Resource Slack, Innovation Ambidexterity, and Quality Performance: Knowledge Heterogeneity Perspective

Abstract. Resource slack and innovation ambidexterity can both be represented and connected conceptually with heterogeneous knowledge structure. Hypothesizing with the logic of knowledge heterogeneity, the present study empirically examined ambidexterity’s mediation effect in the relationship between two forms of resource slacks (i.e., human and financial resources) and product quality. Companies in Taiwanese manufacturing industry were located based on the random inspection conducted by the Department of Budget, Accounting and Statistics of the Government in 2011, and surveyed. Our findings demonstrated that slack resource is only an indirect factor for product quality evaluated by internal developers and producers (i.e. development and delivery processes) and external customers (product-specific quality). Specifically, first, different resource slacks influence differently on ambidexterity; second, both exploration and exploitation positively influence quality of innovation; third, ambidexterity plays a significant mediator’s role that may strategically alter the relationship between slack and quality. Research has paid increasing attention to ambidexterity (i.e., exploration and exploitation) in organizational innovation. Mostly, however, focus on the influencing factors leading to possible ambidextrous design or implementation of innovation. Few have examined ambidexterity’s effects on specific dimensions of innovation as outcomes.Keywords. Resource slacks, Ambidexterity, Quality, Knowledge heterogeneity.JEL. M10; M11; M14

Post-exposure prophylaxis for SIV revisited: Animal model for HIV prevention

BACKGROUND: A 4-week, uninterrupted treatment with 9-(2-phosphonyl-methoxypropyly)adenine (PMPA, commonly called tenofovir) completely prevents simian immunodeficiency virus (SIV(mne)) infection in cynomolgus macaques if treatment begins within 24 hours after SIV(mne )inoculation, but is less effective if treatment is delayed or duration of treatment is shortened. Critical factors for efficacy include timing and duration of treatment, potency of antiretroviral drug and a contribution from antiviral immune responses. Therefore, we evaluated the impact of one or more treatment interruptions plus SIV(mne )re-exposures on efficacy of PMPA treatment to prevent SIV(mne )infection in cynomolgus macaques. We also evaluated whether macaques with pre-existing SIV immune responses show increased efficacy of treatment. Eight PMPA-treated, virus-negative and seronegative macaques, and five PMPA-treated, virus-negative but weakly or strongly seropositive macaques were re-inoculated with SIV(mne )and treated with PMPA starting 24 hr post inoculation. Thereafter, they received either a 5-week treatment involving one interruption plus one SIV(mne )challenge or a 10-week treatment involving six interruptions plus six SIV(mne )challenges early during treatment. Parameters measured were plasma SIV RNA, SIV-antibody response, CD4+ T lymphocyte subsets and in vivo CD8+ cell-suppression of virus infection. RESULTS: All seronegative macaques developed persistent antibody response beginning 4 to 8 weeks after stopping PMPA-treatment in absence of viremia in a majority of macaques and coinciding with onset of intermittent viremia in other macaques. In contrast, all weakly or strongly seropositive macaques showed immediate increase in titers (> 1600) of SIV antibodies, even before the end of PMPA-treatment, and in absence of detectable viremia. However, in vivo CD8+ -cell depletion revealed CD8 cell-suppression of viremia and persistence of virus in the macaques as long as 2 years after PMPA-treatment, even in aviremic macaques. Unlike untreated macaques, a treated macaque controlled viral replication and blocked CD4+ T cell depletion when challenged with a heterologus chimeric SIV/HIV-1 virus called SHIV(89.6P.) CONCLUSION: A single interruption plus one SIV(mne )challenge was as sufficient as six interruptions plus six SIV(mne )challenges in reducing efficacy of PMPA, but results in long-term persistence of virus infection suppressed by CD8+ cells. Efficacy of PMPA treatment was highest in macaques with pre-existing SIV immune responses

Inhibition of gap junctional Intercellular communication in WB-F344 rat liver epithelial cells by triphenyltin chloride through MAPK and PI3-kinase pathways

<p>Abstract</p> <p>Background</p> <p>Organotin compounds (OTCs) have been widely used as stabilizers in the production of plastic, agricultural pesticides, antifoulant plaints and wood preservation. The toxicity of triphenyltin (TPT) compounds was known for their embryotoxic, neurotoxic, genotoxic and immunotoxic effects in mammals. The carcinogenicity of TPT was not well understood and few studies had discussed the effects of OTCs on gap junctional intercellular communication (GJIC) of cells.</p> <p>Method</p> <p>In the present study, the effects of triphenyltin chloride (TPTC) on GJIC in WB-F344 rat liver epithelial cells were evaluated, using the scrape-loading dye transfer technique.</p> <p>Results</p> <p>TPTC inhibited GJIC after a 30-min exposure in a concentration- and time-dependent manner. Pre-incubation of cells with the protein kinase C (PKC) inhibitor did not modify the response, but the specific MEK 1 inhibitor PD98059 and PI3K inhibitor LY294002 decreased substantially the inhibition of GJIC by TPTC. After WB-F344 cells were exposed to TPTC, phosphorylation of Cx43 increased as seen in Western blot analysis.</p> <p>Conclusions</p> <p>These results show that TPTC inhibits GJIC in WB-F344 rat liver epithelial cells by altering the Cx43 protein expression through both MAPK and PI3-kinase pathways.</p

On the Preconditioner of Conjugate Gradient Method a Power Grid Simulation Perspective

Preconditioned Conjugate Gradient (PCG) method has been demonstrated to be effective in solving large-scale linear systems for sparse and symmetric positive definite matrices. One critical problem in PCG is to design a good preconditioner, which can significantly reduce the runtime while keeping memory usage efficient. Universal preconditioners are simple and easy to construct, but their effectiveness is highly problem dependent. on the other hand, domain-specific preconditioners that explore the underlying physical meaning of the matrices usually work better but are difficult to design. in this paper, we study the problem in the context of power grid simulation, and develop a novel preconditioner based on the power grid structure through simple circuit simulations. Experimental results show 43% reduction in the number of iterations and 23% speedup over existing universal preconditioners. © 2011 IEEE

Psychological Pathway from Obesity-Related Stigma to Anxiety via Internalized Stigma and Self-Esteem among Adolescents in Taiwan

The objective of this research was to examine the pathway from public stigma, to perceived stigma, to depression in adolescents via internalized stigma. Adolescents in grade 7 through 9 from a junior high school in Changhua County in Taiwan completed self-administered surveys from March to July in 2018. Adolescents were asked questions regarding depressive symptoms, obesity-related perceived stigma, and internalized stigma. Structural equation modeling was used to fit the pathway model. The pathway was first analyzed with the full sample and then stratified by actual and perceived weight status. Our final analytic sample consisted of 464 adolescents. The pathway model suggested an acceptable model fit. Perceived weight stigma (PWS) was significantly associated with internalized stigma regardless of actual or self-perceived weight status. Internalized stigma was significantly associated with anxiety for both actual (β = 0.186) and self-perceived nonoverweight (non-OW) participants (β = 0.170) but not for overweight (OW) participants (neither actual nor self-perceived). For OW adolescents, perceived weight stigma was associated with anxiety. However, the internalization process did not exist. It may be that the influence of perceived weight stigma is larger than internalized stigma on anxiety. It may also be that the level of internalization was not yet high enough to result in anxiet

RT-SHIV, an infectious CCR5-tropic chimeric virus suitable for evaluating HIV reverse transcriptase inhibitors in macaque models

<p>Abstract</p> <p>Background</p> <p>Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are an important category of drugs for both chemotherapy and prevention of human immunodeficiency virus type 1 (HIV-1) infection. However, current non-human primate (NHP) models utilizing simian immunodeficiency virus (SIV) or commonly used chimeric SHIV (SIV expressing HIV-1 envelope) are inadequate due to the insensitivity to NNRTIs. To develop a NHP model for evaluation of NNRTI compounds, we characterized a RT-SHIV virus that was assembled by replacing the SIV_mac239reverse transcriptase (RT) with that of HIV-1HXB2. Since RT-SHIV exhibited <it>in vitro </it>characteristics of high infectivity, CCR5-usage, and sensitivity to HIV-1 specific NNRTIs, this virus was thought to be suitable for mucosal transmission and then was used to carry out a vaginal transmission study in pigtail macaques (<it>Macaca nemestrina</it>).</p> <p>Results</p> <p>RT-SHIV exhibited <it>in vitro </it>characteristics of an infectious CCR5-tropic chimeric virus. This virus was not only highly sensitive to HIV-1 RT specific NNRTIs; its replication was also inhibited by a variety of NRTIs and protease inhibitors. For <it>in vivo </it>vaginal transmission studies, macaques were either pretreated with a single dose of DMPA (depot medroxyprogesterone acetate) or left untreated before intravaginal inoculation with 500 or 1,000 TCID₅₀of RT-SHIV. All macaques became systemically infected by 2 or 3 weeks post-inoculation exhibiting persistent high viremia, marked CD4⁺T cell depletion, and antiviral antibody response. DMPA-pretreated macaques showed a higher mean plasma viral load after the acute infection stage, highly variable antiviral antibody response, and a higher incidence of AIDS-like disease as compared with macaques without DMPA pretreatment.</p> <p>Conclusion</p> <p>This chimeric RT-SHIV has exhibited productive replication in both macaque and human PBMCs, predominantly CCR5-coreceptor usage for viral entry, and sensitivity to NNRTIs as well as other anti-HIV compounds. This study demonstrates rapid systemic infection in macaques following intravaginal exposure to RT-SHIV. This RT-SHIV/macaque model could be useful for evaluation of NNRTI-based therapies, microbicides, or other preventive strategies.</p

Effects of Childhood Adversity and Resilience on Taiwanese Youth Health Behaviors

Adverse childhood experiences (ACEs) can leave negative impacts on one\u27s health behaviors or social functioning later in life. Resilient characteristics have been shown to mitigate effects against risk behaviors in developing adolescents. However, clinical and research attention has rarely been given to jointly consider the effects of ACEs and resilient characteristics on health behaviors in Taiwanese youth. Method: A total of 200 individuals aged 15–22 years were recruited from primary care settings, communities, and schools. Participants completed questionnaires assessing their ACEs, resilient characteristics, and health behaviors. Univariate analysis was firstly used to describe the correlates of ACEs and resilient characteristics. Further multivariate logistic regression analysis was used to examine the association of both factors with health behaviors. Results: More than half (61.5%) of those surveyed had been exposed to at least one category of ACE. Verbal (37%) and physical (21%) abuses were the most common types of ACEs. The counts in the ACE categories were associated with being involved in physical fights (odds ratio 1.28 [confidence interval 1.01–1.63]), property damage (1.29 [1.03–1.61]), running away from home (1.30 [1.05–1.60]), bullying victimization (1.37 [1.16–1.61]), and sleep problems/tiredness (1.25 [1.03–1.52]). Meanwhile, resilience scores were associated with decreased odds of infrequent seatbelt use (0.47 [0.23–0.97]), low fruit and vegetable intake (0.42 [0.21–0.86]) unsatisfied body image (0.46 [0.22–0.97]), and sleep problems/tiredness (0.37 [0.18–0.79]). Conclusions: ACEs and resilience characteristics play a significant role in shaping youth health behaviors. Further research should be undertaken to identify ways to build resilience against health risks in youth with prior ACE exposure

Long-Chain Fatty Acid Receptors Mediate Relaxation of the Porcine Lower Esophageal Sphincter

Long-chain fatty acids activate the free fatty acid receptor 1 (FFA1) and FFA4. In the gastrointestinal system, FFA1 and FFA4 have been found in the pancreas and intestine. Fatty food and decreased lower esophageal sphincter (LES) motility are associated with gastroesophageal reflux disease. The effect of long-chain fatty acids on the esophageal motility is unknown. The purpose of this study is to investigate the effects of long-chain fatty acids on the porcine LES motility ex vivo using isometric transducers. In endothelin 1-precontracted porcine LES strips, the FFA1 selective agonists, fasiglifam, TUG424, and GW9508, caused marked relaxations in a concentration-dependent manner. The relative efficacies to elicit relaxation were GW9508 &gt; TUG424 &gt; fasiglifam in both clasp and sling strips. In contrast, the FFA4 specific agonists, TUG891 and GSK137647, produced mild relaxations. In addition, the endogenous FFA1 agonist DHA caused a mild relaxation whereas GW1100, an FFA1 antagonist, inhibited GW9508 induced relaxation of the porcine LES clasp and sling muscle. Both real-time PCR and immunohistochemistry revealed that FFA1 and FFA4 were expressed in the porcine LES. Real-time PCR analysis showed that the FFA4 expression was much lower than FFA1. Taken together, long-chain fatty acid receptor agonists elicit relaxation of the porcine LES. FFA1 might influence LES motility

Genetic variability of the envelope gene of Type D simian retrovirus-2 (SRV-2) subtypes associated with SAIDS-related retroperitoneal fibromatosis in different macaque species

BACKGROUND: D-type simian retrovirus-2 (SRV-2) causes an AIDS-like immune deficiency syndrome (SAIDS) in various macaque species. SAIDS is often accompanied by retroperitoneal fibromatosis (RF), an aggressive fibroproliferative disorder reminiscent of Kaposi's sarcoma in patients with HIV-induced AIDS. In order to determine the association of SRV-2 subtypes with SAIDS-RF, and study the evolution and transmission of SRV-2 in captive macaque populations, we have molecularly characterized the env gene of a number of SRV-2 isolates from different macaque species with and without RF. RESULTS: We sequenced the env gene from eighteen SRV-2 isolates and performed sequence comparisons and phylogenetic analyses. Our studies revealed the presence of six distinct subtypes of SRV-2, three of which were associated with SAIDS-RF cases. We found no association between SRV-2 subtypes and a particular macaque species. Little sequence variation was detected in SRV-2 isolates from the same individual, even after many years of infection, or from macaques housed together or related by descent from a common infected parent. Seventy-two amino acid changes were identified, most occurring in the larger gp70 surface protein subunit. In contrast to the lentiviruses, none of the amino acid variations involved potential N-linked glycosylation sites. Structural analysis of a domain within the gp22/gp20 transmembrane subunit that was 100% conserved between SRV-2 subtypes, revealed strong similarities to a disulfide-bonded loop that is crucial for virus-cell fusion and is found in retroviruses and filoviruses. CONCLUSION: Our study suggests that separate introductions of at least six parental SRV-2 subtypes into the captive macaque populations in the U.S. have occurred with subsequent horizontal transfer between macaque species and primate centers. No specific association of a single SRV-2 subtype with SAIDS-RF was seen. The minimal genetic variability of the env gene within a subtype over time suggests that a strong degree of adaptation to its primate host has occurred during evolution of the virus