Do Investors View Excess Capacity as a Determinant of Mergers and Acquisitions in the Pharmaceutical and Biotechnology Industry?

I examine investors’ reaction to the announcement of mergers and acquisitions in the pharmaceutical and biotechnology industry from 2002 to 2008. Over this period, investors anticipate the announcements, as demonstrated by the fact that the cumulative abnormal returns are not statistically significant. In addition, I test to determine the effect of excess capacity on investors’ reactions. From 2002 to 2004, investors do not recognize acquisitions as a response to excess capacity, as the excess capacity measures utilized have no effect on the size of the cumulative abnormal return. From 2005 to 2008, however, excess capacity measures have a positive effect on cumulative abnormal return, indicating that investors started to recognize the threat of excess capacity and acquisitions as a response to that threat

Stress rapidly suppresses in vivo LH pulses and increases activation of RFRP-3 neurons in male mice

Restraint stress is a psychosocial stressor that suppresses reproductive status, including LH pulsatile secretion, but the neuroendocrine mechanisms underlying this inhibition remains unclear. Reproductive neural populations upstream of gonadotropin-releasing hormone (GnRH) neurons, such as kisspeptin, neurokinin B and RFRP-3 (GnIH) neurons, are possible targets for psychosocial stress to inhibit LH pulses, but this has not been well examined, especially in mice in which prior technical limitations prevented assessment of in vivo LH pulse secretion dynamics. Here, we examined whether one-time acute restraint stress alters in vivo LH pulsatility and reproductive neural populations in male mice, and what the time-course is for such alterations. We found that endogenous LH pulses in castrated male mice are robustly and rapidly suppressed by one-time, acute restraint stress, with suppression observed as quickly as 12–18 min. This rapid LH suppression parallels with increased in vivo corticosterone levels within 15 min of restraint stress. Although Kiss1, Tac2 and Rfrp gene expression in the hypothalamus did not significantly change after 90 or 180 min restraint stress, arcuate Kiss1 neural activation was significantly decreased after 180 min. Interestingly, hypothalamic Rfrp neuronal activation was strongly increased at early times after restraint stress initiation, but was attenuated to levels lower than controls by 180 min of restraint stress. Thus, the male neuroendocrine reproductive axis is quite sensitive to short-term stress exposure, with significantly decreased pulsatile LH secretion and increased hypothalamic Rfrp neuronal activation occurring rapidly, within minutes, and decreased Kiss1 neuronal activation also occurring after longer stress durations

Addressable Superconductor Integrated Circuit Memory from Delay Lines

Recent advances in logic schemes and fabrication processes have renewed interest in using superconductor electronics for energy-efficient computing and quantum control processors. However, scalable superconducting memory still poses a challenge. To address this issue, we present an alternative to approaches that solely emphasize storage cell miniaturization by exploiting the minimal attenuation and dispersion properties of superconducting passive transmission lines to develop a delay-line memory system. This fully superconducting design operates at speeds between 20 GHz and 100 GHz, with $\pm$24\% and $\pm$13\% bias margins, respectively, and demonstrates data densities in the 10s of Mbit/cm$^2$ with the MIT Lincoln Laboratory SC2 fabrication process. Additionally, the circulating nature of this design allows for minimal control circuitry, eliminates the need for data splitting and merging, and enables inexpensive implementations of sequential access and content-addressable memories. Further advances in fabrication processes suggest data densities of 100s of Mbit/cm$^2$ and beyondComment: 13 pages, 8 figures, 1 table, under revie

Low-Cost Superconducting Fan-Out with Repurposed Josephson Junctions

Superconductor electronics (SCE) promise computer systems with orders of magnitude higher speeds and lower energy consumption than their complementary metal-oxide semiconductor (CMOS) counterpart. At the same time, the scalability and resource utilization of superconducting systems are major concerns. Some of these concerns come from device-level challenges and the gap between SCE and CMOS technology nodes, and others come from the way Josephson Junctions (JJs) are used. Towards this end, we notice that a considerable fraction of hardware resources are not involved in logic operations, but rather are used for fan-out and buffering purposes. In this paper, we ask if there is a way to reduce these overheads; propose the repurposing of JJs at the cell boundaries for fan-out; and establish a set of rules to discretize critical currents in a way that is conducive to this reassignment. Finally, we demonstrate the accomplished gains through detailed analog simulations and modeling analyses. Our experiments indicate that the introduced method leads to a 48% savings in the JJ count in a tree with a fan-out of 1024, as well as an average of 43% of the JJ count for signal splitting and 32% for clock fan-out in ISCAS'85 benchmarks.Comment: 11 pages, 20 figures, submitted to IEEE TA

Balancing the presentation of information and options in patient decision aids: An updated review

Background: Standards for patient decision aids require that information and options be presented in a balanced manner; this requirement is based on the argument that balanced presentation is essential to foster informed decision making. If information is presented in an incomplete/non-neutral manner, it can stimulate cognitive biases that can unduly affect individuals' knowledge, perceptions of risks and benefits, and, ultimately, preferences. However, there is little clarity about what constitutes balance, and how it can be determined and enhanced. We conducted a literature review to examine the theoretical and empirical evidence related to balancing the presentation of information and options. Methods: A literature search related to patient decision aids and balance was conducted on Medline, using MeSH terms and PubMed; this search supplemented the 2011 Cochrane Collaboration's review of patient decision aids trials. Only English language articles relevant to patient decision making and addressing the balance of information and options were included. All members of the team independently screened clusters of articles; uncertainties were resolved by seeking review by another member. The team then worked in sub-groups to extract and synthesise data on theory, definitions, and evidence reported in these studies. Results: A total of 40 articles met the inclusion criteria. Of these, six explained the rationale for balancing the presentation of information and options. Twelve defined "balance"; the definition of "balance" that emerged is as follows: "The complete and unbiased presentation of the relevant options and the information about those options-in content and in format-in a way that enables individuals to process this information without bias". Ten of the 40 articles reported assessing the balance of the relevant decision aid. All 10 did so exclusively from the users' or patients' perspective, using a five-point Likert-type scale. Presenting information in a side-by-side display form was associated with more respondents (ranging from 70% to 96%) judging the information as "balanced". Conclusion: There is a need for comparative studies investigating different ways to improve and measure balance in the presentation of information and options in patient decision aids

Detection of Bioactive Exometabolites Produced by the Filamentous Marine Cyanobacterium Geitlerinema sp.

Marine cyanobacteria are noted for their ability to excrete metabolites with biotic properties. This paper focuses on such exometabolites obtained from the culture of the marine filamentous cyanobacterium Geitlerinema sp. strain, their purification and subsequent analyses. By this means the recoveries of the active compounds, a prerequisite for properly determining their concentration, are quantified here for the first time. We demonstrate a new procedure using Amberlite XAD-1180 resin in combination with the eluent isopropanol for extraction of the culture media and gas chromatography as simplified chemical analysis. This procedure reduced necessary bacteria cultivation time (from 150 to 21 days) at low volumes of culture media (300 mL) required for identification of two selected bioactive compounds: 4,4′-dihydroxybiphenyl and harmane

MicroRNAs in pulmonary arterial remodeling

Pulmonary arterial remodeling is a presently irreversible pathologic hallmark of pulmonary arterial hypertension (PAH). This complex disease involves pathogenic dysregulation of all cell types within the small pulmonary arteries contributing to vascular remodeling leading to intimal lesions, resulting in elevated pulmonary vascular resistance and right heart dysfunction. Mutations within the bone morphogenetic protein receptor 2 gene, leading to dysregulated proliferation of pulmonary artery smooth muscle cells, have been identified as being responsible for heritable PAH. Indeed, the disease is characterized by excessive cellular proliferation and resistance to apoptosis of smooth muscle and endothelial cells. Significant gene dysregulation at the transcriptional and signaling level has been identified. MicroRNAs are small non-coding RNA molecules that negatively regulate gene expression and have the ability to target numerous genes, therefore potentially controlling a host of gene regulatory and signaling pathways. The major role of miRNAs in pulmonary arterial remodeling is still relatively unknown although research data is emerging apace. Modulation of miRNAs represents a possible therapeutic target for altering the remodeling phenotype in the pulmonary vasculature. This review will focus on the role of miRNAs in regulating smooth muscle and endothelial cell phenotypes and their influence on pulmonary remodeling in the setting of PAH

A Mouse Model of the Human Fragile X Syndrome I304N Mutation

The mental retardation, autistic features, and behavioral abnormalities characteristic of the Fragile X mental retardation syndrome result from the loss of function of the RNA–binding protein FMRP. The disease is usually caused by a triplet repeat expansion in the 5′UTR of the FMR1 gene. This leads to loss of function through transcriptional gene silencing, pointing to a key function for FMRP, but precluding genetic identification of critical activities within the protein. Moreover, antisense transcripts (FMR4, ASFMR1) in the same locus have been reported to be silenced by the repeat expansion. Missense mutations offer one means of confirming a central role for FMRP in the disease, but to date, only a single such patient has been described. This patient harbors an isoleucine to asparagine mutation (I304N) in the second FMRP KH-type RNA–binding domain, however, this single case report was complicated because the patient harbored a superimposed familial liver disease. To address these issues, we have generated a new Fragile X Syndrome mouse model in which the endogenous Fmr1 gene harbors the I304N mutation. These mice phenocopy the symptoms of Fragile X Syndrome in the existing Fmr1–null mouse, as assessed by testicular size, behavioral phenotyping, and electrophysiological assays of synaptic plasticity. I304N FMRP retains some functions, but has specifically lost RNA binding and polyribosome association; moreover, levels of the mutant protein are markedly reduced in the brain specifically at a time when synapses are forming postnatally. These data suggest that loss of FMRP function, particularly in KH2-mediated RNA binding and in synaptic plasticity, play critical roles in pathogenesis of the Fragile X Syndrome and establish a new model for studying the disorder