Miracle-dz/UniFAR-FTUs huggingface dataset:
Childhood maltreatment, altered limbic neurobiology, and substance use relapse severity via trauma-specific reductions in limbic gray matter volume.

IMPORTANCE Substance use disorders (SUDs) are among the most common sequelae of childhood maltreatment, yet the independent contributions of SUDs and childhood maltreatment to neurobiological changes and the effect of the latter on relapse risk (a critical variable in addiction treatment) are relatively unknown. OBJECTIVES To identify structural neural characteristics independently associated with childhood maltreatment (CM; a common type of childhood adversity), comparing a sample with SUD with a demographically comparable control sample, and to examine the relationship between CM-related structural brain changes and subsequent relapse. DESIGN, SETTING, AND PARTICIPANTS Structural magnetic resonance imaging study comparing 79 treatment-engaged participants with SUD in acute remission in inpatient treatment at a community mental health center vs 98 healthy control participants at an outpatient research center at an academic medical center. Both groups included individuals with a range of CM experiences. Participants with SUD were followed up prospectively for 90 days to assess relapse and relapse severity. INTERVENTION Standard 12-step, recovery-based, inpatient addiction treatment for all participants with SUD. MAIN OUTCOMES AND MEASURES Gray matter volume (GMV), subsequent substance use relapse, days to relapse, and severity of relapse. RESULTS Controlling for SUD and psychiatric comorbidity, CM (dichotomously classified) was uniquely associated with lower GMV across all participants in the left hippocampus (cornu ammonis 1-3, dentate gyrus), parahippocampus (presubiculum, parasubiculum, prosubiculum, subiculum, and entorhinal cortex), and anterior fusiform gyrus (corrected P < .05; uncorrected P = .001). Among the sample with SUD, CM prospectively predicted a shorter relapse to use of any drug (P = .048), while CM-related GMV reductions predicted severity of substance use relapse (P = .04). CONCLUSIONS AND RELEVANCE Findings indicate that CM was related to decreased GMV in limbic regions, which in turn predicted increased risk of relapse in SUD. These results suggest that CM may significantly affect the course of SUD treatment outcomes and that SUD treatment planning may benefit from identifying and addressing CM.
Dual Function of Histone H3 Lysine 36 Methyltransferase ASH1 in Regulation of Hox Gene Expression

Hox genes play important roles in haematopoietic development in mammals. ASH1 is a member of the trithorax group (trxG) that is required for proper expression of Hox genes and is preferentially expressed in haematopoietic stem cells. We have recently reported that ASH1 methylates histone H3 at lysine 36 (K36) but its biological function has remained elusive. Here we show that ASH1 regulates Hox gene expression positively and negatively in a leukemic cell line K562 and is required for myelomonocytic differentiation of murine haematopoietic stem cells. ASH1 binds to endogenous Hox loci in K562 cells and its knockdown causes reduced expression of Hox genes. In addition, ASH1 and MLL1 induce more than 100-fold activation of Hox promoters in HeLa cells if expressed simultaneously but not individually. Notably, ASH1 harbouring a point mutation that kills methyltransferase activity is more efficient than wild type ASH1 in Hox gene activation, indicating that K36 methylation is not a prerequisite for Hox gene expression. Moreover, tethering wild type or catalytically inactive methyltransferase domain of ASH1 to a heterologous promoter causes downregulation or upregulation, respectively, of transcription, supporting a hypothesis that K36 methylation imparts repression. Knockdown of ASH1 in K562 cells in vitro causes increased expression of ε-globin gene and reduced expression of myelomonocytic markers GPIIb and GPIIIa, whereas knockdown of ASH1 in murine haematopoietic stem cells in vivo results in decreased number of macrophages and granulocytes, a phenotype similar to that induced by loss of mll1 function. Taken together, our data suggest that ASH1 and MLL1 synergize in activation of Hox genes and thereby regulate development of myelomonocytic lineages from haematopoietic stem cells.
Elevation of serum CXCL16 level correlates well with atherosclerotic ischemic stroke

Introduction Currently there are no reliable biological markers for ischemic stroke. The novel chemokine CXCL16 is known to be involved in the development of atherosclerosis. Nevertheless, the real role of CXCL16 in atherosclerotic disorders remains uncertain. The goal of our study was to investigate the associations between serum-soluble CXCL16 level and atherosclerotic ischemic stroke, including large artery atherosclerosis (LAA) and small artery occlusion (SAO) subtypes, and to explore whether elevation in CXCL16 levels is correlated with the severity of large arterial stenosis. Material and methods The study recruited 227 subjects, including 74 controls and 153 consecutive patients with acute ischemic stroke from atherosclerosis of the carotid artery. The etiology of the acute ischemic strokes was classified into LAA (n = 86) subtype and SAO (n = 67) subtype according to the TOAST criteria, and the severity of carotid artery stenosis was assessed by the NASCET criteria. Serum-soluble CXCL16 concentration was measured by enzyme-linked immunosorbent assay. Results Serum CXCL16 concentrations were significantly increased in both LAA (2.36 ng/ml) and SAO subtypes (2.13 ng/ml) when compared to that of the controls (2.04 ng/ml, p < 0.01 and p < 0.05, respectively), and it was significantly elevated in LAA subtype than in SAO subtype (p < 0.05). However, significant differences in CXCL16 levels between the high-grade stenosis group (2.36 ng/ml) and moderate-grade stenosis group (2.24 ng/ml) of LAA subtype were not found (p > 0.05). A correlation of serum levels of CXCL16 with serum levels of hs-CRP, fibrinogen and lipid parameters was not observed (p > 0.05). Conclusions Increased serum level of soluble CXCL16 was independently associated with atherosclerotic ischemic stroke, particularly LAA subtype.
Supporting and Leveraging Prediction Models for Database Applications

of “Supporting and Leveraging Prediction Models for Database Applications”, by Mert Akdere, Ph.D., Brown University, May 2012. Model-based, data-driven prediction is emerging as an essential ingredient for both userfacing applications, such as predictive analytics, and system-facing applications such as autonomic computing. This thesis studies the two complementary research questions of how to effectively support and leverage predictive models for database applications. We explore the performance and usability advantages of integrated predictive functionality within database systems and argue that next generation database systems should natively support and manage predictive models, tightly integrating them in the process of data management and query processing. This is in contrast to the current practice of implementing such functionality within the application space. We study how various types of predictive models can be efficiently supported by utilizing and extending database system mechanisms. Specifically, we discuss (i) white-box support, in which the knowledge of model semantics facilitates a tight integration, thus introducing rich optimization opportunities and (ii) black-box support, in which no such knowledge is assumed, thus leading to a general but less optimizable system. We derive our results from two detailed case studies. In the first one, we describe white-box model support of Bayesian Networks to enable continuous predictive queries over streaming data. In the second, we describe black-box model support and its application on query performance prediction in database systems. We describe efficient implementations of both applications in open-source database systems. Our experimental studies provide quantitative evidence that predictive functionality can be achieved within databases with a level of performance and accuracy that is competitive with or favorable to that of specialized, custom solutions. Supporting and Leveraging Prediction Models for Database Applications by Mert Akdere B. S. , Bilkent University, Turkey, 2005. Sc. M. , Brown University, USA, 2008. A dissertation submitted in partial fulfillment of the requirements for the Degree of Doctor of Philosophy in the Department of Computer Science at Brown University Providence, Rhode Island May 2012 c © Copyright 2012 by Mert Akdere This dissertation by Mert Akdere is accepted in its present form by the Department of Computer Science as satisfying the dissertation requirement for the degree of Doctor of Philosophy. Date Uǧur Çetintemel, Director Recommended to the Graduate Council Date Eli Upfal, Reader Date Stanley B. Zdonik, Reader Approved by the Graduate Council Date Peter M. Weber Dean of the Graduate School
A classification tree analysis of broadband adoption in Australian households

Broadband communication technologies offer households many opportunities, including greater access to education, health and government services, entertainment and social connectivity. Australia appears, however, to be lagging behind other nations in adopting broadband.This paper reports on a study of the relative importance of factors affecting broadband uptake and usage by Australian households. A large data set with 23,093 records was analysed using an innovative statistical technique known as classification tree analysis.Important adoption factors, in approximate order of importance, were: Frequency of Internet usage (indicating needs and benefits of use); Location, a factor likely to indicate, in part, the availability of services; Technophilia, a tendency to acquire technologies in general in the household; and Subscription to Pay TV. User needs and benefits, rather than cost, were found to be primary drivers.
Self-Organizing Feature Extraction in Recognition of Wood Surface Defects and Color Images

A method for constructing classification features with unsupervised learning is presented. The method is based on clustering of the high dimensional measurements into a small number of features with self-organizing maps. The histograms of the self-organized features are classified with a multilayer perceptron network, that can pick up the relevant features and feature combinations from the histograms. The method is applied in two industrial problems, color image recognition for selection of optimal reproduction parameters in the printing press, and defect classification in wood surfaces. In both applications, the results were evaluated by the domain experts to be sufficient with respect to the application requirements. In the color image recognition the results were compared to the manually selected parameter settings, and in 12% of the test images there were distinquishable differences, with very few clear failures. Performance of the wood defect classification system was evaluated with a set of 400 knot images with 7 classes from spruce boards. The recognition rate was about 85% with only gray level images, giving about 90% accuracy for the final board grading, to be compared to 75–80% accuracy that can be maintained by a human inspector. As the methods are based on rather generic basic features and learning of the final features and classes from the samples, they are easily adaptable to different tasks, such as defect inspection in lumber or veneer, with different tree species or different cutting processes.
The outcome of a developmental screening tool (PEDS) in English and Northern Sotho: A comparative study

ABSTRACT In low- and middle-income countries, there is an increase in the prevalence of developmental delays. In a financially-restricted but linguistically diverse South African primary health care context, adapting assessment tools may be more appropriate than developing new ones. The current study aimed to compare outcomes of the English Parents’ Evaluation of Developmental Status (PEDS) and the Northern Sotho PEDS (PEDS-NS), and to determine language preference. The PEDS was translated into Northern Sotho and back-translated. A panel evaluated the translation to determine the appropriateness of the tool. A total of 95 caregivers were selected via convenience sampling. Participants had to adhere to specific selection criteria. High referral rates were reported, which may be due to participants being from underserved communities. Positive and negative correspondence of the PEDS-NS was high. This proved that the PEDS-NS is an accurate translation of the PEDS. Significant association (p = 0.021) was observed between age and respondents’ language preference.
Association of Acinetobacter baumannii EF-Tu with Cell Surface, Outer Membrane Vesicles, and Fibronectin

A conundrum has long lingered over association of cytosol elongation factor Tu (EF-Tu) with bacterial surface. Here we investigated it with Acinetobacter baumannii, an emerging opportunistic pathogen associated with a wide spectrum of infectious diseases. The gene for A. baumannii EF-Tu was sequenced, and recombinant EF-Tu was purified for antibody development. EF-Tu on the bacterial surface and the outer membrane vesicles (OMVs) was revealed by immune electron microscopy, and its presence in the outer membrane (OM) and the OMV subproteomes was verified by Western blotting with the EF-Tu antibodies and confirmed by proteomic analyses. EF-Tu in the OM and the OMV subproteomes bound to fibronectin as detected by Western blot and confirmed by a label-free real-time optical sensor. The sensor that originates from photonic crystal structure in a total-Internal-reflection (PC-TIR) configuration was functionalized with fibronectin for characterizing EF-Tu binding. Altogether, with a novel combination of immunological, proteomical, and biophysical assays, these results suggest association of A. baumannii EF-Tu with the bacterial cell surface, OMVs, and fibronectin.
Natriuretic peptides and troponins in pulmonary embolism: a meta-analysis

Background: The role of biomarkers such as B-type natriuretic peptides (BNP and NT-proBNP) and troponins in risk stratification of acute pulmonary embolism (APE) is still debated. A meta-analysis was performed to assess the association between raised natriuretic peptide levels, alone or in conjunction with troponins, and all-cause and APE-related mortality, serious adverse events and echographic right ventricular dysfunction. Methods: MEDLINE and EMBASE databases were searched and conference abstracts were hand searched up to February 2008. Studies were included if a 2×2 table could be constructed based on natriuretic peptide results and at least one of the outcomes. Results: Twenty-three studies were included (1127 patients). Raised natriuretic peptide levels were significantly associated with all-cause mortality (odds ratio (OR) 6.2; 95% confidence interval (CI) 3.0 to 12.7), APE-related mortality (OR 5.0; 95% CI 2.2 to 11.5) and serious adverse events (OR 6.7; 95% CI 3.9 to 11.6), with homogeneity across studies. Among patients with raised natriuretic peptide levels, increased serum troponins were associated with a further increase in the risk of adverse outcomes. Analysis of the accuracy of natriuretic peptides in detecting right ventricular dysfunction was limited by heterogeneity across studies. BNP appeared to have better sensitivity and specificity than NT-proBNP in detecting right ventricular dysfunction. Conclusions: Raised levels of B-type natriuretic peptides identified a subset of patients with APE at higher risk of adverse outcomes. Among patients with raised natriuretic peptide levels, increased troponins were found to be an independent prognostic marker. The results of this meta-analysis may have important clinical implications in the management of APE.
Phase 1/2 and extension study of velaglucerase alfa replacement therapy in adults with type 1 Gaucher disease: 48-month experience.

Enzyme replacement therapy is the standard of care for symptomatic Gaucher disease. Velaglucerase alfa is a human beta-glucocerebrosidase produced in a well-characterized human cell line. A 9-month phase 1/2 open-label, single-center trial and ongoing extension study were conducted to evaluate safety and efficacy of velaglucerase alfa. Twelve symptomatic adult type 1 Gaucher patients (intact spleens) received velaglucerase alfa (60 U/kg per infusion) during phase 1/2. An extension study was offered to patients completing the trial; step-wise dose reduction (to 30 U/kg per infusion) was instituted. Eleven patients completed phase 1/2; 10 entered the extension; 9 patients reached 39 months of extension. No drug-related serious adverse events or withdrawals, and no antibodies were observed. Home therapy was successfully implemented during the extension. Statistically significant improvements (P < .004) were noted in mean percentage change from baseline to 9 months and baseline to 48 months for hemoglobin (+19.2%, +21.7%, respectively), platelet counts (+67.6%, +157.8%, respectively), normalized liver volume (-18.2%, -42.8%, respectively), and normalized spleen volume (-49.5%, -79.3%, respectively). These significant clinical changes and safety profile led to phase 3 trials and highlight the potential of velaglucerase alfa as alternative therapy for type 1 Gaucher disease. The extension trial is registered at http://www.clinicaltrials. gov as NCT00391625.
CD4+ T cells cause multinucleated giant cells to form around Cryptococcus neoformans and confine the yeast within the primary site of infection in the respiratory tract

The possible mechanisms by which CD4+ T cells prevent the dissemination of Cryptococcus neoformans from the primary site of infection in the respiratory tract were examined. It was found that even before fungicidal mechanisms are fully induced in the lungs, the host generates a CD4+ T cell-dependent inflammatory response that sequesters yeast within the pulmonary alveoli. This confinement is evident histopathologically and demonstrable objectively as a rapid decline in the ability to dislodge yeast from the lungs by bronchopulmonary lavage. One striking component of this response is the enclosure of cryptococci within multinucleated giant cells in granulomas. Studies in severe combined immunodeficient mice that were engrafted with selected lymphocyte subpopulations show that B cells, and hence anti- Cryptococcus antibodies, are not necessary for the CD4+ T cell- dependent responses that isolate and subsequently destroy this opportunistic pathogen in the lung parenchyma.
Document clustering and topic discovery based on semantic similarity in scientific literature

Unlabeled document collections are becoming increasingly common and mining such databases becomes a major challenge. It is a major issue to retrieve relevant documents from the larger document collection. By clustering the text documents, the documents sharing similar topics are grouped together. Incorporating semantic features will improve the accuracy of document clustering methods. In order to determine at a sight whether the content of a cluster are of user interest or not, topic discovery methods are required to tag each clusters identifying distinct and representative topic of each cluster. Most of the existing topic discovery methods often assign labels to clusters based on the terms that the clustered documents contain. In this paper a modified semantic-based model is proposed where related terms are extracted as concepts for concept-based document clustering by bisecting k-means algorithm and topic detection method for discovering meaningful labels for the document clusters based on semantic similarity by Testor theory. The proposed method is compared to the Topic Detection by Clustering Keywords method using F-measure and purity as evaluation metrics. Experimental results prove that the proposed semantic-based model outperforms the existing work.
Potentiation of decursinol angelate on pentobarbital-induced sleeping behaviors via the activation of GABAA-ergic systems in rodents

Angelicae Gigantis Radix (AGR, Angelica gigas) has been used for a long time as a traditional folk medicine in Korea and oriental countries. Decursinol angelate (DCA) is structurally isomeric decursin, one of the major components of AGR. This study was performed to confirm whether DCA augments pentobarbital-induced sleeping behaviors via the activation of GABAA-ergic systems in animals. Oral administration of DCA (10, 25 and 50 mg/kg) markedly suppressed spontaneous locomotor activity. DCA also prolonged sleeping time, and decreased the sleep latency by pentobarbital (42 mg/kg), in a dose-dependent manner, similar to muscimol, both at the hypnotic (42 mg/kg) and sub-hypnotic (28 mg/kg) dosages. Especially, DCA increased the number of sleeping animals in the sub-hypnotic dosage. DCA (50 mg/kg, p.o.) itself modulated sleep architectures; DCA reduced the counts of sleep/wake cycles. At the same time, DCA increased total sleep time, but not non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. In the molecular experiments. DCA (0.001, 0.01 and 0.1 µg/ml) increased intracellular Cl- influx level in hypothalamic primary cultured neuronal cells of rats. In addition, DCA increased the protein expression of glutamic acid decarboxylase (GAD65/67) and GABAA receptors subtypes. Taken together, these results suggest that DCA potentiates pentobarbital-induced sleeping behaviors through the activation of GABAA-ergic systems, and can be useful in the treatment of insomnia.
The power of batching in the Click modular router

The Click modular router has been one of the most popular software router platforms for rapid prototyping and new protocol development. Unfortunately, its internal architecture has not caught up with recent hardware advancements, and the performance remains sub-optimal in high-speed networks despite its benefit of flexible module composition. In this work, we identify the performance bottlenecks of the existing Click router and extend it to scale with modern computer systems. Our improvements focus on both I/O and computation batching, and include various optimizations for multi-core systems and multi-queue network cards. We find that these techniques improve the performance by almost a factor of 10, and the maximum throughput reaches 28 Gbps of minimum-sized IPv4 packet forwarding speed on a single machine.
ON CRITERIA FOR THE UNIFORM INTEGRABILITY OF BROWNIAN STOCHASTIC EXPONENTIALS

This paper deals with various sufficient (as well as necessary and sufficient) conditions for the uniform integrability of the exponential martingales of the form Zt = exp { Bt∧τ − 1 2 t ∧ τ } , t ≥ 0, where B is a Brownian motion and τ is a stopping time. We give an overview of the known results and present some new criteria (Theorems 3.2, 4.1). As an auxiliary lemma, we prove the following statement that is interesting in itself: for any function φ : R+ → R , the upper limit lim supt↑∞(Bt − φ(t)) either equals +∞ a.s. or equals −∞ a.s. This provides a simple criterion for distinguishing lower and upper functions of a Brownian motion.