Miracle-dz/UniFAR-FTUs huggingface dataset:
Transplanted Neural Precursors Enhance Host Brain-Derived Myelin Regeneration

In multiple sclerosis lesions resident oligodendrocyte progenitor cells (OPCs) are present, but fail to remyelinate. In the current study we examined whether neural precursor cell (NPC) transplantation can facilitate host brain-derived remyelination. We used the chronic cuprizone-induced demyelination model in aged mice, in which slow remyelination follows cuprizone removal. NPCs were transplanted to the lateral ventricles (intracerebroventricular) of cuprizone-induced demyelinated brains. In this experimental setup, transplanted cells remained mostly in the periventricular area in an undifferentiated state. The extent of demyelination, remyelination, and proliferation of host brain regenerative cell population were examined at 1 week posttransplantation in the splenium of the corpus callosum, which was devoid of any transplanted cells. Transplantation of NPCs, but not of control, human embryonic kidney cells, significantly enhanced remyelination compared with sham-operated mice. Remyelination was performed exclusively by host brain OPCs. The proregenerative effect of transplanted NPCs was related to an increase in the proliferation of host brain OPCs. To examine the mechanism that underlies the proregenerative effect of NPCs in vitro, we used an NPC–OPC coculture system. These experiments indicated that NPCs induced the proliferation of OPCs and facilitated their differentiation into mature oligodendrocytes. The mitogenic effect of NPCs was mediated by platelet-derived growth factor-AA and fibroblast growth factor-2. In conclusion, NPC transplantation enhances host-derived myelin regeneration following chronic demyelination. This trophic effect may stimulate resident OPCs to overcome the remyelination failure in multiple sclerosis.
Sexual Satisfaction and Mental Health in Prison Inmates

The main goal of this study was to investigate the association between sexual satisfaction and mental health, and the combined effect of two previously found, statistically significant moderators: partner status and sexual abstinence. In-person interviews were conducted with 223 participants (49.327% males and 50.673% females). The effect of sexual satisfaction on mental health and the interactions of sexual satisfaction × partner status, sexual satisfaction × sexual abstinence, and sexual satisfaction × partner status × sexual abstinence were examined using simple moderation and moderated moderation tests after controlling for a set of sociodemographic, penitentiary, and interpersonal variables. Results revealed a direct relationship between sexual satisfaction and mental health only for the sexually abstinent group. Partner status was not significant as a moderator. It seems that the lack of sexual relationships is more powerful as a moderator than the lack of a romantic relationship. Additionally, the sexually abstinent group showed lower levels of sexual satisfaction in those with a partner outside or inside prison, and lower mental health independently of the current romantic status, than sexually active inmates. These findings point to the importance of sexual satisfaction to mental health in sexual situations of extreme disadvantage.
Fixation time in evolutionary graphs: a mean field approach

A novel analytical method is proposed for calculation of average fixation and extinction times of mutants in a general structured population of two types of species. The method is based on Markov chains and uses a mean field approximation to calculate the corresponding transition matrix. Analytical results are compared with the results of simulation of the Moran process on a number of population structures.
Perioperative ketamine for acute analgesia and beyond

Abstract There has been substantial interest in the use of ketamine for perioperative analgesia. Recently published articles on ‘low dose’ ketamine mark the resurgence in interest in the use of the drug for acute pain. Continued interest in ketamine as an anti-depressant also has opened the door to applications beyond the operating room. In this article, we will review: the history of ketamine’s clinical use; basic ketamine pharmacology; evidence for the use of perioperative ketamine for analgesia; comments on patient selection for ketamine research; a discussion of the safety and side effect profile of ketamine infusions beyond the operating room; and, lastly, ketamine as a treatment option for psychiatric diseases.
Filter feature selectors in the development of binary QSAR models

ABSTRACT The application of machine learning methods to the construction of quantitative structure–activity relationship models is a complex computational problem in which dimensionality reduction of the representation of the molecular structure plays a fundamental role in predicting a target activity. The feature selection pre-processing approach has been indicated to be effective in dimensionality reduction for building simpler and more understandable models. In this paper, a performance comparative study of 13 state-of-the-art feature selection filter methods is conducted. Structure–activity relationship models are constructed using three widely used classifiers and a diverse collection of datasets. The comparative study utilizes robust statistical tests to compare the algorithms. According to the experimental results, there are substantial differences in performance among the evaluated feature selection methods. The methods that exhibit the best performance are correlation-based feature selection, fast clustering-based feature selection and the set cover method.
Genomewide Oligonucleotide Microarray Analysis on Placentae of Pre-Eclamptic Pregnancies

Objective: Human placentae from normal and pre-eclamptic pregnancies were evaluated for possible changes in gene expression by microarray analysis to uncover new clues for the research of the etiology of pre-eclampsia. Methods: Placentae from five normal pregnancies and five pregnancies complicated by pre-eclampsia were collected. mRNA levels of five pre-eclamptic placentae were examined using genome-wide 70-mer oligonucleotide microarrays (CapitalBio, Beijing, China) in comparison with the pooled control consisting of total RNA from five normotensive placentae. Results: Ninety-six genes were found consistently down- or up-regulated in at least four pre-eclamptic samples. Most of them were related to an imbalance of reactive oxygen metabolites in placenta, abnormal trophoblast invasion, disorders of lipoprotein metabolism and signal transduction, or some that have been reported to have close correlation to the pathology of pre-eclampsia. The microarray data were also confirmed by the measurement of real-time PCR. Conclusion: DNA microarray is a high throughput and time-saving method to monitor altered gene expression. The results could provide interesting clues to the etiology of pre-eclampsia and lead to further studies in a more targeted fashion.
Mechanistic insights from the LHX1‐driven molecular network in building the embryonic head

Development of an embryo is driven by a series of molecular instructions that control the differentiation of tissue precursor cells and shape the tissues into major body parts. LIM homeobox 1 (LHX1) is a transcription factor that plays a major role in the development of the embryonic head of the mouse. Loss of LHX1 function disrupts the morphogenetic movement of head tissue precursors and impacts on the function of molecular factors in modulating the activity of the WNT signaling pathway. LHX1 acts with a transcription factor complex to regulate the transcription of target genes in multiple phases of development and in a range of embryonic tissues of the mouse and Xenopus. Determining the interacting factors and transcriptional targets of LHX1 will be key to unraveling the ensemble of factors involved in head development and building a head gene regulatory network.
Improved interleaved discontinuous carrier-based PWM strategy for 3-level coupled inductor inverters

An improved interleaved discontinuous Pulse Width Modulation (PWM) technique is presented for multilevel coupled inductor inverters (CII). The CII performance is dependent to the inductor current ripple and associated coupled inductor losses. A new approach is developed based on interchangeable overlapping switching states in the CII topology. The proposed method maximizes the use of switching states with a high-effective inductance and minimizes the inductor current ripple by inverting the interleaved carrier waveforms for the upper and lower switches in one of the inverter switching phases. The proposed method has a superior performance compared to traditional carrier-based methods by minimizing the inductor losses and, thus, improving the inverter performance. The new method is also superior over the space vector techniques due to its easy implementation and simple algorithm. The inverter performance is validated through simulation analysis and experimental results.
Characterizing Brain Connectivity From Human Electrocorticography Recordings With Unobserved Inputs During Epileptic Seizures

Epilepsy is a neurological disorder characterized by the sudden occurrence of unprovoked seizures. There is extensive evidence of significantly altered brain connectivity during seizure periods in the human brain. Research on analyzing human brain functional connectivity during epileptic seizures has been limited predominantly to the use of the correlation method. However, spurious connectivity can be measured between two brain regions without having direct connection or interaction between them. Correlations can be due to the apparent interactions of the two brain regions resulting from common input from a third region, which may or may not be observed. Hence, researchers have recently proposed a sparse-plus-latent-regularized precision matrix (SLRPM) when there are unobserved or latent regions interacting with the observed regions. The SLRPM method yields partial correlations of the conditional statistics of the observed regions given the latent regions, thus identifying observed regions that are conditionally independent of both the observed and latent regions. We evaluate the performance of the methods using a spring-mass artificial network and assuming that some nodes cannot be observed, thus constituting the latent variables in the example. Several cases have been considered, including both sparse and dense connections, short-range and long-range connections, and a varying number of latent variables. The SLRPM method is then applied to estimate brain connectivity during epileptic seizures from human ECoG recordings. Seventy-four clinical seizures from five patients, all having complex partial epilepsy, were analyzed using SLRPM, and brain connectivity was quantified using modularity index, clustering coefficient, and eigenvector centrality. Furthermore, using a measure of latent inputs estimated by the SLRPM method, it was possible to automatically detect 72 of the 74 seizures with four false positives and find six seizures that were not marked manually.
Wetland use by white-winged scoters (Melanitta fusca) in the Mackenzie Delta region

Reasons for apparent declines in populations of white-winged scoters (Melanitta fusca) in the northern boreal forest are not well understood, but some evidence suggests factors associated with the breeding grounds may be responsible. Climate warming or increased forest fire frequency could adversely affect upland or wetland breeding habitats or key food sources for breeding females or ducklings, which in turn may lower productivity. However, very little is known about wetland habitat preferences of scoters. Determining what habitat features scoters need to breed successfully and whether changes in boreal forest breeding habitat affect scoter productivity are important steps towards understanding their ecology and developing appropriate conservation initiatives. Thus, our overall goal was to characterize features of wetlands used by scoter pairs and broods. Additionally, we compared features of wetlands surrounded by recently burned versus unburned forest to investigate whether fire-induced changes in wetland productivity, water chemistry, or amphipod abundance could affect patterns of scoter habitat use. Scoter pairs and broods used wetlands with more abundant amphipods, a finding that is consistent with other waterfowl studies. However, unlike some previous waterfowl studies, we did not find consistent positive correlations between total phosphorus levels and amphipod abundance or wetland use by scoters. We did not detect differences in our measured water chemistry variables, indices of wetland productivity, or amphipod abundance between wetlands surrounded by burned versus unburned forest.
The Notch ligand DLL1 exerts carcinogenic features in human breast cancer cells

Breast cancer (BC) is the most common type of cancer in women and has a high rate of relapse and death. Notch signaling is crucial for normal breast development and homeostasis. Dysregulation of Notch receptors and ligands has been detected in different BC subtypes and shown to be implicated in tumor development, progression, drug resistance, and recurrence. However, the effects of Notch ligands in various types of BC remain poorly understood. In this study, we investigated the effects of the Notch ligand DLL1 in three different human BC cell lines: MCF-7, BT474, and MDA-MB-231. We showed that DLL1 expression is higher in MCF-7 and BT474 than in MDA-MB-231 cells, and that these cells respond differently to DLL1 downregulation. Functional assays in MCF-7 cells demonstrated that siRNA-mediated DLL1 downregulation reduced colony formation efficiency, migration, proliferation, caused cell cycle arrest at the G1 phase, and induced apoptosis. Gene expression studies revealed that these effects in MCF-7 cells were associated with increased expression of the cell cycle arrest p21 gene and decreased expression of genes that promote cell cycle progression (CDK2, SKP2), and survival (BCL2, BIRC5), unravelling possible mechanisms whereby DLL1 downregulation exerts some of its effects. Moreover, our results demonstrate that treatment with recombinant DLL1 increased MCF-7 cell proliferation and migration, confirming that DLL1 contributes to these processes in this BC cell line. DLL1 downregulation reduced the colony formation efficiency of BT474 cells and decreased the migration and invasion abilities of MDA-MB-231 cells but showed no effects in the proliferation and survival of these cells. Conclusions These findings provide further evidence that DLL1 exerts carcinogenic effects in BC cells. The dissimilar effects of DLL1 downregulation observed amongst MCF-7, BT474, and MDA-MB-231 cells is likely due to their distinctive genetic and biologic characteristics, suggesting that DLL1 contributes to BC through various mechanisms.
Lung allocation score and health-related quality of life in Japanese candidates for lung transplantation.

OBJECTIVES The lung allocation score (LAS) system has been implemented to reduce waiting list time and mortality in the USA, but it remains uncertain how the LAS would reflect the impairment in health-related quality of life (HRQOL), which is another lung transplantation treatment goal to be improved in addition to survival. We thus investigated the relationships of the LAS with mortality and HRQOL in Japanese lung transplantation candidates. METHODS One hundred and two candidates for lung transplantation at Kyoto University Hospital between 2009 and 2013 were consecutively recruited to participate in this study. Their physiological measurements of pulmonary function and 6-min walking distance, as well as patient-reported measurements of HRQOL, dyspnoea and psychological status, were assessed. RESULTS Among these 102 patients, 22 died during a mean follow-up of 11.6 months. The LAS was significantly correlated to mortality (P = 0.0026), although other physiological measurements were not. However, regarding its relationship with HRQOL, correlation coefficients between the LAS, Medical Outcomes Study 36-item short form and St George's Respiratory Questionnaire (SGRQ) were relatively low, with the highest at 0.31. Multivariate analyses showed that the LAS was less significantly related to the SGRQ total score than dyspnoea, and psychological status. CONCLUSIONS The LAS was significantly related to mortality in lung transplant candidates in Japan, while, despite its multidimensional scoring, its relationship with health-related quality of life was only weak. Their severity assessment system may be more focused on patients' health and symptoms.
Chromatin-Dependent Repression of the Arabidopsis Floral Integrator Genes Involves Plant Specific PHD-Containing Proteins[C][W]

This work shows that the Arabidopsis homologs SHL and EBS play independent roles in the repression of flowering and are required to maintain an inactive chromatin configuration in floral integrator genes by preventing high levels of H3 acetylation. SHL and EBS are plant-specific proteins and could represent a fundamental difference in gene expression control between plants and other eukaryotes. The interplay among histone modifications modulates the expression of master regulatory genes in development. Chromatin effector proteins bind histone modifications and translate the epigenetic status into gene expression patterns that control development. Here, we show that two Arabidopsis thaliana paralogs encoding plant-specific proteins with a plant homeodomain (PHD) motif, SHORT LIFE (SHL) and EARLY BOLTING IN SHORT DAYS (EBS), function in the chromatin-mediated repression of floral initiation and play independent roles in the control of genes regulating flowering. Previous results showed that repression of the floral integrator FLOWERING LOCUS T (FT) requires EBS. We establish that SHL is necessary to negatively regulate the expression of SUPPRESSOR OF OVEREXPRESSION OF CO1 (SOC1), another floral integrator. SHL and EBS recognize di- and trimethylated histone H3 at lysine 4 and bind regulatory regions of SOC1 and FT, respectively. These PHD proteins maintain an inactive chromatin conformation in SOC1 and FT by preventing high levels of H3 acetylation, bind HISTONE DEACETYLASE6, and play a central role in regulating flowering time. SHL and EBS are widely conserved in plants but are absent in other eukaryotes, suggesting that the regulatory module mediated by these proteins could represent a distinct mechanism for gene expression control in plants.
Target sequence requirements of a type III-B CRISPR-Cas immune system

CRISPR-Cas systems are RNA-based immune systems that protect many prokaryotes from invasion by viruses and plasmids. Type III CRISPR systems are unique, as their targeting mechanism requires target transcription. Upon transcript binding, DNA cleavage by type III effector complexes is activated. Type III systems must differentiate between invader and native transcripts to prevent autoimmunity. Transcript origin is dictated by the sequence that flanks the 3′ end of the RNA target site (called the PFS). However, how the PFS is recognized may vary among different type III systems. Here, using purified proteins and in vitro assays, we define how the type III-B effector from the hyperthermophilic bacterium Thermotoga maritima discriminates between native and invader transcripts. We show that native transcripts are recognized by base pairing at positions −2 to −5 of the PFS and by a guanine at position −1, which is not recognized by base pairing. We also show that mismatches with the RNA target are highly tolerated in this system, except for those nucleotides adjacent to the PFS. These findings define the target requirement for the type III-B system from T. maritima and provide a framework for understanding the target requirements of type III systems as a whole.
Deployable cylindrical phased-array applicator mimicking a concentric-ring configuration for minimally-invasive delivery of therapeutic ultrasound

A novel design for a deployable catheter-based ultrasound applicator for endoluminal and laparoscopic intervention is introduced. By combining a 1D cylindrical ring phased array with an expandable paraboloid or conical-shaped balloon-based reflector, the applicator can be controllably collapsed for compact delivery and deployed to mimic a forward-firing larger diameter concentric ring array with tight focusing and electronic steering capabilities in depth. Comprehensive acoustic and biothermal parametric studies were employed to characterize the capabilities of the applicator design as a function of transducer dimensions, phased array configuration, and balloon reflector geometry. Modeling results indicate that practical balloon sizes (43–57 mm expanded diameter), transducer array configurations (e.g. 1.5 MHz, 10 mm OD × 20 mm length, 8 or 16 array elements), and sonication durations (30 s) are capable of producing spatially-localized acoustic intensity focal patterns and ablative thermal lesions (width: 2.8–4.8 mm; length: 5.3–40.1 mm) in generalized soft tissue across a 5–100 mm depth range. Larger focal intensity gain magnitudes and narrower focal dimensions are attainable using paraboloid-shaped balloon reflectors with natural geometric focal depths of 25–55 mm, whereas conical-shaped reflectors (angled 45–55°) produce broader foci and extend electronic steering range in depth. A proof-of-concept phased array applicator assembly was fabricated and characterized using hydrophone and radiation force balance measurements and demonstrated good agreement with simulation. The results of this study suggest that combining small diameter cylindrical phased arrays with expandable balloon reflectors can enhance minimally invasive ultrasound-based intervention by augmenting achievable focal gains and penetration depths with dynamic adjustment of treatment depth.
Nanoparticles Containing an Insulin–ChgA Hybrid Peptide Protect from Transfer of Autoimmune Diabetes by Shifting the Balance between Effector T Cells and Regulatory T Cells

Key Points A hybrid insulin peptide (HIP) neoepitope can tolerize diabetogenic T cells. Tolerance induction promotes T cell anergy and increases Treg/Teff ratio. HIPs are potential therapeutics in type 1 diabetes. CD4 T cells play a critical role in promoting the development of autoimmunity in type 1 diabetes. The diabetogenic CD4 T cell clone BDC-2.5, originally isolated from a NOD mouse, has been widely used to study the contribution of autoreactive CD4 T cells and relevant Ags to autoimmune diabetes. Recent work from our laboratory has shown that the Ag for BDC-2.5 T cells is a hybrid insulin peptide (2.5HIP) consisting of an insulin C-peptide fragment fused to a peptide from chromogranin A (ChgA) and that endogenous 2.5HIP-reactive T cells are major contributors to autoimmune pathology in NOD mice. The objective of this study was to determine if poly(lactide-co-glycolide) (PLG) nanoparticles (NPs) loaded with the 2.5HIP Ag (2.5HIP-coupled PLG NPs) can tolerize BDC-2.5 T cells. Infusion of 2.5HIP-coupled PLG NPs was found to prevent diabetes in an adoptive transfer model by impairing the ability of BDC-2.5 T cells to produce proinflammatory cytokines through induction of anergy, leading to an increase in the ratio of Foxp3+ regulatory T cells to IFN-γ+ effector T cells. To our knowledge, this work is the first to use a hybrid insulin peptide, or any neoepitope, to re-educate diabetogenic T cells and may have significant implications for the development of an Ag-specific therapy for type 1 diabetes patients.