Miracle-dz/UniFAR-FTUs huggingface dataset:
Physiological Properties of Cholinergic and Non-Cholinergic Magnocellular Neurons in Acute Slices from Adult Mouse Nucleus Basalis

Background The basal forebrain is a series of nuclei that provides cholinergic input to much of the forebrain. The most posterior of these nuclei, nucleus basalis, provides cholinergic drive to neocortex and is involved in arousal and attention. The physiological properties of neurons in anterior basal forebrain nuclei, including medial septum, the diagonal band of Broca and substantia innominata, have been described previously. In contrast the physiological properties of neurons in nucleus basalis, the most posterior nucleus of the basal forebrain, are unknown. Methodology/Principal Findings Here we investigate the physiological properties of neurons in adult mouse nucleus basalis. We obtained cell-attached and whole-cell recordings from magnocellular neurons in slices from P42-54 mice and compared cholinergic and non-cholinergic neurons, distinguished retrospectively by anti-choline acetyltransferase immunocytochemistry. The majority (70–80%) of cholinergic and non-cholinergic neurons were silent at rest. Spontaneously active cholinergic and non-cholinergic neurons exhibited irregular spiking at 3 Hz and at 0.3 to 13.4 Hz, respectively. Cholinergic neurons had smaller, broader action potentials than non-cholinergic neurons (amplitudes 64±3.4 and 75±2 mV; half widths 0.52±0.04 and 0.33±0.02 ms). Cholinergic neurons displayed a more pronounced slow after-hyperpolarization than non-cholinergic neurons (13.3±2.2 and 3.6±0.5 mV) and were unable to spike at high frequencies during tonic current injection (maximum frequencies of ∼20 Hz and >120 Hz). Conclusions/Significance Our results indicate that neurons in nucleus basalis share similar physiological properties with neurons in anterior regions of the basal forebrain. Furthermore, cholinergic and non-cholinergic neurons in nucleus basalis can be distinguished by their responses to injected current. To our knowledge, this is the first description of the physiological properties of cholinergic and non-cholinergic neurons in the posterior aspects of the basal forebrain complex and the first study of basal forebrain neurons from the mouse.
Why olanzapine beats risperidone, risperidone beats quetiapine, and quetiapine beats olanzapine: an exploratory analysis of head-to-head comparison studies of second-generation antipsychotics.

OBJECTIVE In many parts of the world, second-generation antipsychotics have largely replaced typical antipsychotics as the treatment of choice for schizophrenia. Consequently, trials comparing two drugs of this class--so-called head-to-head studies--are gaining in relevance. The authors reviewed results of head-to-head studies of second-generation antipsychotics funded by pharmaceutical companies to determine if a relationship existed between the sponsor of the trial and the drug favored in the study's overall outcome. METHOD The authors identified head-to-head comparison studies of second-generation antipsychotics through a MEDLINE search for the period from 1966 to September 2003 and identified additional head-to-head studies from selected conference proceedings for the period from 1999 to February 2004. The abstracts of all studies fully or partly funded by pharmaceutical companies were modified to mask the names and doses of the drugs used in the trial, and two physicians blinded to the study sponsor reviewed the abstracts and independently rated which drug was favored by the overall outcome measures. Two authors who were not blinded to the study sponsor reviewed the entire report of each study for sources of bias that could have affected the results in favor of the sponsor's drug. RESULTS Of the 42 reports identified by the authors, 33 were sponsored by a pharmaceutical company. In 90.0% of the studies, the reported overall outcome was in favor of the sponsor's drug. This pattern resulted in contradictory conclusions across studies when the findings of studies of the same drugs but with different sponsors were compared. Potential sources of bias occurred in the areas of doses and dose escalation, study entry criteria and study populations, statistics and methods, and reporting of results and wording of findings. CONCLUSIONS Some sources of bias may limit the validity of head-to-head comparison studies of second-generation antipsychotics. Because most of the sources of bias identified in this review were subtle rather than compelling, the clinical usefulness of future trials may benefit from minor modifications to help avoid bias. The authors make a number of concrete suggestions for ways in which potential sources of bias can be addressed by study initiators, peer reviewers of studies under consideration for publication, and readers of published studies.
Radiation from Structured-Ring Resonators

We investigate the scalar-wave resonances of systems composed of identical Neumann-type inclusions arranged periodically around a circular ring. Drawing on natural similarities with the undamped Rayleigh-Bloch waves supported by infinite linear arrays, we deduce asymptotically the exponentially small radiative damping in the limit where the ring radius is large relative to the periodicity. In our asymptotic approach, locally linear Rayleigh-Bloch waves that attenuate exponentially away from the ring are matched to a ring-scale WKB-type wave field. The latter provides a descriptive physical picture of how the mode energy is transferred via tunnelling to a circular evanescent-to-propagating transition region a finite distance away from the ring, from where radiative grazing rays emanate to the far field. Excluding the zeroth-order standing-wave modes, the position of the transition circle bifurcates with respect to clockwise and anti-clockwise contributions, resulting in striking spiral wavefronts.
On Atomic Surface Roughness Evaluation

The atomic surface finish or roughness can be defined as the roughness limit of a surface. Its value has been demonstrated both in theory and in experiments to be non-zero [1, 2]. This parameter is very important in assessing the quality of high performance nanosurfaces, and so its understanding is very crucial. In this study, multi-pass nanometric atomistic simulations were carried out, with a diamond tool on a copper workpiece to create a nanosurface and the results provide the platform from which the atomic surface roughness was evaluated. The estimated surface roughness (Sa) was in the order of 0.3nm.
Ethnic, Familial, and Religious Identity of Roma Adolescents in Bulgaria, Czech Republic, Kosovo, and Romania in Relation to Their Level of Well-Being.

This study examines ethnic, national, familial, and religious identity and well-being of 632 Roma minority and 589 majority adolescents (age: M = 15.98 years, SD = 1.34) in Bulgaria, the Czech Republic, Kosovo, and Romania. Results indicated that Roma showed lower endorsement of national identity but stronger religious identity than their majority counterparts. Path models showed positive associations of familial and religious identities with well-being, whereas Roma identity was negatively associated with well-being, particularly for Roma in Bulgaria and Kosovo (countries with a less active policy toward improving conditions of Roma). In the latter countries, Roma ethnic identity is less relevant and weakly associated with psychological well-being of youth.
Sequence and analysis of mtDNA control region in Cnaphalacrocis medinalis Guenée and Marasmia patnalis Bradley (Lepidoptera: Pyralidae)

Abstract Rice leaffolders Cnaphalocrocis medinalis and Marasmia patnalis (Lepidoptera: Pyralidae) are important rice pests and morphologically related with same damage methods. The control region of mitochondrial DNA (mtDNA) in two rice leaffolders C. medinalis and M. patnalis were sequenced and analyzed. The control regions of the two rice leaffolders are located between 12S ribosomal RNA and tRNAMet, and exhibit conserved structural elements. We identified the poly T stretches, (TA)n block, and stem-loop structure. There are no long tandem repeats found in mtDNA control region in the two rice leaffolders studied. Nevertheless, we did not find the GA-rich block in mtDNA control regions of the two rice leaffolders. The molecular-based phylogenies support the traditional morphologically based view of relationships of Pyralidae within the Ditrysia. The addition of the C. medinalis and M. patnalis mtDNA control regions to the literature promotes the understanding of the molecular evolution of Pyralidae in Ditrysia.
Oligonucleotides targeting TCF4 triplet repeat expansion inhibit RNA foci and mis-splicing in Fuchs’ dystrophy

Abstract Fuchs’ endothelial corneal dystrophy (FECD) is the most common repeat expansion disorder. FECD impacts 4% of U.S. population and is the leading indication for corneal transplantation. Most cases are caused by an expanded intronic CUG tract in the TCF4 gene that forms nuclear foci, sequesters splicing factors and impairs splicing. We investigated the sense and antisense RNA landscape at the FECD gene and find that the sense-expanded repeat transcript is the predominant species in patient corneas. In patient tissue, sense foci number were negatively correlated with age and showed no correlation with sex. Each endothelial cell has ∼2 sense foci and each foci is single RNA molecule. We designed antisense oligonucleotides (ASOs) to target the mutant-repetitive RNA and demonstrated potent inhibition of foci in patient-derived cells. Ex vivo treatment of FECD human corneas effectively inhibits foci and reverses pathological changes in splicing. FECD has the potential to be a model for treating many trinucleotide repeat diseases and targeting the TCF4 expansion with ASOs represents a promising therapeutic strategy to prevent and treat FECD.
Geometric Detection Algorithms for Cavities on Protein Surfaces in Molecular Graphics: A Survey

Detecting and analysing protein cavities provides significant information about active sites for biological processes (e.g. protein–protein or protein–ligand binding) in molecular graphics and modelling. Using the three‐dimensional (3D) structure of a given protein (i.e. atom types and their locations in 3D) as retrieved from a PDB (Protein Data Bank) file, it is now computationally viable to determine a description of these cavities. Such cavities correspond to pockets, clefts, invaginations, voids, tunnels, channels and grooves on the surface of a given protein. In this work, we survey the literature on protein cavity computation and classify algorithmic approaches into three categories: evolution‐based, energy‐based and geometry‐based. Our survey focuses on geometric algorithms, whose taxonomy is extended to include not only sphere‐, grid‐ and tessellation‐based methods, but also surface‐based, hybrid geometric, consensus and time‐varying methods. Finally, we detail those techniques that have been customized for GPU (graphics processing unit) computing.
Assessing the causal association between 25‐hydroxyvitamin D and the risk of oral and oropharyngeal cancer using Mendelian randomization

Circulating 25‐hydroxyvitamin D (25OHD) is an appealing potential intervention for cancer risk and has been associated with oral and oropharyngeal cancer risk but evidence is inconsistent. The availability of genetic variants, uncorrelated with known confounders, but predictive of 25OHD and genetic data in a large oral and oropharyngeal cancer collaboration aids causal inference when assessing this association. A total of 5,133 oral and oropharyngeal cancer cases and 5,984 controls with genetic data were included in the study. Participants were based in Europe, North America and South America and were part of the Genetic Associations and Mechanisms in Oncology (GAME‐ON) Network. Five genetic variants reliably associated with circulating 25OHD were used to create a relative genetic measure of 25OHD. In the absence of measured 25OHD, two‐sample Mendelian randomization using individual level outcome data were used to estimate causal odds ratios (OR) for cancer case status per standard deviation increase in log25OHD. Analyses were replicated in an independent population‐based cohort (UK Biobank). In the GAME‐ON study, there was little evidence of a causal association between circulating 25OHD and oral cancer (OR = 0.86 [0.68;1.09], p = 0.22), oropharyngeal cancer (OR = 1.28 [0.72;2.26], p = 0.40) or when sites were combined (OR = 1.01 [0.74;1.40], p = 0.93). Replication in UK Biobank and pooled estimates produced similar results. Our study suggests that a clinically relevant protective effect of 25OHD on oral and oropharyngeal cancer risk is unlikely and supplementation of the general population with 25OHD is unlikely to be beneficial in preventing these cancers.
Efficiency Enhancement of Wireless Power Transfer System Using MNZ Metamaterials

In this paper, a simple approach for efficiency enhancement of a wireless power transfer system by using mu near zero (MNZ) type of metamaterial is proposed. A single slab containing onesided periodic structures of 3×3 array of meander-line unit cell has been placed between transmitting and receiving coils in the wireless power transfer system. The presented metamaterial structure is less complex than other reported metamaterial structures in the area of wireless power transfer system. The simulation and measurement have been performed with and without the metamaterial slab. Using the metamaterial slab, the maximum efficiency has been obtained about 55.3%, i.e., an improvement of efficiency around 15.7% is obtained compared to a wireless power transfer system without the metamaterials. Interestingly, the proposed wireless power transfer system shows a steady improvement of efficiency even if the distance between the transmitting and receiving coil is increased.
Phylogeography and taxonomic status of trout and salmon from the Ponto‐Caspian drainages, with inferences on European Brown Trout evolution and taxonomy

Abstract Current taxonomy of western Eurasian trout leaves a number of questions open; it is not clear to what extent some species are distinct genetically and morphologically. The purpose of this paper was to explore phylogeography and species boundaries in freshwater and anadromous trout from the drainages of the Black and the Caspian Seas (Ponto‐Caspian). We studied morphology and mitochondrial phylogeny, combining samples from the western Caucasus within the potential range of five nominal species of trout that are thought to inhabit this region, and using the sequences available from GenBank. Our results suggest that the genetic diversity of trout in the Ponto‐Caspian region is best explained with the fragmentation of catchments. (1) All trout species from Ponto‐Caspian belong to the same mitochondrial clade, separated from the other trout since the Pleistocene; (2) the southeastern Black Sea area is the most likely place of diversification of this clade, which is closely related to the clades from Anatolia; (3) The species from the Black Sea and the Caspian Sea drainages are monophyletic; (4) except for the basal lineage of the Ponto‐Caspian clade, Salmo rizeensis, all the lineages produce anadromous forms; (5) genetic diversification within the Ponto‐Caspian clade is related to Pleistocene glacial waves; (6) the described morphological differences between the species are not fully diagnostic, and some earlier described differences depend on body size; the differences between freshwater and marine forms exceed those between the different lineages. We suggest a conservative taxonomic approach, using the names S. rizeensis and Salmo labrax for trout from the Black Sea basin and Salmo caspius and Salmo ciscaucasicus for the fish from the Caspian basin.
Incentives in the Dark: Multi-armed Bandits for Evolving Users with Unknown Type

Design of incentives or recommendations to users is becoming more common as platform providers continually emerge. We propose a multi-armed bandit approach to the problem in which users types are unknown a priori and evolve dynamically in time. Unlike the traditional bandit setting, observed rewards are generated by a single Markov process. We demonstrate via an illustrative example that blindly applying the traditional bandit algorithms results in very poor performance as measured by regret. We introduce two variants of classical bandit algorithms, upper confidence bound (UCB) and epsilon-greedy, for which we provide theoretical bounds on the regret. We conduct a number of simulation-based experiments to show how the algorithms perform in comparison to traditional UCB and epsilon-greedy algorithms as well as reinforcement learning (Q-learning).
Evolution of Extra-Nigral Damage Predicts Behavioural Deficits in a Rat Proteasome Inhibitor Model of Parkinson's Disease

Establishing the neurological basis of behavioural dysfunction is key to provide a better understanding of Parkinson's disease (PD) and facilitate development of effective novel therapies. For this, the relationships between longitudinal structural brain changes associated with motor behaviour were determined in a rat model of PD and validated by post-mortem immunohistochemistry. Rats bearing a nigrostriatal lesion induced by infusion of the proteasome inhibitor lactacystin into the left-medial forebrain bundle and saline-injected controls underwent magnetic resonance imaging (MRI) at baseline (prior to surgery) and 1, 3 and 5 weeks post-surgery with concomitant motor assessments consisting of forelimb grip strength, accelerating rotarod, and apormorphine-induced rotation. Lactacystin-injected rats developed early motor deficits alongside decreased ipsilateral cortical volumes, specifically thinning of the primary motor (M1) and somatosensory cortices and lateral ventricle hypertrophy (as determined by manual segmentation and deformation-based morphometry). Although sustained, motor dysfunction and nigrostriatal damage were maximal by 1 week post-surgery. Additional volume decreases in the ipsilateral ventral midbrain; corpus striatum and thalamus were only evident by week 3 and 5. Whilst cortical MRI volume changes best predicted the degree of motor impairment, post-mortem tyrosine hydroxylase immunoreactivity in the striatum was a better predictor of motor behaviour overall, with the notable exception of performance in the accelerating rotarod, in which, M1 cortical thickness remained the best predictor. These results highlight the importance of identifying extra-nigral regions of damage that impact on behavioural dysfunction from damage to the nigrostriatal system.
Differences in Nitrogen Metabolism between Cryptococcus neoformans and C. gattii, the Two Etiologic Agents of Cryptococcosis

Two members of the Cryptococcus neoformans-gattii species complex, the etiologic agents of cryptococcosis, can be differentiated by biological, biochemical, serological and molecular typing techniques. Based on their differences in carbon and nitrogen utilization patterns, cost effective and very specific diagnostic tests using D-proline and canvanine-glycine-bromthymol blue (CGB) media have been formulated and are widely used for identification of the two species. However, these methods have yet to be tested for strains with confirmed molecular types to assess the degree of specificity for each molecular type in the two species. We collected global isolates of every major molecular type available and tested their patterns of nitrogen utilization. We confirmed specificity of the CGB test to be 100% regardless of molecular type while the D-proline test yielded 8–38% false negative results in three of the four C. gattii molecular types, VGI–VGIII. The utilization pattern of a new set of amino acids: D-alanine, L-tryptophan and L-phenylalanine, showed species specificity comparable to that of D-proline. We discovered that the transcription factor Gat1 (Are1) regulates the utilization of nitrogen differently between C. neoformans and C. gattii strains. Unlike in C. neoformans, expression of the genes encoding glycine decarboxylase complex in C. gatti was only partially suppressed by nitrogen catabolite repression in the presence of ammonium. GAT1 in C. neoformans controlled the induction of three of the four genes encoding the glycine decarboxylase complex when glycine was used as the sole nitrogen source while in C. gattii its regulation of these genes was less stringent. Moreover, while virulence of C. neoformans strains in mice was not affected by Gat1, the transcription factor positively influenced the virulence of C. gattii strain.
Conceptualizing documentation on the Web: An evaluation of different heuristic-based models for counting links between university Web sites

All known previous Web link studies have used the Web page as the primary indivisible source document for counting purposes. Arguments are presented to explain why this is not necessarily optimal and why other alternatives have the potential to produce better results. This is despite the fact that individual Web files are often the only choice if search engines are used for raw data and are the easiest basic Web unit to identify. The central issue is of defining the Web "document": that which should comprise the single indissoluble unit of coherent material. Three alternative heuristics are defined for the educational arena based upon the directory, the domain and the whole university site. These are then compared by implementing them on a set of 108 UK university institutional Web sites under the assumption that a more effective heuristic will tend to produce results that correlate more highly with institutional research productivity. It was discovered that the domain and directory models were able to successfully reduce the impact of anomalous linking behavior between pairs of Web sites, with the latter being the method of choice. Reasons are then given as to why a document model on its own cannot eliminate all anomalies in Web linking behavior. Finally, the results from all models give a clear confirmation of the very strong association between the research productivity of a UK university and the number of incoming links from its peers' Web sites.
Risk factors predict frequent hospitalization in patients with acute exacerbation of COPD

Purpose COPD is a heterogeneous disease, and the available prognostic indexes are therefore limited. This study aimed to identify the factors associated with acute exacerbation leading to hospitalization. Patients and methods This was a retrospective study of consecutive patients with COPD (meeting the Global Initiative for Chronic Obstructive Lung Disease [GOLD] diagnostic criteria) hospitalized at the Ninth Hospital of Xi’an Affiliated Hospital of Xi’an Jiaotong University between October 2014 and September 2016. During follow-up after first hospitalization, the patients who had been rehospitalized within 1 year for acute exacerbation were grouped into the frequent exacerbation (FE) group, while the others were grouped into the infrequent exacerbation (IE) group. The baseline demographic, clinical, laboratory, pulmonary function, and imaging data were compared between the two groups. Results Compared with the IE group, the FE group had lower forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) (P=0.005), FEV1%pred (P=0.002), maximal mid-expiratory flow (MMEF25–75%pred) (P=0.003), and ratio of carbon monoxide diffusion capacity to alveolar ventilation (DLCO/VA) (P=0.03) and higher resonant frequency (Fres; P=0.04). According to generations of bronchi, the percentage of the wall area (%WA) of lobes was found to be higher in the FE group. Emphysema index (EI), mean emphysema density (MED)whole and MEDleft lung in the FE group were significantly worse than in the IE group (P<0.05). Using logistic regression, exacerbation hospitalizations in the past year (odds ratio [OR] 14.4, 95% CI 6.1–34.0, P<0.001) and EI >10% (OR 2.9, 95% CI 1.2–7.1, P=0.02) were independently associated with frequent acute exacerbation of COPD (AECOPD) hospitalization. Conclusion Exacerbation hospitalizations in the past year and imaging features of emphysema (EI) were independently associated with FE hospitalization.