Manipulating topological states by imprinting non-collinear spin textures

Topological magnetic states, such as chiral skyrmions, are of great scientific interest and show huge potential for novel spintronics applications, provided their topological charges can be fully controlled. So far skyrmionic textures have been observed in noncentrosymmetric crystalline materials with low symmetry and at low temperatures. We propose theoretically and demonstrate experimentally the design of spin textures with topological charge densities that can be tailored at ambient temperatures. Tuning the interlayer coupling in vertically stacked nanopatterned magnetic heterostructures, such as a model system of a Co/Pd multilayer coupled to Permalloy, the in-plane non-collinear spin texture of one layer can be imprinted into the out-of-plane magnetised material. We observe distinct spin textures, e.g. vortices, magnetic swirls with tunable opening angle, donut states and skyrmion core configurations. We show that applying a small magnetic field, a reliable switching between topologically distinct textures can be achieved at remanence

Nitrogen and Carbon Isotopic Dynamics of Subarctic Soils and Plants in Southern Yukon Territory and its Implications for Paleoecological and Paleodietary Studies

We examine here the carbon and nitrogen isotopic compositions of bulk soils (8 topsoil and 7 subsoils, including two soil profiles) and five different plant parts of 79 C3 plants from two main functional groups: herbs and shrubs/subshrubs, from 18 different locations in grasslands of southern Yukon Territory, Canada (eastern shoreline of Kluane Lake and Whitehorse area). The Kluane Lake region in particular has been identified previously as an analogue for Late Pleistocene eastern Beringia. All topsoils have higher average total nitrogen δ15N and organic carbon δ13C than plants from the same sites with a positive shift occurring with depth in two soil profiles analyzed. All plants analyzed have an average whole plant δ13C of −27.5 ± 1.2 ‰ and foliar δ13C of ±28.0 ± 1.3 ‰, and average whole plant δ15N of −0.3 ± 2.2 ‰ and foliar δ15N of ±0.6 ± 2.7 ‰. Plants analyzed here showed relatively smaller variability in δ13C than δ15N. Their average δ13C after suitable corrections for the Suess effect should be suitable as baseline for interpreting diets of Late Pleistocene herbivores that lived in eastern Beringia. Water availability, nitrogen availability, spacial differences and intra-plant variability are important controls on δ15N of herbaceous plants in the study area. The wider range of δ15N, the more numerous factors that affect nitrogen isotopic composition and their likely differences in the past, however, limit use of the modern N isotopic baseline for vegetation in paleodietary models for such ecosystems. That said, the positive correlation between foliar δ15N and N content shown for the modern plants could support use of plant δ15N as an index for plant N content and therefore forage quality. The modern N isotopic baseline cannot be applied directly to the past, but it is prerequisite to future efforts to detect shifts in N cycling and forage quality since the Late Pleistocene through comparison with fossil plants from the same region

Mimicking human neuronal pathways in silico: an emergent model on the effective connectivity

International audienceWe present a novel computational model that detects temporal configurations of a given human neuronal pathway and constructs its artificial replication. This poses a great challenge since direct recordings from individual neurons are impossible in the human central nervous system and therefore the underlying neuronal pathway has to be considered as a black box. For tackling this challenge, we used a branch of complex systems modeling called artificial self-organization in which large sets of software entities interacting locally give rise to bottom-up collective behaviors. The result is an emergent model where each software entity represents an integrate-and-fire neuron. We then applied the model to the reflex responses of single motor units obtained from conscious human subjects. Experimental results show that the model recovers functionality of real human neuronal pathways by comparing it to appropriate surrogate data. What makes the model promising is the fact that, to the best of our knowledge, it is the first realistic model to self-wire an artificial neuronal network by efficiently combining neuroscience with artificial self-organization. Although there is no evidence yet of the model's connectivity mapping onto the human connectivity, we anticipate this model will help neuroscientists to learn much more about human neuronal networks, and could also be used for predicting hypotheses to lead future experiments

Discovery of Q203, a potent clinical candidate for the treatment of tuberculosis

New therapeutic strategies are needed to combat the tuberculosis pandemic and the spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) forms of the disease, which remain a serious public health challenge worldwide1, 2. The most urgent clinical need is to discover potent agents capable of reducing the duration of MDR and XDR tuberculosis therapy with a success rate comparable to that of current therapies for drug-susceptible tuberculosis. The last decade has seen the discovery of new agent classes for the management of tuberculosis3, 4, 5, several of which are currently in clinical trials6, 7, 8. However, given the high attrition rate of drug candidates during clinical development and the emergence of drug resistance, the discovery of additional clinical candidates is clearly needed. Here, we report on a promising class of imidazopyridine amide (IPA) compounds that block Mycobacterium tuberculosis growth by targeting the respiratory cytochrome bc1 complex. The optimized IPA compound Q203 inhibited the growth of MDR and XDR M. tuberculosis clinical isolates in culture broth medium in the low nanomolar range and was efficacious in a mouse model of tuberculosis at a dose less than 1 mg per kg body weight, which highlights the potency of this compound. In addition, Q203 displays pharmacokinetic and safety profiles compatible with once-daily dosing. Together, our data indicate that Q203 is a promising new clinical candidate for the treatment of tuberculosis

Hormonal intervention for the treatment of veterans with COVID-19 requiring hospitalization (HITCH): a multicenter, phase 2 randomized controlled trial of best supportive care vs best supportive care plus degarelix: study protocol for a randomized controlled trial

Background Therapeutic targeting of host-cell factors required for SARS-CoV-2 entry is an alternative strategy to ameliorate COVID-19 severity. SARS-CoV-2 entry into lung epithelium requires the TMPRSS2 cell surface protease. Pre-clinical and correlative data in humans suggest that anti-androgenic therapies can reduce the expression of TMPRSS2 on lung epithelium. Accordingly, we hypothesize that therapeutic targeting of androgen receptor signaling via degarelix, a luteinizing hormone-releasing hormone (LHRH) antagonist, will suppress COVID-19 infection and ameliorate symptom severity. Methods This is a randomized phase 2, placebo-controlled, double-blind clinical trial in 198 patients to compare efficacy of degarelix plus best supportive care versus placebo plus best supportive care on improving the clinical outcomes of male Veterans who have been hospitalized due to COVID-19. Enrolled patients must have documented infection with SARS-CoV-2 based on a positive reverse transcriptase polymerase chain reaction result performed on a nasopharyngeal swab and have a severity of illness of level 3–5 (hospitalized but not requiring invasive mechanical ventilation). Patients stratified by age, history of hypertension, and severity are centrally randomized 2:1 (degarelix: placebo). The composite primary endpoint is mortality, ongoing need for hospitalization, or requirement for mechanical ventilation at 15 after randomization. Important secondary endpoints include time to clinical improvement, inpatient mortality, length of hospitalization, duration of mechanical ventilation, time to achieve a normal temperature, and the maximum severity of COVID-19 illness. Exploratory analyses aim to assess the association of cytokines, viral load, and various comorbidities with outcome. In addition, TMPRSS2 expression in target tissue and development of anti-viral antibodies will also be investigated. Discussion In this trial, we repurpose the FDA approved LHRH antagonist degarelix, commonly used for prostate cancer, to suppress TMPRSS2, a host cell surface protease required for SARS-CoV-2 cell entry. The objective is to determine if temporary androgen suppression with a single dose of degarelix improves the clinical outcomes of patients hospitalized due to COVID-19. Trial registration ClinicalTrials.gov NCT04397718. Registered on May 21, 202

Toxin-Based Therapeutic Approaches

Protein toxins confer a defense against predation/grazing or a superior pathogenic competence upon the producing organism. Such toxins have been perfected through evolution in poisonous animals/plants and pathogenic bacteria. Over the past five decades, a lot of effort has been invested in studying their mechanism of action, the way they contribute to pathogenicity and in the development of antidotes that neutralize their action. In parallel, many research groups turned to explore the pharmaceutical potential of such toxins when they are used to efficiently impair essential cellular processes and/or damage the integrity of their target cells. The following review summarizes major advances in the field of toxin based therapeutics and offers a comprehensive description of the mode of action of each applied toxin

Nitrogen stable isotopes indicate differences in nitrogen cycling between two contrasting Jamaican montane forests

Background and aims The aim of this study is to enhance our knowledge of nitrogen (N) cycling and N acquisition in tropical montane forests through analysis of stable N isotopes (δ15N). Methods Leaves from eight common tree species, leaf litter, soils from three depths and roots were sampled from two contrasting montane forest types in Jamaica (mull ridge and mor ridge) and were analysed for δ15N. Results All foliar δ15N values were negative and varied among the tree species but were significantly more negative in the mor ridge forest (by about 2 ‰). δ15N of soils and roots were also more negative in mor ridge forests by about 3 ‰. Foliar δ15N values were closer to that of soil ammonium than soil nitrate suggesting that trees in these forests may have a preference for ammonium; this may explain the high losses of nitrate from similar tropical montane forests. There was no correlation between the rankings of foliar δ15N in the two forest types suggesting a changing uptake ratio of different N forms between forest types. Conclusions These results indicate that N is found at low concentrations in this ecosystem and that there is a tighter N cycle in the mor ridge forest, confirmed by reduced nitrogen availability and lower rates of nitrification. Overall, soil or root δ15N values are more useful in assessing ecosystem N cycling patterns as different tree species showed differences in foliar δ15N between the two forest types

Meso- and macrozooplankton communities in the Weddell Sea, Antarctica

The present paper describes composition and abundance of meso- and macrozooplankton in the epipelagic zone of the Weddell Sea and gives a systematic review of encountered species regarding results of earlier expeditions. Material was sampled from 6 February to 10 March 1983 from RV Polarstern with a RMT 1+8 m (320 and 4500 μm mesh size). In agreement with topography and water mass distribution three distinct communities were defined, clearly separated by cluster analysis: The Southern Shelf Community has lowest abundances (approx. 9000 ind./1000 m3). Euphausia crystallorophias and Metridia gerlachei are predominating. Compared with the low overall abundance the number of regularly occurring species is high (55) due to many neritic forms. Herbivores and omnivores are dominating (58% and 35%). The North-eastern Shelf Community has highest abundances (about 31 000 ind./1000 m3). It is predominated by copepodites I–III of Calanus propinquus and Calanoides acutus (61%). The faunal composition is characterized by both oceanic and neritic species (64). Fine-filter feeders are prevailing (65%). The Oceanic Community has a mean abundance of approximately 23 000 ind./1000 m3, consisting of 61 species. Dominances are not as pronounced as in the shelf communities. Apart from abundant species like Calanus propinquus, Calanoides acutus, Metridia gerlachei, Oithona spp. and Oncaea spp. many typical inhabitants of the Eastwind Drift are encountered. All feeding types have about the same importance in the Oceanic Community

distribution of tensile properties in aluminium alloys

In this study, the effect of melt quality and quenching temperature on the mechanical properties of 2024, 6063 and 7075 was investigated. The alloys were produced by Strain Induced Melt Activated (SIMA) method. T6 heat treatment was carried out by quenching in two different temperatures: 20 degrees C and 80 degrees C. Scanning electron microscope analyses were carried out on the fracture surfaces. In addition, reduced pressure tests were carried out to correlate the mechanical test results with metal quality. The results were analysed by Weibull statistics. It was found that samples quenched at 80 degrees C showed better mechanical properties and there was a good correlation between bifilm index and Weibull distributions