Miracle-dz/UniFAR-FTUs huggingface dataset:
Activation of ERK, JNK, Akt, and G‐protein coupled signaling by hybrid angiotensin II AT1/bradykinin B2 receptors expressed in HEK‐293 cells

Bradykinin (BK) and angiotensin II (AngII) often have opposite roles in cardiovascular diseases. Our aim here was to construct hybrid receptors which bind AngII but signal as BK. Various sequences of the intracellular face of the AngII type I receptor, AT1R, were replaced with corresponding sequences from the bradykinin B2 receptor (BKB2R). The hybrids demonstrated a number of signaling characteristics of the BKB2R. For example, the hybrids demonstrated BK as opposed to AngII like phosphorylation of Akt and JNK. The hybrids containing the BKB2R intracellular loop 2 (IC2) displayed minimal G‐protein, Gαi/Gαq, linked signaling. Computer based molecular models suggested that Ser‐Met‐Gly from the IC2 of the BKB2R is detrimental for the Gαi/Gαq coupled functions of this hybrid. The return of Lys‐Ser‐Arg of the AT1R to this hybrid led to almost full recovery of Gαi and Gαq activation. The design and production of AT1/BKB2 hybrid receptors is a potential approach in the treatment of hypertension related diseases where the presence of AngII, its AT1 receptor and the consequent signal transduction has proven detrimental. J. Cell. Biochem. 101: 192–204, 2007. © 2007 Wiley‐Liss, Inc.
Resistance to store depletion-induced endothelial injury in rat lung after chronic heart failure.

RATIONALE In chronic heart failure, the lung endothelial permeability response to angiotensin II or thapsigargin-induced store depletion is ablated, although the mechanisms are not understood. OBJECTIVES To determine whether the ablated permeability response to store depletion during heart failure was due to impaired expression of store operated Ca2+ channels in lung endothelium. METHODS Heart failure was induced by aortocaval fistula in rats. Permeability was measured in isolated lungs using the filtration coefficient and a low Ca2+/Ca2+ add-back strategy to identify the component of the permeability response dependent on Ca2+ entry. MAIN RESULTS In fistulas, right ventricular mass and left ventricular end diastolic pressure were increased and left ventricular shortening fraction decreased compared with shams. Thapsigargin-induced store depletion increased lung endothelial permeability in shams, but not in fistulas. Permeability increased in both groups after the Ca2+ ionophore A23187 or 14,15-epoxyeicosatrienoic acid, independent of store depletion. A diacylglycerol analog had no impact on permeability. Increased distance between the endoplasmic reticulum and the plasmalemmal membrane was ruled out as a mechanism for the loss of the permeability response to store depletion. Endothelial expression of the endoplasmic reticulum Ca2+ ATPase was not altered in fistulas compared with shams, whereas the store-operated canonical transient receptor potential channels 1, 3, and 4 were downregulated in extraalveolar vessel endothelium. CONCLUSIONS We conclude that the adaptive mechanism limiting store depletion-induced endothelial lung injury in the aortocaval model of heart failure involves downregulation of store-operated Ca2+ channels.
Small Geographic Area Variations in Prescription Drug Use

BACKGROUND: Despite the frequency of pediatric prescribing little is known about practice differences across small geographic regions and payer type (Medicaid and commercial). OBJECTIVE: The goal of this research was to quantify variation in prescription drug use among northern New England children. METHODS: Northern New England, all-payer administrative data (2007–2010) permitted study of prescriptions for 949 821 children ages 0 to 17 years (1.75 million person-years [PYs]; 54% Medicaid, 46% commercial). Age- and gender adjusted overall and drug group–specific prescription use was quantified according to payer type (Medicaid or commercial) and within payer type across 69 hospital service areas (HSAs). We measured prescription fills per PY (rate) and annual, mean percentage of the population with any drug group–specific fills (prevalence). RESULTS: Overall mean annual prescriptions per PY were 3.4 (commercial) and 5.5 (Medicaid). Generally, these payer type differences were smaller than HSA-level variation within payer type. HSA-level rates of attention-deficit/hyperactivity disorder drug use (5th–95th percentile) varied twofold in Medicaid and more than twofold in commercially insured children; HSA-level antidepressant use varied more than twofold within each payer type. Antacid use varied threefold across HSAs and was highest in infants where commercial use paradoxically exceeded Medicaid. Prevalence of drug use varied as much as rates across HSAs. CONCLUSIONS: Prescription use was higher among Medicaid-insured than commercially insured children. Regional variation generally exceeded payer type differences, especially for drugs used in situations of diagnostic and therapeutic uncertainty. Efforts should advance best pediatric prescribing discussions and shared decision-making.
The Application Of Hidden Markov Models to Protein Secondary Structure Prediction

The functional properties of proteins depend upon their 3D structures, therefore, it is advantageous to deduce the 3D structure of a protein from its amino acid sequence. This is a difficult task because there are 20 different amino acids that can be combined into “many more different proteins than there are atoms in the known universe” [2]. De novo prediction methods often involve a first step of protein secondary structure prediction. The focus of this thesis is on the application of Hidden Markov Models to the prediction of the three classes of secondary structures: helices, strands and coils. A 3-State and 21-State model have been constructed to illustrate the potential, and difficulties these models have in the area of secondary structure prediction.
Imatinib prevents beta cell death in vitro but does not improve islet transplantation outcome

Abstract Introduction Improving islet transplantation outcome could not only bring benefits to individual patients but also widen the patient pool to which this life-changing treatment is available. Imatinib has previously been shown to protect beta cells from apoptosis in a variety of in vitro and in vivo models. The aim of this study was to investigate whether imatinib could be used to improve islet transplantation outcome. Methods Islets were isolated from C57Bl/6 mice and pre-cultured with imatinib prior to exposure to streptozotocin and cytokines in vitro. Cell viability and glucose-induced insulin secretion were measured. For transplantation experiments, islets were pre-cultured with imatinib for either 72 h or 24 h prior to transplantation into streptozotocin-diabetic C57Bl/6 mice. In one experimental series mice were also administered imatinib after islet transplantation. Results Imatinib partially protected islets from beta cell death in vitro. However, pre-culturing islets in imatinib or administering the drug to the mice in the days following islet transplantation did not improve blood glucose concentrations more than control-cultured islets. Conclusion Although imatinib protected against beta cell death from cytokines and streptozotocin in vitro, it did not significantly improve syngeneic islet transplantation outcome.
Medication information extraction with linguistic pattern matching and semantic rules

OBJECTIVE This study presents a system developed for the 2009 i2b2 Challenge in Natural Language Processing for Clinical Data, whose aim was to automatically extract certain information about medications used by a patient from his/her medical report. The aim was to extract the following information for each medication: name, dosage, mode/route, frequency, duration and reason. DESIGN The system implements a rule-based methodology, which exploits typical morphological, lexical, syntactic and semantic features of the targeted information. These features were acquired from the training dataset and public resources such as the UMLS and relevant web pages. Information extracted by pattern matching was combined together using context-sensitive heuristic rules. MEASUREMENTS The system was applied to a set of 547 previously unseen discharge summaries, and the extracted information was evaluated against a manually prepared gold standard consisting of 251 documents. The overall ranking of the participating teams was obtained using the micro-averaged F-measure as the primary evaluation metric. RESULTS The implemented method achieved the micro-averaged F-measure of 81% (with 86% precision and 77% recall), which ranked this system third in the challenge. The significance tests revealed the system's performance to be not significantly different from that of the second ranked system. Relative to other systems, this system achieved the best F-measure for the extraction of duration (53%) and reason (46%). CONCLUSION Based on the F-measure, the performance achieved (81%) was in line with the initial agreement between human annotators (82%), indicating that such a system may greatly facilitate the process of extracting relevant information from medical records by providing a solid basis for a manual review process.
Reaserchnig the Development of the Electrical Power System Using Systemically Evolutionary Algorithm

The paper contains the concept and the results of research concerning the evolutionary algorithm, identified based on the systems control theory, which was called the Systemically of Evolutionary Algorithm (SAE). Special attention was paid to two elements of evolutionary algorithms, which have not been fully solved yet, i.e. to the methods used to create the initial population and the method of creating the robustness (fitness) function. Other elements of the SEA algorithm, i.a. cross-over, mutation, selection, etc. were also defined from a systemic point of view. Computational experiments were conducted using a selected subsystem of the Polish Electrical Power System and three programming languages: Java, C++ and Matlab. Selected comparative results for the SAE algorithm in different implementations were also presented.
Speech Production as State Feedback Control

Spoken language exists because of a remarkable neural process. Inside a speaker's brain, an intended message gives rise to neural signals activating the muscles of the vocal tract. The process is remarkable because these muscles are activated in just the right way that the vocal tract produces sounds a listener understands as the intended message. What is the best approach to understanding the neural substrate of this crucial motor control process? One of the key recent modeling developments in neuroscience has been the use of state feedback control (SFC) theory to explain the role of the CNS in motor control. SFC postulates that the CNS controls motor output by (1) estimating the current dynamic state of the thing (e.g., arm) being controlled, and (2) generating controls based on this estimated state. SFC has successfully predicted a great range of non-speech motor phenomena, but as yet has not received attention in the speech motor control community. Here, we review some of the key characteristics of speech motor control and what they say about the role of the CNS in the process. We then discuss prior efforts to model the role of CNS in speech motor control, and argue that these models have inherent limitations – limitations that are overcome by an SFC model of speech motor control which we describe. We conclude by discussing a plausible neural substrate of our model.
Relative information completeness

The paper investigates the question of whether a partially closed database has complete information to answer a query. In practice an enterprise often maintains master data Dm, a closed-world database. We say that a database D is partially closed if it satisfies a set V of containment constraints of the form "q(D) is a subset of p(Dm)", where q is a query in a language Lc and p is a projection query. The part of D not constrained by (Dm,V) is open, from which some tuples may be missing. The database D is said to be complete for a query Q relative to (Dm,V) if for all partially closed extensions D' of D, Q(D')=Q(D), i.e., adding tuples to D either violates some constraints in V or does not change the answer to Q. We first show that the proposed model can also capture the consistency of data, in addition to its relative completeness. Indeed, integrity constraints studied for consistency can be expressed as containment constraints. We then study two problems. One is to decide, given Dm, V, a query Q in a language Lq and a partially closed database D, whether D is complete for Q relative to (Dm,V). The other is to determine, given Dm, V and Q, whether there exists a partially closed database that is complete for Q relative to (Dm,V). We establish matching lower and upper bounds on these problems for a variety of languages Lq and Lc. We also provide characterizations for a database to be relatively complete, and for a query to allow a relatively complete database, when Lq and Lc are conjunctive queries.
Prevalence of celiac disease among blood donors in Brazil

OBJECTIVE:There are no studies on the prevalence of celiac disease (CD) in either Brazil or, as far as we know, South America. The aim of this study was to determine the prevalence of CD in healthy blood donors in the city of Brasilia, Brazil.METHODS:Sera were obtained, independently of age and gender, from an unselected group of 2045 blood donors attending the Hematological Center of Brasilia. An IgG antigliadin antibody (AGA) test was used as a first-level screening step, followed by IgA-AGA test, serum IgA antiendomysium (EMA), and total serum IgA determination performed in all sera showing abnormally high IgG-AGA results. Jejunal biopsy was suggested for all subjects showing at least one of the following: IgA-EMA positivity; IgG-AGA and IgA-AGA positivity; IgG-AGA positivity and selective IgA deficiency. AGA was determined by an enzyme-linked immunosorbent assay (ELISA) technique and IgA-EMA was ascertained by indirect immunofluorescence on cryostat sections of monkey esophagus. Jejunal mucosa samples were obtained with a Watson capsule.RESULTS:Sixty-two (3.03%) blood donors had IgG-AGA above the cut-off values. Fifty-eight individuals showed isolated high values of IgG-AGA, whereas four had simultaneously increased IgG and IgA-AGA. Three patients had positive IgA-EMA test (one with both IgG- and IgA-AGA and two with only IgG-AGA) and underwent jejunal biopsies that disclosed complete villous atrophy associated with an increased number of intraepithelial lymphocytes and hypertrophic criptae. In this study group, the prevalence of biopsy-proven celiac disease was 1.47 ± 1.66 in 1000 subjects.CONCLUSIONS:We found a prevalence of undiagnosed CD of 1:681 among apparently healthy blood donors. These preliminary results support the view that CD is not a rare disease in Brazil.
THE HUMAN BLOOD INDEX OF MALARIA VECTORS IN RELATION TO EPIDEMIOLOGICAL ASSESSMENT.

The human blood index, or estimated proportion of the blood meals of a mosquito population obtained from man, is provisionally assessed for certain anophelines from blood-meal samples collected during the period 1959-62 and subjected to precipitin testing at the Lister Institute. In malaria eradication programmes this index is relevant to epidemiological assessment and to the modification of measures to interrupt transmission, since a mosquito's vectorial capacity and the malaria reproduction rate both vary as the square of the human blood index.There are serious difficulties in achieving representative sampling for this index and in interpreting the index obtained. These are discussed in some detail. In practice, the human blood index is often best estimated by applying the unweighted mean of a part-sample collected from human dwellings and one from other types of resting-place.Applying this calculation to the samples under review, it appears that DDT exerts a moderate, and dieldrin a more pronounced, impact on the human blood index of Anopheles gambiae and A. funestus; such an effect, indeed, may be general in house-visiting anophelines. Some 18 anopheline species are tentatively graded as having low, medium or high natural human blood indices. Regular and careful sampling, combined with recording of all relevant information, is recommended in view of the epidemiological and operational importance of the human blood index in assessment of eradication programmes.
Mouse T cell repertoires as statistical ensembles : overall characterization and age dependence

Zachary Sethna, ∗ Yuval Elhanati, ∗ Crissy S. Dudgeon, Curtis G. Callan Jr., Arnold Levine, Thierry Mora, and Aleksandra M. Walczak Joseph Henry Laboratories, Princeton University, Princeton, New Jersey 08544 USA Laboratoire de physique théorique, UMR8549, CNRS and École normale supérieure, 24, rue Lhomond, 75005 Paris, France Cancer Institute of New Jersey, New Brunswick, New Jersey 08903 USA Institute for Advanced Study, Princeton New Jersey 08540 USA Laboratoire de physique statistique, UMR8550, CNRS and École normale supérieure, 24, rue Lhomond, 75005 Paris, France (Dated: November 9, 2016)
HBx Down-Regulated Gld2 Plays a Critical Role in HBV-Related Dysregulation of miR-122

miR-122 is a liver-rich-specific microRNA that plays an important role in hepatic gene expression via post-transcription regulation, and it is potentially associated with the development of hepatocellular carcinoma. It has been confirmed that miR-122 is down-regulated during HBV infection; however, how HBV affects miR-122 is still debated. One research provided evidence that HBx could reduce the miR-122 transcription level, but the other insisted that HBV had no significant effect on miR-122 transcription level but reduce miR-122 level via binding and sequestering endogenous miR-122. It is determinate that Gld2 could increase the specific miRNA stabilization by monoadenylation which was a post-transcription regulation. In this study, we aimed to investigate the mechanism of HBV-induced reduction of miR-122 and examine whether Gld2 is involved in it. According to the results of a microRNA microarray, we found miR-122 was the most down-regulated microRNA in HepG2.2. 15 compared to HepG2. As revealed by qRT-PCR and western blotting analyses, both miR-122 and Gld2 levels were reduced in hepatic cell lines with expression of HBV or HBx but not other proteins of HBV, and over-expression of Gld2 could abolish the effect of HBV and HBx on the miR-122 level. What's more, both HBV and HBx have no significant effect on pre-miR-122 levels. And the dual-luciferase assay implicated that HBx could reduce the Gld2 promoter activity but had no significant effect on miR-122 promoter activity. In conclusion, HBx is a critical protein derived from HBV, which regulates miR-122 via down-regulating Gld2.
Statistical timing analysis considering spatial correlations using a single PERT-like traversal

We present an efficient statistical timing analysis algorithm that predicts the probability distribution of the circuit delay while incorporating the effects of spatial correlations of intra-die parameter variations, using a method based on principal component analysis. The method uses a PERT-like circuit graph traversal, and has a run-time that is linear in the number of gates and interconnects, as well as the number of grid partitions used to model spatial correlations. On average, the mean and standard deviation values computed by our method have errors of 0.2% and 0.9%, respectively, in comparison with a Monte Carlo simulation.
Role model based framework design and integration

Today, any large object-oriented software system is built using frameworks. Yet, designing frameworks and defining their interaction with clients remains a difficult task. A primary reason is that today's dominant modeling concept, the class, is not well suited to describe the complexity of object collaborations as it emerges in framework design and integration. We use role modeling to overcome the problems and limitations of class-based modeling. Using role models, the design of a framework and its use by clients can be described succinctly and with much better separation of concerns than with classes. Using role objects, frameworks can be integrated into use-contexts that have not been foreseen by their original designers.
From molecular to genomic epidemiology: transforming surveillance and control of infectious diseases.

The use of increasingly powerful genotyping tools for the characterisation of pathogens has become a standard component of infectious disease surveillance and outbreak investigations. This thematic issue of Eurosurveillance, published in two parts, provides a series of review and original research articles that gauge progress in molecular epidemiology strategies and tools, and illustrate their applications in public health. Molecular epidemiology of infectious diseases combines traditional epidemiological methods with analysis of genome polymorphisms of pathogens over time, place and person across human populations and relevant reservoirs, to study host–pathogen interactions and infer hypotheses about host-to-host or source-to-host transmission [1-3]. Based on discriminant genotyping of human pathogens, clonally derived strains can be identified as likely links in a chain of transmission [1-3]. In this two-part issue of Eurosurveillance, Goering et al. explain that such biological evidence of clonal linkage complements but does not replace epidemiological evidence of personto-person contact or common exposure to a potential source [3]. Muellner et al. provide clear examples how prediction about infectious disease outcome and transmission risks can be enhanced through integration of pathogen genetic information and epidemiological modelling to inform public health decisions about food-borne disease prevention [4].
Association of X-Ray Repair Cross-Complementing Group 1 Arg194Trp, Arg399Gln and Arg280His Polymorphisms with Head and Neck Cancer Susceptibility: A Meta-Analysis

Background Previous studies on the association of X-ray repair cross-complementing group 1 (XRCC1) Arg194Trp, Arg399Gln, and Arg280His polymorphisms with head and neck cancer (HNC) have produced inconsistent results. The aim of the present study was to evaluate the effects of these three polymorphic variants on HNC risk. Methods The PubMed and EMBASE databases were searched for genetic association studies on the XRCC1 Arg194Trp, Arg399Gln, and Arg280His polymorphisms and HNC risk. (The most recent search was conducted on 20 August, 2013.) Twenty-six studies were identified and meta-analysis was performed to evaluate the association between the polymorphism and HNC by calculating combined odds ratios and 95% confidence intervals. Results No significant association was found under the allelic, homozygous, heterozygote, and dominant genetic models in the overall comparison. Further, no significant association between the XRCC1 Arg399Gln and Arg280His polymorphisms and HNC risk was detected under the four genetic models in subgroup analyses based on ethnicity, cancer site, and whether or not the studies had been adjusted for cigarette smoking and alcohol. However, in stratified analyses based on cancer site, a significant association was found between the XRCC1 Arg194Trp polymorphism and oral cancer under the allelic, heterozygote, and dominant models. The XRCC1 Arg194Trp polymorphism was significantly associated with HNC risk in studies that were adjusted for smoking and alcohol under the homozygous and heterozygote models. Conclusion The meta-analysis results suggest that the XRCC1 Arg399Gln and Arg280His polymorphisms are probably not associated with the risk of HNC, but the XRCC1 Arg194Trp polymorphism was associated with increased risk of HNC in the subgroup analysis of studies adjusted for smoking and alcohol and with increased risk of oral cancer in the stratified analyses based on cancer site. Further studies with larger samples are needed to confirm these findings.