Miracle-dz/UniFAR-FTUs huggingface dataset:
Thrombomodulin is an ezrin‐interacting protein that controls epithelial morphology and promotes collective cell migration

Adhesive interactions between cells are needed to maintain tissue architecture during development, tissue renewal and wound healing. Thrombo‐modulin (TM) is an integral membrane protein that participates in cell–cell adhesion through its extracellular lectin‐like domain. However, the molecular basis of TM‐mediated cell–cell adhesion is poorly understood. Here, we demonstrate that TM is linked to the actin cytoskeleton via ezrin. In vitro binding assays showed that the TM cytoplasmic domain bound directly to the N‐terminal domain of ezrin. Mutational analysis of the TM cytoplasmic domain identified 522RKK524 as important ezrin‐binding residues. In epidermal epithelial A431 cells, TM colocalized with ezrin and actin filaments at cell–cell contacts. Knockdown of endogenous TM expression by RNA interference induced morphological changes and accelerated cell migration in A431 cells. Moreover, epidermal growth factor, upstream of ezrin activation, stimulated the interaction between ezrin and TM. In skin wound healing of mice, TM and ezrin were highly expressed in neoepidermis, implying that both proteins are key molecules in reepithelialization that requires collective cell migration of epithelial cells. Finally, exogenous expression of TM in TM‐deficient melanoma A2058 cells promoted collective cell migration. In summary, TM, which associates with ezrin and actin filaments, maintains epithelial morphology and promotes collective cell migration. —Hsu, Y. ‐Y. , Shi, G. ‐Y. , Kuo, C. ‐H. , Liu, S. ‐L. , Wu, C. ‐M. , Ma, C. ‐Y. , Lin, F. ‐Y. , Yang, H. ‐Y. , Wu, H. ‐L. Thrombomodulin is an ezrin‐interacting protein that controls epithelial morphology and promotes collective cell migration. FASEB J. 26, 3440–3452 (2012). www.fasebj. org
Photofission of 238U with monochromatic gamma rays in the energy range 11-16 MeV.

We have measured the angular and mass distributions of the fragments from photofission of {sup 238}U using tagged photons with energies between 11 and 16 MeV. The fission fragments were detected by a 4{pi} arrangement of position-sensitive parallel-plate avalanche counters. Anisotropic angular distributions have been observed for the first time in the energy range where second-chance fission becomes energetically possible. A consistent assignment of {ital J}{sup {pi}} and {ital K} for the fission channels in {sup 237}U has been deduced from a combined analysis of ({gamma},{ital nf}) and ({ital e},{ital e}{prime}{ital f}) data. A clear relationship between the anisotropies and the fragment mass asymmetry has also been established. This correlation, together with the energy dependence of the angular distribution parameters, points to a possible interpretation of the results in terms of a recent theoretical model incorporating multiple exit channels in fission.
ZD1839, a selective oral epidermal growth factor receptor-tyrosine kinase inhibitor, is well tolerated and active in patients with solid, malignant tumors: results of a phase I trial.

PURPOSE To investigate the tolerability, pharmacokinetics, and antitumor activity of the oral, selective epidermal growth factor receptor-tyrosine kinase inhibitor ZD1839 in patients with solid malignant tumors. PATIENTS AND METHODS This was an open, phase I, escalating multiple-dose tolerability and pharmacokinetic trial. ZD1839 was administered once daily for 14 consecutive days followed by 14 days off treatment. Dose escalation started at 50 mg/d and continued to 925 mg or until consistent dose-limiting toxicity (DLT) was observed. RESULTS Sixty-four patients were entered at eight dose levels. The most frequent dose-related grade 1 and 2 adverse events were an acne-like (or folliculitis) rash, nausea, and diarrhea. Three of nine patients treated at 700 mg/d developed DLT (reversible grade 3 diarrhea); grade 3 and 4 events were uncommon. Exposure to ZD1839 was dose proportional, and the mean terminal half-life was 48 hours (range, 37 to 65). Four of 16 patients with non-small-cell lung cancer (NSCLC) had objective partial responses observed from ZD1839 300 to 700 mg/d. Overall, 16 patients remained on study for > or = 3 months, with seven of these patients (five with NSCLC, including three of the patients with partial response) remaining on study for > or = 6 months. CONCLUSION ZD1839 was well tolerated, with DLT observed at a dose well above that at which antitumor activity was seen. Pharmacokinetic analysis confirmed that ZD1839 was suitable for administration as a once-daily oral tablet formulation. Phase II monotherapy and phase III combination trials in NSCLC are being conducted to investigate further the efficacy, tolerability, and optimal daily dose of ZD1839.
Impacts of spatial and environmental heterogeneity on grizzly bear demographics in the greater yellowstone ecosystem : A source-sink dynamic with management consequences

By necessity, grizzly bear demographic models have largely ignored spatial considerations (McLellan 1989, Eberhardt et al. 1994, Eberhardt 1995, Hovey and McLellan 1996). However, ignoring spatial heterogeneity is equivalent to assuming that individuals live in a homogeneous environment and that all members of the population experience the same environmental conditions at any point in time (Pulliam 1996). Knight et al. (1988) were probably the first to recognize the potential effect of habitat heterogeneity on grizzly bear survival and impacts of sink habitats on long-term conservation of the species (see also Doak 1995). These sinks, associated with human activity and development, represented locations where grizzly bears obtained anthropogenic foods and suffered high rates of mortality. Schwartz et al. (2006c) and Haroldson et al. (2006) demonstrated that simple spatial indices of residency were consistently important correlates of survival. To understand the implications of geographically heterogeneous survival, we explored life tables corresponding to hypothetical grizzly bear populations whose residency varied from living entirely within Yellowstone National Park (InYNP), to entirely outside of YNP but within the U.S. Fish and Wildlife Service–designated RZ (OutYNP), and beyond the borders of the RZ (OutRZ), using survival rates of the top models of dependent and independent bears (Haroldson et al. 2006, Schwartz et al. 2006c). These 3 zones correspond to distinct management approaches, although they doubtless ignore finerscale correlates of survival. We further explored consequences of these simulations and discuss them in the context of source–sink theory, deviations from the theory, and implications for management. Additionally, we incorporate significant temporal covariates into our models and explore impacts of temporal heterogeneity (food availability) on population demographics.
Induced Sputum versus Bronchoalveolar Lavage Fluid in the Evaluation of Patients with Idiopathic Pulmonary Fibrosis

Background: Induced sputum (IS) has been proposed as a useful noninvasive method for the assessment of airway diseases. Bronchoalveolar lavage fluid (BALF), an important tool for evaluating interstitial lung diseases, has limited utility due to its invasiveness and the difficulties of performing it in severely ill patients, while it is impractical for follow-up evaluation. Objectives: The aim of this study was to investigate the differences and the possible correlation of cell differential and lymphocyte subpopulations between BALF and IS samples in patients with idiopathic pulmonary fibrosis (IPF). Methods: We studied prospectively 20 patients (18 male, 2 female) of median age 67 years (range 40–75) with IPF and 10 normal subjects (5 female, 5 male) of median age 59 years (range 36–70). IS was performed with hypertonic saline solution using an ultrasonic nebulizer (Ultraneb 2000). BALF was performed by a conventional procedure using fiberoptic bronchoscopy within 3 days from IS. May-Grünewald-Giemsa-stained preps were differentially counted and T-lymphocyte subsets were analyzed by a flow-activated cell sorter. Results: The percentage of macrophages was significantly lower in IS than in BALF (p < 0.0001), while the neutrophils were lower in BALF (p < 0.0001). A significant correlation was found between BALF and IS eosinophil counts (r = 0.54, p = 0.01) and CD4+/CD8+ ratio (r = 0.74, p < 0.0001). Conclusion: Our data suggest that different information is obtained by IS and BALF and thus, the two methods are complementary in IPF.
Physiologic mechanisms of sequential products synthesis in 1,3‐propanediol fed‐batch fermentation by Klebsiella pneumoniae

The glycerol fed‐batch fermentation by Klebsiella pneumoniae CGMCC 1.6366 exhibited the sequential synthesis of products, including acetate, 1,3‐propanediol (1,3‐PD), 2,3‐butanediol, ethanol, succinate, and lactate. The dominant flux distribution was shifted from acetate formation to 1,3‐PD formation in early‐ exponential growth phase and then to lactate synthesis in late‐exponential growth phase. The underlying physiological mechanism of the above observations has been investigated via the related enzymes, nucleotide, and intermediary metabolites analysis. The carbon flow shift is dictated by the intrinsic physiological state and enzymatic activity regulation. Especially, the internal redox state could serve as a rate‐controlling factor for 1,3‐PD production. The q1,3‐PD formation was the combined outcomes of regulations of glycerol dehydratase activity and internal redox balancing. The qethanol/qacetate ratios demonstrated the flexible adaptation mechanism of K. pneumoniae preferring ATP generation in early‐exponential growth phase. A low PEP to pyruvate ratio corresponded LDH activity increase, leading to lactate accumulation in stationary phase. Biotechnol. Bioeng. 2008;100: 923–932. © 2008 Wiley Periodicals, Inc.
CHARACTERIZATION OF DAIRY-ASSOCIATED SPOREFORMERS 1 Identification and Characterization of Psychrotolerant Sporeformers Associated with Fluid 1 Milk Production and Processing 2 3

1 Identification and Characterization of Psychrotolerant Sporeformers Associated with Fluid 1 Milk Production and Processing 2 3 Reid A. Ivy, Matthew L. Ranieri, Nicole H. Martin, Henk C. den Bakker, Bruno M. Xavier, 4 Martin Wiedmann, and Kathryn J. Boor* 5 6 Cornell University, Department of Food Science, Ithaca, NY 14853 7 8 9 Corresponding author 10 Mailing address: 11 260 Roberts Hall 12 Cornell University 13 Ithaca, NY 14853 14 Phone: (607) 255-2241 15 Fax: (607) 254-4868 16 17
Rates of hypoxia induction alter mechanisms of O2 uptake and the critical O2 tension of goldfish

ABSTRACT The rate of hypoxia induction (RHI) is an important but overlooked dimension of environmental hypoxia that may affect an organism's survival. We hypothesized that, compared with rapid RHI, gradual RHI will afford an organism more time to alter plastic phenotypes associated with O2 uptake and subsequently reduce the critical O2 tension (Pcrit) of the rate of O2 uptake (ṀO2). We investigated this by determining Pcrit values for goldfish exposed to short (∼24 min), typical (∼84 min) and long (∼480 min) duration Pcrit trials to represent different RHIs. Consistent with our predictions, long duration Pcrit trials yielded significantly lower Pcrit values (1.0–1.4 kPa) than short and typical duration trials, which did not differ (2.6±0.3 and 2.5±0.2 kPa, respectively). Parallel experiments revealed these time-related shifts in Pcrit were associated with changes to aspects of the O2 transport cascade that took place over the hypoxia exposures: gill surface areas and haemoglobin–O2 binding affinities were significantly higher in fish exposed to gradual RHIs over 480 min than fish exposed to rapid RHIs over 60 min. Our results also revealed that the choice of respirometric technique (i.e. closed versus intermittent) does not affect Pcrit or routine ṀO2, despite the significantly reduced water pH and elevated CO2 and ammonia levels measured following closed-circuit Pcrit trials of ∼90 min. Together, our results demonstrate that gradual RHIs result in alterations to physiological parameters that enhance O2 uptake in hypoxic environments. An organism's innate Pcrit is therefore most accurately determined using rapid RHIs (<90 min) so as to avoid the confounding effects of hypoxic acclimation. Summary: Compared with typical rates of hypoxia induction used in closed-respirometry Pcrit experiments, gradual rates significantly lower the Pcrit of goldfish by increasing gill surface area and Hb–O2 binding affinity.
Investing in Self-Care: A Midrange Theory of Self-Care Grounded in the Lived Experience of Low-Income HIV-Positive White Women

Little is known about the types of interventions that invite low-income women into partnerships that motivate self-care practices when living with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). The increasing incidence of HIV infection in low-income women with histories of inattention to self-care calls for nursing theories that address self-care practices. The purpose of this article is to describe a midrange theory developed from grounded theory research and to discuss implications of theoretical construction for future knowledge development. For the 12 women in this study, self-care practices developed over time and through four categories: focusing self, fitting resources, feeling emotions, and finding meaning. The core category, investing in self-care, linked the categories and carried explanatory power for developing midrange theory. Implications for nursing knowledge development through partnerships with low-income women are discussed.
Forebrain sites differentially sensitive to beta-endorphin and morphine for analgesia and release of Met-enkephalin in the pentobarbital-anesthesized rat.

The mapping of the forebrain regions sensitive to beta-endorphin and morphine for antinociception was performed in pentobarbital-anesthetized rats. The antinociception was assessed by the tail-flick test. The sites most sensitive to beta-endorphin (2 micrograms) for inhibition of the tail-flick response were located in the ventromedial regions of the forebrain such as medial posterior nucleus accumbens, medial preoptic area and arcuate hypothalamic nucleus. Other areas such as anterior nucleus accumbens, dorsomedial hypothalamic nucleus, posterior hypothalamus, lateral hypothalamus, caudate nuclei, thalami and cerebral cortex were not sensitive to beta-endorphin for the tail-flick inhibition. The sites sensitive to morphine sulfate (4 micrograms) for inhibition of the tail-flick response were located in regions of medial preoptic nucleus and arcuate hypothalamic nucleus. Posterior nucleus accumbens, which is sensitive to beta-endorphin, was not sensitive to morphine for antinociception. Morphine injected into this site did not produce tail-flick inhibition in both conscious and pentobarbital-anesthetized rats. The inhibition of the tail-flick response induced by beta-endorphin (2 micrograms) from posterior nucleus accumbens, medial preoptic area and arcuate hypothalamic nucleus was blocked by the administration of beta-endorphin-(1-27), an epsilon opioid receptor blocker, but not by D-Phe-Cys-Tyr-D-Try-Orn-Thr-Pen-Thr-NH2, a mu opioid receptor blocker. On the other hand, the inhibition induced by morphine (4 micrograms) from medial preoptic area and arcuate hypothalamic nucleus was blocked by D-Phe-Cys-Tyr-D-Try-Orn-Thr-Pen-Thr-NH2, but not by beta-endorphin-(1-27). (ABSTRACT TRUNCATED AT 250 WORDS)
Evaluation of the Prognostic Criteria for Medicare Hospice Eligibility

Background Medicare fiscal intermediaries judge the eligibility of patients for the Medicare Hospice Benefit (MHB) using “Local Medical Review Policies” or LMRPs. Because access to quality end-of-life care in the U.S is influenced by such policies, it is important to evaluate their validity and regulatory impact. Methods To evaluate the predictive validity and classificatory errors of the LMRP criteria, a retrospective case-control study was undertaken at a single, large, Medicare-certified hospice in Florida comparing 207 Medicare beneficiaries with primary diagnoses of heart disease, dementia, or acute or chronic stroke who experienced long-term survival post MHB enrollment (>180 days) with 246 patients matched on primary diagnosis and admission site of care (residence or nursing home) who experienced short-term survival
On the recombination of hydronium and hydroxide ions in water

The recombination of hydronium and hydroxide ions following water ionization is one of the most fundamental processes determining the pH of water. The neutralization step once the solvated ions are in close proximity is phenomenologically understood to be fast, but the molecular mechanism has not been directly probed by experiments. We elucidate the mechanism of recombination in liquid water with ab initio molecular dynamics simulations, and it emerges as quite different from the conventional view of the Grotthuss mechanism. The neutralization event involves a collective compression of the water-wire bridging the ions, which occurs in approximately 0.5 ps, triggering a concerted triple jump of the protons. This process leaves the neutralized hydroxide in a hypercoordinated state, with the implications that enhanced collective compressions of several water molecules around similarly hypercoordinated states are likely to serve as nucleation events for the autoionization of liquid water.
Treatment of Infantile Spasms: Results of a Population‐Based Study with Vigabatrin as the First Drug for Spasms

Summary: Purpose: The efficacy of a protocol consisting of vigabatrin (VGB) as the first and adrenocorticotropic hormone (ACTH) or valproate (VPA) as the second drug was studied in the treatment of newly diagnosed infantile spasms (IS) during 1994 to 1997 in a population‐based design.
How do top- and bottom-performing companies differ in using business analytics?

Purpose Business analytics (BA) has attracted growing attention mainly due to the phenomena of big data. While studies suggest that BA positively affects organizational performance, there is a lack of academic research. The purpose of this paper, therefore, is to examine the extent to which top- and bottom-performing companies differ regarding their use and organizational facilitation of BA. Design/methodology/approach Hypotheses are developed drawing on the information processing view and contingency theory, and tested using multivariate analysis of variance to analyze data collected from 117 UK manufacture companies. Findings Top- and bottom-performing companies differ significantly in their use of BA, data-driven environment, and level of fit between BA and data-drain environment. Practical implications Extensive use of BA and data-driven decisions will lead to superior firm performance. Companies wishing to use BA to improve decision making and performance need to develop relevant analytical strategy to guide BA activities and design its structure and business processes to embed BA activities. Originality/value This study provides useful management insights into the effective use of BA for improving organizational performance.
Spatially explicit spreadsheet modelling for optimising the efficiency of reducing invasive animal density

1. Invasive ungulates with eruptive population dynamics can degrade sensitive habitats, harbour disease‐causing pathogens and facilitate the spread of weedy plants. Hence there is a need globally for cost‐effective density reduction and damage mitigation strategies. User‐friendly software tools that facilitate effective decision making by managers (who are not usually scientists) can help in understanding uncertainty and maximising benefits to native biodiversity within a constrained budget.
Circadian period and the timing of melatonin onset in men and women: predictors of sleep during the weekend and in the laboratory

Sleep complaints and irregular sleep patterns, such as curtailed sleep during workdays and longer and later sleep during weekends, are common. It is often implied that differences in circadian period and in entrained phase contribute to these patterns, but few data are available. We assessed parameters of the circadian rhythm of melatonin at baseline and in a forced desynchrony protocol in 35 participants (18 women) with no sleep disorders. Circadian period varied between 23 h 50 min and 24 h 31 min, and correlated positively (n = 31, rs = 0.43, P = 0.017) with the timing of the melatonin rhythm relative to habitual bedtime. The phase of the melatonin rhythm correlated with the Insomnia Severity Index (n = 35, rs = 0.47, P = 0.004). Self‐reported time in bed during free days also correlated with the timing of the melatonin rhythm (n = 35, rs = 0.43, P = 0.01) as well as with the circadian period (n = 31, rs = 0.47, P = 0.007), such that individuals with a more delayed melatonin rhythm or a longer circadian period reported longer sleep during the weekend. The increase in time in bed during the free days correlated positively with circadian period (n = 31, rs = 0.54, P = 0.002). Polysomnographically assessed latency to persistent sleep (n = 34, rs = 0.48, P = 0.004) correlated with the timing of the melatonin rhythm when participants were sleeping at their habitual bedtimes in the laboratory. This correlation was significantly stronger in women than in men (Z = 2.38, P = 0.017). The findings show that individual differences in circadian period and phase of the melatonin rhythm associate with differences in sleep, and suggest that individuals with a long circadian period may be at risk of developing sleep problems.
Fluorescence visualization of receptor-bound low density lipoprotein in human fibroblasts.

AbstractPrevious electron microscopic studies have shown that receptors for plasma low density lipoprotein (LDL) in human fibroblasts are located predominantly in coated pits on the cell surface. In the current studies, LDL receptors were visualized at the light microscopic level by two methods: 1) indirect immuno-fluorescent staining of receptor-bound LDL, and 2) direct visualization of LDL particles that were reconstituted with a fluorescent cholesteryl ester derivative. By both techniques, LDL receptors were seen to be clustered in minute foci that were aligned in linear arrays on the cell surface. These arrays corresponded to linear arrays of coated pits that were visualized by immunofluorescent staining of the coat protein, clathrin. During the internalization of receptor-bound LDL, each fluorescent focus of LDL particles seemed to enter the cell as an individual unit without the formation of large patches. Immediately after the reconstituted fluorescent LDL entered the cell, the fluorescent dots bec.
Investigation of the Structural Relationships Between Social Support, Self-Compassion, and Subjective Well-Being in Korean Elite Student Athletes

The study examined whether self-compassion mediates the relationship between social support and subjective well-being, as perceived by athletes. It also investigated the structural relationships between these variables. Participants were 333 athletes attending high school or university. Structural equation analysis showed that self-compassion partially mediated the relationship between social support and subjective well-being. To test the stability of the model, a multiple group analysis was performed according to sex of participant and school level, and this demonstrated that the model had similar fit to the data regardless of group. The confirmation that self-compassion plays an intermediary role in the relationship between social support and subjective well-being demonstrates that self-compassionate attitudes can be fostered by social support, and that, in turn, has a positive effect on an individual’s subjective well-being.