Miracle-dz/UniFAR-FTUs huggingface dataset:
An Essential Type I Nitroreductase from Leishmania major Can Be Used to Activate Leishmanicidal Prodrugs

Background: Leishmaniasis is a tropical disease prevalent in developing countries. Results: Leishmania major type I nitroreductase (LmNTR) metabolizes nitroaromatic/quinone substrates, an activity essential for parasite viability. Conclusion: LmNTR exhibits biochemical characteristics of its bacterial counterparts, and its activity is essential for parasite growth. Significance: LmNTR can be exploited as a prodrug activation enzyme or as a target for inhibitor design in drug development. Nitroaromatic prodrugs are used to treat a range of microbial infections with selectivity achieved by specific activation reactions. For trypanosomatid parasites, this is mediated by type I nitroreductases. Here, we demonstrate that the causative agent of leishmaniasis, Leishmania major, expresses an FMN-containing nitroreductase (LmNTR) that metabolizes a wide range of substrates, and based on electron donor and acceptor preferences, it may function as an NADH:quinone oxidoreductase. Using gene deletion approaches, we demonstrate that this activity is essential to L. major promastigotes, the parasite forms found in the insect vector. Intriguingly, LmNTR+/− heterozygote promastigote parasites could readily differentiate into infectious metacyclic cells but these were unable to establish infections in cultured mammalian cells and caused delayed pathology in mice. Furthermore, we exploit the LmNTR activity evaluating a library of nitrobenzylphosphoramide mustards using biochemical and phenotypic screens. We identify a subset of compounds that display significant growth inhibitory properties against the intracellular parasite form found in the mammalian hosts. The leishmanicidal activity was shown to be LmNTR-specific as the LmNTR+/− heterozygote promastigotes displayed resistance to the most potent mustards. We conclude that LmNTR can be targeted for drug development by exploiting its prodrug activating property or by designing specific inhibitors to block its endogenous function.
Effects of 7 wk of endurance training on human skeletal muscle metabolism during submaximal exercise.

This is the first study to examine the effects of endurance training on the activation state of glycogen phosphorylase (Phos) and pyruvate dehydrogenase (PDH) in human skeletal muscle during exercise. We hypothesized that 7 wk of endurance training (Tr) would result in a posttransformationally regulated decrease in flux through Phos and an attenuated activation of PDH during exercise due to alterations in key allosteric modulators of these important enzymes. Eight healthy men (22 +/- 1 yr) cycled to exhaustion at the same absolute workload (206 +/- 5 W; approximately 80% of initial maximal oxygen uptake) before and after Tr. Muscle biopsies (vastus lateralis) were obtained at rest and after 5 and 15 min of exercise. Fifteen minutes of exercise post-Tr resulted in an attenuated activation of PDH (pre-Tr: 3.75 +/- 0.48 vs. post-Tr: 2.65 +/- 0.38 mmol.min(-1). kg wet wt(-1)), possibly due in part to lower pyruvate content (pre-Tr: 0.94 +/- 0.14 vs. post-Tr: 0.46 +/- 0.03 mmol/kg dry wt). The decreased pyruvate availability during exercise post-Tr may be due to a decreased muscle glycogenolytic rate (pre-Tr: 13.22 +/- 1.01 vs. post-Tr: 7.36 +/- 1.26 mmol.min(-1). kg dry wt(-1)). Decreased glycogenolysis was likely mediated, in part, by posttransformational regulation of Phos, as evidenced by smaller net increases in calculated muscle free ADP (pre-Tr: 111 +/- 16 vs. post-Tr: 84 +/- 10 micromol/kg dry wt) and P(i) (pre-Tr: 57.1 +/- 7.9 vs. post-Tr: 28.6 +/- 5.6 mmol/kg dry wt). We have demonstrated for the first time that several signals act to coordinately regulate Phos and PDH, and thus carbohydrate metabolism, in human skeletal muscle after 7 wk of endurance training.
Sequence classification for machine translation

Discriminatively trained classiﬁcation techniques have been shown to out-perform generative techniques on many speech and natural language processing problems. However, most of the research in machine translation has been based on generative modeling techniques. The application of classiﬁcation techniques to machine translation requires scaling classiﬁers to deal with very large label sets (the vocabulary of the target language). In this paper, we present a method to scale classiﬁers to very large label sets and apply it to train classiﬁers for machine translation. We contrast this approach to a generatively trained machine translation model represented as a weighted ﬁnite-state transducer. We show translation accuracy results on spoken language corpora in English to Spanish and English to Japanese translation tasks.
Human Cooperative Motion Adapted Wearable Anti-Gravity Muscle Support System

We have developed a wearable anti-gravity muscle support system, which assists daily activities of physically weak persons by reducing the load to lower extremities. Many activities of human beings are performed smartly by cooperative motions of different body parts to distribute loads. In this paper, we propose a dynamics-based support concept adapted to the cooperative motion in order to assist a user smartly and naturally by the wearable support system. Experimental results illustrate the validity of the proposed concept
Freezer on, lights off! Environmental effects on activity rhythms of fish in the Arctic

Polar regions are characterized by acute seasonal changes in the environment, with organisms inhabiting these regions lacking diel photoperiodic information for parts of the year. We present, to our knowledge, the first high-resolution analysis of diel and seasonal activity of free-living fishes in polar waters (74°N), subject to extreme variation in photoperiod, temperature and food availability. Using biotelemetry, we tracked two sympatric ecomorphs of lake-dwelling Arctic charr (Salvelinus alpinus n = 23) over an annual cycle. Charr activity rhythms reflected the above-surface photoperiod (including under ice), with diel rhythms of activity observed. During the dark winter solstice period, charr activity became arrhythmic and much reduced, even though estimated light levels were within those at which charr can feed. When twilight resumed, charr activity ensued as diel vertical migration, which continued throughout spring and with increasing day length, despite stable water temperatures. Diel activity rhythms ceased during the polar day, with a sharp increase in arrhythmic fish activity occurring at ice-break. Despite contrasting resource use, circannual rhythms were mirrored in the two ecomorphs, although individual variability in activity rhythms was evident. Our data support conclusions of functionally adaptive periods of arrhythmicity in polar animals, suggesting maintenance of a circannual oscillator for scheduling seasonal behavioural and developmental processes.
Assessing the impact of Australian journals in the social sciences and humanties

This paper reports on a research project that is assessing a range of ‘alternative’ journal impact measures for the ranking of Australian social sciences and humanities journals. Bibliometric research methods were applied to identify citations to Australian social sciences and humanities journals published between 2001 and 2006. Citations were drawn from three sources: Web of Science; Scopus; and Publish or Perish (Google Scholar). These and other publication data were used to calculate each journal’s impact factor, two forms of diffusion, and h-index. A final measure that is introduced is that of the ‘rankings’ devised as part of the Australian Excellence in Research for Australia (ERA). A list of selected journals ranked by alternative measures is included. Introduction and background Journal publication and citation counts—attempts to measure the impact, influence and reach of individual titles—have been part of the scholarly publishing environment for over 80 years. For much of this time they were the province of researchers in the specialist area of bibliometrics; of occasional interest to collections librarians and publishers, but coming to the attention of few in the broader scholarly community. In recent years, however, there has been an explosion of interest in publication metrics generally, and of journal impact measures in particular (Steele, Butler, & Kingsley, 2006). This has been driven largely by the increased desire of governmentbased research funding bodies to firstly, measure the outputs or effectiveness of money invested in research; and secondly, to find some ‘objective’ criteria by which they can assess the comparative merit of individuals or teams applying for research funding. In seeking to make these assessments journal citation metrics have emerged as the key source of data, to the extent that they have become the critical indicator of research performance used by funding bodies, research institutions, individual researchers and the scholarly publishing industry. This circumstance has applied in Australia, where the Federal Government’s attempts to tie research funding to increased levels of accountability, initially through the aborted Research Quality Framework (RQF) and more recently Excellence in Research for Australia (ERA), have been based on methods of research evaluation that fore ground the importance of journal citation metrics. The adoption of citation metrics for impact assessment and subsequently for grant related purposes has, however, resulted in increased scrutiny of their true value for measuring the impact of either individual researchers or journals (Bowman &
Body weight and beauty: the changing face of the ideal female body weight

By observing the art of different eras, as well as the more recent existence of the media, it is obvious that there have been dramatic changes in what is considered a beautiful body. The ideal of female beauty has shifted from a symbol of fertility to one of mathematically calculated proportions. It has taken the form of an image responding to men's sexual desires. Nowadays there seems to be a tendency towards the destruction of the feminine, as androgynous fashion and appearance dominate our culture. The metamorphosis of the ideal woman follows the shifting role of women in society from mother and mistress to a career‐orientated individual. Her depiction by artists across the centuries reveals this change in role and appearance that should be interpreted within the social and historical context of each era with its own theories of what constituted the ideal female body weight.
PHOSPHORUS AVAILABILITY TO BARLEY FROM MANURES AND FERTILIZERS ON A CALCAREOUS SOIL

High concentrations of animal production in the United States have increased the concern about the environmental fate of phosphorus (P) in manures. We conducted a growth chamber study to develop phosphorus source coefficients (PSCs) for manures and fertilizers typically land applied and incorporated into calcareous soils of the western United States as well as to determine the potential plant P availability of these sources. Six manure types (swine solids from low phytate and regular barley diets, swine liquid, dairy liquid, beef solid, and dairy compost) and four fertilizer (mono calcium phosphate, mono ammonium phosphate, polymer-coated mono ammonium phosphate, and ammonium polyphosphate) P amendments were applied to two Portneuf soils at a rate of 60 mg P kg−1, incubated for 2 weeks, then planted with barley grown for 7 weeks. Soil samples were analyzed before barley planting and then at 4 and 7 weeks after planting, whereas plant samples were analyzed at 4 and 7 weeks. Increases in soil water soluble (WS-P) and bicarbonate P (Olsen P) from P additions generally followed the pattern [fertilizer P] > [liquid manures] > [solid or composted manures]. Plant shoot biomass and plant P accumulation were similar except swine manures were greater than inorganic P sources and beef manure was less than both. Determining relative P solubility of manure and fertilizer sources will be beneficial when estimating P losses from land application of manures and may be used to assign weighting coefficients to manure sources in risk assessments such as a P site index, with limited impact on P availability to crops.
Ambulatory Electrocardiographic Evidence of Transmural Dispersion of Repolarization in Patients With Long-QT Syndrome Type 1 and 2

Background—Transmural dispersion of repolarization (TDR) may be related to the genesis of torsade de pointes (TdP) in patients with the long-QT (LQT) syndrome. Experimentally, LQT2 models show increased TDR compared with LQT1, and &bgr;-adrenergic stimulation increases TDR in both models. Clinically, LQT1 patients experience symptoms at elevated heart rates, but LQT2 patients do so at lower rates. The interval from T-wave peak to T-wave end (TPE interval) is the clinical counterpart of TDR. We explored the relationship of TPE interval to heart rate and to the presence of symptoms in patients with LQT1 and LQT2. Methods and Results—We reviewed Holter recordings from 90 genotyped subjects, 31 with LQT1, 28 with LQT2, and 31 from unaffected family members, to record TPE intervals by use of an automated computerized program. The median TPE interval was greater in LQT2 (112±5 ms) than LQT1 (91±2 ms) or unaffected (86±3 ms) patients (P <0.001 for all group comparisons), and the maximal TPE values differed as well. LQT1 patients showed abrupt increases in TPE values at RR intervals from 600 to 900 ms, but LQT2 patients did so at RR intervals from 600 to 1400 ms (longest RR studied). Asymptomatic and symptomatic patients showed similar TDRs. Conclusions—TDR is greater in LQT2 than in LQT1 patients. LQT1 patients showed a capacity to increase TDR at elevated heart rates, but LQT2 patients did so at a much wider rate range. The magnitude of TDR is not related to a history of TdP.
Suppression of Reactive Oxygen Species Accumulation in Chloroplasts Prevents Leaf Damage but Not Growth Arrest in Salt-Stressed Tobacco Plants

Crop yield reduction due to salinity is a growing agronomical concern in many regions. Increased production of reactive oxygen species (ROS) in plant cells accompanies many abiotic stresses including salinity, acting as toxic and signaling molecules during plant stress responses. While ROS are generated in various cellular compartments, chloroplasts represent a main source in the light, and plastid ROS synthesis and/or elimination have been manipulated to improve stress tolerance. Transgenic tobacco plants expressing a plastid-targeted cyanobacterial flavodoxin, a flavoprotein that prevents ROS accumulation specifically in chloroplasts, displayed increased tolerance to many environmental stresses, including drought, excess irradiation, extreme temperatures and iron starvation. Surprisingly, flavodoxin expression failed to protect transgenic plants against NaCl toxicity. However, when high salt was directly applied to leaf discs, flavodoxin did increase tolerance, as reflected by preservation of chlorophylls, carotenoids and photosynthetic activities. Flavodoxin decreased salt-dependent ROS accumulation in leaf tissue from discs and whole plants, but this decline did not improve tolerance at the whole plant level. NaCl accumulation in roots, as well as increased osmotic pressure and salt-induced root damage, were not prevented by flavodoxin expression. The results indicate that ROS formed in chloroplasts have a marginal effect on plant responses during salt stress, and that sensitive targets are present in roots which are not protected by flavodoxin.
Production of chemokines in the lungs of infants with severe respiratory syncytial virus bronchiolitis.

BACKGROUND Respiratory syncytial virus (RSV) bronchiolitis in infants is characterized by a massive neutrophilic infiltrate into the airways. Chemokines direct migration of leukocytes and contribute to the pathogenesis of RSV disease. However, little is known about pulmonary chemokine responses to RSV in humans. Our aim was to characterize the production of chemokines in the lungs of infants with RSV bronchiolitis and how this production changes over time. METHODS Chemokine mRNA and the concentration of chemokines were measured in nonbronchoscopic bronchoalveolar lavage (BAL) samples from infants with RSV bronchiolitis and from control infants. In infants with RSV bronchiolitis, changes in the concentrations of chemokines during the 7 days after intubation and between the days of intubation and extubation were examined. RESULTS The production of chemokines within the lower respiratory tract was shown in all patients with RSV bronchiolitis. CXC chemokines (particularly CXCL10/interferon-inducible protein 10 and CXCL8/interleukin-8) were found to be the most abundant, but CC chemokines (CCL2/monocyte chemotactic protein 1 and CCL3/macrophage inflammatory protein-1 alpha) were also present. Concentrations of some of these chemokines remained elevated over the course of the illness, whereas others decreased steadily. No differences in the concentrations were found between the days of intubation and extubation. CONCLUSIONS CXC chemokines predominate within the RSV-infected lung. Much of this response comes from inflammatory cells within the lower respiratory tract. Chemokine response patterns vary over time, possibly indicating different cellular sources for individual chemokines in the RSV-infected lung.
IgE cross-reactivity between house dust mite allergens and Ascaris lumbricoides antigens

Background Common antigens between intestinal parasites and environmental allergens may play a role in the modulation of allergic immune responses. There is a growing interest in investigating cross-reactivity between common helminths and dust mites affecting humans, particularly in the tropics. Objective This study examined the cross-reactivity between the human roundworm Ascaris lumbricoides (Al) and three house dust mite (HDM) species. Methods Specific serum IgE levels to HDM species Blomia tropicalis (Bt), Dermatophagoides pteronyssinus (Dp), and Dermatophagoides farinae (Df ); and Al extracts among allergic (n=100) and ascariasis (n=60) subjects were measured through enzyme-linked immunosorbent assay (ELISA). IgE-reactive components of HDM and Al extracts were detected through Western-Blot Analysis. Cross-reactivity between HDMs and Al was determined by ELISA inhibition using HDM and Al-specific sera from allergic (n=15) and ascariasis (n=15) subjects. The IgE-binding capacity of a recombinant paramyosin peptide (Blo t 11-fD) to allergic (n=50) and ascariasis (n=50) subjects' sera were likewise determined. Results Among allergic subjects, 70% exhibited Al-specific positive IgE-reactivity, while 20-28% of ascariasis subjects demonstrated HDM-specific positive IgE-reactivity. Multiple IgE-reactive components of HDM allergens (14-240 kDa) and Al antigens (15-250 kDa) were detected, indicating multi-allergen sensitization among the subjects tested. Al antigens can inhibit up to 92% of HDM-specific IgE-reactivity among allergic subjects, while up to 54% of Al-specific IgE-reactivity among ascariasis subjects was inhibited by HDM allergens. Positive rBlo t 11-fD-specific IgE reactivity was observed in 80% of the allergic subjects and 46% of the ascariasis subjects. Conclusions This study showed the presence of multiple cross-reactive antigens in HDM and Al extracts. Identification of these molecules may provide basis for designing novel diagnostic and therapeutic strategies. The potential role of paramyosin as a specific cross-reactive allergen present in HDMs and Al has been shown.
Let the consumer decide? The regulation of commercial genetic testing

Objectives—The development of predictive genetic tests provides a new area where consumers can gain knowledge of their health status and commercial opportunities. “Over-the-counter” or mail order genetic tests are most likely to provide information on carrier status or the risk of developing a multifactorial disease. The paper considers the social and ethical implications of individuals purchasing genetic tests and whether genetic information is different from other types of health information which individuals can obtain for themselves. Design—The discussion is illustrated by findings from a questionnaire survey of university students as potential consumers. Topics covered included what health tests they had already used, expectations of genetic tests, willingness to pay, who should have access to the results and whether there need to be restrictions on such tests. Sample—Six hundred and fifteen first-year students in the universities of Leuven, Cardiff, Central Lancashire, Vienna and Nijmegen studying either medicine or a non-science subject. Results—Students were enthusiastic about genetic tests and had high expectations of their accuracy and usefulness but most thought they should be available through the health service and a minority thought that some tests, for example for sex selection, should not be available at all. There were few differences in responses by sex or subject of study but some by country. The paper also considers ethical and social issues outside the scope of a questionnaire survey of this type. Conclusion—To address some of these issues the sale of genetic tests to individuals can be made subject to ethical guidelines or codes of practice, for example to protect vulnerable groups, but there are fundamental social and ethical questions which such guidelines cannot address.
Prevalence of Human Papillomavirus (HPV) types in cervical cancer 2003–2008 in Stockholm, Sweden, before public HPV vaccination

Abstract Background. Human papillomavirus (HPV) infection is the major cause of cervical cancer, but the prevalence of different HPV types varies depending on geographical location and may change dramatically after introduction of HPV vaccination. Here, we aimed to gain some information regarding the recent prevalence of different HPV types, in cancer of the uterine cervix in the Stockholm region, before the introduction of public HPV vaccination in Sweden. Material and methods. From 215 diagnosed cervical cancer patients 2003–2008 at the Karolinska University Hospital, 160 pretreatment cervical cancer samples, including both squamous cell carcinomas (SCC) and adenocarcinomas (ADC) could be obtained. DNA was extracted from 154/160 of the SCC and ADC samples and assayed by Luminex Multiplex for 24 different HPV types, including 15 high-risk (HR), three putative HR and six low-risk types (LR). Results. We successfully analysed 154/215 (71.6%) of the locally diagnosed cases and found a high prevalence of HPV with 92.9% in all uterine cervix cancer cases, and 93.3% and 91.4 % in SCC and ADC, respectively. All HPV positive cases harboured HR types, either alone or as multiple infections. In SCC HPV16 dominated and together with HPV18 accounted for 69.7% of the cases, followed in prevalence by HPV33, 31 and 45. In ADC, HPV18 was more common than HPV16, and they were observed in all except one of the HPV positive samples. Conclusion. The prevalence of HPV16 and 18, followed by HPV33, 31 and 45 is high in SCC and ADC in the Stockholm region. Public HPV vaccination could potentially inhibit a large proportion of such tumours underlining the urgency to initiate HPV vaccination.
Optimal consensus of a multi-agent networked systems

Optimal consensus for a network of multiagent systems is one of the most important researched topics due to its importance in Network Analysis of Systems under Dynamic conditions. In this paper the problem is defined explicitly and a topological graph for the network is constructed. Then the Linear Quadratic Regulator Method (LQR) and the Linear Matrix Inequality (LMI) Approach are considered and they are used to achieve consensus. A study about the procedures and their behavior is carried out with simulation of the six vehicle network for the velocity parameter using the robust control toolbox of MATLAB.