Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of beta Arg211 in the active site of human beta-hexosaminidase B.

Tay-Sachs or Sandhoff disease results from a deficiency of either the alpha- or the beta-subunits of beta-hexosaminidase A, respectively. These evolutionarily related subunits have been grouped with the "Family 20" glycosidases. Molecular modeling of human hexosaminidase has been carried out on the basis of the three-dimensional structure of a bacterial member of Family 20, Serratia marcescens chitobiase. The primary sequence identity between the two enzymes is only 26% and restricted to their active site regions; therefore, the validity of this model must be determined experimentally. Because human hexosaminidase cannot be functionally expressed in bacteria, characterization of mutagenized hexosaminidase must be carried out using eukaryotic cell expression systems that all produce endogenous hexosaminidase activity. Even small amounts of endogenous enzyme can interfere with accurate K(m) or V(max) determinations. We report the expression, purification, and characterization of a C-terminal His(6)-tag precursor form of hexosaminidase B that is 99.99% free of endogenous enzyme from the host cells. Control experiments are reported confirming that the kinetic parameters of the His(6)-tag precursor are the same as the untagged precursor, which in turn are identical to the mature isoenzyme. Using highly purified wild-type and Arg(211)Lys-substituted hexosaminidase B, we reexamine the role of Arg(211) in the active site. As we previously reported, this very conservative substitution nevertheless reduces k(cat) by 500-fold. However, the removal of all endogenous activity has now allowed us to detect a 10-fold increase in K(m) that was not apparent in our previous study. That this increase in K(m) reflects a decrease in the strength of substrate binding was confirmed by the inability of the mutant isozyme to efficiently bind an immobilized substrate analogue, i.e., a hexosaminidase affinity column. Thus, Arg(211) is involved in substrate binding, as predicted by the chitobiase model, as well as catalysis.
Nuclear receptors in regulation of biotransformation enzymes and drug transporters in the placental barrier

Abstract Over the past 20 years, the toxicological and protective roles of the placental barrier with respect to drug detoxification and transporter-controlled protection of the fetus have been intensively examined. Several cytochrome P450 enzymes are expressed in placental trophoblast at different stages of pregnancy, though only a few of these have functional activity to metabolize xenobiotics. Drug transporters such as P-glycoprotein/MDR1 or breast cancer resistance protein (BCRP) are highly expressed in the placenta, and their functional activities have been demonstrated in the placenta both in vitro and in vivo. In addition, several studies have reported on ligand-activated transcription factors and nuclear receptors referred to as “xenosensors” in the placenta. The xenosensors control transcriptional regulation of both xenobiotic-metabolizing enzymes and drug transporters in different organs. Their ligands include toxic compounds and environmental pollutants, drugs, as well as herbal, dietary or vitamin supplements. Nevertheless, it remains debatable whether the placental barrier adapts to toxic injuries coming either from maternal medication or environmental contamination and whether the placenta contains a mechanism to respond dynamically in protecting the developing fetus. In the present paper, we summarize current knowledge about the activity and expression of major ligand-activated transcriptional mechanisms involved in biotransformation enzymes and transporters regulation in human placenta. In particular, we highlight the emerging roles of aryl hydrocarbon (AHR), vitamin D (VDR), glucocorticoid (GR) and pregnane X (PXR) receptors in that regulation. We show that the placenta constitute a unique metabolizing organ with significant overlap of exogenous and endogenous compounds metabolism controlled by nuclear receptors.
ESPGHAN and ESPEN Guidelines Paediatric Parenteral Nutrition - Annex: List of Products

BACKGROUNDThese Guidelines for Paediatric Parenteral Nutrition have been developed as a mutual project of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN; www.espghan.org) and the European Society for Clinical Nutrition and Metabolism (ESPEN; www.espen.org). T
Interference-Aware Downlink Resource Management for OFDMA Femtocell Networks

Femtocell is an economical solution to provide high speed indoor communication instead of the conventional macro-cellular networks. Especially, OFDMA femtocell is considered in the next generation cellular network such as 3GPP LTE and mobile WiMAX system. Although the femtocell has great advantages to accommodate indoor users, interference management problem is a critical issue to operate femtocell network. Existing OFDMA resource management algorithms only consider optimizing system-centric metric, and cannot manage the co-channel interference. Moreover, it is hard to cooperate with other femtocells to control the interference, since the self-configurable characteristics of femtocell. This paper proposes a novel interference-aware resource allocation algorithm for OFDMA femtocell networks. The proposed algorithm allocates resources according to a new objective function which reflects the effect of interference, and the heuristic algorithm is also introduced to reduce the complexity of the original problem. The Monte-Carlo simulation is performed to evaluate the performance of the proposed algorithm compared to the existing solutions.
Canada: first public health school rejects tobacco funds.

In an unprecedented move in Canada, three faculties at the University of Alberta passed similar motions in a matter of weeks rejecting tobacco industry funding. One of these faculties was home to a researcher with a US$1.5 million grant by the US Smokeless Tobacco Company (UST). The chain of events leading to this action started inadvertently. Over a year ago, a physician in the department of psychiatry applied for federal research funding designated for tobacco control in special populations. A requirement of the granting body was the absence of tobacco funding in the home department, which could not be complied with due to the alleged presence of a tobacco industry consultant in …
¿Cómo motivar al adulto mayor durante su estimulación cognitiva con el uso de aplicaciones tecnológicas?

Resumen. Este estudio se realizó con el fin de conocer cómo motivar al adulto mayor durante la estimulación cognitiva con el uso de aplicaciones tecnológicas. Para esto fue necesario entrevistar a ocho participantes tanto adultos mayores como personas que están a punto de ingresar a la tercera edad. Se les realizaron preguntas sobre lo que les gusta hacer, cómo les gustaría que los premiaran, entre otras. Dichas entrevistas tuvieron una duración de 30 minutos aproximadamente. Para la evaluación fue necesario analizar cada entrevista y obtener los puntos importantes para poder llegar al prototipo final que consta de un mensaje motivador para el adulto mayor y una conexión con sus familiares felicitándolos por el logro obtenido.
An adaptive vocalic-phoneme learning model

The need of pronouncing specific vocalic phonemes correctly may arise when someone learns a foreign language or attends speech therapy sessions. A solution to this problem consists of using a computer-aided system that mirrors the phoneme learning process that presumably could show up on human learners, e.g. students and neurological patients. The proposed system is built up on a finite-state automata-based syntax-driven transducer and allows tracking any phonetic deviation by means of following specific state-and-transition pathways and updating percentage-based values on correct pronunciation for target phonemes. The employed adaptive pronunciation model makes use of a weight matrix to measure the degree of convergence/divergence in relation with the correct phoneme pronunciation. Thus, the inference mechanism can provide the human learner with appropriate phonetic-based pronunciation feedback as if it were a human teacher or therapist: it knows what has been learned and what must be learned. Consequently, both prediction of the human learner's pronunciation and a set of proposed words as didactic or therapeutic stimuli are delivered as well.
Diagnostic features of mild cellulitis phlegmon in patients with rheumatoid arthritis treated with tocilizumab: a report of two cases

Two cases of subcutaneous soft tissue infection in 30 RA patients treated with tocilizumab are reported. In both patients, local redness, swelling, and heat were observed around the affected site. WBC spikes and such local findings were suggested to be clinically useful for the early detection of low-grade subcutaneous infection in RA patients whose disease is tightly controlled with tocilizumab. Of note, the C-reactive protein (CRP) level and temperature lacked clinical utility for such detection.
Individual Differences Are More Than a Gene × Environment Interaction: The Role of Learning

Individual differences in behavior are understood generally as arising from an interaction between genes and environment, omitting a crucial component. The literature on animal and human learning suggests the need to posit principles of learning to explain our differences. One of the challenges for the advancement of the field has been to establish how general principles of learning can explain the almost infinite variation in behavior. We present a case that: (a) individual differences in behavior emerge, in part, from principles of learning; (b) associations provide a descriptive mechanism for understanding the contribution of experience to behavior; and (c) learning theories explain dissociable aspects of behavior. We use 4 examples from the field of learning to illustrate the importance of involving psychology, and associative theory in particular, in the analysis of individual differences, these are (a) fear learning; (b) behavior directed to cues for outcomes (i.e., sign- and goal- tracking); (c) stimulus learning related to attention; and (d) human causal learning.
Intermediates of recombination during mating type switching in Saccharomyces cerevisiae.

We have identified two novel intermediates of homothallic switching of the yeast mating type gene, from MATa to MAT alpha. Following HO endonuclease cleavage, 5′ to 3′ exonucleolytic digestion is observed distal to the HO cut, creating a 3′‐ended single‐stranded tail. This recision is more extensive in a rad52 strain unable to switch. Surprisingly, the proximal side of the HO cut is protected from degradation; this stabilization depends on the presence of the silent copy donor sequences. A second intermediate was identified by a quantitative application of the polymerase chain reaction (PCR). The Y alpha‐MAT distal covalent fragment of the switched product appears 30 min prior to the appearance of the MAT proximal Y alpha junction. No covalent joining of MAT distal to HML distal sequences is detected. We suggested that the MAT DNA distal to the HO cut invades the intact donor and is extended by DNA synthesis. This step is prevented in a rad52 strain. These intermediates are consistent with a model for MAT switching in which only the distal side of the HO cut is initially active in strand invasion and transfer of information from the donor.
Optimal cooperative placement of GMTI UAVs for ground target tracking

With the recent advent of moderate-cost unmanned (or uninhabited) aerial vehicles (UAV) and their success in surveillance, it is natural to consider the cooperative management of groups of UAVs. The problem considered in this paper is the optimization of the information obtained by a group of UAVs carrying out surveillance of several ground targets distributed over a large area. The UAVs are assumed to be equipped with ground moving target indicator (GMTI) radars, which measure the locations of moving ground targets as well as their radial velocities. In this research, the Fisher information, obtained from the information form of Riccati equation, is used in the objective function. Sensor survival probability and target detection probability for each target-sensor pair are also included in the objective function. The optimal sensor placement problem is solved by a combination of deterministic as well as randomized optimization. Simulation results on two different scenarios are presented for four different types of prior information.
FROM METABOLISM TO POLYMORPHISM IN BACTERIAL POPULATIONS: A THEORETICAL STUDY

Abstract Stable polymorphisms are commonly observed in experimental bacterial populations grown in homogeneous media. Evidence is accumulating that metabolic interactions might be the main mechanism underlying the emergence and maintenance of such polymorphisms. To date, however, attempts to model the evolution of bacterial polymorphism have not considered metabolism as a possible component of polymorphism maintenance. Here, we propose a simulation approach to model the evolution of selected polymorphisms in a bacterial population. Using recent knowledge of the relationship between bacterial fitness and metabolism, we build a simple metabolic model and test the effect of resource competition on polymorphism. Without making an a priori hypothesis on fitness functions, we show that stable polymorphic situations could be observed under high nutrient competition, and we propose a functional, metabolism-based explanation to the debated issue of polymorphism maintenance. Corresponding Editor: H. Ochman
Color image retrieval based on refined edge histograms

Color is an important visual feature of images. However, a major drawback of color histogram is that it will loss spatial information and lead to false retrieval. In this paper, we present a "Back"-shape regional division approach and combine with pyramid histogram of orientated gradients (PHOG) to extract image edge features, termed refined edge histogram (REH). Moreover, the REH descriptor is applied to color image retrieval. Experimental results show that the proposed EDH are suitable for color image retrieval and has higher precision and recall compared to other existing methods.
Management criteria for effective innovation

Analysis of two well documented innovations-the transistor in consumer electronics and the jet engine in subsonic aircraft-leads to criteria which discriminate between profitable and unprofitable new technologies. Technological criteria include constraints removed and added by the innovation, and its capacity to stand alone. Business criteria include changes in existing operations and requirements for new ones, and whether the innovation provides market expansion or lower price. Applied to potential new technologies, these criteria indicate plausibility for a computerized car and implausibility for a US supersonic transport.
The Differential Sensitivity of Acceptability Judgments to Processing Effects

THE DIFFERENTIAL SENSITIVITY OF ACCEPTABILITY JUDGMENTS TO PROCESSING EFFECTS Jon Sprouse University of California, Irvine Rooij, Robert van. 2003. Questioning to resolve decision problems. Linguistics and Philosophy 26:727–763. Sharvit, Yael. 2002. Embedded questions and ‘de dicto’ readings. Natural Language Semantics 10:97–123. Szabolcsi, Anna. 1997. Background notions in lattice theory and generalized quantifiers. In Ways of scope taking, ed. by Anna Szabolcsi, 1–29. Dordrecht: Kluwer.
Signatures of gamma ray bursts in neutrino telescopes.

We show that the detection of neutrinos from a typical {gamma} ray burst requires a kilometer-scale detector. We argue that large bursts should be visible with the neutrino telescopes under construction. We emphasize the three techniques by which neutrino telescopes can perform this search: by triggering on (i) bursts of muons from muon neutrinos, (ii) muons from air cascades initiated by high energy {gamma} rays and (iii) showers made by relatively low energy ({approx_equal}100 MeV) electron neutrinos. The timing of neutrino-photon coincidences may yield a measurement of the neutrino mass to order 10{sup {minus}4}{endash}10{sup {minus}5} eV. {copyright} {ital 1996 The American Physical Society. }
StgDomain—scalable parallel domain software components for particle‐in‐cell finite element methods

Computational models for geodynamics are becoming increasingly complex. The rise in complexity comes from an increasingly complex set of coupled, non‐linear equations as well as increasing problem scales, and attempts to encapsulate effects occurring across different time and length scales. Portability, reuse and scalability of code, and solvers in particular, are thus becoming increasingly important for the community. This paper analyses the scalability of fundamental and highly reused components within a suite of geodynamics codes that utilize the Particle‐In‐Cell Finite Element Method. The components demonstrate highly scalable domain‐decomposed meshes and particle swarms. Performance measures of processor counts, mesh and swarm sizes, and the size/number of state variables are provided, together with factors that can affect scalability (especially 3D decompositions). Copyright © 2009 John Wiley & Sons, Ltd.
Barriers and facilitators to electronic documentation in a rural hospital.

PURPOSE The purpose of the study was to explore nurses' perceptions of barriers and facilitators to adoption of an electronic health record (EHR) in a rural Midwestern hospital. DESIGN This study was a qualitative, descriptive design. The Staggers and Parks Nurse-Computer Interaction Framework was used to guide directed content analysis. METHODS Eleven registered nurses from oncology and medical-surgical units were interviewed using three semistructured interview questions. Predetermined codes and operational definitions were developed from the Staggers and Parks framework. Narrative data were analyzed by each member of the research team and group consensus on coding was reached through group discussions. FINDINGS Participants were able to identify computer-related, nurse-related, and contextual barriers and facilitators to implementation of EHR. In addition, two distinct patterns of perceptions and acceptance were identified. CONCLUSIONS The Staggers and Parks Nurse-Computer Interaction framework was found to be useful in identifying computer, nurse, and contextual characteristics that act as facilitators or barriers to adoption of an EHR system. Acceptance and use of an EHR are enhanced when barriers are managed and facilitators are supported. CLINICAL RELEVANCE Understanding and management of facilitators and barriers to EHR adoption may impact nurses' ability to provide and document nursing care.
Regresión del cuantil aplicada al modelo de redes neuronales artificiales. Una aproximación de la estructura CAVIAR para el mercado de valores colombiano

Existen diversas metodologias para calcular el valor en riesgo (VaR) que pretenden capturar principalmente el riesgo de mercado al que estan expuestas las instituciones financieras. Siendo el modelo de valor en riesgo condicional autorregresivo (CAViaR) de Engle y Manganelli (1999, 2001, 2004) una buena aproximacion empirica para la verdadera medida VaR, tanto para cubrir el riesgo como para el cumplimiento de la regulacion bancaria. Por consiguiente, el objetivo de este articulo es realizar una aproximacion al modelo CAViaR para el mercado de valores colombiano, empleando diferentes factores de riesgo macroeconomicos y financieros como los esbozados en Chernozhukov y Umantsev (2001); ademas, se busca establecer que regla empirica permite una mejor captura del comportamiento del indice general de la Bolsa de Valores de Colombia (IGBC).
Prevalence and penetrance of BRCA1 and BRCA2 gene mutations in unselected Ashkenazi Jewish women with breast cancer.

BACKGROUND Approximately 2.0%-2.5% of Ashkenazi Jewish women carry one of three founding mutations in the BRCA1 and BRCA2 genes, and each mutation is associated with a high lifetime risk of invasive breast cancer. We investigated the extent to which these three mutations contribute to breast cancer incidence in the Ashkenazi Jewish population. METHODS We ascertained 457 Jewish women with prevalent cases of breast cancer who were unselected for age or family history of the disease; 412 of these women were tested for the three founder mutations (case patients). Control subjects consisted of 360 non-Jewish women with breast cancer (control patients) and 380 healthy Jewish women with no history of cancer (control subjects). RESULTS Mutations were found in 48 (11.7%) of 412 Jewish case patients. Forty-six of 48 mutations occurred in women with early-onset breast cancer (<50 years) or a history of ovarian or early-onset breast cancer in a first-, second-, or third-degree relative. The estimated penetrance to age 70 years for breast cancer was 59.9% for the BRCA1 gene mutations and 28.3% for the BRCA2 gene mutation. Compared with Jewish control subjects, the relative risk (RR) of breast cancer for first-degree relatives of mutation carriers was 5.16 (95% confidence interval [CI] = 3.14-8. 48), but risk was also increased for relatives of noncarriers (RR = 1.66; 95% CI = 1.18-2.33). The RR of prostate cancer for first-degree relatives of Jewish case patients was 3.36 (95% CI = 1. 49-7.56). CONCLUSIONS Approximately 12% of breast cancers in the Ashkenazi Jewish population are attributable to mutations in the BRCA1 or BRCA2 gene. Genetic testing may be useful when Jewish women with breast cancer are diagnosed before age 50 years or have a close relative with ovarian or early-onset breast cancer. An association between breast and prostate cancers was observed in our study population.
GS28, a 28-Kilodalton Golgi SNARE That Participates in ER-Golgi Transport

Little is known about the integral membrane proteins that participate in the early secretory pathway of mammalian cells. The complementary DNA encoding a 28-kilodalton protein (p28) of the cis-Golgi was cloned and sequenced. The protein was predicted to contain a central coiled-coil domain with a carboxyl-terminal membrane anchor. An in vitro assay for endoplasmic reticulum-Golgi transport was used to show that p28 participates in the docking and fusion stage of this transport event. Biochemical studies established that p28 is a core component of the Golgi SNAP receptor (SNARE) complex.
Helicobacter pylori infection in perforated peptic ulcer disease

recurrence may reflect surgical implantation from the extrarectal margin or from intraluminal tumour cells',*. With the aim of reducing surgical implantation, we have used high-dose-rate intraluminal brachytherapy (HDRIBT) before operation since 19863. We have not experienced any local recurrence suggestive of surgical implantation in 57 patients who received HDRIBT before rectal resection and coloanal anastomosis.