The Impact of Interorganizational Imitation on New Venture International Entry and Performance

We examine the impact of interorganizational imitation on new venture international entry and subsequent performance. Using a sample of 150 U.S.-based publicly held new ventures, we find that new venture international entry is in part an imitative response to the internationalization of other firms in the venture\u27s home country industry and/or subsets of firms with certain traits or outcomes. We also find that interorganizational imitation moderates the relationship between new venture international entry and profitability, but not the relationship between new venture international entry and sales growth. These findings contribute to the growing body of literature on new venture internationalization

Nitric oxide and cyclic nucleotides: Their roles in junction dynamics and spermatogenesis

Spermatogenesis is a highly complicated process in which functional spermatozoa (haploid, 1n) are generated from primitive mitotic spermatogonia (diploid, 2n). This process involves the differentiation and transformation of several types of germ cells as spermatocytes and spermatids undergo meiosis and differentiation. Due to its sophistication and complexity, testis possesses intrinsic mechanisms to modulate and regulate different stages of germ cell development under the intimate and indirect cooperation with Sertoli and Leydig cells, respectively. Furthermore, developing germ cells must translocate from the basal to the apical (adluminal) compartment of the seminiferous epithelium. Thus, extensive junction restructuring must occur to assist germ cell movement. Within the seminiferous tubules, three principal types of junctions are found namely anchoring junctions, tight junctions, and gap junctions. Other less studied junctions are desmosome-like junctions and hemidesmosome junctions. With these varieties of junction types, testes are using different regulators to monitor junction turnover. Among the uncountable junction modulators, nitric oxide (NO) is a prominent candidate due to its versatility and extensive downstream network. NO is synthesized by nitric oxide synthase (NOS). Three traditional NOS, specified as endothelial NOS (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS), and one testis-specific nNOS (TnNOS) are found in the testis. For these, eNOS and iNOS were recently shown to have putative junction regulation properties. More important, these two NOSs likely rely on the downstream soluble guanylyl cyclase/cGMP/protein kinase G signaling pathway to regulate the structural components at the tight junctions and adherens junctions in the testes. Apart from the involvement in junction regulation, NOS/NO also participates in controlling the levels of cytokines and hormones in the testes. On the other hand, NO is playing a unique role in modulating germ cell viability and development, and indirectly acting on some aspects of male infertility and testicular pathological conditions. Thus, NOS/NO bears an irreplaceable role in maintaining the homeostasis of the microenvironment in the seminiferous epithelium via its different downstream signaling pathways

Abiraterone in metastatic prostate cancer without previous chemotherapy

Background: Abiraterone acetate, an androgen biosynthesis inhibitor, improves overall survival in patients with metastatic castration-resistant prostate cancer after chemotherapy. We evaluated this agent in patients who had not received previous chemotherapy. Methods: In this double-blind study, we randomly assigned 1088 patients to receive abiraterone acetate (1000 mg) plus prednisone (5 mg twice daily) or placebo plus prednisone. The coprimary end points were radiographic progression-free survival and overall survival. Results: The study was unblinded after a planned interim analysis that was performed after 43% of the expected deaths had occurred. The median radiographic progressionfree survival was 16.5 months with abiraterone - prednisone and 8.3 months with prednisone alone (hazard ratio for abiraterone - prednisone vs. prednisone alone, 0.53; 95% confidence interval [CI], 0.45 to 0.62; P<0.001). Over a median follow-up period of 22.2 months, overall survival was improved with abiraterone - prednisone (median not reached, vs. 27.2 months for prednisone alone; hazard ratio, 0.75; 95% CI, 0.61 to 0.93; P = 0.01) but did not cross the efficacy boundary. Abiraterone - prednisone showed superiority over prednisone alone with respect to time to initiation of cytotoxic chemotherapy, opiate use for cancer-related pain, prostate-specific antigen progression, and decline in performance status. Grade 3 or 4 mineralocorticoid-related adverse events and abnormalities on liver-function testing were more common with abiraterone-prednisone. Conclusions: Abiraterone improved radiographic progression-free survival, showed a trend toward improved overall survival, and significantly delayed clinical decline and initiation of chemotherapy in patients with metastatic castration-resistant prostate cancer

Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F-ROH) for >1.4 million individuals, we show that F-ROH is significantly associated (p <0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F-ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F-ROH are confirmed within full-sibling pairs, where the variation in F-ROH is independent of all environmental confounding.Peer reviewe

Scaffold free fabrication of linear multicellular assemblies by dielectrophoretic hydrogel trapping technique

We have designed a scaffold-free cell assembly method which can produce linear structures of individual living cells without using templates. The method involves dielectrophoretic assembly of cells suspended in a solution of a gelling agent above the gelling temperature. After the cell assembly in string-like structures was achieved with the AC electric field still applied, we gelled the solution by cooling it below its gelling point. The hydrogel entraps the assembled cell structure, preventing its disassembly and allowing further analysis without the presence of the external electric field. We pre-functionalised the cells with polyelectrolytes before the dielectrophoretic assembly which allowed us to line them up in multicellular strings and bind them together with oppositely charged polyelectrolyte after the gel formation. Finally, by dissolving the hydrogel, we released the linear chains of living cells which were collected and studied by optical and fluorescence microscopy. Cell viability tests with fluorescein diacetate confirmed that the cells in the formed worm-like structures remain viable after the cell assembly procedure. The linear cell aggregates are stable without the electric field and can be further cultured or treated with additional polyelectrolytes which make the method attractive for tissue engineering. We envisage that this technique could find possible applications for assembly of neuron cells in linear structures and more complex cell networks

Mechanisms of particle transport acceleration in porous media

Experimental data show that the groundwater transport of radionuclides in porous media is frequently facilitated when accompanied with colloid particles. This is usually explained by the size exclusion mechanism which implies that the particles move through the largest pores where the flow velocity is higher. We call attention to three other mechanisms which influence the colloid particle motion, while determining both the probable transport facilitation and retardation. First of all, it is shown that the transport facilitation may be significantly reduced and even transformed into a retardation due to the growth of the effective suspension viscosity (a friction-limited facilitation). Secondly, we will show that the transport of particles through the largest pores can be retarded due to a reduced connectivity of the large-pore cluster (a percolation-breakup retardation). Thirdly, we highlight the Fermi mechanism of acceleration known in statistical physics which is based on the elastic collisions between particles. All three effects are analyzed in terms of the velocity enhancement factor, by using statistical models of porous media in the form of a capillary bundle and a 3D capillary network. Optimal and critical regimes of velocity enhancement are quantified. Estimations show that for realistic parameters, the maximal facilitation of colloid transport is close to the experimentally observed data

The evolving role of immunotherapy in prostate cancer

Item does not contain fulltextThe prognosis for men with metastatic, castration-resistant prostate cancer (CRPC) is limited, and patients have very few treatment options, particularly if the treatment failed with docetaxel (Taxotere). As a result, there is a requirement for novel approaches to therapy. Using immunotherapy to induce immune responses to prostate cancer in preclinical and clinical studies appears to be a valid therapeutic approach. In a pivotal phase III trial, treatment with sipuleucel-T, an autologous cellular vaccine consisting of activated antigen-presenting cells loaded with prostatic acid phosphatase (PAP), gave a median overall survival of 25.8 months compared with 21.7 months for placebo-treated patients, resulting in a 22% relative reduction in the risk of death. Based on these results, sipuleucel-T became the first therapeutic vaccine approved for any type of cancer in the USA. PROSTVAC((R))-VF, a poxvirus-based vaccine engineered to present prostate-specific antigen (PSA) and three immune costimulatory molecules, and GVAX, a vaccine consisting of two prostate cancer cell lines (LnCAP and PC3) and genetically modified to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF), both showed promising results in phase II studies, although GVAX failed to meet its primary end point of overall survival when compared with docetaxel in a phase III study. T-cell modulation is another potential immunotherapeutic strategy for CRPC. Ipilimumab, an antibody against the cytotoxic T-lymphocyte-associated antigen-4, is being evaluated in phase I/II studies, both alone and in combination with chemotherapy, radiotherapy or GVAX, with activity in prostate cancer. CRPC is one of the few tumour types where immunotherapy is the current standard of care. Further research, however, will be necessary to improve antitumour responses and clinical benefits, including the use of novel combinatorial approaches

Third-Year Results from the Circumarctic Lakes Observation Network (CALON) Project

Since 2012, 60 lakes in northern Alaska have been instrumented under the auspices of CALON, a project designed to document landscape-scale variability in physical and biogeochemical processes of Arctic lakes in permafrost terrain. The network has ten observation nodes along two latitudinal transects extending from the Arctic Ocean inland some 200 km to the Brooks Range foothills. At each node, a meteorological station is deployed, and six representative lakes of differing area and depth are instrumented and sampled at different intensity levels to collect basic field measurements. In April, sensors measuring water temperature and depth are deployed through the ice in each lake, ice and snow thickness recorded, and water samples are collected. Data are downloaded, lakes re-sampled, and bathymetric surveys are conducted in August. In 2014, the snow cover on inland lakes was thinner than in previous years but thicker on lakes located near the coast. Lake ice was generally thinner near the coast, but the difference diminished inland. Winters (Oct-March) have been progressively warmer over the 3-year period, which partially explains the thinner lake ice that formed in 2013-14. Lakes are typically well–mixed and largely isothermal, with minor thermal stratification occurring in deeper lakes during calm, sunny periods. These regional lake and meteorological data sets, used in conjunction with satellite imagery, supports the wind-driven lake circulation model for the origin of thermokarst lakes. Results of biogeochemical analyses of lake waters generally show notably higher concentrations of cations/anions, chromophoric dissolved organic matter, and chlorophyll-a during April as compared with August. Dissolved methane concentrations are also much higher under ice than in open water during summer, although all lakes are a source of atmospheric methane. Interviews with indigenous elders in Anaktuvuk Pass indicate that mountain lakes are drying up. During the 2014 breakup period, 350 entrants participated in the 2nd Annual Toolik Lake Ice Classic including elementary school children, the general public, and international researchers. Ice off occurred on 23 June, and 11 people correctly guessed this day. All field data is archived at A-CADIS, and further information is at www.arcticlakes.org