Miracle-dz/UniFAR-FTUs huggingface dataset:
X-ray Crystal Structure of Human Dopamine Sulfotransferase, SULT1A3

Humans are one of the few species that produce large amounts of catecholamine sulfates, and they have evolved a specific sulfotransferase, SULT1A3 (M-PST), to catalyze the formation of these conjugates. An orthologous protein has yet to be found in other species. To further our understanding of the molecular basis for the unique substrate selectivity of this enzyme, we have solved the crystal structure of human SULT1A3, complexed with 3′-phosphoadenosine 5′-phosphate (PAP), at 2.5 Å resolution and carried out quantitative structure-activity relationship (QSAR) analysis with a series of phenols and catechols. SULT1A3 adopts a similar fold to mouse estrogen sulfotransferase, with a central five-stranded β-sheet surrounded by α-helices. SULT1A3 is a dimer in solution but crystallized with a monomer in the asymmetric unit of the cell, although dimer interfaces were formed by interaction across crystallographic 2-fold axes. QSAR analysis revealed that the enzyme is highly selective for catechols, and catecholamines in particular, and that hydrogen bonding groups and lipophilicity (cLogD) strongly influenced K m . We also investigated further the role of Glu146 in SULT1A3 using site-directed mutagenesis and showed that it plays a key role not only in defining selectivity for dopamine but also in preventing many phenolic xenobiotics from binding to the enzyme.
Rituximab and its potential for the treatment of rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder which causes deforming joint disease and a spectrum of extraarticular manifestations. Poor disease control may lead to functional impairment and loss of independence. In recent times a prominent role for B cells in the pathogenesis of RA has been suggested. Two major theories have been postulated to explain the role of rheumatoid factor (RF) in the RA inflammatory process and the reason for RF overproduction; the loss of tolerance model and the autonomous mutated B cell model. With this in mind, strategies have been adopted to deplete B cells including the use of the anti-CD20 antibody rituximab. Rituximab leads to complement mediated lysis of B cells as well as antibody-dependant cellular cytotoxicity. It has been hypothesized that rituximab may also initiate apoptosis in RA and alter the ability of B cells to respond to antigen and other stimuli. Several recent studies using rituximab have demonstrated significant declines in RA activity providing evidence for the role of B cells in RA. Rituximab would appear to be a major addition to the increasing therapeutic options for sufferers of RA.
Bernoulli Mixture Models for Markov Blanket Filtering and Classification

This paper presents the use of Bernoulli mixture models for Markov blanket flltering and classiflcation of binary data. Bernoulli mixture models can be seen as a tool for partitioning an n-dimensional hypercube, identifying regions of high data density on the corners of the hypercube. Once Bernoulli mixture models are computed from a training dataset we use them for determining the Markov blanket of the target variable. An algorithm for Markov blanket flltering was proposed by Koller and Sahami (1996), which is a greedy search method for feature subset selection and it outputs an approximation to the optimal feature selection criterion. However, they use the entire training instances for computing the conditioning sets and have to limit the size of these sets for computational e‐ciency and avoiding data fragmentation. We have adapted their algorithm to use Bernoulli mixture models instead, hence, overcoming the short comings of their algorithm and increasing the e‐ciency of this algorithm considerably. Once a feature subset is identifled we perform classiflcation using these mixture models. We have applied this algorithm to the causality challenge datasets. Our prediction scores were ranked fourth on SIDO and our feature scores were ranked the best for test sets 1 and 2 of the same dataset.
The three‐dimensional feto‐maternal vascular interrelationship during early bovine placental development: a scanning electron microscopical study

Both the fetal and maternal microvasculature of bovine placentomes was examined by scanning electron microscopy of vascular casts. So far the development of the vascular architecture of the bovine placentome in early gestation has only been studied 2‐dimensionally due to technical difficulties arising from the fragility of the early placental blood vessels. Repeated experiments led to the selection of the microvascular corrosion casts presented here. The vasculature of the maternal compartment is supplied by large caruncular stalk or spiral arteries, which release short maternal stem arteries. In the 3rd month of gestation, these arteries branch into several arterioles at their base, thus providing the vascular framework for the lower part of the septal walls of the primary crypts. In the 4th month, due to progressive longitudinal growth of the stem arteries, branching into arterioles occurs not only at the base, but over the whole length of the stem arteries. These arterioles supply the capillary complexes of the septa which resemble the major part of the septal vasculature and face the secondary crypts. Further indentation results in the formation of tertiary crypt capillary complexes, encircling the earlier secondary unit. From the 6th month of gestation the architecture resembles the fully developed maternal placenta with stem arteries running directly to the fetal side to branch into 4 to 6 arterioles, which turn back to enter secondary and tertiary septa. Maternal venules, collecting the blood from the capillary bed of secondary and tertiary septa, converge onto stem veins leaving the caruncle via branches of the uterine vein. The fetal part of the placentome is supplied by the cotyledonary arteries, which branch into fetal stem arteries that are the tributary to single villous trees. Over their whole course towards the maternal side, these give off arterioles entering secondary villi. The tertiary or terminal villous vasculature consists of capillaries, which are organised in serial capillary loops. This system is progressively elaborated in the course of gestation. In the 4th month there are only finger‐like loops, whereas from the 6th month large fan‐like structures can be observed. In early gestation the maternal and fetal blood vessels meet predominantly in a countercurrent fashion, changing to the less efficient crosscurrent exchange when the tertiary unit develops. These results indicate the development of a highly elaborated fetomaternal villous‐crypt exchange system, already established in the 1st half of gestation, thus meeting the increasing needs of the fetus.
Dendritic Cell Apoptosis and the Pathogenesis of Dengue

Dengue viruses and other members of the Flaviviridae family are emerging human pathogens. Dengue is transmitted to humans by Aedes aegypti female mosquitoes. Following infection through the bite, cells of the hematopoietic lineage, like dendritic cells, are the first targets of dengue virus infection. Dendritic cells (DCs) are key antigen presenting cells, sensing pathogens, processing and presenting the antigens to T lymphocytes, and triggering an adaptive immune response. Infection of DCs by dengue virus may induce apoptosis, impairing their ability to present antigens to T cells, and thereby contributing to dengue pathogenesis. This review focuses on general mechanisms by which dengue virus triggers apoptosis, and possible influence of DC-apoptosis on dengue disease severity.
Expression profiling and electrophysiological studies suggest a major role for Orai1 in the store-operated Ca2+ influx pathway of platelets and megakaryocytes

Store-operated Ca2+ influx represents a major route by which cytosolic Ca2+ can be elevated during platelet activation, yet its molecular identity in this cell type remains highly controversial. Using quantitative RT-PCR analysis of candidate receptor-operated cation entry pathways in human platelets, we show a >30-fold higher expression of message for the recently discovered Orai1 store-operated Ca2+ channel, and also the store Ca2+ sensor STIM1, when compared to the non-selective cation channels TRPC1, TRPC6 and TRPM2. Orai1 and STIM1 gene transcripts were also detected at higher levels than TRPC1, TRPC6 and TRPM2 in primary murine megakaryocytes and human megakaryocytic cell lines. In direct electrophysiological recordings from murine megakaryocytes, Ca2+ ionophore-induced store depletion stimulated CRAC currents, which are known to require Orai1, and these overlapped with TRPC6-like currents following P2Y receptor activation. Together with recent transgenic studies, these data provide evidence for STIM1:Orai1 as a primary pathway for agonist-evoked Ca2+ influx in the platelet and megakaryocyte.
Complex Processes from Dynamical Architectures with Time-Scale Hierarchy

The idea that complex motor, perceptual, and cognitive behaviors are composed of smaller units, which are somehow brought into a meaningful relation, permeates the biological and life sciences. However, no principled framework defining the constituent elementary processes has been developed to this date. Consequently, functional configurations (or architectures) relating elementary processes and external influences are mostly piecemeal formulations suitable to particular instances only. Here, we develop a general dynamical framework for distinct functional architectures characterized by the time-scale separation of their constituents and evaluate their efficiency. Thereto, we build on the (phase) flow of a system, which prescribes the temporal evolution of its state variables. The phase flow topology allows for the unambiguous classification of qualitatively distinct processes, which we consider to represent the functional units or modes within the dynamical architecture. Using the example of a composite movement we illustrate how different architectures can be characterized by their degree of time scale separation between the internal elements of the architecture (i.e. the functional modes) and external interventions. We reveal a tradeoff of the interactions between internal and external influences, which offers a theoretical justification for the efficient composition of complex processes out of non-trivial elementary processes or functional modes.
Competition between adaptive agents: from learning to collective efficiency and back

We use the Minority Game and some of its variants to show how efficiency depends on learning in models of agents competing for lim- ited resources. Exact results from statistical physics give a clear under- standing of the phenomenology, and opens the way to the study of reverse problems. What agents can optimize and how well is discussed in details. Designed a simplification of Arthur's El Farol bar problem (1), the Mi- nority Game (2, 3) provides a natural framework for studying how selfish adaptive agents can cope with competition. The major contribution of the Minority Game is not only to symmetrize the problem, which physicists like very much, but also to introduce a well parametrized set of strategies, and more generally to provide a well defined and workable family of models. In this game, N agents have to choose one between two choices at each time step; those who are in the minority win, the other lose. Obviously, it is easier to loose than to win, as the number of winners cannot exceed that of the losers. If the game is played once, only a random choice is reasonable, according to Game Theory (4). When the game is repeated, it is sensible to suppose that agents will try to learn from the past in order to outperform the other agents, hence, the question of learning arises, as the minority mechanism entails a never-ending competition. Let me first introduce the game and the needed formalism. There are N agents, agent i taking action ai ∈ {−1,+1}. A game master aggregates the individual actions into A = PN=1 ai and gives private payoffs −aig(A) to each agent i = 1, � � � , N. The minority structure of the game implies that g must be an odd function of A. The simplest choice for g may seem to be g(A) = sgn(A), but a linear function is better suited to mathematical analysis. The MG is a negative sum game, as the total payoff given to the agents, is − P N=1 aig(A) = −g(A)A < 0, since g is an odd function. In particular, the linear payoff function gives a total loss of A 2 ; when the game is repeated, the average total loss is nothing else than the fluctuations of
On the Use of Evidence in Neural Networks

The Bayesian "evidence" approximation has recently been employed to determine the noise and weight-penalty terms used in back-propagation. This paper shows that for neural nets it is far easier to use the exact result than it is to use the evidence approximation. Moreover, unlike the evidence approximation, the exact result neither has to be re-calculated for every new data set, nor requires the running of computer code (the exact result is closed form). In addition, it turns out that the evidence procedure's MAP estimate for neural nets is, in toto, approximation error. Another advantage of the exact analysis is that it does not lead one to incorrect intuition, like the claim that using evidence one can "evaluate different priors in light of the data". This paper also discusses sufficiency conditions for the evidence approximation to hold, why it can sometimes give "reasonable" results, etc.
Site-Directed Mutagenesis Using Oligonucleotide-Based Recombineering

Methods enabling mutational analysis of distinct chromosomal locations, like site-directed mutagenesis, insertion of foreign sequences or in-frame deletions, have become of fast growing interest since complete bacterial genome sequences became available. Various approaches have been described to modify any nucleotide(s) in almost any manner. Some genetic engineering technologies do not rely on the in vitro reactions carried out by restriction enzymes and DNA ligases (Sawitzke et al., 2001). Complicated genetic constructs that seem to be impossible to generate in vitro can be created within one week using in vivo technologies (Sawitzke et al., 2001).
Evaluation of A2BP1 as an Obesity Gene

OBJECTIVE A genome-wide association study (GWAS) in Pima Indians (n = 413) identified variation in the ataxin-2 binding protein 1 gene (A2BP1) that was associated with percent body fat. On the basis of this association and the obese phenotype of ataxin-2 knockout mice, A2BP1 was genetically and functionally analyzed to assess its potential role in human obesity. RESEARCH DESIGN AND METHODS Variants spanning A2BP1 were genotyped in a population-based sample of 3,234 full-heritage Pima Indians, 2,843 of whom were not part of the initial GWAS study and therefore could serve as a sample to assess replication. Published GWAS data across A2BP1 were additionally analyzed in French adult (n = 1,426) and children case/control subjects (n = 1,392) (Meyre et al. Nat Genet 2009;41:157–159). Selected variants were genotyped in two additional samples of Caucasians (Amish, n = 1,149, and German children case/control subjects, n = 998) and one additional Native American (n = 2,531) sample. Small interfering RNA was used to knockdown A2bp1 message levels in mouse embryonic hypothalamus cells. RESULTS No single variant in A2BP1 was reproducibly associated with obesity across the different populations. However, different variants within intron 1 of A2BP1 were associated with BMI in full-heritage Pima Indians (rs10500331, P = 1.9 × 10−7) and obesity in French Caucasian adult (rs4786847, P = 1.9 × 10−10) and children (rs8054147, P = 9.2 × 10−6) case/control subjects. Reduction of A2bp1 in mouse embryonic hypothalamus cells decreased expression of Atxn2, Insr, and Mc4r. CONCLUSIONS Association analysis suggests that variation in A2BP1 influences obesity, and functional studies suggest that A2BP1 could potentially affect adiposity via the hypothalamic MC4R pathway.
Evaluation of individual cognitive behaviour therapy for older people who are fearful of falling: A pilot study and clinical research portfolio

Objective: It has been found that 50% of older adults who fall will develop fear of falling. Group delivered Cognitive Behaviour Therapy (CBT) has been found to be effective in reducing fear of falling however, research has found that individually delivered CBT may be more effective and acceptable than group delivered CBT. This research is a preliminary study evaluating the effectiveness of an individually delivered CBT intervention for fear of falling in older adults compared to a control group receiving physiotherapy. The study also reports data on indicators of the acceptability and feasibility of CBT in this sample. Method: Eighteen participants were recruited from the NHS Greater Glasgow and Clyde Falls Prevention Service and were allocated to either the CBT or control group according to the treatment site that they attended for the Falls Prevention Service. Measures of fear of falling, anxiety, and quality of life were compared within subjects and between groups at pre and post treatment. Results: On the measure of fear of falling, significant within subject differences for those who received the CBT and between subject differences compared to a group receiving standard physiotherapy were found. No differences were found within subjects or between groups on measures of anxiety or quality or life. The intervention was found to be acceptable to older adults and practical in terms of delivery. Discussion: Individually delivered CBT is an effective and feasible intervention for older adults who are fearful of falling and is more effective than standard physiotherapy. Future studies should aim to investigate if this beneficial effect is replicable.
Literature Survey on Multi-Lingual Multiword Expressions

The literature survey defines the Multiword Expressions and aims to provide a principled way to identify Multiword Expressions in different Indian Languages. Three types of Multiword Expressions namely, Noun + Noun (compound noun), Noun + Verb (conjunct verb) and Verb + Verb (compound verb) sequences are examined. It concentrates on the linguistic methods, like chunker, part-of-speech tagging, and the statistical methods like, point wise mutual information, log-likelihood, to extract the Multiword Expressions. The study focuses on the following: A. isolation Noun + Noun combinations, which are compound nouns, from other noun sequences B. isolating Verb + Verb and Noun + Verb combinations, which are complex predicates, from other verb-verb and noun-verb sequences Along with this, different approaches to extract Multiword Expressions are also discussed at the end.
Pannexins, a family of gap junction proteins expressed in brain

Database search has led to the identification of a family of proteins, the pannexins, which share some structural features with the gap junction forming proteins of invertebrates and vertebrates. The function of these proteins has remained unclear so far. To test the possibility that pannexins underlie electrical communication in the brain, we have investigated their tissue distribution and functional properties. Here, we show that two of these genes, pannexin 1 (Px1) and Px2, are abundantly expressed in the CNS. In many neuronal cell populations, including hippocampus, olfactory bulb, cortex and cerebellum, there is coexpression of both pannexins, whereas in other brain regions, e.g., white matter, only Px1-positive cells were found. On expression in Xenopus oocytes, Px1, but not Px2 forms functional hemichannels. Coinjection of both pannexin RNAs results in hemichannels with functional properties that are different from those formed by Px1 only. In paired oocytes, Px1, alone and in combination with Px2, induces the formation of intercellular channels. The functional characteristics of homomeric Px1 versus heteromeric Px1/Px2 channels and the different expression patterns of Px1 and Px2 in the brain indicate that pannexins form cell type-specific gap junctions with distinct properties that may subserve different functions.
Crohn's disease: does race matter? The Mid-Atlantic Crohn's Disease Study Group.

OBJECTIVE The severity of Crohn's disease (CD) has been reported to be greater in blacks than in whites. This possible disparity may be due, in part, to differences between these groups in health care utilization and accessibility. To explore these issues, we conducted a multicenter survey of patients with CD. METHODS One-hundred and forty-five blacks with CD, recruited from four teaching hospitals and five private practices, and identified by medical record review or ICD-9 code, were enrolled and matched to 407 whites with CD (by age, gender, and practice type [teaching vs. private practice setting]). Participants were interviewed regarding medical history, health status, personal health care practices during the preceding 5 yr, and beliefs regarding health care in the general population. RESULTS Blacks and whites were similar with respect to age of CD onset, lag in time to diagnosis, and number of gastrointestinal (GI)-related hospitalizations and surgeries. Medication usage patterns were also similar in the two groups. Quality of life, measured by SF-36, was lower in all categories for blacks, compared with whites. Blacks were more likely to have had to stop work (p<0.01) and have lost more work days (p<0.01) than were whites. Whites were more likely to have health insurance and be able to identify a regular provider than were blacks. Blacks were more likely to report the following: receiving Medicaid; difficulty affording health care; delaying appointments due to financial concerns; difficulty traveling to their provider's office; and experiencing unreasonable delays at their provider's office. After adjusting for potential confounding variables, we found no differences between the groups, except for the number of days of work lost because of CD. CONCLUSIONS These data suggest that black and white patients have similar reported disease presentations and course, and contrast with prior reports suggesting a more severe disease course among black patients. Although the disease itself appears similar, there were numerous reported differences between the races in health care utilization practices and in disease impact upon daily activities. We suggest that apparent disparities in CD according to race are actually due to social and economic factors, and not to the disease itself.
Anomaly detection in IP networks based on randomized subspace methods

In this paper we propose novel randomized subspace methods to detect anomalies in Internet Protocol networks. Given a data matrix containing information about network traffic, the proposed approaches perform a normal-plus-anomalous matrix decomposition aided by the randomized sampling scheme and subsequently detect traffic anomalies in the anomalous subspace using a statistical test. Simulation results demonstrate improvement over the traditional principal component analysis-based subspace methods in terms of robustness to noise and detection rate.