Miracle-dz/UniFAR-FTUs huggingface dataset:
Dynamic Proteomic Profiling of Extra‐Embryonic Endoderm Differentiation in Mouse Embryonic Stem Cells

During mammalian preimplantation development, the cells of the blastocyst's inner cell mass differentiate into the epiblast and primitive endoderm lineages, which give rise to the fetus and extra‐embryonic tissues, respectively. Extra‐embryonic endoderm (XEN) differentiation can be modeled in vitro by induced expression of GATA transcription factors in mouse embryonic stem cells. Here, we use this GATA‐inducible system to quantitatively monitor the dynamics of global proteomic changes during the early stages of this differentiation event and also investigate the fully differentiated phenotype, as represented by embryo‐derived XEN cells. Using mass spectrometry‐based quantitative proteomic profiling with multivariate data analysis tools, we reproducibly quantified 2,336 proteins across three biological replicates and have identified clusters of proteins characterized by distinct, dynamic temporal abundance profiles. We first used this approach to highlight novel marker candidates of the pluripotent state and XEN differentiation. Through functional annotation enrichment analysis, we have shown that the downregulation of chromatin‐modifying enzymes, the reorganization of membrane trafficking machinery, and the breakdown of cell–cell adhesion are successive steps of the extra‐embryonic differentiation process. Thus, applying a range of sophisticated clustering approaches to a time‐resolved proteomic dataset has allowed the elucidation of complex biological processes which characterize stem cell differentiation and could establish a general paradigm for the investigation of these processes. Stem Cells 2015;33:2712—2725
Impact of a Century of Climate Change on Small-Mammal Communities in Yosemite National Park, USA

We provide a century-scale view of small-mammal responses to global warming, without confounding effects of land-use change, by repeating Grinnell's early–20th century survey across a 3000-meter-elevation gradient that spans Yosemite National Park, California, USA. Using occupancy modeling to control for variation in detectability, we show substantial (∼500 meters on average) upward changes in elevational limits for half of 28 species monitored, consistent with the observed ∼3°C increase in minimum temperatures. Formerly low-elevation species expanded their ranges and high-elevation species contracted theirs, leading to changed community composition at mid- and high elevations. Elevational replacement among congeners changed because species' responses were idiosyncratic. Though some high-elevation species are threatened, protection of elevation gradients allows other species to respond via migration.
Equifinality, Multifinality, and Immorality in a Life of Crime

Although more commonly used in the developmental psychopathology literature (see Cicchetti & Rogosch, 1996), equifinality and multifinality are also important concepts for criminology and criminal justice. Equifinality captures the notion that various background risk factors can eventuate in the same outcome, such as arrest, conviction, or criminal career. An assortment of initial conditions, processes, and constructs produce the same general end result. Multifinality is a concept that shows how a specific condition, process, construct, or risk factor can have multiple manifestations later in life. Often, a negative construct causes harm in multiple contexts and in multiple ways. This is self-evident in the study of antisocial behavior because criminal behavior is often comorbid with other negative and maladaptive behaviors. The articles in this issue of the International Journal of Offender Therapy and Comparative Criminology are an eclectic mix of exciting studies that illustrate the concepts of equifinality and multifinality as they relate to the development of various antisocial conditions and aspects of a criminal career. Utilizing data from the National Institute of Child Health and Human Development Study of Early Child Care, May and Beaver examined the associations between neuropsychological functioning and psychopathic personality traits across four phases of development. They found significant effects whereby children with greater impairments in neuropsychological functioning were more psychopathic in adolescence. Moreover, neuropsychological deficits were also predictive of extreme scores (set at the 95th percentile) in psychopathic personality traits. The neurocognitive problems thus not only cause problems in terms of school functioning but also influence affective, interpersonal, and behavioral displays. Based on data from the Cambridge Study in Delinquent Development, Piquero, Theobald, and Farrington investigated the interplay between offending, violence, and the more specific intimate partner violence. They found dramatic differences in use of violence by offender type. By age 50, for example, just 3.4% of nonoffenders were violent. Among high-rate chronic offenders, the prevalence of violence was 87.5%. Intimate partner violence also figures prominently in two other studies in this issue. Relying on data from the Criminal Justice Drug Abuse Treatment Studies, Minieri and her colleagues reveal that incarcerated women frequently have domestic histories characterized by violent victimization, low relationship power, and
Disruption of the CFTR Gene Produces a Model of Cystic Fibrosis in Newborn Pigs

Almost two decades after CFTR was identified as the gene responsible for cystic fibrosis (CF), we still lack answers to many questions about the pathogenesis of the disease, and it remains incurable. Mice with a disrupted CFTR gene have greatly facilitated CF studies, but the mutant mice do not develop the characteristic manifestations of human CF, including abnormalities of the pancreas, lung, intestine, liver, and other organs. Because pigs share many anatomical and physiological features with humans, we generated pigs with a targeted disruption of both CFTR alleles. Newborn pigs lacking CFTR exhibited defective chloride transport and developed meconium ileus, exocrine pancreatic destruction, and focal biliary cirrhosis, replicating abnormalities seen in newborn humans with CF. The pig model may provide opportunities to address persistent questions about CF pathogenesis and accelerate discovery of strategies for prevention and treatment.
Pro-Atrial Natriuretic Peptide (proANP) A New Prognostic Marker in Clinical Outcome of Critically Ill Patients

The diagnosis of sepsis and the prediction of its outcome are important aims to tackle for this heterogeneous disease. There is a lack of biomarkers to aid in identification of risk groups, inclusion of patients in ongoing studies, and better differentiation of therapeutic strategies. Since the introduction of the prohormone procalcitonin (PCT), many studies have begun to focus on new prohormones. The aim of the study was to evaluate the prognostic value of pro-atrial natriuretic peptide (proANP) as a new marker of sepsis outcome. Material and methods. A cohort of 80 patients developing post-surgical sepsis was consecutively included into this study. Blood samples were obtained for analysis of proANP and determination the serum levels of sTNF-R1, TNF, IL-6, IL-8, IL-10, procalcitonin and neopterin. Cytokine levels were measured repeatedly until the patients ́ discharge from the ICU. Results. 54/80 (67.5%) fulfilled the criteria for severe sepsis and 36/80 (45.0%) developed septic shock. Multiple organ failure occurred within 60/80 patients (75.0%); the overall mortality was 26/80 (32.5%). Concerning the diagnosis of sepsis, severe sepsis, or septic shock, there was no statistical difference in the proANP values. However, there was a statistical difference in the prediction of outcome in that 26 nonsurvivors had 803.5 (441.5/ 1095) pmol/L levels while the survivors level was 315.5 (187/ 594.5) pmol/L. In addition, there were no statistical significant differences between proANP and other cytokines. Conclusions. There was a significant correlation between proANP values and the outcome of critically ill patients. ProANP does not differentiate between clinical features like sepsis, severe sepsis or septic shock.
Self-Injurious Behavior in Prison

The practice of self-injurious behaviors (SIBs) within corrections disproportionately consumes resources and negatively impacts staff. To date, the majority of empirical studies on the topic have relied upon quantitative methodologies that fail to include the perspective of the actual offender who is engaging in self-injury, thus reinforcing mischaracterizations and confusion. In response, this manuscript features a case study of an offender currently housed in a maximum security prison who routinely engages in self-injury. Findings are presented along the tripartite themes of family background, suicidality, and SIB. Policy implications include supporting a systematic reorientation toward therapeutic responses in lieu of the current punitive responses that may in fact be iatrogenic.
Avaliação dos fatores relacionados à ocorrência da incontinência urinária feminina

OBJETIVO: Avaliar os fatores de risco relacionados a ocorrencia da incontinencia urinaria feminina. METODOS: Estudo caso-controle que incluiu 253 mulheres (102 incontinentes e 151 continentes) convidadas a responder a um questionario epidemiologico sobre possiveis fatores de risco para a incontinencia urinaria como: idade, estado hormonal, raca, Indice de Massa Corporal, paridade, tipos de partos (normais, forcipes ou cesarianas), peso do maior recem-nascido, utilizacao de episiotomia e ou analgesia durante o parto, historia de histerectomia, pratica de atividade fisica, tabagismo, diabetes mellitus, constipacao intestinal, historia de asma bronquica e ou doenca pulmonar obstrutiva cronica, uso de diureticos e ou antidepressivos. RESULTADOS: Foram encontrados, apos a aplicacao do modelo de regressao logistica binaria, como fatores de risco para a ocorrencia de incontinencia urinaria: a idade [OR = 1,07 (IC 1,03 - 1,1)], o parto normal [OR = 1,5 (IC 1,1 - 12,0)], o parto forcipe [OR = 35,0 (IC 3,7 - 327)] e o peso do maior recem-nascido [OR = 1,001 (IC 1 - 1,002)]. Alem disso, identificamos como fator de protecao a cesariana [OR = 0,39 (IC 0,23 - 0,65)]. CONCLUSAO: Os fatores de risco independentes para a ocorrencia da incontinencia urinaria foram idade, parto normal, parto forcipe e peso do maior recem-nascido e, como fator de protecao, a cesariana.
The Metastasis Cascade

, 1785 (2008); 321 Science Christoph A. Klein The Metastasis Cascade This copy is for your personal, non-commercial use only. clicking here. colleagues, clients, or customers by , you can order high-quality copies for your If you wish to distribute this article to others here. following the guidelines can be obtained by Permission to republish or repurpose articles or portions of articles ): April 30, 2014 www.sciencemag. org (this information is current as of The following resources related to this article are available online at http://www.sciencemag.org/content/321/5897/1785.full.html version of this article at: including high-resolution figures, can be found in the online Updated information and services, http://www.sciencemag.org/content/321/5897/1785.full.html#related found at: can be related to this article A list of selected additional articles on the Science Web sites http://www.sciencemag.org/content/321/5897/1785.full.html#ref-list-1 , 3 of which can be accessed free: cites 10 articles This article 10 article(s) on the ISI Web of Science cited by This article has been http://www.sciencemag. org/content/321/5897/1785.full. html#related-urls 7 articles hosted by HighWire Press; see: cited by This article has been http://www.sciencemag. org/cgi/collection/medicine Medicine, Diseases subject collections: This article appears in the following
Pulsatile Stimulation Determines Timing and Specificity of NF-κB-Dependent Transcription

The nuclear factor κB (NF-κB) transcription factor regulates cellular stress responses and the immune response to infection. NF-κB activation results in oscillations in nuclear NF-κB abundance. To define the function of these oscillations, we treated cells with repeated short pulses of tumor necrosis factor–α at various intervals to mimic pulsatile inflammatory signals. At all pulse intervals that were analyzed, we observed synchronous cycles of NF-κB nuclear translocation. Lower frequency stimulations gave repeated full-amplitude translocations, whereas higher frequency pulses gave reduced translocation, indicating a failure to reset. Deterministic and stochastic mathematical models predicted how negative feedback loops regulate both the resetting of the system and cellular heterogeneity. Altering the stimulation intervals gave different patterns of NF-κB–dependent gene expression, which supports the idea that oscillation frequency has a functional role.
Decoding delay reduction in broadcast erasure channels with memory for network coding

This paper studies feedback based instantly decodable network coding with the aim of minimizing decoding delay per transmission over wireless broadcast erasure channels with memory. We model such channels with a Gilbert-Elliott two-state Markov model with good and bad states. We first present a weighted sum generalized instantly decodable network coding (G-IDNC) scheme, where the aim is to service a subset of receivers with expected good channel state. We then propose an improved variation of the weighted sum G-IDNC that appropriately targets a broader set of receivers (while giving initial priority to receivers with expected good channel state) to reduce decoding delay over a wider range of erasure channels with memory. Simulation results show that our proposed improved weighted sum G-IDNC algorithm always considerably outperforms an earlier approach in the literature for erasure channels with memory, namely the weighted sum strict instantly decodable network coding (S-IDNC).
Effect of NG-Nitro-L-Arginine Methyl Ester on Intestinal Permeability following Intestinal Ischemia-Reperfusion Injury in a Rat Model

Subclinical intestinal ischemia-reperfusion injury (IRI) causes an increase in mucosal permeability and may represent an early event in the pathogenesis of necrotizing enterocolitis in premature infants. Previous studies suggested that continuous, endogenous formation of nitric oxide (NO) maintains the mucosal integrity of the intestine, thus protecting the gut from injuries from blood-borne toxins and tissue-destructive mediators. This study was undertaken to assess whether the inhibition of NO production causes an increase in intestinal permeability in rats following IRI. Sprague-Dawley rats weighing 200–300 g were divided into 4 groups: (1) untreated group (normal control); (2) ischemia-reperfusion group; (3) early NG-nitro-L-arginine methyl ester (L-NAME), a specific inhibitor of NO production, treatment group, and (4) late L-NAME treatment group. Transient IRI was induced by 30-min occlusion, followed by reperfusion of the isolated ileal loop. The L-NAME was administered 15 min before and after mesenteric ischemia as a 25-mg/kg bolus. Fluorescein isothiocyanate-dextran (FITC-D) was used to quantitatively assess the alteration in mucosal permeability of the intestine. There was no significant increase in the portal vein FITC-D level among normal controls, ischemia-reperfusion group and late L-NAME-treated group, but there was an approximately 6-fold increase in the early L-NAME treatment group. The pathological features of the intestine following IRI include denudation of the villus epithelium and reduction of villus height, associated with marked inflammatory cell infiltration over the lamina propria. These results suggest that endogenous NO may play a role in the protecting intestinal integrity after IRI.
Rapid Membrane Disruption by a Perforin-Like Protein Facilitates Parasite Exit from Host Cells

Perforin-like proteins are expressed by many bacterial and protozoan pathogens, yet little is known about their function or mode of action. Here, we describe Toxoplasma perforin-like protein 1 (TgPLP1), a secreted perforin-like protein of the intracellular protozoan pathogen Toxoplasma gondii that displays structural features necessary for pore formation. After intracellular growth, TgPLP1-deficient parasites failed to exit normally, resulting in entrapment within host cells. We show that this defect is due to an inability to rapidly permeabilize the parasitophorous vacuole membrane and host plasma membrane during exit. TgPLP1 ablation had little effect on growth in culture but resulted in a reduction greater than five orders of magnitude of acute virulence in mice. Perforin-like proteins from other intracellular pathogens may play a similar role in microbial egress and virulence.
Stress-Inducible Regulation of Heat Shock Factor 1 by the Deacetylase SIRT1

Heat shock factor 1 (HSF1) is essential for protecting cells from protein-damaging stress associated with misfolded proteins and regulates the insulin-signaling pathway and aging. Here, we show that human HSF1 is inducibly acetylated at a critical residue that negatively regulates DNA binding activity. Activation of the deacetylase and longevity factor SIRT1 prolonged HSF1 binding to the heat shock promoter Hsp70 by maintaining HSF1 in a deacetylated, DNA–binding competent state. Conversely, down-regulation of SIRT1 accelerated the attenuation of the heat shock response (HSR) and release of HSF1 from its cognate promoter elements. These results provide a mechanistic basis for the requirement of HSF1 in the regulation of life span and establish a role for SIRT1 in protein homeostasis and the HSR.
Survival from Hypoxia in C. elegans by Inactivation of Aminoacyl-tRNA Synthetases

Hypoxia is important in a wide range of biological processes, such as animal hibernation and cell survival, and is particularly relevant in many diseases. The sensitivity of cells and organisms to hypoxic injury varies widely, but the molecular basis for this variation is incompletely understood. Using forward genetic screens in Caenorhabditis elegans, we isolated a hypoxia-resistant reduction-of-function mutant of rrt-1 that encodes an arginyl–transfer RNA (tRNA) synthetase, an enzyme essential for protein translation. Knockdown of rrt-1, and of most other genes encoding aminoacyl-tRNA synthetases, rescued animals from hypoxia-induced death, and the level of hypoxia resistance was inversely correlated with translation rate. The unfolded protein response was induced by hypoxia and was required for the hypoxia resistance of the reduction-of-function mutant of rrt-1. Thus, translational suppression produces hypoxia resistance, in part by reducing unfolded protein toxicity.
Hypoxia Inducible Factor‐1α Potentiates Jagged 1‐Mediated Angiogenesis by Mesenchymal Stem Cell‐Derived Exosomes

Insufficient vessel growth associated with ischemia remains an unresolved issue in vascular medicine. Mesenchymal stem cells (MSCs) have been shown to promote angiogenesis via a mechanism that is potentiated by hypoxia. Overexpression of hypoxia inducible factor (HIF)‐1α in MSCs improves their therapeutic potential by inducing angiogenesis in transplanted tissues. Here, we studied the contribution of exosomes released by HIF‐1α‐overexpressing donor MSCs (HIF‐MSC) to angiogenesis by endothelial cells. Exosome secretion was enhanced in HIF‐MSC. Omics analysis of miRNAs and proteins incorporated into exosomes pointed to the Notch pathway as a candidate mediator of exosome communication. Interestingly, we found that Jagged1 was the sole Notch ligand packaged into MSC exosomes and was more abundant in HIF‐MSC than in MSC controls. The addition of Jagged1‐containing exosomes from MSC and HIF‐MSC cultures to endothelial cells triggered transcriptional changes in Notch target genes and induced angiogenesis in an in vitro model of capillary‐like tube formation, and both processes were stimulated by HIF‐1α. Finally, subcutaneous injection of Jagged 1‐containing exosomes from MSC and HIF‐MSC cultures in the Matrigel plug assay induced angiogenesis in vivo, which was more robust when they were derived from HIF‐MSC cultures. All Jagged1‐mediated effects could be blocked by prior incubation of exosomes with an anti‐Jagged 1 antibody. All together, the results indicate that exosomes derived from MSCs stably overexpressing HIF‐1α have an increased angiogenic capacity in part via an increase in the packaging of Jagged1, which could have potential applications for the treatment of ischemia‐related disease. Stem Cells 2017;35:1747–1759
Research Impact: A United Kingdom Occupational Therapy Research Foundation Perspective

Introduction: The United Kingdom Occupational Therapy Research Foundation provides profession-specific funding for research, but what is its impact? An exploratory study was undertaken to gather intelligence on the impact of completed projects. Method: Eleven grant holders were invited to complete a research impact assessment form based on the multidimensional Becker Medical Library Model. Four domains of impact were included: research outputs and advancement of knowledge, clinical implementation, community and public benefit, and economic benefit. Results: Eight impact assessment forms were returned (73%); these reflected grants awarded across the four funding streams, although there were no returns from grant holders receiving over £50,000. Clearly evident was that most researchers were seeking publication in a range of journals, and disseminating findings at conferences. Other notable impacts included the extent to which participants were using findings in educational activities; the apparent importance of the collaborative partnerships in terms of the clinical application of findings post project; the active engagement of practitioners and service users; and the opportunities arising for follow-on funding or projects. Conclusion: Capturing research impact is complex, but vital. The project provided a strong argument to adopt a prospective approach to impact reporting throughout, and beyond, the life of a grant.
Rapid tranquillisation: a questionnaire survey of practice

A postal survey of the drug treatment of behavioural emergencies by senior registrars and consultants in psychiatry revealed that 90% would initially use a non-depot antipsychotic (including 24% who would combine it with a benzodiazepine if the situation warranted), and 10% the short-acting depot, zuclopenthixol acetate, with another antipsychotic or a benzodiazepine, or both. The choice was made from a restricted range of drugs, with haloperidol being the most popular antipsychotic and diazepam the most popular benzodiazepine. Half of respondents did not consider British National Formulary maximum dose recommendations to be useful for rapid tranquillisation and many would exceed them. A substantial minority did not consider that adequate resuscitation was available at their unit and deficiencies were revealed in the training of junior doctors and in the audit of rapid tranquillisation. Very few psychiatrists reported that their units had written guidelines.
A gated clock scheme for low power scan testing of logic ICs or embedded cores

Test power is now a big concern in large system-on-chip designs. In this paper, we present a novel approach for minimizing power consumption during scan testing of integrated circuits or embedded cores. The proposed low power technique is based on a gated clock scheme for the scan path and the clock tree feeding the scan path. The idea is to reduce the clock rate on scan cells during shift operations without increasing the test time. Numerous advantages can be found in applying such a technique.
Control-flow checking via regular expressions

The present paper explains a new approach to program control flow checking. The check has been inserted at source-code level using a signature methodology based on regular expressions. The signature checking is performed without a dedicated watchdog processor but resorting to inter-process communication (IPC) facilities offered by most of the modern operating systems. The proposed approach allows very low memory overhead and trade-off between fault latency and program execution time overhead.