Miracle-dz/UniFAR-FTUs huggingface dataset:
Correction: Mice Lacking the p43 Mitochondrial T3 Receptor Become Glucose Intolerant and Insulin Resistant during Aging

Thyroid hormones (TH) play an important regulatory role in energy expenditure regulation and are key regulators of mitochondrial activity. We have previously identified a mitochondrial triiodothyronine (T3) receptor (p43) which acts as a mitochondrial transcription factor of the organelle genome, which leads in vitro and in vivo, to a stimulation of mitochondrial biogenesis. Recently, we generated mice carrying a specific p43 invalidation. At 2 months of age, we reported that p43 depletion in mice induced a major defect in insulin secretion both in vivo and in isolated pancreatic islets, and a loss of glucose-stimulated insulin secretion. The present study was designed to determine whether p43 invalidation influences life expectancy and modulates blood glucose and insulin levels as well as glucose tolerance or insulin sensitivity during aging. We report that from 4 months old onwards, mice lacking p43 are leaner than wild-type mice. p432/2 mice also have a moderate reduction of life expectancy compared to wild type. We found no difference in blood glucose levels, excepted at 24 months old where p432/2mice showed a strong hyperglycemia in fasting conditions compared to controls animals. However, the loss of glucose-stimulated insulin secretion was maintained whatever the age of mice lacking p43. If up to 12 months old, glucose tolerance remained unchanged, beyond this age p432/2 mice became increasingly glucose intolerant. In addition, if up to 12 months old p43 deficient animals were more sensitive to insulin, after this age we observed a loss of this capacity, culminating in 24 months old mice with a decreased sensitivity to the hormone. In conclusion, we demonstrated that during aging the depletion of the mitochondrial T3 receptor p43 in mice progressively induced an increased glycemia in the fasted state, glucose intolerance and an insulin-resistance several features of type-2 diabetes. Citation: Bertrand C, Blanchet E, Pessemesse L, Annicotte JS, Feillet-Coudray C, et al. (2013) Mice Lacking the p43 Mitochondrial T3 Receptor Become Glucose Intolerant and Insulin Resistant during Aging. PLoS ONE 8(9): e75111. doi:10.1371/journal.pone. 0075111 Editor: Vincent Laudet, Ecole Normale Supérieure de Lyon, France Received May 31, 2013; Accepted August 9, 2013; Published September 30, 2013 Copyright: 2013 Bertrand et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by grants from the Institut National de la Recherche Agronomique (INRA) and the Société Francophone du Diabète (SFD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: casasf@supagro.inra. fr
Pb-Pb Isotopic and X-ray Tomographic Constraints on the Origin of Chondrules

Pb-Pb Isotopic and X-ray Tomographic Constraints on the Origin of Chondrules Christopher R.J. Charles Doctor of Philosophy Graduate Department of Earth Sciences University of Toronto 2013 207Pb*/206Pb* chronometry was used to obtain the ages of Ca,Al-rich inclusions (CAIs) and chondrules found in ancient meteorites. Assuming a 238U/235U=137.88, Pb/Pb ages of chondrules in NWA801 (a CR2 meteorite) are 4564.6±1.0 Ma, chondrules in Mokoia (a CV3 chondrite) are 4564.2±1.1Ma, and CAIs in Mokoia are 4567.9±5.4 Ma. The Pb/Pb age of NWA801 chondrules is concordant with 26Al/26Mg ages of CR chondrules. However if a 238U/235U<137.88 is used, the age for NWA801 chondrules becomes younger by ∼1Ma and discordant with 26Al/26Mg ages of CR chondrules. This suggests either a discrepancy with the U compositions or the initial Mg isotopic compositions of NWA801 chondrules. The shapes of NWA801 chondrules, and blebs of FeNi metal in the meteorite matrix, were further studied by 3D X-ray micro-computed tomography (CT). Most chondrules (92%) were ‘armoured’ with one discontinuous layer of FeNi metal. Two layers of FeNi metal (one on the exterior and one concentric through the interior separated by silicate) were rare <8%. Chondrules and matrix blebs occur as oblates, prolate, spheres and triaxial spheroids. It is proposed that the shapes were made free-floating in the nebula likely by flash-melting precursors into molten droplets that were vibrating as harmonic oscillators that ‘froze-in’ their shapes during cooling. Parent-body metamorphism and shock are not likely processes affecting the matrix-bleb and chondrule shapes. Chondrules with ≥2 FeNi metal layers were likely formed by mergers and not by successive deposition and annealing of metal in multiple flash-melting events. Attempts to obtain 207Pb*/206Pb* ages from chondrules and CAIs by thermal extraction (TE)TIMS were unsuccessful. However LA-ICP-MS was shown to be useful for rapidly determining Pb isotopic trends in meteorites and unknown objects. In particular, it was shown that 137La (T1/2=60ky) should be detectable in recently fallen meteorites using LaF − 4 to suppress the 137Ba
A low phase noise and large tuning range 2.4GHz LC voltage-controlled oscillator

This paper presents the design of a 2.4GHz LC VCO implemented using CMOS technology. Designed using a combination of both 0.13um and 0.35um CMOS process, this cross-coupled CMOS LC VCO achieves a simulated phase noise of −114.8dBc/Hz at 1MHz of offset frequency. The output frequency of the VCO can be tuned from 1.973GHz to 2.667GHz, which correspond to 694MHz tuning range, obtained by tuning the control voltage to the junction varactor pairs. The VCO consumes 12mW power from a 3V DC supply voltage.
A Comparison of NOOP to Structural Domain-Theoretic Models of Object-Oriented Programming

Mainstream object-oriented programming languages such as Java, C#, C++ and Scala are all almost entirely nominally-typed. NOOP is a recently developed domain-theoretic model of OOP that was designed to include full nominal information found in nominally-typed OOP. This paper compares NOOP to the most widely known domain-theoretic models of OOP, namely, the models developed by Cardelli and Cook, which were structurally-typed models. Leveraging the development of NOOP, the comparison presented in this paper provides a clear and precise mathematical account for the relation between nominal and structural OO type systems.
Efeito da irrigação na produção e qualidade de pastagens durante o período da seca

The main obstacle to animal production based on the use of pasture is climate change, which occurs in Brazil throughout the year. This variation creates delays in fattening and finishing of grazing animals, which ultimately often compromising the quality of products from animals pastures. Water is the most limiting factor to forage production, the stress generated by water deficit leads to senescence of plant tissues, reducing its nutritional value. Besides reducing the nutritional quality of plant water shortage also decreases the supply of forage, thus reducing the carrying capacity of the pasture. In this sense, the irrigation of pasture during drought is an alternative that aims to minimize the effects caused by lack of water in the grazing system. The adequate supply of water the plant allows it reaches its productive potential and maintain their nutritional quality.
Pragmatic prioritization of software quality assurance efforts

A plethora of recent work leverages historical data to help practitioners better prioritize their software quality assurance efforts. However, the adoption of this prior work in practice remains low. In our work, we identify a set of challenges that need to be addressed to make previous work on quality assurance prioritization more pragmatic. We outline four guidelines that address these challenges to make prior work on software quality assurance more pragmatic: 1) Focused Granularity (i.e., small prioritization units), 2) Timely Feedback (i.e., results can be acted on in a timely fashion), 3) Estimate Effort (i.e., estimate the time it will take to complete tasks), and 4) Evaluate Generality (i.e., evaluate findings across multiple projects and multiple domains). We present two approaches, at the code and change level, that demonstrate how prior approaches can be more pragmatic.
Development of Maps of Simple and Complex Cells in the Primary Visual Cortex

Hubel and Wiesel (1962) classified primary visual cortex (V1) neurons as either simple, with responses modulated by the spatial phase of a sine grating, or complex, i.e., largely phase invariant. Much progress has been made in understanding how simple-cells develop, and there are now detailed computational models establishing how they can form topographic maps ordered by orientation preference. There are also models of how complex cells can develop using outputs from simple cells with different phase preferences, but no model of how a topographic orientation map of complex cells could be formed based on the actual connectivity patterns found in V1. Addressing this question is important, because the majority of existing developmental models of simple-cell maps group neurons selective to similar spatial phases together, which is contrary to experimental evidence, and makes it difficult to construct complex cells. Overcoming this limitation is not trivial, because mechanisms responsible for map development drive receptive fields (RF) of nearby neurons to be highly correlated, while co-oriented RFs of opposite phases are anti-correlated. In this work, we model V1 as two topographically organized sheets representing cortical layer 4 and 2/3. Only layer 4 receives direct thalamic input. Both sheets are connected with narrow feed-forward and feedback connectivity. Only layer 2/3 contains strong long-range lateral connectivity, in line with current anatomical findings. Initially all weights in the model are random, and each is modified via a Hebbian learning rule. The model develops smooth, matching, orientation preference maps in both sheets. Layer 4 units become simple cells, with phase preference arranged randomly, while those in layer 2/3 are primarily complex cells. To our knowledge this model is the first explaining how simple cells can develop with random phase preference, and how maps of complex cells can develop, using only realistic patterns of connectivity.
Epigenetic Genes and Emotional Reactivity to Daily Life Events: A Multi-Step Gene-Environment Interaction Study

Recent human and animal studies suggest that epigenetic mechanisms mediate the impact of environment on development of mental disorders. Therefore, we hypothesized that polymorphisms in epigenetic-regulatory genes impact stress-induced emotional changes. A multi-step, multi-sample gene-environment interaction analysis was conducted to test whether 31 single nucleotide polymorphisms (SNPs) in epigenetic-regulatory genes, i.e. three DNA methyltransferase genes DNMT1, DNMT3A, DNMT3B, and methylenetetrahydrofolate reductase (MTHFR), moderate emotional responses to stressful and pleasant stimuli in daily life as measured by Experience Sampling Methodology (ESM). In the first step, main and interactive effects were tested in a sample of 112 healthy individuals. Significant associations in this discovery sample were then investigated in a population-based sample of 434 individuals for replication. SNPs showing significant effects in both the discovery and replication samples were subsequently tested in three other samples of: (i) 85 unaffected siblings of patients with psychosis, (ii) 110 patients with psychotic disorders, and iii) 126 patients with a history of major depressive disorder. Multilevel linear regression analyses showed no significant association between SNPs and negative affect or positive affect. No SNPs moderated the effect of pleasant stimuli on positive affect. Three SNPs of DNMT3A (rs11683424, rs1465764, rs1465825) and 1 SNP of MTHFR (rs1801131) moderated the effect of stressful events on negative affect. Only rs11683424 of DNMT3A showed consistent directions of effect in the majority of the 5 samples. These data provide the first evidence that emotional responses to daily life stressors may be moderated by genetic variation in the genes involved in the epigenetic machinery.
Regulation of Mercury Resistance in the Crenarchaeote Sulfolobus solfataricus

ABSTRACT Mercuric ion, Hg(II), inactivates generalized transcription in the crenarchaeote Sulfolobus solfataricus. Metal challenge simultaneously derepresses transcription of mercuric reductase (merA) by interacting with the archaeal transcription factor aMerR. Northern blot and primer extension analyses identified two additional Hg(II)-inducible S. solfataricus genes, merH and merI (SSO2690), located on either side of merA. Transcription initiating upstream of merH at promoter merHp was metal inducible and extended through merA and merI, producing a merHAI transcript. Northern analysis of a merRA double mutant produced by linear DNA recombination demonstrated merHp promoter activity was dependent on aMerR to overcome Hg(II) transcriptional inhibition. Unexpectedly, in a merA disruption mutant, the merH transcript was transiently induced after an initial period of Hg(II)-mediated transcription inhibition, indicating continued Hg(II) detoxification. Metal challenge experiments using mutants created by markerless exchange verified the identity of the MerR binding site as an inverted repeat (IR) sequence overlapping the transcription factor B binding recognition element of merHp. The interaction of recombinant aMerR with merHp DNA, studied using electrophoretic mobility shift analysis, demonstrated that complex formation was template specific and dependent on the presence of the IR sequence but insensitive to Hg(II) addition and site-specific IR mutations that relieved in vivo merHp repression. Despite containing a motif resembling a distant ArsR homolog, these results indicate aMerR remains continuously DNA bound to protect and coordinate Hg(II)-responsive control over merHAI transcription. The new genetic methods developed in this work will promote experimental studies on S. solfataricus and other Crenarchaeota.
Endothelial cell plasticity: how to become and remain a lymphatic endothelial cell

Lineage commitment and differentiation into mature cell types are mostly considered to be unidirectional and irreversible processes. However, recent results have challenged this by showing that terminally differentiated cell types can be reprogrammed into other cell types, an important step towards devising strategies for gene therapy and tissue regeneration. In this Review, we summarize recent data on the earliest steps in the development of the mammalian lymphatic vasculature: the specification of lymphatic endothelial cells (LECs). We elaborate on a developmental model that integrates the different steps leading to LEC differentiation and lymphatic network formation, discuss evidence that suggests that LEC fate is plastic, and consider the potentially far-reaching implications of the ability to convert one cell type into another.
Dissection of the essential steps for condensin accumulation at kinetochores and rDNAs during fission yeast mitosis

The condensin complex has a fundamental role in chromosome dynamics. In this study, we report that accumulation of Schizosaccharomyces pombe condensin at mitotic kinetochores and ribosomal DNAs (rDNAs) occurs in multiple steps and is necessary for normal segregation of the sister kinetochores and rDNAs. Nuclear entry of condensin at the onset of mitosis requires Cut15/importin α and Cdc2 phosphorylation. Ark1/aurora and Cut17/Bir1/survivin are needed to dock the condensin at both the kinetochores and rDNAs. Furthermore, proteins that are necessary to form the chromatin architecture of the kinetochores (Mis6, Cnp1, and Mis13) and rDNAs (Nuc1 and Acr1) are required for condensin to accumulate specifically at these sites. Acr1 (accumulation of condensin at rDNA 1) is an rDNA upstream sequence binding protein that physically interacts with Rrn5, Rrn11, Rrn7, and Spp27 and is required for the proper accumulation of Nuc1 at rDNAs. The mechanism of condensin accumulation at the kinetochores may be conserved, as human condensin II fails to accumulate at kinetochores in hMis6 RNA interference–treated cells.
Coronavirus HKU1 and Other Coronavirus Infections in Hong Kong

ABSTRACT We have recently described the discovery of a novel coronavirus, coronavirus HKU1 (CoV-HKU1), associated with community-acquired pneumonia. However, the clinical spectrum of disease and the epidemiology of CoV-HKU1 infections in relation to infections with other respiratory viruses are unknown. In this 12-month prospective study, 4,181 nasopharyngeal aspirates from patients with acute respiratory tract infections were subjected to reverse transcription-PCRs specific for CoV-HKU1 and human coronaviruses NL63 (HCoV-NL63), OC43 (HCoV-OC43), and 229E (HCoV-229E). Coronaviruses were detected in 87 (2.1%) patients, with 13 (0.3%) positive for CoV-HKU1, 17 (0.4%) positive for HCoV-NL63, 53 (1.3%) positive for HCoV-OC43, and 4 (0.1%) positive for HCoV-229E. Of the 13 patients with CoV-HKU1 infections, 11 were children and 8 had underlying diseases. Similar to the case for other coronaviruses, upper respiratory infection was the most common presentation of CoV-HKU1 infections, although pneumonia, acute bronchiolitis, and asthmatic exacerbation also occurred. Despite a shorter duration of fever (mean, 1.7 days) and no difference in maximum temperature in children with CoV-HKU1 infections compared to patients with most other respiratory virus infections, a high incidence of febrile seizures (50%) was noted, which was significantly higher than those for HCoV-OC43 (14%), adenovirus (9%), human parainfluenza virus 1 (0%), and respiratory syncytial virus (8%) infections. CoV-HKU1 and HCoV-OC43 infections peaked in winter, although cases of the former also occurred in spring to early summer. This is in contrast to HCoV-NL63 infections, which mainly occurred in early summer and autumn but were absent in winter. Two genotypes of CoV-HKU1 cocirculated during the study period. Continuous studies over a longer period are warranted to ascertain the seasonal variation and relative importance of the different coronaviruses. Similar studies in other countries are required to better determine the epidemiology and genetic diversity of CoV-HKU1.
Annular Variability and Eddy–Zonal Flow Interactions in a Simplified Atmospheric GCM. Part I: Characterization of High- and Low-Frequency Behavior

Abstract Experiments have been performed using a simplified, Newtonian forced, global circulation model to investigate how variability of the tropospheric jet can be characterized by examining the combined fluctuations of the two leading modes of annular variability. Eddy forcing of this variability is analyzed in the phase space of the leading modes using the vertically integrated momentum budget. The nature of the annular variability and eddy forcing depends on the time scale. At low frequencies the zonal flow and baroclinic eddies are in quasi equilibrium and anomalies propagate poleward. The eddies are shown primarily to reinforce the anomalous state and are closely balanced by the linear damping, leaving slow evolution as a residual. At high frequencies the flow is strongly evolving and anomalies are initiated on the poleward side of the tropospheric jet and propagate equatorward. The eddies are shown to drive this evolution strongly: eddy location and amplitude reflect the past baroclinicity, while .
A Scoring System to Predict the Development of Bone Metastasis After Radical Resection of Colorectal Cancer.

BACKGROUND/AIM To develop a scoring system to predict bone metastasis after radical resection within 5 years. PATIENTS AND METHODS We evaluated the patient records of 1,749 patients, of whom 50 patients developed bone metastasis. Treatment-related factors (age, gender, localization, histology, preoperative carbohydrate antigen 199 level, T-stage, lymph node metastasis (LN) and pulmonary metastasis (PM)) were analyzed. RESULTS We found three independent risk factors, namely rectal cancer (p=0.038), LN (p=0.006) and metachronous PM (p<0.001). Scoring was conducted by adding zero or one point from each variable and resulted in four groups of 0, 1, 2 or 3 points. Three groups were formed, with 0-1 points vs. 2 points vs. 3 points (1.5% vs. 6.6% and 10.5%, p<0.001). CONCLUSION This new score can help clinicians identify patients at risk for continuous monitoring and optimize surveillance to be able to detect and treat bone metastases very early in order to avoid skeletal complications.
Alterations in regional homogeneity of resting-state cerebral activity in patients with chronic prostatitis/chronic pelvic pain syndrome

The purpose of this study was to explore the neural mechanism in Chronic prostatitis/Chronic pelvic pain syndrome (CP/CPPS) using resting-state functional magnetic resonance imaging. The functional magnetic resonance imaging was performed on 31 male CP/CPPS-patients and 31 age and education matched male healthy controls on a 3-T magnetic resonance imaging unit. A two-sample t-test was adopted to reveal the regional homogeneity between the patients and healthy controls. The mean regional homogeneity values in the alerted brain regions of patients were correlated with the clinical measurements by using Pearson's correlation analyses. The CP/CPPS-patients had significantly decreased regional homogeneity in the bilateral anterior cingulate cortices, insular cortices and right medial prefrontal cortex, while significantly increased regional homogeneity in the brainstem and right thalamus compared with the healthy controls. In the CP/CPPS-patients, the mean regional homogeneity value in the left anterior cingulate cortex, bilateral insular cortices and brainstem were respectively correlated with the National Institutes of Health Chronic Prostatitis Symptom Index total score and pain subscale. These brain regions are important in the pain modulation process. Therefore, an impaired pain modulatory system, either by decreased descending pain inhibition or enhanced pain facilitation, may explain the pain symptoms in CP/CPPS.