julilili42/papers huggingface dataset:
Intranasal Neuropeptide Administration To Target the Human Brain in Health and Disease
2015-04-16

Central nervous system control of metabolic function relies on the input of endocrine messengers from the periphery, including the pancreatic hormone insulin and the adipokine leptin. This concept primarily derives from experiments in animals where substances can be directly applied to the brain. A feasible approach to study the impact of peptidergic messengers on brain function in humans is the intranasal (IN) route of administration, which bypasses the blood-brain barrier and delivers neuropeptides to the brain compartment, but induces considerably less, if any, peripheral uptake than other administration modes. Experimental IN insulin administration has been extensively used to delineate the role of brain insulin signaling in the control of energy homeostasis, but also cognitive function in healthy humans. Clinical pilot studies have found beneficial effects of IN insulin in patients with memory deficits, suggesting that the IN delivery of this and other peptides bears some promise for new, selectively brain-targeted pharmaceutical approaches in the treatment of metabolic and cognitive disorders. More recently, experiments relying on the IN delivery of the hypothalamic hormone oxytocin, which is primarily known for its involvement in psychosocial processes, have provided evidence that oxytocin influences metabolic control in humans. The IN administration of leptin has been successfully tested in animal models but remains to be investigated in the human setting. We briefly summarize the literature on the IN administration of insulin, leptin, and oxytocin, with a particular focus on metabolic effects, and address limitations and perspectives of IN neuropeptide administration.
Finite-temperature Yang-Mills theory in the Hamiltonian approach in Coulomb gauge from a compactified spatial dimension
2015-04-16

Yang-Mills theory is studied at finite temperature within the Hamiltonian\\napproach in Coulomb gauge by means of the variational principle using a\\nGaussian type ansatz for the vacuum wave functional. Temperature is introduced\\nby compactifying one spatial dimension. As a consequence the finite temperature\\nbehavior is encoded in the vacuum wave functional calculated on the spatial\\nmanifold where is the\\ntemperature. The finite-temperature equations of motion are obtained by\\nminimizing the vacuum energy density to two-loop order. We show analytically\\nthat these equations yield the correct zero-temperature limit while at infinite\\ntemperature they reduce to the equations of the + -dimensional theory in\\naccordance with dimensional reduction. The resulting propagators are compared\\nto those obtained from the grand canonical ensemble where an additional ansatz\\nfor the density matrix is required.\\n
Cholesteatoma � Pathology and Treatment
2015-04-16

(1) The prerequisite for development of cholesteatoma is a cholesteatoma bed, that is a loose subepithelial connective tissue layer which acts as a nutrient bed and makes papillary growth of squamous epithelium possible. (2) The formation of cholesteatoma is facilitated by disturbed tubal function with reduced ventilation of the middle ear. (3) The progression of cholesteatoma, especially the bone destruction, is due to enzyme-activated cell groups. The epidermal layer in the postero-superior area of the tympanic membrane has a higher papillary content and during an inflammatory process there is a marked vascular reaction. This particular area has a special nutritional zone and the epidermis is especially well nourished [Lange, 1925]. The main artery to the tympanic membrane travels along the handle of the malleus and gives off branches. In our animal experiments epithelial cones grew into this well-nourished subepithelial zone and formed cholesteatoma. The importance of tubal function as regards cholesteatoma formation can be seen in everyday clinical practice. In stapedectomy patients, the lateral attic wall is usually removed to allow full visualisation of the stapes, but retraction pockets in this area are never seen at subsequent follow-up. However, if the lateral attic wall is removed during surgery for chronic otitis media, reconstruction with cartilage or ceramic is necessary to prevent retraction. This adds weight to the hypothesis that tubal dysfunction is an important aetiological factor in cholesteatoma. This is further supported by the 30 times greater incidence of retraction pockets in patients with cleft palate.
Buried far from home: Sasanian graves at Jebel al‐Emeilah (Sharjah, UAE)
2015-04-16

Human skeletons were recovered in two unmarked burials blown to the surface of a dune south‐west of Jebel al‐Emeilah in the Central Region of the Sharjah Emirate ( UAE ). Sasanian stamp seals were found associated with one of the individuals. A bone fragment of this individual provided a direct radiocarbon date placing it in the Middle Sasanian period. With the aid of strontium isotope analysis it was possible to determine that the two individuals were immigrants to the area that is now part of the UAE .
Classification of Leukemic Cells by Ia Alloantigens and Complement Receptors
2015-04-16

Of particular interest in the study of cell membrane markers of leukemic cells were cytotoxic and immunofluorescent results obtained in comparing Ia alloantigen and complement receptor (CR) expression on normal leukocytic and leukemic cell types. Using discontinuous Ficoll gradients, Ia alloantigens were found on varying numbers of leukemic myelo- and lymphoblasts, and on the early stages of normal melocytes. Ia alloantigens, however, were not detectable on mature polymorphonuclear cells. This establishes human Ia alloantigens as cell surface differentiation markers. The appearance of complement receptors was observed later than that of Ia alloantigens. CR1 (EAC1-4b) showed up later in the differentiation than CR2 (EAC1-3d). Thus, an immunological discrimination between AML blasts and CML blast crisis blasts appears to be possible: AML blasts are mostly Ia-positive but CR-negative, whilst CML blast crisis cells are only 20-30% Ia-positive and carry complement receptors in at least equal amounts. The AML blast cell would appear as the less-differentiated cell type when compared to the CML blast crisis cells. The picture, however, remains complex since in CML blast crisis at least three different types of blast cells can be identified: an Ia-positive and an Ia-negative myeloid blast as well as an Ia-positive lymphoid blast. The quantitative composition of these three elements within the myeloid differentiation profile can vary somewhat from patient to patient. Furthermore, these studies revealed a disturbed differentiation of leukemic cell types.
Self‐esteem Is Mostly Stable Across Young Adulthood: Evidence from Latent STARTS Models
2015-04-17

Abstract How stable is self‐esteem? This long‐standing debate has led to different conclusions across different areas of psychology. Longitudinal data and up‐to‐date statistical models have recently indicated that self‐esteem has stable and autoregressive trait‐like components and state‐like components. We applied latent STARTS models with the goal of replicating previous findings in a longitudinal sample of young adults ( N = 4,532; M age = 19.60, SD = 0.85; 55% female). In addition, we applied multigroup models to extend previous findings on different patterns of stability for men versus women and for people with high versus low levels of depressive symptoms. We found evidence for the general pattern of a major proportion of stable and autoregressive trait variance and a smaller yet substantial amount of state variance in self‐esteem across 10 years. Furthermore, multigroup models suggested substantial differences in the variance components: Females showed more state variability than males. Individuals with higher levels of depressive symptoms showed more state and less autoregressive trait variance in self‐esteem. Results are discussed with respect to the ongoing trait–state debate and possible implications of the group differences that we found in the stability of self‐esteem.
Does Formal Complexity Reflect Cognitive Complexity? Investigating Aspects of the Chomsky Hierarchy in an Artificial Language Learning Study
2015-04-17

This study investigated whether formal complexity, as described by the Chomsky Hierarchy, corresponds to cognitive complexity during language learning. According to the Chomsky Hierarchy, nested dependencies (context-free) are less complex than cross-serial dependencies (mildly context-sensitive). In two artificial grammar learning (AGL) experiments participants were presented with a language containing either nested or cross-serial dependencies. A learning effect for both types of dependencies could be observed, but no difference between dependency types emerged. These behavioral findings do not seem to reflect complexity differences as described in the Chomsky Hierarchy. This study extends previous findings in demonstrating learning effects for nested and cross-serial dependencies with more natural stimulus materials in a classical AGL paradigm after only one hour of exposure. The current findings can be taken as a starting point for further exploring the degree to which the Chomsky Hierarchy reflects cognitive processes.
Reactions with a Metalloid Tin Cluster {Sn10[Si(SiMe3)3]4}2−: Ligand Elimination versus Coordination Chemistry
2015-04-17

Abstract Chemistry that uses metalloid tin clusters as a starting material is of fundamental interest towards understanding the reactivity of such compounds. Since we identified {Sn 10 [Si(SiMe 3 ) 3 ] 4 } 2− 7 as an ideal candidate for such reactions, we present a further step in the understanding of metalloid tin cluster chemistry. In contrast to germanium chemistry, ligand elimination seems to be a major reaction channel, which leads to the more open metalloid cluster {Sn 10 [Si(SiMe 3 ) 3 ] 3 } − 9 , in which the Sn core is only shielded by three Si(SiMe 3 ) 3 ligands. Compound 9 is obtained through different routes and is crystallised together with two different countercations. Besides the structural characterisation of this novel metalloid tin cluster, the electronic structure is analysed by 119 Sn Mössbauer spectroscopy. Additionally, possible reaction pathways are discussed. The presented first step into the chemistry of metalloid tin clusters thus indicates that, with respect to metalloid germanium clusters, more reaction channels are accessible, thereby leading to a more complex reaction system.
DNA Methylation: A Possible Target for Current and Future Studies on Cancer?
2015-04-17

The field of epigenetics encompasses studies about the ways in which genes are influenced by various external stimuli, such as drugs, chemicals, and the environment. Over the last few years, it has become an increasingly important area of research. Recently, substantial evidence has been presented for the claim that certain diseases, including cancer, exhibit epigenetic changes. In the present overview, we will give a brief summary of recent observations on epigenetics and cancer as well as of the ways in which various small molecules may influence the epigenetic state of cells. Keywords: Cancer, CpG islands, DNA methylation, epigenetic drugs, epigenetics, TET proteins.
Parental environmental effects due to contrasting watering adapt competitive ability, but not drought tolerance, in offspring of a semi‐arid annual Brassicaceae
2015-04-18

Summary Parental effects ( PE ) can be adaptive and improve offspring performance when parents and offspring experience similar environmental conditions. However, it is unknown whether adaptive PE exist also in habitats where such similarity is unlikely due to strong temporal variation. In particular, we do not know whether PE can adapt offspring to fluctuating levels of neighbour competition in such habitats. Here, we tested for adaptive PE in terms of two key environmental factors in a semi‐arid annual system, competition and drought. While rainfall was stochastic in the study site, the competitive environment was partly predictable: higher plant densities followed after favourable (rainy) years due to high seed production. We therefore expected PE to adapt the offspring's competitive ability to these (predictable) fluctuations in plant densities, rather than to adapt the offspring's drought tolerance to the (unpredictable) occurrence of intensified drought. Parental plants of Biscutella didyma , an annual Brassicaceae, were raised under favourable watering and under drought conditions. Offspring performance was then tested under a full‐factorial combination of two neighbour regimes and six watering levels in the glasshouse. Offspring of parents grown under favourable conditions were stronger competitors. This was associated with a small shift in phenology but not with higher parental seed provisioning. Offspring from parents grown under drought showed no improved drought tolerance. Moreover, no PE were detectable when offspring were grown without neighbours. Our results suggest a novel path of adaptive PE : higher competitive ability was induced in offspring that were more likely to experience high neighbour densities. Together with the lack of adaptive PE towards drought tolerance, this emphasizes that a correlation between parental and offspring environment is crucial for adaptive PE to evolve. Our results also call for the inclusion of competitive effects in future PE studies. Synthesis . This study demonstrates the important role of adaptive PE for plant fitness (regarding competition) but also their limits (regarding drought) in temporally variable environments, based on the predictability of the respective environmental factor.
Contemporary evolution during invasion: evidence for differentiation, natural selection, and local adaptation
2015-04-20

Abstract Biological invasions are ‘natural’ experiments that can improve our understanding of contemporary evolution. We evaluate evidence for population differentiation, natural selection and adaptive evolution of invading plants and animals at two nested spatial scales: (i) among introduced populations (ii) between native and introduced genotypes. Evolution during invasion is frequently inferred, but rarely confirmed as adaptive. In common garden studies, quantitative trait differentiation is only marginally lower (~3.5%) among introduced relative to native populations, despite genetic bottlenecks and shorter timescales (i.e. millennia vs. decades). However, differentiation between genotypes from the native vs. introduced range is less clear and confounded by nonrandom geographic sampling; simulations suggest this causes a high false‐positive discovery rate (&gt;50%) in geographically structured populations. Selection differentials (¦s¦) are stronger in introduced than in native species, although selection gradients (¦ β ¦) are not, consistent with introduced species experiencing weaker genetic constraints. This could facilitate rapid adaptation, but evidence is limited. For example, rapid phenotypic evolution often manifests as geographical clines, but simulations demonstrate that nonadaptive trait clines can evolve frequently during colonization (~two‐thirds of simulations). Additionally, Q ST ‐ F ST studies may often misrepresent the strength and form of natural selection acting during invasion. Instead, classic approaches in evolutionary ecology (e.g. selection analysis, reciprocal transplant, artificial selection) are necessary to determine the frequency of adaptive evolution during invasion and its influence on establishment, spread and impact of invasive species. These studies are rare but crucial for managing biological invasions in the context of global change.
Predictive soil mapping with limited sample data
2015-04-20

Summary Existing predictive soil mapping ( PSM ) methods often require soil sample data to be sufficient to represent soil–environment relationships throughout the study area. However, in many parts of the world with only a limited quantity of soil sample data to represent the study area, this is still an issue for PSM application. This paper presents a method, named ‘individual predictive soil mapping’ ( iPSM ), which can make use of limited soil sample data for PSM . With the assumption that similar environmental conditions have similar soils, iPSM uses the soil–environment relationship at each individual soil sample location to predict soil properties at unvisited locations and estimate prediction uncertainty. Specifically, the environmental similarities of an unvisited location to a set of soil sample locations are used in a weighted average method to integrate the soil–environment relationships at sample locations for prediction and uncertainty estimation. As a case study, iPSM was applied to map soil organic matter ( SOM ) content (%) in the topsoil layer using two sets of soil samples. Compared with multiple linear regression ( MLR ), iPSM produced a more accurate SOM map (root mean squared error ( RMSE ) 1.43, mean absolute error ( MAE ) 1.16) than MLR ( RMSE 8.54, MAE 7.34) the ability of the sample set to represent the study area is limited and achieved a comparable accuracy ( RMSE 1.10, MAE 0.69) with MLR ( RMSE 1.01, MAE 0.73) when the sample set could represent the study area better. In addition, the prediction uncertainty estimated by iPSM was positively related to prediction residuals in both scenarios. This study demonstrates that iPSM is an effective alternative when existing soil samples are limited in their ability to represent the study area and the prediction uncertainty in iPSM can be used as an indicator of its prediction accuracy.
The Response of the Alpine Dwarf Shrub Salix herbacea to Altered Snowmelt Timing: Lessons from a Multi-Site Transplant Experiment
2015-04-20

Climate change is altering spring snowmelt patterns in alpine and arctic ecosystems, and these changes may alter plant phenology, growth and reproduction. To predict how alpine plants respond to shifts in snowmelt timing, we need to understand trait plasticity, its effects on growth and reproduction, and the degree to which plants experience a home-site advantage. We tested how the common, long-lived dwarf shrub Salix herbacea responded to changing spring snowmelt time by reciprocally transplanting turfs of S. herbacea between early-exposure ridge and late-exposure snowbed microhabitats. After the transplant, we monitored phenological, morphological and fitness traits, as well as leaf damage, during two growing seasons. Salix herbacea leafed out earlier, but had a longer development time and produced smaller leaves on ridges relative to snowbeds. Longer phenological development times and smaller leaves were associated with reduced sexual reproduction on ridges. On snowbeds, larger leaves and intermediate development times were associated with increased clonal reproduction. Clonal and sexual reproduction showed no response to altered snowmelt time. We found no home-site advantage in terms of sexual and clonal reproduction. Leaf damage probability depended on snowmelt and thus exposure period, but had no short-term effect on fitness traits. We conclude that the studied populations of S. herbacea can respond to shifts in snowmelt by plastic changes in phenology and leaf size, while maintaining levels of clonal and sexual reproduction. The lack of a home-site advantage suggests that S. herbacea may not be adapted to different microhabitats. The studied populations are thus unlikely to react to climate change by rapid adaptation, but their responses will also not be constrained by small-scale local adaptation. In the short term, snowbed plants may persist due to high stem densities. However, in the long term, reduction in leaf size and flowering, a longer phenological development time and increased exposure to damage may decrease overall performance of S. herbacea under earlier snowmelt.
The Novel Extracellular Cyclophilin A (CyPA) - Inhibitor MM284 Reduces Myocardial Inflammation and Remodeling in a Mouse Model of Troponin I -Induced Myocarditis
2015-04-20

Cyclophilins are a group of highly conserved cytosolic enzymes that have a peptidylprolyl cis/trans isomerase activity. Cyclophilin A (CyPA) can be secreted in the extracellular space by inflammatory cells and upon cell death. The presence of CyPA in patients with non-ischemic cardiomyopathy is associated with poor clinical prognosis. Here, we investigated the inhibition of extracellular CyPA in a mouse model of troponin I-induced autoimmune myocarditis using the strictly extracellular CyPA-inhibitor MM284. Since A/J mice develop severe inflammation and fibrosis after immunization with murine cardiac troponin I (mcTn I), we used this model to analyze the effects of an extracellular CyPA inhibition. As extracellular CyPA-inhibitor we used the recently described CsA-derivate MM284. In vitro studies confirmed that MM284 inhibits CyPA-induced monocytic migration and adhesion. A/J mice immunized with mcTnI were treated with MM284 or vehicle every second day. After 28 days, we found a considerable reduction of myocardial injury and fibrosis. Further analysis revealed a reduced myocardial presence of T-cells and macrophages compared to control treated animals. Whereas MMP-9 expression was reduced significantly by MM284, we observed no significant reduction of inflammatory cytokines such as IL-6 or TNFα. Extracellular CyPA plays an important role in autoimmune myocarditis for myocardial damage and fibrosis. Our data suggest a new pharmacological approach for the treatment of myocardial inflammation and reduction of cardiac fibrosis by inhibition of extracellular CyPA.
Sequence Variability of Hepatitis A Virus and Factor VIII Associated Hepatitis A Infections in Hemophilia Patients in Europe
2015-04-20

AbstractOutbreaks and sporadic cases of hepatitis A have been observed in 4 European countries in hemophilia patients receiving factor VIII preparations. PCR amplification of potential hepatitis A virus (HAV) nucleic acid present in plasma pools, purified factor VIII and acute-phase sera from infected individuals has been performed and the nucleic acid sequence determined for those samples that resulted in a positive PCR product. HAV sequences were detected in the serum of 2 German patients, but not in the factor VIII lots administered to these individuals. Screening of plasma pools and the corresponding 5 lots of factor VIII associated with the outbreak in Ireland did not reveal any HAV sequences. In contrast, a study of samples from Italy detected HAV sequences in 5 of 12 lots and in 2 hemophilia patients who developed hepatitis A. These data suggest that implicated factor VIII preparations might have been involved in the outbreaks of HAV infection among Italian hemophiliacs. However, no molecular evidence was obtained for a similar association in Germany or Ireland. The preliminary data from these two investigations must be verified by animal inoculation studies and supported by epidemiologic analysis.
Detection of Hepatitis A Virus in a Factor VIII Preparation by Antigen Capture/PCR
2015-04-20

AbstractThe antigen capture/PCR (AC/PCR) has been applied in the analysis of various factor VIII preparations, which were suspected to be contaminated with hepatitis A virus (HAV). AC/PCR involves capturing the antigen, i.e. the intact virus particles, by binding to the HAV monoclonal antibody mAb 7e7, reverse transcription of the viral RNA and amplification of the cDNA with HAV-specific primer pairs. The PCR analysis of one factor VIII concentrate yielded an HAV-specific DNA product, which could be confirmed by Southern blot analysis. The HAV strain recovered by AC/PCR from this factor VIII concentrate could be classified into genotype III after solid-phase sequencing of the product and comparison with the consensus sequences for the known HAV genotypes. Analysis of the sera from 3 haemophiliacs treated with this batch has not resulted in a reliable product. However, the results obtained indicate that HAV can be detected in purified factor VIII preparations by AC/PCR.