Substrate Specificity of Human Cutaneous Alcohol Dehydrogenase and Erythema Provoked by Lower Aliphatic Alcohols

The substrate utilization rates of human cutaneous alcohol dehydrogenase were determined for 7 lower aliphatic primary alcohols: ethanol, propanol, butanol, pentanol, 2-methylpropanol, 3-methylbutanol, and 2,2-dimethylpropanol. 1-Pentanol gave the highest relative activity and 2,2-dimethyipropanol the lowest. The frequency of erythemogenesis was determined in vivo for these 7 lower aliphatic primary alcohols. The frequency of erythemogenesis correlated strongly and significantly with the rate of substrate utilization by alcohol dehydrogenase. These results are consistent with the view that the reaction to primary alcohols applied topically to human skin is provoked, in large part, by the corresponding aldehyde

An Assessment to Benchmark the Seismic Performance of a Code-Conforming Reinforced-Concrete Moment-Frame Building

This report describes a state-of-the-art performance-based earthquake engineering methodology that is used to assess the seismic performance of a four-story reinforced concrete (RC) office building that is generally representative of low-rise office buildings constructed in highly seismic regions of California. This “benchmark” building is considered to be located at a site in the Los Angeles basin, and it was designed with a ductile RC special moment-resisting frame as its seismic lateral system that was designed according to modern building codes and standards. The building’s performance is quantified in terms of structural behavior up to collapse, structural and nonstructural damage and associated repair costs, and the risk of fatalities and their associated economic costs. To account for different building configurations that may be designed in practice to meet requirements of building size and use, eight structural design alternatives are used in the performance assessments. Our performance assessments account for important sources of uncertainty in the ground motion hazard, the structural response, structural and nonstructural damage, repair costs, and life-safety risk. The ground motion hazard characterization employs a site-specific probabilistic seismic hazard analysis and the evaluation of controlling seismic sources (through disaggregation) at seven ground motion levels (encompassing return periods ranging from 7 to 2475 years). Innovative procedures for ground motion selection and scaling are used to develop acceleration time history suites corresponding to each of the seven ground motion levels. Structural modeling utilizes both “fiber” models and “plastic hinge” models. Structural modeling uncertainties are investigated through comparison of these two modeling approaches, and through variations in structural component modeling parameters (stiffness, deformation capacity, degradation, etc.). Structural and nonstructural damage (fragility) models are based on a combination of test data, observations from post-earthquake reconnaissance, and expert opinion. Structural damage and repair costs are modeled for the RC beams, columns, and slabcolumn connections. Damage and associated repair costs are considered for some nonstructural building components, including wallboard partitions, interior paint, exterior glazing, ceilings, sprinkler systems, and elevators. The risk of casualties and the associated economic costs are evaluated based on the risk of structural collapse, combined with recent models on earthquake fatalities in collapsed buildings and accepted economic modeling guidelines for the value of human life in loss and cost-benefit studies. The principal results of this work pertain to the building collapse risk, damage and repair cost, and life-safety risk. These are discussed successively as follows. When accounting for uncertainties in structural modeling and record-to-record variability (i.e., conditional on a specified ground shaking intensity), the structural collapse probabilities of the various designs range from 2% to 7% for earthquake ground motions that have a 2% probability of exceedance in 50 years (2475 years return period). When integrated with the ground motion hazard for the southern California site, the collapse probabilities result in mean annual frequencies of collapse in the range of [0.4 to 1.4]x10 -4 for the various benchmark building designs. In the development of these results, we made the following observations that are expected to be broadly applicable: (1) The ground motions selected for performance simulations must consider spectral shape (e.g., through use of the epsilon parameter) and should appropriately account for correlations between motions in both horizontal directions; (2) Lower-bound component models, which are commonly used in performance-based assessment procedures such as FEMA 356, can significantly bias collapse analysis results; it is more appropriate to use median component behavior, including all aspects of the component model (strength, stiffness, deformation capacity, cyclic deterioration, etc.); (3) Structural modeling uncertainties related to component deformation capacity and post-peak degrading stiffness can impact the variability of calculated collapse probabilities and mean annual rates to a similar degree as record-to-record variability of ground motions. Therefore, including the effects of such structural modeling uncertainties significantly increases the mean annual collapse rates. We found this increase to be roughly four to eight times relative to rates evaluated for the median structural model; (4) Nonlinear response analyses revealed at least six distinct collapse mechanisms, the most common of which was a story mechanism in the third story (differing from the multi-story mechanism predicted by nonlinear static pushover analysis); (5) Soil-foundation-structure interaction effects did not significantly affect the structural response, which was expected given the relatively flexible superstructure and stiff soils. The potential for financial loss is considerable. Overall, the calculated expected annual losses (EAL) are in the range of $52,000 to$97,000 for the various code-conforming benchmark building designs, or roughly 1% of the replacement cost of the building ($8.8M). These losses are dominated by the expected repair costs of the wallboard partitions (including interior paint) and by the structural members. Loss estimates are sensitive to details of the structural models, especially the initial stiffness of the structural elements. Losses are also found to be sensitive to structural modeling choices, such as ignoring the tensile strength of the concrete (40 EAL) or the contribution of the gravity frames to overall building stiffness and strength (15 change in EAL). Although there are a number of factors identified in the literature as likely to affect the risk of human injury during seismic events, the casualty modeling in this study focuses on those factors (building collapse, building occupancy, and spatial location of building occupants) that directly inform the building design process. The expected annual number of fatalities is calculated for the benchmark building, assuming that an earthquake can occur at any time of any day with equal probability and using fatality probabilities conditioned on structural collapse and based on empirical data. The expected annual number of fatalities for the code-conforming buildings ranges between 0.05*10 -2 and 0.21*10 -2 , and is equal to 2.30*10 -2 for a non-code conforming design. The expected loss of life during a seismic event is perhaps the decision variable that owners and policy makers will be most interested in mitigating. The fatality estimation carried out for the benchmark building provides a methodology for comparing this important value for various building designs, and enables informed decision making during the design process. The expected annual loss associated with fatalities caused by building earthquake damage is estimated by converting the expected annual number of fatalities into economic terms. Assuming the value of a human life is$3.5M, the fatality rate translates to an EAL due to fatalities of $3,500 to$5,600 for the code-conforming designs, and $79,800 for the non-code conforming design. Compared to the EAL due to repair costs of the code-conforming designs, which are on the order of$66,000, the monetary value associated with life loss is small, suggesting that the governing factor in this respect will be the maximum permissible life-safety risk deemed by the public (or its representative government) to be appropriate for buildings. Although the focus of this report is on one specific building, it can be used as a reference for other types of structures. This report is organized in such a way that the individual core chapters (4, 5, and 6) can be read independently. Chapter 1 provides background on the performance-based earthquake engineering (PBEE) approach. Chapter 2 presents the implementation of the PBEE methodology of the PEER framework, as applied to the benchmark building. Chapter 3 sets the stage for the choices of location and basic structural design. The subsequent core chapters focus on the hazard analysis (Chapter 4), the structural analysis (Chapter 5), and the damage and loss analyses (Chapter 6). Although the report is self-contained, readers interested in additional details can find them in the appendices

Protracted Effects of Juvenile Stressor Exposure Are Mitigated by Access to Palatable Food

Stressor experiences during the juvenile period may increase vulnerability to anxiety and depressive-like symptoms in adulthood. Stressors may also promote palatable feeding, possibly reflecting a form of self-medication. The current study investigated the short- and long-term consequences of a stressor applied during the juvenile period on anxiety- and depressive-like behavior measured by the elevated plus maze (EPM), social interaction and forced swim test (FST). Furthermore, the effects of stress on caloric intake, preference for a palatable food and indices of metabolic syndrome and obesity were assessed. Male Wistar rats exposed to 3 consecutive days of variable stressors on postnatal days (PD) 27–29, displayed elevated anxiety-like behaviors as adults, which could be attenuated by consumption of a palatable high-fat diet. However, consumption of a palatable food in response to a stressor appeared to contribute to increased adiposity

Parent of Origin, Mosaicism, and Recurrence Risk: Probabilistic Modeling Explains the Broken Symmetry of Transmission Genetics

Most new mutations are observed to arise in fathers, and increasing paternal age positively correlates with the risk of new variants. Interestingly, new mutations in X-linked recessive disease show elevated familial recurrence rates. In male offspring, these mutations must be inherited from mothers. We previously developed a simulation model to consider parental mosaicism as a source of transmitted mutations. In this paper, we extend and formalize the model to provide analytical results and flexible formulas. The results implicate parent of origin and parental mosaicism as central variables in recurrence risk. Consistent with empirical data, our model predicts that more transmitted mutations arise in fathers and that this tendency increases as fathers age. Notably, the lack of expansion later in the male germline determines relatively lower variance in the proportion of mutants, which decreases with paternal age. Subsequently, observation of a transmitted mutation has less impact on the expected risk for future offspring. Conversely, for the female germline, which arrests after clonal expansion in early development, variance in the mutant proportion is higher, and observation of a transmitted mutation dramatically increases the expected risk of recurrence in another pregnancy. Parental somatic mosaicism considerably elevates risk for both parents. These findings have important implications for genetic counseling and for understanding patterns of recurrence in transmission genetics. We provide a convenient online tool and source code implementing our analytical results. These tools permit varying the underlying parameters that influence recurrence risk and could be useful for analyzing risk in diverse family structures

Climate Change and Biosphere Response: Unlocking the Collections Vault

Natural history collections (NHCs) are an important source of the long-term data needed to understand how biota respond to ongoing anthropogenic climate change. These include taxon occurrence data for ecological modeling, as well as information that can be used to reconstruct mechanisms through which biota respond to changing climates. The full potential of NHCs for climate change research cannot be fully realized until high-quality data sets are conveniently accessible for research, but this requires that higher priority be placed on digitizing the holdings most useful for climate change research (e.g., whole-biota studies, time series, records of intensively sampled common taxa). Natural history collections must not neglect the proliferation of new information from efforts to understand how present-day ecosystems are responding to environmental change. These new directions require a strategic realignment for many NHC holders to complement their existing focus on taxonomy and systematics. To set these new priorities, we need strong partnerships between NHC holders and global change biologists

Clinical and virologic efficacy of herpes simplex virus type 2 suppression by acyclovir in a multicontinent clinical trial.

Acyclovir suppressive therapy (400 mg twice daily) reduces herpes simplex virus (HSV) type 2-associated genital ulcer disease and lesional HSV shedding. In an international trial of acyclovir for suppression of HSV type 2 to prevent human immunodeficiency virus (HIV) acquisition (HIV Prevention Trials Network 039), acyclovir had a smaller effect on the frequency of genital ulcer disease as well as a smaller effect on the frequency and quantity of lesional HSV DNA in African women and Peruvian men, compared with its effects in men in the United States. The observed regional variation in the clinical and virologic efficacy of acyclovir for HSV suppression warrants further evaluation of determinants of responses to acyclovir. (ClinicalTrials.gov identifier: NCT00076232.)

Palatable Food Dampens the Long-Term Behavioral and Endocrine Effects of Juvenile Stressor Exposure but May Also Provoke Metabolic Syndrome in Rats

The juvenile period is marked by a reorganization and growth of important brain regions including structures associating with reward seeking behaviors such as the nucleus accumbens (NA) and prefrontal cortex (PFC). These changes are impacted by stressors during the juvenile period and may lead to a predisposition to stress induced psychopathology and abnormal development of brain reward systems. Like in humans, adult rodents engage certain coping mechanisms such as increases in the consumption of calorie-rich palatable foods to reduce stress, but this behavior can lead to obesity and metabolic disorders. In this study, we examined whether stressors during the juvenile period led to increased caloric intake when a palatable diet was accessible, and whether this diet attenuated adult stress responses. In addition, we examined if the stress buffering effects produced by the palatable diet were also accompanied by an offset propensity towards obesity, and by alterations in mRNA expression of dopamine (DA) receptors in the NA and PFC in adulthood. To this end, juvenile male Wistar rats underwent episodic stressor exposure (forced swim, elevated platform stress and restraint) on postnatal days (PD) 27-29 and received access to regular chow or daily limited access to a palatable diet until adulthood. At the age of 2 months, rats were tested on a social interaction test that screens for anxiety-like behaviors and their endocrine responses to an acute stressor. Animals were sacrificed, and their brains processed to detect differences in DA receptor subtype expression in the PFC and NA using qPCR. Results showed that rats that were stressed during the juvenile period displayed higher social anxiety and a sensitized corticosterone response as adults and these effects were attenuated by access to the palatable diet. Nevertheless, rats that experienced juvenile stress and consumed a palatable diet showed greater adiposity in adulthood. Interestingly, the same group displayed greater mRNA expression of DA receptors at the NA. This suggests that access to a palatable diet mitigates the behavioral and endocrine effects of juvenile stressor exposure in adulthood, but at the cost of metabolic imbalances and a sensitized dopaminergic system

CSP Hybrid Space Computing for STP-H5/ISEM on ISS

The Space Test Program (STP) at the Department of Defense (DoD) supports the development, evaluation, and advancement of new technologies needed for the future of spaceflight. STP-Houston provides opportunities for DoD and civilian space agencies to perform on-orbit research and technology demonstrations from the International Space Station (ISS). The STP-H5/ISEM (STP-Houston 5, ISS SpaceCube Experiment Mini) payload is scheduled for launch on the upcoming SpaceX 10 mission and will feature new technologies, including a hybrid space computer developed by the NSF CHREC Center, working closely with the NASA SpaceCube Team, known as the CHREC Space Processor (CSP). In this paper, we present the novel concepts behind CSP and the CSPv1 flight technologies on the ISEM mission. The ISEM-CSP system was subjected to environmental testing, including a thermal vacuum test, a vibration test, and two radiation tests, and results were encouraging and are presented. Primary objectives for ISEM-CSP are highlighted, which include processing, compression, and downlink of terrestrial-scene images for display on Earth, and monitoring of upset rates in various subsystems to provide environmental information for future missions. Secondary objectives are also presented, including experiments with features for fault-tolerant computing, reliable middleware services, FPGA partial reconfiguration, device virtualization, and dynamic synthesis

Open urethroplasty versus endoscopic urethrotomy - clarifying the management of men with recurrent urethral stricture (the OPEN trial) : study protocol for a randomised controlled trial

Peer reviewedPublisher PD

Test Structures for Characterising the Silver Chlorination Process During Integrated Ag/AgCl Reference Electrode Fabrication

Robust and repeatable processes are required to fabricate reference electrodes for micro-scale integrated electrochemical sensors. One method for this is to produce a “silver/silver chloride” (Ag/Agel) electrode through chemical chlorination of a thin film silver layer. This paper presents test structures, which can electrically characterise the process to aid process development and in-line control of the chlorination process