Miracle-dz/UniFAR-FTUs huggingface dataset:
Neuroregenerative Mechanisms of Allopregnanolone in Alzheimer’s Disease

The proliferative pool and regenerative potential of neural stem cells diminishes with age, a phenomenon that may be exacerbated in prodromal and mild Alzheimer’s disease (AD) brains. In parallel, the neuroactive progesterone metabolite, allopregnanolone (APα), along with a host of other factors, is decreased in the AD brain. Results of preclinical analyses demonstrate that APα is a potent inducer of neural progenitor proliferation of both rodent and human derived neural progenitor cells in vitro. In vivo, APα significantly increased neurogenesis within the subgranular zone of the dentate gyrus and subventricular zone of the 3xTgAD mouse model. Functionally, APα reversed the learning and memory deficits of 3xTgAD mice prior to and following the onset of AD pathology and was comparably efficacious in aged normal mice. In addition to inducing regenerative responses in mouse models of AD, APα significantly reduced beta-amyloid burden, beta-amyloid binding alcohol dehydrogenase load, and microglial activation. In parallel, APα increased markers of white matter generation and cholesterol homeostasis. Analyses to determine the optimal treatment regimen in the 3xTgAD mouse brain indicated that a treatment regimen of APα once per week was optimal for both inducing neurogenesis and reducing AD pathology. Pharmacokinetic analyses indicated that APα is rapidly increased in both plasma and brain following a single dose. APα is most efficacious when administered once per week which will contribute to its margin of safety. Further, analyses in both animals and humans have provided parameters for safe APα dosage exposure in humans. From a translational perspective, APα is a small molecular weight, blood brain barrier penetrant molecule with substantial preclinical efficacy data as a potential Alzheimer’s therapeutic with existing safety data in animals and humans. To our knowledge, APα is the only small molecule that both promotes neural progenitor regeneration in brain and simultaneously reduces AD pathology burden.
Pathways and variability of the off-equatorial undercurrents in the Atlantic Ocean

The cold upwelling waters of the eastern tropical oceans not only interact with the atmospheric circulation via changing the sea surface temperatures but also influence the biological activity via affecting the nutrient and oxygen contents of the upwelling waters. While the sources of the equatorial upwelling associated with the Equatorial Undercurrent (EUC) have been studied extensively, the relevance of the northern and southern off-equatorial undercurrents (NEUC, SEUC) for the off-equatorial upwelling regions has remained unclear. In this study we use output from a high-resolution, 1/12° model (FLAME) to investigate the mean pathways and variability of the off-equatorial undercurrents (OEUCs) in the Atlantic. In particular, a calculation of Lagrangian trajectories helps to gain insight into the source waters of the OEUCs and their connection to the upwelling regions in the eastern tropical Atlantic. In the model solution the sources of both OEUCs belong almost exclusively to the Southern Hemisphere. The pathways of the source waters are found to be governed by strong recirculations between the different eastward and westward zonal currents because of intense eddy motions associated with the tropical instability wave activity. Whereas the SEUC is predominantly fed through the recirculation in the ocean interior, the NEUC is also fed by a weak inflow from the western boundary current. Investigation of the fate of the NEUC shows only a weak direct supply to the upwelling in the Guinea Dome and along the African coast but a significant contribution to the equatorial upwelling.
PREDICTIVE MODEL FOR ATMOSPHERIC CORROSION OF ALUMINIUM ALLOY BY ARTIFICIAL NEURAL NETWORK

Atmospheric corrosion of aluminium alloy was predicted using BP neural network,and relation between training error and predicting error was researched.Artificial neural network(ANN) model is composed of seven input nodes,five hidden layer nodes and one output node.Correlation coefficient for model is 0.8821,ANN prediction result is close to practical data.By sensitivity analysis method,metallurgical factor and environmental factor influence for atmospheric corrosion rate of aluminium alloy was researched.
Rethinking the sGLOH Descriptor

sGLOH (shifting GLOH) is a histogram-based keypoint descriptor that can be associated to multiple quantized rotations of the keypoint patch without any recomputation. This property can be exploited to define the best distance between two descriptor vectors, thus avoiding computing the dominant orientation. In addition, sGLOH can reject incongruous correspondences by adding a global constraint on the rotations either as an a priori knowledge or based on the data. This paper thoroughly reconsiders sGLOH and improves it in terms of robustness, speed and descriptor dimension. The revised sGLOH embeds more quantized rotations, thus yielding more correct matches. A novel fast matching scheme is also designed, which significantly reduces both computation time and memory usage. In addition, a new binarization technique based on comparisons inside each descriptor histogram is defined, yielding a more compact, faster, yet robust alternative. Results on an exhaustive comparative experimental evaluation show that the revised sGLOH descriptor incorporating the above ideas and combining them according to task requirements, improves in most cases the state of the art in both image matching and object recognition.
Systematic ajmaline challenge in patients with long QT 3 syndrome caused by the most common mutation: a multicentre study

Aims Overlap syndromes of long QT 3 syndrome (LQT3) and the Brugada syndrome (BrS) have been reported. Identification of patients with an overlapping phenotype is crucial before initiation of Class I antiarrhythmic drugs for LQT3. Aim of the present study was to elucidate the yield of ajmaline challenge in unmasking the Brugada phenotype in patients with LQT3 caused by the most common mutation, SCN5A-E1784K. Methods and results Consecutive families in tertiary referral centres diagnosed with LQT3 caused by SCN5A-E1784K were included in the study. Besides routine clinical work-up, ajmaline challenge was performed after informed consent. A total of 23 subjects (11 female, mean age 27 ± 14 years) from 4 unrelated families with a family history of sudden cardiac death and familial diagnosis of the SCN5A-E1784K mutation underwent ajmaline challenge and genetic testing. Sixteen subjects (9 female) were found to be heterozygous carriers of SCN5A-E1784K. Ajmaline challenge was positive in 12 out of the 16 (75%) mutation carriers, but negative in all non-carriers. Following ajmaline, a significant shortening of the rate-corrected JT (JTc) interval was observed in mutation carriers. The baseline JTc interval was significantly longer in mutation carriers with a positive ajmaline challenge compared with those with a negative one. Conclusion Overlap of LQT3 and BrS in patients carrying the most common mutation is high. Therefore, ajmaline challenge represents an important step to rule out potential BrS overlap in these patients before starting sodium channel blockers for the beneficial effect of QT shortening in LQT3.
DNA from the Past Informs Ex Situ Conservation for the Future: An “Extinct” Species of Galápagos Tortoise Identified in Captivity

Background Although not unusual to find captive relicts of species lost in the wild, rarely are presumed extinct species rediscovered outside of their native range. A recent study detected living descendents of an extinct Galápagos tortoise species (Chelonoidis elephantopus) once endemic to Floreana Island on the neighboring island of Isabela. This finding adds to the growing cryptic diversity detected among these species in the wild. There also exists a large number of Galápagos tortoises in captivity of ambiguous origin. The recently accumulated population-level haplotypic and genotypic data now available for C. elephantopus add a critical reference population to the existing database of 11 extant species for investigating the origin of captive individuals of unknown ancestry. Methodology/Findings We reanalyzed mitochondrial DNA control region haplotypes and microsatellite genotypes of 156 captive individuals using an expanded reference database that included all extant Galápagos tortoise species as well as the extinct species from Floreana. Nine individuals (six females and three males) exhibited strong signatures of Floreana ancestry and a high probability of assignment to C. elephantopus as detected by Bayesian assignment and clustering analyses of empirical and simulated data. One male with high assignment probability to C. elephantopus based on microsatellite genotypic data also possessed a “Floreana-like” mitochondrial DNA haplotype. Significance Historical DNA analysis of museum specimens has provided critical spatial and temporal components to ecological, evolutionary, taxonomic and conservation-related research, but rarely has it informed ex situ species recovery efforts. Here, the availability of population-level genotypic data from the extinct C. elephantopus enabled the identification of nine Galápagos tortoise individuals of substantial conservation value that were previously misassigned to extant species of varying conservation status. As all captive individuals of C. elephantopus ancestry currently reside at a centralized breeding facility on Santa Cruz, these findings permit breeding efforts to commence in support of the reestablishment of this extinct species to its native range.
Allegiance and knowledge levels of professionals working with early intensive behavioural intervention in autism

Early intensive behavioural intervention (EIBI) for children with autism spectrum disorder (ASD) is often delivered using a community model. Behaviour modification experts train and supervise non‐experts (e.g. preschool personnel) to teach children according to applied behaviour analysis principles in their natural environment. Several factors predict EIBI outcomes in ASD, for example, knowledge of EIBI and EIBI allegiance among trainers. The aim of the present study was to survey levels of knowledge about and allegiance towards EIBI.
Ca2+ Extrusion by NCX Is Compromised in Olfactory Sensory Neurons of OMP−/− Mice

Background The role of olfactory marker protein (OMP), a hallmark of mature olfactory sensory neurons (OSNs), has been poorly understood since its discovery. The electrophysiological and behavioral phenotypes of OMP knockout mice indicated that OMP influences olfactory signal transduction. However, the mechanism by which this occurs remained unknown. Principal Findings We used intact olfactory epithelium obtained from WT and OMP−/− mice to monitor the Ca2+ dynamics induced by the activation of cyclic nucleotide-gated channels, voltage-operated Ca2+ channels, or Ca2+ stores in single dendritic knobs of OSNs. Our data suggested that OMP could act to modulate the Ca2+-homeostasis in these neurons by influencing the activity of the plasma membrane Na+/Ca2+-exchanger (NCX). Immunohistochemistry verifies colocalization of NCX1 and OMP in the cilia and knobs of OSNs. To test the role of NCX activity, we compared the kinetics of Ca2+ elevation by stimulating the reverse mode of NCX in both WT and OMP−/− mice. The resulting Ca2+ responses indicate that OMP facilitates NCX activity and allows rapid Ca2+ extrusion from OSN knobs. To address the mechanism by which OMP influences NCX activity in OSNs we studied protein-peptide interactions in real-time using surface plasmon resonance technology. We demonstrate the direct interaction of the XIP regulatory-peptide of NCX with calmodulin (CaM). Conclusions Since CaM also binds to the Bex protein, an interacting protein partner of OMP, these observations strongly suggest that OMP can influence CaM efficacy and thus alters NCX activity by a series of protein-protein interactions.
Coupling immunity and programmed cell suicide in prokaryotes: Life‐or‐death choices

Host‐pathogen arms race is a universal, central aspect of the evolution of life. Most organisms evolved several distinct yet interacting strategies of anti‐pathogen defense including resistance to parasite invasion, innate and adaptive immunity, and programmed cell death (PCD). The PCD is the means of last resort, a suicidal response to infection that is activated when resistance and immunity fail. An infected cell faces a decision between active defense and altruistic suicide or dormancy induction, depending on whether immunity is “deemed” capable of preventing parasite reproduction and consequent infection of other cells. In bacteria and archaea, immunity genes typically colocalize with PCD modules, such as toxins‐antitoxins, suggestive of immunity‐PCD coupling, likely mediated by shared proteins that sense damage and “predict” the outcome of infections. In type VI CRISPR‐Cas systems, the same enzyme that inactivates the target RNA might execute cell suicide, in a case of ultimate integration of immunity and PCD.
Aerial image geolocalization by matching its line structure with route map

The classic way of aerial photographs geolocation is to bind their local coordinates to a geographic coordinate system using GPS and IMU data. At the same time the possibility of geolocation in a jammed navigation field is also of interest for practical purposes. In this paper we consider one approach to visual localization relatively to a vector road map without GPS. We suggest a geolocalization algorithm which detects image line segments and looks for a geometrical transformation which provides the best mapping between the obtained segments set and line segments in the road map. We consider IMU and altimeter data still known which allows to work with orthorectified images. The problem is hence reduced to a search for a transformation which contains an arbitrary shift and bounded rotation and scaling relatively to the vector map. These parameters are estimated using RANSAC by matching straight line segments from the image to vector map segments. We also investigate how the proposed algorithm’s stability is influenced by segment coordinates (two spatial and one angular).
Polymeric corrugated membranes of PMMA fabricated by micro-casting technique for moems and optical aplications

A new micro-casting technique, applied in micrometric scale, is proposed as an alternative method to fabricate PMMA microstructures with strong 3D geometry for MOEMS and optical applications. The process is based on the deposition and subsequent evaporation of adequate PMMA solution on a Si mold fabricated by bulk micromachining. The structures in the Si mold are pyramidal cavities with 100, 200 and 400 μm in the base and the resulting PMMA corrugated membranes exhibit a well-defined inverted image of the mold. Depending of the volume of PMMA solution deposited on the mold, the obtained membranes can be corrugated on both or just on one side. The membranes are characterized by optical and scanning electron microscopy and its optical behavior as diffractive element is also presented.
The tumorigenic potential of pluripotent stem cells: What can we do to minimize it?

Human pluripotent stem cells (hPSCs) have the potential to fundamentally change the way that we go about treating and understanding human disease. Despite this extraordinary potential, these cells also have an innate capability to form tumors in immunocompromised individuals when they are introduced in their pluripotent state. Although current therapeutic strategies involve transplantation of only differentiated hPSC derivatives, there is still a concern that transplanted cell populations could contain a small percentage of cells that are not fully differentiated. In addition, these cells have been frequently reported to acquire genetic alterations that, in some cases, are associated with certain types of human cancers. Here, we try to separate the panic from reality and rationally evaluate the true tumorigenic potential of these cells. We also discuss a recent study examining the effect of culture conditions on the genetic integrity of hPSCs. Finally, we present a set of sensible guidelines for minimizing the tumorigenic potential of hPSC‐derived cells. © 2016 The Authors. Inside the Cell published by Wiley Periodicals, Inc.
Fast admixture analysis and population tree estimation for SNP and NGS data

Motivation: Structure methods are highly used population genetic methods for classifying individuals in a sample fractionally into discrete ancestry components. Contribution: We introduce a new optimization algorithm for the classical STRUCTURE model in a maximum likelihood framework. Using analyses of real data we show that the new method finds solutions with higher likelihoods than the state‐of‐the‐art method in the same computational time. The optimization algorithm is also applicable to models based on genotype likelihoods, that can account for the uncertainty in genotype‐calling associated with Next Generation Sequencing (NGS) data. We also present a new method for estimating population trees from ancestry components using a Gaussian approximation. Using coalescence simulations of diverging populations, we explore the adequacy of the STRUCTURE‐style models and the Gaussian assumption for identifying ancestry components correctly and for inferring the correct tree. In most cases, ancestry components are inferred correctly, although sample sizes and times since admixture can influence the results. We show that the popular Gaussian approximation tends to perform poorly under extreme divergence scenarios e.g. with very long branch lengths, but the topologies of the population trees are accurately inferred in all scenarios explored. The new methods are implemented together with appropriate visualization tools in the software package Ohana. Availability and Implementation: Ohana is publicly available at https://github.com/jade‐cheng/ohana. In addition to source code and installation instructions, we also provide example work‐flows in the project wiki site. Contact: jade.cheng@birc.au. dk Supplementary information: Supplementary data are available at Bioinformatics online.
ROC surface assessment of the ANB angle and Wits appraisal’s diagnostic performance with a statistically derived ‘gold standard’: does normalizing measurements have any merit?

Objective To assess the ANB angle's and Wits appraisal's diagnostic performance using an extended version of Receiver Operating Curve (ROC) analysis, which renders ROC surfaces. These were calculated for both the conventional and normalized cephalometric tests (calculated by exchanging the patient's reference landmarks with those of the Procrustes superimposed sample mean shape). The required 'gold standard' was derived statistically, by applying generalized Procrustes superimposition (GPS) and principal component analysis (PCA) to the digitized landmarks, and ordering patients based upon their PC2 scores. Methods Digitized landmarks of 200 lateral cephalograms (107 males, mean age: 12.8 years, SD: 2.2, 93 females, mean age: 13.2 years, SD: 1.7) were subjected to GPS and PCA. Upon calculating the conventional and normalized ANB and Wits values, ROC surfaces were constructed by varying not just the cephalometric test's cut-off value within each ROC curve, but also the gold standard cut-off value over different ROC curves in 220 steps between -2 and 2 standard deviations along PC2. The volume under the resulting ROC surfaces (VUS) served as a measure of overall diagnostic performance. The statistical significance of the volume differences was determined using permutation tests (1000 rounds, with replacement). Results The diagnostic performance of the conventional ANB and Wits was remarkably similar for both Class I/II (81.1 and 80.75% VUS, respectively, P > 0.05). Normalizing the measurements improved all VUS highly significantly (91 and 87.2 per cent, respectively, P < 0.001). Conclusion The conventional ANB and Wits do not differ in their diagnostic performance. Normalizing the measurements does seem to have some merit.
Auditory verbal hallucinations in first-episode psychosis: a phenomenological investigation

Background In dimensional understanding of psychosis, auditory verbal hallucinations (AVH) are unitary phenomena present on a continuum from non-clinical voice hearing to severe mental illness. There is mixed evidence for this approach and a relative absence of research into subjective experience of AVH in early psychosis. Aims To conduct primary research into the nature of subjective experience of AVH in first-episode psychosis. Method A phenomenological study using diary and photo-elicitation qualitative techniques investigating the subjective experience of AVH in 25 young people with first-episode psychosis. Results AVH are characterised by: (a) entity, as though from a living being with complex social interchange; and (b) control, exerting authority with ability to influence. AVH are also received with passivity, often accompanied by sensation in other modalities. Conclusions A modern detailed phenomenological investigation, without presupposition, gives results that echo known descriptive psychopathology. However, novel findings also emerge that may be features of AVH in psychosis not currently captured with standardised measures. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.
Sodium‐dependent Vitamin C transporter 2 deficiency impairs myelination and remyelination after injury: Roles of collagen and demethylation

Peripheral nerve myelination involves rapid production of tightly bound lipid layers requiring cholesterol biosynthesis and myelin protein expression, but also a collagen‐containing extracellular matrix providing mechanical stability. In previous studies, we showed a function of ascorbic acid in peripheral nerve myelination and extracellular matrix formation in adult mice. Here, we sought the mechanism of action of ascorbic acid in peripheral nerve myelination using different paradigms of myelination in vivo and in vitro. We found impaired myelination and reduced collagen expression in Sodium‐dependent Vitamin C Transporter 2 heterozygous mice (SVCT2+/‐) during peripheral nerve development and after peripheral nerve injury. In dorsal root ganglion (DRG) explant cultures, hypo‐myelination could be rescued by precoating with different collagen types. The activity of the ascorbic acid‐dependent demethylating Ten‐eleven‐translocation (Tet) enzymes was reduced in ascorbic acid deprived and SVCT2+/‐ DRG cultures. Further, in ascorbic acid‐deprived DRG cultures, methylation of a CpG island in the collagen alpha1 (IV) and alpha2 (IV) bidirectional promoter region was increased compared to wild‐type and ascorbic acid treated controls. Taken together, these results provide further evidence for the function of ascorbic acid in myelination and extracellular matrix formation in peripheral nerves and suggest a putative molecular mechanism of ascorbic acid function in Tet‐dependent demethylation of collagen promoters.