Miracle-dz/UniFAR-FTUs huggingface dataset:
Localization of mTORC2 activity inside cells

Activation of protein kinase Akt via its direct phosphorylation by mammalian target of rapamycin (mTOR) complex 2 (mTORC2) couples extracellular growth and survival cues with pathways controlling cell growth and proliferation, yet how growth factors target the activity of mTORC2 toward Akt is unknown. In this study, we examine the localization of the obligate mTORC2 component, mSin1, inside cells and report the development of a reporter to examine intracellular localization and regulation by growth factors of the endogenous mTORC2 activity. Using a combination of imaging and biochemical approaches, we demonstrate that inside cells, mTORC2 activity localizes to the plasma membrane, mitochondria, and a subpopulation of endosomal vesicles. We show that unlike the endosomal pool, the activity and localization of mTORC2 via the Sin1 pleckstrin homology domain at the plasma membrane is PI3K and growth factor independent. Furthermore, we show that membrane recruitment is sufficient for Akt phosphorylation in response to growth factors. Our results indicate the existence of spatially separated mTORC2 populations with distinct sensitivity to PI3K inside cells and suggest that intracellular localization could contribute to regulation of mTORC2 activity toward Akt.
Rôle des étangs de barrage à vocation piscicole dans la dynamique des micropolluants en têtes de bassins versants

En Lorraine, environ 7000 ha d’etangs sont exploites pour la production piscicole. Le present travail a ete consacre a la comprehension des mecanismes de transfert des micropolluants dans les etangs en mettant l'accent sur trois questions : (1) evaluer l'ampleur de la contamination metallique des etangs (n=45) ; (2) evaluer l'influence des etangs (n=3) sur les concentrations, le risque de toxicite et les flux de pesticides; (3) evaluer l'importance relative des voies de transfert des PCB vers le poisson. (1) Les enrichissements calcules soulignent des contaminations generalement faibles a moderes a l’exception des etangs localises dans la Voge et de deux etangs localises dans la Woevre. Cet enrichissement est plus prononce pour le Cd et semble etre lie a la richesse du sediment en matiere organique et carbonates (perte au feu). (2) Dans les cours d’eau de tete de bassin versant sur lesquels s’inscrivent ces trois etangs de barrage, les concentrations les plus elevees etaient generalement reduites de plus de 90% entre l'amont et l'aval de l'etang. Le risque de toxicite, evalue par la methode de l'unite toxique, etait attenue en aval des etangs. Lorsqu’on considere les flux de pesticides, les resultats obtenus suggerent que, selon les substances considerees, les charges en pesticides sont reduites de 10 a 100% entre l'amont et l'aval de l'etang. (3) Les resultats montrent que le sediment contamine n’a pas d’impact sur la biodisponibilite orale des trois congeneres de PCB chez la carpe commune. L’effet geosorbant du sediment, qui explique son role de reservoir environnemental de PCB, parait insuffisant dans les conditions du tractus digestif de la carpe commune, pour eviter un transfert vers le poisson
Iron supplementation for acute blood loss anemia after coronary artery bypass surgery: a randomized, placebo-controlled study.

OBJECTIVE To evaluate the use of oral iron replacement therapy as an effective treatment for acute surgically induced anemia. DESIGN Double-blind, placebo-controlled, randomized clinical trial. SETTING Perioperative acute care hospital and a surgery clinic for a single cardiothoracic physician group. PATIENTS One hundred twenty-eight men and postmenopausal women, 50 years of age or older, admitted for elective coronary artery bypass surgery over a consecutive 8-month period. OUTCOME MEASURES Before surgery: serum iron, serum ferritin, hemoglobin and hematocrit. Six days after surgery: hemoglobin and hematocrit. Mean of 59 days after surgery: serum iron, serum ferritin, hemoglobin and hematocrit. INTERVENTION Patients were randomized to one of four groups: control group; placebo group; low-dose group, 50 mg elemental iron + 60 mg ascorbic acid in a multi-vitamin daily; and usual-dose group, 200 mg elemental iron daily. RESULTS One hundred twenty-one subjects completed the study: 100 men (82.6%) mean age 64.5 years and 21 women (17.4%), mean age 65.7 years. There were no statistically significant age or gender differences among groups. Statistical analysis revealed, except for side effects, no differences between or among groups for any variable measured during the last two time intervals. The mean hemoglobin and hematocrit of the entire sample at 6 days was 9.5 +/- 1.2 gm/dl and 28% +/- 2.3%, respectively. At a mean of 59 days later these values increased equally for all groups to a mean for the cohort of 13.6 +/- 1 gm/dl for hemoglobin and 40.6% +/- 3 for hematocrit. Serum iron and ferritin were within the normal range. The 200 mg group experienced significantly more side effects (p < 0.01). CONCLUSION Thus the use of oral iron supplements for the treatment of acute blood loss anemia after uncomplicated coronary artery bypass surgery did not assist in restoring red blood cell mass or help maintain total body iron stores.
El último milenio a.C. en la Cuenca delDuero. Reflexiones sobre la secuencia cultural

espanolEn la Submeseta Septentrional, se reconoce un importante poso indigena del Bronce Final (Cogotas I), con poblaciones itinerantes condicionadas por actividades ganaderas evidenciadas por la inconsistencia de sus habitats. -- Las ceramicas y los poblados estables, que parecen ejercer un intenso control territorial, evidencian discontinuidad entre Cogotas I la "I Edad del Hierro". Aun sin explicaciones invasionistas, la laguna en la investigacion de fines del siglo IX y comienzos del VIII a.C. impide conocer el proceso de tales cambios. Se puede aceptar continuidad entre el Hierro I y II, pero es cierto el papel de los grupos con ceramicas a peine del S.O. De la Meseta, en la formacion de los pueblos de la segunda Edad del Hierro, pues, tipos ceramicos nuevos aparecen sin repercusion alguna y otros se diluyen al introducirse las especies a torno y pintadas de la II Edad del Hierro. EnglishImportant remains frotn the Late Bronze Age (Cogotas 1) can be recognised, concerning to populations with a nomadic way of life conditioned by stockraising, indicated by insubstantial dwellings. There is a marked contrast between Cogotas I and the «Early Iron Age» groups, both in pottery and in their stable settlements, which appear to have exercised tight territorial control. Thus there is a lack of continuity, even if invasionist explanations of the cultural change are avoided, although there is a gap in investigation between the end of the 9th and beginning of the 8th century B. C. The continuitv between Early and Lote Iron Ages can be accepted, but the role of the groups with combed pottery in the S W of the Meseta in building the peoples of the Late Iron Age is open to question, since new types of pottery appear in the Early Iron Age groups and the thrown and painted types characteristic of the height of the Late Iron Age are introduced without any repercussions.
Loss of caspase-2 augments lymphomagenesis and enhances genomic instability in Atm-deficient mice

Significance The cysteine protease caspase-2 has been implicated in the suppression of oncogene-mediated tumor formation. However, the mechanisms underlying the function of caspase-2 as a tumor suppressor are not well defined. In this study, we use a well-characterized mouse lymphoma model and demonstrate a critical role for caspase-2 in maintaining genome stability and in the suppression of tumorigenesis following loss of the essential DNA repair gene ataxia telangiectasia mutated (Atm). Our findings suggest that caspase-2 cooperates with ATM to suppress genomic instability, oxidative stress, and tumor progression. Caspase-2, the most evolutionarily conserved member of the caspase family, has been shown to be involved in apoptosis induced by various stimuli. Our recent work indicates that caspase-2 has putative functions in tumor suppression and protection against cellular stress. As such, the loss of caspase-2 enhances lymphomagenesis in Eµ-Myc transgenic mice, and caspase-2 KO (Casp2−/−) mice show characteristics of premature aging. However, the extent and specificity of caspase-2 function in tumor suppression is currently unclear. To further investigate this, ataxia telangiectasia mutated KO (Atm−/−) mice, which develop spontaneous thymic lymphomas, were used to generate Atm−/−Casp2−/− mice. Initial characterization revealed that caspase-2 deficiency enhanced growth retardation and caused synthetic perinatal lethality in Atm−/− mice. A comparison of tumor susceptibility demonstrated that Atm−/−Casp2−/− mice developed tumors with a dramatically increased incidence compared with Atm−/− mice. Atm−/−Casp2−/− tumor cells displayed an increased proliferative capacity and extensive aneuploidy that coincided with elevated oxidative damage. Furthermore, splenic and thymic T cells derived from premalignant Atm−/−Casp2−/− mice also showed increased levels of aneuploidy. These observations suggest that the tumor suppressor activity of caspase-2 is linked to its function in the maintenance of genomic stability and suppression of oxidative damage. Given that ATM and caspase-2 are important components of the DNA damage and antioxidant defense systems, which are essential for the maintenance of genomic stability, these proteins may synergistically function in tumor suppression by regulating these processes.
A scalar finite-difference time-domain approach to guided-wave optics

A finite-difference time-domain approach that solves the scalar wave equations is proposed and validated. The propagation, reflection, scattering, and radiation of electromagnetic waves in weakly guiding optical devices are described explicitly in the time domain. The method is applied to the simulation of guided-wave devices such as directional couplers and distributed feedback reflectors. A comparison to known analytical solutions shows good agreement. <<ETX>>
H. pylori induces the expression of Hath1 in gastric epithelial cells via interleukin‐8/STAT3 phosphorylation while suppressing Hes1

Chronic gastritis associated with Helicobacter pylori is a leading cause of gastric intestinal metaplasia (IM), which arises from abnormal cell differentiation of the epithelium in the gastric mucosa. However, the mechanisms involved in H. pylori‐mediated IM remain elusive. The aim of our study was to explore the effects and the underlying mechanisms of H. pylori on the abnormal expression of Hath1 and Sox2 and to reveal its relationship to the development of gastric IM. We found that Hath1 and Sox2 were overexpressed in gastric IM tissue. Hath1 expression was up‐regulated, whereas Sox2 expression, which was independent of the CagA virulence factor, was down‐regulated in gastric epithelial cells and coincided with increased IL‐6 and IL‐8 levels in the culture media. Stimulation with H. pylori‐related cytokine IL‐8, but not IL‐6 or IL‐1β, was induced by Hath1 expression in the gastric epithelial cells. Although IL‐8 and IL‐6 levels correlated with STAT3 (signal transducer and activator of transcription) phosphorylation before and after H. pylori eradication in the gastric mucosa, only the blocking of IL‐8‐induced STAT3 activation using AG490 or STAT3‐targeting RNA interference altered Hath1 expression. Additionally, we found that H. pylori down‐regulated Hes1, which is a direct downstream target gene of Notch signaling and a repressor of Hath1 expression. These findings suggest that H. pylori induced inflammation up‐regulate Hath1 expression via interleukin‐8/STAT3 (IL‐8) phosphorylation while suppressing Hes1, which provides a novel molecular connection between a H. pylori infection and intestinal metaplasia. J. Cell. Biochem. 113: 3740–3751, 2012. © 2012 Wiley Periodicals, Inc.
Centralized student learning platform

How does a future centralized learning platform for students in an academic environment look like? What are the needs and requirements for current and potential academic users? Are Facebook, WhatsApp and Dropbox the winners? Which recommendations can be worked out for a suitable IT landscape and how does an integrated data security concept look like? This paper analyses the needs and requirements for a centralized learning platform from a students' point of view.
Differential Requirements for RAD51 in Physcomitrella patens and Arabidopsis thaliana Development and DNA Damage Repair[W]

RAD51, the eukaryotic homolog of the bacterial RecA recombinase, plays a central role in homologous recombination (HR) in yeast and animals. Loss of RAD51 function causes lethality in vertebrates but not in other animals or in the flowering plant Arabidopsis thaliana, suggesting that RAD51 is vital for highly developed organisms but not for others. Here, we found that loss of RAD51 function in the moss Physcomitrella patens, a plant of less complexity, caused a significant vegetative phenotype, indicating an important function for RAD51 in this organism. Moreover, loss of RAD51 caused marked hypersensitivity to the double-strand break-inducing agent bleomycin in P. patens but not in Arabidopsis. Therefore, HR is used for somatic DNA damage repair in P. patens but not in Arabidopsis. These data imply fundamental differences in the use of recombination pathways between plants. Moreover, these data demonstrate that the importance of RAD51 for viability is independent of taxonomic position or complexity of an organism. The involvement of HR in DNA damage repair in the slowly evolving species P. patens but not in fast-evolving Arabidopsis suggests that the choice of the recombination pathway is related to the speed of evolution in plants.
Impaired regulatory T cell function in germ‐free mice

Regulatory T cells (Treg) are crucial for the maintenance of tolerance to auto‐antigens and harmless exogenous antigens. Here, we studied the role of the commensal microbiota for the development and function of Treg. CD4+CD25+ T cells were obtained from peripheral lymph nodes (PLN) and mesenteric lymph nodes (MLN) of germ‐free (GF) and conventional (conv) NMRI mice and tested for phenotype and functional suppressive capacity. CD4+CD25+ T cells from GF mice showed a lower relative gene expression of fork head box p3 gene (Foxp3) and were not as potent suppressors in vitro as CD4+CD25+ T cells from conv animals. Intracellular staining for Foxp3 and CTLA‐4 revealed proportional and regional differences in putative Treg subsets between conv and GF mice. Fewer of the CD4+CD25+ T cells in GF MLN expressed Foxp3 and CTLA‐4, while the expression of these markers was similar amongst the CD4+CD25+ T cells in PLN of conv and GF mice. The largest difference between conv and GF Treg was observed in the liver draining celiac lymph node, where GF mice had fewer putative Treg as compared to conv mice. We propose that the presence of a microbial flora favors the development of a fully functional Treg population.
The Comparative Release of FGF1 by Hypoxia and Temperature Stress

Abstract The signal peptide-less FGF gene family prototype, FGF1 is released in response to temperature stress in vitro as a latent reducing agent-sensitive homodimer non-covalently complexed with the extravesicular p40 domain of p65 synaptotagmin (Syt)1. Because FGF1 is well recognized as an angiogenesis factor in vivo and angiogenesis is known to be induced by hypoxia, we examined the release of FGF1 and p40 Syt1 under conditions of hypoxia and temperature stress using a chemostatic microcarrier cell culture system. We report that like the pathway used by FGF1 and p40 Syt1 release under temperature stress, hypoxia also induces the release of FGF1 and p40 Syt1 with similar kinetic and pharmacologic properties including the requirement for functional cysteine residues. Lastly, FGF1 and p40 Syt1 release in response to hypoxia and temperature stress is sensitive to lipoxygenase and cyclooxygenase inhibitors suggesting that arachidonic acid metabolism may play an important role in the mechanism of FGF1 release in vitro.
Cerebral vasculopathy with aneurysm formation in HIV-infected young adults

The article by Kossorotoff et al. highlights the importance of vigilance for HIV-associated cerebral aneurysms in adults as a cause of stroke.1 They discuss two patients with HIV, ages 23 and 32, who had strokes and were found to have ectasias and aneurysms of the large cerebral arteries (which they term CVA [cerebral vasculopathy with aneurysm]). Although the definitive cause of CVA in HIV-infected persons remains unclear, there is evidence that immune reconstitution in patients with AIDS leads to a vasculopathy complicating a chronic endothelial infection.2 Immune reconstitution inflammatory syndrome (IRIS) is …
IN-SITU DEGASSING STUDIES ON CRYSTAL-FREE AND CRYSTAL-BEARING STROMBOLI BASALTS : IMPLICATIONS FOR STROMBOLI VOLCANO ERUPTIONS Thesis

II RÉSUMÉ . III LIST OF FIGURES . VI LIST OF TABLES . VIII ACKNOWLEDGEMENTS . IX PREFACE . X CHAPTER 1: GENERAL INTRODUCTION . 1 CHAPTER 2: CRYSTALLIZATION EXPERIMENTS, DEGASSING E XPERIMENTS AND PERMEABILITY STUDY METHODS . 10 2.1 DEGASSING EXPERIMENTS ON CRYSTAL-FREE SAMPLES . 10 2.2 CRYSTALLIZATION AND DEGASSING EXPERIMENTS ON CR YSTALBEARING SAMPLES . 12 2.3 PERMEABILITY STUDY METHODS. 1 3 2.3.1 Defining permeability in porous media . 13 2.3.2 Lattice-Boltzmann simulations . 15 2.3. 3 Permeability measurement techniques . 17 CHAPTER 3: INVESTIGATING THE EFFECTS OF SAMPLE SIZE AND RESOLULTION ON POROSITY AND PERMEABILITY . 19 3.1 SAMPLE SIZE EFFECTS ON PERMEABILITY FROM LATTIC E-BOLTZMANN SIMULATIONS . 19 3.2 RESOLUTION EFFECTS ON POROSITY AND CALCULATED P ERMEABILITY . 20 CHAPTER 4: PERMEABILITY RESULS FROM MEASUREMENTS AN D LATTICEBOLTZMANN SIMULATIONS . 27
Detailed characterization of MLH1 p.D41H and p.N710D variants coexisting in a Lynch syndrome family with conserved MLH1 expression tumors

Lynch syndrome (LS) is an autosomal dominant cancer‐susceptibility disease caused by inactivating germline mutations in mismatch repair (MMR) genes. Variants of unknown significance (VUS) are often detected in mutational analysis of MMR genes. Here we describe a large family fulfilling Amsterdam I criteria carrying two rare VUS in the MLH1 gene: c.121G > C (p.D41H) and c.2128A > G (p.N710D). Collection of clinico‐pathological data, multifactorial analysis, in silico predictions, and functional analyses were used to elucidate the clinical significance of the identified MLH1 VUS. Only the c.121G > C variant cosegregated with LS‐associated tumors in the family. Diagnosed colorectal tumors were microsatellite unstable although immunohistochemical staining revealed no loss of MMR proteins expression. Multifactorial likelihood analysis classified c.2128A > G as a non‐pathogenic variant and c.121G > C as pathogenic. In vitro functional tests revealed impaired MMR activity and diminished expression of c.121G > C. Accordingly, the N710 residue is located in the unconserved MLH1 C‐terminal domain, whereas D41 is highly conserved and located in the ATPase domain. The obtained results will enable adequate genetic counseling of c.121G > C and c.2128A > G variant carriers and their families. Furthermore, they exemplify how cumulative data and comprehensive analyses are mandatory to refine the classification of MMR variants.
Coalescence of two spinning black holes: an effective one-body approach

We generalize to the case of spinning black holes a recently introduced ``effective one-body'' approach to the general relativistic dynamics of binary systems. The combination of the effective one-body approach, and of a Pad\'e definition of some crucial effective radial functions, is shown to define a dynamics with much improved post-Newtonian convergence properties, even for black hole separations of the order of $6 GM / c^2$. We discuss the approximate existence of a two-parameter family of ``spherical orbits'' (with constant radius), and, of a corresponding one-parameter family of ``last stable spherical orbits'' (LSSO). These orbits are of special interest for forthcoming LIGO/VIRGO/GEO gravitational wave observations. It is argued that for most (but not all) of the parameter space of two spinning holes the effective one-body approach gives a reliable analytical tool for describing the dynamics of the last orbits before coalescence. This tool predicts, in a quantitative way, how certain spin orientations increase the binding energy of the LSSO. This leads to a detection bias, in LIGO/VIRGO/GEO observations, favouring spinning black hole systems, and makes it urgent to complete the conservative effective one-body dynamics given here by adding (resummed) radiation reaction effects, and by constructing gravitational waveform templates that include spin effects. Finally, our approach predicts that the spin of the final hole formed by the coalescence of two arbitrarily spinning holes never approaches extremality.
Spoken Term Detection Results Using Plural Subword Models by Estimating Detection Performance for Each Query

The present paper proposes a new integration method of plural spoken term detection (STD) results obtained from plural subword models that we previously proposed. We confirmed that these new subword models, which are the 1/2 phone model, the 1/3 phone model, and the sub-phonetic segment (SPS) model, are effective for STD systems, which must be vocabulary-free in order to process arbitrary query words. In addition, these models are more sophisticated on the time axis than conventional phone models, such as the triphone model. In the present study, we utilize the results of the subword models explicitly when integrating the plural results. For this purpose, we introduce an STD performance index that expresses the degree of detection difficulty for each query word. The index is approximated by the recognition accuracy of the query subword sequence. We demonstrate improved performance through experiments using an actual presentation speech corpus.
Protection of mice against the intracellular bacterium Listeria monocytogenes by recombinant immune interferon

Immune interferon, available at high specific activity through recombinant DNA technology, is known to activate macrophages to intra‐ and extracellular cytotoxicity. We now report that murine recombinant IFN‐γ activates macrophages to cytotoxicity also when applied in vivo. Furthermore, recombinant IFN‐γ can protect mice in vivo against the intracellular bacterial pathogen Listeria monocytogenes in a local as well as in a systemic infection model. The role of T lymphocyte‐produced lymphokines in acquired resistance to facultative intracellular pathogens and their possible involvement in novel immunotherapy are discussed.