THE EFFECT OF INNOVATION STRATEGY ON POST-M&A INNOVATION PERFORMANCE: AN EVIDENCE FROM PHARMACEUTICAL INDUSTRY

M&A is a popular strategy for pharmaceutical industry due to high R&D risk and costs. Prior research related to post-M&A performance mainly focused on the financial and technology resource perspectives. This study aims to provide a new perspective of innovation strategy which is inspired by the research of March (1991), who noted the difference between exploration and exploitation. Moreover, we build the bridge between M&A and innovation strategy by applying the resource-based view theory. We argue that the acquirer’s exploration strategy will negatively influence the post-M&A innovation performance and the innovation strategy similarity between the acquirer and the target is beneficial for future innovation. Furthermore, we hypothesize that there is a negatively moderating effect caused by the acquirer’s exploration strategy on the effect of innovation strategy similarity. On the basis of 89 M&A deals in the pharmaceutical industry, our empirical results suggest two important findings. First, post- M&A innovation performance is influenced by acquirer’s innovation strategy, more specifically, acquirer’s exploration is harmful for post-M&A innovation. Second, the similarity effect is moderated by acquirer’s innovation strategy. Precisely, acquirer’s exploration will diminish the positive effect of similarity

New Technologies for Cancer Immunotherapy and Disease Profiling

Mutant tumor antigens have recently emerged as major targets of endogenous tumor-specific T cells. Vaccination against these neoantigens therefore provides the opportunity to augment antitumor lymphocyte responses. In this context, we developed a technology to prime and expand desired populations of antigen-specific T cells based on programmed self-assembly of cognate peptide-MHC (pMHC). We capitalized on the unique properties of the protein annexin V (ANXA5) to couple the early onset of TCR signaling to stabilization of pMHC-TCR interactions, repeated pMHC encounter, and extensive TCR crosslinking. This system amplified lymphocyte activation by over 1,000-fold, bypassed the need for costimulation, and overcame tolerance to a model self-antigen in vivo. These studies lay the foundation for immune modulation via a positive feedback-driven self-assembly platform. Furthermore, we created a single-molecule imaging approach for quantitative and structural analysis of circulating mutant tumor proteins, which may ultimately be applied to identify tumor neoantigens. We demonstrated in preclinical models that mutant tumor proteins are released from tumor cells into the blood early in tumor progression. We then utilized this technology to profile circulating mutant p53 in ovarian cancer patients. Single-molecule structural analysis revealed that, in a subset of patients, circulating mutant p53 aggregates into complexes. Moreover, patients lacking circulating mutant p53 displayed abundant anti-p53 autoantibodies, suggesting that host immune responses clear mutant tumor antigens from the blood. Finally, we propose that structural analysis of circulating mutant tumor proteins by single-molecule imaging may be employed to discover and screen tumor neoantigens for vaccination

Reliability of flexible low temperature poly-silicon thin film transistor

This work reports the effect of mechanical stress-induced degradation in flexible low-temperature polycrystalline-silicon thin-film transistors. After 100,000 iterations of channel-width-direction mechanical compression at R=2mm, a significant shift of extracted threshold voltage and an abnormal hump at the subthreshold region were found. Simulation reveals that both the strongest mechanical stress and electrical field takes place at both sides of the channel edge, between the polycrystalline silicon and gate insulator. The gate insulator suffered from a serious mechanical stress and result in a defect generation in the gate insulator. The degradation of the threshold voltage shift and the abnormal hump can be ascribed to the electron trapping in these defects. In addition, this work introduced three methods to reduce the degradation cause by the mechanical stress, including the quality improvement of the gate insulator, organic trench structure and active layer with a wing structure. Please click Additional Files below to see the full abstract

Interoceptive awareness: MBSR training alters information processing of salience network

Mindfulness refers to a mental state of awareness of internal experience without judgment. Studies have suggested that each mindfulness practice may involve a unique mental state, but the underlying neurophysiological mechanisms remain unknown. Here we examined how distinct mindfulness practices after mindfulness-based intervention alter brain functionality. Specifically, we investigated the functional alterations of the salience network (SN) using functional magnetic resonance imaging (fMRI) among the two interoceptive mindfulness practices—breathing and body scan—associated with interoceptive awareness in fixed attention and shifted attention, respectively. Long-distance functional connectivity (FC) and regional homogeneity (ReHo) approaches were applied to measure distant and local neural information processing across various mental states. We hypothesized that mindful breathing and body scan would yield a unique information processing pattern in terms of long-range and local functional connectivity (FC). A total of 18 meditation-naïve participants were enrolled in an 8-week mindfulness-based stress reduction (MBSR) program alongside a waitlist control group (n = 14), with both groups undergoing multiple fMRI sessions during breathing, body scan and resting state for comparison. We demonstrated that two mindfulness practices affect both the long-distance FCSN and the local ReHo, only apparent after the MBSR program. Three functional distinctions between the mindfulness practices and the resting state are noted: (1) distant SN connectivity to occipital regions increased during the breathing practice (fixed attention), whereas the SN increased connection with the frontal/central gyri during the body scan (shifting attention); (2) local ReHo increased only in the parietal lobe during the body scan (shifting attention); (3) distant and local connections turned into a positive correlation only during the mindfulness practices after the MBSR training, indicating a global enhancement of the SN information processing during mindfulness practices. Though with limited sample size, the functional specificity of mindfulness practices offers a potential research direction on neuroimaging of mindfulness, awaiting further studies for verification

Transcriptomic analyses of regenerating adult feathers in chicken

Transcriptome Expression Data. Table of mapped reads to Galgal4 transcripts for all 15 data sets. FPKM (Fragments per kilobase of exon per million fragments mapped): normalized transcript abundance values for each gene in the indicated tissues. (CSV 1314 kb

miRTarBase: a database curates experimentally validated microRNA–target interactions

MicroRNAs (miRNAs), i.e. small non-coding RNA molecules (∼22 nt), can bind to one or more target sites on a gene transcript to negatively regulate protein expression, subsequently controlling many cellular mechanisms. A current and curated collection of miRNA–target interactions (MTIs) with experimental support is essential to thoroughly elucidating miRNA functions under different conditions and in different species. As a database, miRTarBase has accumulated more than 3500 MTIs by manually surveying pertinent literature after data mining of the text systematically to filter research articles related to functional studies of miRNAs. Generally, the collected MTIs are validated experimentally by reporter assays, western blot, or microarray experiments with overexpression or knockdown of miRNAs. miRTarBase curates 3576 experimentally verified MTIs between 657 miRNAs and 2297 target genes among 17 species. miRTarBase contains the largest amount of validated MTIs by comparing with other similar, previously developed databases. The MTIs collected in the miRTarBase can also provide a large amount of positive samples to develop computational methods capable of identifying miRNA–target interactions. miRTarBase is now available on http://miRTarBase.mbc.nctu.edu.tw/, and is updated frequently by continuously surveying research articles

Prime Focus Spectrograph (PFS) for the Subaru Telescope: Overview, recent progress, and future perspectives

PFS (Prime Focus Spectrograph), a next generation facility instrument on the 8.2-meter Subaru Telescope, is a very wide-field, massively multiplexed, optical and near-infrared spectrograph. Exploiting the Subaru prime focus, 2394 reconfigurable fibers will be distributed over the 1.3 deg field of view. The spectrograph has been designed with 3 arms of blue, red, and near-infrared cameras to simultaneously observe spectra from 380nm to 1260nm in one exposure at a resolution of ~1.6-2.7A. An international collaboration is developing this instrument under the initiative of Kavli IPMU. The project is now going into the construction phase aiming at undertaking system integration in 2017-2018 and subsequently carrying out engineering operations in 2018-2019. This article gives an overview of the instrument, current project status and future paths forward.Comment: 17 pages, 10 figures. Proceeding of SPIE Astronomical Telescopes and Instrumentation 201

Tumor-Targeted Delivery of IL-2 by NKG2D Leads to Accumulation of Antigen-Specific CD8+ T Cells in the Tumor Loci and Enhanced Anti-Tumor Effects

Interleukin-2 (IL-2) has been shown to promote tumor-specific T-cell proliferation and differentiation but systemic administration of IL-2 results in significant toxicity. Therefore, a strategy that can specifically deliver IL-2 to the tumor location may alleviate concerns of toxicity. Because NKG2D ligands have been shown to be highly expressed in many cancer cells but not in healthy cells, we reason that a chimeric protein consisting of NKG2D linked to IL-2 will lead to the specific targeting of IL-2 to the tumor location. Therefore, we created chimeric proteins consisting of NKG2D linked to Gaussia luciferase (GLuc; a marker protein) or IL-2 to form NKG2D-Fc-GLuc and NKG2D-Fc-IL2, respectively. We demonstrated that NKG2D linked to GLuc was able to deliver GLuc to the tumor location in vivo. Furthermore, we showed that TC-1 tumor-bearing mice intramuscularly injected with DNA encoding NKG2D-Fc-IL2, followed by electroporation, exhibited an increased number of luciferase-expressing E7-specific CD8+ T cells at the tumor location. More importantly, treatment with the DNA construct encoding NKG2D-Fc-IL2 significantly enhanced the therapeutic anti-tumor effects generated by intradermal vaccination with therapeutic HPV DNA in tumor-bearing mice. Therefore, by linking NKG2D to IL2, we are able to specifically deliver IL-2 to the tumor location, enhancing antigen-specific T-cell immune response and controlling tumor growth. Our approach represents a platform technology to specifically deliver proteins of interest to tumor loci

THEMIS: A Parameter Estimation Framework for the Event Horizon Telescope

The Event Horizon Telescope (EHT) provides the unprecedented ability to directly resolve the structure and dynamics of black hole emission regions on scales smaller than their horizons. This has the potential to critically probe the mechanisms by which black holes accrete and launch outflows, and the structure of supermassive black hole spacetimes. However, accessing this information is a formidable analysis challenge for two reasons. First, the EHT natively produces a variety of data types that encode information about the image structure in nontrivial ways; these are subject to a variety of systematic effects associated with very long baseline interferometry and are supplemented by a wide variety of auxiliary data on the primary EHT targets from decades of other observations. Second, models of the emission regions and their interaction with the black hole are complex, highly uncertain, and computationally expensive to construct. As a result, the scientific utilization of EHT observations requires a flexible, extensible, and powerful analysis framework. We present such a framework, Themis, which defines a set of interfaces between models, data, and sampling algorithms that facilitates future development. We describe the design and currently existing components of Themis, how Themis has been validated thus far, and present additional analyses made possible by Themis that illustrate its capabilities. Importantly, we demonstrate that Themis is able to reproduce prior EHT analyses, extend these, and do so in a computationally efficient manner that can efficiently exploit modern high-performance computing facilities. Themis has already been used extensively in the scientific analysis and interpretation of the first EHT observations of M87