University of Graz

Spintronics, or spin electronics, involves the study of active control and manipulation of spin degrees of freedom in solid-state systems. This article reviews the current status of this subject, including both recent advances and well-established results. The primary focus is on the basic physical principles underlying the generation of carrier spin polarization, spin dynamics, and spin-polarized transport in semiconductors and metals. Spin transport differs from charge transport in that spin is a nonconserved quantity in solids due to spin-orbit and hyperfine coupling. The authors discuss in detail spin decoherence mechanisms in metals and semiconductors. Various theories of spin injection and spin-polarized transport are applied to hybrid structures relevant to spin-based devices and fundamental studies of materials properties. Experimental work is reviewed with the emphasis on projected applications, in which external electric and magnetic fields and illumination by light will be used to control spin and charge dynamics to create new functionalities not feasible or ineffective with conventional electronics.

The International Panel on MS Diagnosis presents revised diagnostic criteria for multiple sclerosis (MS). The focus remains on the objective demonstration of dissemination of lesions in both time and space. Magnetic resonance imaging is integrated with dinical and other paraclinical diagnostic methods. The revised criteria facilitate the diagnosis of MS in patients with a variety of presentations, including "monosymptomatic" disease suggestive of MS, disease with a typical relapsing-remitting course, and disease with insidious progression, without clear attacks and remissions. Previously used terms such as "clinically definite" and "probable MS" are no longer recommended. The outcome of a diagnostic evaluation is either MS, "possible MS" (for those at risk for MS, but for whom diagnostic evaluation is equivocal), or "not MS."

DeepMind presented notably accurate predictions at the recent 14th Critical Assessment of Structure Prediction (CASP14) conference. We explored network architectures that incorporate related ideas and obtained the best performance with a three-track network in which information at the one-dimensional (1D) sequence level, the 2D distance map level, and the 3D coordinate level is successively transformed and integrated. The three-track network produces structure predictions with accuracies approaching those of DeepMind in CASP14, enables the rapid solution of challenging x-ray crystallography and cryo-electron microscopy structure modeling problems, and provides insights into the functions of proteins of currently unknown structure. The network also enables rapid generation of accurate protein-protein complex models from sequence information alone, short-circuiting traditional approaches that require modeling of individual subunits followed by docking. We make the method available to the scientific community to speed biological research.

Natural products and their structural analogues have historically made a major contribution to pharmacotherapy, especially for cancer and infectious diseases. Nevertheless, natural products also present challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization, which contributed to a decline in their pursuit by the pharmaceutical industry from the 1990s onwards. In recent years, several technological and scientific developments - including improved analytical tools, genome mining and engineering strategies, and microbial culturing advances - are addressing such challenges and opening up new opportunities. Consequently, interest in natural products as drug leads is being revitalized, particularly for tackling antimicrobial resistance. Here, we summarize recent technological developments that are enabling natural product-based drug discovery, highlight selected applications and discuss key opportunities.

Six DNA regions were evaluated as potential DNA barcodes for Fungi, the second largest kingdom of eukaryotic life, by a multinational, multilaboratory consortium. The region of the mitochondrial cytochrome c oxidase subunit 1 used as the animal barcode was excluded as a potential marker, because it is difficult to amplify in fungi, often includes large introns, and can be insufficiently variable. Three subunits from the nuclear ribosomal RNA cistron were compared together with regions of three representative protein-coding genes (largest subunit of RNA polymerase II, second largest subunit of RNA polymerase II, and minichromosome maintenance protein). Although the protein-coding gene regions often had a higher percent of correct identification compared with ribosomal markers, low PCR amplification and sequencing success eliminated them as candidates for a universal fungal barcode. Among the regions of the ribosomal cistron, the internal transcribed spacer (ITS) region has the highest probability of successful identification for the broadest range of fungi, with the most clearly defined barcode gap between inter- and intraspecific variation. The nuclear ribosomal large subunit, a popular phylogenetic marker in certain groups, had superior species resolution in some taxonomic groups, such as the early diverging lineages and the ascomycete yeasts, but was otherwise slightly inferior to the ITS. The nuclear ribosomal small subunit has poor species-level resolution in fungi. ITS will be formally proposed for adoption as the primary fungal barcode marker to the Consortium for the Barcode of Life, with the possibility that supplementary barcodes may be developed for particular narrowly circumscribed taxonomic groups.

Although fire is now rarely used in synthetic chemistry, it was not until Robert Bunsen invented the burner in 1855 that the energy from this heat source could be applied to a reaction vessel in a focused manner. The Bunsen burner was later superseded by the isomantle, oil bath, or hot plate as a source for applying heat to a chemical reaction. In the past few years, heating and driving chemical reactions by microwave energy has been an increasingly popular theme in the scientific community. This nonclassical heating technique is slowly moving from a laboratory curiosity to an established technique that is heavily used in both academia and industry. The efficiency of "microwave flash heating" in dramatically reducing reaction times (from days and hours to minutes and seconds) is just one of the many advantages. This Review highlights recent applications of controlled microwave heating in modern organic synthesis, and discusses some of the underlying phenomena and issues involved.

The number of online experiments conducted with subjects recruited via online platforms has grown considerably in the recent past. While one commercial crowdworking platform – Amazon’s Mechanical Turk – basically has established and since dominated this field, new alternatives offer services explicitly targeted at researchers. In this article, we present www.prolific.ac and lay out its suitability for recruiting subjects for social and economic science experiments. After briefly discussing key advantages and challenges of online experiments relative to lab experiments, we trace the platform’s historical development, present its features, and contrast them with requirements for different types of social and economic experiments.

Abstract High-quality and complete reference genome assemblies are fundamental for the application of genomics to biology, disease, and biodiversity conservation. However, such assemblies are available for only a few non-microbial species 1–4 . To address this issue, the international Genome 10K (G10K) consortium 5,6 has worked over a five-year period to evaluate and develop cost-effective methods for assembling highly accurate and nearly complete reference genomes. Here we present lessons learned from generating assemblies for 16 species that represent six major vertebrate lineages. We confirm that long-read sequencing technologies are essential for maximizing genome quality, and that unresolved complex repeats and haplotype heterozygosity are major sources of assembly error when not handled correctly. Our assemblies correct substantial errors, add missing sequence in some of the best historical reference genomes, and reveal biological discoveries. These include the identification of many false gene duplications, increases in gene sizes, chromosome rearrangements that are specific to lineages, a repeated independent chromosome breakpoint in bat genomes, and a canonical GC-rich pattern in protein-coding genes and their regulatory regions. Adopting these lessons, we have embarked on the Vertebrate Genomes Project (VGP), an international effort to generate high-quality, complete reference genomes for all of the roughly 70,000 extant vertebrate species and to help to enable a new era of discovery across the life sciences.

Medicinal plants have historically proven their value as a source of molecules with therapeutic potential, and nowadays still represent an important pool for the identification of novel drug leads. In the past decades, pharmaceutical industry focused mainly on libraries of synthetic compounds as drug discovery source. They are comparably easy to produce and resupply, and demonstrate good compatibility with established high throughput screening (HTS) platforms. However, at the same time there has been a declining trend in the number of new drugs reaching the market, raising renewed scientific interest in drug discovery from natural sources, despite of its known challenges. In this survey, a brief outline of historical development is provided together with a comprehensive overview of used approaches and recent developments relevant to plant-derived natural product drug discovery. Associated challenges and major strengths of natural product-based drug discovery are critically discussed. A snapshot of the advanced plant-derived natural products that are currently in actively recruiting clinical trials is also presented. Importantly, the transition of a natural compound from a "screening hit" through a "drug lead" to a "marketed drug" is associated with increasingly challenging demands for compound amount, which often cannot be met by re-isolation from the respective plant sources. In this regard, existing alternatives for resupply are also discussed, including different biotechnology approaches and total organic synthesis. While the intrinsic complexity of natural product-based drug discovery necessitates highly integrated interdisciplinary approaches, the reviewed scientific developments, recent technological advances, and research trends clearly indicate that natural products will be among the most important sources of new drugs also in the future.

A new high-resolution regional climate change ensemble has been established for Europe within the World Climate Research Program Coordinated Regional Downscaling Experiment (EURO-CORDEX) initiative. The first set of simulations with a horizontal resolution of 12.5 km was completed for the new emission scenarios RCP4.5 and RCP8.5 with more simulations expected to follow. The aim of this paper is to present this data set to the different communities active in regional climate modelling, impact assessment and adaptation. The EURO-CORDEX ensemble results have been compared to the SRES A1B simulation results achieved within the ENSEMBLES project. The large-scale patterns of changes in mean temperature and precipitation are similar in all three scenarios, but they differ in regional details, which can partly be related to the higher resolution in EURO-CORDEX. The results strengthen those obtained in ENSEMBLES, but need further investigations. The analysis of impact indices shows that for RCP8.5, there is a substantially larger change projected for temperature-based indices than for RCP4.5. The difference is less pronounced for precipitation-based indices. Two effects of the increased resolution can be regarded as an added value of regional climate simulations. Regional climate model simulations provide higher daily precipitation intensities, which are completely missing in the global climate model simulations, and they provide a significantly different climate change of daily precipitation intensities resulting in a smoother shift from weak to moderate and high intensities.

autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Mobilization of fatty acids from triglyceride stores in adipose tissue requires lipolytic enzymes. Dysfunctional lipolysis affects energy homeostasis and may contribute to the pathogenesis of obesity and insulin resistance. Until now, hormone-sensitive lipase (HSL) was the only enzyme known to hydrolyze triglycerides in mammalian adipose tissue. Here, we report that a second enzyme, adipose triglyceride lipase (ATGL), catalyzes the initial step in triglyceride hydrolysis. It is interesting that ATGL contains a "patatin domain" common to plant acyl-hydrolases. ATGL is highly expressed in adipose tissue of mice and humans. It exhibits high substrate specificity for triacylglycerol and is associated with lipid droplets. Inhibition of ATGL markedly decreases total adipose acyl-hydrolase activity. Thus, ATGL and HSL coordinately catabolize stored triglycerides in adipose tissue of mammals.

In the X‐ray scattering curve of chain‐molecules in solution, essentially four regions may be distinguished as is shown by a more detailed mathematical discussion: The scattering at the smallest angles, showing an approximately Gaussean course, whose ordinate, when extrapolated to zero angle, is proportional to the square of the mol. weight. It is due to the diffraction effect of the whole coiled chain‐molecule. This is followed by a region of v ‐values where the scattering falls off as 1/ v 2 . It is due to parts of the chain molecule which themselves already occur in all possible orientations. After a transition region (which is also accounted for by the theory) there follows a scattering which is proportional to 1/ v . It is to be considered as the scattering of mostly straight parts of the molecule. The scattering at large angles, caused by smaller parts of the molecule (monomer group and single atoms), which at the same time indicates the periodicity (= length of structural unit in the direction of the chain axis) by a step, at an angle corresponding to Bragg's law. Its sharpness, too, is a measure for the coiling of the molecule. It can be shown that the abscissa of the intersecting point of the 1/ v 2 and 1/ v branches, when extrapolated to the transition region, is connected in a characteristic way with the statistical chain element or the “length of persistance”, which represent two different measures for the stiffness of the chain molecule. Measurements with polyvinyl bromide lead to a length of persistance of 11 ± 1 Å, which agrees satisfactorily with the value of 13 Å for polyvinyl chloride as derived from the birefringence of flow. At large angles two weak steps were found, one of which corresponds to the monomer length of 2.56 Å. Measurements on solutions of cellulose nitrate gave a curve ∼ 1/ v without any steeper ascent up to the smallest angles, corresponding to 300 Å. We have, therefore, to conclude that the chain‐element of cellulose nitrate is in any case larger than 150 Å, which again is in agreement with the results of other physical measurements. Though only a small number of experimental results is available so far, it seems to be established that the procedure yields a direct evaluation of the shape of chain molecules in solution and, in this respect, appears superior to other methods. However, the experimental difficulties are considerable.

[1] Precipitation downscaling improves the coarse resolution and poor representation of precipitation in global climate models and helps end users to assess the likely hydrological impacts of climate change. This paper integrates perspectives from meteorologists, climatologists, statisticians, and hydrologists to identify generic end user (in particular, impact modeler) needs and to discuss downscaling capabilities and gaps. End users need a reliable representation of precipitation intensities and temporal and spatial variability, as well as physical consistency, independent of region and season. In addition to presenting dynamical downscaling, we review perfect prognosis statistical downscaling, model output statistics, and weather generators, focusing on recent developments to improve the representation of space-time variability. Furthermore, evaluation techniques to assess downscaling skill are presented. Downscaling adds considerable value to projections from global climate models. Remaining gaps are uncertainties arising from sparse data; representation of extreme summer precipitation, subdaily precipitation, and full precipitation fields on fine scales; capturing changes in small-scale processes and their feedback on large scales; and errors inherited from the driving global climate model.

The essential oil of black cumin seeds, Nigella sativa L., was tested for a possible antioxidant activity. A rapid evaluation for antioxidants, using two TLC screening methods, showed that thymoquinone and the components carvacrol, t-anethole and 4-terpineol demonstrated respectable radical scavenging property. These four constituents and the essential oil possessed variable antioxidant activity when tested in the diphenylpicrylhydracyl assay for non-specific hydrogen atom or electron donating activity. They were also effective.OH radical scavenging agents in the assay for non-enzymatic lipid peroxidation in liposomes and the deoxyribose degradation assay. GC-MS analysis of the essential oil obtained from six different samples of Nigella sativa seeds and from a commercial fixed oil showed that the qualitative composition of the volatile compounds was almost identical. Differences were mainly restricted to the quantitative composition.

Lipids are produced, transported, and recognized by the concerted actions of numerous enzymes, binding proteins, and receptors. A comprehensive analysis of lipid molecules, "lipidomics," in the context of genomics and proteomics is crucial to understanding cellular physiology and pathology; consequently, lipid biology has become a major research target of the postgenomic revolution and systems biology. To facilitate international communication about lipids, a comprehensive classification of lipids with a common platform that is compatible with informatics requirements has been developed to deal with the massive amounts of data that will be generated by our lipid community. As an initial step in this development, we divide lipids into eight categories (fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, sterol lipids, prenol lipids, saccharolipids, and polyketides) containing distinct classes and subclasses of molecules, devise a common manner of representing the chemical structures of individual lipids and their derivatives, and provide a 12 digit identifier for each unique lipid molecule. The lipid classification scheme is chemically based and driven by the distinct hydrophobic and hydrophilic elements that compose the lipid. This structured vocabulary will facilitate the systematization of lipid biology and enable the cataloging of lipids and their properties in a way that is compatible with other macromolecular databases.

In 2005, the International Lipid Classification and Nomenclature Committee under the sponsorship of the LIPID MAPS Consortium developed and established a "Comprehensive Classification System for Lipids" based on well-defined chemical and biochemical principles and using an ontology that is extensible, flexible, and scalable. This classification system, which is compatible with contemporary databasing and informatics needs, has now been accepted internationally and widely adopted. In response to considerable attention and requests from lipid researchers from around the globe and in a variety of fields, the comprehensive classification system has undergone significant revisions over the last few years to more fully represent lipid structures from a wider variety of sources and to provide additional levels of detail as necessary. The details of this classification system are reviewed and updated and are presented here, along with revisions to its suggested nomenclature and structure-drawing recommendations for lipids.

The kinetics of the oxidation of human low density lipoprotein (LDL) can be measured continuously by monitoring the change of the 234 nm diene absorption. The time-course shows three consecutive phases, a lag-phase during which the diene absorption increases only weakly, a propagation phase with a rapid increase of the diene absorption and finally a decomposition phase. The increase of the dienes is highly correlated with the increase of MDA or lipid hydroperoxides. The duration of the lag-phase is determined by the endogenous antioxidants contained in LDL (vitamin E, carotenoids, retinylstearate). Water-soluble antioxidants (ascorbic acid, urate) added in micromolar concentrations prolong the lag-phase in a concentration-dependent manner. The determination of the lag-phase is a convenient and objective procedure for determining the susceptibility of LDL from different donors towards oxidation as well as effects of pro- and antioxidants.

Electrodermal activity is characterized by the superposition of what appear to be single distinct skin conductance responses (SCRs). Classic trough-to-peak analysis of these responses is impeded by their apparent superposition. A deconvolution approach is proposed, which separates SC data into continuous signals of tonic and phasic activity. The resulting phasic activity shows a zero baseline, and overlapping SCRs are represented by predominantly distinct, compact impulses showing an average duration of less than 2 s. A time integration of the continuous measure of phasic activity is proposed as a straightforward indicator of event-related sympathetic activity. The quality and benefit of the proposed measure is demonstrated in an experiment with short interstimulus intervals as well as by means of a simulation study. The advances compared to previous decomposition methods are discussed.

ABSTRACT This paper develops a model of dynamic capital structure choice in the presence of recapitalization costs. The theory provides the optimal dynamic recapitalization policy as a function of firm‐specific characteristics. We find that even small recapitalization costs lead to wide swings in a firm's debt ratio over time. Rather than static leverage measures, we use the observed debt ratio range of a firm as an empirical measure of capital structure relevance. The results of empirical tests relating firms' debt ratio ranges to firm‐specific features strongly support the theoretical model of relevant capital structure choice in a dynamic setting.