pinecone/core-2020-05-10-deduplication huggingface dataset:
Cbx4 maintains the epithelial lineage identity and cell proliferation in the developing stratified epithelium.

During development, multipotent progenitor cells establish lineage-specific programmers of gene activation and silencing underlying their differentiation into specialized cell types. We show that the Polycomb component Cbx4 serves as a critical determinant that maintains the epithelial identity in the developing epidermis by repressing nonepidermal gene expression programs. Cbx4 ablation in mice results in a marked decrease of the epidermal thickness and keratinocyte (KC) proliferation associated with activation of numerous neuronal genes and genes encoding cyclin-dependent kinase inhibitors (p16/p19 and p57). Furthermore, the chromodomain- and SUMO E3 ligase–dependent Cbx4 activities differentially regulate proliferation, differentiation, and expression of nonepidermal genes in KCs. Finally, Cbx4 expression in KCs is directly regulated by p63 transcription factor, whereas Cbx4 overexpression is capable of partially rescuing the effects of p63 ablation on epidermal development. These data demonstrate that Cbx4 plays a crucial role in the p63-regulated program of epidermal differentiation, maintaining the epithelial identity and proliferative activity in KCs via repression of the selected nonepidermal lineage and cell cycle inhibitor genes
Mice carrying a complete deletion of the talin2 coding sequence are viable and fertile.

Mice homozygous for several Tln2 gene targeted alleles are viable and fertile. Here we show that although the expression of talin2 protein is drastically reduced in muscle from these mice, other tissues continue to express talin2 albeit at reduced levels. We therefore generated a Tln2 allele lacking the entire coding sequence (Tln2(cd)). Tln2(cd/cd) mice were viable and fertile, and the genotypes of Tln2(cd/+) intercrosses were at the expected Mendelian ratio. Tln2(cd/cd) mice showed no major difference in body mass or the weight of the major organs compared to wild-type, although they displayed a mildly dystrophic phenotype. Moreover, Tln2(cd/cd) mouse embryo fibroblasts showed no obvious defects in cell adhesion, migration or proliferation. However, the number of Tln2(cd/cd) pups surviving to adulthood was variable suggesting that such mice have an underlying defect.The Wellcome Trust and Cancer Research UK  supported this work.Peer-reviewedPublisher Versio
Communication: Simple approach for calculating the binding free energy of a multivalent particle.

We present a simple yet accurate numerical approach to compute the free energy of binding of multivalent objects on a receptor-coated surface. The method correctly accounts for the fact that one ligand can bind to at most one receptor. The numerical approach is based on a saddle-point approximation to the computation of a complex residue. We compare our theory with the powerful Valence-Limited Interaction Theory (VLIT) [P. Varilly et al., J. Chem. Phys. 137, 094108 (2012); S. Angioletti-Uberti et al., ibid. 138, 021102 (2013)] and find excellent agreement in the regime where that theory is expected to work. However, the present approach even works for low receptor/ligand densities, where VLIT breaks down
Compensatory embryonic response to allele-specific inactivation of the murine X-linked gene Hcfc1.

Early in female mammalian embryonic development, cells randomly inactivate one of the two X chromosomes to achieve overall equal inactivation of parental X-linked alleles. Hcfc1 is a highly conserved X-linked mouse gene that encodes HCF-1 - a transcriptional co-regulator implicated in cell proliferation in tissue culture cells. By generating a Cre-recombinase inducible Hcfc1 knock-out (Hcfc1(lox)) allele in mice, we have probed the role of HCF-1 in actively proliferating embryonic cells and in cell-cycle re-entry of resting differentiated adult cells using a liver regeneration model. HCF-1 function is required for both extraembryonic and embryonic development. In heterozygous Hcfc1(lox/+) female embryos, however, embryonic epiblast-specific Cre-induced Hcfc1 deletion (creating an Hcfc1(epiKO) allele) around E5.5 is well tolerated; it leads to a mixture of HCF-1-positive and -negative epiblast cells owing to random X-chromosome inactivation of the wild-type or Hcfc1(epiKO) mutant allele. At E6.5 and E7.5, both HCF-1-positive and -negative epiblast cells proliferate, but gradually by E8.5, HCF-1-negative cells disappear owing to cell-cycle exit and apoptosis. Although generating a temporary developmental retardation, the loss of HCF-1-negative cells is tolerated, leading to viable heterozygous offspring with 100% skewed inactivation of the X-linked Hcfc1(epiKO) allele. In resting adult liver cells, the requirement for HCF-1 in cell proliferation was more evident as hepatocytes lacking HCF-1 fail to re-enter the cell cycle and thus to proliferate during liver regeneration. The survival of the heterozygous Hcfc1(epiKO/+) female embryos, even with half the cells genetically compromised, illustrates the developmental plasticity of the post-implantation mouse embryo - in this instance, permitting survival of females heterozygous for an X-linked embryonic lethal allele
The pattern of amyloid accumulation in the brains of adults with Down’s syndrome

INTRODUCTION: Adults with Down’s syndrome (DS) invariably develop Alzheimer’s disease neuropathology. Understanding amyloid deposition in DS can yield crucial information about disease pathogenesis.
METHODS: Forty–nine adults with DS aged 25 to 65 underwent positron emission tomography with Pittsburgh Compound–B (PIB). Regional PIB binding was assessed with respect to age, clinical and cognitive status.
RESULTS: Abnormal PIB binding became evident from 39 years, first in striatum followed by rostral prefrontal–cingulo–parietal regions, then caudal frontal, rostral temporal, primary sensorimotor and occipital, and lastly parahippocampal cortex, thalamus and amygdala. PIB binding was related to age, diagnostic status and cognitive function.
DISCUSSION: PIB binding in DS, first appearing in striatum, began around age 40 and was strongly associated with dementia and cognitive decline. The absence of a substantial time lag between amyloid accumulation and cognitive decline contrasts to sporadic/familial Alzheimer’s disease and suggests this population’s suitability for an amyloid primary prevention trial.This research was generously supported by a grant from the Medical Research Council (grant ID number: 98480). Additional support came from the NIHR Cambridge Biomedical Research Centre, the NIHR Collaborations in Leadership for Applied Health Research and Care (CLAHRC) for the East of England, the NIHR Cambridge Dementia Biomedical Research Unit, The Down Syndrome Association, and The Health Foundation.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.jalz.2015.07.49
Measurement of the fragmentation fraction ratio fs/fd and its dependence on B meson kinematics

The relative production rate of  B[superscript 0][subscript s]  and B[superscript 0] mesons is determined with the hadronic decays  B[superscript 0][subscript s]→D[superscript −][subscript s]π[superscript +]  and B[superscript 0] → D[superscript −]K[superscript +]. The measurement uses data corresponding to 1.0 fb[superscript −1] of pp collisions at a centre-of-mass energy of  s√=7s=7  TeV recorded in the forward region with the LHCb experiment. The ratio of production rates, f[subscript s]/f[subscript d], is measured to be 0.238 ± 0.004 ± 0.015 ± 0.021, where the first uncertainty is statistical, the second systematic, and the third theoretical. This is combined with a previous LHCb measurement to obtain f[subscript s]/f[subscript d] = 0.256 ± 0.020. The dependence of f[subscript s]/f[subscript d] on the transverse momentum and pseudorapidity of the B meson is determined using the decays  B[superscript 0][subscript s]→D[superscript −][subscript s]π[superscript +] and B[superscript 0] → D[superscript −]π[superscript +]. There is evidence for a decrease with increasing transverse momentum, whereas the ratio remains constant as a function of pseudorapidity. In addition, the ratio of branching fractions of the decays B[superscript 0] → D[superscript −]K[superscript +] and B[superscript 0] → D[superscript −]π[superscript +] is measured to be 0.0822 ± 0.0011 (stat) ± 0.0025 (syst).National Science Foundation (U.S.
QuadLab: A Project-Based Learning Toolkit for Automation and Robotics Engineering Education

It is frequently claimed that the students must have an active role in building and transforming their own knowledge, and the teacher's labor is to provide the students the necessary tools in order to reach specific learning objectives, included in a course program. This paper presents an aerial robotic system as a toolkit, and proposes a series of activities focused on the learning in automation and robotics. These proposed activities have been designed based upon the project-based learning methodology, and they facilitate the achievement of the learning objectives presented by Spanish automation committee(CEA) in conjunction with The International Society of Automation (ISA) to satisfy the Accreditation Board for Engineering and Technology (ABET) standard. The toolkit and the activities are oriented to impulse the practical teaching, giving the student additional motivation and, in consequence, improving his or her active role. Besides, the toolkit and the activities give the teacher a tool in which it is possible to assess the students learning process
The impact of the air-fluorescence yield on the reconstructed shower parameters of ultra-high energy cosmic rays.

An accurate knowledge of the fluorescence yield and its dependence on atmospheric properties such as pressure, temperature or humidity is essential to obtain a reliable measurement of the primary energy of cosmic rays in experiments using the fluorescence technique. In this work, several sets of fluorescence yield data (i.e. absolute value and quenching parameters) are described and compared. A simple procedure to study the effect of the assumed fluorescence yield on the reconstructed shower parameters (energy and shower maximum depth) as a function of the primary features has been developed. As an application, the effect of water vapor and temperature dependence of the collisional cross section on the fluorescence yield and its impact on the reconstruction of primary energy and shower maximum depth has been studied. Published by Elsevier B.V
Synthesis and biological evaluation of N-cyanoalkyl-, Naminoalkyl-, and N-guanidinoalkyl-substituted 4-aminoquinoline derivatives as potent, selective, brain permeable antitrypanosomal agents

YesCurrent drugs against human African trypanosomiasis (HAT) suffer from several serious drawbacks. The search for novel, effective, brain permeable, safe, and inexpensive antitrypanosomal compounds is therefore an urgent need. We have recently reported that the 4-aminoquinoline derivative huprine Y, developed in our group as an anticholinesterasic agent, exhibits a submicromolar potency against Trypanosoma brucei and that its homo- and hetero-dimerization can result in to up to three-fold increased potency and selectivity. As an alternative strategy towards more potent smaller molecule anti-HAT agents, we have explored the introduction of ω-cyanoalkyl, ω-aminoalkyl, or ω-guanidinoalkyl chains at the primary amino group of huprine or the simplified 4-aminoquinoline analogue tacrine. Here, we describe the evaluation of a small in-house library and a second generation of newly synthesized derivatives, which has led to the identification of 13 side chain modified 4-aminoquinoline derivatives with submicromolar potencies against T. brucei. Among these compounds, the guanidinononyltacrine analogue 15e exhibits a 5-fold increased antitrypanosomal potency, 10-fold increased selectivity, and 100-fold decreased anticholinesterasic activity relative to the parent huprine Y. Its biological profile, lower molecular weight relative to dimeric compounds, reduced lipophilicity, and ease of synthesis, make it an interesting anti-HAT lead, amenable to further optimization to eliminate its remaining anticholinesterasic activity.Wellcome TrustGol
New production technologies in aerospace industry - 5th machining innovations conference (MIC 2014) conceptual design for electromagnetic guided rotary table in machine tools

Difficult-to-machine materials are still challenging the production industry. Examples are highly complex components of aircraft engines. Alongside innovative processes, also improved machine tool components are helping to comply with the demands of this task. This paper presents a design approach of a rotary table with an active magnetic bearing. Opportunities in machining through employing magnetic guides are presented and discussed in the beginning. In the following, a workflow for the magnetic bearing design in swivel rotary tables is proposed. The mentioned steps are executed based on a presently under design rotary table.DFG/CRC/87
Evolution of Martensitic Microstructure on Carbon Steel Tempered at Low Temperatures

This work presents the microstructural changes of a carbon steel during tempering at low temperatures (first stage of tempering), and its effects in the second and third stages. These changes are determined by internal friction. Internal friction is measured in a forced vibration mode at 5 Hz, in a temperature range from 300 to 600K. Four internal friction peaks appear: S1 at 350K, P1 at 380K, P2 at 440K, P3 at 480K. S1 only appears in the sample tempered at 380K for 20 hours, and this can be related to the reduction of the martensite tetragonality. The height of P1 is lowest when the intensity of tempering is increased. This height can be related to the quantity of epsilon carbide than precipitate. The heights of P2 and P3 are not changed significantly, but the difference of temperature between both is lowest when the tempering intensity is increased. This suggests than the dissolution of epsilon carbide and formation of cementite takes places in a lowest range of temperature.Fil: Hoyos, J.. Comisión Nacional de Energía Atómica. Gerencia del Area de Energía Nuclear. Instituto Balseiro; Argentina. Comision Nacional de Energia Atomica. Gerencia del Area de Investigaciones y Aplicaciones no Nucleares. Gerencia de Fisica (CAB); Argentina. Universidad Nacional de Cuyo; ArgentinaFil: Ghilarducci, Ada Albertina. Comisión Nacional de Energía Atómica. Gerencia del Area de Energía Nuclear. Instituto Balseiro; Argentina. Comision Nacional de Energia Atomica. Gerencia del Area de Investigaciones y Aplicaciones no Nucleares. Gerencia de Fisica (CAB); Argentina. Universidad Nacional de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Salva, Horacio Ramon. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comision Nacional de Energia Atomica. Gerencia del Area de Investigaciones y Aplicaciones no Nucleares. Gerencia de Fisica (CAB); Argentina. Universidad Nacional de Cuyo; Argentina. Comisión Nacional de Energía Atómica. Gerencia del Area de Energía Nuclear. Instituto Balseiro; ArgentinaFil: Vélez, J. M.. Universidad Nacional de Colombia; Colombi
Individual differences in children’s private speech: The role of imaginary companions

AbstractRelations between children’s imaginary companion status and their engagement in private speech during free play were investigated in a socially diverse sample of 5-year-olds (N=148). Controlling for socioeconomic status, receptive verbal ability, total number of utterances, and duration of observation, there was a main effect of imaginary companion status on type of private speech. Children who had imaginary companions were more likely to engage in covert private speech compared with their peers who did not have imaginary companions. These results suggest that the private speech of children with imaginary companions is more internalized than that of their peers who do not have imaginary companions and that social engagement with imaginary beings may fulfill a similar role to social engagement with real-life partners in the developmental progression of private speech
Everyday tactics in local moral worlds: E-cigarette practices in a working-class area of the UK

AbstractResearch into e-cigarette use has largely focused on their health effects and efficacy for smoking cessation, with little attention given to their potential effect on health inequalities. Drawing on three years of ethnographic research between 2012 and 2015, I investigate the emerging e-cigarette practices of adult smokers and quitters in a working-class area of the UK. I first use de Certeau's notion of ‘tactics’ to describe the informal economy of local e-cigarette use. Low-priced products were purchased through personal networks and informal sources for financial reasons, but also as a solution to the moral problems of addiction and expenditure on the self, particularly for older smokers. E-cigarette practices were produced in local moral worlds where smoking and cessation had a complex status mediated through norms of age and gender. For younger men, smoking cessation conflicted with an ethic of working-class hedonism but e-cigarette use allowed cessation to be incorporated into male sociality. Continued addiction had moral implications which older men addressed by constructing e-cigarette use as functional rather than pleasurable, drawing on a narrative of family responsibility. The low priority which older women with a relational sense of identity gave to their own health led to a lower tolerance for e-cigarette unreliability. I draw on Kleinman's local moral worlds to make sense of these findings, arguing that smoking cessation can be a risk to moral identity in violating local norms of age and gender performance. I conclude that e-cigarettes did have some potential to overcome normative barriers to smoking cessation and therefore to reduce health inequalities, at least in relation to male smoking. Further research which attends to local meanings of cessation in relation to age and gender will establish whether e-cigarettes have similar potential elsewhere
Differences in white matter reflect atypical developmental trajectory in autism: A Tract-based Spatial Statistics study

AbstractAutism is a neurodevelopmental disorder in which white matter (WM) maturation is affected. We assessed WM integrity in 16 adolescents and 14 adults with high-functioning autism spectrum disorder (ASD) and in matched neurotypical controls (NT) using diffusion weighted imaging and Tract-based Spatial Statistics. Decreased fractional anisotropy (FA) was observed in adolescents with ASD in tracts involved in emotional face processing, language, and executive functioning, including the inferior fronto-occipital fasciculus and the inferior and superior longitudinal fasciculi. Remarkably, no differences in FA were observed between ASD and NT adults.We evaluated the effect of age on WM development across the entire age range. Positive correlations between FA values and age were observed in the right inferior fronto-occipital fasciculus, the left superior longitudinal fasciculus, the corpus callosum, and the cortical spinal tract of ASD participants, but not in NT participants.Our data underscore the dynamic nature of brain development in ASD, showing the presence of an atypical process of WM maturation, that appears to normalize over time and could be at the basis of behavioral improvements often observed in high-functioning autism
Soft A4→Z3 symmetry breaking and cobimaximal neutrino mixing

AbstractI propose a model of radiative charged-lepton and neutrino masses with A4 symmetry. The soft breaking of A4 to Z3 lepton triality is accomplished by dimension-three terms. The breaking of Z3 by dimension-two terms allows cobimaximal neutrino mixing (θ13≠0, θ23=π/4, δCP=±π/2) to be realized with only very small finite calculable deviations from the residual Z3 lepton triality. This construction solves a long-standing technical problem inherent in renormalizable A4 models since their inception
Constructing warm inflationary model in brane–antibrane system

AbstractRecently, various observational data predicted a possibility that inflation may naturally occur in a warm region. In this scenario, radiation is produced during the inflation epoch and reheating is avoided. The main question arises as to what is the origin of warm inflation in 4D universe? We answer this question in brane–antibrane system. We propose a model that allows all cosmological parameters like the scale factor a, the Hubble parameter H and phantom energy density depend on the equation of state parameter in transverse dimension between two branes. Thus, an enhancement in these parameters can be a signature of some evolutions in extra dimension. In our model, the expansion of 4D universe is controlled by the separation distance between branes and evolves from non-phantom phase to phantom one. Consequently, phantom-dominated era of the universe accelerates and ends up in big-rip singularity. Also, we show that as the tachyon potential increases, the effect of interaction between branes on the 4D universe expansion becomes systematically more effective, because at higher energies there exist more channels for flowing energy from extra dimension to other four dimensions. Finally, we test our model against WMAP and Planck data and obtain the ripping time. According to experimental data, N≃50 case leads to ns≃0.96, where N and ns are the number e-folds and the spectral index respectively. This standard case may be found in 0.01<RTensor–scalar<0.22, where RTensor–scalar is the tensor–scalar ratio. At this point, the finite time at which Big Rip singularity occurs is trip=33 (Gyr)
Inflammatory Markers and Incident Heart Failure Risk in Older Adults The Health ABC (Health, Aging, and Body Composition) Study

ObjectivesThe purpose of this study was to evaluate the association between inflammation and heart failure (HF) risk in older adults.BackgroundInflammation is associated with HF risk factors and also directly affects myocardial function.MethodsThe association of baseline serum concentrations of interleukin (IL)-6, tumor necrosis factor-α, and C-reactive protein (CRP) with incident HF was assessed with Cox models among 2,610 older persons without prevalent HF enrolled in the Health ABC (Health, Aging, and Body Composition) study (age 73.6 ± 2.9 years; 48.3% men; 59.6% white).ResultsDuring follow-up (median 9.4 years), HF developed in 311 (11.9%) participants. In models controlling for clinical characteristics, ankle-arm index, and incident coronary heart disease, doubling of IL-6, tumor necrosis factor-α, and CRP concentrations was associated with 29% (95% confidence interval: 13% to 47%; p < 0.001), 46% (95% confidence interval: 17% to 84%; p = 0.001), and 9% (95% confidence interval: −1% to 24%; p = 0.087) increase in HF risk, respectively. In models including all 3 markers, IL-6, and tumor necrosis factor-α, but not CRP, remained significant. These associations were similar across sex and race and persisted in models accounting for death as a competing event. Post-HF ejection fraction was available in 239 (76.8%) cases; inflammatory markers had stronger association with HF with preserved ejection fraction. Repeat IL-6 and CRP determinations at 1-year follow-up did not provide incremental information. Addition of IL-6 to the clinical Health ABC HF model improved model discrimination (C index from 0.717 to 0.734; p = 0.001) and fit (decreased Bayes information criterion by 17.8; p < 0.001).ConclusionsInflammatory markers are associated with HF risk among older adults and may improve HF risk stratification