Miracle-dz/UniFAR-FTUs huggingface dataset:
Anti-idiotypic Antibodies against BP-IgG Prevent Type XVII Collagen Depletion

Bullous pemphigoid (BP) mainly targets type XVII collagen (COL17). Intravenous immunoglobulin (IVIg) is used to treat numerous autoimmune diseases, including BP. The major mechanism of action for IVIG is thought to be its immunomodulatory effect. However, little is known about the precise mechanisms of IVIg in BP. We investigate the cellular effects of IVIg, toward treatments for BP. Keratinocytes were treated with IgG from BP patients (BP-IgG) and with IVIg, and then the COL17 expression was detected by Western blotting. Cell adhesion and ex vivo dermal–epidermal separation were also investigated for the condition with BP-IgG and IVIg. BP-IgG targeting the non-collagenous 16A domain induces the depletion of COL17 in cultured keratinocytes (DJM-1 cells). The COL17 levels in DJM-1 cells were decreased by 50% after 4 h of BP-IgG stimulation as determined by Western blotting. By contrast, BP-IgG with IVIg was found to result in 70–90% increases in COL17 and to restore adhesion to the plate. Interestingly, IVIg significantly inhibited the binding of BP-IgG to the COL17-enzyme-linked immunosorbent assay plate, and this was due to anti-idiotypic antibodies against BP-IgG. When anti-idiotypic antibodies against BP-IgG in 0.02% of IVIg were depleted from IVIg, those antibodies did not exhibit inhibitory effects on COL17 depletion. When cryosections of human skin were incubated with BP-IgG in the presence of leukocytes, dermal–epidermal separation was observed. BP-IgG treatment with IVIg or anti-idiotypic antibodies did not induce such separation. These findings strongly suggest the presence of anti-idiotypic antibodies against anti-COL17 IgG in IVIg. This mechanism of IVIg could be a target for therapies against BP.
Psychological health in early pregnancy: relationship with nausea and vomiting

The psychological health of women in early pregnancy was investigated in a sample of 273 women (mean gestational age 12.8 weeks, SD = 2.8) using the General Health Questionnaire (GHQ) and mood and illness perception visual analogue scales, and compared with the prevalence and severity of nausea and vomiting as measured using the Nausea and Vomiting in Pregnancy Instrument (NVPI). Using a cut-off of 4/5 for the GHQ, 50.5% of pregnant women were found to have potential psychiatric problems. However, perceived mental health and physical illness was significantly better than anticipated. The severity of nausea and vomiting correlated independently with GHQ subscales for somatic symptoms, social dysfunction, anxiety/insomnia and severe depression. The contradiction between high GHQ scored and high perceived wellbeing might be explained through cognitive processing. Nausea and vomiting in early pregnancy is associated with psychiatric morbidity. The causal relationship between the two conditions has not been established.
Linear time bounds for median computations

New upper and lower bounds are presented for the maximum number of comparisons, f(i,n), required to select the i-th largest of n numbers. An upper bound is found, by an analysis of a new selection algorithm, to be a linear function of n: f(i,n) ≤ 103n/18 < 5.73n, for 1 ≤ i ≤ n. A lower bound is shown deductively to be: f(i,n) ≥ n+min(i,n−i+l) + [log2(n)] − 4, for 2 ≤ i ≤ n−1, or, for the case of computing medians: f([n/2],n) ≥ 3n/2 − 3
Fast arbiters for on-chip network switches

The need for efficient implementation of simple crossbar schedulers has increased in the recent years due to the advent of on-chip interconnection networks that require low latency message delivery. The core function of any crossbar scheduler is arbitration that resolves conflicting requests for the same output. Since, the delay of the arbiters directly determine the operation speed of the scheduler, the design of faster arbiters is of paramount importance. In this paper, we present a new bit-level algorithm and new circuit techniques for the design of programmable priority arbiters that offer significantly more efficient implementations compared to already-known solutions. From the experimental results it is derived that the proposed circuits are more than 15% faster than the most efficient previous implementations, which under equal delay comparisons, translates to 40% less energy.
ALFRED: A Practical Method for Alignment-Free Distance Computation

Alignment-free approaches are gaining persistent interest in many sequence analysis applications such as phylogenetic inference and metagenomic classification/clustering, especially for large-scale sequence datasets. Besides the widely used k-mer methods, the average common substring (ACS) approach has emerged to be one of the well-known alignment-free approaches. Two recent works further generalize this ACS approach by allowing a bounded number k of mismatches in the common substrings, relying on approximation (linear time) and exact computation, respectively. Albeit having a good worst-case time complexity [Formula: see text], the exact approach is complex and unlikely to be efficient in practice. Herein, we present ALFRED, an alignment-free distance computation method, which solves the generalized common substring search problem via exact computation. Compared to the theoretical approach, our algorithm is easier to implement and more practical to use, while still providing highly competitive theoretical performances with an expected run-time of [Formula: see text]. By applying our program to phylogenetic inference as a case study, we find that our program facilitates to exactly reconstruct the topology of the reference phylogenetic tree for a set of 27 primate mitochondrial genomes, at reasonably acceptable speed. ALFRED is implemented in C++ programming language and the source code is freely available online.
Fail-Safe Hierarchical Organization for Wireless Sensor Networks

This paper presents the definition and evaluation of a new protocol for providing a wireless sensor network (WSN) with a hierarchical organization. Differently from previously proposed solutions, our protocol, termed CC ("double c," for clique clustering), includes in its operation a fail-safe mechanism for dealing with node failure or removal, which are typical of WSNs. More specifically, the network is partitioned into clusters that are cliques, i.e., nodes in each clusters are directly connected to each others. An efficient mechanism for building a connected backbone among the clique clusters is provided. Clustering, backbone formation and backbone maintenance are completely localized, in the precise sense that only nodes physically close to a failing node are involved in the reconfiguration process. We compare the performance of CC with that of DMAC, a protocol that has been previously proposed for building and maintaining clusters and backbones in presence of node removal. Our comparison concerns metrics that are central to WSN research, such as time for clustering and backbone reorganization, corresponding overhead (in bytes and transmission energy), backbone size, extent of the reorganization (i.e., the number of nodes involved in it), and backbone route length. Our ns2-based simulation results show that the design criteria chosen for CC are effective in producing backbones that can be reconfigured quickly (63% faster than DMAC's) and with remarkably lower overhead.
An instructional DVD fall-prevention program for patients with cancer and family caregivers.

PURPOSE/OBJECTIVES Determine the efficacy of a fall-prevention skills training program for patients with cancer and family caregivers. DESIGN Randomized, controlled trial with repeated measures and postintervention measure of fall occurrence. SETTING A comprehensive cancer center in the midwestern United States. SAMPLE 132 patient and family caregiver dyads. METHODS Dyads were randomly assigned to one of two groups: a control group that received standard fall-prevention education or a treatment group that received standard education and a fall-prevention DVD program to view at home. Participants completed surveys at baseline, one week, one month, and three months. Follow-up phone calls were made at three months. MAIN RESEARCH VARIABLES Fall occurrence, perceptions of fall risks, and fall-prevention knowledge. FINDINGS Patients in the treatment group were significantly more likely to report not falling at three months than patients in the control group. The number of falls was lower for the treatment group. The difference was not statistically significant. Dyads in the treatment group showed significantly greater improvement over time in fall risk awareness and fall-prevention knowledge. CONCLUSIONS Mobility skills training is a promising educational intervention for reducing fall occurrences in the home for patients with cancer. IMPLICATIONS FOR NURSING Efforts are needed for improving the knowledge and skills of cancer survivors and their family members in recognizing patient fall risks, making home adjustments, and performing mobility skills competently.
Expression-associated polymorphisms of CAV1-CAV2 affect intraocular pressure and high-tension glaucoma risk

Purpose The human CAV1-CAV2 locus has been associated with susceptibility to primary open-angle glaucoma in four studies of Caucasian, Chinese, and Pakistani populations, although not in several other studies of non-Korean populations. In this study with Korean participants, the CAV1-CAV2 locus was investigated for associations with susceptibility to primary open-angle glaucoma accompanied by elevated intraocular pressure (IOP), namely, high-tension glaucoma (HTG), as well as with IOP elevation, which is a strong risk factor for glaucoma. Methods Two single nucleotide polymorphisms (SNPs) were genotyped in 1,161 Korean participants including 229 patients with HTG and 932 healthy controls and statistically examined for association with HTG susceptibility and IOP. One SNP was rs4236601 G>A, which had been reported in the original study, and the other SNP was rs17588172 T>G, which was perfectly correlated (r2=1) with another reported SNP rs1052990. Expression quantitative trait loci (eQTL) analysis was performed using GENe Expression VARiation (Genevar) data. Results Both SNPs were associated with HTG susceptibility, but the rs4236601 association disappeared when adjusted for the rs17588172 genotype and not vice versa. The minor allele G of rs17588172 was associated significantly with 1.5-fold increased susceptibility to HTG (p=0.0069) and marginally with IOP elevation (p=0.043) versus the major allele T. This minor allele was also associated with decreased CAV1 and CAV2 mRNA in skin and adipose according to the Genevar eQTL analysis. Conclusions The minor allele G of rs17588172 in the CAV1-CAV2 locus is associated with decreased expression of CAV1 and CAV2 in some tissues, marginally with IOP elevation, and consequently with increased susceptibility to HTG.
Maternal gene-micronutrient interactions related to one-carbon metabolism and the risk of myelomeningocele among offspring.

BACKGROUND Few studies have evaluated interactions between maternal genetic variation in 5,10-methylenetetrahydrofolate reductase (MTHFR) and micronutrient intake on the risk of myelomeningocele (MM) in offspring. Therefore, we sought to determine if the role of maternal MTHFR C677T and A1298C on MM risk is altered by maternal intake of micronutrients related to one-carbon metabolism. METHODS The study consisted of 220 MM case-parent trios recruited from 1996 to 2006. A dietary questionnaire was used to obtain information on maternal dietary intake on eight micronutrients including folate and cobalamin. TaqMan assays were used to generate MTHFR C677T and A1298C genotypes. Log-linear models were used to evaluate the joint effects of maternal genotype and micronutrient intake dichotomized as at or above versus below the United States Recommended Dietary Allowance (US RDA) on MM. RESULTS There was little evidence to suggest maternal MTHFR genotypes interacted with micronutrient intake to influence the risk of MM. For instance, the effect of MTHFR 677T was similar for mothers with cobalamin intake below US RDA (relative risk [RR] = 0.97) versus at or above US RDA cobalamin intake (RR = 0.81, interaction p = 0.87). However, some differences were noted. For example, the effect of MTHFR 1298C appeared to be different between those mothers below US RDA folate intake (RR = 0.98) versus those at or above US RDA folate intake (RR = 0.68), but the interaction was not statistically significant (interaction p = 0.27). CONCLUSION There did not appear to be strong effects of maternal micronutrient intake on the role of maternal genetic polymorphisms in MTHFR C677T and A1298C on MM risk. Birth Defects Research 109:99-105, 2017. © 2016 Wiley Periodicals, Inc.
Pedagogical Virtual Agents an Overview

A pedagogical virtual agent can provide help on different levels with problems arising in a learning environment. During the course of this paper, agents developed over the past years are used to illustrate benefits and technical issues. In a study with one of the agents, researchers inspected the motivational aspect of an agent’s presence in an enviroment. The persona effect established in this study has been confirmed in similar investigations. Apart from motivating the user, other benefits emerge. An agent allows interactive demonstrations by employing gaze and gesture to refer to objects. By using nonverbal features in the dialogues, the agent can further enhance its explanations. Several technical issues arise from implementing a PVA in a learning environment. Both in the agent’s behaviour generation and behaviour control a dynamic and static approach exist. Furthermore it is important that the agent is aware of the environment it navigates in. A lifelike behaviour adds to a believable appearance the user enjoys to interact with.
Open-slip coupled model for simulating three-dimensional bond behavior of reinforcing bars in concrete

The bond mechanism for reinforcing bars in concrete is equivalent to the normal contact and friction between the inclined ribs and the surrounding concrete. Based on the contact density model for the computation of shear transfer across cracks, an open-slip coupled model was developed for simulating three-dimensional bond behavior for reinforcing bars in concrete. A parameter study was performed and verified by simulating pull-out experiments of extremely different boundary conditions: short bar embedment with a huge concrete cover, extremely long bar embedment with a huge concrete cover, embedded aluminum bar and short bar embedded length with an insufficient concrete cover. The bar strain effect and splitting of the concrete cover on a local bond can be explained by finite element (FE) analysis. The analysis shows that the strain effect results from a large local slip and the splitting effect of a large opening of the interface. Finally, the sensitivity of rebar geometry was also checked by FE analysis and implies that the open-slip coupled model can be extended to the case of plain bar.
Mass Spectrometry Offers Insight into the Role of Ser/Thr/Tyr Phosphorylation in the Mycobacteria

Phosphorylation is a post translational modification which can rapidly regulate biochemical pathways by altering protein function, and has been associated with pathogenicity in bacteria. Once engulfed by host macrophages, pathogenic bacteria are exposed to harsh conditions and must respond rapidly in order to survive. The causative agent of TB, Mycobacterium tuberculosis, is unusual amongst the bacteria because it can survive within the host macrophage for decades in a latent state, demonstrating a remarkable capacity to successfully evade the host immune response. This ability may be mediated in part by regulatory mechanisms such as ser/thr/tyr phosphorylation. Mass spectrometry-based proteomics has afforded us the capacity to identify hundreds of phosphorylation sites in the bacterial proteome, allowing for comparative phosphoproteomic studies in the mycobacteria. There remains an urgent need to validate the reported phosphosites, and to elucidate their biological function in the context of pathogenicity. However, given the sheer number of putative phosphorylation events in the mycobacterial proteome, and the technical difficulty of assigning biological function to a phosphorylation event, it will not be trivial to do so. There are currently six published phosphoproteomic investigations of a member of mycobacteria. Here, we combine the datasets from these studies in order to identify commonly detected phosphopeptides and phosphosites in order to present high confidence candidates for further validation. By applying modern mass spectrometry-based techniques to improve our understanding of phosphorylation and other PTMs in pathogenic bacteria, we may identify candidates for therapeutic intervention.
Development and Implementation of an Objective Structured Clinical Examination to Provide Formative Feedback on Communication and Interpersonal Skills in Geriatric Training

Teaching and assessment of communication and interpersonal skills, one of the American Council for Graduate Medical Education–designated core competencies, is an important but difficult task in the training of physicians. Assessment of trainees offers an opportunity to provide explicit feedback on their skills and encourages learning. This article describes a pilot study in which clinician‐educators affiliated with the geriatrics training programs at Beth Israel Deaconess Medical Center and Boston University Medical Center designed and piloted a novel Objective Structured Clinical Examination (OSCE) to assess the communication and interpersonal skills of medical, dental, and geriatric psychiatry fellows. The OSCE consisted of three stations where geriatricians and standardized patients evaluated candidates using specifically designed checklists and an abbreviated version of the Master Interview Rating Scale. Communication skills were assessed through performance of specific “real life” clinical tasks, such as obtaining a medical history, explaining a diagnosis and prognosis, giving therapeutic instructions, and counseling. Interpersonal skills were assessed through the effect of the communication between doctor and standardized patient on fostering trust, relieving anxiety, and establishing a therapeutic relationship. This pilot study demonstrated that the OSCE format of assessment provides a valid means of evaluating the communication and interpersonal skills of interdisciplinary geriatric trainees and provides a valuable forum for formative assessment and feedback. Given that geriatricians and non geriatricians involved in elder care both need communication and interpersonal skills, this novel OSCE can be used for assessment of these skills in trainees in diverse healthcare subspecialties.
Seed-Relative Segmentation Robustness of Watershed and Fuzzy Connectedness Approaches

This paper analyzes the robustness issue in three segmentation approaches: the iterative relative fuzzy object extraction, the watershed transforms (WT) by image foresting transform and by minimum spanning forest. These methods need input seeds, which can be source of variability in the segmentation result. So, the robustness of these segmentation methods in relation to the input seeds is focused. The core of each seed is defined as the region where the seed can be moved without altering the segmentation result. We demonstrate that the core is identical for the three methods providing that the tie-zone transform has previously been applied on these methods. Indeed, as the two WT approaches do not return unique solution, the set of possible solutions has to be considered in a unified solution. So does the tie-zone transform. As opposed to what we could think, we show that the core is included in but different from the catchment basin. We also demonstrate that the tie-zone transforms of these WTs are always identical. Furthermore, the framework of minimal sets of seeds, an inverse problem of segmentation, is extended to the pixel level and related to the cores. A new algorithm for the computation of minimal seed sets is finally proposed.
Serial propagation of human endothelial cells in vitro

Human umbilical vein (HUV) endothelial cells were grown for 15 to 21 passages at a split ratio of 1:5 (at least 27 population doublings) on a human fibronectin (HFN) matrix in Medium 199 supplemented with fetal bovine serum (FBS) and endothelial-cell growth factor (ECGF). This system also permitted the growth of HUV endothelial cells at cell densities as low as 1.25 cells/cm2. In addition to delaying the premature senescence of HUV endothelial cells, ECGF also reduced the serum requirement for low-density HUV endothelial-cell growth; 2.5% serum and ECGF yields half-maximum growth as compared to high serum controls. Significant HUV endothelial-cell growth was also observed in medium supplemented with either ovine hypophysectomized (HYPOX) serum, plasma-derived serum (PDS), or HYPOX-PDS in the presence of ECGF, suggesting that neither the pituitary nor the platelet contributes to HUV endothelial-cell growth.
The CRYPTOCHROME1-Dependent Response to Excess Light Is Mediated through the Transcriptional Activators ZINC FINGER PROTEIN EXPRESSED IN INFLORESCENCE MERISTEM LIKE1 and ZML2 in Arabidopsis[C][W]

This work identifies ZML2 and its homolog ZML1 as key regulators of gene expression in the cry1-dependent response to excess light. ZML1/2 bind to the CryR1 cis-element in vitro and in vivo, and T-DNA insertion lines for ZML2 and ZML1 were sensitive to excess light, demonstrating misregulation of several cry1-dependent genes in response to excess light. Exposure of plants to light intensities that exceed the electron utilization capacity of the chloroplast has a dramatic impact on nuclear gene expression. The photoreceptor Cryptochrome 1 (cry1) is essential to the induction of genes encoding photoprotective components in Arabidopsis thaliana. Bioinformatic analysis of the cry1 regulon revealed the putative cis-element CryR1 (GnTCKAG), and here we demonstrate an interaction between CryR1 and the zinc finger GATA-type transcription factors ZINC FINGER PROTEIN EXPRESSED IN INFLORESCENCE MERISTEM LIKE1 (ZML1) and ZML2. The ZML proteins specifically bind to the CryR1 cis-element as demonstrated in vitro and in vivo, and TCTAG was shown to constitute the core sequence required for ZML2 binding. In addition, ZML2 activated transcription of the yellow fluorescent protein reporter gene driven by the CryR1 cis-element in Arabidopsis leaf protoplasts. T-DNA insertion lines for ZML2 and its homolog ZML1 demonstrated misregulation of several cry1-dependent genes in response to excess light. Furthermore, the zml1 and zml2 T-DNA insertion lines displayed a high irradiance-sensitive phenotype with significant photoinactivation of photosystem II (PSII), indicated by reduced maximum quantum efficiency of PSII, and severe photobleaching. Thus, we identified the ZML2 and ZML1 GATA transcription factors as two essential components of the cry1-mediated photoprotective response.
All-trans retinol and retinol-binding protein from embryonic cerebrospinal fluid exhibit dynamic behaviour during early central nervous system development

Embryonic cerebrospinal fluid (E-CSF) is involved in the regulation of survival, proliferation and neurogenesis of neuroectodermal progenitor cells, as well as in the control of mesencephalic gene expression in collaboration with the isthmic organizer. Recently, we showed the presence of retinol-binding protein (RBP) within the E-CSF proteome. RBP is an all-trans retinol carrier, a molecule that can be metabolized into retinoic acid, a morphogen involved in central nervous system (CNS) morphogenesis and patterning. Here we demonstrate the presence of all-trans retinol within the E-CSF and analyse the dynamics of RBP and all-trans retinol within this fluid, as well as the expression of retinoic acid-synthesizing enzymes during early CNS development. Our results suggest a relationship between the dynamics of these molecules and the early events of CNS patterning.