Dynamic response of HTS composite tapes to pulsed currents

Dynamic voltage-current characteristics of an HTS Ag/BiSCCO composite tape are studied both experimentally and theoretically. The tape is subjected by pulsed currents with different shapes and magnitude and voltage traces are measured using the four-point method with different location of potential taps on the sample surface. Clockwise and anticlockwise hysteresis loops are obtained for the same sample depending on location of the potential taps. The dynamic characteristics deviate substantially from the DC characteristic, especially in the range of low voltages where a criterion for the critical current value is usually chosen (1-10 mkV/cm). The critical current determined from dynamic characteristics and its change with the pulse magnitude depend on location of the potential taps and on the curve branch chosen for the critical current determination (ascending or descending). The theoretical analysis is based on a model of the magnetic flux diffusion into a composite tape for a superconductor described by the flux creep characteristic. Numerical simulation based on this model gives the results in good agreement with the experimental ones and explains the observed peculiarities of the dynamic characteristics of HTS composite tapes. The difference between the magnetic diffusion into a tape and a slab is discussed.Comment: 18 pages, 13 figure

From tropical shelters to temperate defaunation: the relationship between agricultural transition stage and the distribution of threatened mammals

Aim Agriculture is a key threat to biodiversity, however its relationship with biodiversity patterns is understudied. Here, we evaluate how the extent, intensity, and history of croplands relate to the global distribution of threatened mammals. We propose two hypotheses to explain these relationships: shelter, which predicts that threatened species concentrate in areas with low human land use; and threat, according to which threatened species should concentrate in areas of high human land use. Location Global. Time period c.B.C.6000 - 2014. Major taxa studied Terrestrial mammals. Methods We used boosted regression trees (BRT) that include spatial autocorrelation to investigate the relationship between the proportion of threatened terrestrial mammals (as defined by the IUCN Red List) and multiple metrics describing agricultural extent, intensity and history derived from remote sensing data and statistical projections. Data were analysed with a grain size of ~110 x 110 km at both global and biogeographic-realm scales. Results Agricultural extent and intensity were the most relevant indicator types, with specific metrics important for each realm. Forest cover (extent) was identified as important in several regions. Tropical regions in early agricultural transition stages (e.g., frontier landscapes) were consistent with the shelter hypothesis, whereas patterns found for regions in later stages (e.g., intensified agricultural landscapes) were mostly found in temperate regions and agreed with the threat hypothesis. Main conclusions These results highlight the need to consider multiple land-use indicators when addressing threats to biodiversity and to separately assess areas with divergent human and ecological histories in global-scale studies. Different relationships associated with different agricultural transition stages suggest that high concentrations of threatened species may have contrasting meanings in different regions worldwide. We propose a new unifying hypothesis following a cyclic relationship along agricultural transition stages resulting in alternating negative and positive relationships between agriculture and threatened species richness

The Relationship between Proteinuria and Coronary Risk: A Systematic Review and Meta-Analysis

Vlado Perkovic and colleagues show, through a systematic review and meta-analysis of cohort studies, that there is a strong and continuous association between proteinuria and subsequent risk of coronary heart disease

Trypanosoma brucei Glycogen Synthase Kinase-3, A Target for Anti-Trypanosomal Drug Development: A Public-Private Partnership to Identify Novel Leads

Over 60 million people in sub-Saharan Africa are at risk of infection with the parasite Trypanosoma brucei which causes Human African Trypanosomiasis (HAT), also known as sleeping sickness. The disease results in systemic and neurological disability to its victims. At present, only four drugs are available for treatment of HAT. However, these drugs are expensive, limited in efficacy and are severely toxic, hence the need to develop new therapies. Previously, the short TbruGSK-3 short has been validated as a potential target for developing new drugs against HAT. Because this enzyme has also been pursued as a drug target for other diseases, several inhibitors are available for screening against the parasite enzyme. Here we present the results of screening over 16,000 inhibitors of human GSK-3β (HsGSK-3) from the Pfizer compound collection against TbruGSK-3 short. The resulting active compounds were tested for selectivity versus HsGSK-3β and a panel of human kinases, as well as their ability to inhibit proliferation of the parasite in vitro. We have identified attractive compounds that now form potential starting points for drug discovery against HAT. This is an example of how a tripartite partnership involving pharmaceutical industries, academic institutions and non-government organisations such as WHO TDR, can stimulate research for neglected diseases

The regulation and deregulation of Wnt signaling by PARK genes in health and disease

Wingless/Int (Wnt) signaling pathways are signal transduction mechanisms that have been widely studied in the field of embryogenesis. Recent work has established a critical role for these pathways in brain development, especially of midbrain dopaminergic neurones. However, the fundamental importance of Wnt signaling for the normal function of mature neurones in the adult central nervous system has also lately been demonstrated by an increasing number of studies. Parkinson's disease (PD) is the second most prevalent neurodegenerative disease worldwide and is currently incurable. This debilitating disease is characterized by the progressive loss of a subset of midbrain dopaminergic neurones in the substantia nigra leading to typical extrapyramidal motor symptoms. The aetiology of PD is poorly understood but work performed over the last two decades has identified a growing number of genetic defects that underlie this condition. Here we review a growing body of data connecting genes implicated in PD--most notably the PARK genes--with Wnt signaling. These observations provide clues to the normal function of these proteins in healthy neurones and suggest that deregulated Wnt signaling might be a frequent pathomechanism leading to PD. These observations have implications for the pathogenesis and treatment of neurodegenerative diseases in general

Elevated serum neutrophil elastase is related to prehypertension and airflow limitation in obese women

<p>Abstract</p> <p>Background</p> <p>Neutrophil elastase level/activity is elevated in a variety of diseases such as atherosclerosis, systolic hypertension and obstructive pulmonary disease. It is unknown whether obese individuals with prehypertension also have elevated neutrophil elastase, and if so, whether it has a deleterious effect on pulmonary function. Objectives: To determine neutrophil elastase levels in obese prehypertensive women and investigate correlations with pulmonary function tests.</p> <p>Methods</p> <p>Thirty obese prehypertensive women were compared with 30 obese normotensive subjects and 30 healthy controls. The study groups were matched for age. Measurements: The following were determined: body mass index, waist circumference, blood pressure, lipid profile, high sensitivity C-reactive protein, serum neutrophil elastase, and pulmonary function tests including forced expiratory volume in one second (FEV₁), forced vital capacity (FVC) and FEV₁/FVC ratio.</p> <p>Results</p> <p>Serum neutrophil elastase concentration was significantly higher in both prehypertensive (405.8 ± 111.6 ng/ml) and normotensive (336.5 ± 81.5 ng/ml) obese women than in control non-obese women (243.9 ± 23.9 ng/ml); the level was significantly higher in the prehypertensive than the normotensive obese women. FEV1, FVC and FEV1/FVC ratio in both prehypertensive and normotensive obese women were significantly lower than in normal controls, but there was no statistically significant difference between the prehypertensive and normotensive obese women. In prehypertensive obese women, there were significant positive correlations between neutrophil elastase and body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, total cholesterol, triglyceride, low density lipoprotein cholesterol, high sensitivity C-reactive protein and negative correlations with high density lipoprotein cholesterol, FEV1, FVC and FEV1/FVC.</p> <p>Conclusion</p> <p>Neutrophil elastase concentration is elevated in obese prehypertensive women along with an increase in high sensitivity C-reactive protein which may account for dyslipidemia and airflow dysfunction in the present study population.</p

P301S Mutant Human Tau Transgenic Mice Manifest Early Symptoms of Human Tauopathies with Dementia and Altered Sensorimotor Gating

Tauopathies are neurodegenerative disorders characterized by the accumulation of abnormal tau protein leading to cognitive and/or motor dysfunction. To understand the relationship between tau pathology and behavioral impairments, we comprehensively assessed behavioral abnormalities in a mouse tauopathy model expressing the human P301S mutant tau protein in the early stage of disease to detect its initial neurological manifestations. Behavioral abnormalities, shown by open field test, elevated plus-maze test, hot plate test, Y-maze test, Barnes maze test, Morris water maze test, and/or contextual fear conditioning test, recapitulated the neurological deficits of human tauopathies with dementia. Furthermore, we discovered that prepulse inhibition (PPI), a marker of sensorimotor gating, was enhanced in these animals concomitantly with initial neuropathological changes in associated brain regions. This finding provides evidence that our tauopathy mouse model displays neurofunctional abnormalities in prodromal stages of disease, since enhancement of PPI is characteristic of amnestic mild cognitive impairment, a transitional stage between normal aging and dementia such as Alzheimer's disease (AD), in contrast with attenuated PPI in AD patients. Therefore, assessment of sensorimotor gating could be used to detect the earliest manifestations of tauopathies exemplified by prodromal AD, in which abnormal tau protein may play critical roles in the onset of neuronal dysfunctions