Miracle-dz/UniFAR-FTUs huggingface dataset:
Changing a Causal Hypothesis without Changing the Fit: some Rules for Generating Equivalent Path Models.

Since computer programs have been available for estimating and testing linear causal models (e.g. LISREL by Jöreskog & Sörbom) these models have been used increasingly in the behavioral sciences. This paper discusses the problem that very different causal structures may fit the same set of data equally well. Equivalence of models is defined as undecidability in principle and four rules are presented showing how equivalent models may be generated. Rules I and II refer to inversions in the causal order of variables and Rules III and IV to replacements of paths by the assumption of correlated residuals. Three examples are given to illustrate how the rules are applied.
Factors Influencing Delayed Health Care Seeking Among Pulmonary Tuberculosis Suspects in Rural Communities in Ntcheu District, Malawi

Delayed diagnosis and treatment of tuberculosis (TB) among individuals suspected of having TB may lead to continued transmission of Mycobacterium tuberculosis in communities, higher mortality rates, and increase in government health expenditure because of prolonged illness due to late diagnosis and treatment initiation. The study explored factors leading to delayed health care seeking among individuals living in Ntcheu District, Malawi. Two key informant interviews, 16 in-depth interviews, and three focus group discussions were conducted. Participants were aged 18 years and older and never had TB. Data were analyzed using content analysis and factors were identified: inadequate knowledge about cause and transmission of TB, low self-awareness of personal risk to TB, cultural and traditional beliefs about sources of TB, stigma, and strong belief in witchcraft as a cause of illness. The TB Control Program needs to invest in social mobilization and education of communities to mitigate early health care seeking.
A human phospholipid phosphatase activated by a transmembrane control module[S]

In voltage-sensitive phosphatases (VSPs), a transmembrane voltage sensor domain (VSD) controls an intracellular phosphoinositide phosphatase domain, thereby enabling immediate initiation of intracellular signals by membrane depolarization. The existence of such a mechanism in mammals has remained elusive, despite the presence of VSP-homologous proteins in mammalian cells, in particular in sperm precursor cells. Here we demonstrate activation of a human VSP (hVSP1/TPIP) by an intramolecular switch. By engineering a chimeric hVSP1 with enhanced plasma membrane targeting containing the VSD of a prototypic invertebrate VSP, we show that hVSP1 is a phosphoinositide-5-phosphatase whose predominant substrate is PI(4,5)P2. In the chimera, enzymatic activity is controlled by membrane potential via hVSP1’s endogenous phosphoinositide binding motif. These findings suggest that the endogenous VSD of hVSP1 is a control module that initiates signaling through the phosphatase domain and indicate a role for VSP-mediated phosphoinositide signaling in mammals.
Seven-year follow-up study of symptoms in asylum seekers and refugees with PTSD treated with trauma-focused groups.

OBJECTIVE To examine sustainability of symptom outcomes of a 1-year phase-based trauma-focused, multimodal, and multicomponent group therapy in a day treatment program for posttraumatic stress disorder (PTSD) over an average period of 7 years. METHOD Iranian and Afghan patients (N = 69) were assessed with self-rated symptom checklists for PTSD, anxiety, and depression symptoms before (T1), after (T2), and up to 11 years upon completion of the treatment (T3). A series of mixed model regression analyses was applied to determine the course of the measured symptoms over time. RESULTS At T2, all symptoms were reduced, but PTSD symptoms showed the strongest reduction. The trend of symptom reduction continued up to 5 years posttreatment and was similar for all the examined symptoms. After 5 years, all symptoms started to worsen, but remained under baseline levels at T3. CONCLUSIONS The applied treatment appears to improve mental health of the studied sample on both the short and longer term.
Chemotherapy with cyclophosphamide, vincristine and dacarbazine for malignant paraganglioma and pheochromocytoma: systematic review and meta‐analysis

Chemotherapy with cyclophosphamide, vincristine and dacarbazine (CVD) can be used for palliative treatment of malignant pheochromocytoma and paraganglioma. However, the precise effect of this chemotherapeutic regimen on tumour volume is unclear. The main objective of this study was to perform a systematic review and meta‐analysis assessing the effect of chemotherapy with CVD on tumour volume in patients with malignant paraganglioma/pheochromocytoma.
Classifying Short Messages using Collaborative Knowledge Bases: Reading Wikipedia to Understand Twitter

To detect concepts from tweets, we leverage the content of Wikipedia. This is a form of semantic transformation: ideas that emerge in short texts are mapped onto more extensive texts that contain additional structure. This additional structure is used to amplify the signal in the short text. This idea is rooted in our previous research [1, 2], as well as in the work of other authors pursuing similar goals [3-5]. Our method has two main stages. First, we recognize candidate concepts—partsof-tweets—that may be valid entities in the tweet. These concepts are then classified into four categories: Locations, People, Organizations, and Miscellaneous. Candidate concepts are identified by mapping tweets to Wikipedia pages, and the networks of these concepts in Wikipedia are used for filtering and classification. We believe this technique can be applied more generally to the understanding of many forms of short messages, not just tweets, utilizing many forms of collaborative knowledge bases, not just Wikipedia.
Infectious particles, stress, and induced prion amyloids

Transmissible encephalopathies (TSEs) are believed by many to arise by spontaneous conversion of host prion protein (PrP) into an infectious amyloid (PrP-res, PrPSc) without nucleic acid. Many TSE agents reside in the environment, with infection controlled by public health measures. These include the disappearance of kuru with the cessation of ritual cannibalism, the dramatic reduction of epidemic bovine encephalopathy (BSE) by removal of contaminated feed, and the lack of endemic scrapie in geographically isolated Australian sheep with susceptible PrP genotypes. While prion protein modeling has engendered an intense focus on common types of protein misfolding and amyloid formation in diverse organisms and diseases, the biological characteristics of infectious TSE agents, and their recognition by the host as foreign entities, raises several fundamental new directions for fruitful investigation such as: (1) unrecognized microbial agents in the environmental metagenome that may cause latent neurodegenerative disease, (2) the evolutionary social and protective functions of different amyloid proteins in diverse organisms from bacteria to mammals, and (3) amyloid formation as a beneficial innate immune response to stress (infectious and non-infectious). This innate process however, once initiated, can become unstoppable in accelerated neuronal aging.
The Impact of Ownership *

This paper analyses the relation between SME ownership and international involvement. With a wide sample of Spanish firms, from 1991 to 1999, we test the following hypotheses. Family SMEs results in lower involvement in international markets, due to difficult access to necessary strategic resources. SMEs with another company as a large-block shareholder will be more involved internationally, as they do have access more strategic resources. Likewise, when another company invests in a family SME, international involvement increases.
The C star outer disk population of M 31 seen with the SLOAN filters

We employ the CFHT Megacam camera to survey ∼one deg 2 of the southern outer disc of M 31, a region which includes the area where Battinelli et al. (2003, AJ, 125, 1298) have identified nearly one thousand C stars. In the outer M 31 region not previously surveyed, we identify 361 new C star candidates, having similar photometric properties to the known ones, and confirm the slight decrease in the luminosity or C stars with galactocentric distances. We show that the Sloan g', r', i' filters are a viable approach, comparable to (CN - TiO), to identify C stars. We find that the (g' - r') colours of cool C stars can be so red that prohibitively long g' exposures are needed to acquire faint extragalactic C stars. This makes the Sloan filters a less promising approach to extend a C star survey to several Mpc. Our uniform large field survey detects the edge of M31 disk at ∼35 kpc. The intermediate-age population, represented by C stars, extends further to ∼40 kpc.
MEF2C-dysregulated pediatric T-cell acute lymphoblastic leukemia is associated with CDKN1B deletions and a poor response to glucocorticoid therapy

Abstract T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological disease in which multiple genetic abnormalities cooperate in the malignant transformation of T-lymphoid progenitors. Although in pediatric T-ALL, CDKN1B deletions occur in about 12% of the cases and represent one of the most frequent copy number alterations, neither their association with other genetic alterations nor the clinical characteristics of these patients have been determined yet. In this study, we show that loss of CDKN1B increased the prevalence of cell cycle regulator defects in immature T-ALL, usually only ascribed to CDKN2A/B deletions, and that CDKN1B deletions frequently coincide with expression of MEF2C, considered as one of the driving oncogenes in immature early T-cell precursor (ETP) ALL. However, MEF2C-dysregulation was only partially associated with the immunophenotypic characteristics used to define ETP-ALL. Furthermore, MEF2C expression levels were significantly associated with or may even be predictive of the response to glucocorticoid treatment.
Causal Inference on Multidimensional Data Using Free Probability Theory

In this paper, we deal with the problem of inferring causal relations for multidimensional data. Based on the postulate that the distribution of the cause and the conditional distribution of the effect given cause are generated independently, we show that the covariance matrix of the mean embedding of the cause in reproducing kernel Hilbert space (RKHS) is free independent with the covariance matrix of the conditional embedding of the effect given cause. This, called freeness condition, induces a cause–effect asymmetry that a designed measurement is 0 in the causal direction but smaller than 0 in the anticausal direction, and it uncovers the causal direction. One important novel aspect of this paper is that we interpret the independence as a freeness condition between covariance matrices of RKHS distribution embeddings, and it has a wide applicability. We show that our freeness condition-based inference method succeeds in scenarios like additive noise cases, where other methods fail, by theoretical analysis and experimental results.
Anti-inflammatory action of Tamarind seeds reduces hyperglycemic excursion by repressing pancreatic β-cell damage and normalizing SREBP-1c concentration

Context: Tamarindus indica L. (Leguminosae) is widely used as a traditional medicine for the management of diabetes mellitus (DM) in India, in addition to its anti-inflammatory activity. The present study has been designed to understand the correlation involved between antidiabetic and anti-inflammatory action of aqueous seed extract of T. indica (TSE) in diabetic rats. Objective: In view of the fact that fatty acid synthesis and insulin release from islets of pancreas are regulated by sterol regulatory element-binding proteins (SREBP-1c) and cytosolic calcium, respectively, the objectives of present study were to determine the influence of TSE on SREBP-1c mRNA and to investigate the intracellular islets calcium [Ca2+]I involvement and β-cell mass preservation in insulin secretagogue action of TSE. Materials and methods: The effect of 4 weeks oral treatment (120 and 240 mg/kg) of high-performance liquid chromatography (HPLC) standardized TSE was studied in streptozotocin (STZ)-induced diabetic male Wistar rats. Reverse transcription-PCR (RT-PCR) and a spectrofluorometer were used for mRNA concentration and islets [Ca2+]I determination, respectively. The TUNEL assay was followed to study the pancreatic apoptosis. Results: TSE (120 and 240 mg/kg) showed positive correlation with [Ca2+]I and insulin release. The anti-inflammatory action of TSE was significant on nitric oxide (NO) and tumor necrosis factor-α (TNF-α) in addition to a favorable effect on β-cell neogenesis and improved mRNA concentration of SREBP-1c. Discussion and conclusion: The results suggest that anti-inflammatory action of Tamarind seeds on β-cell cells of islets and cytokines contribute toward its antidiabetic activity by way of complex mechanisms of [Ca2+]I handling and through SREBP-1c gene in liver.
Efficiency in Ambiguity: Two Models of Probabilistic Semantics for Natural Language

This paper explores theoretical issues in constructing an adequate probabilistic semantics for natural language. Two approaches are contrasted. The first extends Montague Semantics with a probability distribution over models. It has nice theoretical properties, but does not account for the ubiquitous nature of ambiguity; moreover inference is NP hard. An alternative approach is described in which a sequence of pairs of sentences and truth values is generated randomly. By sacrificing some of the nice theoretical properties of the first approach it is possible to model ambiguity naturally; moreover inference now has polynomial time complexity. Both approaches provide a compositional semantics and account for the gradience of semantic judgements of belief and inference.
The Human Transporter Associated with Antigen Processing

Background: The transporter associated with antigen processing (TAP) is an ABC transporter whose experimental structure is not known. Results: We have modeled TAP based on the crystal structures of three related ABC transporters. Conclusion: We identified a possible peptide binding conformation in the transport cycle of TAP. Significance: These models help interpret experimental data and give information about the transport cycle of ABC transporters in general. The human transporter associated with antigen processing (TAP) is a member of the ATP binding cassette (ABC) transporter superfamily. TAP plays an essential role in the antigen presentation pathway by translocating cytosolic peptides derived from proteasomal degradation into the endoplasmic reticulum lumen. Here, the peptides are loaded into major histocompatibility class I molecules to be in turn exposed at the cell surface for recognition by T-cells. TAP is a heterodimer formed by the association of two half-transporters, TAP1 and TAP2, with a typical ABC transporter core that consists of two nucleotide binding domains and two transmembrane domains. Despite the availability of biological data, a full understanding of the mechanism of action of TAP is limited by the absence of experimental structures of the full-length transporter. Here, we present homology models of TAP built on the crystal structures of P-glycoprotein, ABCB10, and Sav1866. The models represent the transporter in inward- and outward-facing conformations that could represent initial and final states of the transport cycle, respectively. We described conserved regions in the endoplasmic reticulum-facing loops with a role in the opening and closing of the cavity. We also identified conserved π-stacking interactions in the cytosolic part of the transmembrane domains that could explain the experimental data available for TAP1-Phe-265. Electrostatic potential calculations gave structural insights into the role of residues involved in peptide binding, such as TAP1-Val-288, TAP2-Cys-213, TAP2-Met-218. Moreover, these calculations identified additional residues potentially involved in peptide binding, in turn verified with replica exchange simulations performed on a peptide bound to the inward-facing models.
Metabolomic analysis of lung epithelial secretions in rats: An investigation of bronchoalveolar lavage fluid by GC-MS and FT-IR

ABSTRACT Objective: Rat bronchoalveolar lavage fluid (BALF) metabolome can be used to obtain valuable, precise, and accurate information about underlying lung conditions in an experiment. The present study focuses on the evaluation of the lung epithelium metabolome in a rat model using techniques including bronchoalveolar lavage, gas chromatography-mass spectroscopy (GC-MS), and Fourier transform infrared spectroscopy (FT-IR). Materials and methods: Untargeted metabolites in BALF were extracted in ethyl acetate and derivatized by standard methods for the analysis by GC-MS. FT-IR spectra of ethyl acetate extract of BALF were obtained and read for the characteristic fingerprint of rats under investigation. Analyses were done in individual animals to obtain consistent data. BALF cells were counted by flow cytometry to monitor any inflammatory condition in rats. Results: FT-IR analysis finds two peaks which are characteristically different from the extract medium, which is ethyl acetate. FT-IR peaks correspond to that of amino acids and carbohydrates, including β-D-glucose, α-D-glucose, and β-D-galactose. GC-MS evaluation of the BALF finds several products of the metabolism or its participants. Main compounds in the BALF detected by GC-MS include succinate, fumarate, glycine, alanine, 2-methyl-3-oxovaleric acid, dodecanoic acid, tetradecanoic acid, hexadecanoic acid, octanoic acid, trans-9-octadecanoic acid, octadecanoic acid, and Prostaglandin F1α. Conclusion: Several research reports reveal metabolomic parameters in murine model lung tissue or BALF, but they rarely reported a complete metabolomics model profile, particularly in rats. The present data of GC-MS and FT-IR suggest that the set up can be exploited to study metabolomic alterations in several lung conditions including acute lung toxicity, inflammation, asthma, bronchitis, fibrosis, and emphysema.
On the identification of nonlinear behavior of highly filled elastomers

Solid propellants are highly filled elastomers used as propulsion medium. Because of the high volume filler fraction of 80% − 90%, several sizes of fillers are used and as a consequence of the complex microstructure the material presents important nonlinearities in the macroscopic behavior. An abrupt increase in the viscoelastic storage and loss modulus has been experimentally observed in [2]. The objective of this paper is to explore numerically a highly filled elastic composite under the assumptions of "rigid" fillers, an elastic matrix and large strains. The present numerical analysis is based on several artificially created microstructures. The results show the influence of the material behavior of the matrix on the global stiffness. The computed mechanical response is in agreement with experiment observations. The mechanical response of the composite under a uniaxial loading presents a linear and a nonlinear part. Both are analyzed to understand the microstructural effects that lead to the macroscopic behavior. The apparent modulus of the linear part increases with respect to the volume fraction of fillers and the stiffening effect occurring in the nonlinear part is not dependent of the matrix behavior.
Functional Implications of Novel Human Acid Sphingomyelinase Splice Variants

Background Acid sphingomyelinase (ASM) hydrolyses sphingomyelin and generates the lipid messenger ceramide, which mediates a variety of stress-related cellular processes. The pathological effects of dysregulated ASM activity are evident in several human diseases and indicate an important functional role for ASM regulation. We investigated alternative splicing as a possible mechanism for regulating cellular ASM activity. Methodology/Principal Findings We identified three novel ASM splice variants in human cells, termed ASM-5, -6 and -7, which lack portions of the catalytic- and/or carboxy-terminal domains in comparison to full-length ASM-1. Differential expression patterns in primary blood cells indicated that ASM splicing might be subject to regulatory processes. The newly identified ASM splice variants were catalytically inactive in biochemical in vitro assays, but they decreased the relative cellular ceramide content in overexpression studies and exerted a dominant-negative effect on ASM activity in physiological cell models. Conclusions/Significance These findings indicate that alternative splicing of ASM is of functional significance for the cellular stress response, possibly representing a mechanism for maintaining constant levels of cellular ASM enzyme activity.
The effects of loperamide, or loperamide plus simethicone, on the distribution of gut water as assessed by MRI in a mannitol model of secretory diarrhoea

Loperamide (LOP) is an anti‐diarrhoeal agent which is thought to act largely by slowing transit with an uncertain effect on the fluid content of the small and large bowel in humans. Adding simethicone (SIM) to LOP improves its efficacy, but the mechanism of interaction is unclear. Novel MRI techniques to assess small bowel water content (SBWC) have shown that mannitol solutions markedly increase SBWC and can be used as a model of diarrhoea.
Self-renewal and Differentiation of Muscle Satellite Cells Are Regulated by the Fas-associated Death Domain*

Background: The balance between self-renewal and differentiation in muscle stem cells is critical for tissue homeostasis. Results: Fas-associated death domain (FADD) phosphorylation mutation regulates muscle satellite cell cycle progression, inhibits muscle stem cell differentiation, and promotes muscle stem cell self-renewal. Conclusion: FADD regulates muscle stem cell fate decisions. Significance: The characterization of proteins involved in fate decisions in muscle stem cells is crucial for muscle stem cell biology. Making the decision between self-renewal and differentiation of adult stem cells is critical for tissue repair and homeostasis. Here we show that the apoptotic adaptor Fas-associated death domain (FADD) regulates the fate decisions of muscle satellite cells (SCs). FADD phosphorylation was specifically induced in cycling SCs, which was high in metaphase and declined in later anaphase. Furthermore, phosphorylated FADD at Ser-191 accumulated in the uncommitted cycling SCs and was asymmetrically localized in the self-renewing daughter SCs. SCs containing a phosphoryl-mimicking mutation at Ser-191 of FADD (FADD-D) expressed higher levels of stem-like markers and reduced commitment-associated markers. Moreover, a phosphoryl-mimicking mutation at Ser-191 of FADD suppressed SC activation and differentiation, which promoted the cycling SCs into a reversible quiescent state. Therefore, these data indicate that FADD regulates the fate determination of cycling SCs.
A component based software reliability model

This paper presents a component based software reliability model. The proposed model provides software system reliability estimates from the reliability of software components and the usage ratio of each component. Issues relating to the techniques for estimating the model parameters are discussed and the assumptions of the model are investigated. A component impact analysis method which could help in focusing testing efforts is also presented.