Miracle-dz/UniFAR-FTUs huggingface dataset:
How to perform knowledge creation successfully in international strategic alliances: A multilevel perspective

For companies in emerging countries, international strategic alliances provide excellent opportunities for knowledge transfer and creation. In practice, it is easy to observe there is a nested relationship between international strategic alliances and a company, and this relationship covers micro strategic alliances level and macro organizational level. In order to more precisely explore knowledge creation in international strategic alliances, this study explores the antecedents of both strategic alliances level and organizational level on knowledge creation. Empirical results show that knowledge transfer which is from strategic alliance level has a positively significant impact on knowledge creation; company scale, R&D intensity and business group scale which are from organizational level have a positively significant effect on knowledge creation. And, both of company scale and business group scale have a cross-level moderating effect on the relationship between knowledge transfer and knowledge creation.
Molecular dissection of the response of the rice Systemic Acquired Resistance Deficient 1 (SARD1) gene to different types of ionizing radiation

Abstract Purpose: Exposure to ionizing radiation induces plant defenses by regulating the expression of response genes. The systemic acquired resistance deficient 1 (SARD1) is a key gene in plant defense response. In this study, the function of Oryza sativa SARD1 (OsSARD1) was investigated after exposure of seeds/plants to ionizing radiation, jasmonic acid (JA) or salicylic acid (SA). Materials and methods: Rice seeds exposed to two types of ionizing radiations (gamma ray [GR] and ion beam [IB]) were analyzed by quantitative reverse transcription PCR (qRT-PCR) to identify the genes that are altered in response to ionizing radiation. Then, OsSARD1-overexpressing homozygous Arabidopsis plants were generated to assess the effects of OsSARD1 in the response to irradiation. The phenotypes of these transgenic plants, as well as control plants, were monitored after GR irradiation at doses of 200 and 300 Gray (Gy). Results: The OsSARD1 transcript was strongly downregulated after exposure to GR and IB irradiation. Previous phylogenetic analysis showed that the Arabidopsis SARD1 (AtSARD1) protein is closely related to Arabidopsis calmodulin-binding protein 60g (AtCBP60g), which is known to be required for activation of SA biosynthesis. In this study, phylogenetic analysis showed that OsSARD1 was grouped with AtSARD1. The OsSARD1 gene was induced after exposure to SA and JA. The biological phenotype of OsSARD1-overexpressing Arabidopsis plants was examined. OsSARD1-overexpressing plants displayed resistance to GR; in comparison with wild-type plants, the height and weight of OsSARD1-overexpressing plants were significantly greater after GR irradiation. In addition, OsSARD1 protein was abundantly accumulated in the nucleus. Conclusions: The results indicate that OsSARD1 plays an important role in the regulation of the defense responses to GR and IB irradiation and exhibits phytohormone induced expression.
Hepatocellular Carcinoma and Hepatitis B Virus

Chronic hepatitis B is the most common cause of hepatocellular carcinoma (HCC) in Asia. Integration of hepatitis B virus (HBV) genome is likely an early event of carcinogenesis. The integrated HBV genome may activate neighboring cellular genes directly to offer a selective growth advantage to the liver cells. Production of hepatitis B X protein can act as a transactivator on various cellular genes for tumor development. Hepatic inflammation and cirrhosis also favors the process of carcinogenesis. Various viral factors associated with hepatocellular carcinoma development include HBV genotype, basal core promoter mutations, and high viral load. Polymorphisms at the androgen receptor-regulating genes and cytokine genes are possible host factors associated with HCC. This review article summarizes the pathogenesis of HBV-related carcinogenesis and the viral and host factors that may increase the risk of HCC development.
Calcineurin A–Binding Protein, a Novel Modulator of the Calcineurin-Nuclear Factor of Activated T-Cell Signaling Pathway, Is Overexpressed in Wilms' Tumors and Promotes Cell Migration

Current therapeutic strategies against Wilms' tumor (WT) reach 80% to 85% success rate. In spite of this, a remaining 15% to 20% of tumors relapse and are associated with increased metastasis and poor prognosis. To identify new regulators of WT progression, we screened for developmental target genes of Pax2, a key regulator of kidney development and a WT signature gene. We show that one of these target genes, calcineurin A–binding protein (CnABP), is coexpressed with Pax2 during kidney development and is overexpressed in >70% of WT samples analyzed. The CnABP gene encodes a novel protein product conserved in higher vertebrates. We show that CnABP promotes cell proliferation and migration in cell culture experiments. Biochemical analyses additionally identified an interaction between CnABP and calcineurin Aβ, the catalytic subunit of the calcium-responsive serine/threonine phosphatase calcineurin. We show that this interaction leads to the inhibition of calcineurin phosphatase activity and prevents nuclear factor of activated T-cell (NFAT) nuclear translocation. Inhibition of NFAT nuclear localization results in decreased NFAT transcriptional response. Together, these data identify a new modulator of calcineurin signaling up-regulated in WTs. (Mol Cancer Res 2009;7(6):821–31)
The importance of secondary trauma exposure for post-disaster mental disorder

Background. Interventions to treat mental disorders after natural disasters are important both for humanitarian reasons and also for successful post-disaster physical reconstruction that depends on the psychological functioning of the affected population. A major difficulty in developing such interventions, however, is that large between-disaster variation exists in the prevalence of post-disaster mental disorders, making it difficult to estimate need for services in designing interventions without carrying out a post-disaster mental health needs assessment survey. One of the daunting methodological challenges in implementing such surveys is that secondary stressors unique to the disaster often need to be discovered to understand the magnitude, type, and population segments most affected by post-disaster mental disorders. Methods. This problem is examined in the current commentary by analyzing data from the WHO World Mental Health (WMH) Surveys. We analyze the extent to which people exposed to natural disasters throughout the world also experienced secondary stressors and the extent to which the mental disorders associated with disasters were more proximally due to these secondary stressors than to the disasters themselves. Results. Lifetime exposure to natural disasters was found to be high across countries (4.4–7.5%). 10.7–11.4% of those exposed to natural disasters reported the occurrence of other related stressors (e.g. death of a loved one and destruction of property). A monotonic relationship was found between the number of additional stressors and the subsequent onset of mental disorders Conclusions. These results document the importance of secondary stressors in accounting for the effects of natural disasters on mental disorders. Implications for intervention planning are discussed.
Conformational Dynamics of Human AP Endonuclease in Base Excision and Nucleotide Incision Repair Pathways

Abstract APE1 is a multifunctional enzyme that plays a central role in base excision repair (BER) of DNA. APE1 is also involved in the alternative nucleotide incision repair (NIR) pathway. We present an analysis of conformational dynamics and kinetic mechanisms of the full-length APE1 and truncated NΔA61-APE1 lacking the N-terminal 61 amino acids (REF1 domain) in BER and NIR pathways. The action of both enzyme forms were described by identical kinetic schemes, containing four stages corresponding to formation of the initial enzyme-substrate complex and isomerization of this complex; when a damaged substrate was present, these stages were followed by an irreversible catalytic stage resulting in the formation of the enzyme-product complex and the equilibrium stage of product release. For the first time we showed, that upon binding AP-containing DNA, the APE1 structure underwent conformational changes before the chemical cleavage step. Under BER conditions, the REF1 domain of APE1 influenced the stability of both the enzyme-substrate and enzyme-product complexes, as well as the isomerization rate, but did not affect the rates of initial complex formation or catalysis. Under NIR conditions, the REF1 domain affected both the rate of formation and the stability of the initial complex. In comparison with the full-length protein, NΔA61-APE1 did not display a decrease in NIR activity with a dihydrouracil-containing substrate. BER conditions decrease the rate of catalysis and strongly inhibit the rate of isomerization step for the NIR substrates. Under NIR conditions AP-endonuclease activity is still very efficient.
A practical method for obtaining prior distributions in reliability

In this paper, we propose a comprehensive methodology to specify prior distributions for commonly used models in reliability. The methodology is based on characteristics easy to communicate by the user in terms of time to failure. This information could be in the form of intervals for the mean and standard deviation, or quantiles for the failure-time distribution. The derivation of the prior distribution is done for two families of proper initial distributions, namely s-normal-gamma, and uniform distribution. We show the implementation of the proposed method to the parameters of the s-normal, lognormal, extreme value, Weibull, and exponential models. Then we show the application of the procedure to two examples appearing in the reliability literature, and . By estimating the prior predictive density, we find that the proposed method renders consistent distributions for the different models that fulfill the required characteristics for the time to failure. This feature is particularly important in the application of the Bayesian approach to different inference problems in reliability, model selection being an important example. The method is general, and hence it may be extended to other models not mentioned in this paper.
The microalga Parachlorella kessleri––A novel highly efficient lipid producer

The alga Parachlorella kessleri, strain CCALA 255, grown under optimal conditions, is characterized by storage of energy in the form of starch rather than lipids. If grown in the complete medium, the cultures grew rapidly, producing large amounts of biomass in a relatively short time. The cells, however, contained negligible lipid reserves (1–10% of DW). Treatments inducing hyperproduction of storage lipids in P. kessleri biomass were described. The cultures were grown in the absence or fivefold decreased concentration of either nitrogen or phosphorus or sulfur. Limitation by all elements using fivefold or 10‐fold diluted mineral medium was also tested. Limitation with any macroelement (nitrogen, sulfur, or phosphorus) led to an increase in the amount of lipids; nitrogen limitation was the most effective. Diluted nutrient media (5‐ or 10‐fold) were identified as the best method to stimulate lipid overproduction (60% of DW). The strategy for lipid overproduction consists of the fast growth of P. kessleri culture grown in the complete medium to produce sufficient biomass (DW more than 10 g/L) followed by the dilution of nutrient medium to stop growth and cell division by limitation of all elements, leading to induction of lipid production and accumulation up to 60% DW. Cultivation conditions necessary for maximizing lipid content in P. kessleri biomass generated in a scale‐up solar open thin‐layer photobioreactor were described. Biotechnol. Bioeng. 2013; 110: 97–107. © 2012 Wiley Periodicals, Inc.
Extracellular signal regulated kinase 5 and inflammasome in progression of mesothelioma

Malignant mesothelioma is an aggressive cancer in desperate need of treatment. We have previously shown that extracellular signaling regulated kinase 5 (ERK5) plays an important role in mesothelioma pathogenesis using ERK5 silenced human mesothelioma cells exhibiting significantly reduced tumor growth in immunocompromised mice. Here, we used a specific ERK 5 inhibitor, XMD8-92 in various in vitro and in vivo models to demonstrate that inhibition of ERK5 can slow down mesothelioma tumorigenesis. First, we show a dose dependent toxicity of XMD8-92 to 2 human mesothelioma cell lines growing as a monolayer. We also demonstrate the inhibition of ERK5 phosphorylation in various human mesothelioma cell lines by XMD8-92. We further confirmed the toxicity of XMD8-92 towards mesothelioma cell lines grown as spheroids in a 3-D model as well as in intraperitoneal (immune-competent) and intrapleural (immune-deficient) mouse models with and without chemotherapeutic drugs. To ascertain the mechanism, we explored the role of the nod-like receptor family member containing a pyrin domain 3 (NLRP3) inflammasome in the process. We found XMD8-92 attenuated naïve and chemotherapeutic-induced inflammasome priming and activation in mesothelioma cells. It can thus be concluded that ERK5 inhibition attenuates mesothelioma tumor growth and this phenomenon in part is regulated by the inflammasome.
Selective inhibition of brain endothelial Rho-kinase-2 provides optimal protection of an in vitro blood-brain barrier from tissue-type plasminogen activator and plasmin

Rho-kinase (ROCK) inhibition, broadly utilised in cardiovascular disease, may protect the blood-brain barrier (BBB) during thrombolysis from rt-PA-induced damage. While the use of nonselective ROCK inhibitors like fasudil together with rt-PA may be hindered by possible hypotensive side-effects and inadequate capacity to block detrimental rt-PA activity in brain endothelial cells (BECs), selective ROCK-2 inhibition may overcome these limitations. Here, we examined ROCK-2 expression in major brain cells and compared the ability of fasudil and KD025, a selective ROCK-2 inhibitor, to attenuate rt-PA-induced BBB impairment in an in vitro human model. ROCK-2 was highly expressed relative to ROCK-1 in all human and mouse brain cell types and particularly enriched in rodent brain endothelial cells and astrocytes compared to neurons. KD025 was more potent than fasudil in attenuation of rt-PA- and plasminogen-induced BBB permeation under normoxia, but especially under stroke-like conditions. Importantly, only KD025, but not fasudil, was able to block rt-PA-dependent permeability increases, morphology changes and tight junction degradation in isolated BECs. Selective ROCK-2 inhibition further diminished rt-PA-triggered myosin phosphorylation, shape alterations and matrix metalloprotease activation in astrocytes. These findings highlight ROCK-2 as the key isoform driving BBB impairment and brain endothelial damage by rt-PA and the potential of KD025 to optimally protect the BBB during thrombolysis.
Improvements in planar feature reconstructions in atom probe tomography

Standard atom probe tomography spatial reconstruction techniques have been reasonably successful in reproducing single crystal datasets. However, artefacts persist in the reconstructions that can be attributed to the incorrect assumption of a spherical evaporation surface. Using simulated and experimental field evaporation, we examine the expected shape of the evaporating surface and propose the use of a variable point projection position to mitigate to some degree these reconstruction artefacts. We show initial results from an implementation of a variable projection position, illustrating the effect on simulated and experimental data, while still maintaining a spherical projection surface. Specimen shapes during evaporation of model structures with interfaces between regions of low‐ and high‐evaporation‐field material are presented. Use of two‐and three‐dimensional projection‐point maps in the reconstruction of more complicated datasets is discussed.
Individual Thigmotactic Preference Affects the Fleeing Behavior of the American Cockroach (Blattodea: Blattidae)

Abstract Positive thigmotactic behavior is associated with the ability to hide from predators and is important to explain aggregation and collective patterns in various animals. For example, this behavior has been observed in woodlice, domiciliary cockroaches, ants, and fish. Lately, research on different species is focused on the importance of animal personality for ecological and evolutionary processes, individual fitness and group cohesion. In fact, it is generally expected to find some degree of interindividual consistent differences for a behavior, unless specific circumstances, like predator attacks, hide the presence of personalities. In this research, we analyzed the individual thigmotactic preference of domiciliary cockroaches (Periplaneta americana (Linnaeus, 1758) (Blattodea: Blattidae)) and how it affected the fleeing behavior of isolated individuals inside a shelter after receiving a light stimulus. We notably highlight how isolated individuals show different consistent preferences regarding their position in the shelter, which is due to the individual thigmotaxis level, before the fleeing behavior. During the fleeing itself, cockroaches nearer to the wall, and therefore with more positive thigmotaxis, showed slower reaction lantencies to the stimulus. We propose that thigmotaxis homogenizes the interindividual differences among individuals and is important to explain the individual and collective fleeing behavior.
Progressive abrogation of TGF‐β‐1 and EGF growth control is associated with tumour progression in ras‐transfected human keratinocytes

This study examined the response of human keratinocytes in different stages of transformation to exogenous TGF‐β 1 and EGF as well as their receptor and growth‐factor expression. Cells of the spontaneously immortalized HaCaT cell line and c‐Ha‐ras transfected clones (1–6, 1–7, 11–3, 11–4) exhibited different tumorigenic potentials when transplanted to athymic mice. HaCaT‐ and 1–6 cells were non‐tumorigenic, 1–7 cells formed persisting epidermal cysts (benign tumours) and 11‐3 and 11‐4 cells developed into invasive squamous‐cell carcinomas. TGF‐β 1 inhibited thymidine uptake in a dose‐dependent manner, a progressive decrease in response being associated with an increasing malignant potential (HaCaT > 1–6 > 1–7 = 11‐4). HaCaT‐cells and ras‐clones expressed TGF‐β I mRNA at similar levels, but cells of increasing malignant potential secreted markedly less receptor‐binding TGF‐P (HaCaT > 1–6 = 1–7 > 11‐3 > 11‐4) into the culture medium. Whilst ras‐transfected cells expressed fewer TGF‐P receptors than HaCaT cells, there was little difference between TGF‐p receptor number or affinity between the 4 transfected cell clones. The same was true for the TGF‐p receptor types, but Type‐11 receptors were expressed at lower levels by the malignant clones 11‐3 and 11‐4. When HaCaT and ras‐transfected cells were investigated for their response to exogenous EGF, cells were refractory (1–7, 11‐4), partially stimulated (1–6) or fully stimulated (HaCaT). Cells with increasing malignant potential produced increasing amounts of endogenous TGF‐α (11‐4 = 11‐3 > 1–7 = 1–6 > HaCaT). All tumorigenic ras clones expressed higher mRNA levels than HaCaT‐cells. Ras‐transfected clones expressed fewer high‐ and low‐affinity EGF receptors than HaCaT cells with a tendency toward increased numbers of high‐affinity EGF receptors associated with increasing malignant potential (11‐4 = 11‐3 > 1–7 > 1–6) but these changes were associated with a progressive decrease in receptor affinity. The results indicate that tumour progression in human epidermal keratinocytes transfected with c‐Ha‐ras is associated with a progressive abrogation of TGF‐β 1 and EGF growth control. They suggest that the increased autonomous growth potential associated with advanced stages of epithelial tumour progression can be defined more closely using a cellular profile of TGF‐β and EGF. © 1992 Wiley‐Liss, Inc.
Social contacts and depression in middle and advanced adulthood: Findings from a US national survey, 2005–2008

Aim: Empirical evidence has linked social contacts with mental stability. The aim is to assess how social contacts are associated with depression among the general population. Methods: We analysed the data of 5,681 adults aged 40 or older, who completed a depression screening as a part of the National Health and Nutrition Examination Survey, 2005–2008. Depression was ascertained using the Patient Health Questionnaire (PHQ), a nine-item screening instrument asking about the frequency of depression symptoms over the past two weeks. A PHQ score of 10 or higher was defined as depression. Results: The prevalence of depression was 5.54% (SE = 0.64) and 8.49% (SE = 0.71), respectively, among men and women. The association between social contacts and depression were more salient among men than women. The odds ratios (ORs) of depression were 2.43 (95% CI = 1.44−4.10), 2.42 (95% CI = 1.37−4.28), 1.00 (reference) and 1.94 (95% CI = 0.80−4.71), respectively, among men who never attended church, attended occasionally, weekly and more than weekly. The corresponding ORs were 1.79 (95% CI = 1.10−2.91), 1.72 (95% CI = 1.06−2.80), 1.00(reference) and 0.98 (95% CI = 0.52−1.84) for women. Compared with the respondents who had 10 or more friends, the ORs of depression were 4.01 (95% CI = 1.89−8.50) and 1.86 (95% CI = 0.92−3.79), respectively, for men and women who had no close friends. Conclusions: The current study concluded that traditional social contacts remain strongly associated with depression in the digital era. Digital social networking is one of the biggest growing industries, creating a new platform to make social contacts. There is an urgent need to explore how to maximize the potential of digital social networking to strengthen social bonds while minimizing its negative effects.
Functional Evaluation in Patients With Chronic Obstructive Pulmonary Disease: Pulmonary Function Test Versus Cardiopulmonary Exercise Test

The pulmonary function test (PFT) alone may be inadequate for predicting work-related exercise capacity in patients who file workers’ compensation claims for respiratory limitation and compensation. Two hundred sixteen ambulatory patients with chronic obstructive pulmonary disease (forced expiratory volume in 1 second = 54.1 ± 16.8% predicted) were administered the PFT and cardiopulmonary exercise test, and the results were analyzed by categorical statistical comparison, based on standard medical impairment classifications. Sixty-five patients (30.1%) were similarly classified by the two methods. Of the remaining patients, 132 (61.1%) were found to be less impaired according to the cardiopulmonary exercise test than according to the PFT, and 19 (8.8%) were more impaired according to the PFT. The results favor the use of the cardiopulmonary exercise test for the routine evaluation of respiratory impairment in patients with chronic obstructive pulmonary disease, particularly for patients with mild or moderate impairment revealed by the PFT. The large discrepancy between the two procedures emphasizes the need for a novel approach.