Startle response probability and amplitude may be independently modulated by affective foreground stimulation as acoustic probe intensity decreases

The magnitude of the eyeblink reflex to an acoustic startle probe is reliable potentiated to highly arousing unpleasant foreground stimuli and inhibited to highly arousing pleasant foreground stimuli across all probe intensity levels. The present study examined the response magnitude findings of Cuthbert, Bradley, and Lang (1996) as response amplitude and probability. Medium arousal pleasant pictures produced larger blink amplitude responses than unpleasant pictures of the same arousal level to 80 and 95, but not 105 dB acoustic startle probes. This effect was opposite for high arousal pictures at all intensity levels. Response probability means decreased from pleasant to unpleasant across all arousal levels to 80 dB probes. The current study provides insight into the differential activation of response amplitude and probability to affective foreground stimulation at lower acoustic stimulus intensities and possible implications for mechanisms involved in the orienting and defensive responses

A typology of drought decision making: Synthesizing across cases to understand drought preparedness and response actions

Drought is an inescapable reality in many regions, including much of the western United States. With climate change, droughts are predicted to intensify and occur more frequently, making the imperative for drought management even greater. Many diverse actors – including private landowners, business owners, scientists, non-governmental organizations (NGOs), and managers and policymakers within tribal, local, state, and federal government agencies – play multiple, often overlapping roles in preparing for and responding to drought. Managing water is, of course, one of the most important roles that humans play in both mitigating and responding to droughts; but, focusing only on “water managers” or “water management” fails to capture key elements related to the broader category of drought management. The respective roles played by those managing drought (as distinct from water managers), the interactions among them, and the consequences in particular contexts, are not well understood. Our team synthesized insights from 10 in-depth case studies to understand key facets of decision making about drought preparedness and response. We present a typology with four elements that collectively describe how decisions about drought preparedness and response are made (context and objective for a decision; actors responsible; choice being made or action taken; and how decisions interact with and influence other decisions). The typology provides a framework for system-level understanding of how and by whom complex decisions about drought management are made. Greater system-level understanding helps decision makers, program and research funders, and scientists to identify constraints to and opportunities for action, to learn from the past, and to integrate ecological impacts, thereby facilitating social learning among diverse participants in drought preparedness and response

Challenges and opportunities in transdisciplinary science: The experience of next generation scientists in an agriculture and climate research collaboration

Agriculture in the twenty-first century faces unprecedented challenges from increasing climate variability to growing demands on natural resources to globalizing economic markets. These emerging agricultural issues, spanning both human and natural dimensions, are uniquely formulated, exceedingly complex, and difficult to address within existing disciplinary domains (Eigenbrode et al. 2007; Reganold et al. 2011; Foley et al. 2005; Hansen et al. 2013). Therefore, the next generation of scientists working on these issues must not only be highly trained within a disciplinary context but must also have the capacity to collaborate with others to solve systems-level problems

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Performance and Operation of the CMS Electromagnetic Calorimeter

The operation and general performance of the CMS electromagnetic calorimeter using cosmic-ray muons are described. These muons were recorded after the closure of the CMS detector in late 2008. The calorimeter is made of lead tungstate crystals and the overall status of the 75848 channels corresponding to the barrel and endcap detectors is reported. The stability of crucial operational parameters, such as high voltage, temperature and electronic noise, is summarised and the performance of the light monitoring system is presented

Quasispecies Theory and the Behavior of RNA Viruses

A large number of medically important viruses, including HIV, hepatitis C virus, and influenza, have RNA genomes. These viruses replicate with extremely high mutation rates and exhibit significant genetic diversity. This diversity allows a viral population to rapidly adapt to dynamic environments and evolve resistance to vaccines and antiviral drugs. For the last 30 years, quasispecies theory has provided a population-based framework for understanding RNA viral evolution. A quasispecies is a cloud of diverse variants that are genetically linked through mutation, interact cooperatively on a functional level, and collectively contribute to the characteristics of the population. Many predictions of quasispecies theory run counter to traditional views of microbial behavior and evolution and have profound implications for our understanding of viral disease. Here, we discuss basic principles of quasispecies theory and describe its relevance for our understanding of viral fitness, virulence, and antiviral therapeutic strategy

Exploring Off-Targets and Off-Systems for Adverse Drug Reactions via Chemical-Protein Interactome — Clozapine-Induced Agranulocytosis as a Case Study

In the era of personalized medical practice, understanding the genetic basis of patient-specific adverse drug reaction (ADR) is a major challenge. Clozapine provides effective treatments for schizophrenia but its usage is limited because of life-threatening agranulocytosis. A recent high impact study showed the necessity of moving clozapine to a first line drug, thus identifying the biomarkers for drug-induced agranulocytosis has become important. Here we report a methodology termed as antithesis chemical-protein interactome (CPI), which utilizes the docking method to mimic the differences in the drug-protein interactions across a panel of human proteins. Using this method, we identified HSPA1A, a known susceptibility gene for CIA, to be the off-target of clozapine. Furthermore, the mRNA expression of HSPA1A-related genes (off-target associated systems) was also found to be differentially expressed in clozapine treated leukemia cell line. Apart from identifying the CIA causal genes we identified several novel candidate genes which could be responsible for agranulocytosis. Proteins related to reactive oxygen clearance system, such as oxidoreductases and glutathione metabolite enzymes, were significantly enriched in the antithesis CPI. This methodology conducted a multi-dimensional analysis of drugs' perturbation to the biological system, investigating both the off-targets and the associated off-systems to explore the molecular basis of an adverse event or the new uses for old drugs

Treatment in advanced colorectal cancer: what, when and how?

Treatment of advanced colorectal cancer (CRC) increasingly requires a multidisciplinary approach and multiple treatment options add to the complexity of clinical decision-making. Recently novel targeted therapy against angiogenesis and epidermal growth factor receptor completed a plethora of phase III studies. The addition of bevacizumab to chemotherapy improved the efficacy over chemotherapy alone in both first and second line settings, although the magnitude of benefit may not be as great when a more optimal chemotherapy platform is used. Studies performed thus far did not address conclusively whether bevacizumab should be continued in subsequent lines of treatment. Anti-angiogenesis tyrosine kinase inhibitors have not shown any additional benefit over chemotherapy alone so far. Although some benefits were seen with cetuximab in all settings of treating advanced CRC, K-ras mutation status provides an important determinant of who would not benefit from such a treatment. Caution should be exercised in combining anti-angiogenesis with anti-EGFR strategy until further randomised data become available. In this review, we have focused on the implications of these trial results on the everyday management decisions of treating advanced CRC

Calibration of the CMS Drift Tube Chambers and Measurement of the Drift Velocity with Cosmic Rays

Peer reviewe

CMS Data Processing Workflows during an Extended Cosmic Ray Run

Peer reviewe