Miracle-dz/UniFAR-FTUs huggingface dataset:
Toxin Pores Endocytosed During Plasma Membrane Repair Traffic into the Lumen of MVBs for Degradation

Cells permeabilized by the bacterial pore‐forming toxin streptolysin O (SLO) reseal their plasma membrane in a Ca2+‐dependent manner. Resealing involves Ca2+‐dependent exocytosis of lysosomes, release of acid sphingomyelinase and rapid formation of endosomes that carry the transmembrane pores into the cell. The intracellular fate of the toxin‐carrying endocytic vesicles, however, is still unknown. Here, we show that SLO pores removed from the plasma membrane by endocytosis are sorted into the lumen of lysosomes, where they are degraded. SLO‐permeabilized cells contain elevated numbers of total endosomes, which increase gradually in size while transitioning from endosomes with flat clathrin coats to large multivesicular bodies (MVBs). Under conditions that allow endocytosis and plasma membrane repair, SLO is rapidly ubiquitinated and gradually degraded, in a process sensitive to inhibitors of lysosomal hydrolysis but not of proteasomes. The endosomes induced by SLO permeabilization become increasingly acidified and promote SLO degradation under normal conditions, but not in cells silenced for expression of Vps24, an ESCRT‐III complex component required for the release of intraluminal vesicles into MVBs. Thus, cells dispose of SLO transmembrane pores by ubiquitination/ESCRT‐dependent sorting into the lumen of late endosomes/lysosomes.
Different Effects of the Liver Mitogens Triiodo-Thyronine and Ciprofibrate on the Development of Rat Hepatocellular Carcinoma

Previous work has shown that treatment with thyroid hormone (T3) decreased the incidence of rat hepatocellular carcinoma (HCC). The present study was designed to determine whether the inhibitory effect of T3 on HCC development was limited to early steps of the carcinogenetic process or, whether a similar effect could also be exerted by starting T3 treatment at later stages. Hepatic nodules were induced in Fischer rats by a single dose of DENA, followed by a 2-week exposure of the animals to 2-AAF and partial hepatectomy. Rats were then divided into 3 groups: group 1 was maintained on basal diet; group 2 was fed a diet containing 4 mg/kg T3 for a week, every month/7 months, starting 9 weeks after DENA administration; group 3 was exposed to cycles of T3 starting 8 months after initiation. Results demonstrate that inhibition of HCC development was essentially similar in rats exposed to T3 starting either 9 weeks or 8 months after initiation (50% inhibition compared to control rats). We have previously shown that T3-induced nodule regression and HCC inhibition occurred in spite of its mitogenic effect. Therefore, we next wished to determine whether a similar antitumoral effect could be exerted by other liver mitogens, such as peroxisome proliferators. Rats exposed to the initiation-promotion protocol described previously, were subjected to 11 cycles of a T3 or a ciprofibrate-supplemented diet, each cycle consisting of 7 days/month; the incidence of HCC and lung metastases was determined 13.5 months after initiation. Results showed that although treatment with T3 strongly inhibited HCC development (only 31% of T3+ rats showed HCC vs 91% of controls), rats given ciprofibrate developed the same number of HCC as T3-untreated rats. In conclusion, the results of this study showed that the anticarcinogenic effect of T3 is maintained also when treatment begins late in the process, and its antitumoral property appears to be specific and may not be shared by other liver mitogens.
SIGIRR Genetic Variants in Premature Infants With Necrotizing Enterocolitis

Necrotizing enterocolitis (NEC) is a severe form of bowel disease that develops in premature infants. Although animal data and human studies suggest that aberrant activation of the intestinal immune system contributes to NEC, the pathogenesis remains unclear. We hypothesized that inherited defects in the regulation of Toll-like receptor signaling can contribute to NEC susceptibility in premature infants. A forward genetic screen done in an infant with lethal NEC using exome sequencing identified a novel stop mutation (p.Y168X) and a rare missense variant (p.S80Y) in SIGIRR, a gene that inhibits intestinal Toll-like receptor signaling. Functional studies carried out in human embryonic kidney cells and intestinal epithelial cells demonstrated that SIGIRR inhibited inflammation induced by lipopolysaccharide, a cell wall component of Gram-negative bacteria implicated in NEC. The genetic variants identified in the infant with NEC resulted in loss of SIGIRR function and exaggerated inflammation in response to lipopolysaccharide. Additionally, Sanger sequencing identified missense, stop, or splice region SIGIRR variants in 10 of 17 premature infants with stage II+ NEC. To the best of our knowledge, this is one of the first reports of a phenotype associated with SIGIRR in humans. Our data provide novel mechanistic insight into the probable causation of NEC and support additional investigation of the hypothesis that inherited defects in the regulation of innate immune signaling can contribute to NEC susceptibility in premature infants.
Frequent promoter hypermethylation and low expression of the MGMT gene in oligodendroglial tumors

Allelic losses on the chromosome arms 1p and 19q have been associated with favorable response to chemotherapy and good prognosis in anaplastic oligodendroglioma patients, but the molecular mechanisms responsible for this relationship are as yet unknown. The DNA repair enzyme O6‐methylguanine DNA methyltransferase (MGMT) may cause resistance to DNA‐alkylating drugs commonly used in the treatment of anaplastic oligodendrogliomas and other malignant gliomas. We report on the analysis of 52 oligodendroglial tumors for MGMT promoter methylation, as well as mRNA and protein expression. Using sequencing of sodium bisulfite‐modified DNA, we determined the methylation status of 25 CpG sites within the MGMT promoter. In 46 of 52 tumors (88%), we detected MGMT promoter hypermethylation as defined by methylation of more than 50% of the sequenced CpG sites. Real‐time reverse transcription‐PCR showed reduced MGMT mRNA levels relative to non‐neoplastic brain tissue in the majority of tumors with hypermethylation. Similarly, immunohistochemical analysis showed either no or only small fractions of MGMT positive tumor cells. MGMT promoter hypermethylation was significantly more frequent and the percentage of methylated CpG sites in the investigated MGMT promoter fragment was significantly higher in tumors with loss of heterozygosity on chromosome arms 1p and 19q as compared to tumors without allelic losses on these chromosomes arms. Taken together, our data suggest that MGMT hypermethylation and low or absent expression are frequent in oligodendroglial tumors and likely contribute to the chemosensitivity of these tumors.
Effects of stock density on the laying performance, blood parameter, corticosterone, litter quality, gas emission and bone mineral density of laying hens in floor pens

The effects of stocking density on the performance, egg quality, leukocyte concentration, blood biochemistry, corticosterone levels, bone mineral density, and noxious gas emission of laying hens were investigated. Eight hundred 34-week-old Hy-Line Brown laying hens (Gallus gallus domesticus) were randomly assigned to one of 4 treatments, each of which was replicated 4 times. Four stocking densities, including 5, 6, 7, and 10 birds/m2, were compared. A commercial-type basal diet was formulated to meet or exceed nutrient recommendations for laying hens from the National Research Council. The diet was fed to the hens ad libitum for 8 wk. Results indicated that hen-day egg production, egg mass, and feed intake were less for (P < 0.01) 10 birds/m2 stock density than other stock densities. Production rate of floor and broken eggs and eggshell strength were greater (P < 0.01) for 10 birds/m2 stock density than other stock densities. There were no significant differences in the level of leukocytes among densities. However, heterophils and the H/L ratio were greater (P < 0.01) for 10 birds/m2 than in stock density of 6 or 7 birds/m2. Serum corticosterone was greater (P < 0.01) 10 birds/m2 than stock density than other stock densities. Litter moisture and gas emission (CO2 and NH3) were greater (P < 0.01) for 10 birds/m2 than stock density than 6 and 7 birds/m2 stock density. Bone mineral content was not influenced by increasing stock density. However, bone mineral density was less (P < 0.05) for 10 m2 stock density than other stock densities. These results indicate that increasing the density beyond 5 birds/m2 elicits some negative effects on laying performance of Hy-Line brown laying hens.
The PillCam™ Colon Capsule for Colon Cancer Screening: Comparison Between the First- and Second-Generation Capsules

Abstract Population-based screening for colorectal cancer is widely recommended, with conventional colonoscopy (CC) being considered the preferred modality. However, compliance with colonoscopy screening is low, ranging between 20% and 50%, and manpower capacity for performing CC is limited. Therefore, a new, minimally invasive diagnostic tool, the PillCam™ Colon Capsule Endoscope (PCCE) was developed to become a desirable, patient-friendly, alternative strategy. This article will review the data regarding the 2 available generations of the PCCE.
Veterinary and human vaccine evaluation methods

Despite the universal importance of vaccines, approaches to human and veterinary vaccine evaluation differ markedly. For human vaccines, vaccine efficacy is the proportion of vaccinated individuals protected by the vaccine against a defined outcome under ideal conditions, whereas for veterinary vaccines the term is used for a range of measures of vaccine protection. The evaluation of vaccine effectiveness, vaccine protection assessed under routine programme conditions, is largely limited to human vaccines. Challenge studies under controlled conditions and sero-conversion studies are widely used when evaluating veterinary vaccines, whereas human vaccines are generally evaluated in terms of protection against natural challenge assessed in trials or post-marketing observational studies. Although challenge studies provide a standardized platform on which to compare different vaccines, they do not capture the variation that occurs under field conditions. Field studies of vaccine effectiveness are needed to assess the performance of a vaccination programme. However, if vaccination is performed without central co-ordination, as is often the case for veterinary vaccines, evaluation will be limited. This paper reviews approaches to veterinary vaccine evaluation in comparison to evaluation methods used for human vaccines. Foot-and-mouth disease has been used to illustrate the veterinary approach. Recommendations are made for standardization of terminology and for rigorous evaluation of veterinary vaccines.
Using Hybrid Methods for Relevance Assessment in TREC Crowd '12

Abstract : The University of Iowa (UIowaS) submitted three runs to the TRAT subtask of the 2012 TREC Crowdsourcing track. The task objective was to evaluate approaches to crowdsourcing high quality relevance judgments for a text document collection. We used this as an opportunity to examine three hybrid (combination of human-based and machine-based) approaches while simultaneously limiting time and cost. We create a training set from topics, which were previously assessed for relevance on the same document set, and use this training set to build strategies. We apply machine approaches, including clustering, to order documents for each topic, and then ask crowdworkers to provide relevance judgments for a subset of documents. One of our runs provides the best logistic average misclassification (LAM) rates of all submitted TRAT runs.
High temperature design and testing of a DC-DC power converter with Si and SiC devices

Performance of a 2 kW, 40 kHz, 270 V/500 V boost dc-dc power converter as a function of temperature is reported for the following four power semiconductor device combinations: Si IGBT/Si diode, Si IGBT/SiC diode, Si MOSFET/Si diode, and Si MOSFET/SiC diode. The test results show the possibility of designing 200/spl deg/C power converters with Si MOSFET, SiC Schottky, carefully selected soft-switching circuit topology, and devices with optimized packaging.
Historical and present status of the pearl oyster, Pinctada margaritifera, at Pearl and Hermes Atoll, Northwestern Hawaiian Islands

Populations of the black-lipped pearl oyster, Pinctada margaritifera, at Pearl and Hermes Atoll in the Northwestern Hawaiian Islands were first reported in 1928 and heavily harvested over the next years. Approximately 1 0,000 pearl oysters were either exported or killed during the exploitation. An expedition in 1 0 to assess postharvest population status found 0 P. margaritifera and determined the population to be severely depleted. Limited surveys in 1 and 000 found only a few pearl oysters and led to the conclusion that the population was still depleted. In 00 , the National Oceanic and Atmospheric Administration (NOAA)-led multi-agency marine debris removal team spent several months conducting surveys at Pearl and Hermes Atoll that included quantitative observations of Pinctada margaritifera. Data were collected on location, size, depth, habitat, and orientation of individual pearl oysters on the reef. Analyses of the 1930 and 2003 data sets revealed similar size-frequency distributions of the P. margaritifera population. The population has a spatial distribution within the Atoll similar to the 1 0 post-harvest distribution, and some sustained level of reproduction. Density and depth distribution comparisons from the two survey periods suggest that pearl oysters are significantly more abundant in the shallow waters where they were harvested during the fishery but at a similar density overall as they were during the 1930 survey. Although no estimates of absolute population size are available for any time period, the large number of oysters harvested prior to the 1 0 survey, together with estimates of oyster density in 1 0 and 00 , suggest that the population may never have recovered to its pre-exploitation level.
The Costs of Caring for a Child with an Autism Spectrum Disorder

Background: The primary purpose of this exploratory autism research was to examine the lived experiences of female primary caregivers of children with an autism spectrum disorder (ASD). Methods: Specifically the costs and benefits of the primary caregivers’ experiences were examined through semi-structured one-one-one interviews. The specific focus of this paper was to examine the costs of caring for a child with an ASD, whereby costs did not refer solely to monetary costs, but were related to all aspects of the caregivers’ lives. Interviews were completed with 8 mothers of children that had been formally diagnosed with an ASD. Results: Undoubtedly all family members within the family unit were affected by a child’s diagnosis with ASD as evidenced by the costs revealed by mothers. The subthemes derived from the theme of costs included the following: financial and work costs, costs to the health of family, social costs, and costs to overall family life. The results from this research provide evidence of the challenges associated with caring for a child with an ASD. Conclusions: It is anticipated that the insights provided by these mothers can act as a source of support for others faced with a similar situation. Additionally health care professionals may be able to use the knowledge gained from such qualitative endeavors in order to help parents cope more effectively with their caregiving responsibilities associated with children with ASDs. The mothers within this study are remarkable women that, for the most part, were able to rise above the negatives/costs associated with caring for a child with an ASD and find the silver linings amidst the turmoil. As remarkable as these women are in the daily struggles they face with their children, it is evident that more resources and support are required to assist these women and their families.
Dietary format alters fecal bacterial populations in the domestic cat (Felis catus)

The effects of short‐term (5‐week) exposure to wet or dry diets on fecal bacterial populations in the cat were investigated. Sixteen mixed‐sex, neutered, domestic short‐haired cats (mean age = 6 years; mean bodyweight = 3.4 kg) were randomly allocated to wet or dry diets in a crossover design. Fecal bacterial DNA was isolated and bacterial 16S rRNA gene amplicons generated and analyzed by 454 Titanium pyrosequencing. Cats fed dry diets had higher abundances (P < 0.05) of Actinobacteria (16.5% vs. 0.1%) and lower abundances of Fusobacteria (0.3% vs. 23.1%) and Proteobacteria (0.4% vs. 1.1%) compared with cats fed the wet diet. Of the 46 genera identified, 30 were affected (P < 0.05) by diet, with higher abundances of Lactobacillus (31.8% vs. 0.1%), Megasphaera (23.0% vs. 0.0%), and Olsenella (16.4% vs. 0.0%), and lower abundances of Bacteroides (0.6% vs. 5.7%) and Blautia (0.3% vs. 2.3%) in cats fed the dry diet compared with cats fed the wet diet. These results demonstrate that short‐term dietary exposure to diet leads to large shifts in fecal bacterial populations that have the potential to affect the ability of the cat to process macronutrients in the diet.
Harnessing the Power of Self-Organization in an Online Community During Organizational Crisis

Organizational crisis management has traditionally favored a centralized plan-and-control approach. This study explores the possibility for an orderly crisis management process to arise unintentionally from decentralized and spontaneous actions in an online community (i.e., self-organization). Based on complex adaptive systems theory, a multilevel model is developed to account for the logical relation between individual-level actions and interactions in an online community and an organizational-level orderly and rational crisis management process, as described by the organizational crisis management literature. We apply this multilevel model to an analysis of 89,596 posts from an online community that was deeply embedded in an earthquake-induced organizational crisis. Results indicate that fluctuation of message content themes in this online community served to energize continuous input from ordinary organization members. These input actualized new possibilities offered by the technology platform for crisis management actions (i.e., actualized IT affordances). Concatenation of immediate impacts of message content themes and actualized IT affordances formed feedback loops that moderated the crisis management activities toward an efficient trajectory. Our findings challenge the traditional assumption that macro-level order requires micro-level order-seeking behaviors. They suggest the viability of self-organization as a new source of organizational order that complements the traditional centralized plan-and-control approach. Theoretical and empirical implications for harnessing the power of ordinary organization members connected by today's technology platforms are discussed.
Reduction in Axial Length with Age: An Emmetropizing Mechanism for the Adult Eye?

Mechanisms accounting for the fact that the eye tends to become and remain emmetropic have been proposed for the developing eye, but no such mechanisms have been proposed for the adult eye. In the study reported here, refractive component data published by Sorsby and his co-workers were reanalyzed in terms of the variations in these components with age. Included in the analysis are component data for one eye of each of 271 subjects from age 4 to age 70 years, whose ocular refraction was between piano and +2.00 D. The results of this analysis show that the axial length of the eye appears to decrease during the adult years of life, concurrently with a decrease in anterior chamber depth and an increase in the refractive power of both the cornea and the lens. It is proposed that a reduction in the axial length of the adult eye serves as an emmetropizing mechanism, occurring in harmony with the increase in the refracting power of the eye, which would otherwise cause the refraction of the eye to move in the myopic direction.
Core Self-Evaluation and Burnout among Nurses: The Mediating Role of Coping Styles

Objectives This study aimed to determine the potential association between core self-evaluation and the burnout syndrome among Chinese nurses, and the mediating role of coping styles in this relationship. Methods A cross-sectional survey was conducted in Shenyang, China, from May to July, 2013. A questionnaire which consisted of the Maslach Burnout Inventory-General Survey (MBI-GS), the Core Self-Evaluation Scale (CSE), and the Simplified Coping Style Questionnaire (CSQ), was completed by a total of 1,559 nurses. Hierarchical linear regression analyses and the Sobel test were performed to determine the mediating role of coping styles on the relationship between CSE and burnout. Results Nurses who had higher self-evaluation characteristics, reported less emotional exhaustion and cynicism, and higher professional efficacy. Coping style had a partial mediating effect on the relationship between CSE and the burnout syndrome among nurses. Conclusions Core self-evaluation had effects on burnout and coping style was a mediating factor in this relationship among Chinese nurses. Therefore, the improvement of coping strategies may be helpful in the prevention of burnout among nurses, thus enhancing professional performance.
The impact of preschool wheezing patterns on health-related quality of life at age 4 years

We assessed whether dynamic preschool wheezing patterns affect health-related quality of life (HRQOL) at age 4 years. The study included 3878 children participating a prospective cohort study. Information on preschool wheezing was obtained by questionnaire and children were categorised into: never, early, late and persistent wheezing. At age 4 years HRQOL was measured using the Child Health Questionnaire (CHQ). Persistent wheezing was associated with reduced scores for nine out of 13 CHQ scales. No differences in psychosocial CHQ scores (p>0.05), but lower physical CHQ scores were found in children with late and persistent wheezing, compared to children who never wheezed (p<0.001). Mean scores on general health perceptions were, respectively, eight and 12 points lower (on a 0–100 scale) in children with late and persistent wheezing (p<0.001), and children with one to three episodes and four or more episodes of wheezing in the fourth year respectively scored seven and 24 points lower (p<0.001), compared to children who never wheezed. Persistent wheezing during preschool age independently affects a child's HRQOL, particularly general health perceptions and physical domains at age 4 years. HRQOL was more affected by frequent wheezing episodes in the fourth year of life, rather than by the duration of wheezing at age 0–4 years.
Anthropogenic Warming of the Oceans: Observations and Model Results

Abstract Observations show the oceans have warmed over the past 40 yr, with appreciable regional variation and more warming at the surface than at depth. Comparing the observations with results from two coupled ocean–atmosphere climate models [the Parallel Climate Model version 1 (PCM) and the Hadley Centre Coupled Climate Model version 3 (HadCM3)] that include anthropogenic forcing shows remarkable agreement between the observed and model-estimated warming. In this comparison the models were sampled at the same locations as gridded yearly observed data. In the top 100 m of the water column the warming is well separated from natural variability, including both variability arising from internal instabilities of the coupled ocean–atmosphere climate system and that arising from volcanism and solar fluctuations. Between 125 and 200 m the agreement is not significant, but then increases again below this level, and remains significant down to 600 m. Analysis of PCM’s heat budget indicates that the warming is dr.