Miracle-dz/UniFAR-FTUs huggingface dataset:
NFAT5-dependent transcriptional stress control of endothelial cells prevents maladaptive remodeling of pulmonary arterioles in the hypoxic lung

Aims Chronic hypoxia causes detrimental structural alterations in the lung, which are partially dependent on stress responses of the endothelium. In this context, we revealed that hypoxia-exposed murine lung endothelial cells (MLEC) activate nuclear factor of activated T-cells 5 (NFAT5) - a transcription factor that adjusts the cellular transcriptome to cope with multiple environmental stressors. Here, we studied the functional relevance of NFAT5 for the control of hypoxia-induced transcription in MLEC. Methods and Results Targeted ablation of Nfat5 in endothelial cells did not evoke phenotypic abnormalities in normoxia-exposed mice. However, MLEC in Nfat5-deficient mice up-regulated energy- and protein-metabolism-associated gene expression under normobaric hypoxia (10% O2) for seven days as evidenced by microarray- and scRNA-seq-based analyses. Moreover, loss of NFAT5 boosted the expression and release of platelet-derived growth factor B (Pdgfb) - a HIF1α-regulated driver of vascular smooth muscle cell (VSMC) growth - in capillary MLEC of hypoxia-exposed mice, which was accompanied by exaggerated coverage of distal pulmonary arterioles by VSMC, increased pulmonary vascular resistance and impaired right ventricular functions. In vitro, knockout of Nfat5 in cultured MLEC stimulated Pdgfb expression and release after exposure to hypoxia and amplified binding of HIF1α in the Pdgfb promoter region. Conclusion Collectively, our study identifies NFAT5 as a protective transcription factor required to rapidly adjust the transcriptome of MLEC to hypoxia. Specifically, NFAT5 restricts HIF1α-mediated Pdgfb expression and consequently limits muscularization and resistance of pulmonary arterioles. Highlights Hypoxia stimulates the transcriptional activity of NFAT5 in MLEC. Loss of NFAT5 in hypoxia-exposed MLEC results in EC subtype-specific maladaption of growth factor-, energy- and protein-metabolism-associated gene expression. Specifically, NFAT5-deficient capillary lung EC unleash HIF1α-regulated Pdgfb expression and release, which results in excessive coverage of pulmonary arterioles by VSMC. NFAT5-dependent control of early stress responses of capillary MLEC is required to limit the increase in pulmonary vascular resistance and impairment of right ventricular functions. Graphical Abstract
Pathogenic CD8 T cell responses are driven by neutrophil-mediated hypoxia in cutaneous leishmaniasis

Cutaneous leishmaniasis caused by Leishmania parasites exhibits a wide range of clinical manifestations. Although parasites influence disease severity, cytolytic CD8 T cell responses mediate disease. While these responses originate in the lymph node, we find that expression of the cytolytic effector molecule granzyme B is restricted to lesional CD8 T cells in Leishmania- infected mice, suggesting that local cues within inflamed skin induce cytolytic function. Expression of Blimp-1 (Prdm1), a transcription factor necessary for cytolytic CD8 T cell differentiation, is driven by hypoxia within the inflamed skin. Hypoxia is further enhanced by the recruitment of neutrophils that consume oxygen to produce reactive oxygen species, ultimately increasing granzyme B expression in CD8 T cells. Importantly, lesions from cutaneous leishmaniasis patients exhibit hypoxia transcription signatures that correlate with the presence of neutrophils. Thus, targeting hypoxia-driven signals that support local differentiation of cytolytic CD8 T cells may improve the prognosis for patients with cutaneous leishmaniasis, as well as other inflammatory skin diseases where cytolytic CD8 T cells contribute to pathogenesis.
Probing the Structure and Functional Properties of the Dropout-induced Correlated Variability in Convolutional Neural Networks

Computational neuroscience studies have shown that the structure of neural variability to an unchanged stimulus affects the amount of information encoded. Some artificial deep neural networks, e.g. those with Monte Carlo dropout layers, also have variable responses when the input is fixed. However, the structure of the trial-by-trial neural co-variance in neural networks with dropout has not been studied and its role in decoding accuracy is unknown. We studied the above questions in a convolutional neural network model with dropout in both the training and testing phase. We found that trial-by-trial correlation between neurons, i.e. noise correlation, is positive and low-dimensional. Neurons that are close in a feature map have larger noise correlation. These properties are surprisingly similar to the findings in the visual cortex. We further analyzed the alignment of the main axes of the covariance matrix. We found that different images share a common trial-by-trial noise covariance subspace, and they are aligned with the global signal covariance. The above evidence that the noise covariance is aligned with signal covariance suggests that noise covariance in dropout neural networks reduces network accuracy, which we further verified directly with a trial-shuffling procedure commonly used in neuroscience. These findings highlight a previously overlooked as-pect of dropout layers that can affect network performance. Such dropout networks could also potentially be a computational model of neural variability.
Host-pathogen-vector continuum in a changing landscape: Drivers of Bartonella prevalence and evidence of historic spillover in a multi-host community

Small mammals and their ectoparasites present a unique system to investigate the eco-epidemiology of multi-host vector-borne pathogens and identify specific bacterial spillover determinants. We applied ecological and evolutionary analyses in a rainforest-human-use mosaic to investigate Bartonella spp. across small mammal and ectoparasite communities. We observed substantial overlap among small mammal communities in different habitat types, predominantly driven by habitat generalists. Most ectoparasites were generalists, infecting multiple hosts. We observed high Bartonella prevalence at both study sites –a forest-plantation mosaic (47.4%) and a protected area (28.8%). Seven of the ten ectoparasite species sampled were also positive for Bartonella, following prevalence trends in their hosts. A generalised linear model revealed an independent association between aggregated ectoparasite load in hosts and Bartonella prevalence, implicating ectoparasites in transmission. Bartonella lineages from small mammals were host-specific, while ectoparasites carried Bartonella associated with other small mammal hosts, indicating the potential for cross-species transmission. Phylogenetic ancestral trait reconstruction of Bartonella haplotypes suggest historic spillover events in the small mammal community, validating the potential for contemporary spillover events. These results highlight the necessity to disentangle the complex relationship between hosts, ectoparasites, and pathogens to understand the zoonotic implications of undetected spillover events in such multi-host communities.
Onramping of Cold Oceanic Lithosphere in a Forearc Setting: The Southeast Bohol Ophiolite Complex, Central Philippines

Geochemical and mineralogical data show that the Early Cretaceous Southeast Bohol Ophiolite Complex on Bohol island, Central Philippines, was generated in a subduction-related marginal basin. The volcanic-hypabyssal rocks show negative Nb, Zr, and Ti anomalies, suggesting an island-arc affinity. This signature is consistent with the high anorthite contents of the gabbro and norite plagioclases, although the ultramafic rocks contain low XCr [Cr/(Cr + Al) < 0.60] spinels. The ophiolite is thrust on top of a tectonic melange, the Cansiwang Melange, which in turn is thrust over the Alicia Schist, a metamorphosed oceanic crust sliver made up of chlorite schist, amphibolite schist, and quartz-sericite schist. The presence of serpentinite between the ophiolite and the Alicia Schist indicates that the amphibolite schist cannot represent the emplacement-related metamorphic sole of the Southeast Bohol Ophiolite Complex. The composition of the associated serpentinite sole (Cansiwang Melange) of the ophiolite complex suggests that this crust-mantle sequence was emplaced at a relatively low temperature (<500°C). The onramping of the Southeast Bohol Ophiolite Complex as a forearc ophiolite, followed by its collision and suturing with the Alicia Schist, occurred during the Late Cretaceous. This ophiolite could represent a fragment of the Cretaceous proto-Philippine Sea plate.
Orthacea from the Montoya Group (Ordovician) of trans-Pecos Texas

Orthacea in the Upham, Aleman, and Cutter formations include Glyptorthis insulpta maquoketensis Ladd, Hesperorthis kirki n. sp. , Plaesiomys bellistriatus Wang, P. cf. P. subquadratus (Hall), P. subquadratus cutterensis n. subsp. , Hebertella occidentalis montoyensis n. subsp. , Austinella kankakensis (McChesney), Platystrophia prayi n. sp. , and an unnamed species of Platystrophia. Comparison of muscle scar patterns in Plaesiomys shows difficulty of basing specific differentiation upon pedicle valve musculature; number of costae per unit distance along the anterior margin, when correlated with shell size, proves to be more reliable. The Aleman and Cutter are correlated with the Maquoketa Shale of Iowa (Cincinnatian).
CTCs Detection from Intraoperative Salvaged Blood in RCC-IVC Thrombus Patients by Negative Enrichment and iFISH Identi�cation - A Preliminary Study

Background: Intra-operative cell salvage (IOCS) and leukocyte-depleted �lter (LDF) are widely used and effective in saving blood. However, the safety issue concerning reinfusion of IOCS-LDF processed blood to renal cell carcinoma (RCC) patients with inferior vena cava (IVC) thrombus were inconclusive for fear of increased risk of cancer metastases. This study intends to analyze the circulating tumor cell (CTC) eliminating effect of IOCS-LDF in 5 RCC-IVC thrombus patients. Methods: A novel strategy integrating negative enrichment by immunomagnetic beads and immunostaining-�uorescence in situ hybridization with probes identifying aneuploid of 8 and/or 7 were used to detect CTCs from salvages blood. Blood samples were collected from 4 stages in each patient. Results: The CTCs number decreased (from 3, 4, 10, 7, 3, respectively, to all zero) after IOCS-LDF treatment. And the triploidy of chrmosome 7 and/or chromosome 8 were most common karyotype for RCC patients with IVC thrombus. Tetraploid of chromosome 8 concurred in only one sample and no polypoid (number of chromosome(cid:0)4) were found. Conclusion: IOCS-LDF might be a viable option for reduction of allogeneic product transfusion based on current preliminary outcome. More convincing conclusions are to be drawn with enlarged sample size and long-term follow-up of patients prognosis. As blood resource is limited, scheduled surgeries are always delayed. A recent meta-analysis has shown that the infusion of allogeneic blood during radical prostatectomy, radical nephrectomy and cystectomy lead to worsened prognosis for patients [33], and this may be related to transfusion-related immunomodulation [34]. The application of IOCS-LDF is an effective alternative for massive blood transfusion. A study concerning the IVC tumor thrombus extending to right atrium has shown that the use of cardiopulmonary bypass and cell-saver technique in borderline situations like combined oncologic and cardiovascular surgery without increasing the risk of hematogenous tumor dissemination. Postoperative cytological investigation showed that the tumor cells were only found on the internal surface of the heart-lung machine arterial �lters. No distant metastasis was found in all surviving patients [35].
Aggregate Dynamics in Lumpy Economies ⇤

We develop new tools to analyze the aggregate implications of lumpiness in microeconomic adjustment. We derive a set of structural relationships between the steady state moments and the business cycle dynamics, and we show how to discipline these relationships using micro panel data. As an application, we implement our machinery in a standard framework of ﬁrm investment with ﬁxed adjustment costs. We demonstrate analytically that, in order to explain aggregate capital dynamics, that model must match two steady state moments related to capital misallocation and the time since the last investment. Using plant–level data from Chile, we compute these two moments, and discover that there does not exist a calibration of the lumpy investment model that is consistent with the data.
Understanding Emissions of Ammonia from Buildings and Fertilizer Use Printer-friendly Version Interactive Discussion Understanding Emissions of Ammonia from Buildings and Application of Fertilizers: an Example from Poland Bgd Understanding Emissions of Ammonia from Buildings and Fertilizer Use Print

This discussion paper is/has been under review for the journal Biogeosciences (BG). Please refer to the corresponding final paper in BG if available. Abstract A Europe-wide dynamic ammonia (NH 3) emissions model has been applied for one of the large agricultural countries in Europe, and its sensitivity on the distribution of emissions among different agricultural functions was analysed by comparing with observed ammonia concentrations and by implementing all scenarios in a chemical transport 5 model (CTM). The results suggest that the dynamic emission model is most sensitive to emission from animal manure, in particular how animal manure and its application on fields is connected to national regulations. In contrast, the model is most robust with respect to emission from buildings and storage. To incorporate the national regulations , we obtained activity information on agricultural operations at the sub-national 10 level for Poland, information about infrastructure on storages, and current regulations on manure practice from Polish authorities. The information was implemented in the existing emission model and was connected directly with the NWP calculations from the Weather Research and Forecasting model (WRF-ARW). The model was used to calculate four emission scenarios with high spatial (5 km × 5 km) and temporal resolution 15 (3 h) for the entire year 2010. In the four scenarios, we have compared the Europe-wide default model settings against (1) a scenario that focuses on emission from agricultural buildings, (2) the existing emission method used in WRF-Chem in Poland, and (3) a scenario that takes into account Polish infrastructure and agricultural regulations. The ammonia emission was implemented into the CTM FRAME and modelled ammonia 20 concentrations was compared with measurements. The results suggest that the default setting in the dynamic model is an improvement compared to a non-dynamical emission profile. The results also show that further improvements can be obtained on the national scale by replacing the default information on manure practice with information that is connected with local practice and national regulations. Implementing a 25 dynamical approach for simulation of ammonia emission is a viable objective for all CTM models that continue to use fixed emission profiles. Such models should handle ammonia emissions in a similar way to other climate-dependent emissions genic volatile organic compounds). Our results, compared with previous results from the DEHM and the GEOS-CHEM models, suggest that implementing dynamical approaches improves simulations in general, even in areas with limited information about the location …
Minsky models. A structured survey

Minsky’s ideas have recently gained prominence in the mainstream as well as in the heterodox literature. However, there exists no agreement upon the formal presentation of Minsky’s insights. The aim of this paper is to survey the literature and identify differences and similarities in the ways through which Minskyan ideas have been formalised. We distinguish between the models that focus on the dynamics of debt or interest, with no or a secondary role for asset prices, and the models in which asset prices play a key role in the dynamic behaviour of the economy. Within the first category of models we make a classification between (i) the Kalecki-Minsky models, (ii) the Kaldor-Minsky models, (iii) the Goodwin-Minsky models, (iv) the credit rationing Minsky models, (v) the endogenous target debt ratio Minsky models and (vi) the Minsky-Veblen models. Within the second category of models, we distinguish between (i) the equity price Minsky models and (ii) the real estate price Minsky models. Key limitations of the models and directions for future research are outlined.
Social Comparison and Risk Taking Behavior

We study theoretically and experimentally decision making under uncertainty in a social environment. We introduce an interdependent preferences model that assumes that the decision maker evaluates monetary outcomes in relation both with his individual and his social reference point. In the experiment we reproduce a workplace environment whereby subjects interact in an e ffort task, earn (possibly) diff erent wages from this task and then undertake a risky decision that may give them an extra bonus. Controlling for intrinsic risk attitudes, we find that both downward and upward social comparison strongly influence risk attitudes and that they both generate more risk loving behavior. Moreover, we fi nd that a propension to envy counterposes such eff ect, by increasing risk aversion.
Immune responses to gut bacteria associated with time to diagnosis and clinical response to T cell–directed therapy for type 1 diabetes prevention

Immune-targeted therapies have efficacy for treatment of autoinflammatory diseases. For example, treatment with the T cell–specific anti-CD3 antibody teplizumab delayed disease onset in participants at high risk for type 1 diabetes (T1D) in the TrialNet 10 (TN-10) trial. However, heterogeneity in therapeutic responses in TN-10 and other immunotherapy trials identifies gaps in understanding disease progression and treatment responses. The intestinal microbiome is a potential source of biomarkers associated with future T1D diagnosis and responses to immunotherapy. We previously reported that antibody responses to gut commensal bacteria were associated with T1D diagnosis, suggesting that certain antimicrobial immune responses may help predict disease onset. Here, we investigated anticommensal antibody (ACAb) responses against a panel of taxonomically diverse intestinal bacteria species in sera from TN-10 participants before and after teplizumab or placebo treatment. We identified IgG2 responses to three species that were associated with time to T1D diagnosis and with teplizumab treatment responses that delayed disease onset. These antibody responses link human intestinal bacteria with T1D progression, adding predictive value to known T1D risk factors. ACAb analysis provides a new approach to elucidate heterogeneity in responses to immunotherapy and identify individuals who may benefit from teplizumab, recently approved by the U.S. Food and Drug Administration for delaying T1D onset. Description Antibody reactivities to intestinal bacteria predict beneficial responses to teplizumab in a type 1 diabetes prevention trial. Editor’s summary The U.S. FDA recently approved the immune-targeted therapy teplizumab as the first disease-modifying therapy for delaying onset of type 1 diabetes (T1D) in at-risk individuals. Examining participant data from the TrialNet 10 trial that supported this decision, Xie et al. now report that IgG2 antibodies against three gut microbial commensals are associated with the teplizumab response and with time to T1D diagnosis. They also found evidence of these relationships in an independent clinical trial, suggesting that anticommensal immune responses may play a role in T1D progression and may additionally be useful to identify individuals who will benefit from treatment in this setting. —Catherine Charneski
Let us pause before sending them: an appraisal of the socio-economic condition of return migrants in Tamale Ghana.

Though migration has been found to benefit the individual household and communities of the migrant the appalling conditions in which migrants find themselves have necessitated the move by various agencies to send them back home. Many returned migrants in Ghana are largely found in the Northern part of the country which has served as the major sending regions in Ghana. The “rescued” migrants who are largely female are trained in one of three skills which are dressmaking hair dressing and textile designing (tie and dye or batik) and afterwards sent home. Not much attempt has been made to address the socio-economic condition in the home communities from which they migrated and returning. The study explored how the return migrants in the northern part of Ghana are able to cope with the unchanged condition and how they are making use of the skills acquired and also how these return migrants assess their conditions during migration and on return to their home communities. The findings of the study show that the majority of the return migrants have not found any improvement in their situations in their home communities and that their conditions in migration were better. Most of them do not make use of the skills they have acquired and remained unemployed. Because of their unimproved situations they work towards re-migrating. The study recommends that any attempt to return migrants should seek to improve the conditions in the sending communities. The skills given to the migrants should be market sensitive. Efforts should be made to improve on the living and working conditions of the migrant in the receiving community to help them achieve the purpose of migrating and then return home voluntarily.
Flow categorization model for improving forecasting

Prediction of high magnitude flows is of interest in many hydrological applications such as operation of flood control reservoirs, flood forecasting and gated spillways. Of the various types of existing streamflow prediction approaches, data driven models (such as ANN) are increasingly being preferred over the traditional conceptual models due to their simplicity, fast speed and ease of use. For models that consider only historical streamflow data, an attempt has been made to design a robust model over a wide range of streamflow magnitudes. The model inputs are the immediate past streamflow data which generally do not predict the typically high flows well, particularly for large lead times. In this study, the flow range is divided into three regions (low, medium and high flow regions) and the attributes are decided based on the underlying hydrological process of the flow region. A flow forecasting model is applied for each flow region, using only the historical streamflow data as input. The proposed approach is implemented in Tryggevaelde Catchment (Denmark) for 1- and 3-lead days, using the Support Vector Machine (SVM), which yields promising results, particularly for high flows in a 3-lead day model.