Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel insights into renal fibrosis

Purpose of reviewRenal fibrosis characterizes a common endpoint of diverse renal diseases which leads to functional impairment ultimately resulting in terminal renal failure. Recent findingsRecent advances in this field led to the discovery of several novel mediators as well as novel aspects of known mediators. Studies on the origin and role of specific renal cell types involved in renal fibrosis identified bone marrow derived mesangial progenitors and offered substantial evidence for the concept of epithelial to mesenchymal transition. Much progress has also been made in better understanding of the interactions between different mediators and between mediators and renal target cells. Compounds designed on the basis of this current knowledge have proven to be potent inhibitors of the development of renal fibrosis or might even induce resolution of renal fibrosis. SummaryThe number and diversity of recent studies in this field offer hope for new treatment regimes in our clinical efforts towards prevention and regression of progressive fibrosing renal diseases.
IL‐33 induces IL‐13 production by mouse mast cells independently of IgE‐FcεRI signals

The IL‐1‐related molecules, IL‐1 and IL‐18, can promote Th2 cytokine production by IgE/antigen‐FcεRI‐stimulated mouse mast cells. Another IL‐1‐related molecule, IL‐33, was identified recently as a ligand for T1/ST2. Although mouse mast cells constitutively express ST2, the effects of IL‐33 on mast cell function are poorly understood. We found that IL‐33, but not IL‐1β or IL‐18, induced IL‐13 and IL‐6 production by mouse bone marrow‐derived, cultured mast cells (BMCMCs) independently of IgE. In BMCMCs incubated with the potently cytokinergic SPE‐7 IgE without specific antigen, IL‐33, IL‐1β, and IL‐18 each promoted IL‐13 and IL‐6 production, but the effects of IL‐33 were more potent than those of IL‐1β or IL‐18. IL‐33 promoted cytokine production via a MyD88‐dependent but Toll/IL‐1R domain‐containing adaptor‐inducing IFN‐β‐independent pathway. By contrast, IL‐33 neither induced nor enhanced mast cell degranulation. At 200 ng/ml, IL‐33 prolonged mast cell survival in the absence of IgE and impaired survival in the presence of SPE‐7 IgE, whereas at 100 ng/ml, IL‐33 had no effect on mast cell survival in the absence of IgE and reduced mast cell survival in the presence of IgE. These observations suggest potential roles for IL‐33 in mast cell‐ and Th2 cytokine‐associated immune responses and disorders.
Testing the semantic control hypothesis for stroke aphasics with semantic deficits

Testing the semantic control hypothesis for stroke aphasics with semantic deficits by Azli Hassan Some studies of stroke patients with semantic deficits have found no effect of word frequency on semantic tasks, as well as inconsistent performance across items and tasks. A deficit in semantic control has been suggested as the source of the deficit i.e., an inability to focus on semantic features appropriate to the task. In the present study, two stroke patients performed significantly better in single-distractor versions (low semantic control) than multiple-distractor versions of semantic tasks (high semantic control) of comprehension tasks, which appears consistent with the semantic control hypothesis. On the other hand, two aphasic patients showed substantially better performance for auditory than visual presentation of words in comprehension tasks – a finding that is not expected on the basis of semantic control. Experiment 1 evaluated whether performance on a multiple-distractor comprehension task could be predicted solely on the basis of performance on a single-distractor version using Luce’s choice axiom. Single distractor performance significantly predicted performance and no convincing evidence was obtained for a role for semantic control. Experiment 2, which examined the modality effect, showed that for one of the patients, worse performance with auditory presentation was most likely due to rapid decay of phonological representations. For the other, worse performance was most likely due to a disruption to phonological representations of words ! or to their connection to semantic representations. In all, the results suggest that word comprehension deficits in aphasia can result from a variety of sources and not all are due to semantic control deficits.
Cooperative binding of the E2 protein of bovine papillomavirus to adjacent E2-responsive sequences

The DNA-binding properties of purified full-length E2 protein from bovine papillomavirus type 1 have been investigated by utilizing a quantitative gel shift analysis. By using a recombinant baculovirus which express the E2 open reading frame from the polyhedrin promoter, the full-length E2 protein was synthesized in insect cells and purified to homogeneity by using an E2 binding site (ACCGN4CGGT)-specific oligonucleotide column. The Kd of E2 binding to a 41-bp oligonucleotide containing a single binding site was found to be 2 x 10(-11) M. When two binding sites were included on an oligonucleotide, cooperative binding to these sites by the E2 protein was observed. A cooperativity parameter of 8.5 was determined for E2 binding to two sites. An 86-amino-acid peptide encompassing the C terminus of the protein retains the ability to bind E2 binding sites with a Kd of 4 x 10(-10) M but exhibits slight cooperativity of binding to two adjacent sites. A major determinant for cooperative binding of the full-length E2 protein is thus encoded by the N-terminal amino acids outside the minimal DNA binding domain.
(4RS)-Methyl 4-cyano-4-cyclohexyl-4-phenylbutanoate

In the crystal structure of the title compound, C18H23NO2, there are only van der Waals interactions present. The cyclohexyl ring has a chair conformation. The longer axes of the displacement parameters of the non-H atoms forming the ethylmethylcarboxylate skeleton are perpendicular to the plane through the non-H atoms of this skeleton.
Joint 3D laser and visual fiducial marker based SLAM for a micro aerial vehicle

Laser scanners have been proven to provide reliable and highly precise environment perception for micro aerial vehicles (MAV). This oftentimes makes them the first choice for tasks like obstacle avoidance, close inspection of structures, self-localization, and mapping. However, artificial environments may pose problems if the scene is self-similar or symmetric and, hence, localization becomes ambiguous if only relying on distance measurements (e.g., when flying along a parallel aisle). In this paper, we propose to tackle these instances by introducing visual fiducial markers into the scene, detecting them with copter-mounted cameras and fusing these detections with laser-based self-localization in a graph optimization. Our approach abstracts the underlying multiple stages of laser-based SLAM to a slim interface that is only connected to the map building process and augments the self-localization in uncertain situations. We demonstrate the applicability of our approach during experiments in an indoor scenario with sparsely distributed fiducial markers. The test encompasses accurate map building with both the laser scanner and video cameras and subsequent relocalization relying on the detection of fiducial markers only.
Situated Wireless Networks Optimisation Through Model-Based Relocation of Nodes

The design and deployment of networked embedded systems is challenging. In particular, the environment in which the system operates has a severe impact on the final performance. Existing tools trade generality for specificity with arbitrary setups, e.g., in simulation, or specific configurations, e.g., in public testbeds. As a result, the peculiar effect of the target deployment scenario on the system performance can only be experienced by hand. Optimising and adapting the system to the operational environment becomes then a trial and error, impractical challenge. We introduce MOTION, a hybrid modelling technique able to characterise indoor wireless communication in the target environment from measurements and descriptions, e.g., maps, of the deployment area. By exploiting all available knowledge, our model is able to increase the achieved accuracy by up to 35% in our primary evaluation scenario with respect to conventional approaches. The computed models can then support traditional design and analysis tools in investigating the impact of arbitrary displacements of devices in the target environment. E.g., by controlling the relocation of a single node based on the information provided by the model, we were able to reduce the latency of a typical application by up to 21.4%. Ultimately, our work allows situated network optimisation of wireless systems where devices can be freely moved in the environment and the corresponding impact on the network performance can be estimated beforehand.
Syntactic Computation in the Human Brain: The Degree of Merger as a Key Factor

Our goal of this study is to characterize the functions of language areas in most precise terms. Previous neuroimaging studies have reported that more complex sentences elicit larger activations in the left inferior frontal gyrus (L. F3op/F3t), although the most critical factor still remains to be identified. We hypothesize that pseudowords with grammatical particles and morphosyntactic information alone impose a construction of syntactic structures, just like normal sentences, and that “the Degree of Merger” (DoM) in recursively merged sentences parametrically modulates neural activations. Using jabberwocky sentences with distinct constructions, we fitted various parametric models of syntactic, other linguistic, and nonlinguistic factors to activations measured with functional magnetic resonance imaging. We demonstrated that the models of DoM and “DoM+number of Search (searching syntactic features)” were the best to explain activations in the L. F3op/F3t and supramarginal gyrus (L. SMG), respectively. We further introduced letter strings, which had neither lexical associations nor grammatical particles, but retained both matching orders and symbol orders of sentences. By directly contrasting jabberwocky sentences with letter strings, localized activations in L. F3op/F3t and L. SMG were indeed independent of matching orders and symbol orders. Moreover, by using dynamic causal modeling, we found that the model with a inhibitory modulatory effect for the bottom-up connectivity from L. SMG to L. F3op/F3t was the best one. For this best model, the top-down connection from L. F3op/F3t to L. SMG was significantly positive. By using diffusion-tensor imaging, we confirmed that the left dorsal pathway of the superior longitudinal and arcuate fasciculi consistently connected these regions. Lastly, we established that nonlinguistic order-related and error-related factors significantly activated the right (R.) lateral premotor cortex and R. F3op/F3t, respectively. These results indicate that the identified network of L. F3op/F3t and L. SMG subserves the calculation of DoM in recursively merged sentences.
A Prevalence of Imprinted Genes within the Total Transcriptomes of Human Tissues and Cells

Genomic imprinting is an epigenetic phenomenon that causes a differential expression of paternally and maternally inherited alleles of a subset of genes (the so-called imprinted genes). Imprinted genes are distributed throughout the genome and it is predicted that about 1% of the human genes may be imprinted. It is recognized that the allelic expression of imprinted genes varies between tissues and developmental stages. The current study represents the first attempt to estimate a prevalence of imprinted genes within the total human transcriptome. In silico analysis of the normalized expression profiles of a comprehensive panel of 173 established and candidate human imprinted genes was performed, in 492 publicly available SAGE libraries. The latter represent human cell and tissue samples in a variety of physiological and pathological conditions. Variations in the prevalence of imprinted genes within the total transcriptomes (ranging from 0.08% to 4.36%) and expression profiles of the individual imprinted genes are assessed. This paper thus provides a useful reference on the size of the imprinted transcriptome and expression of the individual imprinted genes.
Immunization of HLA-A*0201 and/or HLA-DPβ1*04 Patients with Metastatic Melanoma Using Epitopes from the NY-ESO-1 Antigen

HLA class I-restricted peptides are often used in peptide vaccine regimens. There is strong evidence that many of these peptides can generate specific CD8+ T-cell responses in vivo; however, only occasional objective clinical responses have been reported. To test whether provision of "help" would enhance antitumor immunity, the authors initiated a clinical trial in which patients with metastatic melanoma were immunized against the NY-ESO-1 tumor antigen, using an HLA-A2-restricted peptide (ESO-1:165V), an HLA-DP4-restricted peptide (NY-ESO-1:161-180), or both peptides given concomitantly. The first cohorts received only ESO-1:165V, using three vaccination schedules. Immunologically, most patients developed immune responses to the HLA-A2-restricted native ESO-1 epitope after vaccination. Peptide vaccine given daily for 4 days appeared to induce immunologic responses more rapidly than if given once a week or once every 3 weeks. In contrast, vaccination using the NY-ESO-1:161-180 peptide induced immune responses in only a few patients. Clinically, one patient who received NY-ESO-1:161-180 peptide alone had a partial response lasing 12 months. Concomitant vaccination with the HLA class II-restricted peptide did not alter the immune response to the HLA class I-restricted peptide form NY-ESO-1. However, vaccination with the HLA-A2-restricted epitope generated primarily T cells that did not recognize tumor after in vitro sensitization. This result raises questions about the use of synthetic peptides derived from NY-ESO-1 as a sole form of immunization.
Domain motion and interdomain hot spots in a multidomain enzyme

The aim of this article is to analyze conformational changes by comparing 10 different structures of Pseudomonas aeruginosa phosphomannomutase/phosphoglucomutase (PMM/PGM), a four‐domain enzyme in which both substrate binding and catalysis require substantial movement of the C‐terminal domain. We focus on changes in interdomain and active site crevices using a method called computational solvent mapping rather than superimposing the structures. The method places molecular probes (i.e., small organic molecules containing various functional groups) around the protein to find hot spots. One of the most important hot spots is in the active site, consistent with the ability of the enzyme to bind both glucose and mannose phosphosugar substrates. The protein has eight additional hot spots at domain‐domain interfaces and hinge regions. The locations and nature of six of these hot spots vary between the open, half‐open, and closed conformers of the enzyme, in good agreement with the ligand‐induced conformational changes. In the closed structures the number of probe clusters at the hinge region significantly depends on the position of the phosphorylated oxygen in the substrate (e.g., glucose 1‐phosphate versus glucose 6‐phosphate), but the protein remains almost unchanged in terms of the overall RMSD, indicating that computational solvent mapping is a more sensitive approach to detect changes in binding sites and interdomain crevices. Focusing on multidomain proteins we show that the subresolution conformational differences revealed by the mapping are in fact significant, and present a general statistical method of analysis to determine the significance of rigid body domain movements in X‐ray structures.
From paradigm lost or paradigm regained?; the case for an actor-oriented sociology of development.

This article is divided into two parts. The first maps out the paradigmatic character of structural versus actor-oriented approaches to the study of development and social change, and argues for the injection of a more thoroughgoing, and better theorized, actor perspective into empirical research. The second traces my own struggle with theory and practice during the course of my Latin American work in Peru and Mexico. The conclusion takes up the issue of paradigm change and the so-called theoretical 'crisis' in the contemporary sociology of devel opment.1
Essays in Behavioral Economics and Risk Management

Author(s): HOLMAN, JEFFREY TREVOR | Advisor(s): Anderson, Robert M | Abstract: In the first chapter, I develop a model of prospective memory, defined as thecapacity to recall actions to be carried out in the future. An agent faces sometask with stochastic cost ct , benefit b, and T periods until some exogenouslyimposed deadline. The agent can only execute the task at time t if the task isrecalled in that period. The memory process exhibits the rehearsal propertythat the probability of recall is lower if the task was forgotten in the recentpast. The agent sets a threshold cost each period based on her expectationsof whether she will recall and carry out the task in future periods. If the taskis recalled at time t, and the draw from the cost distribution is below thisthreshold, the task is executed. We then introduce memory overconfidenceinto the model, which we define as either overestimating the base likelihoodof recall in future periods or underestimating the effect of temporary forgettingon subsequent recall. Memory overconfidence leads not only to inefficientlylow rates of task completion, but also to the prediction that the probabilityof task completion may vary inversely with the length of time allocated tocompleting the task. We discuss the interaction of these effects with present-biased preferences, and provide examples of economic scenarios where thisdynamic may be exploited by firms to the detriment of consumers.In the second chapter, I introduce a new copula which simultaneously allowsfully-general correlation structures in the bulk of a multivariate distributionand an arbitrarily high degree of dependence in the left tails. This isideally suited for modeling financial assets which may display moderate correlation in normal times, but which experience simultaneous left tail events,such as during a financial crisis. The new copula is shown to be fully flexiblein the sense that the user can specify a desired structure for a sequence ofincreasingly dire events in the left tail, while still retaining the same correlationstructure in the bulk. Finally, I illustrate the use of this copula with anapplication to hedge fund returns.
Using Commonsense Knowledge to Disambiguate Prepositional Phrase Modifiers

This paper describes a method using commonsense knowledge for discarding spurious syntactic ambiguities introduced by post-verbal prepositional phrase attachment during parsing. A completely naive parser will generate three parses for sentences of the form NP-V-Det-N-PP. The prepositions alone are insufficiently precise in meaning to guide selection among competing parses. The method is imbedded in the Kind Types System (KT) which employs commonsense knowledge of concepts, including prototype and inherent features (generic information) and ontological classifications. The generic information is drawn from published psycholinguistic studies on how average people typically view the world. This method is employed in preference strategies which appeal to the meaning of the preposition combined with information about the verbs and nouns associated with it drawn from the text and from the generic and ontological databases. These determine which syntactic structures generated by a semantically naive parser are commonsensically plausible. The method was successful in 93% of cases tested.
Temporal Transcriptomic Microarray Analysis of “Dehalococcoides ethenogenes” Strain 195 during the Transition into Stationary Phase

ABSTRACT “Dehalococcoides” bacteria can reductively dehalogenate a wide range of halogenated organic pollutants. In this study, DNA microarrays were used to monitor dynamic changes in the transcriptome as “Dehalococcoides ethenogenes” strain 195 transitioned from exponential growth into stationary phase. In total, 415 nonredundant genes were identified as differentially expressed. As expected, genes involved with translation and energy metabolism were down-regulated while genes involved with general stress response, transcription, and signal transduction were up-regulated. Unexpected, however, was the 8- to 10-fold up-regulation of four putative reductive dehalogenases (RDases) (DET0173, DET0180, DET1535, and DET1545). Another unexpected finding was the up-regulation of a large number of genes located within integrated elements, including a putative prophage and a multicopy transposon. Finally, genes encoding the dominant hydrogenase-RDase respiratory chain of this strain (Hup and TceA) were expressed at stable levels throughout the experiment, providing molecular evidence that strain 195 can uncouple dechlorination from net growth.
Independent regulation of gene expression level and noise by histone modifications

The inherent stochasticity generates substantial gene expression variation among isogenic cells under identical conditions, which is frequently referred to as gene expression noise or cell-to-cell expression variability. Similar to (average) expression level, expression noise is also subject to natural selection. Yet it has been observed that noise is negatively correlated with expression level, which manifests as a potential constraint for simultaneous optimization of both. Here, we studied expression noise in human embryonic cells with computational analysis on single-cell RNA-seq data and in yeast with flow cytometry experiments. We showed that this coupling is overcome, to a certain degree, by a histone modification strategy in multiple embryonic developmental stages in human, as well as in yeast. Importantly, this epigenetic strategy could fit into a burst-like gene expression model: promoter-localized histone modifications (such as H3K4 methylation) are associated with both burst size and burst frequency, which together influence expression level, while gene-body-localized ones (such as H3K79 methylation) are more associated with burst frequency, which influences both expression level and noise. We further knocked out the only “writer” of H3K79 methylation in yeast, and observed that expression noise is indeed increased. Consistently, dosage sensitive genes, such as genes in the Wnt signaling pathway, tend to be marked with gene-body-localized histone modifications, while stress responding genes, such as genes regulating autophagy, tend to be marked with promoter-localized ones. Our findings elucidate that the “division of labor” among histone modifications facilitates the independent regulation of expression level and noise, extend the “histone code” hypothesis to include expression noise, and shed light on the optimization of transcriptome in evolution.