Miracle-dz/UniFAR-FTUs huggingface dataset:
Mutational Analysis of the Antagonist-binding Site of the Histamine H1 Receptor*

We combined in a previously derived three-dimensional model of the histamine H1 receptor (Ter Laak, A. M., Timmerman, H., Leurs, H., Nederkoorn, P. H. J., Smit, M. J., and Donne-Op den Kelder, G. M. (1995) J. Comp. Aid. Mol. Design. 9, 319–330) a pharmacophore for the H1 antagonist binding site (Ter Laak, A. M., Venhorst, J., Timmerman, H., and Donné-Op de Kelder, G. M. (1994) J. Med. Chem. 38, 3351–3360) with the known interacting amino acid residue Asp116 (in transmembrane domain III) of the H1 receptor and verified the predicted receptor-ligand interactions by site-directed mutagenesis. This resulted in the identification of the aromatic amino acids Trp167, Phe433, and Phe436 in transmembrane domains IV and VI of the H1 receptor as probable interaction points for the trans-aromatic ring of the H1 antagonists. Subsequently, a specific interaction of carboxylate moieties of two therapeutically important, zwitterionic H1 antagonists with Lys200 in transmembrane domain V was predicted. A Lys200 → Ala mutation results in a 50- (acrivastine) to 8-fold (d-cetirizine) loss of affinity of these zwitterionic antagonists. In contrast, the affinities of structural analogs of acrivastine and cetirizine lacking the carboxylate group, triprolidine and meclozine, respectively, are unaffected by the Lys200 → Ala mutation. These data strongly suggest that Lys200, unique for the H1receptor, acts as a specific anchor point for these “second generation” H1 antagonists.
Materials and Methods Figs. S1 to S4 Tables S1 and S2 References Niemann-pick C1 like 1 Protein Is Critical for Intestinal Cholesterol Absorption

Dietary cholesterol consumption and intestinal cholesterol absorption contribute to plasma cholesterol levels, a risk factor for coronary heart disease. The molecular mechanism of sterol uptake from the lumen of the small intestine is poorly defined. We show that Niemann-Pick C1 Like 1 (NPC1L1) protein plays a critical role in the absorption of intestinal cholesterol. NPC1L1 expression is enriched in the small intestine and is in the brush border membrane of enterocytes. Although otherwise phenotypically normal, NPC1L1-deficient mice exhibit a substantial reduction in absorbed cholesterol, which is unaffected by dietary supplementation of bile acids. Ezetimibe, a drug that inhibits cholesterol absorption, had no effect in NPC1L1 knockout mice, suggesting that NPC1L1 resides in an ezetimibe-sensitive pathway responsible for intestinal cholesterol absorption. Whole-body cholesterol homeostasis is a highly regulated balance of de novo synthesis, dietary cholesterol absorption, and biliary clearance and excretion. The cholesterol biosynthetic and clearance pathways are well defined. An understanding of the biosynthetic pathway has led to the development of the statin class of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMG-CoA reductase) inhibitors for the management of hypercholesterolemia and associated cardiovascular disease (1). In contrast, the mechanisms controlling cholesterol absorption are less well understood. The adenosine triphosphate (ATP)– binding cassette (ABC) A1 transporter and scavenger receptor type B1 (SR-BI) were postulated to play a role in intestinal cholesterol absorption (2–4), but targeted inactivation of these genes in mice had no effect on cholesterol uptake (5–7). The ABCG5 and ABCG8 transporters, which are defective in the sterol absorption disease sitosterolemia, provide an apparatus for efficient shunting of sterols away from the transfer pathway directing the production of cholesteryl esters by acyl-CoA cholesterol acyl transferase 2 (ACAT2) (8–10). However, none of these mechanisms appear to be involved in the initial uptake of cholesterol. In humans, cholesterol absorption occurs in the proximal jejunum of the small intestine, where both dietary cholesterol and biliary cholesterol are available for uptake from the intestinal lumen. The second-order kinetics of cholesterol absorption (11), its sterol specificity (12, 13), and its inhibition by drugs such as ezetimibe (14) all suggest that this process is mediated by a specific transport protein(s). However, the identity of this putative cholesterol transporter has remained elusive. To identify genes involved in cholesterol uptake, we used a genomic-bioinformatics approach. Because sequences from gastrointesti-nal tissues are poorly represented in the public sequence databases, we prepared two cDNA libraries for sequencing, one from rat jejunum mucosal scrapings …
A Self Stabilising Multiplexed Interferometer for On-line Surface Measurement

This paper introduces a new surface measurement method for potential online surface measurement application. It features high stability due to using near common-path configuration combined with active stabilisation. The active stabilisation is supplied by the use of a multiplexed reference interferometer and piezo-electric translator mounted mirror. The active compensation makes the system resistant to disturbance, pointing toward the possibility of on line use. The method should be of great benefit to advanced manufacturing, especially for quality and process control in precision manufacturing and on the production line. Proof-of-concept experiments have been successfully conducted by measuring the system stability over time.
Learning from Ontology Streams with Semantic Concept Drift

Data stream learning has been largely studied for extracting knowledge structures from continuous and rapid data records. In the semantic Web, data is interpreted in ontologies and its ordered sequence is represented as an ontology stream. Our work exploits the semantics of such streams to tackle the problem of concept drift i.e., unexpected changes in data distribution, causing most of models to be less accurate as time passes. To this end we revisited (i) semantic inference in the context of supervised stream learning, and (ii) models with semantic embeddings. The experiments show accurate prediction with data from Dublin and Beijing.
Applying recommendation techniques to support conceptual negotiation processes

According to [1], in order to share knowledge and information it is necessary to share a set of conceptual structures within a collaborative network. Therefore, to develop an organizational information system it is required to engage in a negotiation process so that it is possible to obtain a common vocabulary. To support and improve such process, this paper presents an approach that takes advantage of some of the features of recommendation systems (RS), which will be extremely useful to help collaborative networks construct a high-level conceptualization about a specific domain.
Implementing Arrow-Debreu equilbria by continuous trading of a few long-lived securities

AbstractA two-period (0 and T) Arrow-Debreu economy is set up with a general model of uncertainty. We suppose that an equilibrium exists for this economy. The Arrow-Debreu economy is placed in a Radner (dynamic) setting; agents may trade claims at any time during [0, T]. Under appropriate conditions it is possible to implement the original Arrow-Debreu equilibrium, which may have an infinite-dimensional commodity space, in a Radner equilibrium with only a finite number of securities. This is done by opening the “right” set of security markets, a set which effectively completes markets for the Radner economy.
Effects of Endurance Exercise Training on Plasma HDL Cholesterol Levels Depend on Levels of Triglycerides: Evidence From Men of the Health, Risk Factors, Exercise Training and Genetics (HERITAGE) Family Study

High density lipoprotein (HDL) cholesterol concentrations have been shown to increase with regular endurance exercise and, therefore, can contribute to a lower risk of coronary heart disease in physically active individuals compared with sedentary subjects. Although low HDL cholesterol levels are frequently observed in combination with hypertriglyceridemia, some individuals may be characterized by isolated hypoalphalipoproteinemia, ie, low HDL cholesterol levels in the absence of elevated triglyceride (TG) concentrations. The present study compared the responses of numerous lipoprotein-lipid variables to a 20-week endurance exercise training program in men categorized on the basis of baseline TG and HDL cholesterol concentrations: (1) low TG and high HDL cholesterol (normolipidemia), (2) low TG and low HDL cholesterol (isolated low HDL cholesterol), (3) high TG and high HDL cholesterol (isolated high TGs), and (4) high TGs and low HDL cholesterol (high TG/low HDL cholesterol). A series of physical and metabolic variables was measured before and after the training program in a sample of 200 men enrolled in the Health, Risk Factors, Exercise Training and Genetics (HERITAGE) Family Study. At baseline, men with high TG/low HDL cholesterol had more visceral adipose tissue than did men with isolated low HDL cholesterol and men with normolipidemia. The 0.4% (not significant) exercise-induced increase in HDL cholesterol levels in men with isolated low HDL cholesterol suggests that they did not benefit from the “HDL-raising” effect of exercise. In contrast, men with high TG/low HDL cholesterol showed a significant increase in HDL cholesterol levels (4.9%, P <0.005). Whereas both subgroups of men with elevated TG levels showed reductions in plasma TGs (≈−15.0%, P <0.005), only those with high TG/low HDL cholesterol showed significantly reduced apolipoprotein B levels at the end of the study (−6.0%, P <0.005). Multiple regression analyses revealed that the exercise-induced change in abdominal subcutaneous adipose tissue (10.6%, P <0.01) was the only significant correlate of the increase in plasma HDL cholesterol with training in men with high TG/low HDL cholesterol. Results of the present study suggest that regular endurance exercise training may be particularly helpful in men with low HDL cholesterol, elevated TGs, and abdominal obesity.
Sectorized space-time multiuser detection for CDMA systems

Space-time multiuser detection (STMD) is an emerging technique for wideband CDMA mobile communication systems, where the problems of multiuser access interference (MUAI) and intersymbol interference (ISI) can be solved simultaneously. However, complexity becomes one of the key problems in its practical implementation because of the exponential increment of computation burden due to the increased number of users. In this paper, we propose the sectorized STMD scheme that confines detection within a given sector. In the proposed scheme, the number of users in the sector becomes smaller, and, consequently, the system complexity becomes lower. Due to the sectorized beamforming, the signal-to-noise ratios of the users' multipath rays are enhanced, leading to performance improvements in the signature waveforms' estimation and detection.
Bayesian decision theory on three layered neural networks

We treat the Bayesian decision problem, mainly the two-category case. A three layered neural network, having a logistic output unit and a small number of hidden layer units, can approximate the a posteriori probability in L 2 -norm, without knowing the type of the probability distribution before learning, if the log ratio of the a posteriori probabilities is a polynomial of low degree as in the case of most familiar probability distributions. This is because the log ratio itself can be well approximated by a linear sum of outputs of the hidden layer units in L 2 -norm.
Cooling flows as a calorimeter of active galactic nucleus mechanical power

ABSTRA C T The assumption that radiative cooling of gas in the centres of galaxy clusters is approximately balanced by energy input from a central supermassive black hole implies that the observed X-ray luminosity of the cooling flow region sets a lower limit on active galactic nucleus (AGN) mechanical power. The conversion efficiency of the mechanical power of the AGN into gas heating is uncertain, but we argue that it can be high even in the absence of strong shocks. These arguments inevitably lead to the conclusion that the time-averaged mechanical power of AGNs in cooling flows is much higher than the bolometric luminosity of these objects observed currently. The energy balance between cooling losses and AGN mechanical power requires some feedback mechanism. We consider a toy model in which the accretion rate on to a black hole is set by the classic Bondi formula. Application of this model to the best studied case of M87 suggests that accretion proceeds at approximately the Bondi rate down to a few gravitational radii with most of the power (at the level of a few per cent of the rest mass) being carried away by an outflow.
Intergroup exposure in wilderness programming and effects on prospective college belonging among low-income adolescents

ii List of Tables.vii List of Figures.viii Chapter 1: Introduction . 1 Chapter 2: Literature Review . 4 Higher education and the opportunity gap . 4 Non-cognitive factors . 5 Social-belonging and college persistence . 6 Outdoor experiential education . 8 Contact theory . 9 Contact theory and OEE . 10 Facilitative group processes in structured youth activity settings . 11 OEE and interpersonal mediating mechanisms . 12 Empathy and perspective-taking . 13 Summer Search program model . 13 The current study . 17 Aim 1.17 Aim 2.18 Chapter 3: Method.19 Participants . 19 Procedure . 19
Evaluation of model-based feature enhancement on the AURORA-4 task

In this paper we focus on the challenging task of noise robustness for large vocabulary Continuous Speech Recognition (LVCSR) systems in non-stationary noise environments. We have extended our Model-Based Feature Enhancement (MBFE) algorithm – that we earlier successfully applied to small vocabulary CSR in the AURORA-2 framework – to cope with the new demands that are imposed by the large vocabulary size in the AURORA-4 task. To incorporate a priori knowledge of the background noise, we combine scalable Hidden Markov Models (HMMs) of the cepstral feature vectors of both clean speech and noise, using a Vector Taylor Series approximation in the power spectral domain. Then, a global MMSE-estimate of the clean speech is calculated based on this combined HMM. This technique is easily embeddable in the feature extraction module of a recogniser and is intrinsically suited for the removal of non-stationary additive noise. Our approach is validated on the AURORA-4 task, revealing a signiﬁcant gain in noise robustness over the baseline.
Inference with l 0-norm-based Sparsity Prior on Discrete Framework

We present a new penalizing scheme for a recently introduced prior model [8] on discrete frameworks. The model convincingly assumes that the optimal solutions for the frameworks possess sparse representation on certain transform domains, and applies this sparsity assumption as a prior information for inference problems. Promoting the sparsity, we proposes to penalize l0-norm of coefficient vector of the transform bases, instead of l1-norm employed in that recent work. Experiments compare the proposed prior with previous ones and show enhanced performance, both in qualitative and quantitative manner.
Cranberries and Cancer: An Update of Preclinical Studies Evaluating the Cancer Inhibitory Potential of Cranberry and Cranberry Derived Constituents

Cranberries are rich in bioactive constituents reported to influence a variety of health benefits, ranging from improved immune function and decreased infections to reduced cardiovascular disease and more recently cancer inhibition. A review of cranberry research targeting cancer revealed positive effects of cranberries or cranberry derived constituents against 17 different cancers utilizing a variety of in vitro techniques, whereas in vivo studies supported the inhibitory action of cranberries toward cancers of the esophagus, stomach, colon, bladder, prostate, glioblastoma and lymphoma. Mechanisms of cranberry-linked cancer inhibition include cellular death induction via apoptosis, necrosis and autophagy; reduction of cellular proliferation; alterations in reactive oxygen species; and modification of cytokine and signal transduction pathways. Given the emerging positive preclinical effects of cranberries, future clinical directions targeting cancer or premalignancy in high risk cohorts should be considered.
Scientific Collaboration in Research Networks: A Quantification Method by Using Gini Coefficient

In the scientific community, it is very common to try to create sound metrics for practically everything that can be measured. One of the current trends is to consider aspects from social networks for defining evaluation metrics. Following such a trend, our work proposes applying the Gini coefficient for evaluating research networks from two different perspectives. The first one analyzes the temporal evolution of research networks by considering the Gini coefficient of the distribution of researchers who have co-authored publications. The second one compares different internal collaboration networks of graduate programs and applies the Gini coefficient to support the ranking creation task. Both ideas are demonstrated through experiments that show the validity and applicability of our approach for quantifying scientific collaborations. Moreover, we also propose a new index that combines two metrics for evaluating the collaboration network of graduate programs. We believe that this index should be easily applied to other groups and research areas. This is the first time that the Gini coefficient is applied over social networks for evaluating research.
Self-Calibrating Cameras Using Semidefinite Programming

Novel methods are proposed for self-calibrating a pure-rotating camera using semidefinite programming (SDP). Key to the approach is the use of the positive-definiteness requirement for the dual image of the absolute conic (DIAC). The problem is couched within a convex optimization framework and convergence to the global optimum is guaranteed. Experiments on various data sets indicate that the proposed algorithms more reliably deliver accurate and meaningful results. This work points the way to an alternative and more general approach to self-calibration using the advantageous properties of SDP. Algorithms are also discussed for cameras undergoing general motion.
Specific Changes of Serum Proteins in Parkinson's Disease Patients

The aim of this study is to identify and validate protein change in the serum from PD patients. We used serum samples from 21 PD patients and 20 age-matched normal people as control to conduct a comparative proteomic study. We performed 2-DE and analyzed the differentially expressed protein spots by LC-MS/MS. In PD group 13 spots were shown to be differentially expressed compared to control group. They were identified as 6 proteins. Among these, 3 proteins were confirmed by Western blot analysis. It showed that the frequency of fibrinogen γ-chain (FGG) appeared 70% in PD, which could not be detected in control group. The protein of inter-alpha-trypsin inhibitor heavy chain H4 (ITI-H4) was found to exist two forms in serum. The full size (120 kDa) of the protein was increased and the fragmented ITI-H4 (35 kDa) was decreased in PD group. The ratio of full size ITI-H4 to fragmented ITI-H4 in PD patients was 3.85±0.29-fold higher than in control group. Furthermore, fragmented Apo A-IV (∼26 kDa) was mainly detected in control group, while it was rare to be found in PD group. Above findings might be useful for diagnosis of PD. When the expressions of FGG and 120 kDa ITI-H4 are increase, as well as ∼26 kDa Apo A-IV disappear would provide strong evidence for PD.
Named Entity Recognition from Scratch on Social Media

With the extensive amount of textual data flowing through social media platforms, the interest in Information Extraction (IE) on such textual data has increased. Named Entity Recognition (NER) is one of the basic problems of IE. State-of-the-art solutions for NER face an adaptation problem to informal texts from social media platforms. In this study, we addressed this generalization problem with the NLP from scratch idea that has been shown to be successful for several NLP tasks on formal text. Experimental results have shown that word embeddings can be successfully used for NER on informal text.
Telbivudine or lamivudine use in late pregnancy safely reduces perinatal transmission of hepatitis B virus in real-life practice

Little observational data exist describing telbivudine (LdT) or lamivudine (LAM) use in late pregnancy for preventing hepatitis B mother‐to‐child transmission (MTCT) in real‐world settings. During the period of January 2009 to March 2011, we enrolled hepatitis B e antigen–positive mothers with HBV DNA >6 log10 copies/mL in China. At gestation week 28, the mothers received LdT or LAM until postpartum week 4 or no treatment (NTx). The study endpoints were the safety of LdT/LAM use and MTCT rates. Of the 700 mothers enrolled, 648 (LdT/LAM/NTx = 252/51/345) completed the 52‐week study with 661 infants (LdT/LAM/NTx = 257/52/352). On treatment, viral rebound occurred in 1.6% of mothers, all resulting from medication noncompliance. There was no genotypic mutation detected. At delivery, significantly lower HBV DNA levels were noted in mothers who received LdT or LAM versus NTx. Alanine aminotransferase flares were observed in 17.1% of treated mothers versus 6.3% of untreated mothers (P < 0.001). At birth, hepatitis B surface antigen (HBsAg) was detected in 20% and 24% of newborns in the treated and NTx groups, respectively. At week 52, an intention‐to‐treat analysis indicated 2.2% (95% confidence [CI]: 0.6‐3.8) of HBsAg+ infants from the treated group versus 7.6% (95% CI: 4.9‐10.3) in the NTx group (P = 0.001) and no difference of HBsAg+ rate between infants in the LdT and LAM groups (1.9% vs. 3.7%; P = 0.758). On‐treatment analysis indicated 0% of HBsAg+ infants in the treated group versus 2.84% in the NTx group (P = 0.002). There were no differences for gestational age or infants' height, weight, Apgar scores, or birth defect rates between infants from the treated and untreated groups. Conclusions: LdT and LAM use in late pregnancy for highly viremic mothers was equally effective in reducing MTCT. The treatment was well tolerated with no safety concerns identified. (Hepatology 2014;60:468–476)
Reduce FFT memory reference for low power applications

Memory reference is one of the major courses of power consumption incurred in a microprocessor. In this paper, we propose two matrix transformation techniques to reduce the number of memory references in the FFT computation. With the first transformation, all the butterflies sharing the same twiddle factor will be clustered and computed together to eliminate redundant memory access to load twiddle factors. With the second transformation, all remaining (N − 1) butterflies involving the twiddle factor WN0 are computed using a register-based breadth-first tree traversal algorithm so that load/store operations of intermediate data arrays are minimized. The proposed two transformations together have led to a novel twiddle-factor-based FFT algorithm. The test results on the TI TMS320C62x digital signal processor show that, for a 32-point FFT, the new algorithm exhibits as much as 20% reduction in clock cycles and an average of 30% reduction in memory access than that of the conventional DIF FFT.