The Physics Beyond Colliders initiative is an exploratory study aimed at exploiting the full scientific potential of the CERN's accelerator complex and scientific infrastructures through projects ...complementary to the LHC and other possible future colliders. These projects will target fundamental physics questions in modern particle physics. This document presents the status of the proposals presented in the framework of the Beyond Standard Model physics working group, and explore their physics reach and the impact that CERN could have in the next 10-20 years on the international landscape.
Segmentation of the vertebrate hindbrain leads to the formation of rhombomeres, each with a distinct anteroposterior identity. Specialised boundary cells form at segment borders that act as a source ...or regulator of neuronal differentiation. In zebrafish, there is spatial patterning of neurogenesis in which non-neurogenic zones form at boundaries and segment centres, in part mediated by Fgf20 signalling. To further understand the control of neurogenesis, we have carried out single cell RNA sequencing of the zebrafish hindbrain at three different stages of patterning. Analyses of the data reveal known and novel markers of distinct hindbrain segments, of cell types along the dorsoventral axis, and of the transition of progenitors to neuronal differentiation. We find major shifts in the transcriptome of progenitors and of differentiating cells between the different stages analysed. Supervised clustering with markers of boundary cells and segment centres, together with RNA-seq analysis of Fgf-regulated genes, has revealed new candidate regulators of cell differentiation in the hindbrain. These data provide a valuable resource for functional investigations of the patterning of neurogenesis and the transition of progenitors to neuronal differentiation.
The establishment and maintenance of precisely organized tissues requires the formation of sharp borders between distinct cell populations. The maintenance of segregated cell populations is also ...required for tissue homeostasis in the adult, and deficiencies in segregation underlie the metastatic spreading of tumor cells. Three classes of mechanisms that underlie cell segregation and border formation have been uncovered. The first involves differences in cadherin-mediated cell-cell adhesion that establishes interfacial tension at the border between distinct cell populations. A second mechanism involves the induction of actomyosin-mediated contraction by intercellular signaling, such that cortical tension is generated at the border. Third, activation of Eph receptors and ephrins can lead to both decreased adhesion by triggering cleavage of E-cadherin, and to repulsion of cells by regulation of the actin cytoskeleton, thus preventing intermingling between cell populations. These mechanisms play crucial roles at distinct boundaries during development, and alterations in cadherin or Eph/ephrin expression have been implicated in tumor metastasis.
Whether or not the scale of a society's income inequality is a determinant of population health is still regarded as a controversial issue. We decided to review the evidence and see if we could find ...a consistent interpretation of both the positive and negative findings.
We identified 168 analyses in 155 papers reporting research findings on the association between income distribution and population health, and classified them according to how far their findings supported the hypothesis that greater income differences are associated with lower standards of population health. Analyses in which
all adjusted associations between greater income equality and higher standards of population health were statistically significant and positive were classified as “wholly supportive”; if none were significant and positive they were classified as “unsupportive”; and if some but not all were significant and supportive they were classified as “partially supportive”. Of those classified as either wholly supportive or unsupportive, a large majority (70 per cent) suggest that health is less good in societies where income differences are bigger.
There were substantial differences in the proportion of supportive findings according to whether inequality was measured in large or small areas. We suggest that the studies of income inequality are more supportive in large areas because in that context income inequality serves as a measure of the scale of social stratification, or how hierarchical a society is.
We suggest three explanations for the unsupportive findings reported by a minority of studies. First, many studies measured inequality in areas too small to reflect the scale of social class differences in a society; second, a number of studies controlled for factors which, rather than being genuine confounders, are likely either to mediate between class and health or to be other reflections of the scale of social stratification; and third, the international relationship was temporarily lost (in all but the youngest age groups) during the decade from the mid-1980s when income differences were widening particularly rapidly in a number of countries. We finish by discussing possible objections to our interpretation of the findings.
Population health tends to be better in societies where income is more equally distributed. Recent evidence suggests that many other social problems, including mental illness, violence, imprisonment, ...lack of trust, teenage births, obesity, drug abuse, and poor educational performance of schoolchildren, are also more common in more unequal societies. Differences in the prevalence of ill health and social problems between more and less equal societies seem to be large and to extend to the vast majority of the population. Rather than referencing all the literature, this paper attempts to show which interpretations of these relationships are consistent with the research evidence. After discussing their more important and illuminating characteristics, we conclude that these relationships are likely to reflect a sensitivity of health and social problems to the scale of social stratification and status competition, underpinned by societal differences in material inequality.
High-resolution human cytomegalovirus transcriptome Gatherer, Derek; Seirafian, Sepehr; Cunningham, Charles ...
Proceedings of the National Academy of Sciences - PNAS,
12/2011, Letnik:
108, Številka:
49
Journal Article
Recenzirano
Odprti dostop
Deep sequencing was used to bring high resolution to the human cytomegalovirus (HCMV) transcriptome at the stage when infectious virion production is under way, and major findings were confirmed by ...extensive experimentation using conventional techniques. The majority (65.1%) of polyadenylated viral RNA transcription is committed to producing four noncoding transcripts (RNA2.7, RNA1.2, RNA4.9, and RNA5.0) that do not substantially overlap designated protein-coding regions. Additional noncoding RNAs that are transcribed antisense to protein-coding regions map throughout the genome and account for 8.7% of transcription from these regions. RNA splicing is more common than recognized previously, which was evidenced by the identification of 229 potential donor and 132 acceptor sites, and it affects 58 protein-coding genes. The great majority (94) of 96 splice junctions most abundantly represented in the deep-sequencing data was confirmed by RT-PCR or RACE or supported by involvement in alternative splicing. Alternative splicing is frequent and particularly evident in four genes (RL8A, UL74A, UL124, and UL150A) that are transcribed by splicing from any one of many upstream exons. The analysis also resulted in the annotation of four previously unrecognized protein-coding regions (RL8A, RL9A, UL150A, and US33A), and expression of the UL150A protein was shown in the context of HCMV infection. The overall conclusion, that HCMV transcription is complex and multifaceted, has implications for the potential sophistication of virus functionality during infection. The study also illustrates the key contribution that deep sequencing can make to the genomics of nuclear DNA viruses.
The role of classroom discussions in comprehension and learning has been the focus of investigations since the early 1960s. Despite this long history, no syntheses have quantitatively reviewed the ...vast body of literature on classroom discussions for their effects on students' comprehension and learning. This comprehensive meta-analysis of empirical studies was conducted to examine evidence of the effects of classroom discussion on measures of teacher and student talk and on individual student comprehension and critical-thinking and reasoning outcomes. Results revealed that several discussion approaches produced strong increases in the amount of student talk and concomitant reductions in teacher talk, as well as substantial improvements in text comprehension. Few approaches to discussion were effective at increasing students' literal or inferential comprehension and critical thinking and reasoning. Effects were moderated by study design, the nature of the outcome measure, and student academic ability. While the range of ages of participants in the reviewed studies was large, a majority of studies were conducted with students in 4th through 6th grades. Implications for research and practice are discussed.
The formation of sharp borders, across which cell intermingling is restricted, has a crucial role in the establishment and maintenance of organized tissues. Signaling of Eph receptors and ephrins ...underlies formation of a number of boundaries between and within tissues during vertebrate development. Eph–ephrin signaling can regulate several types of cell response—adhesion, repulsion and tension—that can in principle underlie the segregation of cells and formation of sharp borders. Recent studies have implicated each of these cell responses as having important roles at different boundaries: repulsion at the mesoderm–ectoderm border, decreased adhesion at the notochord–presomitic mesoderm border, and tension at boundaries within the hindbrain and forebrain. These distinct responses to Eph receptor and ephrin activation may in part be due to the adhesive properties of the tissue.
•Eph receptor and ephrin signaling mediate boundary formation.•Eph–ephrin signaling can act by regulating adhesion, tension and/or repulsion.•The predominant mechanism may depend upon adhesive properties of the tissue.
Recent studies of several multi-body D0 meson decays have revealed that the final states are dominantly CP-even. However, the small value of the width difference between the two physical eigenstates ...of the D0–D‾0 system indicates that the total widths of decays to CP-even and CP-odd final states should be the same to within about a percent. The known contributions to the width difference from hadronic D0 decays are discussed, and it is shown that an apparent excess of quasi-CP-even modes is balanced, within current uncertainty, by interference effects in quasi-flavour-specific decays. Decay modes which may significantly affect the picture with improved measurements are considered.
•A review of flow cytometry for monitoring probiotic culture viability was undertaken.•Flow cytometry had good correlation with plate counts for concentrated fresh cultures.•Sample clean up steps are ...extremely important to achieve optimal resolution.•Flow cytometry generates multi-parametric data not always reflecting plate counts.•Regulatory definitions of cell viability and cell vitality needs clarification.
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