Miracle-dz/UniFAR-FTUs huggingface dataset:
Synergistic induction of early stage of bone formation by combination of recombinant human bone morphogenetic protein-2 and epidermal growth factor

This study evaluates whether the combination of the rhBMP‐2 and various types of growth factors including EGF, FGF, PDGF and VEGF increases osteoinductivity compared to the single use of rhBMP‐2 through in vitro and in vivo study. Cultured human MSCs were treated with rhBMP‐2 only or in combination with growth factors. For in vivo evaluation, rhBMP‐2 only or with growth factors was implanted into the calvarial defect made on SD rats. Both EGF and PDGF significantly increased both ALP activity and expression level in hMSCs when treated in combination with rhBMP‐2 at 3 and 7 days of differentiation and significantly raised the accumulation of the calcium at day 14. Furthermore, micro‐CT scanning revealed that the EGF an FGF groups show significantly increased new bone surface ratio compared to the rhBMP‐2 only group and, the EGF treatment significantly up regulated percent bone volume and trabecular number at two weeks after the surgery. VEGF treatment also significantly raised trabecular number and FGF treatment significantly increased the trabecular thickness. Histological examination revealed that the EGF combination group showed enhanced bone regeneration than the rhBMP‐2 only group two weeks after the implantation. Even though the treatment of rhBMP‐2 with PDGF and FGF failed to show enhanced osteogenesis in vitro and in vivo simultaneously, these results suggest that the positive effect of the combination of EGF and rhBMP‐2 is expected to induce the bone formation earlier compared to the single use of rhBMP‐2 in vitro and in vivo. © 2014 The Authors. Journal of Tissue Engineering and Regenerative Medicine published by John Wiley & Sons Ltd.
Morphologies of protostellar outflows: an ALMA view

The formation of stars is usually accompanied by the launching of protostellar outflows. Observations with the Atacama Large Millimeter/sub-millimeter Array (ALMA) will soon revolutionize our understanding of the morphologies and kinematics of these objects. In this paper, we present synthetic ALMA observations of protostellar outflows based on numerical magnetohydrodynamic collapse simulations. We find significant velocity gradients in our outflow models and a very prominent helical structure within the outflows. We speculate that the disc wind found in the ALMA Science Verification Data of HD 163296 presents a first instance of such an observation.
Changes in coming out milestones across five age cohorts

ABSTRACT This quantitative study examined differences in the coming-out process between self-identified lesbian, gay, and bisexual (LGB) participants in five age cohorts. An Internet survey and convenience sampling strategy was used to recruit 1,131 participants (ages 18 to 85). Participants provided demographic information and information about their home environment growing up, completed the Lesbian, Gay, and Bisexual Identity Scale (LGBIS) (Mohr & Fassinger, 2000), and shared ages that they achieved important milestones in the coming-out process. ANCOVA of differences between men and women in the five cohorts on the age that significant milestones were achieved resulted in significant findings for all comparisons (p < .001). In post hoc analysis, 52% of the 450 pairwise comparisons were significant at at least the . 05 level. Generally speaking, two significant trends were found in this sample: (a) that the average age of achieving milestones has decreased over time; and (b) that a gender gap in the age of achieving milestones between men and women has disappeared. The current study supports and extends research that suggests a strong connection between social acceptance of LGB people and coming out at younger ages.
Role of MicroRNAs in Controlling Gene Expression in Different Segments of the Human Epididymis

Background The molecular mechanisms implicated in regionalized gene expression in the human epididymis have not yet been fully elucidated. Interestingly, more than 200 microRNAs (miRNAs) have been identified in the human epididymis and could be involved in the regulation of mRNA stability and post-transcriptional expression in this organ. Methods Using a miRNA microarray approach, we investigated the correlation between miRNA signatures and gene expression profiles found in three distinct regions (caput, corpus and cauda) of human epididymides from 3 donors. In silico prediction of transcript miRNA targets was performed using TargetScan and Miranda software's. FHCE1 immortalized epididymal cell lines were cotransfected with mimic microRNAs and plasmid constructs containing the 3′UTR of predicted target genes downstream of the luciferase gene. Results We identified 35 miRNAs differentially expressed in the distinct segments of the epididymis (fold change ≥2, P-value≤0.01). Among these miRNAs, miR-890, miR-892a, miR-892b, miR-891a, miR-891b belonging to the same epididymis-enriched cluster located on the X chromosome, are significantly more expressed in the corpus and cauda regions than in the caput. Interestingly, a strong negative correlation (r = −0,89, P-value≤0.001) was found between the pattern of expression of miR-892b and its potential mRNA target Esrrg (Estrogen Related Receptor Gamma) and with miR-145 and Cldn10 mRNA (r = −0,92, P-value≤0.001). We confirmed that miR-145 and miR-892b inhibit the expression of the luciferase reporter via Cldn10 and Esrrg 3′ UTRs, respectively. Conclusion Our study shows that the expression of miRNAs is segmented along the human epididymis and correlates with the pattern of target gene expression in different regions. Therefore, epididymal miRNAs may be in control of the maintenance of gene expression profile in the epididymis, which dictates segment-specific secretion of proteins and establishes physiological compartments that directly or indirectly affect sperm maturation and fertility.
Oxcarbazepine final market image tablet formulation bioequivalence study after single administration and at steady state in healthy subjects.

A final market image (FMI) tablet formulation of oxcarbazepine was compared with the marketed formulation (current market formulation (CMF)) and with the clinical trial formulation (CTF) tablet used during clinical efficacy and safety studies. The goal of the study was to compare the bioavailability after single doses and at steady state of the FMI versus CMF and CTF as well. Additionally, the effect of food was evaluated on the final market formulation. The study was an open-label, single-center, 4-way crossover trial. Each treatment period consisted of a single dose of 600 mg OXC on Day 1. From Day 4 up to including Day 7, 600 mg b.i. d. were administered. A final dose of 600 mg was administered in the morning on Day 8. Blood samples were taken on Day 1 before and on Day 7 (predose) and on Day 8 (morning dose). Plasma concentrations of MHD (the main metabolite of OXC) were determined by using a validated HPLC assay. FMI as test formulation was compared with the CMF and CTF as reference formulations. FMI under fed conditions was also compared with FMI under fasting conditions. These comparisons were made using data following single-dose administration and steady state conditions. Plasma AUC for single dose or AUC(0-12h) for steady state, and plasma Cmax, log-transformed (natural base), were used for the assessment of bioequivalence. The 90% confidence interval (CI) approach was used for testing bioequivalence. Bioequivalence was accepted if the CI was contained within the region (0.8, 1.25). At steady state under fed conditions, tested formulation (FMI) was bioequivalent to CTF and with the reference marketed formulation (CMF) with regard to AUC and Cmax. After single dose under fed conditions, FMI and CTF were bioequivalent with regard to AUC and Cmax, and FMI and CMF were equivalent with regard to AUC but not Cmax. Food had no effect on the bioavailability of the FMI. These results clearly support the switch from the current market formulation (CMF) to the final market image tablet in the countries where Trileptal is or was already registered.
Joint Clustering and Classification for Multiple Instance Learning

The Multiple Instance Learning (MIL) framework has been extensively used to solve weakly labeled visual classification problems, where each image or video is treated as a bag of instances. Instance Space based MIL algorithms construct a classifier by modifying standard classifiers by defining the probability that a bag is of the target class as the maximum over the probabilities that its instances are of the target class. Although they are the most commonly used MIL algorithms, they do not account for the possibility that the instances may have multiple intermediate concepts, and that these concepts may have unequal weighting in predicting the overall target class. On the other hand, Embedding-space (ES) based MIL approaches are able to tackle this issue by defining a set of concepts, and then embedding each bag into a concept space, followed by training a standard classifier in the embedding space. In previous ES based approaches, the concepts were discovered separately from the classifier, and thus were not optimized for the final classification task. Here we propose a novel algorithm to estimate concepts and classifier parameters by jointly optimizing a classification loss. This approach discovers a small set of discriminative concepts, which yield superior classification performance. The proposed algorithm is referred to as Joint Clustering Classification for MIL data (JC2MIL) because the discovered concepts induce clusters of data instances. In comparison to previous approaches JC2MIL obtains state-of-the-art results on several MIL datasetsCorel-2000, image annotation datasets (Elephant, Tiger and Fox), and UCSB Breast Cancer dataset.
Alkaloids from Croton flavens l. and their affinities to GABA-receptors

Phytochemical investigation of several plants of Croton flavens L. from Barbados has led to the isolation of the tetrahydroprotoberberine alkaloids scoulerine and coreximine, as well as the morphinanedienones salutaridine and its racemic form salutarine, sebiferine, norsinoacutine and flavinantine. In a screening for 3H-GABA displacing activity coreximine showed the highest affinity to the GABAA receptor.
Genome‐wide survey of artificial mutations induced by ethyl methanesulfonate and gamma rays in tomato

Summary Genome‐wide mutations induced by ethyl methanesulfonate (EMS) and gamma irradiation in the tomato Micro‐Tom genome were identified by a whole‐genome shotgun sequencing analysis to estimate the spectrum and distribution of whole‐genome DNA mutations and the frequency of deleterious mutations. A total of ~370 Gb of paired‐end reads for four EMS‐induced mutants and three gamma‐ray‐irradiated lines as well as a wild‐type line were obtained by next‐generation sequencing technology. Using bioinformatics analyses, we identified 5920 induced single nucleotide variations and insertion/deletion (indel) mutations. The predominant mutations in the EMS mutants were C/G to T/A transitions, while in the gamma‐ray mutants, C/G to T/A transitions, A/T to T/A transversions, A/T to G/C transitions and deletion mutations were equally common. Biases in the base composition flanking mutations differed between the mutagenesis types. Regarding the effects of the mutations on gene function, >90% of the mutations were located in intergenic regions, and only 0.2% were deleterious. In addition, we detected 1 140 687 spontaneous single nucleotide polymorphisms and indel polymorphisms in wild‐type Micro‐Tom lines. We also found copy number variation, deletions and insertions of chromosomal segments in both the mutant and wild‐type lines. The results provide helpful information not only for mutation research, but also for mutant screening methodology with reverse‐genetic approaches.
Augmented and alternative NLP techniques for augmentative and alternative communication

Current communication devices designed for non-speaking users are inadequate to support conversation because the speed with which a user can input information is typically very limited. We describe some practical work on word prediction, and discuss its limitations as a technique for speeding up free text entry. We then out-line an alternative approach, currently under development, which combines prediction with a constrained technique for nat-ural language generation
Neutrophil extracellular traps exacerbate Th1‐mediated autoimmune responses in rheumatoid arthritis by promoting DC maturation

Aberrant formation of neutrophil extracellular traps (NETs) is a key feature in rheumatoid arthritis (RA) and plays a pivotal role in disease pathogenesis. However, the mechanism through which NETs shape the autoimmune response in RA remains elusive. In this study, we demonstrate that inhibition of peptidylarginine deiminases activity in collagen‐induced arthritis (CIA) mouse model significantly reduces NET formation, attenuates clinical disease activity, and prevents joint destruction. Importantly, peptidylarginine deiminase 4 blocking markedly reduces the frequency of collagen‐specific IFN‐γ‐producing T helper 1 (Th1) cells in the draining lymph nodes of immunized mice. Exposure of dendritic cells (DCs) to CIA‐derived NETs induces DC maturation characterized by significant upregulation of costimulatory molecules, as well as elevated secretion of IL‐6. Moreover, CIA‐NET‐treated DCs promote the induction of antigen‐specific Th1 cells in vitro. Finally, NETs from RA patients show an increased potential to induce the maturation of DCs from healthy individuals, corroborating the findings obtained in CIA mouse model. Collectively, our findings delineate an important role of NETs in the induction and expansion of Th1 pathogenic cells in CIA through maturation of DCs and reveal a novel role of NETs in shaping the RA‐autoimmune response that could be exploited therapeutically.
Effect of Sublethal Concentrations of Cadmium, Lead and Chromium on Some Enzymatic Activities of Common Carp; Cyprinus carpio

The aim of this study was to assess the effect of heavy metal agents on two biochemical enzyme activities, alanine aminotransaminase (ALT) and aspartate aminotransaminase (AST), as well as alkaline phosphatase (AP) and amylase. For these studies, triplicate groups of adult fish and a control group (50 fish/group) were exposed to sublethal concentrations (10% of LC -96 hr values) of cadmium chloride, 50 chromium (III) chloride and lead (II) nitrate for a period of 33 days. The results indicated that AST levels were significantly (p Cd>Cr. The present investigation illustrates that Cd, Pb and Cr are differentially toxic to the common carp following sub-chronic exposure.
A Log-Structured Block Preservation and Restoration System for Proactive Forensic Data Collection in the Cloud

Preservation and data collection in cloud environments are difficult because forensic data are volatile and they are scattered in many servers. This paper describes a novel surveillance mechanism for virtual block devices on IaaS cloud environments. We first describe some related work on backup applications, versioning file systems, and virtual machine introspection systems that can be applied to cloud forensics. The proposed log-structured block preservation and restoration system can be used for recording cloud consumers' write operations on virtual block devices and for restoring the state of a virtual block device at an arbitrary point in time. This paper presents a design and an implementation of the proposed system by using Xen hypervisor. The prototype implementation achieved better read and write performance compared to the baseline driver provided by Xen when we ran four or more virtual machines simultaneously. This paper shows two forensic applications for preserved data blocks: a file tracking application and a novel diff command that supports time travel.
Assessment of the relationship of bispectral index values, hemodynamic changes, and recovery times associated with sevoflurane or propofol anesthesia in pigs.

OBJECTIVE To evaluate bispectral index (BIS) values in pigs during anesthesia maintained with sevoflurane-fentanyl or propofol-fentanyl as a predictor of changes in hemodynamic parameters and duration of recovery from anesthesia. ANIMALS 12 pigs. PROCEDURE Pigs were randomly allocated to undergo 1 of 2 anesthetic regimens. Anesthesia was induced with propofol (2 mg/kg, i.v.); 6 pigs were administered sevoflurane via inhalation (1 minimum alveolar concentration [MAC] at a fresh gas flow rate of 3 L/min; group I), and 6 were administered propofol (11 mg/kg/h, i.v.; group II). All pigs received fentanyl (2.5 mg/kg, i.v., q 30 min). After abdominal surgery, pigs were allowed to recover from anesthesia. Cardiovascular variables and BIS values were recorded at intervals throughout the procedure; duration of recovery from anesthesia was noted. RESULTS No correlation was established between arterial blood pressure and BIS and between heart rate and BIS. Mean BIS at discontinuation of administration of the anesthetic agent was greater in group-II pigs (65.2 +/- 10.6 minutes) than in group-I pigs (55.8 +/- 2.9 minutes). However, recovery from anesthesia was significantly longer in group II (59.80 +/- 2.52 minutes) than in group I (9.80 +/- 2.35 minutes). CONCLUSIONS AND CLINICAL RELEVANCE In swine anesthetized with sevoflurane or propofol and undergoing abdominal surgery, the BIS value derived from an electroencephalogram at the end of anesthesia was not useful for predicting the speed of recovery from anesthesia. Moreover, BIS was not useful as a predictor of clinically important changes in arterial blood pressure and heart rate in those anesthetized pigs.
FRET-Based Localization of Fluorescent Protein Insertions Within the Ryanodine Receptor Type 1

Fluorescent protein (FP) insertions have often been used to localize primary structure elements in mid-resolution 3D cryo electron microscopic (EM) maps of large protein complexes. However, little is known as to the precise spatial relationship between the location of the fused FP and its insertion site within a larger protein. To gain insights into these structural considerations, Förster resonance energy transfer (FRET) measurements were used to localize green fluorescent protein (GFP) insertions within the ryanodine receptor type 1 (RyR1), a large intracellular Ca2+ release channel that plays a key role in skeletal muscle excitation contraction coupling. A series of full-length His-tagged GFP-RyR1 fusion constructs were created, expressed in human embryonic kidney (HEK)-293T cells and then complexed with Cy3NTA, a His-tag specific FRET acceptor. FRET efficiency values measured from each GFP donor to Cy3NTA bound to each His tag acceptor site were converted into intermolecular distances and the positions of each inserted GFP were then triangulated relative to a previously published X-ray crystal structure of a 559 amino acid RyR1 fragment. We observed that the chromophoric centers of fluorescent proteins inserted into RyR1 can be located as far as 45 Å from their insertion sites and that the fused proteins can also be located in internal cavities within RyR1. These findings should prove useful in interpreting structural results obtained in cryo EM maps using fusions of small fluorescent proteins. More accurate point-to-point distance information may be obtained using complementary orthogonal labeling systems that rely on fluorescent probes that bind directly to amino acid side chains.
T-Cell Tropism and the Role of ORF66 Protein in Pathogenesis of Varicella-Zoster Virus Infection

ABSTRACT The pathogenesis of varicella-zoster virus (VZV) involves a cell-associated viremia during which infectious virus is carried from sites of respiratory mucosal inoculation to the skin. We now demonstrate that VZV infection of T cells is associated with robust virion production and modulation of the apoptosis and interferon pathways within these cells. The VZV serine/threonine protein kinase encoded by ORF66 is essential for the efficient replication of VZV in T cells. Preventing ORF66 protein expression by stop codon insertion (pOka66S) impaired the growth of the parent Oka (pOka) strain in T cells in SCID-hu T-cell xenografts in vivo and reduced formation of VZV virions. The lack of ORF66 protein also increased the susceptibility of infected T cells to apoptosis and reduced the capacity of the virus to interfere with induction of the interferon (IFN) signaling pathway following exposure to IFN-γ. However, preventing ORF66 protein expression only slightly reduced growth in melanoma cells in culture and did not diminish virion formation in these cells. The pOka66S virus showed only a slight defect in growth in SCID-hu skin implants compared with intact pOka. These observations suggest that the ORF66 kinase plays a unique role during infection of T cells and supports VZV T-cell tropism by contributing to immune evasion and enhancing survival of infected T cells.
DOUBLE BASS INTONATION: A SYSTEMATIC APPROACH TO SOLO AND ENSEMBLE PLAYING

ed, categorized data which will be losing salience in STM without rehearsal or reinforcement. A fact which seems quite odd, given how sensitive musicians seem to be about intonation, is that humans are generally described as having very good intercategory discrimination but very poor intracategory discrimination. In other words, once we have decided an interval is a perfect fifth, we either don’t notice or it doesn’t matter if the two tones are slightly narrow or wide of our ideal perfect fifth. Before we scrap this notion of intonation sensitivity, let us consider two parallel ideas. The first is that the processing we’ve been discussing is to a very large extent at the subconscious level in STM and is highly contextualized, aside from the trace copies sent directly into focused awareness. When that perfect fifth is played, one might not identify it as a perfect fifth by name and maybe not as any interval in particular at all. But, the subconscious processing of its size and meaning is occurring none the less. The labeling of the interval is a different process than for observing the procession of pitches occurring in focused awareness. The second idea is that intonation is a nuance particularly of high-resolution pitch information in focused awareness interacting with the categorized interval. Especially with trained musicians, intonation is the sense of precisely where within an interval category two pitches fall, but because a nuance is not in itself categorized so as to protect the necessary data resolution, it is not processed directly by the memory systems and is not retained. Thus, it is perfectly reasonable that musicians in particular are able to discriminate what an interval “is,” i.e., assign it a categorical interval size, to a broad extent, yet be able to 73 See Larson 1994 and Larson 1997. 74 For nuance as a technical term; see Snyder 2000, 86. 75 Burns & Houtsma 1999
Host plant genus‐level diversity is the best predictor of ectomycorrhizal fungal diversity in a Chinese subtropical forest

Microbial diversity is generally far higher than plant diversity, but the relationship between microbial diversity and plant diversity remains enigmatic. To shed light on this problem, we examined the diversity of a key guild of root‐associated microbes, that is, ectomycorrhizal (EM) fungi along a plant diversity gradient in a Chinese subtropical forest. The results indicated that EM fungal diversity was positively correlated with host plant diversity. Furthermore, this relationship was best predicted by host genus‐level diversity, rather than species‐level diversity or family‐level diversity. The generality of this finding was extended beyond our study system through the analyses of 100 additional studies of EM fungal communities from tropical and temperate forests. Here as well, EM fungal lineage composition was significantly affected by EM plant diversity levels, and some EM fungal lineages were co‐associated with some host plant genera. These results suggest a general diversity maintenance mechanism for host‐specific microbes based on higher order host plant phylogenetic diversity.