Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterisation of diverse PRF1 mutations leading to decreased natural killer cell activity in North American families with haemophagocytic lymphohistiocytosis

Haemophagocytic lymphohistiocytosis (HLH, OMIM #267700, #603553) is a rare, lethal, cellular immunological disorder that draws attention to critical, genetically determined checkpoints in the regulatory pathways that normally maintain homeostasis within the immune system and ensure the natural termination of effector immune responses. HLH encompasses several entities, including the primary or familial form and the secondary forms associated with infections or malignancies.1,2 In all forms, HLH is believed to be a reactive process resulting from hyperactivation, proliferation, and migration of macrophages and type 1 T cells.3 Cytotoxic chemotherapy and/or immune suppressive therapy are usually effective in achieving symptomatic remission of HLH.4,5 The proven curative potential of haematopoietic stem cell transplantation underscores the premise that all forms of HLH result from genetic defects intrinsic to the immune system.5–7 Abnormalities in the function (but rarely the quantity) of cytotoxic immune cells, principally natural killer (NK) cells, but also cytotoxic T cells, have been observed in patients with HLH for nearly 20 years.8–11 Several genetic changes are thought to contribute to the development of HLH. Linkage analysis identified two loci at 10q21 and 9q21;12,13 additional studies provided evidence for the presence of at least one more locus.14 In 1999, the first molecular aetiology of HLH was described. Deficiency of perforin, a key lytic molecule of cytotoxic cells, was identified in a proportion of patients with HLH.15 Mutations of the coding sequence of PRF1 have since been reported in approximately 20–30% of primary HLH cases.16,17 Most of the families involved in previous studies came from southern Europe, North Africa, Turkey, and Japan.16–20 Only four cases from North America have previously been published.21 In the present study, we investigated the immunophenotypes of HLH in relation to the presence …
Site-directed mutagenesis of adeno-associated virus type 2 structural protein initiation codons: effects on regulation of synthesis and biological activity

It has been shown that two of the three adeno-associated virus type 2 capsid proteins, B and C, are synthesized from a single spliced transcript. Protein C arises from an AUG codon at nucleotide 2810, whereas protein B is initiated by a unique eucaryotic initiation codon (ACG) that lies 65 triplets upstream from the C origin. The third capsid component, protein A, is synthesized from a second spliced transcript which uses an alternative 3' acceptor site. In this study we used oligonucleotide-directed mutagenesis to confirm the positions of the B initiation codon and the 3' acceptor sites for the alternatively spliced B/C and A protein messages. We also located definitively the protein A initiation codon, an AUG triplet mapping to nucleotide 2203. Mutagenesis of the B initiator permitted a direct test of the effect of increased B initiator strength on the translational efficiencies of the B and C proteins. It was found that conversion of the relatively inefficient protein B initiator (ACG) to an AUG enhanced the level of B synthesis while abolishing the synthesis of C from its downstream AUG initiator. Protein C synthesis thus depends on the strength of the B initiator, i.e., the relatively higher levels of C (approximately 20-fold greater than B) must result from frequent readthrough of the weak B initiator. Finally, we examined the abilities of mutants deficient in the synthesis of A, B, or C to produce infectious virions. We found that at least two of the structural proteins, B and C, are required for the production of infectious virions and that sequestration of single-stranded adeno-associated virus genomes from the pool of replicating DNA molecules does not occur in the absence of either of these proteins.
Sources of Predictability of European Stock Markets for High-technology Firms

Abstract The paper reports on studies of return predictability of stock indexes of blue-chip firms and high-technology firms in Germany, France and the UK during the second half of the 1990s. Return predictability was measured in terms of first-order autocorrelation coefficients, and evidence was found for the return predictability of stock indexes of high-technology firms, but not for the return predictability of stock indexes of blue-chip firms. These findings suggest that a candidate for explaining the economic sources of the return predictability of these stock indexes of high-technology firms is transaction costs in the form of the costs of gathering and processing information in new technological fields.
GENETIC CONTROL OF IMMUNE RESPONSES IN VITRO

The conditions for cooperative interactions between nonresponder B10.S B cells and GAT-primed irradiated (C57BL/6 x SJL)F1 T cells in the response by cultures of mouse spleen cells to GAT were investigated. GAT-specific antibody responses could be elicited by soluble GAT in cultures of GAT-primed irradiated (C57BL/6 x SJL)F1 T cells with C57BL/6 B cells but not with B10.S B cells. In contrast, when GAT was presented to the cultures on F1 macrophages or as aggregates of GAT with MBSA, GAT-specific PFC responses were observed with both B10.S or C57BL/6 B cells. Irradiated GAT-primed T cells were nevertheless essential for the development of these responses. The GAT-specific response of B10.S B cells in these cultures was inhibited by the addition of soluble GAT at culture initiation. These results indicate that genetic disparity at Ir loci is not an absolute barrier to T-B-cell cooperative interactions in the response to antigens under Ir gene control. The significance of these data for the function of Ir gene products in immunocompetent cells is discussed.
Automatic Detection of Translated Text and its Impact on Machine Translation

We investigate the possibility of automatically detecting whether a piece of text is an original or a translation. On a large parallel English-French corpus where reference information is available, we ﬁnd that this is possible with around 90% accuracy. We further study the implication this has on Machine Translation performance. After separating our corpus according to translation direction, we train direction-speciﬁc phrase-based MT systems and show that they yield improved translation performance. This suggests that taking directionality into account when training SMT systems may have a signiﬁcant effect on output quality.
Embedded System Integrated Into a Wireless Sensor Network for Online Dynamic Torque and Efficiency Monitoring in Induction Motors

The system proposed in this paper aims at monitoring the torque and efficiency in induction motors in real time by employing wireless sensor networks (WSNs). An embedded system is employed for acquiring electrical signals from the motor in a noninvasive manner, and then performing local processing for torque and efficiency estimation. The values calculated by the embedded system are transmitted to a monitoring unit through an IEEE 802.15. 4-based WSN. At the base unit, various motors can be monitored in real time. An experimental study was conducted for observing the relationship between the WSN performance and the spectral occupancy at the operating environment. This study demonstrated that the use of intelligent nodes, with local processing capability, is essential for this type of application. The embedded system was deployed on a workbench, and studies were conducted to analyze torque and system efficiency.
A brief risk-stratification tool to predict repeat emergency department visits and hospitalizations in older patients discharged from the emergency department.

OBJECTIVES To evaluate the predictive ability of a simple six-item triage risk screening tool (TRST) to identify elder emergency department (ED) patients at risk for ED revisits, hospitalization, or nursing home (NH) placement within 30 and 120 days following ED discharge. METHODS Prospective cohort study of 650 community-dwelling elders (age 65 years or older) presenting to two urban academic EDs. Subjects were prospectively evaluated with a simple six-item ED nursing TRST. Participants were interviewed 30 and 120 days post-ED index visit and the utilization of EDs, hospitals, or NHs was recorded. Main outcome measurement was the ability of the TRST to predict the composite endpoint of subsequent ED use, hospital admission, or NH admission at 30 and 120 days. Individual outcomes of ED use, hospitalization, and NH admissions were also examined. RESULTS Increasing cumulative TRST scores were associated with significant trends for ED use, hospital admission, and composite outcome at both 30 and 120 days (p < 0.0001 for all, except 30-day ED use, p = 0.002). A simple, unweighted five-item TRST ("lives alone" item removed after logistic regression modeling) with a cut-off score of 2 was the most parsimonious model for predicting composite outcome (AUC = 0.64) and hospitalization at 30 days (AUC = 0.72). Patients defined as high-risk by the TRST (score > or = 2) were significantly more likely to require subsequent ED use (RR = 1.7; 95% CI = 1.2 to 2.3), hospital admission (RR = 3.3; 95% CI = 2.2 to 5.1), or the composite outcome (RR = 1.9; 95% CI 1.7 to 2.9) at both 30 days and 120 days than the low-risk cohort. CONCLUSIONS Older ED patients with two or more risk factors on a simple triage screening tool were found to be at significantly increased risk for subsequent ED use, hospitalization, and nursing home admission.
Numerical Investigation of Monitoring Antenna Influence on Shielding Effectiveness Characterization

─ This paper deals with an impact of receiving antenna placed in a metal enclosure on an electromagnetic field distribution within the enclosure, and thus on its shielding effectiveness. In an experimental setup, a frequently used tool for measuring the electromagnetic field level at certain points within the enclosure is a dipole antenna connected to a measuring instrument via a coaxial cable. For modeling a coupling between the electromagnetic field and antenna in the protective enclosure we use the Transmission-Line Matrix (TLM) method, enhanced with the compact wire model. The numerical model is verified through comparison with the available experimental results and then used to investigate the influence of physical dimensions of dipole antenna and its cable connection on the detected level of shielding effectiveness. Index Terms ─ Dipole antenna, enclosure, shielding effectiveness, TLM wire model.
Hyponatremia Associated with Selective Serotonin-Reuptake Inhibitors in Older Adults

Objective: To review the incidence, risk factors, mechanism, times of onset and resolution, and treatment of hyponatremia associated with selective serotonin-reuptake inhibitors (SSRIs). Data Sources: An English-language literature search was conducted using MEDLINE (1966–December 2005) using the search terms selective serotonin-reuptake inhibitor, hyponatremia, syndrome of inappropriate secretion of antidiuretic hormone, citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline. Additional references were identified by reviewing bibliographies of articles retrieved. Study Selection and Data Extraction: Relevant data were extracted from published reports, letters, and studies of humans with hyponatremia and/or syndrome of inappropriate secretion of antidiuretic hormone (SIADH) secondary to SSRIs. All articles identified from data sources were reviewed for relevant information. Applicable information was included in this review. Data Synthesis: Numerous case reports, observational studies, and case-controlled studies, as well as one prospective clinical trial, have reported hyponatremia associated with SSRI use, with the incidence varying from 0.5% to 32%. Risk factors for the development of hyponatremia with SSRIs include older age, female gender, concomitant use of diuretics, low body weight, and lower baseline serum sodium concentration. In published reports, hyponatremia developed within the first few weeks of treatment and resolved within 2 weeks after therapy was discontinued. The mechanism by which SSRIs cause hyponatremia is thought to be secondary to development of SIADH. Treatment of isovolemia hypotonic hyponatremia associated with SSRI use includes water restriction and mild diuresis with a loop diuretic. More severe cases may be treated with higher doses of loop diuretics and hypertonic saline. There have been few reports of rechallenge with the same or another SSRI or substitution of another agent from a different therapeutic class. In some, but not all, cases hyponatremia recurred. Conclusions: Practitioners should be on the alert for this potentially life-threatening adverse event, especially in older adults with other risk factors for developing hyponatremia.
Clinical Epidemiology of Mineral Bone Disorder Markers in Prevalent Hemodialysis Patients in the Xinjiang Uyghur Autonomous Region in China

We investigated the clinical epidemiology of mineral bone disorder markers in prevalent hemodialysis (HD) patients in Xinjiang, the largest province in China. Data were obtained from 59 hospitals. A total of 3725 patients tracked from January 1 to December 31, 2014, were enrolled. Serum calcium (Ca) levels, phosphorus (P) levels, and intact parathyroid hormone (iPTH) levels were analyzed. Serum Ca levels were lower compared to the International Dialysis Outcomes and Practice Patterns Study (DOPPS4) and the Chinese DOPPS. The hypercalcemia rate was similar to DOPPS4 and lower than in the Chinese DOPPS. Serum P levels were higher than in DOPPS4 and lower than those in the Chinese DOPPS. Hyperphosphatemia rates were higher than DOPPS4 and lower than Chinese DOPPS. Serum iPTH levels were higher than in DOPPS4 and the Chinese DOPPS. We demonstrated higher serum P and iPTH levels in Xinjiang HD patients than in the DOPPS4 and Chinese DOPPS. In contrast, serum Ca levels were lower than the other two studies. High hypocalcemia and hyperphosphatemia rates may suggest that HD services in Xinjiang are inadequate. A multidiscipline chronic kidney disease (CKD) care program needs to be established to improve chronic kidney disease-mineral and bone disorder (CKD-MBD) target achievement in Xinjiang.
Serum enzyme levels in patients with myasthenia gravis after aerobic and ischaemic exercise1

This study was designed to test the hypothesis that there is a myopathic component in myasthenia gravis. Serum enzyme analyses and lactate and pyruvate assays were undertaken before and after exercise in order to detect possible leakage from defective muscle membrane. A patient and a control group were exercised under (1) aerobic conditions, (2) ischaemic conditions, and (3) aerobic conditions under the influence of edrophonium chloride. The patient group showed a higher resting level of lactate in the aerobic state than did the controls. In addition, the average change in SGOT values in the patient group after one minute of aerobic exercise under the influence of edrophonium chloride exceeded that of the control group. Both these findings suggest possible leakage of enzyme and metabolite from the myasthenic muscle due to a membrane defect and support the hypothesis that there may be a myopathic component in myasthenia gravis. However, the two groups showed no significant differences in CPK values, which are often elevated in primary muscle diseases.
Increased Prevalence of Severe Subclinical Atherosclerotic Findings in Long-Term Treated Rheumatoid Arthritis Patients Without Clinically Evident Atherosclerotic Disease

We conducted the current study to search for subclinical atherosclerosis in patients with rheumatoid arthritis (RA) without clinically evident atherosclerosis or its complications who had been treated for a long duration, and to assess whether demographic or clinical factors affect the development of atherosclerotic disease. Forty-seven white patients fulfilling the 1987 American College of Rheumatology classification criteria for RA were recruited from Hospital Xeral-Calde, Lugo, Spain. Patients were required to have been treated for at least 5 years, including current treatment with 1 or more disease-modifying antirheumatic drugs. Patients with diabetes mellitus, renal insufficiency, hypertension, cardiovascular or cerebrovascular disease, and smokers were excluded. Forty-seven matched controls were also studied. Carotid intima-media wall thickness (IMT) and carotid plaques were measured in the right common carotid artery. The study was performed using high-resolution B-mode ultrasound.Patients had greater carotid IMT (0.779 ± 0.164 mm) than did controls (0.699 ± 0.129 mm); (p = 0.010). Sixteen (34%) patients showed carotid plaques compared with only 7 (15%) controls (p = 0.031). There was a positive correlation between the age at the time of study and the carotid IMT. Patients with carotid plaques had significantly greater carotid IMT (0.859 ± 0.116 mm) than those without plaques (0.739 ± 0.171 mm) (p = 0.014). Also, RA patients with carotid plaques had a significantly longer disease duration (mean, 21.0 yr) and more extraarticular manifestations (63%) than those without plaques (mean, 12.7 yr and 26%, respectively). Age at the time of the study and disease duration were the best predictive factors for the development of severe morphologic expression of atherosclerotic disease.The present study confirms an increased frequency of severe subclinical atherosclerotic findings in long-term actively treated RA patients from northwest Spain.
The first pathogenic Yersinia enterocolitica bioserotype 4/O:3 strain isolated from a hunted wild boar (Sus scrofa) in Poland

SUMMARY The objective of this study was to identify the bioserotypes and virulence markers of Yersinia enterocolitica strains isolated from wild boars in Poland. Bacteriological examination of 302 rectal swabs from 151 wild boars resulted in the isolation of 40 Y. enterocolitica strains. The majority of the examined strains (n = 30), belonged to bioserotype 1A/NI. The presence of individual Y. enterocolitica strains belonging to bioserotypes 1B/NI (3), 1A/O:8 (2), 1A/O:27 (2), 2/NI (1), 2/O:9 (1) and 4/O:3 (1) was also demonstrated. Amplicons corresponding to ail and ystA genes were observed only in one Y. enterocolitica strain – bioserotype 4/O:3. The ail and ystB gene amplicons were noted in 11 Y. enterocolitica biotype 1A strains, although single amplicons of ystB gene were found in 28 of the tested samples. In four out of eight cases when two Y. enterocolitica strains were isolated from the same animal, the strains differed in biotype, serotype or virulence markers. The European population of wild boars continues to grow and spread to new areas, therefore, wild boars harbouring potentially pathogenic Y. enterocolitica 4/O:3 strains pose a challenge to public health.
Some comparisons of impact craters on Mercury and the Moon

Although the general morphologies of fresh mercurian and lunar craters are remarkably similar, comparisons of ejecta deposits, interior structures, and changes in morphology with size reveal important differences between the two populations of craters. The differences are attributable to the different gravity fields in which the craters were formed and have significant implications for the interpretation of cratering processes and their effects on all planetary bodies.
Psychological Factors Influencing Exercise Adherence among Females

Social pressures focusing on health and physical attractiveness have been used to promote exercise among women (Prichard & Tiggemann, 2008). However, research has shown that motives driven by external sources result in decreased exercise participation (Deci & Ryan, 1985). The current study examined differences in motivation, self-efficacy, and mood between 64 exercise adherent and non-adherent women over four weeks. Women who were non-adherent to their exercise goals were more likely to report external motives, specifically body and health related motives. At the initial measurement, adherents reported significantly lower self-efficacy, positive affect, and life satisfaction compared to non-adherents. However, after the four weeks, adherents’ self-reports indicated a significant increase in these variables compared to no change in non-adherents’ self-reports.
Clustering of FGFR2 gene mutations inpatients with Pfeiffer and Crouzon syndromes (FGFR2-associated craniosynostoses)

A cohort of 36 unrelated German patients with craniosynostosis syndromes of the Crouzon and Pfeiffer type were analyzed for FGFR mutations. Mutations in FGFR2 were identified in 25 Crouzon and 5 Pfeiffer syndrome patients, whereas no sequence alterations were found in the remaining patients, even after screening of the relevant parts of FGFR1, FGFR3, and TWIST. Mutations in FGFR2 clustered at two critical cysteine residues, 278 and 342, which were involved in 18 of 30 cases (60%). These two mutational hot spots, therefore, are prime targets for an efficient mutation-screening strategy. The spectrum of mutations overlapped the two syndromes and thus reflected the phenotypic similarities observed in both patient groups. In 21 families, the origin of the mutation could be traced by analyzing parents and relatives. Eleven mutations arose de novo, indicating a high mutation rate for FGFR2. In the 10 familial cases, the clinical presentation varied considerably within the pedigree, but both syndromes “bred true,” i.e., a Pfeiffer syndrome phenotype was never observed in a Crouzon syndrome family and vice versa.
A transgenic mouse expressing human CYP4B1 in the liver.

The human CYP4B1 protein was expressed in the liver of a transgenic mouse line under the control of the promoter of the human apolipoprotein E (apo E) gene. Hepatic microsomes of transgenic mice catalyzed omega-hydroxylation of lauric acid and also activated 2-aminofluorene (2-AF), which is a typical substrate for CYP4B1, to mutagenic compounds detected by an umu gene expression assay. These activities observed in transgenic mouse were efficiently inhibited by CYP4B1 antibody. However, such inhibition was not observed in control mice. This is the first report to indicate catalytic activities of human CYP4B1. For further characterization of human CYP4B1, a fusion protein of CYP4B1 and NADPH-P450 reductase was expressed in yeast cells. It was able to activate 2-AF and was also able to catalyze omega-hydroxylation of lauric acid. This transgenic mouse line and the recombinant fusion protein provide a useful tool to study human CYP4B1 and its relation to chemical toxicity and carcinogenesis.
Profile of Benign Breast Diseases in an African Population

Benign Breast Diseases (BBD) refer to all non-malignant conditions of the breast and it received little attention in the past because most of the focus was on breast cancer, despite the fact that it constitutes majority of the presentation in breast clinics. The objective of this study was to evaluate comprehensively the profile of BBD in our environment, highlight the age group distribution of these BBDs and its different modes of presentation. This was a prospective cross-sectional study conducted between May 2009 and April 2010 at the Taimako Breast and Cervical Screening Centre on women who presented for breast screening. There were two thousand and sixty five study subjects, out of which one hundred and fifty women were diagnosed with BBD (7.3%), while one thousand nine hundred and fifteen (92.7%) had normal screening results. The mean age of those with BBD was 27.9 ± 9.6 with an age range of 15 to 60 years. Breast lumps constituted 44.7% of the presentation of BBD and was the most common mode of presentation, while 17.3% of those diagnosed with BBD had no symptoms and were discovered following triple assessment. More than half (56.8%) of the women who complained of breast lumps did not actually have lumps following triple assessment. BBD comprised a spectrum of disorders, with Fibroadenoma being the commonest and occurred most frequently in the younger 2nd and 3rd decades as opposed to older decades.