Miracle-dz/UniFAR-FTUs huggingface dataset:
The Echinocandins: Comparison of Their Pharmacokinetics, Pharmacodynamics and Clinical Applications

Caspofungin, micafungin and anidulafungin are three drugs of the echinocandin class of antifungals available for intravenous treatment of invasive candidiasis and aspergillosis. They exhibit high in vitro and in vivo activities against Candida spp. and Aspergillus spp. In various clinical studies investigating candidemia and invasive candidiasis, Candida esophagitis, and fever in neutropenia, the clinical efficacy of the echinocandin tested was similar to that of established antifungals. Antifungal activity against strains no longer susceptible to conventional antifungal agents, such as fluconazole and amphotericin B suggests that echinocandins can be used as salvage therapy in life-threatening fungal infections. There is no cross-resistance to other antifungals. Excellent safety and tolerability of treatment with caspofungin has been documented over a total of 4.3 million patient days. Echinocandins are poor substrates of the cytochrome P450 enzyme family and can be safely co-administered with most drugs without the need for dosage adaptation. No dose reduction is required in renal impairment. A reduction in the daily maintenance dose has been recommended for caspofungin, but not for micafungin and anidulafungin in patients presenting with mild to moderate hepatic failure.
The impact of customer knowledge capability and relational capability on new product development performance in Taiwan's hospitals

New product development (NPD) has been the critical pathway to strengthening their competitive advantage for knowledge intensive organizations. This study intends to explore the impact of the customer knowledge integration capability (CKIC), customer knowledge absorptive capability (CKAC), customer knowledge creation capability (CKCC), and customer relationship capability (CRC) on NPD performance for hospitals from customer knowledge and customer relationship perspectives. Self-report questionnaires were sent out to 460 hospitals in Taiwan accredited as district hospitals and above. 185 valid questionnaires were returned in three months. After testing the fitness of sample representativeness, nonresponse error, common method variance, reliability, and validity, we adopt structure equation model to test the research model. Empirical results indicate the CKAC of a hospital is positively associated with NPD performance, and fully mediates the relationship between CKIC and NPD performance. However, CRC and CKAC both have positive influence on CKCC, but CKCC of a hospital does not produce a statistically significant impact on NPD performance. Customer knowledge capabilities are indeed important factors in NPD performance.
Association of cyclin D and estrogen receptor α36 with hepatocellular adenomas of female mice under chronic endoplasmic reticulum stress

Hepatocellular adenomas (HCAs) are benign tumors that can lead to medical complications. Chronic inflammation and mutations in β‐catenin, hepatocyte nuclear factor 1α, or glycoprotein 130 are potential causes for human HCA. However, additional causes may exist due to heterogeneity of HCA. We investigated whether HCA are caused by endoplasmic reticulum (ER) stress.
Write Code, Save Lives: How a Community Uses Open Innovation to Address a Societal Challenge

This study explores how a community uses open innovation over time to tackle a global societal challenge. we conduct an in&#8208;depth case study of OpenMRS, an open&#8208;source software community providing affordable medical record&#8208;keeping software in developing nations. We develop a process model that describes how inbound, outbound, and coupled open innovation influenced the community through four discrete phases of community development. We explain how the founders&#8217; vision led to the creation of the community, and how increasing community participation and community governance facilitated its growth. Interestingly, we found that economic opportunities made possible by open innovation may paradoxically create challenges to community sustainability. Ultimately, this study expands our understanding of open innovation communities in different settings, and their role in addressing societal challenges.
High‐frequency oscillation (HFO) prevents activation of NF‐κB found with conventional mechanical ventilation (CMV) in surfactant‐depleted rabbit lung

High‐frequency oscillation (HFO) has been recognized as an effective ventilatory strategy to minimize lung injury during respiratory support. Conventional mechanical ventilation (CMV) compared with HFO was shown to result in an increased number of PMNs and inflammatory cytokines in the lung lavage fluid. However how mechanical forces can be sensed by cells and converted into biochemical signals for intracellular signal transduction is still unknown. In this current study, we sought to determine whether the activation of Nuclear factor‐kappa B (NF‐κB) might be involved in the lung injury caused by CMV. Surfactant‐depleted Japanese white rabbits received 1‐ or 4‐hr CMV or 1‐ or 4‐hr HFO. Then, activation of NF‐κB in the lungs was assessed by conducting electrophoretic mobility shift assays (EMSA). In the experiment with whole lungs, NF‐κB activity was much higher in the 4‐hr CMV lungs than in the 4‐hr HFO lungs. To clarify the origin of the cells in which NF‐κB was activated, we did a second lung lavage at the end of ventilation and washed out the cells that had infiltrated the alveoli. The levels of NF‐κB activity were the similar in the lungs of 4‐hr HFO rabbits and in those of 4‐hr CMV ones. On the other hand, NF‐κB activity was much higher in the 4‐hr CMV lungs than in the 4‐hr HFO lungs in the experiment with the lung lavage fluid cells. These results show that the increase in NF‐κB activity in the lungs of 4‐hr CMV rabbits was due mainly to the cells that had infiltrated the alveoli. Pediatr Pulmonol. 2007; 42:440–445. © 2007 Wiley‐Liss, Inc.
SVAR description of ECB monetary policy effects via banking sector in individual EA countries: case of Slovenia

This paper constructs structural vector autoregression (SVAR) model for individual EA member states that is able to capture effects of European Central Bank's (ECB) unconventional measures. We separately model innovation to ECB key interest rate representing standard interest rate policy as exogenous variable and effects of balance sheet policies through change in claims against domestic sector of individual central banks as endogenous variable. By incorporating banking sector, we specifically examine effects of monetary policy on credit provisioning in individual countries. This model is applied on Slovenian economy after the euro adoption in 2007. Our results suggest that while standard interest rate policy has an effect on long-term interest rates for government bonds and interest rates on loans to households, the balance sheet policy brings about an additional impulse affecting bank interest rates but fails to affect bank spreads, government bonds or directly the credit provisioning.
REPRODUCTIVE BEHAVIOR OF FEMALE BUNTINGS: ISOLATING MECHANISMS IN A HYBRIDIZING PAIR OF SPECIES

The plumage characteristics of male Indigo and Lazuli Buntings are distinct, but the two species can learn each other's songs. Populations comprising Indigo, Lazuli and hybrid individuals occur in the Great Plains of North America, and assortative mating has been inferred from morphometric data. We devised a laboratory assay for determining female preferences for visual and vocal characteristics of conspecific and heterospecific males and for mixtures of these characteristics, such as might be encountered in an overlap population. Females of both species gave more copulation‐solicitation displays when exposed to conspecific plumage and vocalizations than when exposed to heterospecific plumage and vocalizations. Females gave intermediate and similar responses to the combinations of conspecific plumage with heterospecific vocalizations and heterospecific plumage with conspecific vocalizations. Thus, in the absence of other potentially important variables, female reproductive behavior is consistent with the hypothesis of assortative mating, based upon both vocal and visual traits of the males and caused by female choice in this semispecies pair.
Aging With Purpose: Systematic Search and Review of Literature Pertaining to Older Adults and Purpose

Purpose can provide a sense of intentionality, guide behavior to achieve personal aims and living objectives, and may offer insight into how and why certain people remain healthy over time. A review of the literature sought to identify contemporary research pertaining to purpose and older adults. Thirty-one studies were selected for evaluation based on inclusion criteria. Research outcomes suggest that greater reported purpose is related to a range of better health and well-being outcomes for older adults. With few exceptions, the literature demonstrates that purpose declines with age. Nevertheless, the potential to experience purpose persists across the life span, by providing opportunities for older adults to continue contributing roles, participate in meaningful activities, and sustain their social value and sense of relevance. Further research could explore how purpose is experienced by the oldest-old age-group, those living within noncommunity settings, and people with age-related cognitive impairment such as dementia.
STRIP1, a core component of STRIPAK complexes, is essential for normal mesoderm migration in the mouse embryo

Significance Striatin-interacting phosphatases and kinases (STRIPAK) complexes can regulate the cytoskeleton and cell migration in cell lines, but their roles in vivo in mammals are not known. Here, we show that mouse embryos that lack striatin-interacting protein 1 (STRIP1), a core component of STRIPAK complexes, arrest at midgestation with striking morphological defects. Strip1 mutants lack a trunk, and both paraxial and axial mesoderm fail to elongate along the anterior–posterior body axis. Mesodermal cells from Strip1 mutants have defects in actin organization, focal adhesions, and cell migration that can account for the failure of normal mesoderm migration. The findings demonstrate that STRIPAK is a critical regulator of mammalian cell migration and is likely to have important roles in tumor progression as well as development. Regulated mesoderm migration is necessary for the proper morphogenesis and organ formation during embryonic development. Cell migration and its dependence on the cytoskeleton and signaling machines have been studied extensively in cultured cells; in contrast, remarkably little is known about the mechanisms that regulate mesoderm cell migration in vivo. Here, we report the identification and characterization of a mouse mutation in striatin-interacting protein 1 (Strip1) that disrupts migration of the mesoderm after the gastrulation epithelial-to-mesenchymal transition (EMT). STRIP1 is a core component of the biochemically defined mammalian striatin-interacting phosphatases and kinase (STRIPAK) complexes that appear to act through regulation of protein phosphatase 2A (PP2A), but their functions in mammals in vivo have not been examined. Strip1-null mutants arrest development at midgestation with profound disruptions in the organization of the mesoderm and its derivatives, including a complete failure of the anterior extension of axial mesoderm. Analysis of cultured mesoderm explants and mouse embryonic fibroblasts from null mutants shows that the mesoderm migration defect is correlated with decreased cell spreading, abnormal focal adhesions, changes in the organization of the actin cytoskeleton, and decreased velocity of cell migration. The results show that STRIPAK complexes are essential for cell migration and tissue morphogenesis in vivo.
Governments, decentralisation, and the risk of electoral defeat

Abstract In the last three decades several countries around the world have transferred authority from their national to their regional governments. However, not all their regions have been empowered to the same degree and important differences can be observed between and within countries. Why do some regions obtain more power than others? Current literature argues that variation in the redistribution of power and resources between regions is introduced by demand. Yet these explanations are conditional on the presence of strong regionalist parties or territorial cleavages. This article proposes instead a theory that links the government’s risk of future electoral defeat with heterogeneous decentralisation, and tests its effects using data from 15 European countries and 141 regions. The results provide evidence that parties in government protect themselves against the risk of electoral defeat by selectively targeting decentralisation towards regions in which they are politically strong. The findings challenge previous research that overestimates the importance of regionalist parties while overlooking differences between regions.
Hormonal responsiveness of a preadipose cell line derived from newborn mouse calvaria

We established a clonal preadispose cell line from newborn mouse calvaria. Cells of this cell line, designated MC3T3‐G2/PA6, had the capacity to convert to adipose cells, to accumulate triglycerides in their cytoplasm, and to mature to differentiated fat cells in a resting state. This adipose conversion was markedly accelerated by addition of dexamethasone, which was the most potent inducer among the steroid hormones tested. The presence of dexamethasone was needed during logarithmic growth phase for maximal conversion. The frequency of adipose conversion was dependent on exposure time to the hormone, but cells already committed to differentiation continued to accumulate lipid and developed into mature adipose cell even in its absence. This indicates that the hormone accelerates the initiation of the adipose conversion, but is not required for the ongoing conversion process. In fact, it was rather inhibitory for the process of fat accumulation. Insulin alone slightly inhibited the adipose conversion, but its combination with dexamethasone neutralized the above inhibitory effect of dexamehasone. The responsiveness of this cell line is consistent with that observed for mouse bone marrow preadipocytes in primary culture but differs from that for preadipose cell lines derived from extramedullary tissues. These results strongly suggest that the MC3T3‐G2/PA6 cell line was derived from bone marrow.
Reduction of uranium transfer by local chelation in simulated wounds in rats

The aim of the paper is to develop a new approach to treat uranium-contaminated wounds. The efficacy of a local uranium chelator, carballylic amido bis phosphonic acid (CAPBP) was assessed using two different uranium compounds. Rats were contaminated by intramuscular injections of uranyl nitrate or an industrial U04 compound to simulate wound contamination. CAPBP was injected intramuscularly (im) or intraperitoneally (ip) at a dosage of 30,umol kg-. In one experiment, the local administration of CAPBP was combined with a systemic administration of ethane-1-hydroxy-1,1-biphosphonate (EHBP). The local CAPBP treatment resulted in increased retention of uranium at the wound site: about 30% for uranyl nitrate or U04 after the first day and about 15% of U04 after the third day. Consequently, it reduced uranium translocation into the blood and deposition in the kidneys and bone. The combined treatment reduced the uranium deposits in the kidneys, bone and carcass to about one-half of those observed in controls 3 days after U04 contamination. The local CAPBP treatment increased the interval of time between contamination and uranium deposit in the target organs. Thus, it can increase the efficacy of nonspecific local treatments or specific systemic treatments. It could be given rapidly through spray or gel after an accident.
The Evolution of Wealth-Income Ratios in India 1860-2012

This article is about the metamorphoses of aggregate Indian wealth over fifteen politically transformative decades. Based on a comprehensive new database, I find that wealth-income ratios have fluctuated by large margins in the twentieth century. In emerging India of the twenty first century, wealth is steadily approaching the same disproportionate size (relative to national income) that was seen during sharp economic downturns in interwar colonial India. The long run 1939-2012 U shaped trajectories of wealth-income ratios are reasonably explained by a mid century asset price slowdown and the return of high land shares in national wealth. These results corroborate the secular increase of wealth-income ratios in most large economies since the 1980s. The manifestation of this phenomena appears to be independent of the stage of development.
Genomics and successful aging: grounds for renewed optimism?

BACKGROUND Successful aging depends in part on delaying age-related disease onsets until later in life. Conditions including coronary artery disease, Alzheimer's disease, prostate cancer, and type 2 diabetes are moderately heritable. Genome-wide association studies have identified many risk associated single-nucleotide polymorphisms for these conditions, but much heritability remains unaccounted for. Nevertheless, a great deal is being learned. METHODS Here, we review age-related disease associated single-nucleotide polymorphisms and identify key underlying pathways including lipid handling, specific immune processes, early tissue development, and cell cycle control. RESULTS Most age-related disease associated single-nucleotide polymorphisms do not affect coding regions of genes or protein makeup but instead influence regulation of gene expression. Recent evidence indicates that evolution of gene regulatory sites is fundamental to interspecies differences. Animal models relevant to human aging may therefore need to focus more on gene regulation rather than testing major disruptions to fundamental pathway genes. Recent larger scale human studies of in vivo genome-wide expression (notably from the InCHIANTI aging study) have identified changes in splicing, the "fine tuning" of protein sequences, as a potentially important factor in decline of cellular function with age. Studies of expression with muscle strength and cognition have shown striking concordance with certain mice models of muscle repair and beta-amyloid phagocytosis respectively. CONCLUSIONS The emerging clearer picture of the genetic architecture of age-related diseases in humans is providing new insights into the underlying pathophysiological pathways involved. Translation of genomics into new approaches to prevention, tests and treatments to extend successful aging is therefore likely in the coming decades.
Implementation Multi-criteria Decision Making Technique in Overhaul Power Plants Projects

The aim of this study is to propose a multi-criteria decision making approach (MCDM) in order to evaluate Qualitative Factors in Overhaul Power Plants Projects, with due attention to the rating of qualitative criteria are considered as linguistic variables. Overhaul of the power generation plants affects the performance process. Some qualitative factors are of great importance in improving the quality of the process and avoiding wasting resources. The combined method of Analytic Network Process (ANP) and DEMATEL technique were used in this study. Four main and 16 secondary factors were identified in the final classification. Empirical results show that the proposed method is viable approaches in solving problem. When the performance ratings are vague and imprecise, this MCDM is a preferred solution method. The results show 8 highest Factors effects on the overhaul of the power plants respectively.
Effect of copper supplementation on the copper status of pasture-fed young Thoroughbreds.

The effect of copper supplementation of pasture fed mares and foals on the copper status of the foals, in terms of plasma, soft tissue and bone copper concentrations and caeruloplasmin activity, was investigated. Twenty-one Thoroughbred foals from either control mares (n = 9), or copper-supplemented mares (n = 12) were divided randomly into control (pasture only, n = 10) or supplemented (pasture and oral copper sulphate, n = 11) groups. The pasture diet was grazed by all animals, and contained 4.4-8.6 mg Cu/kg dry matter (DM). The copper supplement for the mares contained copper sulphate equivalent to 0.5 mg Cu/kg liveweight (LW)/day. This daily dose was converted to allow administration as a thrice weekly dose (i.e. multiplied by 7/3) which was given for 13-25 weeks prior to foaling. The supplemented foals, also dosed 3 times a week, received 0.2 mg Cu/kg LW/day at age 21 days, which was increased to 0.5 mg Cu/kg LW/day at 49 days and was continued at this level until euthanasia at 150 days. Foal plasma copper concentration and caeruloplasmin activity increased from birth to 21 days post partum and then plateaued at a concentration similar to the mare, but the rise in these indices was not affected by copper supplementation of the mare or foal. Copper supplementation of the foal increased foal liver copper concentration at 150 days (P<0.03). Copper intake of diets containing approximately 8-28 mg Cu/kg DM is well reflected by liver copper concentration, but is poorly reflected by bone, other soft tissue copper concentrations and circulating copper status indices.
Induction of micronucleated cells in the shed skin of salamanders (Ambystoma sp.) treated with colchicine or cyclophosphamide

The micronucleus (MN) assay can be used to detect the genotoxic effects of chemical agents in virtually any cell that divides frequently. Salamanders (Ambystoma sp.) are amphibians that can be easily maintained and bred in the laboratory and spontaneously shed their skin every 2.5–4 days. In this present study, we have evaluated the usefulness of this shed skin for the MN assay. We exposed salamanders to different concentrations of both the aneugen colchicine (COL) and the clastogen cyclophosphamide (CP) and we determined the frequency of micronucleated cells (MNCs) in their sheds. Fragments of shed skin were placed on clean slides, fixed, stained, observed with a light microscope, and the number of MNCs was counted. The MNC frequency was increased significantly by all doses of COL and CP tested, administered either as single or repeated exposures. The presence of MNCs in the shed skin and the speed of sloughing lead us to propose that the sheds of Ambystoma sp. , or other amphibians that slough their skin, are suitable alternative models for detecting genotoxic exposures relevant to aquatic environments. Environ. Mol. Mutagen. , 2004. © 2004 Wiley‐Liss, Inc.
Hierarchical 3D interconnection architecture with tightly-coupled processor-memory integration

In this paper, two designs of a 3D interconnection architecture for stacked processor-memory large-scale integrations (LSIs) were investigated. With consideration given to stacking formation, a hierarchical 3D interconnection architecture with a tightly coupled processor-memory stacking configuration is proposed for achieving both higher throughput per unit area and lower power consumption in the vertical communications. Compared with a baseline stacking configuration, the proposed architecture has the 38% fewer vertical interconnects for the same throughput and reduces power consumption by 21%. The performances of three-dimensional stacking chips with 64-processor cores are also estimated. As a result, the proposed architecture achieves twenty-times-lower power consumption of inter-chip communications than conventional 2D integration. A uni-directional interconnect configuration and a 3D two-way flow-control protocol were also developed to achieve maximal utilization of the 3D interconnection network. According to simulations using a cycle-accurate stacking LSI model, the proposed technique achieves 90% utilization of the interconnection network, while a conventional design achieves less than 60%.