Miracle-dz/UniFAR-FTUs huggingface dataset:
The membrane (M1) protein of influenza virus occurs in two forms and is a phosphoprotein

The membrane (M1) protein of influenza virus was found to be heterogenous and to occur in two forms in the virus particle. The two forms of M1 were found in virus which was produced both early and late after infection and in infected cells. The two forms could be separated on polyacrylamide gels under specific conditions. The two components of M1 contained similar tryptic peptides. However, a small proteolytic difference between the two proteins could not be ruled out. Both M1 proteins were present in phosphorylated form in the virus particle. The phosphorylated M1 components were not readily distinguished from phosphorylated nonstructural protein (NS1) when cytoplasm of infected cells was analyzed on polyacrylamide gels. The two phosphorylated M1 components could, however, be detected in infected cells by immunoprecipitation. One M1 component contained only phosphoserine whereas the second contained phosphoserine and a small amount of phosphothreonine as well. In addition to the phosphorylated nucleoprotein and M1, a third phosphorylated protein was routinely detected in virus particles. It was a surface component of the virus, since it could be removed from whole virus with chymotrypsin and contained phosphate at serine residues. The identity of this component was not known.
Assessment of the Impact of Aggregated Economic Factors on Optimal Consumption in Models of Economic Growth

The problem of consumption-optimal economic growth is considered. In the model there are three factors of production: capital, labor and useful work, that interact in the production of homogenous output. At any instant of time a fraction of this homogeneous output can be allocated to investment in accumulation of capital and useful work. The gross domestic product (GDP) of a country is presented by the linear-exponential (LINEX) production function. The general goals of the research can be formulated as follows: -analysis of properties of the LINEX production function and identification of parameters under restrictions on elasticity coefficients; -analysis of the Hamiltonian system of differential equations for the Pontryagin maximum principle in the optimal control problem; -elaboration of an algorithm for constructing synthetic trajectories of optimal economic growth; -development of software for numerical simulation and sensitivity analysis; -comparison of real and synthetic trajectories of economic growth, and simulation of future scenarios.
Characterization of the In Vivo Dynamics of Medullary CD4+CD8− Thymocyte Development1

Our previous studies have defined a differentiation program followed by the newly generated single-positive (SP) thymocytes before their emigration to the periphery. In the present study, we further characterize the development of CD4SP cells in the thymic medulla using mainly intrathymic adoptive transfer assays. By analyzing the differentiation kinetics of the donor cells, which were shown to home correctly to the medullary region following adoptive transfer, we established the precursor–progeny relationship among the four subsets of CD4SP thymocytes (SP1–SP4) and demonstrated that the progression from SP1 to SP4 was unidirectional and largely synchronized. Notably, while the phenotypic maturation from SP1 to SP4 was achieved in 2–3 days, a small fraction of donor cells could be retained in the thymus for a longer period, during which they further matured in function. BrdU incorporation indicated that cell expansion occurred at multiple stages except SP1. Nevertheless, CFSE labeling revealed that only a limited number of cells actually divided during their stay in the medulla. As to the thymic emigration, there was a clear bias toward cells with increasing maturity, but no distinction was found between dividing and nondividing thymocytes. Collectively, these data not only provide solid evidence for a highly ordered differentiation program for CD4SP thymocytes, but they also illustrate several important features associated with the developmental process.
OBESITY AND ASSOCIATED RISK OF CORONARY ARTERY DISEASE AMONG PATIENTS OF PRIMARY HEALTH CARE CENTERS IN ABHA, SAUDI ARABIA

Objective: To estimate the magnitude of obesity and its relation to the 10 year probability of developing coronary artery disease (CAD) in patients attending primary health care centers (PHCCs) in Abha, southern Saudi Arabia. Subjects and Methods: Saudi patients aged between 30-70 years who had attended three PHCCs in Abha city over a 6-month period (January to June 1998) and agreed to participate in the study were enrolled. All such patients had their weights and heights measured, body mass index (BMI) was calculated and they were screened for risk factors of CAD and requested to provide a fasting venous sample for lipoprotein analysis. The probability of developing coronary artery disease (PCAD) over the next ten years was calculated for each patient by means of the computer model based on Framingham heart study.2 Results: A total of 858 subjects were studied: 46% males and 54% females. The percentage of obesity was 49% and overweight 35%; Females were dominantly obese while overweight was more prevalent in males. Of the study subjects 11.5% were hypertensive with significantly higher BMI than normotensives (P=<0.001); diabetes mellitus was represented in 29.6% with no significant difference in their BMI from nondiabetics. Smokers were 4.2% and they had a significantly lower BMI than non-smokers. Individuals with high-risk threshold of TC/HDL-c ratio (≥ 5.6% for women and ≥ 6.4% for men) represented 70.48% and had significantly higher BMI than those with low risk threshold. There was no direct relationship between BMI and PCAD10 (r2=0.007, p<0.12). Conclusion: (1) Obesity is an epidemic health problem with an expected upward trend in Saudi Arabia similar to that of LISA and Western Europe. (2) The risk factors for CAD were highly prevalent among the PHCC patients and had a strong significant association with obesity; thus weight control should be an integral part of the prevention of CAD at PHCCs level. (3) Although obesity was found to have a significant individual association with CAD risk factors, obesity per se had no significant direct relationship with the probability of CAD at 10 years. This confirms the conclusion reached by NCEP 11 that obesity caused CAD through the associated risk factors.
Cross-Racial Trust Factors: Exploring the Experiences of Blacks Who Have Had White Mentors in the Counseling Profession

CROSS-RACIAL TRUST FACTORS: EXPLORING THE EXPERIENCES OF BLACKS WHO HAVE HAD WHITE MENTORS THEY TRUST IN THE COUNSELING PROFESSION Eric M. Brown Old Dominion University, 2016 Director: Dr. Tim Grothaus The primary researcher conducted a phenomenological study on cross-racial trust factors between Black doctoral students (n = 10) and their White mentors within the counseling profession. Three participants identified having a White professor as a mentor; two participants identified having White supervisors as mentors; five of the participants reported having both faculty members and supervisors as White mentors. Through semi-structured interviews, the primary researcher sought to ascertain what factors engendered cross-racial trust between Black doctoral students and White mentors within the counseling profession. The research team identified four superordinate themes related to cross-racial trust: contributors to trust, reasons for mistrust, critical consciousness, and benefits of cross-racial mentoring. In addition, the research team identified 22 themes and 22 subthemes through consensual coding of the data. The findings of this study may inform multicultural competence and practice in mentoring and supervision within counselor education.
Surgeons’ aims and pain assessment strategies when managing paediatric post-operative pain

Children experience moderate to severe pain post-operatively. Nurses have been found to have a variety of aims in this context. Surgeons’ aims when managing post-operative pain have not been explored. This qualitative study set out to explore paediatric surgeons’ aims when managing post-operative pain in one paediatric hospital in Canada. Consultant surgeons (n = 8) across various specialities took part in semi-structured interviews. Surgeons’ overarching aim was to keep the child comfortable. Various definitions of comfortable were given, relating to the child’s experience of pain itself and their ability to undertake activities of daily living. Children’s behavioural pain cues seem to be a primary consideration when making treatment decisions. Parents’ views regarding their child’s pain were also seen as important, suggesting children may not be seen as competent to make decisions on their own behalf. The need to maintain a realistic approach was emphasised and pain management described as a balancing act. Surgeons may draw on both tacit and explicit knowledge when assessing children’s pain. There appears to be an expectation among surgeons that some pain is to be expected post-operatively and that the diagnostic value of pain may, in some cases, supersede concerns for the child’s pain experience.
Calsequestrin 2 deletion causes sinoatrial node dysfunction and atrial arrhythmias associated with altered sarcoplasmic reticulum calcium cycling and degenerative fibrosis within the mouse atrial pacemaker complex1.

AIMS Loss-of-function mutations in Calsequestrin 2 (CASQ2) are associated with catecholaminergic polymorphic ventricular tachycardia (CPVT). CPVT patients also exhibit bradycardia and atrial arrhythmias for which the underlying mechanism remains unknown. We aimed to study the sinoatrial node (SAN) dysfunction due to loss of CASQ2. METHODS AND RESULTS In vivo electrocardiogram (ECG) monitoring, in vitro high-resolution optical mapping, confocal imaging of intracellular Ca(2+) cycling, and 3D atrial immunohistology were performed in wild-type (WT) and Casq2 null (Casq2(-/-)) mice. Casq2(-/-) mice exhibited bradycardia, SAN conduction abnormalities, and beat-to-beat heart rate variability due to enhanced atrial ectopic activity both at baseline and with autonomic stimulation. Loss of CASQ2 increased fibrosis within the pacemaker complex, depressed primary SAN activity, and conduction, but enhanced atrial ectopic activity and atrial fibrillation (AF) associated with macro- and micro-reentry during autonomic stimulation. In SAN myocytes, CASQ2 deficiency induced perturbations in intracellular Ca(2+) cycling, including abnormal Ca(2+) release, periods of significantly elevated diastolic Ca(2+) levels leading to pauses and unstable pacemaker rate. Importantly, Ca(2+) cycling dysfunction occurred not only at the SAN cellular level but was also globally manifested as an increased delay between action potential (AP) and Ca(2+) transient upstrokes throughout the atrial pacemaker complex. CONCLUSIONS Loss of CASQ2 causes abnormal sarcoplasmic reticulum Ca(2+) release and selective interstitial fibrosis in the atrial pacemaker complex, which disrupt SAN pacemaking but enhance latent pacemaker activity, create conduction abnormalities and increase susceptibility to AF. These functional and extensive structural alterations could contribute to SAN dysfunction as well as AF in CPVT patients.
A Simulator Study Comparing Characteristics of Manual and Automated Driving During Lane Changes of Long Combination Vehicles

This paper presents a back-to-back performance comparison of lane-change maneuvers using two automated driving approaches and manual driving. The lane changes were conducted in a moving-base truck driving simulator using an A-double long combination vehicle. One of the automated driving approaches was based on driver model control and the other used optimization-based control. The comparison addresses lane change and braking, both initiation and execution, from the perspective of driver behavior and defined characteristic variables. We also discuss combined braking and steering behavior using a moderately safety-critical lane-change scenario. The purpose of this paper is to improve driving automation in early development by comparing and learning from professional truck drivers to enable higher driver acceptance.
Identification of I137M and Other Mutations That Modulate Incubation Periods for Two Human Prion Strains

ABSTRACT We report here the transmission of human prions to 18 new transgenic (Tg) mouse lines expressing 8 unique chimeric human/mouse prion proteins (PrP). Extracts from brains of two patients, who died of sporadic Creutzfeldt-Jakob disease (sCJD), contained either sCJD(MM1) or sCJD(VV2) prion strains and were used for inocula. Mice expressing chimeric PrP showed a direct correlation between expression level and incubation period for sCJD(MM1) prions irrespective of whether the transgene encoded methionine (M) or valine (V) at polymorphic residue 129. Tg mice expressing chimeric transgenes encoding V129 were unexpectedly resistant to infection with sCJD(VV2) prions, and when transmission did occur, it was accompanied by a change in strain type. The transmission of sCJD(MM1) prions was modulated by single amino acid reversions of each human PrP residue in the chimeric sequence. Reverting human residue 137 in the chimeric transgene from I to M prolonged the incubation time for sCJD(MM1) prions by more than 100 days; structural analyses suggest a profound change in the orientation of amino acid side chains with the I→M mutation. These findings argue that changing the surface charge in this region of PrP greatly altered the interaction between PrP isoforms during prion replication. Our studies contend that strain-specified replication of prions is modulated by PrP sequence-specific interactions between the prion precursor PrPC and the infectious product PrPSc.
Sequential binding of SeqA protein to nascent DNA segments at replication forks in synchronized cultures of Escherichia coli

To demonstrate that sequestration A (SeqA) protein binds preferentially to hemimethylated GATC sequences at replication forks and forms clusters in Escherichia coli growing cells, we analysed, by the chromatin immunoprecipitation (ChIP) assay using anti‐SeqA antibody, a synchronized culture of a temperature‐sensitive dnaC mutant strain in which only one round of chromosomal DNA replication was synchronously initiated. After synchronized initiation of chromosome replication, the replication origin oriC was first detected by the ChIP assay, and other six chromosomal regions having multiple GATC sequences were sequentially detected according to bidirectional replication of the chromosome. In contrast, DNA regions lacking the GATC sequence were not detected by the ChIP assay. These results indicate that SeqA binds hemimethylated nascent DNA segments according to the proceeding of replication forks in the chromosome, and SeqA releases from the DNA segments when fully methylated. Immunofluorescence microscopy reveals that a single SeqA focus containing paired replication apparatuses appears at the middle of the cell immediately after initiation of chromosome replication and the focus is subsequently separated into two foci that migrate to 1/4 and 3/4 cellular positions, when replication forks proceed bidirectionally an approximately one‐fourth distance from the replication origin towards the terminus. This supports the translocating replication apparatuses model.
Expression and differential signaling of heregulins in pancreatic cancer cells

The EGF family of ligands and receptors plays an important role in the pathogenesis of pancreatic ductal adenocarcinoma (PDAC) and contributes to its aggressiveness. A number of molecular approaches have been developed to block these pathways, and studies have already proven the clinical benefit of this concept in PDAC. In the present study, we sought to determine the potential role of heregulins (HRGs), a family of EGF‐like growth factors, in PDAC. Quantitative RT‐PCR analysis revealed that HRGs as well as its signaling ErbB receptors were present in 4 of 4 human pancreatic cancer cell lines (PCCL). HRG‐β1 stimulated the growth of 3 of 4 PCCL, whereas HRG‐α1 inhibited cell growth in 3 of 4 cell lines. Responses towards HRGs could in part be predicted by ErbB2 and ErbB3 expression levels. HRGs induced phosphorylation of different ErbB receptors as well as activation of MAPK, p38MAPK, JNK and PI3K in a cell‐ and ligand‐specific manner. In vivo, HRG was upregulated in pancreatic cancer tissues and localized predominantly in the cancer cells. High HRG‐β levels but not HRG‐α levels were associated with decreased patient survival. In conclusion, HRG is expressed by pancreatic cancer cells and influences pancreatic cancer cell growth and patient survival. © 2006 Wiley‐Liss, Inc.
A new class of bispecific antibodies to redirect T cells for cancer immunotherapy

Various constructs of bispecific antibodies (bsAbs) to redirect effector T cells for the targeted killing of tumor cells have shown considerable promise in both preclinical and clinical studies. The single-chain variable fragment (scFv)-based formats, including bispecific T-cell engager (BiTE) and dual-affinity re-targeting (DART), which provide monovalent binding to both CD3 on T cells and to the target antigen on tumor cells, can exhibit rapid blood clearance and neurological toxicity due to their small size (~55 kDa). Herein, we describe the generation, by the modular DOCK-AND-LOCKTM (DNLTM) method, of novel T-cell redirecting bispecific antibodies, each comprising a monovalent anti-CD3 scFv covalently conjugated to a stabilized dimer of different anti-tumor Fabs. The potential advantages of this design include bivalent binding to tumor cells, a larger size (~130 kDa) to preclude renal clearance and penetration of the blood-brain barrier, and potent T-cell mediated cytotoxicity. These prototypes were purified to near homogeneity, and representative constructs were shown to provoke the formation of immunological synapses between T cells and their target tumor cells in vitro, resulting in T-cell activation and proliferation, as well as potent T-cell mediated anti-tumor activity. In addition, in vivo studies in NOD/SCID mice bearing Raji Burkitt lymphoma or Capan-1 pancreatic carcinoma indicated statistically significant inhibition of tumor growth compared with untreated controls.
Metabolic and cytoprotective effects of in vivo peri-patellar hyaluronic acid injections in cultured tenocytes

Abstract The purpose of this study was to investigate tenocyte mechanobiology after sudden-detraining and to examine the hypothesis that repeated peri-patellar injections of hyaluronic acid (HA) on detrained patellar tendon (PT) may reduce and limit detrained-associated damage in tenoctyes. Twenty-four male Sprague–Dawley rats were divided into three groups: Untrained, Trained and Detrained. In the Detrained rats, the left tendon was untreated while the right tendon received repeated peri-patellar injections of either HA or saline (NaCl). Tenocyte morphology, metabolism and synthesis of C-terminal-propeptide of type I collagen, collagen-III, fibronectin, aggrecan, tenascin-c, interleukin-1β, matrix-metalloproteinase-1 and-3 were evaluated after 1, 3, 7 and 10 days of culture. Transmission-electronic-microscopy showed a significant increase in mitochondria and rough endoplasmic reticulum in cultured tenocytes from Detrained-HA with respect to those from Detrained-NaCl. Additionally, Detrained-HA cultures showed a significantly higher proliferation rate and viability, and increased synthesis of C-terminal-Propeptide of type I collagen, fibronectin, aggrecan, tenascin-c and matrix-metalloproteinase-3 with respect to Detrained-NaCl ones, whereas synthesis of matrix-metalloproteinase-1 and interleukin-1β was decreased. Our study demonstrates that discontinuing training activity in the short-term alters tenocyte synthetic and metabolic activity and that repeated peri-patellar infiltrations of HA during detraining allow the maintenance of tenocyte anabolic activity.
Liver transplantation for alcoholic liver disease: a systematic review of psychosocial selection criteria.

AIMS To examine the evidence base for psychosocial selection criteria for liver transplant candidates with alcoholic liver disease. METHOD Systematic review using three electronic databases supplemented by hand searches. RESULTS Out of 96 published studies, 22 were included. All but one were cohort design, most were retrospective, single centre, and small sample. Methodology varied considerably, such that meta-analysis was not feasible. CONCLUSIONS Social stability, no close relatives with an alcohol problem, older age, no repeated alcohol-treatment failures, good compliance with medical care, no current polydrug misuse, and no co-existing severe mental disorder have all been associated with future abstinence in more studies than not, in those that examined these variables. Duration of preoperative abstinence was a poor predictor. We recommend that, if predicting future abstinence is considered necessary by transplant teams, a standardized approach is agreed and deployed amongst transplant units, then audited and reviewed.
An Examination of Problem-Based Learning and its Impact on Medical Students' Attitudes and Academic Outcomes: A Meta-Analysis

ii Acknowledgements . iii List of Tables . ix List of Figures . x List of Abbreviations . xi Chapter I: Introduction . 1 The Flexner Report . 1 John Hopkins . 2 Signature Pedagogies . 2 Active Learning . 3 Student Engagement . 7 Learner Centered Environments . 7 Statement of the Problem . 9 Purpose of the Study . 10 Research Questions . 11 Overview of Methodology . 11 Meta-Analysis . 11 Limitations of Meta-Analysis . 12 Delimitations of the Study . 13 Assumptions of the Study . 14
The great contribution: Index Medicus, Index-Catalogue, and IndexCat.

OBJECTIVE The systematic indexing of medical literature by the Library of the Surgeon-General's Office (now the National Library of Medicine) has been called "America's greatest contribution to medical knowledge. " In the 1870s, the library launched two indexes: the Index Medicus and the Index-Catalogue of the Library of the Surgeon-General's Office. Index Medicus is better remembered today as the forerunner of MEDLINE, but Index Medicus began as the junior partner of what the library saw as its major publication, the Index-Catalogue. However, the Index-Catalogue had been largely overlooked by many medical librarians until 2004, when the National Library of Medicine released IndexCat, the online version of Index-Catalogue. Access to this huge amount of material raised new questions: What was the coverage of the Index-Catalogue? How did it compare and overlap with the Index Medicus? METHOD Over 1,000 randomly generated Index Medicus citations were cross-referenced in IndexCat. RESULTS Inclusion, form, content, authority control, and subject headings were evaluated, revealing that the relationship between the two publications was neither simple nor static through time. In addition, the authors found interesting anomalies that shed light on how medical literature was selected and indexed in "America's greatest contribution to medical knowledge. "