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The submucosal glands (SMGs) of the respiratory system are specialized structures essential for maintaining human airway homoeostasis. The significance of these glands is highlighted by their involvement in serious respiratory diseases, such as cystic fibrosis, where their phenotype and function are severely altered. Surprisingly, very little is known about SMG development and differentiation. To understand the molecular mechanisms involved we have investigated the development of nasal and tracheal SMGs in the Fgf10 mutant mouse. Fgf10 is expressed in the mesenchyme around the developing SMGs, and in heterozygous mice the tracheal glands have reduced branching. These mice also have an altered A/P distribution of the glands post-natally, a deficit that is not recovered in adults. In the nasal glands, some but not all glands were lost in the homozygous mutant, indicating that not all glands require Fgf10 for initiation. Some of the glands present in the Fgf10 homozygote were missing in the Fgfr2b mutant, suggesting compensation by another Fgf ligand. We aim to uncover the expression patterns of a number of Fgfs during early gland development and to study the functional consequence of loss of SMGs in Fgf10 heterozygotes by assessing the ability of these mice to respond to respiratory challenges.
The importance of epigenetic regulation of gene expression during heart development is becoming increasingly apparent. CHD7 is a large nucleosome-remodelling protein, which shows ATP-dependent helicase activity. Haploinsufficiency for CHD7 is implicated in CHARGE syndrome, and patients with reported CHD7 mutations present with a range of congenital cardiovascular defects. Mesodermal ablation of Chd7 in mice, driven by Mesp1-Cre, results in a severe cardiovascular phenotype and embryonic lethality around E15.5–E16.5. Embryos show haemorrhage, oedema, structural heart defects and a low penetrance of great vessel defects. Interestingly, given this haemorrhagic phenotype, data collected on embryos lacking Chd7 in the endothelial lineage did not result in haemorrhaging or any other major cardiovascular phenotype, while Mef2c-Cre-driven knockout in the second heart field produced a subset of the mesodermal cardiovascular phenotype. Early cardiomyocyte lineage-specific ablation is currently being investigated.
Microarray analysis and qRT-PCR has been used to identify genes that are dysregulated in the heart after mesodermal Chd7 ablation. Key developmental signalling pathways are found to be disrupted, which can be linked with the cardiovascular defects observed. Alongside detailed characterization of temporal- and tissue-specific Chd7 expression as the heart develops, this is leading towards insights into the role of CHD7 in cardiovascular development.
In mammals the Y-linked gene Sry is a dominant male determinant, whose expression initiates the cascade of events that drive differentiation of the testis. In the mouse, Sry follows a distinctive spatiotemporal pattern and must be sufficiently expressed within an appropriate temporal window to enable activation of the male pathway. Deficiencies in a number of genes have been shown to disrupt the timely onset of Sry expression and lead to XY sex reversal, including the kinase MAP3K4. XY embryos lacking MAP3K4 exhibit delayed, insufficient expression of Sry and develop ovaries on the C57BL/6J (B6) background. While its loss results in failed testis determination, we have found that gain of MAP3K4 function using BAC transgenesis can rescue sex-reversal in B6 embryos carrying the Y chromosome from the Mus poschiavinus strain. Furthermore, loss of a copy of Map3k4 results in more severe sex reversal in these embryos. Transcriptional profiling shows that delayed Sry expression underlies B6-YPOS sex reversal and that overexpressing Map3k4 partially restores the normal expression profile of Sry. We now aim to explore the epigenetic landscape of the Sry POS locus in order to elucidate regulatory mechanisms contributing to B6-YPOS sex reversal and its modification by transgenic expression of Map3k4.
The nephron is the single most important excretory tissue in mammals and its segments regulate water homoeostasis, blood filtration and metabolite excretion. Accordingly, when its function is disrupted complex pathological features are found. In spite of its importance little is known about how the nephron becomes patterned and segmented. We have identified the genetic mechanism that controls the patterning of the nephron. Our data show that the developing nephron is patterned by a gradient in the transcriptional activity of β-catenin that lies longitudinal to the proximal-to-distal axis of the nephron tubule. By modifying β-catenin activity we force cells within nephrons to adapt to the imposed β-catenin activity level, thereby causing spatial shifts in nephron-segments. The β-catenin signalling gradient interacts with the BMP pathway. BMP, through PTEN/PI3K/AKT signalling, antagonizes the β-catenin activity gradient and promotes segment-identities associated with low β-catenin activity. The β-catenin activity gradient also integrates with Notch function. Modulating β-catenin activity rescues segment-identities normally lost by inhibition of Notch. Similarly, co-suppression of Notch and PI3K restores the medial domain thus indicating that Notch promotes the medial domain by blocking PI3K activity to prevent excessive AKT and medial growth. Our data therefore identifies a comprehensive genetic network for nephron patterning.
Cell-cycle progression is central to embryonic development. Fucci (Fluorescent Ubiquitination-based cell cycle indicator) is a genetically encoded cell-cycle reporter system originally developed by the Miyawaki lab to visualize cell-cycle progression. The original probes were expressed ubiquitously and consisted of separate genetic constructs and mouse lines to label G1 and S/G2/M phases; consisting of fluorophores fused to the regulatory domains of hCdt1(30/120) and hGeminin(1/110), respectively. The relative abundances of these two probes are tightly regulated during cell-cycle progression, allowing one to define the cell-cycle status of a cell by its colour. We describe a modified version of the Fucci system (Fucci2a). Fucci2a fuses the Fucci probes using the self-cleaving Thosea asigna virus 2A peptide sequence (t2a) allowing the expression of the two probes from a single promoter. The single construct greatly simplifies the process of generating, maintaining and crossing mouse lines. It also provides the opportunity to incorporate other fluorescently tagged proteins into the construct, separated by a further self-cleaving peptide. We have characterized the behaviour of our Fucci2a constructs in stable cell lines and have made a Cre-inducible transgenic mouse line by targeting to the ROSA26 locus.
Neural tube defects (NTDs), such as spina bifida and exencephaly, affect approximately 1 in 1000 pregnancies. They are caused by failure of neural tube closure during development, and can lead to lifelong disability or death. The Splotch mouse carries a mutation in the Pax3 gene and is predisposed to NTDs. However, the mechanism underlying development of NTDs are not well understood. Three theories have been proposed for causes of spina bifida in the Splotch mouse – premature neuronal differentiation, excess apoptosis and reduced proliferation. I have been investigating these theories to find out if any of them could be the cause of the spina bifida in Splotch embryos. Although excess apoptosis and premature neuronal differentiation are not detected in Splotch mutant embryos, reduced proliferation is present and hence may be causative. Additionally, genetic crosses in mice identified a potential link between the Pax3 and canonical Wnt signalling pathways. These studies show that canonical Wnt signalling influences frequency of Pax3-related NTDs.
Cilia are cellular organelles which perform sensory, motility and signalling functions crucial for development and homoeostasis. Their dysfunction often leads to ciliopathic diseases. While a significant portion of the cell's proteome is devoted to cilium formation/function, many cilia components and their roles remain unknown. Phylogenetic conservation of core ciliary genes and their regulation by key transcription factors, conserved across metazoans, has allowed the use of model organisms to identify new ciliary/ciliopathy candidate genes.
Broadly, all ciliary genes are transcriptionally controlled by RFXs; additional co-operation with FoxJ1 is required for motile cilia formation. Mammals have evolved further complexity for specialized motile cilia sub-types. Paring this complexity down to the relatively simpler model of Drosophila mechanosensory cilia led to the identification of novel ciliary genes Heatr2 and Zmynd10 controlled by an Rfx-Fox transcriptional code. Mechanosensory neurons being the only somatic cells in flies with cilia most akin to mammals, fly RNAi mutants for these genes displayed characteristic ciliopathy-like defects; these data will be presented. Mutations in these genes have recently been reported to cause a classic motile ciliopathy in humans called PCD. A novel PCD causing HEATR2 mutation will be presented. Findings on the transcriptional control of these genes and expression studies in the mouse will also be presented.
Cilia are required for normal embryonic patterning and adult physiology; defects in their assembly cause disorders known as ciliopathies. Atmin (ATM interactor) is a transcriptional activator, previously implicated in DNA repair. We independently identified it as the gene mutated in the lethal ciliopathy gasping6 (gpg6). In gpg6 one of Atmin's zinc fingers loses its function, resulting in defective ciliogenesis in multiple embryonic tissues and a ciliopathy-like phenotype. Transcriptional profiling has demonstrated altered expression of genes implicated in ciliogenesis. We have investigated their relationship with Atmin and our results points to an Atmin-dependent pathway impacting ciliogenesis, most likely though modulation of intraflagellar transport.
Tulp3 has been identified among the genes required for neural tube development, and acts as a negative regulator of the Shh signalling pathway. In early embryonic development, Shh signalling is required for neural tube formation and dorsal ventral patterning. The role of Tulp3 is as part of a transportation complex that delivers specific G-coupled receptor proteins to the primary cilia. This current model is based on a range of discoveries that include associating Tulp3 with IFTA complex proteins and, more recently, primary cilia transportation of G-protein-coupled receptor Gpr161. In our Laboratory, we identified Rgnef (p190RhoGEF) as a Tulp3 interacting protein through yeast2-hybrid experiments. We further show that Rgnef is expressed ventrally in the neural tube of developing mouse embryos. Through cell-based Shh pathway activation assay, we show that siRNA knock-down of Rgnef expression suppresses pathway activation induced by agonist purmorphamine. Furthermore, overexpression of Rgnef results in significant pathway activation. In conclusion, these results demonstrate a role for Rgnef in Shh pathway activation.
The international Mouse Phenotyping Consortium will generate 5000 conditional KO mouse lines by 2015 and make them available to the research community together with a broad phenotypic characterization and the expression profile of the targeted locus. MRC Harwell is responsible for producing, distributing and analysing 500 of these lines. We will present the pipeline of work focusing on the characterization of the embryonic lethal lines, including the identification of the window of lethality, gene expression at E12.5 and acquisition of morphological data by OPT and microCT. We will describe the first mutants analysed by this programme.
Chromosome segregation is a vital process, and its precise regulation is required to ensure that each daughter cell receives a correct chromosome complement. Mistakes in this process result in aneuploidy and tumour development. Our work shows that frequencies of aneuploid cells show profound variability between different stages of haematopoietic differentiation. In addition, we show that a mouse model with a hypomorphic mutation in a ubiquitously expressed subunit of Condensin II (Caph2nes/nes ) exhibits mitotic abnormalities in the T-cell and erythroid, but not B cell lineages. The mutation results in a developmental block specifically in the T-cell lineage – with the numbers of B cells and erythroid cells relatively unaffected. T-cell numbers are rescued in Caph2nes/nes; P53−/− double-mutant animals. The most common cause of death in p53 mutant mice is thymic lymphoma, and interestingly the double-mutant mice succumb to thymic tumours significantly more rapidly than either Caph2−/− or p53−/− single mutants. From these data, we suggest that cells at different stages of haematopoietic development vary in their susceptibility to chromosome instability, which may explain why certain stages of differentiation are particularly vulnerable to transformation.
Gametogenesis in mammals is characterized by epigenetic reprogramming. This involves DNA methylation erasure in primordial germ cells, followed by methylation establishment, which in the female germline takes place after birth during oocyte growth. In oocytes, it was previously observed that methylated CpG islands (CGIs) often localize within active transcription units, as in the case of the differentially methylated regions of imprinted genes. Moreover, it was demonstrated that methylation in oocytes is not limited to CGIs, but extends over whole gene bodies, appearing to divide the genome into hypermethylated domains over transcription units and hypomethylated domains devoid of transcription. This suggests that transcription is a key determinant of the DNA methylation landscape in oocytes. In many cases, when annotated transcription start sites (TSSs) are methylated, upstream unannotated oocyte-specific TSSs could be identified, providing transcription across the corresponding CGI. Therefore, standard genome annotation is not suitable for genome-wide correlation of oocyte transcriptome and methylation. Using deep RNA-sequencing, we mapped the oocyte transcriptome and rigorously tested the correlation with methylated domains. Our data also demonstrate, with greater precision that previously, that methylated CGIs are mostly intragenic, while unmethylated CGIs are intergenic or associated with active TSSs. Oocyte transcriptome annotation together with genome-wide TSS mapping allowed us to identify TSSs active in oocytes. This will be used to investigate the timing of induction of TSSs during oocyte growth and correlation with initiation of de novo methylation of specific CGIs in vivo in size selected oocytes, as well as in cultures of growing oocytes.
Delta-like homologue 1 (Dlk1) is a paternally expressed imprinted gene whose product is a Notch family protein present in both membrane-bound and soluble forms. DLK1 has been implicated in the development of a wide variety of embryonic tissues, as well as in post-natal roles such as adipogenesis. Dlk1 is expressed at high levels in numerous tissues in the embryo and young neonate; additionally, in these animals soluble DLK1 is present at high concentrations in the blood plasma. In contrast, Dlk1 expression is low and highly restricted in the adult animal and plasma DLK1 levels are also low. The exception to this is pregnancy, when maternal plasma DLK1 dramatically increases, peaking at term at concentrations approximately eightfold that of non-pregnant adults. This project investigates the source of this additional plasma DLK1 and its effects upon maternal metabolism and resource partitioning during pregnancy.
Chromatin immunoprecipitation and next-generation sequencing are being used to interrogate the coincident and allele-specific binding of the proteins CTCF, Cohesin, ATRX and MeCP2 genomewide in the murine brain, a tissue that expresses a significant proportion of imprinted transcripts. Identifying regions co-binding these proteins will help generate a model to understand how these proteins influence gene expression, particularly at imprinted loci. Using these tools we aim to understand more about the proteins that participate in the genomic landscape around imprinted loci and drive this unusual mode of gene regulation. These loci will act as models for studying DNA-binding proteins and their roles in transcription.
At the level of the individual locus, mechanisms of gene regulation are being investigated using imprinted retrogenes as a model. Retrogenes are transcriptionally active intronless genes located within an intron of a ‘host’ gene. The role of epigenetic factors influencing gene transcription are being investigated at the Mcts2/H13 locus. Expression of an intronic retrogene can cause premature termination of a ‘host’ transcript from the same allele. Our hypothesis is that this premature termination is caused by transcription of the retrogene interfering with host gene transcription. These studies will provide a mechanistic component to our whole genome analyses.
Fetal growth involves highly complex molecular pathways. IGF2 is a key paternally expressed growth hormone that is critical for in utero growth in mice. Its role in human fetal growth has remained ambiguous, as it has only been studied in term tissues. Conversely the maternally expressed growth suppressor, PHLDA2, has a significant negative correlation between its term placental expression and birth weight.
The aim of this study is to address the role in early gestation of expression of IGF1, IGF2, their receptors IGF1R and IGF2R, and PHLDA2 on term birth weight. Real-time quantitative PCR was used to investigate mRNA expression of the aforementioned genes in chorionic villus samples (n=260). Expression was correlated with term birth weight using statistical package R including correction for several confounding factors.
Transcript levels of IGF2 and IGF2R revealed a significant positive correlation with birth weight (0·009 and 0·04, respectively). No effect was observed for IGF1, IGF1R or PHLDA2 and birth weight. Critically, small for gestational age (SGA) neonates had significantly lower IGF2 levels than appropriate for neonates (p = 3·6 × 10−7).
Our findings show that IGF2 mRNA levels at 12 weeks gestation could provide a useful predictor of future fetal growth to term, potentially predicting SGA babies. This research reveals an imprinted, parentally driven rheostat for in utero growth.
The reprogramming of epigenetic marks is a genomewide process and yet CpG islands (among a few other sequence classes) escape this overall trend. Nevertheless, not all CpG islands respond similarly; while the majority of them resist the global de novo DNA methylation establishment, around 1000 CpG islands acquire methylation in oocyte (most of them remain un-methylated in sperm therefore, they called germ line differentially methylated regions [gDMRs]). Additionally, about 25 gDMRs maintain this acquired germ line methylation during pre-implantation development and in the somatic cells (permanent gDMRs) while the rest lose their methylation after fertilization. Emerging sequencing technology contributes to the understanding of the molecular mechanisms for some of these modifications; yet the role of the DNA sequence remains to be determined. Here, we investigated the role of the DNA sequence of CpG islands in attracting the specific protein complexes for either establishing or maintaining the DNA methylation at specific oocyte-methylated CpG islands and protecting the default un-methylated state of the majority of CpG islands during oogenesis and pre-implantation embryos. The results of association studies shows high correlation between CpG islands gene-body methylation and transcription initiated at upstream promoters in oocytes, supporting previous observations. Although de novo motif finding has successfully identified TGCCGC (the recognition site of Zfp57/Kap1 protein complex), it did not uncover any similarly significant motif at permanent gDMRs, suggesting the absence of another DNA-interacting protein complex that may maintain the DNA methylation at these regions post fertilization. Further analysis on this motif indicates that its density, in addition to its coverage, is indispensable discriminative feature that distinguishes permanent gDMRs from other CpG islands. Furthermore, the absence of discriminative motifs and the lack of 8–10 bp CpG spacing and global periodicity at either oocyte-methylated CpG islands (including permanent gDMRs) or their shores relative to oocyte un-methylated CpG islands support a sequence-independent mechanism for de novo methylation establishment during oogenesis. Finally, a CG-rich, independent of CpG density motif that is significantly similar to E2F1 recognition site is overrepresented at oocyte un-methylated relative to methylated CpG islands. Results from logistic linear regression showed that this motif acts independently of transcriptional activation at un-methylated CpG islands, proposing a role in protecting them from de novo methylation.
Control of retinoic acid (RA) homoeostasis/dosage is required for normal development and the Cyp26 enzymes are known to metabolize RA to less active forms. Cyp26b1 null mice display cardiovascular and thymic phenotypes at E15.5 which are reminiscent of 22q11-deletion syndrome phenotypes. These include small/ectopic thymus and abnormal development of the outflow tract (OFT), ventricular septum and aortic arch remodelling. Developmental anomalies of the pharyngeal arch arteries, neural crest and OFT detected at E10.5 may underlie these later phenotypes.
Animal models and non-deleted patient data suggest haploinsufficiency of TBX1 is a major underlying cause of 22q11DS and Tbx1 mutant embryos recapitulate the majority of the 22q11DS phenotype. Cyp26b1 expression is down-regulated/altered in Tbx1 mutant mice both by RT-PCR and in situ hybridization. As described above the cardiovascular phenotype of both Tbx1 and Cyp26b1 mutant mice is very similar. To determine if Tbx1 and Cyp26b1 might be acting within the same genetic pathway crosses between Tbx1mcm/+ and Cyp26b1+/− mice were performed and analysed at E15.5. The results suggest that a Tbx +/− 1 allelle in a Cyp26b1 null context can modify the aortic arch phenotype observed.
Our work utilizes embryoid bodies formed from mouse embryonic stem cells as a model system. The outer-most cell layer of an embryoid body is an epithelial cell type comparable with the primitive endoderm. To investigate the relationship between cell polarity and fate of the primitive endoderm in an embryoid body, we have utilized a pharmacological small-molecule inhibitor approach. A role for the MAPK signalling cascade in the development of the primitive endoderm has previously been shown both in embryoid bodies and in vivo. Upon pharmacological inhibition of both the FGFR receptor and MAPK signalling cascade, as expected we observed a loss of primitive endoderm cell fate markers in the cells of the outer layer of the embryoid body. Interestingly, we also observed a disruption in polarization of the epithelial layer, demonstrated by mislocalization of an apical polarity complex protein, tight junction and adherens junction proteins as well as a disruption of the basement membrane. We believe that this work demonstrates an important role for the MAPK signalling cascade in the polarization of the primitive endoderm in embryoid bodies.
NIPBL – Nipped B like – is one of the human components of the cohesin complex, which is a highly conserved protein complex with two main functions: (1) to control sister chromatid cohesion during S phase and (2) to regulate gene expression. Mutations in NIPBL account for 50% of the cases in Cornelia de Lange Syndrome (CdLS), a congenital birth defect affecting almost any organ, with an estimated incidence of 1:10000 births and with variable phenotype severity. It has been reported that NIPBL is expressed in the fetal kidney, the foetal liver, in the cephalic neural tissues, the limb buds and branchial arches. However, a detailed expression analysis of Nipbl during embryogenesis that will help explain the genotype/phenotype of this congenital malformation has not been reported. The aim of this project was to characterize in detail Nipbl gene expression in mouse embryos at different stages of development. Using in situ hybridization on paraffin sections of different stage mouse embryos we found strong expression in the developing heart, in the lung epithelium, in the gut, and in the developing cerebellum. These previously unreported sites of expression correlate to CdLS affected organs and complement our recent study on Danio rerio embryos.
Cleft lip and palate (CLP) is well known to be among the most common birth defects, but we still have difficulty to explain why the majority of cases occur. In general, sporadic cases with no family history may be more related to environmental risks, while the presence of one or more affected relatives in the same family will suggest genetic factors as the main contributor. The aim of this study is to identify new CLP genes using next generation sequencing (exome sequencing) methodologies. We have collected an extensive set of DNA samples from multigeneration CLP families and we have chosen to investigate those where there are four or more affected members. We analysed exome data both within and between families to identify unique and shared rare variants. Further characterization involves segregation analysis and replication screening in large patients’ cohorts. The identification of new genes responsible for CLP will be vital to improve our understanding of normal and abnormal lip and palate development and we hope to be able to make use of this information to develop accurate diagnosis and future risk assessment as well as the potential to develop novel treatment or preventative therapies.
GNB1L is located on chromosome 22q11.2, within the 22q11 Deletion Syndrome (22q11DS) critical region. 22q11DS is characterized by abnormal development of pharyngeal arch derivatives and is associated with increased risk for a range of behavioural disorders, including autism and schizophrenia. GNB1L has been implicated in both autism and schizophrenia by a number of genetic studies, independent of 22q11DS. Mice hemizygous for Gnb1l display neuro-behavioural deficits. We have therefore sought to discover the function of GNB1L in order to determine its possible role in autism and schizophrenia.
GNB1L consists of six WD40 repeats, a loosely conserved motif that mediates protein–protein interaction. A yeast two-hybrid screen identified interaction of GNB1L with HIPK1. Hipk1 has been previously shown to be involved in neural development and to act as a modulator of Wnt-signalling. We show that GNB1L acts as a negative regulator of Wnt-signalling and likely acts in the same pathway as HIPK1. Mutations in the WNT-signalling pathway have been previously linked with both autism and schizophrenia. Our results suggest that this pathway is dysregulated in 22q11DS and may contribute to the behavioural disorders seen in these patients.


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Dominik Piechocki aka Switch Technique, is a drum and bass producer from Pniewy, Poland. Over the last few years, he has emerged as one of the leading forces in Polish Drum and Bass movement. His adventure with music began in 1999 from the game "Extream G2", the soundtrack of which was his the first encounter with the above mentioned phenomenon, commonly known as Drum and Bass.
While exploring billions of broken sounds Dominik began experimenting with software in the search of the perfect beat and his individual approach to music resulted in a one-of-a-kind style. His individual and collaborated releases are fresh, fully packed with energy and the harder ones are influenced by Hardcore sounds. Since his first record release, his tunes have been dance floor killers tracklisted by the biggest and most influential Dj's such as Evol Intent, The Panacea, Limewax, DJ Hidden, Eye-D, Masheen, and freaking many others.
After more than a decade with handfuls of releases, hundreds of hours spent on perfecting his standout sound there has come a time for his fascination of Hardcore to take him to a whole new level of music production. Switch technique has created a new unique and completely fresh production standard defined by combination Hardcore and Drum and Bass. simultaneously, he's pushing his ideas of regular DNB which he loves to interpret and translate into hard oriented techstep and darkstep.

domain: artistic


The House Appropriations Committee has passed a provision known as the Joyce amendment, which prevents the U.S. Department of Justice from spending federal funds on prosecuting state-legal medical cannabis businesses. The amendment will move toward the House floor, where it will be read into the record as a part of the full Commerce, Justice, Science (CJS) spending bill.
In the past, since 2014, versions of the Rohrabacher-Blumenauer amendment had been added into short-term spending bills and approved amid broader appropriations packages. This latest committee vote attaches the Joyce amendment directly to appropriations legislation that covers U.S. Attorney General Jeff Sessions’ purview.
“Today marks a victory for medical marijuana programs and a loss for Attorney General Jeff Sessions. Passage of this amendment through regular order in the appropriations committee represents another big step in the normalization of state level marijuana reform in the Congress of the United States,” said NORML Political Director Justin Strekal in a public statement.
Indeed, the committee vote marks an important milestone in recent federal legislative history. This move tees up a full House floor vote on a measure that would directly impact medical cannabis businesses -- an opportunity that's been halted by U.S. Rep. Pete Sessions (R-Texas, House Rules Committee chairman) for the past two years, according to Marijuana Moment reporting.
“By adding this important provision in committee, members have ensured it will not get blocked like it did last year,” MPP’s director of conservative outreach, Don Murphy, said in a public statement. “We commend Rep. Joyce and his colleagues for taking this step to protect state medical marijuana laws. Hopefully this is a sign that members of both parties are ready to take meaningful action on this subject and move our country toward a more sensible approach to marijuana policy — one that respects states’ rights and reduces wasteful spending while allowing seriously ill people to access medical marijuana if it will improve their quality of life.”
Top photo courtesy of Adobe Stock


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From Our Editors
Exotic Pets and Supplies in Okeechobee is a great place to bring your pet and shop for his or her favorites, such as wet food and tasty treats.
For your convenience, there are plenty of parking spots for you to make use of during your visit. You don't have to travel far for great pet supplies. Exotic Pets and Supplies in Okeechobee is close by and offers endless deals.

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Organize full albums and play them with AlbumPlayer, just by browsing your covers. The browser makes it possible to group and sort on album attributes making play list creation easy. For touch screen users a special interface is available with bigger buttons and alternative track selection method supporting screens with minimum size 800x480. The Database Shuffle (also known as Autocue) feature, lets the AlbumPlayer automatically pick tracks or albums from your collection based on user criteria. The AlbumPlayer contains an equalizer and a normalization function, which can play a play list at one volume level using Replay Gain calculation. It supports Last.fm, Winamp DSP plug-ins and Evillyrics.


Who is john bell edwards?
John Bel Edwards is an American politician, military veteran, and attorney serving as the 56th governor of Louisiana since 2016. A member of the Democratic Party, he previously served as the Democratic leader of the Louisiana House of Representatives for two terms.
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Two-photon polymerization, optionally combined with stimulated emission depletion (STED) lithography, allows two and three dimensional polymer fabrication with structure sizes and resolution below the diffraction limit. Structuring of polymers with photons, whose wavelength is within the visible range of the electromagnetic spectrum, gives new opportunities to a large field of applications e.g. in the field of biotechnology and tissue engineering . Radical photoinitiator molecules (fluorophores) in an acrylic negative tone photoresist are excited with a near infrared laser via two photon absorption; this allows writing of features as small as ~100 nm. To achieve spatial polymerization restriction similar to STED-microscopy [2, 3], the excited photoinitiators are depleted in the outer rim of the excitation volume via stimulated emission by a second laser beam. An appropriate beam shaping shrinks the volume of excited photoinitiators. Thereby, polymerization initiation is furtherly confined. The feature size can be decreased to several tens of nanometers in any desired geometry using stimulated emission depletion (STED) [2-5]. Currently, feature sizes as small as 55 nm and a lateral resolution of 120 nm of adjacent lines can be achieved [5, 6]. Feature size as well as structure resolution are mainly limited by the used photoresists.
Future applications of sub-diffraction optical lithography include optical data storage and nanophotonic devices. Recently, STED lithography allows us to produce well characterized, biocompatible nanoanchors as platforms for single, biochemically active proteins, applicable to many biological assays [6, 7].
1. Maruo, S., O. Nakamura, and S. Kawata, Three-dimensional microfabrication with two-photon-absorbed photopolymerization. Opt Lett, 1997. 22(2): p. 132-4.
2. Klar, T.A. and S.W. Hell, Subdiffraction resolution in far-field fluorescence microscopy. Opt Lett, 1999. 24(14): p. 954-6.
3. Klar, T.A., et al., Fluorescence microscopy with diffraction resolution barrier broken by stimulated emission. Proc Natl Acad Sci U S A, 2000. 97(15): p. 8206-10.
4. Fischer, J., G. von Freymann, and M. Wegener, The Materials Challenge in Diffraction-Unlimited Direct-Laser-Writing Optical Lithography. Advanced Materials, 2010. 22(32): p. 3578-+.
5. Wollhofen, R., et al., 120 nm resolution and 55 nm structure size in STED-lithography. Opt Express, 2013. 21(9): p. 10831-40.
6. Klar, T.A., R. Wollhofen, and J. Jacak, Sub-Abbe resolution: from STED microscopy to STED lithography. Physica Scripta, 2014. 162: p.14049
7. Wolfesberger, C., et al., Streptavidin functionalized polymer nanodots fabricated by visible light lithography. J Nanobiotechnology, 2015. 13(1): p. 27.

domain: chemistry


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HOME > NORTH
TAIWAN > TAIPEI > DINING >
FUN MAGAZINE, December 2003.
45, ZhongXiao E. Rd., Sec. 4, 11F (Inside ZhongXiao
Credit cards accepted; 10% service charge
YOUR RATING & REVIEW | VIEW
VISITOR RATINGS & REVIEWS
is located within a department store, but the interior
has an ingenious New Deco look: black and white, well-lit
and simple, with a large blackboard adorning the wall.
The blackboard is covered with writing, but diners can
get only a vague impression of what it means. The interior
features a glass facade and a skilful arrangement of
single and double seats. An open-style kitchen lets one
see the chef prepare dishes. As its name suggests, this
restaurant offers food with an herbal theme. Herbs are
added to give the food a simple and light feeling. At
the same time, a distinctive fusion flavor is evident.
The menu includes Roasted Basil Lamb Chop And Risotto,
Stewed Rosemary Beef Knuckles, and Beef Fillet Steak
With Green Pepper Sauce. The manager, Bruno, welcomes
people with a smile, and especially recommends the Oregano
Seafood Soup (NT$220) and Herbs Baked Seafood (NT$450).
Many drinks and deserts are available; people are often
curious about the Soy Milk Latte (NT$140), which combines
coffee and soybean milk. The Cappuccino Cheesecake (NT$110)
helps add to the restaurant's fragrant aroma. -- By Josie
Wu, Translated by Michael Le Houllier

domain: food


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Ethiopia’s Relation With Neighboring, Influential Countries Improved Significantly: Panelists
www.fanabc.com | March 23, 2019
Addis Ababa, – Scholars have described the peace deal between the Ethiopian and Eritrean governments as a major diplomatic step taken in the history of the country.
Speaking about Ethiopia’s foreign policy and African participation at a panel that opened yesterday, the panelists also said the country’s relation with neighboring countries and influential countries has improved significantly.
African Union advisor and consultant, Abdul Mohammed said the change from hard border to soft border has created a spirit of peace among the border residents of Ethiopia and Eritrea, and demonstrated the fruits of diplomatic way of conflict resolution.
He pointed out that Ethiopia’s role in the Horn of Africa emanates from the significant responsibility that the country is shouldering to bring peace in the region in multi-lateral regional relations.
“We need to investigate our vulnerability and the opportunities we can get from the events unfolding in the Red Sea littoral countries,” he further pointed out.
Former UN Special Envoy for the Sahle, Hirut Gebresellassie said there is a need to bring together those who live in the cross-border areas of the country to benefit more from the Ethio-Eritrea peace and to support Ethiopia’s reform in the diplomatic arena.
Former diplomat and IGAD’s Head of Capacity Building Department, Hiruy Emmanuel said peace benefits any of the countries in setting a proper framework for settling disputes and to cooperate for mutual development.
He noted that embassies must scale up their efforts in promoting foreign relation to strengthen the relations of the country with other nations.
Foreign policy analyst, Solomon Ayele said Ethiopia and Eritrea must promote economic integration.
He emphasized on the need to create a joint forum with the Gulf countries on the basis of institutional relations.
Ethiopia must also strengthen its role in the United Nations and work on multi-lateral relations, he said.
A two-day forum dialogue under the theme, “Ethiopia’s foreign policy and African participation”, kicked off in Addis Ababa yesterday in lieu of the first year of Prime Minister Abiy’s administration, according to ENA.

domain: news


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domain: sociology


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This blog has my random thoughts; game-related posts go here.
People sometimes get tooth implants to replace missing or decayed teeth. Currently they're milled or 3d printed. But I think we could do much more. Why not put bluetooth into your tooth? We'd get:
- Speaker so that you could listen to tunes streamed from your phone.
- Microphone attached to the bone so that you could make phone calls without nearby people overhearing what you say.
- Sensors to measure and report the status of your mouth. Real time graphs of saliva, food, and dental bacteria can be sent to your phone, like a Fitbit for your mouth.
It'll finally turn the "tooth fillings pick up radio signals" myth into reality. Would you get one? I would!
Many or perhaps all of the smells produced by your body are produced by the bacterial ecosystems living on and in you. Some of these smells are things we can detect; others we're unaware of. Certain strains of skin bacteria attract mosquitos. By altering the ecosystem on our skin, we can repel mosquitos. Cool!
With genetic engineering, we can do even more. We can replace the bacteria that turn sweat into unpleasant smells with bacteria that turn sweat into floral scents! No more deodorant!
Today's tattoos are boring. Future tech will bring:
- Bioluminescent tattoos: using bioluminescent chemicals, your tattoos will glow or pulse, either all the time, or synchronized with a clock, or triggered by movement or light or sound. Imagine going to a dance club with this.
- E-ink tattoos: with e-ink particles embedded in your skin, you'll be able to change the pattern by applying an external array of electric fields. You'll place the “printer” on your arm, apply a new pattern, and then it'll hold that pattern until you want to change it.
- Biosensor tattoos: with e-ink particles attached to a layer of biosensor molecules, you'll be able to find out what's going on in your blood. You'll set up blocks that are sensitive to 50, 100, 150, 200 mg/dL of glucose, and then by seeing how many bars are “lit up”, you'll have a rough estimate of your blood sugar. You could do this for everything in your bloodstream.
Cool? or creepy?
I know there are lots of advanced technologies being developed for treating disease, but the same technologies could be used for non-disease applications. I wrote a little about this a few years ago. So I want to propose something that I think a lot of people would like:
There are people working on 3d printed organs. Wouldn't it be cool to get a 3d printed bladder? Would you like to super-size that?
Even better, wouldn't it be cool if your supplemental bladder automatically ran tests on your urine, like these Japanese toilets do? The toilets developed in 2004 can measure glucose levels but I'm sure there are other tests that will be practical too. Plus, if it's done in your 3d printed bladder, it can be transmitted to your smartphone in real time over low energy bluetooth, like a Fitbit.
I'd want one. Wouldn't you?
We're starting to learn how important gut bacteria are. Antibiotics can mess up the ecosystem in your gut. We have probiotics to try to restore the natural ecosystem.
This is assuming that natural is good. But the natural gut bacteria are evolved to match our natural diet. Most of us don't eat a natural diet.
I want unnatural gut bacteria.
We know cells can do amazing things. The cells in our body can turn fat and sugar into energy. Bacterial cells can do a far great variety of things, such as turning algae into oil, collecting gold atoms into gold veins, generate light, and process heavy metals. So let's design our own gut bacteria! I want to implant gut bacteria that turn chocolate cake into vitamins. I want gut bacteria to turn potato chips into omega 3.
Most people are drawn towards unhealthy food. We keep telling them to stop eating it, and eat healthy food instead. What if we could instead turn all unhealthy food into healthy food? (Also see my previous post on this subject.) I think that's a world-changing technology waiting to happen.

domain: health


IPHONE 8 VS SAMSUNG GALAXY S8: APPLE VS ANDROID SHOWDOWN With the iPhone 8 finally official, the biggest smartphone battle of the year is about to kick-off. Samsung has returned to form after the failed Galaxy Note 7, with the Galaxy S8 and Note 8 both featuring stunning designs and high-end features. But can the… Continue Reading Apple iPhone 8 Vs Samsung Galaxy S8: What’S The differen?
Apple’s new iPhones have finally been announced following months and months of speculation. They come in the form of the iPhone 8, 8 Plus and a more premium model called the iPhone X but Apple is still selling the iPhone 7 models and the iPhone 6S models. That means if you’re in the market for a new iPhone, you have a… Continue Reading Apple iPhone 8 Vs iPhone 7 Vs iPhone 6s: What’S The Difference?
10.5-inch iPad Pro vs 12.9-inch iPad Pro: What’s the difference between the newly launched 10.5-inch iPad Pro and the refreshed 12.9-inch model? We take a look. As expected, WWDC has yielded a new iPad Pro. The 10.5-inch tablet arrives alongside a refresh for the 12.9-inch model, as Apple adds new processors and screen tech to… Continue Reading 10.5-inch iPad Pro VS 12.9-inch iPad Pro: Except for different sizes and also those characteristics?
OUR EARLY VERDICT Apple’s most powerful tablet just got an energy boost – it’s still expensive, but the improvements to the screen and internal performance make this a very attractive tablet indeed. FOR Great screen quality Dynamic refreshing Extra power AGAINST Too expensive as a laptop replacement for some We’re big fans of the first… Continue Reading REVIEW HANDS ON: 2017 iPad Pro 2 12.9inch China Price, Release Date, Features & Specs
Key Features Screen: 4.7-inch Resolution: 1334×750 (326ppi) Processor: Apple A10 Fusion RAM: 2GB Storage: 32 /128 / 256 GB Operating system: iOS 10 Camera: 12MP rear camera, 7MP front-facing camera Connectivity: LTE, Wi-Fiac, NFC, IR, Bluetooth 4.2, Lightning and GPS Dimensions: 138.3 x 67.1 x 7.1mm Weight: 138g Design There is no doubt that the… Continue Reading Apple iPhone 7 Wholesale distributors in China


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"Management fads in higher education will never be the same. Birnbaum's penetrating analysis reveals in the clearest possible terms why fads die an early death."--Burton R. Clark, Allan M. Carter Professor Emeritus of Higher Education and Sociology, University of California, Los Angeles"Anyone in higher education leadership should read this critical and amusing book. It goes much further than the dull descriptions of management techniques for universities and colleges. It is fair, convincing, and well documented."--Frans van Vught, Rector Magnificus, University of Twente, The Netherlands When is a management innovation truly a good idea, and when is it only a fad? In this thoughtful book, Robert Birnbaum scrutinizes the rise and fall of management fads in higher education since the 1960s. He shows administrators and faculty how to move beyond the hype of new fads to make wise, informed decisions and adopt sound management policies. Birnbaum begins by analyzing the historical development of seven major management systems in higher education.
From these histories, he develops a model for understanding the life cycle of management innovations, including their creation, development, and eventual adoption or abandonment. He then explains the social and environmental factors that make institutions vulnerable to fads, plus the psychological issues that may lead academic managers to support failing fads. This comprehensive resource is for anyone who wants to understand how management innovations can be used to strengthen the educational and social purposes of higher education.
ROBERT BIRNBAUM is professor of higher education at the University of Maryland, College Park, where he teaches and writes about higher academic leadership and organization. He was previously vice chancellor of the City University of New York, vice chancellor of the New Jersey Department of Higher Education, and chancellor of the University of Wisconsin, Oshkosh. He is also author, coauthor, and editor of numerous articles and books, including How Academic Leadership Works and How Colleges Work.
DEVELOPING ACADEMIC MANAGEMENT FADS. Seeking the Grail: The Never-Ending Quest. We're From the Government and We're Here to Help Planning Programming Budgeting System (PPBS): More Bang for the Buck Management by Objectives (MBO): The Illusion of Empowerment Zero Base Budgeting (ZBB): Denying History. Survival in a Changing Environment Strategic Planning: The Grand Name Without the Grand Thing Benchmarking: Why Not the Best? Higher Education as a Commodity Total Quality Management/Continuous Quality Improvement (TQM/CQI): Every Day, in Every Way, Getting Better and Better Business Process Reengineering (BPR): Starting from Scratch. UNDERSTANDING ACADEMIC MANAGEMENT FADS. The Life Cycle of Academic Management Fads. Organizations and Fads. Managers and Fads. WORKING WITH ACADEMIC MANAGEMENT FADS. The Legacy of Fads. Managing Fads.

domain: library


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School of Magic 3D Screensaver presents users with a screen saver inspired by the world of Harry Potter. This screensaver tool brings the grand corridors and hallways of the School of Witchcraft and Wizardy.
Users will be able to view classrooms and even interact by searching for secret passages and rooms. The environment of the School of Magic 3D Screensaver is entirely in 3D, which makes for high-quality animations and realistic graphics.
It has a wide variety of settings accompanied by fitting music and sound effects, as well as a FPS counter. The School of Magic 3D Screensaver also has a digital clock that is automatically updated.

domain: design


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Focuses on Commodity Trading, Financial Services and Logistics Businesses;
Enters New Development Stage
HONG KONG — HNA Holding Group Co. Limited (“HNA Holding” or the “Company”, stock code: 521.HK) announced that it has officially changed its name from “HNA Holding Group Co. Limited” to “CWT International Limited” on 11 December 2017, the resolution of which was 100% approved by shareholders at the General Meeting held on 29 November 2017. In addition, the Company completed today the acquisition of all equity of CWT Limited (“CWT”, together with its subsidiaries “CWT Group”, SGX: C14), and as stated in the relevant announcements, CWT will delist from the official list of the SGX-ST from 9:00 a.m. on 18 December 2017.
The stock code of the CWT International Limited on the Hong Kong Stock Exchange (“HKSE”) remains as “521”. The stock short name of the Company for trading of shares on the HKSE will change from “HNA HOLDING” , to “CWT INT’L” , effective from 9:00 a.m. on 20 December 2017. The website address of the Company will also change from www.hnaholdinghk.com to www.cwtinternational.com, effective from 20 December 2017.
CWT International Limited commented, “After the acquisition of CWT Limited is completed, the Company will have an optimized business structure. The new name ‘CWT International Limited’ depicts a big picture with more dedicate presence of the Company’s new businesses and future strategies. Looking forward, the Company will place more focus on bulk commodity trading, logistics warehousing and ancillary financial services businesses. With a new corporate image, it will take advantage of China’s ‘One Belt One Road’ Initiative to explore new development opportunities, all to the end of creating better returns for shareholders.”
CWT Limited, a Singapore-listed integrated logistics service provider taking the leading position in the international logistics and commodity trading industries and has business presence in about 90 countries around the world. CWT prides ownership of international logistics, commodity trading and financial service platforms and has been committed to providing integrated logistics solutions covering from capital to service to customers.
After the acquisition is completed, CWT International Limited will strive to develop into a leading integrated commodity trading services provider with global reach drawing on the CWT Limited’s established global network, brand and resources advantages and mature capital operation experience. The combination of strengths and synergies that brings will enable CWT International Limited to actively seize the opportunities arising from the “One Belt One Road” Initiative, focusing on bulk commodity trading, ancillary financial services and logistics businesses, helping the company further enhance its business in the China market and boost economy of scale.

domain: finance


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Join Date: Aug 2011
Location: Southern California
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More Sad News from Utah - Avalanche Kills 24 yr old Boarder
Man who died in Utah avalanche identified
The Associated Press
Posted: 01/29/2012 01:54:30 PM PST
Updated: 01/29/2012 01:54:31 PM PST
SALT LAKE CITY—Police have identified the victim of a Utah backcountry avalanche as a 24-year-old man from the Salt Lake City area.
Unified Police Lt. Justin Hoyal says snowboarder Alecsander Barton triggered the avalanche Saturday after he started to descend Kessler Peak into Big Cottonwood Canyon near Salt Lake City.
Two other male companions—a snowboarder and a skier—watched as Barton was swept 2,400 feet down the slope. They later found his body completely buried near the bottom of the slide.
The other two men, who also are from the Salt Lake area, escaped unharmed.
Hoyal says Barton's death is a reminder that backcountry conditions are extremely dangerous and the public should stay away from steep terrain.
The death marks the ninth avalanche fatality in the West this season.

domain: geography


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KONE ropes in contracts in China and Australia
Finnish elevator and escalator giant KONE is involved, on a number of levels, in supplying two skyscraper projects in the central business districts of Beijing and Melbourne.
Metso wins a double deal in Russia
Finnish Metso has been chosen to deliver two complete grinding lines to Russia. The value of the order is not disclosed.
Glaston receives order from the US
Finnish glass processing expert Glaston has received an order for an FC Series tempering furnace and ProL lamination line from US-based Manko Windows Systems.
Finnish Raumaster continues strong growth
Finnish material handling specialist Raumaster has delivered a comprehensive cleantech solution to China and also secured a 20 million-euro order in Finland.
Wärtsilä makes acquisition and upgrades project
Finnish technology group Wärtsilä has agreed to acquire Sweden-based Puregas Solutions. Wärtsilä is also co-operating with its subsidiary American Hydro to increase the efficiency and production capacity of a pump-generating plant in the US.
MacGregor establishes head office in Singapore
MacGregor, part of Cargotec, has established its head office in Singapore in order to strengthen its local presence in Asia.
Konecranes signs big numbers in Belgium
Konecranes’ Antwerp-based service organisation will take care of all of the maintenance and repair work on more than 150 Konecranes Noell Straddle Carriers.
Valmet receives order from South Africa
Finnish industrial company Valmet will deliver a new gravity feed chipper to the Sappi Ngodwana mill in South Africa.
Kalmar and Glaston deliver to Australia and the US
Kalmar, part of Cargotec, is continuing its co-operation with Australia’s largest stevedore DP World Australia and will deliver 38 machines to DP World Logistics Australia. Finnish glass processing company Glaston, meanwhile, has received a significant order from the US.
KONE to equip cruise ships and mega yachts
Finnish elevator and escalator industry giant KONE is to equip two new MV WERFTEN cruise ships being built in Germany. In addition, the company will deliver elevators and escalators to two MV WERFTEN ‘Endeavor’ expedition mega yachts that will operate in the Arctic, Antarctic and in the Tropics.
Wärtsilä powers world first for fish farming industry
Finnish technology group Wärtsilä has been contracted to deliver the ship design for a new processing and transportation vessel to be built at the Balenciaga shipyard in Spain.

domain: economics


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Kentucky State Representative Attica Scott was arrested in connection with Breonna Taylor’s protest. Scott is the only black female legislator in the state and she was arrested alongside her daughter, 19-year-old Ashanti, by the Louisville Metro police on Thursday. Both of them were charged with rioting, failure to disperse, and unlawful assembly before they were released on Friday.
But Scott stated that she was not involved in any protests and that she just happened to be arrested a few minutes before the 9 pm curfew kicked in. She said she was on her way to the First Unitarian Church which allowed people to stay within its premises if they were caught outside during the curfew.
Mayor Greg Fischer and Kentucky Attorney General Daniel Cameron had implemented a curfew throughout the state as from 9 pm but stipulated that the curfew will not apply to people going to places of worship. Scott said she and 24 other people were on their way to seek refuge in the church at about 8:58 pm when they were blocked by a team of policemen and subsequently arrested.
The Louisville Metro Police Department said in a statement that some demonstrators in downtown Louisville threw a flare into a library, broke the windows of a restaurant, and caused general damage in the area before the 9 pm curfew took effect. They accused Scott and 24 others as being part of the protesters who flouted the curfew to cause damage in town.
“In Breonna’s name, neither I or my teenage daughter who was arrested with me tried to burn down a library that our people need,” Scott said after her release on Friday. “Those are some ridiculous charges that are levied against us.”
As proof of her innocence, she showed a video recording that she personally made during the short walk to the church before police officers blocked their approach to the house of worship. In the video, she was walking with other people and recording the surrounding area which had police vans and police officers in riot gear. The video showed a policeman approaches her and asked her if she was recording and to put off her phone.
“You might want to turn it off so it doesn’t get broke, OK? Turn it off and put it in your pocket, okay? Alright, go ahead and turn it off and put it in your pocket, I’m trying to be as nice as I can,” the officer told her before the video recording stopped abruptly.
Scott has steadily confessed that she does not regret the arrest and would put up a fight to get justice for Breonna Taylor who was killed by police officers in her home in May.

domain: law


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This post was last updated on January 27th, 2019 at 07:33 pm
Creamfields 2019 is set to be one of the greatest festivals of this summer; from the lineup to the tickets, this article will guide you through the UK festival.
We know, 2018 edition has ended only some weeks ago but, Creamfields UK has just started to sell the tickets for the 2019 edition.
Considered one of the biggest and greatest electronic dance music festival around the globe and, for sure, the greatest festival in the UK, Creamfields has welcomed this year 70000 people from over the world plus more than 7 million have watched the performance of over 300 artists online.
Carl Cox, Axwell & Ingrosso, Steve Angello, Major Lazer, Tiësto, Fatboy Slim, Pete Tong, Annie Mac, Camelphat, Hot Since 82, Kaleidoscope Orchestra, and Solardo are only a few names that have joined Creamfields UK this year and, the organization has assured us that it will be even better.
Tickets for both festival and camping are now on sale for 2018 edition and we suggest you save it before prize go higher. Big performances are going to happen next year and, we’re sure you don’t want to miss it.
Creamfields UK 2019 when and where?
Creamfields UK 2019 will take place at Daresbury, Cheshire UK (In between Liverpool and Manchester) from the 22nd to the 25th of August.
Creamfields UK 2019 tickets are divided in several categories and the price increases over time. Categories are:
- Standard Camping
- Standard Day
- Bronze Camping
- Silver Camping
- Gold Camping
- Gold Day
Tickets for single days are divided into Saturday, Sunday or two days. Deposit schemes and VIP accommodations are available as well. Read more.
Creamfields UK has now confirmed the four headliners for the 2019 edition. It includes the only UK show of the Swedish House Mafia reunion tour, Deadmau5, the first UK appearance of Adam Beyer and Cirez D show and, last but not least, The Chemical Brothers will return for another impressive performance.
The complete lineup will be added as soon as will be announced.
The full festival maps, as well as the number of the stages and their location is still TBA.


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|Best price found||£277||The best flight deal from Southampton to Asia found on momondo in the last 72 hours is £277|
|Fastest flight time||13h 35m||The fastest flight from Southampton to Asia takes 13h 35m.|
|Direct flights||None||There are no direct flights from Southampton to Asia. Popular non-direct routes for this connection are Southampton Eastleigh - Denpasar Bali Ngurah Rai, Southampton Eastleigh - Bangkok Suvarnabhumi and Southampton Eastleigh - Incheon Intl.|
Pros: I've never been on a flight with such narrow seat and thin cushion. There was no entertainment offered for the almost 4 hour flight. There was no means of charging any electronic gears. The airplane seems to be 30 years behind time. Crew was unfriendly and smiling faces are not part of the uniform.
Cons: Very narrow seats and thim cushion. No entertainment offered an do means of recharging electronic devices.
Cons: It was late
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You can take advantage of momondo’s Price Alerts by first searching for your flights to Southampton from Asia. Flight offers will be shown to you in real-time. From there you can create a Price Alert by using our on-site widget.
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We aggregate our prices from over 700+ competitors from airlines to OTAs. We operate in over 30 markets worldwide to show you a wide range of travel options.

domain: travel


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If there was only one reason to go to next week’s Anzac Day services, 99-year-old Max Hammond would be it.
The World War II veteran, who served in both the Middle East and the Pacific, marks April 25 as a sacred day on the calendar.
“To me, it’s to honour the chaps you went to war with who didn’t come home. We left some awfully good people behind who laid their lives down for this country,” Mr Hammond said of the significance of Anzac Day.
“We did it hard and we remember the fellas that didn’t come back. That’s what it’s all about, mateship. We just remember those fellas, we come in their honour.”
Mr Hammond said the younger generations were showing a growing interest in the ceremony.
“It shows to me the respect that the citizens of Warrnambool, schools in particular, show to we veterans. It’s amazing the respect these kids show towards us,” he said.
Mr Hammond turns 100 in December, which would make him the first Warrnambool veteran to reach the milestone.
Fellow veteran Margaret Morton served in the Women's Royal Australian Naval Service at the Cerberus training base during the Second World War.
“It was the best time of my life. It was the meeting of the people, the other girls, I made some fantastic friends and I still keep in touch with a few,” she said.
“I march in Warrnambool and Dennington (on Anzac Day). I’m very proud, actually, of the service, because I was there myself but also because of my family, my siblings.”
Now 91, Mrs Morton has been selling badges for a local Anzac Appeal for many years.
RSL president John Miles said badge sellers were out in force at Warrnambool’s shopping centres and main streets.
Mr Miles said all money raised from the appeal would go towards veterans and their families.
“We’ve got younger veterans coming in seeking assistance. We just need penny to help them,” he said.
“We’re hoping people will dig deep and support our appeal. Every cent that is raised will go to what it is meant to go to.
“If people donate $1 that $1 will go towards RSL welfare.”
- Warrnambool’s Anzac Day commemorations will begin with the dawn service at 6am next Wednesday. The march will gather at 5.45am outside the library before making its way to the war memorial. Due to the Liebig Street works, the march before the 11am service will begin on Timor Street outside the bowling alley at 10.45am.


text: Coady (The Chocolate Companion; Chocolate: Food of the Gods) acquired an international following with her London chocolate shop, Rococo. Her new, lavishly illustrated book features recipes as well as a history of chocolate and “master classes” on ganache, tempering, and other special techniques. Along with indulgent, mouth-watering desserts and other treats (e.g., drinks such as Chocolate Manhattans), she offers an eclectic selection of savory recipes, from Chocolate Tempura to Pan-Roasted Chicken with Chocolate Vinegar (some of her “nonsweets” may be a bit too exotic for many readers). It’s a bit surprising that she doesn't include more information on chocolates with “high cocoa content” (i.e., extra bittersweet and the like) that are increasingly available to consumers. Nevertheless, professionals and other chocolate lovers will find her latest book delectable and a bargain; for most baking collections.


The House Subcommittee on Aviation held its first hearing in seven years on the FAA’s oversight of commercial space last month. Members heard from a heavily industry-centric panel of experts who largely praised the moratorium on regulations that is in place until 2023.
The National Transportation Safety Board’s scathing criticism of the FAA’s oversight role on SpaceShipTwo prior to the accident was briefly discussed on a couple of occasions, as were the potential conflicts between FAA’s dual roles of oversight and promotion.
Taber MacCallum of World View Enterprises dismissed the criticism of FAA Associate Administrator George Nield and the FAA’s performance prior to the crash as Monday morning quarterbacking. He also called for a permanent extension of the moratorium on regulations.
Michael López-Alegría also claimed that the FAA had done its job properly. He dismissed the idea that regulating the industry would make it any safer.
- Dr. George C. Nield, Associate Administrator for Commercial Space Transportation, Federal Aviation Administration | Written Testimony
- Dr. Gerald L. Dillingham, Director of Civil Aviation Issues, Government Accountability Office | Written Testimony
- Mr. Michael Gold, Chair, Commercial Space Transportation Advisory Committee | Written Testimony
- Mr. Michael López-Alegría, Vice Chair, Commercial Space Transportation Advisory Committee | Written Testimony
- Mr. Taber MacCallum, Chief Technology Officer, World View Enterprises | Written Testimony


A 24-hour long strike is to be held by more than 500 ambulance personnel nationwide on Friday in an ongoing row over union recognition.
The almost year-long impasse has resulted in protracted strikes and are planned to continue until the Health Service Executive (HSE) agrees to negotiations and the agreement that union members from the National Ambulance Service Representative (NASRA) branch of the Psychiatric Nurses Association (PNA) will be recognised.
The union represents paramedics, advanced paramedics and emergency medical technicians
NASRA have confirmed that the strikes will take place on May 31 and June 1, the start of the bank holiday weekend. More 24-hour strikes will follow on dates yet to be announced by the union in the coming weeks.
Peter Hughes, PNA General Secretary, said once again the HSE was forcing an escalation in a dispute that is entirely of the HSE’s making. To date, PNA ambulance branch members have engaged in a work to rule and have undertaken six strike days since the dispute began.
Mr Hughes said: “It has become very clear that not alone has the HSE refused to engage in the normal industrial relations protocol of agreeing contingency plans for our previous strike days, but it has also exploited the professionalism and dedication of ambulance personnel to ensure that ambulance services are provided even in a strike situation.
“HSE management have sat back and placed the responsibility of maintaining ambulance cover on our members. As we move to 24 hour strikes it is incumbent on the Executive to comply with custom and practice and negotiate contingency arrangements for the planned (day-long) strike days.”
He added: “The demand by more than 500 of our members to be members of, and represented by, the PNA now has strong cross-party political support in the Dáil. However, despite (the Minister for Health’s) comments in the Dáil that he wants this dispute referred to the Workplace Relations Commission, the Minister Simon Harris has been incapable of bringing the HSE to its senses and ending this divisive dispute.”
It should now be a priority for the new HSE Director General, Paul Reid, to bring this dispute to an end, and stop trying to force ambulance personnel into unions that they have made it clear they are not prepared to be members of. Mr Reid has an opportunity to end this dispute which is impacting on performance and morale within the ambulance services - a vital area of frontline health services.
The ongoing strike is the first time in 100 years that members of the Ambulance service have taken to the picket line as an independent body - separate to other HSE employees.
The HSE has consistently insisted that the PNA does not have negotiating rights and said they will only deal with the union Siptu. They would also not comment on High Court moves to gain an injunction.
However, the Executive defended its stances in relation to NASRA and said ambulance personnel were well represented through agreed industrial relations processes.
Army ambulance crews helped shore up services during six previous 12-hour strikes and are expected to be on standby again.


Ghana: GDP breaks downward trend; registers impressive growth rate of 8.5%
- October 4, 2018
Ghana’s Gross Domestic Product (GDP) registered an impressive growth rate of 8.5 percent in 2017 from a rate of 3.5 percent in 2016, breaking the downward trend since 2011, while per capita growth increased from 1.4 percent in 2016 to 6.1 percent in 2017.
In 2017, the services sector, which represents more than half of GDP, registered a growth rate of 4.3 percent, compared to 5.7 percent in 2016, while industry, the second largest sector, recorded an increase of 16.7 percent in 2017, compared to a decrease of 0.5 in 2016.
For the agricultural sector, a growth rate of 8.4 percent was recorded in 2017, as against 3.0 percent in 2016.
These are contained in the State of the Ghanaian Economy Report, 2017, which was launched in Accra, on October 2, 2018.
Prof. Felix Ankomah Asante, Director, University Of Ghana’s Institute of Statistical, Social and Economic Research (ISSER) presented the Report which was launched by Nana Osei-Bonsu, Chief Executive Officer, Private Enterprise Foundation, and Chairman for the occasion.
The Report explains that the outstanding performance by the industrial sector in 2017 was attributable to the production in upstream oil and gas, and has little direct impact bearing on diversification of the Ghanaian economy based on value addition.
According to the Report, the end-of-year inflation rate in 2017 was 11.8 percent as against 15.4 percent in 2016, with the average annual inflation rate falling substantially from 17.5 percent in 2016 to 12.4 percent on 2017 and achieving the target rate.
Broad money supply, including foreign currency deposits, the Report says, grew by 16.7 percent in 2017 as against 22.0 percent in 2016.
The Report notes that a new medium-term national development framework—An Agenda for Jobs: Creating Prosperity and Equal Opportunity for All, 2018-2021 (First Step)—has been developed, and indicates that since many of the projects under the framework were initiated in 2017, it is too early to effectively assess progress.
However, the Report says it is anticipated that the four initiatives under the policy will expand employment across districts, increase the supply of secondary school graduates and strengthen local authorities financially.
The Report notes that implementation of the initiatives under the new development framework will require additional financial resources, with possible adverse implications for fiscal balance.
The chairman for the occasion, Nana Osei-Bonsu, stressed the need to address revenue shortages by reducing tax exemptions.
Nana Osei-Bonsu said Ghana’s future depended on proper and strategic planning, while on corruption, he said the citizenry had a responsibility to support government in fighting it.
ISSER is one of the three Research institutions at the University of Ghana, Legon. The other two are the Regional Institute for Population Studies and the Institute of African Studies.
Source: ISD (G.D. Zaney, Esq.)
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RNA transcription is needed for memory formation. However, the ability to identify genes whose expression is altered by learning is greatly impaired because of methodological difficulties in profiling gene expression in specific neurons involved in memory formation. Here, we report a novel approach to monitor the expression of genes after learning in neurons in specific brain pathways needed for memory formation. In this study, we aimed to monitor gene expression after fear learning. We retrogradely labeled discrete thalamic neurons that project to the lateral amygdala (LA) of rats. The labeled neurons were dissected, using laser microdissection microscopy, after fear conditioning learning or unpaired training. The RNAs from the dissected neurons were subjected to microarray analysis. The levels of selected RNAs detected by the microarray analysis to be altered by fear conditioning were also assessed by nanostring analysis. We observed that the expression of genes involved in the regulation of translation, maturation and degradation of proteins was increased 6 h after fear conditioning compared to unpaired or naïve trained rats. These genes were not expressed 24 h after training or in cortical neurons that project to the LA. The expression of genes involved in transcription regulation and neuronal development was altered after fear conditioning learning in the cortical-LA pathway. The present study provides key information on the identity of genes expressed in discrete thalamic and cortical neurons that project to the LA after fear conditioning. Such an approach could also serve to identify gene products as targets for the development of a new generation of therapeutic agents that could be aimed to functionally identified brain circuits to treat memory-related disorders.
Bibliographical notePublisher Copyright:
© 2014 International Society for Neurochemistry.
- cortical-LA pathway
- fear conditioning
- gene expression
- learning and memory
- thalamic-LA pathway
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience

domain: psychology


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High Linoleic Safflower Oil
- Data Sheet (英语)
Sesajal S.A. de C.V. is a supplier of functional ingredients for the food industry. Sesajal S.A. de C.V. has a wide range of products including oily seeds, fruit juice powder, and oils. Sesajal S.A. de C.V. uses advanced processes and technology to create high quality products that have many benefits such as the removal of oxalic acid, preservation of lignans and tocopherols, and gluten free grades.


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POSTED ON Jul 06 , 2022
Does this kid want an anime sex doll that can have sex? For those who like big breasted dolls and want a daughter, it is very particular. The details are finely crafted, especially the cute shape is very eye-catching, and the 63 cm is easy to carry and the body is small. Lightweight and easier to store, clean and maintain. The whole body is comfortable and comfortable, and it is very satisfying to sleep together, and it will be perfectly reproduced like the real thing! It still feels good, the restoration is very realistic, there are many ways to enjoy photography and cosplay, let's enjoy it together!


Motorcycle Centerstand Kawasaki KLR 650 (08 – 18)
A motorcycle Center-stand is the must-have accessory to ease basic chain maintenance, tyre changes, parking, and bike cleaning. This center-stand includes a foot lever arm to aid in raising the bike off the ground.
- Steel construction.
- Double Safety retention spring.
- Powder coated gloss black finish for a long service life.
- Allows maintenance in any location.
- Foot lever for deployment leverage.
- Simple to fit.
Special Note: We do not recommend installing the Motorcycle Center-stand on bikes with a lowered rear suspension because use on a lowered bike may result in:
- Ground clearance and cornering clearance problems.
- Difficulty in lifting the lowered bike onto the center-stand.
- Accurate processed Centerstand.
- Powder-coated Surface.
- Makes maintenance work possible in any location.
- Design allows adequate leverage for easy use.
- Optimal lean angle and ground clearance.
- Mounting material.
- Mounting instructions.


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Do not hesitage to give us a call. We are an expert team and we are happy to talk to you.
This 7 days tour from Tangier to Marrakech takes you on a journey through some of Morocco‘s most beautiful and historic destinations. You will start your journey in the charming blue-washed town of Chefchaouen, then travel south to Fes, one of Morocco’s most ancient cities.
From there, you will venture into the Sahara Desert and spend a night in a traditional Berber camp. You will also have the opportunity to explore the stunning Dades Valley and visit the famous Ait Benhaddou Kasbah before finally arriving in Marrakech, one of Morocco’s most vibrant and bustling cities. Throughout the tour, you will be accompanied by an experienced guide who will help you discover the rich history, culture, and traditions of Morocco.
Overall, this tour is a great way to experience the diverse and enchanting landscapes of Morocco, from the picturesque blue streets of Chefchaouen to the breathtaking Sahara Desert. You will have the chance to explore ancient medinas, hike through stunning valleys, ride camels in the desert, and immerse yourself in Moroccan culture and traditions. This tour is perfect for travelers who want to experience the best of Morocco in just seven days.
3 Hours Before Flight Time
Your 7 days tour of Morocco will begin in Tangier, where you will be picked up by your tour guide and driven to the charming town of Chefchaouen. The journey will take approximately 2.5 hours, and you will have the opportunity to admire the beautiful scenery of the Rif Mountains along the way. Upon arrival in Chefchaouen, you will check into your hotel and have some free time to explore the town’s picturesque blue-washed streets and alleyways.
After breakfast at your hotel, you will continue your journey south towards the imperial city of Fes. The drive will take approximately 4 hours, but you will have plenty of opportunities to stop and take in the breathtaking views of the Moroccan countryside along the way. Upon arrival in Fes, you will check into your hotel and have the rest of the day to relax or explore the city on your own.
Today, you will have a full day to explore the ancient city of Fes with your tour guide. You will visit the famous medina, which is a UNESCO World Heritage Site and one of the largest car-free urban areas in the world. You will also visit the Bou Inania Madrasa, the Royal Palace, and the Jewish Quarter. In the evening, you will return to your hotel in Fes.
After breakfast, you will leave Fes and head south towards the Sahara Desert. Along the way, you will pass through the Middle Atlas Mountains and the Ziz Valley, which is known for its stunning palm groves. You will arrive in Merzouga in the late afternoon, where you will check into your hotel and enjoy a traditional Moroccan dinner.
Today, you will experience the beauty of the Sahara Desert with a full-day desert tour. You will ride camels through the Erg Chebbi dunes, visit a Berber village, and enjoy a traditional lunch in the desert. In the evening, you will return to your hotel in Merzouga and have dinner.
After breakfast, you will leave Merzouga and continue your journey towards the Dades Valley. Along the way, you will pass through the Todra Gorge, where you will have the opportunity to take a short hike and admire the stunning scenery. You will arrive in the Dades Valley in the late afternoon, where you will check into your hotel and have dinner.
Today is your final day of the tour. After breakfast at your hotel, you will leave the Dades Valley and head towards the vibrant city of Marrakech. Along the way, you will pass through the High Atlas Mountains and stop at the famous Ait Benhaddou Kasbah, which is a UNESCO World Heritage Site. You will arrive in Marrakech in the late afternoon, where you will be dropped off at your hotel or the airport.


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The next-gen update for The Witcher 3 has finally arrived. The update rolled out on Tuesday across various platforms, with the Xbox Series X|S and Windows versions launching late afternoon. The update is one of the most anticipated gaming events of 2022, despite being for a seven year old game. What’s included in the update? Read on to find out.
- 60fps for the first time on consoles
- Ray tracing (with lower framerate)
- Enhanced textures and shadow quality
- Improved draw distances
The new Photo Mode allows players to capture the stunning scenery of the Continent. This feature will add a whole new dynamic to the game for many players, especially those with a photographer’s eye.
Netflix series tie-ins
- There is an alternative appearance for the character Dandelion inspired by the Netflix show, as well as a Nilfgaardian Armor set.
- The new quest In the Eternal Fire’s Shadow is inspired by the show.
There are also several quality of life improvements to be had in The Witcher 3 next-gen update. Among them are the ability to pause during cutscenes, and a quick sign-casting feature that makes casting magic a breeze. And a slow-walk feature for controller users makes navigating the game world more friendly than ever.
There are a host of other smaller changes as well—far too many to go into here. You can find the full patch notes via the link at the beginning.
Via Pure Xbox.

domain: entertainment


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Indexed on: 21 Jul '04Published on: 21 Jul '04Published in: Circulation
Nephrotic syndrome (NS) is associated with hyperlipidemia, altered lipid regulatory enzymes and receptors, and increased risk of progressive renal and cardiovascular diseases. Acyl-coenzyme A:cholesterol acyltransferase (ACAT) catalyzes intracellular esterification of cholesterol and plays an important role in production of apolipoprotein B-containing lipoproteins, regulation of cholesterol-responsive proteins, and formation of foam cells. Because hepatic ACAT-2 is markedly upregulated in NS, we tested the hypothesis that inhibition of ACAT may improve cholesterol metabolism in NS.Rats with puromycin-induced NS were treated with either the ACAT inhibitor CI-976 or placebo for 2 weeks. Normal rats served as controls. Plasma lipids, renal function, and key lipid regulatory factors were measured. Untreated NS rats showed heavy proteinuria; hypoalbuminemia; elevated plasma cholesterol, triglyceride, LDL, VLDL, and total cholesterol-to-HDL cholesterol ratio; increased hepatic ACAT activity, ACAT-2 mRNA, and ACAT-2 protein; and reduced LDL receptor, HDL receptor, otherwise known as scavenger receptor B-1 (SRB-1) and plasma lecithin-cholesterol acyltransferase (LCAT). ACAT inhibitor reduced plasma cholesterol and triglycerides, normalized total cholesterol-to-HDL cholesterol ratio, and lowered hepatic ACAT activity without changing ACAT-2 mRNA or protein. This was accompanied by near normalizations of plasma LCAT, hepatic SRB-1, and LDL receptor and a significant amelioration of proteinuria and hypoalbuminemia.Pharmacological inhibition of ACAT reverses NS-induced LDL receptor, HDL receptor, and LCAT deficiencies; improves plasma lipid profile; and ameliorates proteinuria in nephrotic animals. Further studies are needed to explore the effect of ACAT inhibition in nephrotic humans.

domain: literature