Probing the thermal state of the intergalactic medium at z > 5 with the transmission spikes in high-resolution Ly α forest spectra

We compare a sample of five high-resolution, high S/N Ly$\alpha$ forest spectra of bright $6<z \lesssim 6.5$ QSOs aimed at spectrally resolving the last remaining transmission spikes at $z>5$ with those obtained from mock absorption spectra from the Sherwood and Sherwood-Relics suites of hydrodynamical simulations of the intergalactic medium (IGM). We use a profile fitting procedure for the inverted transmitted flux, $1-F$, similar to the widely used Voigt profile fitting of the transmitted flux $F$ at lower redshifts, to characterise the transmission spikes that probe predominately underdense regions of the IGM. We are able to reproduce the width and height distributions of the transmission spikes, both with optically thin simulations of the post-reionization Universe using a homogeneous UV background and full radiative transfer simulations of a late reionization model. We find that the width of the fitted components of the simulated transmission spikes is very sensitive to the instantaneous temperature of the reionized IGM. The internal structures of the spikes are more prominant in low temeperature models of the IGM. The width distribution of the observed transmission spikes, which require high spectral resolution ($\leq$ 8 km/s) to be resolved, is reproduced for optically thin simulations with a temperature at mean density of $T_0= (11000 \pm 1600,10500\pm 2100,12000 \pm 2200)$ K at $z= (5.4,5.6,5.8)$. This is weakly dependent on the slope of the temperature-density relation, which is favoured to be moderately steeper than isothermal. In the inhomogeneous, late reionization, full radiative transfer simulations where islands of neutral hydrogen persist to $z\sim5.3$, the width distribution of the observed transmission spikes is consistent with the range of $T_0$ caused by spatial fluctuations in the temperature-density relation

Specific phobia predicts psychopathology in young women

Contains fulltext : 90255.pdf (publisher's version ) (Closed access)Although specific phobia is characterized by an early age at onset and by high rates of comorbidity, few studies have examined comorbid relationships prospectively. The present study investigated the association between specific phobia and the risk of a broad range of psychopathology among young women in the community. Data came from the Dresden Predictor Study in which 1,538 German women (18-25 years) completed a diagnostic interview at two time points. Women with specific phobia had a twofold increase in odds of developing any anxiety disorder, generalized anxiety disorder, depression, and any somatoform disorder during 17 months, compared to women without specific phobia. Except for depression, these associations persisted after adjustment for all comorbid mental disorders. Specific phobia thus appears to be a risk factor for a variety of problems. The result further underpins the necessity for early intervention for specific phobia to prevent later mental health problems

A Novel Mutation in LEPRE1 That Eliminates Only the KDEL ER- Retrieval Sequence Causes Non-Lethal Osteogenesis Imperfecta

Prolyl 3-hydroxylase 1 (P3H1), encoded by the LEPRE1 gene, forms a molecular complex with cartilage-associated protein (CRTAP) and cyclophilin B (encoded by PPIB) in the endoplasmic reticulum (ER). This complex is responsible for one step in collagen post-translational modification, the prolyl 3-hydroxylation of specific proline residues, specifically α1(I) Pro986. P3H1 provides the enzymatic activity of the complex and has a Lys-Asp-Glu-Leu (KDEL) ER-retrieval sequence at the carboxyl terminus. Loss of function mutations in LEPRE1 lead to the Pro986 residue remaining unmodified and lead to slow folding and excessive helical post-translational modification of type I collagen, which is seen in both dominant and recessive osteogenesis imperfecta (OI). Here, we present the case of siblings with non-lethal OI due to novel compound heterozygous mutations in LEPRE1 (c.484delG and c.2155dupC). The results of RNA analysis and real-time PCR suggest that mRNA with c.2155dupC escapes from nonsense-mediated RNA decay. Without the KDEL ER- retrieval sequence, the product of the c.2155dupC variant cannot be retained in the ER. This is the first report of a mutation in LEPRE1 that eliminates only the KDEL ER-retrieval sequence, whereas other functional domains remain intact. Our study shows, for the first time, that the KDEL ER- retrieval sequence is essential for P3H1 functionality and that a defect in KDEL is sufficient for disease onset

Mutations in FKBP10 can cause a severe form of isolated Osteogenesis imperfecta

<p>Abstract</p> <p>Background</p> <p>Mutations in the <it>FKBP10 </it>gene were first described in patients with Osteogenesis imperfecta type III. Two follow up reports found <it>FKBP10 </it>mutations to be associated with Bruck syndrome type 1, a rare disorder characterized by congenital contractures and bone fragility. This raised the question if the patients in the first report indeed had isolated Osteogenesis imperfecta or if Bruck syndrome would have been the better diagnosis.</p> <p>Methods</p> <p>The patients described here are affected by severe autosomal recessive Osteogenesis imperfecta without contractures.</p> <p>Results</p> <p>Homozygosity mapping identified <it>FKBP10 </it>as a candidate gene, and sequencing revealed a base pair exchange that causes a C-terminal premature stop codon in this gene.</p> <p>Conclusions</p> <p>Our study demonstrates that <it>FKBP10 </it>mutations not only cause Bruck syndrome or Osteogenesis imperfecta type III but can result in a severe type of isolated Osteogenesis imperfecta type IV with prenatal onset. Furthermore, it adds dentinogenesis imperfecta to the spectrum of clinical symptoms associated with <it>FKBP10 </it>mutations.</p

Clustering daily patterns of human activities in the city

Data mining and statistical learning techniques are powerful analysis tools yet to be incorporated in the domain of urban studies and transportation research. In this work, we analyze an activity-based travel survey conducted in the Chicago metropolitan area over a demographic representative sample of its population. Detailed data on activities by time of day were collected from more than 30,000 individuals (and 10,552 households) who participated in a 1-day or 2-day survey implemented from January 2007 to February 2008. We examine this large-scale data in order to explore three critical issues: (1) the inherent daily activity structure of individuals in a metropolitan area, (2) the variation of individual daily activities—how they grow and fade over time, and (3) clusters of individual behaviors and the revelation of their related socio-demographic information. We find that the population can be clustered into 8 and 7 representative groups according to their activities during weekdays and weekends, respectively. Our results enrich the traditional divisions consisting of only three groups (workers, students and non-workers) and provide clusters based on activities of different time of day. The generated clusters combined with social demographic information provide a new perspective for urban and transportation planning as well as for emergency response and spreading dynamics, by addressing when, where, and how individuals interact with places in metropolitan areas.Massachusetts Institute of Technology. Dept. of Urban Studies and PlanningUnited States. Dept. of Transportation (Region One University Transportation Center)Singapore-MIT Alliance for Research and Technolog

EMQN best practice guidelines for the laboratory diagnosis of osteogenesis imperfecta

Osteogenesis imperfecta (OI) comprises a group of inherited disorders characterized by bone fragility and increased susceptibility to fractures. Historically, the laboratory confirmation of the diagnosis OI rested on cultured dermal fibroblasts to identify decreased or abnormal production of abnormal type I (pro)collagen molecules, measured by gel electrophoresis. With the discovery of COL1A1 and COL1A2 gene variants as a cause of OI, sequence analysis of these genes was added to the diagnostic process. Nowadays, OI is known to be genetically heterogeneous. About 90% of individuals with OI are heterozygous for causative variants in the COL1A1 and COL1A2 genes. The majority of remaining affected individuals have recessively inherited forms of OI with the causative variants in the more recently discovered genes CRTAP, FKBP10, LEPRE1,PLOD2, PPIB, SERPINF1, SERPINH1 and SP7, or in other yet undiscovered genes. These advances in the molecular genetic diagnosis of OI prompted us to develop new guidelines for molecular testing and reporting of results in which we take into account that testing is also used to ‘exclude' OI when there is suspicion of non-accidental injury. Diagnostic flow, methods and reporting scenarios were discussed during an international workshop with 17 clinicians and scientists from 11 countries and converged in these best practice guidelines for the laboratory diagnosis of OI

Paving (through) Amazonia: Neoliberal Urbanism and the Reperipheralization of Roraima

This paper examines the neoliberal reshaping of infrastructure provision in Brazil's extreme north since the mid-1990s, when roadway investments resulted in unprecedented regional connectivity. The BR-174 upgrade, the era's most important project, marked a transition from resource-based developmentalism to free-market transnationalism. Primarily concerned with urban competitiveness, the federal government funded the trunk roadway's paving to facilitate manufacturing exports from Manaus. While an effort was made to minimize deforestation, planners sidelined development implications in adjacent Roraima. The state's urban system has thus experienced reperipheralization and intensified primacy. Market-led growth now compounds the inheritance of hierarchical centralism and ongoing governmental neglect. Our study shows a vast territory dependent on primate cities for basic goods and services. Travelling with Roraimans from bypassed towns, we detected long-distance passenger transportation and surface logistics with selective routes. Heterogeneous Roraiman (im)mobilities comprise middle-class tourism and heightened consumerism as well as informal mobility tactics and transnational circulations of precarious labor. The paper exhorts neoliberal urbanism research to look beyond both Euro America's metropoles and their Global South counterparts. Urbanization dynamics in Brazil's extreme north demonstrate that market-disciplined investments to globalize cities produce far-reaching spatial effects. These are felt even by functionally-articulated-yet-marginalized peripheries in ostensibly remote locations

FRET characterisation for cross-bridge dynamics in single-skinned rigor muscle fibres

In this work we demonstrate for the first time the use of Förster resonance energy transfer (FRET) as an assay to monitor the dynamics of cross-bridge conformational changes directly in single muscle fibres. The advantage of FRET imaging is its ability to measure distances in the nanometre range, relevant for structural changes in actomyosin cross-bridges. To reach this goal we have used several FRET couples to investigate different locations in the actomyosin complex. We exchanged the native essential light chain of myosin with a recombinant essential light chain labelled with various thiol-reactive chromophores. The second fluorophore of the FRET couple was introduced by three approaches: labelling actin, labelling SH1 cysteine and binding an adenosine triphosphate (ATP) analogue. We characterise FRET in rigor cross-bridges: in this condition muscle fibres are well described by a single FRET population model which allows us to evaluate the true FRET efficiency for a single couple and the consequent donor–acceptor distance. The results obtained are in good agreement with the distances expected from crystallographic data. The FRET characterisation presented herein is essential before moving onto dynamic measurements, as the FRET efficiency differences to be detected in an active muscle fibre are on the order of 10–15% of the FRET efficiencies evaluated here. This means that, to obtain reliable results to monitor the dynamics of cross-bridge conformational changes, we had to fully characterise the system in a steady-state condition, demonstrating firstly the possibility to detect FRET and secondly the viability of the present approach to distinguish small FRET variations

Fighting Putin and the Kremlin’s grip in neo-authoritarian Russia: the experience of liberal journalists

Slavtcheva-Petkova, V. (2017). Fighting Putin and the Kremlin’s grip in neo-authoritarian Russia: the experience of liberal journalists. Journalism. Copyright © [2017]. Reprinted by permission of SAGE Publications.Russia is one of the most dangerous countries for journalists and the conflict with Ukraine and Russia’s involvement in Syria present even further challenges for the future of Russian journalism. In addition to the financial pressures, physical attacks, abductions and harassment, liberal journalists now face an increasing threat to the democratising role they see themselves as playing. President Vladimir Putin’s soaring popularity and the elaborate range of tactics used to suppress press freedom are forcing liberal media to rethink their mission(s) and identity(ies). This paper presents empirical evidence on the range of tactics used by Russian authorities as well as the coping strategies adopted by journalists. The study shows that some Russian media and journalists demonstrate a great degree of resilience in their efforts to expose wrongdoings and hold the powerful to account. The article questions the applicability of Western-centric normative media system theories because it shows that the breadth, depth, and mechanisms of control in modern-day Russia are very different from the ones used during Soviet times, and yet, Russian media and society do not appear to be on a linear journey from authoritarianism to democracy. The article presents the findings of a semi-ethnographic study of some of Russia’s most influential liberal news outlets – Novaya Gazeta, Radio Echo of Moscow and Radio Free Europe/Liberty. The study was conducted in May 2014 in the midst of the conflict with Ukraine. It involved observations of editorial meetings, documentary analysis and interviews with editors, deputy editors and journalists