Miracle-dz/UniFAR-FTUs huggingface dataset:
Editing of the HLA‐DR‐peptide repertoire by HLA‐DM.

Antigenic peptide loading of classical major histocompatibility complex (MHC) class II molecules requires the exchange of the endogenous invariant chain fragment CLIP (class II associated Ii peptide) for peptides derived from antigenic proteins. This process is facilitated by the non‐classical MHC class II molecule HLA‐DM (DM) which catalyzes the removal of CLIP. Up to now it has been unclear whether DM releases self‐peptides other than CLIP and thereby modifies the peptide repertoire presented to T cells. Here we report that DM can release a variety of peptides from HLA‐DR molecules. DR molecules isolated from lymphoblastoid cell lines were found to carry a sizeable fraction of self‐peptides that are sensitive to the action of DM. The structural basis for this DM sensitivity was elucidated by high‐performance size exclusion chromatography and a novel mass spectrometry binding assay. The results demonstrate that the overall kinetic stability of a peptide bound to DR determines its sensitivity to removal by DM. We show that DM removes preferentially those peptides that contain at least one suboptimal side chain at one of their anchor positions or those that are shorter than 11 residues. These findings provide a rationale for the previously described ligand motifs and the minimal length requirements of naturally processed DR‐associated self‐peptides. Thus, in endosomal compartments, where peptide loading takes place, DM can function as a versatile peptide editor that selects for high‐stability MHC class II‐peptide complexes by kinetic proofreading before these complexes are presented to T cells.
An evolutionary strategy for a stealthy intracellular Brucella pathogen

Summary: Brucella is an intracellular bacterial pathogen that causes abortion and infertility in mammals and leads to a debilitating febrile illness that can progress into a long lasting disease with severe complications in humans. Its virulence depends on survival and replication properties in host cells. In this review, we describe the stealthy strategy used by Brucella to escape recognition of the innate immunity and the means by which this bacterium evades intracellular destruction. We also discuss the development of adaptive immunity and its modulation during brucellosis that in course leads to chronic infections. Brucella has developed specific strategies to influence antigen presentation mediated by cells. There is increasing evidence that Brucella also modulates signaling events during host adaptive immune responses.
Dual bidirectional promoters at the mouse dhfr locus: cloning and characterization of two mRNA classes of the divergently transcribed Rep-1 gene

The mouse dihydrofolate reductase gene (dhfr) is a housekeeping gene expressed under the control of a promoter region embedded in a CpG island--a region rich in unmethylated CpG dinucleotides. A divergent transcription unit exists immediately upstream of the dhfr gene which is coamplified with dhfr in some but not all methotrexate-resistant cell lines. We show that the promoter region for this gene pair consists of two bidirectional promoters, a major and minor promoter, which are situated within a 660-base-pair region upstream of the dhfr ATG translation initiation codon. The major promoter controls over 90% of dhfr transcription, while the minor promoter directs the transcription of the remaining dhfr mRNAs. The major promoter functions bidirectionally, transcribing a divergent 4.0-kilobase poly(A) mRNA (class A) in the direction opposite that of dhfr transcription. The predicted protein product of this mRNA is 105 kilodaltons. The minor promoter also functions bidirectionally, directing the transcription of at least two divergent RNAs (class B). These RNAs, present in quantities approximately 1/10 to 1/50 that of the class A mRNAs, are 4.4- and 1.6-kilobase poly(A) mRNAs. cDNAs representing both class A and class B mRNAs have been cloned from a mouse fibroblast cell line which has amplified the dhfr locus (3T3R500). DNA sequence analysis of these cDNAs reveals that the class A and class B mRNAs share, for the most part, the same exons. On the basis of S1 nuclease protection analysis of RNA preparations from several mouse tissues, both dhfr and divergent genes showed similar levels of expression but did show some specificity in start site utilization. Computer homology searches have revealed sequence similarity of the divergent transcripts with bacterial genes involved in DNA mismatch repair, and we therefore have named the divergently transcribed gene Rep-1.
Inflation Expectations in Advanced Economies

Anchored inflation expectations are important for price stability because expectations affect current actions. Although all inflation expectations measures provide some information about future inflation, professional forecasters have been the most accurate in predicting future inflation, while market-implied and consumer measures have tended to be less so. Recent declines in inflation expectations have been concentrated in the measures that have historically been less accurate predictors. The more accurate measures have been more stable and have remained close to central banks' inflation targets.
Health status and occupational risk factors in Greek small fisheries workers.

BACKGROUND Fishing is an extremely dangerous occupational activity that predisposes to occupational diseases and accidents. Greece, with about 16,000 km of coastline and its unique morphological characteristics with small islands and peninsulas, represents a strong proof of its great tradition in the fisheries sector since ancient times. The aim of the study was to examine the health status and the health risk factors present in Greek fishery workers, by exploring their working environment, thus providing a current baseline for documentation of the needs for prevention and health promotion. MATERIALS AND METHODS An interviewer-administered questionnaire was distributed in 2013 to a random sample of 172 professional small-scale fishermen of the Evros district in North-Eastern Greece. RESULTS Eighty-eight per cent worked in coastal fisheries and 73% were using small fishing vessels, less than 10 m in length overall. Health disorders included musculoskeletal, cardiovascular and visual problems and to a minor degree by hearing, dermatologic and respiratory problems in all age groups. Seventy per cent had experienced at least one occupational accident. Heavy smoking and daily alcohol consumption was seen among nearly half of the fishermen. CONCLUSIONS The health effects observed are causally related to the work process exposures on board and to diet, smoking, and lack of exercise. This in turn relates to the specific working conditions, the culture and level of education in small-scale fishing that need to be taken into consideration together in the prevention programmes.
Influences on Maltese children’s food intake : proposing a ‘socio-ecological culture-cuisine food model’

“It is sometimes wrongly assumed that just by providing people with information they will automatically be able to make healthy choices. While more knowledge, information and health education is important, the evidence shows that decisions to adopt health-enhancing behaviourfor example eating healthily.are often constrained by the broader physical, social, economic and cultural environments which influence the choices that individuals, groups and local communities make. ” (WHO, 1999).
Effect of Direct Ovarian Infusion of Bone Morphogenetic Protein 6 (BMP6) on Ovarian Function in Sheep1

Bone morphogenetic protein 6 (BMP6) has been suggested as an important local factor capable of modulating the stimulatory actions of follicle-stimulating hormone in granulosa cells in vitro. The objective of this experiment was to determine the effect of direct ovarian infusion of BMP6 (2 μg/h) on ovarian function in ewes with an autotransplanted ovary. Treated ewes (n = 6) and vehicle-treated controls (n = 6) were infused during the early follicular phase, between 12 and 24 h after luteal regression, and ovarian response was determined by collection of samples of ovarian venous blood and transdermal ultrasound. In the absence of any change in circulating gonadotropins or in the antral follicle population, BMP6 infusion resulted in acute but transient increases in ovarian inhibin A, androstenedione, and estradiol secretion (P < 0.05) during the second half of the infusion period. Thereafter, treated animals had an advance in the time of the LH surge by around 10 h (43.3 ± 2.8 h in treated vs. 53.3 ± 2.7 h in controls; P < 0.05) and smaller preovulatory follicles (4.1 ± 0.2 mm in treated vs. 5.3 ± 0.1 mm in controls; P < 0.01), which gave rise to smaller corpora lutea (9.5 ± 0.8 mm in treated vs. 11.7 ± 0.6 mm in controls; P < 0.05). There was, however, no effect of infusion on ovulation rate. Despite the changes in the size of the ovulatory follicles, when the hormonal data were aligned to the time of the luteinizing hormone surge, there were no differences in preovulatory estradiol, androstenedione, or inhibin A between groups. This study therefore provides strong in vivo evidence to support the hypothesis that BMP6 is an important local regulator of ovarian function and that alterations in BMP6 cellular signaling may explain some of the effects of the FecB mutation in inducing precocious maturation of ovulatory follicles.
Genetic and infective diversity of the liver fluke Fasciola hepatica (Trematoda: Digenea) from Cuba

Abstract In this study we present the first approach to exploration of the genetic diversity of Cuban Fasciola hepatica populations using microsatellite markers, coupled with observed prevalence in slaughterhouses. Nine populations of flukes recovered from cows and buffalos were studied in the central-western region of Cuba. The observed infection rates of definitive hosts (bovines) were 70–100% in most cases. An important amount of polymorphism was found in the four loci explored. However, no apparent genetic differences were found between populations from different provinces or bovine species. The absence of deviations from Hardy–Weinberg equilibrium suggests a high rate of cross-fertilization between F. hepatica individuals. This result was confirmed when all multilocus genotypes were tested for clonal reproduction and only four individuals differed statistically (P sex< 0.05). High values of expected heterozygosity coupled with highly probable mixing among strains make the metapopulation genetically diversified but similar in terms of certain alleles (low F ST values). These results suggest a close relationship between parasite diversity and cattle management in Cuba. Our findings should be taken into consideration by veterinary authorities to help mitigate fasciolosis transmission.
High prevalence of peripheral arterial disease in hypertensive patients: the Evaluation of Ankle-Brachial Index in Hungarian Hypertensives screening program

Aims: Peripheral arterial disease (PAD) can be diagnosed in asymptomatic stage, measuring ankle-brachial index (ABI). Low ABI is an indicator of increased cardiovascular risk and its inclusion to traditional risk factors can improve risk prediction. The objective of the present cross-sectional part of our large-scale, multicenter, observational study was to evaluate the prevalence of PAD in a large cohort of hypertensive patients. Methods and results: A total of 21 892 hypertensive men and women (9162 men; mean age 61.45 years) were included in our prospective study in hypertension clinics. Clinical history, physical examination, and blood analysis were taken, and the ABI was measured with the Doppler method in all patients. The prevalence of PAD (ABI ⩽0.9) was 14.4%. In 15.6% of the patients an ABI of 0.91–0.99, and in 9.4% of the patients high ABI (>1.3) was measured. In the low, moderate, high, and very high Systematic Coronary Risk Evaluation risk groups, the prevalence of low ABI was 8.1, 11.1, 16.3, and 26%, respectively. The prevalence of PAD was lower in hypertensive patients achieving their blood pressure target (9.6 vs. 16.8%; P < 0.001). Conclusions: Asymptomatic PAD was highly prevalent in the studied hypertensive population. The use of ABI screening may improve cardiovascular risk prediction. Optimal blood pressure goal values in PAD patients and cardiovascular morbidity/mortality data will be evaluated after the 5-year long prospective phase of the Evaluation of Ankle-Brachial Index in Hungarian Hypertensives program.
Botanical Characterization of Guiera senegalensis Leaves

Abstract Guiera senegalensis J. F. Gmel. (Combretaceae) is one of the most important West African medicinal plants, often used to treat a variety of microbial infections. The most frequently used plant part is the leaf, its medicinal use being corroborated by several in vitro antimicrobial activity studies. However, quality criteria for pharmaceutical use, including botanical identification, are not yet determined. Aiming the establishment of such criteria, the present work deepens today's knowledge on G. senegalensis leaf morphology and anatomy, the anatomical characters of both leaf transversal section and powdered leaves being hereby presented for the first time. The most useful characters for identification purposes are leaf isobilateral organization, with similar upper and lower surfaces and a palisade parenchyma on both surfaces; trichome insertion points on both epidermis, surrounded by polar arrangements of cells; tomentose indumentum on the upper epidermis consisting of compartmented and uniseriated trichomes with long, curved, or straight terminal cells; brown scales, isolated or inserted into the epidermis, formed by radially arranged cells surrounding a central cell, with a more or less circular form and a conspicuous base; calcium oxalate cluster crystals, isolated or inserted into the palisade parenchyma and absent in lateral veins.
Adenosine A3 Receptor Activation Modulates the Capillary Endothelial Glycocalyx

Abstract— The endothelial glycocalyx is a dynamic extracellular matrix composed of cell surface proteoglycans, glycoproteins, and adsorbed serum proteins that has been implicated in the regulation and modulation of capillary tube hematocrit, permeability, and hemostasis. High tissue adenosine levels have been shown to adversely affect microvascular function and tissue survival after an ischemic episode, and previous work in this laboratory has shown that adenosine causes arteriolar constriction and degranulation of mast cells via the A3 receptor (A3AR). We hypothesized that adenosine exerts at least part of its effect through modification of the glycocalyx via the A3AR. We used an in vivo cremaster model (hamster and mouse) in which circulating plasma was labeled with a 70-kDa FITC-dextran, and the capillaries were examined before and after superfusion with varying concentrations of adenosine (or other vasoactive molecules). Measurements of the dextran exclusion from an endothelial cell surface layer and red cell separation from the endothelial cell surface were made for up to 30 minutes. Our data indicate that adenosine causes a rapid and profound decrease in the ability of the glycocalyx to exclude dextran but only affects red blood cell exclusion at pharmacological levels. Knockout mice deficient in the A3AR were completely protected from glycocalyx changes attributable to adenosine. These data show a potential link between a known vasoactive tissue metabolite, adenosine, and regulation of the glycocalyx, which may be important during (patho)physiological changes in microvascular function during inflammatory insults.
New algorithm for the depression diagnosis using HRV: A neuro-fuzzy approach

Recent research indicates a significant relationship between the severity of depression and heart rate variability (HRV). This paper presents a neuro-fuzzy approach-based classification algorithm, which distinguishes patients with depression from controls by a neuro-fuzzy network with a weighted fuzzy membership function (NEWFM) using the two time domain and four frequency domain features of HRV. The HRV data were collected from 10 patients with depression and an equal number of healthy controls. Wearing a wireless Holter monitor, each subject underwent a 13-minute multimodal affective contents stimulus, which can induce a variety of emotions. HRV activity was transformed and recorded from periods of 13-minute ECG signals. With a reliable accuracy rate of 95%, the six HRV features were extracted and used as NEWFM input features for depression classification. The standard deviation of the RR intervals (SDNN) and very low frequency (VLF) of HRV were evaluated as good features-from six features-by a non-overlap area distribution measurement method. The two features reflected conspicuous differences between the depression diagnosed and the healthy subjects, which indicates a significant association between depression and the autonomic nervous system. The proposed algorithm will be implemented as a depression monitoring system in a Smartphone application.
University/industry collaboration in developing a simulation based software project management training course

A significant factor in the success of a software project is the management skill of the project leader. The ability to effectively plan and track a software project utilizing appropriate techniques and tools requires training, mentoring and experience. This paper describes a collaborative effort between Arizona State University and Motorola University to develop a software project management training course. Although many such courses exist in academia and industry, this course incorporates a system dynamics simulator of the software development process. The use of this simulator to train future software project managers is analogous to the use of a flight simulator to train pilots. This paper describes the software project simulator and how it is utilized in the software project management training course. Feedback from the training course participants is also shared and discussed.
Neuropsychological significance of anosmia following traumatic brain injury.

OBJECTIVES To investigate the incidence of anosmia following traumatic brain injury (TBI) using a standardized instrument and to test hypotheses that post-TBI anosmics perform significantly more poorly than do post-TBI normosmics on measures of executive skills and functional outcome. DESIGN Prospective quasi-experimental between-groups design. PARTICIPANTS Sixty-eight adults diagnosed with TBI. SETTING Brain injury rehabilitation program based at a Midwestern medical center. MAIN OUTCOME MEASURES University of Pennsylvania Smell Identification Test (UPSIT), selected neuropsychological measures of executive skills, the Disability Rating Scale (DRS), and the Community Integration Questionnaire (CIQ). RESULTS Forty-four subjects (65%) demonstrated impaired olfaction; only 13 (30%) acknowledged smell dysfunction. Anosmic and normosmic groups did not differ in demographics, IQ, chronicity, or admission Glasgow Coma Scale (GCS). Anosmics had longer coma (P =. 01), more severe deficits in complex attention (Trailmaking Test, Part B, P =.01), new learning/memory (California Verbal Learning Test Trial V [CVLT-V], P =.001), and problem solving (Wisconsin Card Sorting Test [WCST], P =.001), leading to greater functional impairment (Disability Rating Scale [DRS], P =.003). No differences emerged on the CIQ. CONCLUSIONS Anosmia is a common sequela of TBI, although only a minority of patients are aware of this deficit. Further, anosmics demonstrated greater impairment in a variety of frontal-lobe mediated executive functions, as well as greater functional disability.
Workplace bullying in the foodservice industry

ABSTRACT In the United States alone, it is estimated that that more than 53.5 million Americans have been victims of bullying at work. As one of the largest private-sector employers in the United States, it stands to reason that the foodservice industry is exceedingly susceptible to this workplace phenomenon. Thus, the purpose of this study was to investigate the presence of workplace bullying behaviors in the foodservice industry. A survey of 440 hospitality workers indicated that foodservice workers witness exclusion, verbal abuse, sexual intimidation, inappropriate jokes, teasing, and mean pranks significantly more frequently than non-foodservice hospitality workers. Practical implications and recommendations for future study are provided.
Hypogonadal men nonresponders to the PDE5 inhibitor tadalafil benefit from normalization of testosterone levels with a 1% hydroalcoholic testosterone gel in the treatment of erectile dysfunction (TADTEST study).

INTRODUCTION Addition of testosterone (T) may improve the action of phosphodiesterase type 5 inhibitors (PDE5-Is) in patients with erectile dysfunction not responding to PDE5-Is with low or low-normal T levels. AIMS To confirm this add-on effect of T in men optimally treated with PDE5-Is and to specify the baseline T levels at which such an effect becomes significant. METHODS A multicenter, multinational, double-blind, placebo-controlled study of 173 men, 45-80 years, nonresponders to treatment with different PDE5-Is, with baseline total T levels ≤ 4 ng/mL or bioavailable T ≤ 1 ng/mL. Men were first treated with tadalafil 10 mg once a day (OAD) for 4 weeks; if not successful, they were randomized in a double-blind, placebo-controlled design to receive placebo or a 1% hydroalcoholic T gel (50 mg/5 g gel), to be increased to 10 mg T if results were clinically unsatisfactory. Main Outcomes Measures. Mean change from baseline in the Erectile Function Domain Score of the International Index of Erectile Function and rate of successful intercourses (Sexual Encounter Profile 3 question). RESULTS Erectile function progressively improved over a period of at least 12 weeks in both the placebo and T treatment groups. In the overall population with a mean baseline T level of 3.37 ± 1.48 ng/mL, no additional effect of T administration to men optimally treated with PDE5-Is was encountered. The differences between the T and placebo groups were significant for both criteria only in the men with baseline T ≤ 3 ng/mL. CONCLUSIONS The maximal beneficial effects of OAD dosing with 10 mg tadalafil may occur only after as many as 12 weeks. Furthermore, addition of T to this PDE5-I regimen is beneficial, but only in hypogonadal men with baseline T levels ≤ 3 ng/mL.
Optimal Training and Pilot Pattern Design for OFDM Systems in Rayleigh Fading

This paper deals with two major considerations for pilot symbol assisted orthogonal frequency division multiplexing (PSA-OFDM) systems when operated over Rayleigh fading channels. One of them is to decide how many pilot symbols should be used and the other is where to place these pilot symbols, i.e. pilot pattern. Incorporating linear interpolation and choosing appropriate system parameters, we first derive analytically the bit-error-rate (BER) for frequency-selective fading, time-selective fading and correlated fading, respectively. Based on the theoretical BER, the optimal training can be determined numerically for a specific fading environment. Furthermore, we propose a new and simple pilot pattern for PSA-OFDM system and its performance is analyzed in terms of the BER. The proposed scheme clusters two neighboring pilots together so as to increase the channel estimate accuracy by averaging over the two pilot symbols. Analytical and simulation results show that this clustered pilot pattern gives better performance in terms of BER than the existing equi-spaced pilot pattern when the channel SNR is moderate, without sacrificing the bandwidth efficiency