Miracle-dz/UniFAR-FTUs huggingface dataset:
Selection for ovulation rate in rabbits: correlated response on litter size and its components.

The aim of this work was to evaluate the response t o six generations of selection for ovulation rate. The line was derived from a line selected for litte r size during 12 generations and then for uterine capacity for 10 generations. Selection was relaxed during 6 generations and then animals were selected for ovulation rate during 6 generations. S election was based on phenotypic value for ovulation rate and pressure of selection for does w a close to 30%. To avoid increase of inbreeding, males were selected within sire families. Line size was approximately 20 males and 80 females per generation. Does were mated for the first time at 1 8-20 weeks of age and 11-12 days after each parturition thereafter. Laparoscopies were performe d on all does at day 12 of their second gestation. Traits recorded in second parity were: ovulation ra te (OR), estimated as number of corpora lutea; number of implanted embryos (IE) estimated as numbe r of implantation sites; litter size (LS) estimated as total number of born rabbits, and prenatal survi val (PS=LS/OR). All the traits were recorded only i n the second parity with the exception of LS which wa s recorded over four parities. Data from 524 laparoscopies and 1874 parities were analyzed using Bayesian methods. Heritabilities of OR, IE, LS and PS were 0.27, 0.18, 0.06 and 0.07. Selection in creased OR in 1.5 oocytes but correlated response on LS was lower (0.4 kits). Correlated response on IE and PS were 1.25 and -0.04, respectively.
Glycogen Synthase Kinase 3 Phosphorylates Hypoxia-Inducible Factor 1α and Mediates Its Destabilization in a VHL-Independent Manner

ABSTRACT Hypoxia-inducible transcription factor 1α (HIF-1α) is a key player in the response to hypoxia. Additionally, HIF-1α responds to growth factors and hormones which can act via protein kinase B (Akt). However, HIF-1α is not a direct substrate for this kinase. Therefore, we investigated whether the protein kinase B target glycogen synthase kinase 3 (GSK-3) may have an impact on HIF-1α. We found that the inhibition or depletion of GSK-3 induced HIF-1α whereas the overexpression of GSK-3β reduced HIF-1α. These effects were mediated via three amino acid residues in the oxygen-dependent degradation domain of HIF-1α. In addition, mutation analyses and experiments with von Hippel-Lindau (VHL)-defective cells indicated that GSK-3 mediates HIF-1α degradation in a VHL-independent manner. In line with these observations, the inhibition of the proteasome reversed the GSK-3 effects, indicating that GSK-3 may target HIF-1α to the proteasome by phosphorylation. Thus, the direct regulation of HIF-1α stability by GSK-3 may influence physiological processes or pathophysiological situations such as metabolic diseases or tumors.
The fiscal impact of 30 years of immigration in France: an accounting approach

This article aims to evaluate the net contribution of immigration to the public finances of France between the late 1970s and the early 2010s. We developed an accounting method that disaggregates the primary deficit into the specific contributions of immigrant population and native population. We show that the net contribution of immigrants is generally negative over a relatively long period, but remains at an extremely low level (+/-0:5% of the french GDP, reduced to +/-0:2%, with the exception of 2011). The relatively negligible effect of immigrants on the public accounts is explained by a favourable demographic structure offsetting their lower net individual contribution. However, the 2008 financial crisis has significantly degraded the economic condition of immigrants. The net per capita contribution of EU immigrants has significantly declined since 2000 and is now similar to values from third country immigrants.
Understanding Multilateral Treaty-Making as Constitutive Practice

Multilateral treaty-making is a venerable tool for navigating a sovereignty-constrained world. But that is not all; it is also a taken-for-granted practice of the international system, constitutive of both state actors and the international system itself. Constitutive practices are meaningful social actions that serve to circumscribe thought and action in the social world, delineating and in part generating both agents and the system in which they operate. Multilateral treaty-making is one such practice. While states make treaties, so too does treaty-making make states. Multilateral treaty-making can and does serve the instrumental interests of states, but exploring the constitutive nature of treaty-making is an inquiry into the foundations upon which those instrumental calculations are made—why have states turned to this practice in pursuit of their interests? In this article we provide a mixed-method approach to observing the constitutive dynamics described by practice theory that have thus far proven relatively elusive to capture empirically. In so doing our inquiry provides a fuller understanding of a foundation of competent statehood and of the international system in which states operate.
Novel Insights into Interleukin 6 (IL-6) Cis- and Trans-signaling Pathways by Differentially Manipulating the Assembly of the IL-6 Signaling Complex*

Background: The IL-6 signaling complex consists of a hexameric structure essential for IL-6 cis- and trans-signaling. Results: mAb 25F10 targets site IIb of IL-6R and disrupts hexamer assembly to selectively block trans-signaling. Conclusion: Cis- and trans-signaling in mice utilize distinct mechanisms to mediate assembly of the IL-6R complex. Significance: Therapeutic targeting of site IIb of IL-6R provides a unique mode of action for IL-6 inhibition. The IL-6 signaling complex is described as a hexamer, formed by the association of two IL-6·IL-6 receptor (IL-6R)·gp130 trimers, with gp130 being the signal transducer inducing cis- and trans-mediated signaling via a membrane-bound or soluble form of the IL-6R, respectively. 25F10 is an anti-mouse IL-6R mAb that binds to both membrane-bound IL-6R and soluble IL-6R with the unique property of specifically inhibiting trans-mediated signaling events. In this study, epitope mapping revealed that 25F10 interacts at site IIb of IL-6R but allows the binding of IL-6 to the IL-6R and the recruitment of gp130, forming a trimer complex. Binding of 25F10 to IL-6R prevented the formation of the hexameric complex obligate for trans-mediated signaling, suggesting that the cis- and trans-modes of IL-6 signaling adopt different mechanisms for receptor complex assembly. To study this phenomenon also in the human system, we developed NI-1201, a mAb that targets, in the human IL-6R sequence, the epitope recognized by 25F10 for mice. Interestingly, NI-1201, however, did not selectively inhibit human IL-6 trans-signaling, although both mAbs produced beneficial outcomes in conditions of exacerbated IL-6 as compared with a site I-directed mAb. These findings shed light on the complexity of IL-6 signaling. First, triggering cis- versus trans-mediated IL-6 signaling occurs via distinctive mechanisms for receptor complex assembly in mice. Second, the formation of the receptor complex leading to cis- and trans-signaling biology in mice and humans is different, and this should be taken into account when developing strategies to inhibit IL-6 clinically.
Architecture of the yeast origin recognition complex bound to origins of DNA replication

In many organisms, the replication of DNA requires the binding of a protein called the initiator to DNA sites referred to as origins of replication. Analyses of multiple initiator proteins bound to their cognate origins have provided important insights into the mechanism by which DNA replication is initiated. To extend this level of analysis to the study of eukaryotic chromosomal replication, we have investigated the architecture of the Saccharomyces cerevisiae origin recognition complex (ORC) bound to yeast origins of replication. Determination of DNA residues important for ORC-origin association indicated that ORC interacts preferentially with one strand of the ARS1 origin of replication. DNA binding assays using ORC complexes lacking one of the six subunits demonstrated that the DNA binding domain of ORC requires the coordinate action of five of the six ORC subunits. Protein-DNA cross-linking studies suggested that recognition of origin sequences is mediated primarily by two different groups of ORC subunits that make sequence-specific contacts with two distinct regions of the DNA. Implications of these findings for ORC function and the mechanism of initiation of eukaryotic DNA replication are discussed.
Applying Meta-Theory to Qualitative and Mixed-Methods Research

Meta-theory refers to broad perspectives, which make claims regarding the nature of reality. Meta-theories philosophically underpin research and practice. Despite this centrality of meta-theory to research and practice, research studies seldom have a strong articulated philosophical basis. There are persuasive philosophical arguments for invoking meta-theory in qualitative and mixed-methods research. We argue that selecting and applying a particular meta-theory is a matter of personal expression and historicity. In this article, we describe the meta-theory of critical realism (CR), which underpins our research around complex heart failure disease management interventions. CR posits that reality is mind independent and views this reality via a stratified ontology. Its explanatory focus, generative logic, multifactorial and open systems approach, and its openness to a variety of methods make it a viable meta-theory for research in a variety of disciplines, utilizing qualitative, quantitative, and mixed methods. CR hermeneutics, ethnographies, grounded theories, mixed-methods studies, and critical realist reviews follow the meta-theoretical assumptions of CR; these are extremely useful in exploring complex interventions holistically, including their components, contexts, and mechanisms.
Robust thermal microstructure for designing flow sensors and pressure sensors

This paper presents a multifunctional hot-wire based microstructure enabling the design of pressure sensors and wall shear stress sensors for aerodynamic applications. The hotwire is suspended over the substrate using periodic silicon oxide micro-bridges, allowing thermal insulation and mechanical toughness. The microstructure design was exploited to realize both wall shear stress sensors experimented in wind tunnel, and pressure sensors demonstrating a high sensitivity in a wide range around atmospheric pressure.
Integración en el mercado laboral colombiano : 1945-1998

Expone algunas consideraciones teoricas sobre los conceptos de integracion y convergencia aplicados al analisis de los mercados laborales. Describe el comportamiento historico del mercado laboral colombiano, haciendo el analisis estadistico de los salarios rurales y urbanos durante el periodo 1945-1998. Presenta los resultados de las pruebas de cointegracion y convergencia durante estos mismos anos.
Design and baseline characteristics of participants in the Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial on the cardiovascular effects of dulaglutide

The aim was to determine the effects of dulaglutide, a synthetic once‐weekly, injectable human glucagon‐like peptide 1 analogue that lowers blood glucose, body weight, appetite and blood pressure, on cardiovascular outcomes. People with type 2 diabetes, aged ≥50 years, with glycated haemoglobin (HbA1c) ≤9.5%, and either a previous cardiovascular event, evidence of cardiovascular disease or ≥2 cardiovascular risk factors were randomly allocated to a weekly subcutaneous injection of either dulaglutide (1.5 mg) or placebo and followed within the ongoing Researching cardiovascular Events with a Weekly INcretin in Diabetes (REWIND) trial every 3 to 6 months. The primary cardiovascular outcome is the first occurrence of the composite of cardiovascular death or non‐fatal myocardial infarction or non‐fatal stroke. Secondary outcomes include each component of the primary composite cardiovascular outcome, a composite clinical microvascular outcome comprising retinal or renal disease, hospitalization for unstable angina, heart failure requiring hospitalization or an urgent heart failure visit, and all‐cause mortality. Follow‐up will continue until the accrual of 1200 confirmed primary outcomes. Recruitment of 9901 participants (mean age 66 years, 46% women) occurred in 370 sites located in 24 countries over a period of 2 years. The mean duration of diabetes was 10 years, mean baseline HbA1c was 7.3%, and 31% had prior cardiovascular disease. The REWIND trial's international scope, high proportion of women, high proportion of people without prior cardiovascular disease and inclusion of participants whose mean baseline HbA1c was 7.3% suggests that its cardiovascular and safety findings will be directly relevant to the typical middle‐aged patient seen in general practice throughout the world.
Estradiol potentiation of NR2B‐dependent EPSCs is not due to changes in NR2B protein expression or phosphorylation

The hormone, 17β‐estradiol (E2), influences the structure and function of synapses in the CA1 region of the hippocampus. E2 increases the density of dendritic spines and excitatory synapses on CA1 pyramidal cells, increases CA1 cells' sensitivity to excitatory synaptic input mediated by the NMDA receptor (NMDAR), enhances NMDAR‐dependent long‐term potentiation, and improves hippocampus‐dependent working memory. Smith and McMahon ( 2006 J Neurosci 26:8517–8522) reported that the larger NMDAR‐mediated excitatory postsynaptic currents (EPSCs) recorded after E2 treatment are due primarily to an increased contribution of NR2B‐containing NMDARs. We used a combination of electrophysiology, Western blot, and immunofluorescence to investigate two potential mechanisms by which E2 could enhance NR2B‐dependent EPSCs: An increase in NMDAR subunit protein levels and/or a change(s) in NR2B phosphorylation. Our studies confirmed the E2‐induced increase in NR2B‐dependent EPSC amplitude, but we found no evidence that E2 affects protein levels for the NR1, NR2A, or NR2B subunit of the NMDAR, nor that E2 affects phosphorylation of NR2B. Our findings suggest that the effects of E2 on NMDAR‐dependent synaptic physiology in the hippocampus likely result from recruitment of NR2B‐containing NMDARs to synapses rather than from increased expression of NMDARs or changes in their phosphorylation state. © 2010 Wiley‐Liss, Inc.
Birth spacing, human capital, and the motherhood penalty at midlife in the United States

Background: Researchers have examined how first-birth timing is related to motherhood wage penalties, but research that examines birth spacing is lacking. Furthermore, little research has examined the persistence of penalties across the life course. Objective: The objective is to estimate the effects of birth spacing on midlife labor market outcomes and assess the extent to which these effects vary by education and age at first birth. Methods: I use data from the United States from the 1979–2010 waves of the National Longitudinal Survey of Youth 1979 and dynamic inverse probability of treatment weighting to estimate the effects of different birth intervals on mothers’ midlife cumulative work hours, cumulative earnings, and hourly wages. I examine how education and age at first birth moderate these effects. Results: Women with birth intervals longer than two years but no longer than six years have the smallest penalties for cumulative outcomes; in models interacting the birth interval with age at first birth, postponement of a first birth to at least age 30 appears to be more important for cumulative outcomes than birth spacing. College-educated women benefit more from a longer birth interval than less educated women. Conclusions: Childbearing strategies that result in greater accumulation of human capital provide long-run labor market benefits to mothers, and results suggest that different birth-spacing patterns could play a small role in facilitating this accumulation, as theorized in past literature. Contribution: I contribute to the demographic literature by testing the theory that birth spacing matters for mothers’ labor market outcomes and by assessing the effects at midlife rather than immediately following a birth.
Opposite and Coordinated Rotation of Amphitrichous Flagella Governs Oriented Swimming and Reversals in a Magnetotactic Spirillum

ABSTRACT Current knowledge regarding the mechanism that governs flagellar motor rotation in response to environmental stimuli stems mainly from the study of monotrichous and peritrichous bacteria. Little is known about how two polar flagella, one at each cell pole of the so-called amphitrichous bacterium, are coordinated to steer the swimming. Here we fluorescently labeled the flagella of Magnetospirillum magneticum AMB-1 cells and took advantage of the magnetically controllable swimming of this bacterium to investigate flagellar rotation in moving cells. We identified three motility behaviors (runs, tumbles, and reversals) and two characteristic fluorescence patterns likely corresponding to flagella rotating in opposite directions. Each AMB-1 locomotion mode was systematically associated with particular flagellar patterns at the poles which led us to conclude that, while cell runs are allowed by the asymmetrical rotation of flagellar motors, their symmetrical rotation triggers cell tumbling. Our observations point toward a precise coordination of the two flagellar motors which can be temporarily unsynchronized during tumbling. IMPORTANCE Motility is essential for bacteria to search for optimal niches and survive. Many bacteria use one or several flagella to explore their environment. The mechanism by which bipolarly flagellated cells coordinate flagellar rotation is poorly understood. We took advantage of the genetic amenability and magnetically controlled swimming of the spirillum-shaped magnetotactic bacterium Magnetospirillum magneticum AMB-1 to correlate cell motion with flagellar rotation. We found that asymmetric rotation of the flagella (counterclockwise at the lagging pole and clockwise at the leading pole) enables cell runs whereas symmetric rotation triggers cell tumbling. Taking into consideration similar observations in spirochetes, bacteria possessing bipolar ribbons of periplasmic flagella, we propose a conserved motility paradigm for spirillum-shaped bipolarly flagellated bacteria.
Entrepreneurial overconfidence and firm survival: an analysis using the Kauffman firm survey

ABSTRACT We used the Kauffman Firm Survey of ventures founded in the year 2004 to identify overconfident (OC) entrepreneurs and found, contrary to the existing literature, that the hazard ratio for these entrepreneurs was lower than the corresponding value for their non-OC peers. We categorized an entrepreneur as OC if he or she believed that his or her firm enjoys a competitive advantage over its industry peers, while simultaneously underperforming relative to the industry in terms of average initial ROA. Specifically, we looked at the average ROA during the years 2004–2007 and compared it to the industry median. In addition to our hazard findings, we discovered that these OC entrepreneurs, while starting with lower initial ROA levels relative to their industry peers, may have enjoyed slightly better movement in ROA over the intervening years. Our results are explained in the context of the psychological literature on optimism.
Siderophore-Based Iron Acquisition and Pathogen Control

SUMMARY High-affinity iron acquisition is mediated by siderophore-dependent pathways in the majority of pathogenic and nonpathogenic bacteria and fungi. Considerable progress has been made in characterizing and understanding mechanisms of siderophore synthesis, secretion, iron scavenging, and siderophore-delivered iron uptake and its release. The regulation of siderophore pathways reveals multilayer networks at the transcriptional and posttranscriptional levels. Due to the key role of many siderophores during virulence, coevolution led to sophisticated strategies of siderophore neutralization by mammals and (re)utilization by bacterial pathogens. Surprisingly, hosts also developed essential siderophore-based iron delivery and cell conversion pathways, which are of interest for diagnostic and therapeutic studies. In the last decades, natural and synthetic compounds have gained attention as potential therapeutics for iron-dependent treatment of infections and further diseases. Promising results for pathogen inhibition were obtained with various siderophore-antibiotic conjugates acting as “Trojan horse” toxins and siderophore pathway inhibitors. In this article, general aspects of siderophore-mediated iron acquisition, recent findings regarding iron-related pathogen-host interactions, and current strategies for iron-dependent pathogen control will be reviewed. Further concepts including the inhibition of novel siderophore pathway targets are discussed.
“It’s fun, but …” Children with cerebral palsy and their experiences of participation in physical activities

Abstract Purpose: To explore the experiences of children with cerebral palsy (CP) regarding participation in physical activities, and to describe facilitators and barriers. Methods: Sixteen children with CP 8–11 years old who varied in gross motor, cognitive and communicative function participated in either an individual interview or a focus group. Results: Two categories and 10 sub-categories emerged from the content analysis. The category “Being physically active, because …” describes facilitators for being physically active divided into the sub-categories “Enjoying the feeling”, “Being capable”, “Feeling of togetherness”, “Being aware it is good for me”, and “Using available opportunities”. The second category “Being physically active, but …” describes barriers to being physically active, divided into the sub-categories “Getting tired and experiencing pain”, “Something being wrong with my body”, “Being dependent on others”, “Not being good enough” and “Missing available opportunities”. Conclusions: Asking children with CP about the physical activities they enjoy, and giving them the opportunity of trying self-selected activities with the right support is important for facilitating an increased participation in physical activities. Having fun with family and friends when being physically active, and enjoying the sensation of speed should be taken into consideration when designing interventions. When supporting children to become and remain physically active, attention should be paid to pain, fatigue and the accessibility of activities and locations. Implications for Rehabilitation Children want to be physically active together with friends or others. Children want to have fun and enjoy the sensation of speed when being physically active. Self-selected physical activities and the opportunity of trying new activities with the right support is essential for facilitating an increased participation in physical activities. Service planning and design may be facilitated by asking children about the physical activities they enjoy.