastasis. Introduction Breast cancer accounts for approximately 30% of all female cancers AM 580 diagnosed in the European Union and is the leading cause of female cancer deaths. Over 85 0 women (many in their reproductive and economically productive years) succumbed to the disease in 2006 . Although there have been substantial improvements in breast cancer treatment targeted adjuvant therapies are restricted to treating those patients whose tumor cells express high levels of the few targetable breast cancer molecular markers namely the estrogen and HER2 (human epidermal growth factor receptor 2) receptors. It AM 580 is therefore clear that further improvements are needed in the molecular understanding diagnosis and treatment of breast cancer. Most breast cancers originate AM 580 in the epithelial cells lining breast ducts. Epithelial cell polarity in normal ducts is maintained via intercellular multiprotein adhesion complexes which facilitate adhesion and allow communication between neighboring cells. Loss of epithelial polarity and consequent disruptions in tissue architecture a hallmark of de-differentiation are early features of breast cancer and other malignancies . Emerging evidence points toward an important role for proteins of the intercellular tight junction (TJ) complex in mediating tumorigenesis. To date several TJ proteins have been shown to be dysregulated in breast carcinoma with claudins-3 and -4 highly upregulated Rabbit Polyclonal to ATF6B.  and claudin-7 downregulated in in situ and invasive ductal carcinomas . Furthermore loss of the TJ-associated protein ZO-1 (zona occludens-1) in breast cancer correlates with both poor prognosis  and increased expression of proteinases important for tumor invasion . Interestingly adhesion/polarity proteins have recently been shown to be targeted by oncogenes (such as ERBB2  and MYC ) resulting in the disruption of tissue organization often observed during cancer development. Together these studies provide strong evidence that adhesion proteins may act as key regulators of breast cancer initiation and progression. The junctional adhesion molecule (JAM) family of TJ proteins has important functions in numerous cellular adhesive processes including intercellular junction assembly and cell polarity  cell morphology  platelet activation  and leukocyte migration . Pathophysiologically JAM-A has been linked to..

domain: medical


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Good morning folks.
Another Tuesday morning, my aren't the days passing quickly, October nearly over!
Anyway it also means a new challenge over at Cardz4Guyz. This week I'm choosing the theme and I want to see your projects that feature -
So we want to see any project for a male that is to do with numbers, as simple as that!
It could be for a child's birthday, an older gent's birthday, anniversary or even Dec 25th.
Here is my card.
I made this as you can see for my OH's birthday. He's now into the next decade but still likes to play with his toys, hence the blue tractor!
I love this little tractor stamp from Molly Bloom, it appears that Clare Rowland has stopped designing her own stamps, as I've seen nothing new for over a year. :( .
Anyways this little chap on his tractor was stamped masked then coloured with Copics to match the new tractor that has been a godsend as the little grey Fergie is not up to it these days, it's older than the OH.
The 'new' one allows him to move soil and logs around more easily, he even bought a log splitter that goes on the back and works off the hydraulics, so no more log splitting by hand.
The '60' was outlined in pencil using a computer generated outline, on a square base card before cutting away the edges and middles, the raw edges were shaded with Copics to give a 3D effect then some Nitwits DP was stuck to the back to make a little meadow scene. The sentiment is from LOTV and I cut a sun freehand from a scalloped circle diecut before mounting the sentiment.
OK, that's about it for me, check out the rest of the DT's fab inspiration and why not join us this week. I would love to see what you come up with!
I'd like to join in over at:-
Bright or Pastels
I go for brights especially for birthday cards for men, they seem much more appropriate and I prefer them to the grungy male colours!
Anything Goes - option of a sketch (no sketch for me this week)

domain: design


text:
If you have teeth that are short, discolored, crooked or chipped, porcelain veneers restore flawless beauty to your smile. Veneers are wafer-thin shells that fit over the front surfaces of teeth to conceal irregularities and whiten teeth. They can also be used to reduce or eliminate gaps and “straighten” teeth. Veneers are handcrafted by our trusted dental laboratory to ensure you receive the most perfect-looking restoration. Practice good oral hygiene to prolong the life of your veneers, which should last a decade or longer.
Porcelain veneers can be completed in as little as two visits to our office, giving you a fabulous smile you desire. Drs. Campbell and Schmidt have been placing custom-made cosmetic veneers in the North Chicago suburbs for over 20 years, and they continue to attend cosmetic dentistry hands-on courses to improve their skills each year.
Cosmetic Dental Bonding
Teeth that are marred by chips, cracks, decay, and discoloration can be aesthetically improved with dental bonding. Dr. Campbell and Dr. Schmidt match the color of the bonding material to your surrounding teeth using a professional shade guide. A composite resin in this exact color is applied to the damaged area. Our dentists then expose the resin to a high-intensity light, which hardens it in position for durable wear. The resin will be shaped and polished, so the restored tooth looks and feels natural. Cosmetic bonding is ideal if you need to fix your tooth immediately, without the need for waiting on a dental lab. Patients sometimes choose cosmetic bonding as a permanent method teeth whitening since the composite can be chosen in a whiter shade, or selected to blend with your other teeth.
A brilliant smile can revitalize your face and dramatically improve your appearance. The in-office whitening technology featured at our practice far surpasses any home treatment currently available. While at-home treatments can temporarily and subtly lighten teeth, the Zoom!® in-office system whitens teeth by an average of eight shades in approximately one hour. For those patients with more extensive or deep-set staining, we may recommend dental bleaching using the KoR system. This system combines in-office whitening with continued take-home treatments to achieve the desired results. Both of our professional-grade whitening systems provide superior results compared to store-bought varieties.
Tooth whitening in Lake Forest is not only fast but safe and comfortable. It is the perfect choice for the busy individual who wants dramatic, predictable results. Teeth whitening products available in stores do not provide the same astonishing results and may end up being a waste of money. As we age, the natural white color of our teeth gradually fades, and teeth become darker, which makes teeth whitening a popular, yet affordable option to improve your smile. Zoom!® and KoR whitening restores the beautiful, bright color you are looking for. You may call our office to schedule a consultation to find out more.
The appearance of a “gummy” smile can be improved with the advanced laser dentistry techniques available at Lake Forest Smiles. With a laser, our dentists sculpt excessive and uneven gum tissue to create a more appealing smile line. At the beginning of the gum recontouring procedure, the patient’s gums are numbed with anesthetic, and they are then reshaped by an extremely safe, highly precise laser. The laser immediately seals the gum tissue for a faster, more comfortable recovery compared to traditional surgical methods. In most cases, patients resume their regular routine following their appointment as there is little to no downtime.
Blurring the line between cosmetic and restorative dental care, metal-free crowns, inlays, onlays, and other restorations from our office provide patients complete repair of damaged teeth in form, function, and cosmetic appearance. Crafted from tooth-colored ceramic, these restorations can be made in our office for same-day smile repair or by our trusted dental lab. The effective, durable restorations are ideal for front-facing teeth, patients who want a cosmetically superior treatment option, and for patients who have allergies or sensitivities to metal.
With the technology available at our office and the skill of our doctors, Lake Forest Smiles transforms any smile into a beautiful smile. By combining and customizing dental procedures, we are able to dramatically improve the appearance of teeth that are discolored, damaged, or misaligned. Whether you are looking for a quick fix that can be achieved in a single visit, or you decide to undergo orthodontics that may take a year or more to achieve fabulous results, Lake Forest Smiles has options that are suitable for every patient. Based on the type and extent of your tooth damage, Dr. Campbell and Dr. Schmidt create a smile makeover treatment plan tailored specifically to your dental needs.
Who Should Consider Cosmetic Dentistry?
Anyone who is unhappy with their smile should consider cosmetic dentistry. From quick teeth whitening to orthodontics, Lake Forest Smiles has a solution for every dental problem.
- Do you have crooked teeth?
- Are your teeth stained?
- Do you have misshapen teeth?
- Are your front teeth gapped?
- Do you have a broken or chipped tooth?
- Do you have missing teeth?
- Do you just wish that your teeth looked like a celebrity’s smile?
These are common reasons why patients choose cosmetic dentistry. Whether you are looking to fix one problem tooth or revamp your entire smile, we can help. No smile is out of reach! And, Drs. Campbell and Schmidt believe that you are never too old to achieve the smile of your dreams. It all starts with a consultation.
Schedule a Consultation
Deciding to undergo cosmetic dentistry is not an easy decision. From choosing the best cosmetic dentist in Lake Forest to figuring out how to afford your dental treatments, Drs. Campbell and Schmidt and their team of caring dental professionals strive to make it an easy process. If you are interested in learning more about cosmetic dentistry, schedule a consultation to find out which procedures are best for you. We employ sophisticated technology to make your experience simple yet achieves beautiful results.
If you are a new patient, we begin your consultation by assessing your oral health because it is essential to address any underlying dental problems before investing in cosmetic dentistry. Digital x-rays may also be needed so that we can capture the health of your jawbone and tooth roots. During this visit, we encourage you to be open and honest about how your smile makes you feel so that we can present options to help you achieve the best results. Let us know if you have any specific timelines, like a special event that is quickly approaching, as this may play a part in choosing your options.
Affordable Cosmetic Dentistry
Many patients assume that cosmetic dentistry is unaffordable. While it does come at a price, the cost is well worth it in the end. The best way to know how much dental treatments will cost is to schedule a consultation with Lake Forest Smiles. Once your treatment plan has been determined, we will discuss the price of each procedure. Our payment options include cash, check, and major credit cards, as well as special financing through these trusted third-parties, CareCredit, and Springstone Financing. In some cases, interest-free financing is available. Lake Forest Smiles wants every patient to be able to achieve the smile that they desire, which is why we also offer in-house financing. To learn more about our payment or financing options, please contact our office.
What Happens After My Treatment?
Cosmetic dentistry is an investment, and like anything else you spend your hard-earned money on, you want to take care of it so that it will last. Your teeth are no different. Good oral hygiene and regular dental visits twice a year are an essential part of maintaining your new, gorgeous smile. To keep your cosmetic dental work looking good for the long haul, be sure to take care of your teeth every day. Follow-up appointments and instructions will be provided during each step of the process.
If you would like to learn more about cosmetic dentistry, and find out which options are best for you, schedule a consultation with Lake Forest Smiles by calling (847) 234-4800. Worried about going to the dentist because of dental anxiety? Ask us about sedation dentistry options, ideal for lengthy appointments, or for people who have a fear of going to the dentist. Lake Forest Smiles has been providing elite dental care to the communities of Lake Forest, Lake Bluff, and Lincolnshire for more than 30 years. We welcome you to our practice.


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Batman & Mr. Freeze, subzero ; Batman beyond : the movie.
- 1 of 1 copy available at Bethlehem Area Public Library System.
- 1 of 2 copies available at Lehigh Valley Library System. (Show)
0 current holds with 2 total copies.
|Location||Call Number / Copy Notes||Barcode||Shelving Location||Status||Due Date|
|Bethlehem Main Library||JDVD (Text)||33062009257560||New Juv DVD Fiction||Available||-|
- Physical Description: 1 videodisc (300 min.) : sound, color ; 4 3/4 in.
- Publisher: [Burbank, CA] : Warner Home Video,
Title from web page.
Battle battles his biggest foes in two action-packed features. Batman faces his coolest case ever in Batman & Mr. Freeze: SubZero when Batgirl is kidnapped by the cold-blooded villain Mr. Freeze. And as new villains overrun Gotham City of the future, a triumphant new Batman is born in Batman Beyond.
|System Details Note:||
DVD, stereo; full screen.
English dialogue; English or Spanish subtitles.
Search for related items by subject
|Subject:||Batman (Fictitious character) > Juvenile films.
Mr. Freeze (Fictitious character) > Juvenile films.
Superheroes > Juvenile films.
Batman (Fictitious character) > Drama.
Mr. Freeze (Fictitious character) > Drama.
Superheroes > Drama.

domain: library


It’s not every school that has a New York City YouTube sensation as part of its field day.
But unlike every school, the Harley School is the alma mater of Andrew Rea, the creator of the hit YouTube series, “Binging with Babish.” The series, which began as a test of his new documentary filming equipment, now has 2.5 million viewers who follow Rea as he recreates foods from television shows and other pop-culture media.
“I never intended to do more than one episode,” Rea said, after filming his version of a cook-off from “Parks & Rec” that pit a beef hamburger against a super-deluxe turkey burger with aioli. The beef burger won on the show, and Rea won a loyal following when he posted his experiment.
Tuesday morning in the Maker Space in Harley’s Commons Building, Rea explained that he usually creates a faithful reproduction of the food he found on TV and then goes on to make a more tasteful version.
The plan was to make “cheesy blasters” from the former situation comedy “30 Rock,” which character Liz Lemon (played by Tina Fey) described as a hot dog stuffed with jack cheese and rolled in a pizza. Then Rea planned to make a calzone along the same lines, but with ricotta cheese, sausage and capicola.
As sometimes happens in his episodes, the featured ingredients came from Wegmans. The hot dogs were Zweigle’s.
About 20 students gathered to watch Rea organize his materials and equipment as he prepared to film his show. Not long after, news would be shared that the school was declaring Tuesday as May Day, Harley’s version of a field day in which classes are suspended and a variety of fun activities are held instead.
Harley teacher Michael Frank, who teaches digital media, said Rea’s filming would be one of the May Day activities.
“He’s making a lot of smart decisions,” Frank said. “His framing keeps it very simple, but interesting. He uses pop culture as a (vehicle) for communicating about food.”
Viewers never see Rea’s face on the episodes, as the camera captures the food and mostly his forearms and torso. There were “aaahs” of recognition among the students when he pulled out his signature black apron and donned it.
Rea’s appearance at Harley, from which he graduated in 2005, was orchestrated after several current students discovered that he had attended their school. It was Harrison Davis, a sophomore, who heard that Rea was from the Rochester area, and then tracked down his Harley connection online, confirming it with a photo of Rea in a Harley yearbook. Then Noah Lee and Talon Mossbrook, who are both sophomores, too, contacted Rea through Reddit, a web-based forum.
“He responded back pretty quickly,” Lee said. Mossbrook said Rea told them he’d be glad to stop by when he was in the area—he timed it to coincide with a visit to see his new nephew. After students made that initial contact, Upper School Head Larry Frye reached out by email to invite Rea formally.
Rea brought along his friend and lawyer, Sawyer Jacobs, who also graduated from Harley in 2005.
“We’ve always held the school in a special place,” Rea said. Both alums were impressed by the school’s Commons, a barn-like building with greenhouse, cooking facilities and workshop. “They’ve invested in their interests in such a creative way,” Rea said.
“It’s a quantum leap past what we experienced,” Jacobs added.
Similarly, “Binging with Babish” is going new places too. Rea said he began working full time on creating “Binging with Babish” episodes in June 2017, but he and Jacobs are now planning to inspire other YouTube creators to do the same. They’ve moved an office into Rea’s new apartment in the SoHo neighborhood of New York City, and are embarking on a venture to create a network of like-minded YouTube creators who are invested in positive hobbies.
“Empowering stuff,” Jacobs said. And, perhaps, also delicious.
The cheesy blaster episode, by the way, is scheduled to be posted May 15.
[email protected]/(585) 363-7275e


Many of you may remember my Summer Solstice
quilt... A.K.A "I Am Not Afraid of Color". I finally was able to get it quilted!! I have attached the binding by machine and just need to turn it to the back and hand sew it down. Then it will officially be complete!!
But I couldn't wait to share the quilting with you. Let's take a little tour...
Here is the entire quilt and you can see lots of feathers and tons of quilting. I used variegated thread from Superior... their Rainbows and Lava. I switched them to match the fabrics. I love the sheen that they provide.
In the NYB sections some loops and stitch in the ditch.
In the Lone Star areas some feathers.
The borders some feathers and beads.
Pardon some of the cat fur on the black batik area. The cats obviously approve!!
An area with a small feather and more fur... LOL!
Lone Star feathers!
Flame like quilting in the NYB area.
The quilting on the backing fabric. The backing fabric is a Philip Jacobs fabric and can be found here.
The quilt... Details...
(click on any of the below to find the items)
Until Next Time...


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Please enter the dates of your stay, number of rooms, and guests to see a list of available rooms.
Stay at this family friendly Washougal, Washington hotel located on the Columbia River, near the Columbia River Gorge National Park and Vancouver.
Welcome to the Best Western Plus Parkersville Inn & Suites located on the beautiful Columbia River. This Washougal hotel is located minutes from the Pendleton Woolen Mills, the Columbia River Gorge and the nationally known Washougal MX Motocross Track. The Portland Airport is just 14 miles from this Best Western hotel.
The Best Western Plus Parkersville Inn & Suites proudly offers 79 spaciously appointed guest rooms featuring cable TV with Showtime premium channel and free high-speed Wi-Fi access. Hotel guests will wake each morning to a delicious complimentary full breakfast before taking a dip in the indoor heated swimming pool and hot tub or working out in the fitness center. This 100% non-smoking hotel also features business services and meeting facilities accommodating up to 50 guests.
The Best Western Plus Parkersville Inn & Suites is close to a variety of summer and winter outdoor activities including historic Parkersville Landing and Lewis and Clark trails located next to the hotel. This Washington hotel is also the best place to stay for families attending sporting events at the Harmony Sports Complex. Hotel guests will also enjoy activities such as fishing in the Columbia River and Lacamas Lake.
The Best Western Plus Parkersville Inn & Suites is proud to offer superior customer service and a convenient location in Washougal. Make a reservation today and save! Enjoy your stay.
We have stayed here many times because of it's location. It has always been a good place to stay, but now it is even better under new ownership. A very good breakfast, pool and fitness room. The...READ FULL REVIEW
I stayed with them a couple weeks ago and they were great and gave me a discount because I contract to the railroad and then I just called the other day and I was told yes I would get the same...READ FULL REVIEW
This was a clean, comfortable and quiet hotel. Very adequate for a weekend stay. Beds were comfortable and clean- and the price was excellent considering we rec'd a full hot breakfast with LOTS of...READ FULL REVIEW
Stayed here for a week while visiting family. Rooms are clean. Faced the river. Staff friendly and accomadating. Full breakfasts, eggs, bacon, sausage, gravy and bisquets, very good coffee, waffles...READ FULL REVIEW
This hotel was clean, comfortable and well situated for our needs. The staff was very helpful. Our family lives in nearby Camas, Washington which makes this location ideal! The breakfast was OK but...READ FULL REVIEW

domain: travel


HPE Smart Array E208i-a SR Gen10 (8 Internal Lanes/No Cache) 12G SAS Modular Controller
Are you looking for a cost effective, enterprise-class controller for internal attached drives without occupying a PCIe expansion slot? The HPE Smart Array E208i-a SR Gen10 Controller, supporting 12 Gb/s SAS and PCIe 3.0, provides a cost-effective storage solution with enterprise-class reliability supporting RAID 0, 1, 5, and 10 and software-defined storage (SDS). This controller has eight internal SAS lanes, allowing connection to SAS or SATA drives, supports Mixed Mode operations of RAID and HBA simultaneously, and offers encryption for data-at rest on any drive. This type-a modular controller occupies a dedicated storage slot without occupying a PCIe expansion slot.
Cost-Effective SAS Storage Connectivity
The HPE Smart Array E208i-a SR Gen10 Controller is a cost effective enterprise-class controller that provides the basic building blocks for simple RAID storage solutions while delivering 12 Gb/s SAS connectivity on HPE ProLiant Gen10 Servers when connected to 12 Gb/s internal storage devices.
Offers a low-cost solution to enable software-defined storage.
Built-in Reliability and Security
The HPE Smart Array E208i-a SR Gen10 Controller protects data-at-rest on any drive attached to the controller with HPE Smart Array SR Secure Encryption (optional license).
Comply with regulations for sensitive data, such as HIPAA and Sarbanes-Oxley with HPE Smart Array SR Secure Encryption.
Preserve data integrity with HPE SmartSSD Wear Gauge, which alerts you to potential drive issues before a drive fails.
Improved Efficiency and Storage Management
The HPE Smart Array E208i-a SR Gen10 Controller has increased flexibility with Mixed Mode which operates in RAID and HBA simultaneously and eliminates the expense of having to purchase another controller.
Rapidly configure simple RAID volumes on servers with the UEFI storage configuration tool, which also facilitates scripting support to configure an array via iLO through RESTful interface.
Quickly set up, configure, and manage drives attached to the controller with HPE Smart Storage Administrator (SSA), an intuitive interface used to create RAID volumes, manage advanced controller features, and deploy Smart Array solutions.
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92% Polyester, 8% Spandex Imported Pull-On closure Machine Wash 【High quality material】: Sauna Vest internal heating polymer fabric can increase your core temperature and accelerate sweating. The anti-roll silicone waistband is used to stay in place every time you work out. 【Sweat more】: Wearing our men's waist trainer during sports or daily activities provides you with a hot sauna-like experience, allowing you to raise your body temperature, sweat more and burn more calories while exercising. It is 5 times more sweaty than a regular undershirt. 【Compression and support】: Men's compression tank top can effectively control the abdomen. The scientific design and compression help tighten your abdomen and make you look slimmer. In addition, it provides you with back support to prevent injuries during exercise.
Men's Sauna Vest Workout Sweat Tank Top Waist Trainer for Men Compression Sweat Enhancing Vest - BJL79TT6O


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Brazil’s government has slashed enforcement of environmental regulations protecting the Amazon and allowed illegal grazing and slashing to accelerate during the COVID-19 pandemic, multiple reports claim, placing multinational meat and soya traders in danger of investor and consumer backlash.
Reports in The Economist and The New York Times cite environmental groups and supply chain traceability groups as saying that the government of President Jair Bolsonaro has gone to great lengths to commodify the delicate Amazonian ecosystem.
“Illegal loggers, miners and land grabbers have cleared vast areas of the Amazon with impunity in recent months as law enforcement efforts were hobbled by the pandemic,” states The New York Times report. While The Economist report includes a graphic showing how the majority of the deforestation occurs in the state of Mato Grosso and implicates multinational firms such as JBS USA, Minerva Foods and Cargill.
Deforestation of the Amazon presents a problem familiar to supply chain managers and compliance professionals: managing a supply chain in which third- and fourth-tier suppliers escape regulatory oversight and standard auditing procedures.
In the case of the Amazon, cattle ranchers slash timber illegally, graze their cattle on the slashed land for a few years and then move the cattle to legally deforested land for fattening before selling them to downstream traders and exporters. The illegally deforested land is then often sold on to soybean farmers, contaminating the soya supply chain as well.
The increased deforestation under the Bolsonaro government will contribute to a rise in carbon emissions and has made moot a ten-year agreement between multinational commodity traders to monitor and enforce environmentally sound practices within their supply chains.
Commitment to zero deforestation
“The cattle sector in the Brazilian Amazon is the largest driver of deforestation in the world,” the report stated. “[It is] responsible for more forest loss than the total deforestation in any country outside Brazil except Indonesia.”
The report had a dramatic effect on commodity traders’ behavior, resulting in an agreement, “Minimum Criteria For Industrial Scale Cattle Operations In The Brazilian Amazon Biome,” which laid out stipulations for cattle ranching in the Amazon.
Within a period of six months after the signing of the commitment to adopt these criteria, COMPANIES commit to proving, in a manner that can be monitored, verified and reported, that no rural property which directly supplies cattle for slaughtering (fattening farms) and is engaged in deforestation in the Amazon biome after the reference date of this agreement, is on its supplier list.
In the ten years following the agreement, deforestation was limited. Since the Bolsonaro government rose to power, illegal deforestation by speculators and small firms has increased dramatically, The Economist reports.
In the first four months of 2020 an estimated 1,202 square km (464 square miles) were cleared in the Brazilian Amazon, 55% more than during the same period in 2019, which was the worst year in a decade. Come August, when ranchers set fire to cleared areas to prepare them for grazing, runaway blazes could outnumber those that shocked the world last year. Scientists say tree loss is nearing a “tipping point”, after which trees will dry out and die, releasing billions of tonnes of carbon into the atmosphere.
Monitoring, auditing and enforcing
Much of the data regarding deforestation in the Amazon comes from groups such as Greenpeace, the Climate Observatory—an association of Brazilian research organizations—and Trase, which specializes in supply chain mapping and transparency.
Trase has developed a supply chain mapping tool that focuses on production in the Amazon. The tool shows commodity flows from the Brazilian Amazon through traders and multinational firms, such as Cargill, to markets in North America, Europe, China, Russia and the Middle East.
Firms that initially agreed to sustainable sourcing a decade ago have the tools to monitor suppliers. Given the current Brazilian government’s willingness to scrap domestic environmental regulations, remove and sideline environmental authorities, and pursue large-scale deforestation of the Amazon in the name of economic growth, it is imperative that private companies take supply chain mapping and auditing into their own hands.
The risks are currently low, in terms of consumer and stakeholder backlash, but that is a matter of “when,” not “if”—BlackRock Inc., a global investment firm with more than USD 7 trillion under management, recently divested from firms that derive more than a quarter of their profits from fossil fuels. The move was made in response to growing concerns by major stakeholders over the effects of climate change. Brazil’s willingness to cut down vast swathes of the Amazon will have a dramatic effect on carbon emissions, a leading cause of global climate change. It is only a matter of time before stakeholders target the soya and beef industries as well. Companies would do well to be proactive.
Brazil has accelerated illegal deforestation, leading to beef and soya entering the supply chain from questionable sources.
Stakeholders have already demonstrated their willingness to divest from companies that do not take climate change seriously. Companies with stakes in the Amazon should be proactively mapping their supply chains to ensure commodities are responsibly sourced.

domain: economics


Hodgdon h4831sc for sale is a powder widely used in the field of reloading ammunition. It is known for its versatility and popularity among handloaders.
H4831SC is a single-based, extruded powder that falls under the medium-burning rate category. It is often used in a variety of rifle cartridges, including popular calibers such as .270 Winchester, 7mm Remington Magnum, and .300 Winchester Magnum.
One of the key characteristics of H4831SC is its consistent burn rate. This allows for reliable and predictable performance shot after shot, contributing to improved accuracy and precision. Handloaders appreciate its ability to provide consistent velocities, making it a reliable choice for both hunting and long-range shooting.
Another advantage of H4831SC is its temperature stability. It performs well across a range of temperatures, ensuring consistent performance regardless of environmental conditions. This stability is especially important for shooters who may encounter different weather conditions during their shooting sessions.
H4831SC has proven to be a versatile powder for a wide range of bullet weights and applications. It is often used with medium to heavy bullets, making it a popular choice for larger game hunting and long-range shooting. Its versatility allows handloaders to tailor their ammunition to suit their specific needs and preferences.
As with any reloading powder, it is essential to follow safe reloading practices and refer to reliable reloading manuals for accurate load data. Different firearms, cartridges, and bullet combinations may have specific load recommendations that should be adhered to for safety purposes.
Overall, Hodgdon h4831sc for sale is a versatile and dependable powder frequently used by handloaders. Its consistent burn rate, temperature stability, and suitability for a variety of rifle cartridges make it a popular choice for those seeking accuracy and performance in their handloaded ammunition.


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The European contribution to a global civil navigation satellite system
Space technology revolutionizes navigation. It will become the method for any task of position, velocity, range determination and time distribution. The existing navigation satellite systems of the USA (GPS) and of Russia (GLONASS) are military systems. They only partly meet the requirements of civil safety critical applications. A global civil navigation satellite system (GNSS) is required. The European Union (EU) has recognized the importance of satellite based navigation and its role for transportation in general and for the development of the Trans-European Network (TEN) in particular. It has therefore decided to become a major partner in the development of the GNSS. In this article a concept is proposed which starts with a European regional segment (ENSS) as an element for the integrated global system. This concept requires the establishment of international standards to enable seamless global service. It has the advantage of meeting both the particular demands of regions and civil user groups.

domain: geography


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Sen. Tammy Baldwin says this crusade is personal -- and if she can force a vote, she will.
A post shared by Justin Bieber (@justinbieber) on Jul 9, 2018 at 3:14pm PDT
Justin Bieber and Hailey Baldwin only got engaged last week, but they are wasting no time planning their nuptials. According to Us Weekly, the couple want a "very small wedding." "They want something private, intimate," a
Singer Justin Bieber is engaged to his off-and-on girlfriend, model Hailey Baldwin.Read more about this at fox4news.com.

domain: news


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The Advantages of Setting Up a Trust in Virginia
Estate planning is not just about distributing assets; it’s about ensuring your legacy and supporting your survivors in the wake of your incapacitation or death. Unfortunately, it is a crucial task that is frequently overlooked or postponed, often resulting in family members navigating intricate legal matters and potential disagreements. As such, prompt action in estate planning is essential to spare your loved ones unnecessary strain during an already difficult time. A cornerstone of robust estate planning is setting up a trust, which is a powerful tool that offers numerous benefits. At Commonwealth Life & Legacy Counsel, we possess the expertise and experience in designing trusts that best serve the distinct needs of our clients across Central Virginia.
Virginia Trusts: An Effective Estate Planning Tool
A trust is an agreement where one party (the trustee) holds and manages assets for the benefit of herself or others (the beneficiaries). In Virginia, trusts offer several advantages for estate planning purposes. They allow you to retain control over your assets, avoid probate, provide financial support to your loved ones, and ensure privacy.
Firstly, trusts allow you to dictate how your assets will be used after you pass, giving you a greater degree of control over your estate. Secondly, assets held in a trust avoid the lengthy and costly probate process, ensuring a quicker and more efficient distribution of your assets upon your death. Lastly, unlike wills, trusts aren’t public record, offering a level of privacy many individuals prefer.
Types of Trusts in Virginia
In Virginia, there are various types of trusts you can create to suit your specific needs and objectives. For instance, Revocable Living Trusts provide flexibility as they can be altered during your lifetime. On the other hand, Irrevocable Trusts offer estate tax benefits but cannot be changed once established. Additionally, Special Needs Trusts can be set up for loved ones with disabilities without affecting their eligibility for government benefits. Understanding your unique circumstances allows us to help you select the right type of trust for your situation.
Creating a Trust: A Step-by-Step Approach
The process of creating a trust in Virginia involves several key steps. Firstly, it’s important to identify your goals and decide which type of trust best meets your needs. Next, you’ll need to select a trustee to manage your trust. After that, you’ll identify the beneficiaries and define the terms of the trust. During your lifetime, you can fulfill all of these roles yourself. Lastly, you’ll fund the trust with assets. This process can be complex, and our team at Commonwealth Life & Legacy Counsel can guide you through each step, ensuring you understand your options and make informed decisions.
Commonwealth Life & Legacy Counsel: Assisting with Trust Setup in Central Virginia
At Commonwealth Life & Legacy Counsel, we believe in providing personalized solutions for your estate planning needs. If you are considering setting up a trust in Central Virginia, our knowledgeable team can help. We’ll work closely with you to understand your objectives, explain your options, and establish a trust that accurately reflects your wishes. Setting up a trust can be a vital part of securing your legacy and providing for your loved ones. Don’t leave your estate planning to chance – let us help you navigate the process with confidence.
Call Commonwealth Life & Legacy Counsel in Central Virginia at (434) 589-2958 or in Powhatan at (804) 598-1348 or reach out online to set up a free consultation to discuss your trust setup needs.

domain: finance


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Editorial: Fresh approaches needed for removing forest fuels
It’s an objective few would find fault with: Removing debris and overgrowth from forests in the Lake Tahoe Basin to reduce the severity of wildfires.
How to accomplish that goal is where things get contentious.
The debate dates back a decade or more. Each fall the U.S. Forest Service begins reducing the so-called “forest fuels” through prescribed burns (also known as controlled burns). And each fall the burns spark complaints about the harmful impacts of the smoke the burns produce.
Forest Service officials contend that prescribed burns are the best way to clear tons of debris from remote, roadless terrain.
“In these all-too-common remote areas, handwork followed by pile burning is efficient, quick and least expensive,” said Rex Norman, spokesman for the U.S. Forest Service Lake Tahoe Basin Management Unit.
And acknowledging that some people are sensitive to the smoke, the forest service burns on days when winds carry the smoke up and out of the basin, minimizing health impacts, Norman said.
Zephyr Cove dentist Jack Harrington, who for years has criticized the burns, is among those who disagree with the Forest Service.
In a letter to the editor in today’s Opinion section, Harrington says: “Am I to conclude from this statement that because something ‘is quick and least expensive’ that it is OK, despite the negative impact on human beings? If so, why not just dump our sewage into Lake Tahoe, since that would certainly be quick and less expensive than pumping it out of the basin?”
Aside from potential health impacts, prescribed burns have other shortcomings. The devastating Angora fire this summer increased the urgency for clearing out excess forest fuels. But the number of days prescribed burns can be conducted is limited by weather conditions and air quality regulations.
In addition, forest fuels gathered up into “hand piles” in many cases must sit and dry for at least a year before they’re ready to burn.
And although safety must be our top concern, the timing of the burns is another irritant.
Just when Tahoe residents are looking forward to enjoying crisp fall days outdoors without summer or winter tourist crowds, the basin is covered with haze from prescribed burns – and the the more sensitive of us suffer stinging eyes and burning lungs.
With all that in mind, we are disappointed the Forest Service is not making more effort to develop new or improved non-burning methods to reduce forest fuels.
Admittedly, clearing areas deep within the forest may require burns, as hauling debris out over miles and miles wouldn’t be feasible.
Yet forest service officials tell us their current emphasis is reducing fuels in the “wildland urban interface,” areas where homes or other structures abut the forest. These zones are by definition near developed areas – presumably not far from roads – and taking fuels out rather than burning them would seem to be an option.
Another alternative to burning is increasing the use of chippers, machines that chop up forest debris and spread it so it burns at lower intensity during a wildfire.
An added incentive for carting debris out of the forest is the growing demand for “biomass,” woody material burned to produce energy.
For example, an $8-million wood-fueled plant providing electricity, heat and hot water to Northern Nevada Correctional Center in Carson City began running last month, amid questions whether the facility could find enough fuel to continue operating.
The Angora fire has already spurred innovation, as seen by the specialized equipment being tested for its ability to clear fuels along Heavenly Valley Creek without disrupting the sensitive stream zone.
We would like to see that kind of innovation further applied to reducing forest fuels, so that prescribed burns can be discontinued or at least used less often.


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'Homeland' & 'The Affair' Renewed by Showtime!
Great news for fans of the Showtime series Homeland and The Affair – the network has picked up both shows for additional seasons!
The Affair, starring Dominic West, Ruth Wilson, and Joshua Jackson, will be getting a 10-episode second season while Claire Danes‘ hit drama Homeland will be getting a 12-episode fifth season, which will air in 2015.
The Affair is averaging 3.9 million weekly viewers across all platforms while Homeland has been averaging 6 million for the new season and it has been growing each of the last three weeks.
“In its fourth season, Homeland has brilliantly reinvented itself. It continues to capture the attention of a devoted fan base, and has provided an enviable platform for the successful launch of The Affair,” Showtime president David Nevins said in a statement. “With thought-provoking, relevant and addictive storylines, both series have been embraced, dissected and much debated week after week. We’re excited to see more from these complex shows in 2015.”
ARE YOU EXCITED for the additional seasons of Homeland and The Affair?

domain: entertainment


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Making Inferences Adapted Book - Silly Penguins
This 20 page interactive adapted book requires students to read or listen to the description, make an inference and choose the appropriately dressed penguin from a field of 3. There are 20 unique penguin costumes corresponding to twenty pages of descriptions.
While created for students with autism to practice descriptive language, this book can be great for any special education classroom.
Please note: This is a digital download. You will download, print, and prep as needed. No physical items will be sent to you.

domain: literature


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Author: Anne S Ticknor (East Carolina University)
As public schools become more diverse in terms of student population, the US teaching force remains relatively stable. For this reason, teacher education programs need to provide and sustain social justice learning to ensure pre-service teachers enter classrooms prepared to teach all students. This article examines how pre-service teachers took up identities as social justice educators and sustained social justice learning during lapses in teacher education curricula. Analysis reveals that teacher educators can incorporate methods into course curriculum to ensure social justice learning is sustained in teacher education. Implications for teacher educators include strategies to provide social justice pedagogy scaffolding and offer plausible suggestions to incorporate and sustain social justice education for pre-service teachers when absent in future teacher education curricula.
Keywords: literacy, social justice, teacher education, identity
How to Cite: Ticknor, A. S. (2015) “Sustaining Social Justice Learning: What Teacher Educators Can Do”, Journal of Critical Thought and Praxis. 4(1).

domain: sociology


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An Architects' Vision
Native Land and joint venture partners Hotel Properties Limited and Amcorp Properties Berhad collaborated with world-renowned architect firm Rogers Stirk Harbour + Partners to produce a bespoke design that was fitting to their vision for Burlington Gate – a new residence with London’s first arcade since the 1930s.
Quintessentially British and finished to the highest of international standards, Burlington Gate boasts contemporary architecture inspired by Mayfair’s rich cultural heritage and numerous neighbourhood galleries, the design explores the concept of living in an art space and has been beautifully crafted with all the grace, elegance and light of the most inspiring gallery.
The penthouses in particular are the epitome of this approach. Their open interiors and double height staircases provide an exceptional canvas for your own take on contemporary living.
Light-filled rooms and elegant, innovative details are the hallmarks of the apartments here. Residents are welcomed home through a spacious atrium offering a tranquil retreat from the city, with green-leaved trees gracefully reaching skywards.
The styling and attention to detail is both exquisite and carefully considered. The result is a design tailor-made for Burlington Gate.

domain: artistic


Get your orders in now for Christmas! Air scribes are FLYING out - are you one of the lucky recipients?
Optical glass prismatic lenses: Ground and polished to precision optical standards—bevel edged and mounted in an interchangeable plastic frame.
High quality polished optical glass (crown ophthalmic) lenses. Made in USA to high quality standards. Specifically designed for the Optivisor DA range of headband magnifiers.
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In this blog post, we'll explore the causes of sleep deprivation, the risks associated with it, and some solutions for improving sleep quality.
Causes of Sleep Deprivation As We Age
There are several factors that can contribute to sleep deprivation in seniors:
- Changes in sleep patterns: As we age, our sleep patterns can change. Seniors may experience changes in the amount of time they spend in each stage of sleep, leading to less restful sleep overall.
- Medical conditions: Many medical conditions common in seniors can affect sleep, including chronic pain, sleep apnea, and restless leg syndrome.
- Medications: Some medications can interfere with sleep, including those used to treat high blood pressure, asthma, and depression.
- Lifestyle factors: Seniors may be more likely to experience stress, anxiety, and depression, which can all affect sleep. They may also be more likely to consume alcohol or caffeine, which can interfere with sleep.
Risks of Sleep Deprivation As We Age
Sleep deprivation in seniors can have serious health consequences, including:
- Cognitive decline: Sleep is essential for cognitive function, and sleep deprivation has been linked to an increased risk of cognitive decline and dementia.
- Depression: Poor sleep can contribute to depression, and depression can make it harder to sleep, creating a vicious cycle.
- Increased risk of falls: Sleep deprivation can affect balance and coordination, increasing the risk of falls and fractures.
- Impaired immune function: Sleep is important for immune function, and sleep deprivation can weaken the immune system, making seniors more susceptible to infections.
Solutions for Improving Sleep Quality
Fortunately, there are several steps we can take to help improve our sleep quality.
- Establish a sleep routine: Seniors should try to go to bed and wake up at the same time each day to establish a regular sleep schedule. This routine can help regulate their internal clock and promote better sleep.
- Create a sleep-friendly environment: A quiet, dark, and cool environment can promote better sleep. Seniors should also invest in a comfortable mattress, pillows, and bedding to ensure maximum comfort.
- Exercise regularly: Exercise can help seniors fall asleep faster and stay asleep longer. However, it's important to avoid vigorous exercise close to bedtime as it may disrupt sleep.
- Limit caffeine and alcohol: Seniors should limit their intake of caffeine and alcohol as they can interfere with sleep. Caffeine should be avoided in the afternoon and evening, and alcohol should be consumed in moderation and at least several hours before bedtime.
Supplementation: There are several supplements that can potentially improve sleep quality. Those that contain natural ingredients such as chamomile, hibiscus and gamma-aminobutyric acid (GABA) play an important role in promoting healthy sleep and may be involved in the regulation of other physiological processes that occur during sleep, such as the consolidation of memories and the restoration of the body's immune system.
- Manage stress: Stress and anxiety can interfere with sleep. Seniors should try relaxation techniques such as deep breathing, meditation, or yoga to manage stress and promote relaxation.
- Address sleep disorders: Seniors should speak to their healthcare provider if they have trouble sleeping, as there may be an underlying sleep disorder such as sleep apnea or restless leg syndrome that requires treatment.
In conclusion, seniors can take several steps to improve their sleep quality. Establishing a regular sleep routine, creating a sleep-friendly environment, exercising regularly, limiting caffeine and alcohol, supplementation, managing stress, and addressing sleep disorders can all contribute to better sleep and an improved quality of life.

domain: biology


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QUALIFICATIONS AND JOB DESCRIPTION
In its business segments, voestalpine is a globally leading technology group with a unique combination of materials and processing expertise. With its top-quality products and system solutions using steel and other metals, it is a leading partner of the automotive and consumer goods industries as well as of the aerospace and oil & gas industries. voestalpine is also the world market leader in complete railway systems as well as in tool steel and special sections.
voestalpine High Performance A.Ş. is now looking for a FINANCE DIRECTOR to be based in Gebze, Kocaeli HQ. The position will directly report to General Manager.
1. Provide strategic recommendations to the management team.
2. Manage all financial and accounting operations including general accounting, cost accounting, reporting, tax, budget and forecasting.
3. Work on continuous forecasting of future performance and development of budgeting and modeling tools to evaluate strategic initiatives.
4. Coordinate and conduct of annual audit activities within the required time and quality and maintain relationships with external auditors.
5. Lead treasury and risk management, including borrowing, cash flow control and forecasting, investments, insurance, treaty compliance and feasibility calculations.
1. Bachelor's degree in Finance, Economics, Business Administration or related field from reputable universities (MBA is plus).
2. More than 15 years experience in financial management, especially in production.
3. Experience in a similar role.
4. Team management experience.
5. Excellent command of written and spoken English.
6. Excellent presentation and communication skills to both internal and external stakeholders.
7. Proven ability to manage multiple projects / tasks and well-developed time management skills.
8. Audit and finance sector background are preferred.
9. Good knowledge of SAP


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Hungry Shark Evolution for Windows 8 22.214.171.124
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Take control of the most violent shark in the ocean ...Hungry Shark Evolution is a game that lets you take control of a greedy shark ... ocean In Hungry Shark Evolution, you live the life of a shark, starting from ...
- PROS: Core gameplay of original game, Lots of variety, Weird unlockables
- CONS: Unlocking new sharks and objects takes a lot of time