Study of proton radiation effects on solar vehicle electronic system

Radiation effects on electronic equipment of solar spacecraft - shielding requirement

Health effects of acid aerosols formed by atmospheric mixtures.

Under ambient conditions, sulfur and nitrogen oxides can react with photochemical products and airborne particles to form acidic vapors and aerosols. Inhalation toxicological studies were conducted, exposing laboratory animals, at rest and during exercise, to multicomponent atmospheric mixtures under conditions favorable to the formation of acidic reaction products. Effects of acid and ozone mixtures on early and late clearance of insoluble radioactive particles in the lungs of rats appeared to be dominated by the oxidant component (i.e., the mixture did cause effects that were significantly different from those of ozone alone). Histopathological evaluations showed that sulfuric acid particles alone did not cause inflammatory responses in centriacinar units of rat lung parenchyma (expressed in terms of percent lesion area) but did cause significant damage (cell killing followed by a wave of cell replication) in nasal respiratory epithelium, as measured by uptake of tritiated thymidine in the DNA of replicating cells. Mixtures of ozone and nitrogen dioxide, which form nitric acid, caused significant inflammatory responses in lung parenchyma (in excess of effects seen in rats exposed to ozone alone), but did not damage nasal epithelium. Mixtures containing acidic sulfate particles, ozone, and nitrogen dioxide damaged both lung parenchyma and nasal epithelia. In rats exposed at rest, the response of the lung appeared to be dominated by the oxidant gas-phase components, while responses in the nose were dominated by the acidic particles. In rats exposed at exercise, however, mixtures of ozone and sulfuric acid particles significantly (2.5-fold) elevated the degree of lung lesion formation over that seen in rats exposed to ozone alone under an identical exercise protocol

Inhalation exposure of animals.

Relative advantages and disadvantages and important design criteria for various exposure methods are presented. Five types of exposures are discussed: whole-body chambers, head-only exposures, nose or mouth-only methods, lung-only exposures, and partial-lung exposures. Design considerations covered include: air cleaning and conditioning; construction materials; losses of exposure materials; evenness of exposure; sampling biases; animal observation and care; noise and vibration control, safe exhausts, chamber loading, reliability, pressure fluctuations; neck seals, masks, animal restraint methods; and animal comfort. Ethical considerations in use of animals in inhalation experiments are also discussed

Decaying Hidden Dark Matter in Warped Compactification

The recent PAMELA and ATIC/Fermi/HESS experiments have observed an excess of electrons and positrons, but not anti-protons, in the high energy cosmic rays. To explain this result, we construct a decaying hidden dark matter model in string theory compactification that incorporates the following two ingredients, the hidden dark matter scenario in warped compactification and the phenomenological proposal of hidden light particles that decay to the Standard Model. In this model, on higher dimensional warped branes, various warped Kaluza-Klein particles and the zero-mode of gauge field play roles of the hidden dark matter or mediators to the Standard Model.Comment: 15 pages; v4, several clarifications added, update on Fermi/HESS result

Precision medicine for suicidality: from universality to subtypes and personalization

Suicide remains a clear, present and increasing public health problem, despite being a potentially preventable tragedy. Its incidence is particularly high in people with overt or un(der)diagnosed psychiatric disorders. Objective and precise identification of individuals at risk, ways of monitoring response to treatments and novel preventive therapeutics need to be discovered, employed and widely deployed. We sought to investigate whether blood gene expression biomarkers for suicide (that is, a ‘liquid biopsy’ approach) can be identified that are more universal in nature, working across psychiatric diagnoses and genders, using larger cohorts than in previous studies. Such markers may reflect and/or be a proxy for the core biology of suicide. We were successful in this endeavor, using a comprehensive stepwise approach, leading to a wealth of findings. Steps 1, 2 and 3 were discovery, prioritization and validation for tracking suicidality, resulting in a Top Dozen list of candidate biomarkers comprising the top biomarkers from each step, as well as a larger list of 148 candidate biomarkers that survived Bonferroni correction in the validation step. Step 4 was testing the Top Dozen list and Bonferroni biomarker list for predictive ability for suicidal ideation (SI) and for future hospitalizations for suicidality in independent cohorts, leading to the identification of completely novel predictive biomarkers (such as CLN5 and AK2), as well as reinforcement of ours and others previous findings in the field (such as SLC4A4 and SKA2). Additionally, we examined whether subtypes of suicidality can be identified based on mental state at the time of high SI and identified four potential subtypes: high anxiety, low mood, combined and non-affective (psychotic). Such subtypes may delineate groups of individuals that are more homogenous in terms of suicidality biology and behavior. We also studied a more personalized approach, by psychiatric diagnosis and gender, with a focus on bipolar males, the highest risk group. Such a personalized approach may be more sensitive to gender differences and to the impact of psychiatric co-morbidities and medications. We compared testing the universal biomarkers in everybody versus testing by subtypes versus personalized by gender and diagnosis, and show that the subtype and personalized approaches permit enhanced precision of predictions for different universal biomarkers. In particular, LHFP appears to be a strong predictor for suicidality in males with depression. We also directly examined whether biomarkers discovered using male bipolars only are better predictors in a male bipolar independent cohort than universal biomarkers and show evidence for a possible advantage of personalization. We identified completely novel biomarkers (such as SPTBN1 and C7orf73), and reinforced previously known biomarkers (such as PTEN and SAT1). For diagnostic ability testing purposes, we also examined as predictors phenotypic measures as apps (for suicide risk (CFI-S, Convergent Functional Information for Suicidality) and for anxiety and mood (SASS, Simplified Affective State Scale)) by themselves, as well as in combination with the top biomarkers (the combination being our a priori primary endpoint), to provide context and enhance precision of predictions. We obtained area under the curves of 90% for SI and 77% for future hospitalizations in independent cohorts. Step 5 was to look for mechanistic understanding, starting with examining evidence for the Top Dozen and Bonferroni biomarkers for involvement in other psychiatric and non-psychiatric disorders, as a mechanism for biological predisposition and vulnerability. The biomarkers we identified also provide a window towards understanding the biology of suicide, implicating biological pathways related to neurogenesis, programmed cell death and insulin signaling from the universal biomarkers, as well as mTOR signaling from the male bipolar biomarkers. In particular, HTR2A increase coupled with ARRB1 and GSK3B decreases in expression in suicidality may provide a synergistic mechanistical corrective target, as do SLC4A4 increase coupled with AHCYL1 and AHCYL2 decrease. Step 6 was to move beyond diagnostics and mechanistical risk assessment, towards providing a foundation for personalized therapeutics. Items scored positive in the CFI-S and subtypes identified by SASS in different individuals provide targets for personalized (psycho)therapy. Some individual biomarkers are targets of existing drugs used to treat mood disorders and suicidality (lithium, clozapine and omega-3 fatty acids), providing a means toward pharmacogenomics stratification of patients and monitoring of response to treatment. Such biomarkers merit evaluation in clinical trials. Bioinformatics drug repurposing analyses with the gene expression biosignatures of the Top Dozen and Bonferroni-validated universal biomarkers identified novel potential therapeutics for suicidality, such as ebselen (a lithium mimetic), piracetam (a nootropic), chlorogenic acid (a polyphenol) and metformin (an antidiabetic and possible longevity promoting drug). Finally, based on the totality of our data and of the evidence in the field to date, a convergent functional evidence score prioritizing biomarkers that have all around evidence (track suicidality, predict it, are reflective of biological predisposition and are potential drug targets) brought to the fore APOE and IL6 from among the universal biomarkers, suggesting an inflammatory/accelerated aging component that may be a targetable common denominator

Estimated Exposure Risks from Carcinogenic Nitrosamines in Urban Airborne Particulate Matter

Organic nitrogen (ON) compounds are present in atmospheric particulate matter (PM), but compared to their inorganic, hydrocarbon and oxygenated counterparts, they are difficult to characterize due to their complex chemical composition. Nitrosamines are a class of ON compounds known to be highly carcinogenic, and include species formed from nicotine degradation, but there are no detailed estimates of their abundance in ambient air. We use a highly sensitive analytical method, which is capable of separating over 700 ON compounds, to determine daily variability in nicotine, and 8 non specific and 4 tobacco specific nitrosamines in ambient PM from central London over two periods in winter and summer. The average total nitrosamine concentration was 5.2 ng m-3, substantially exceeding a current public recommendation of 0.3 ng m-3 on a daily basis. The lifetime cancer risk from nitrosamines in urban PM exceeded the U.S. Environmental Protection Agency guideline of 1 excess cancer cases per 1 million population exposed after 1 hour of exposure to observed concentrations per day over the duration of an adult lifetime. A clear relationship between ambient nitrosamines and total PM2.5 was observed with 1.2 ng m-3 ± 2.6 ng m-3 (total nitrosamine) per 10 µg m-3 PM2.5

Inhalation exposure methodology.

Modern man is being confronted with an ever-increasing inventory of potentially toxic airborne substances. Exposures to these atmospheric contaminants occur in residential and commercial settings, as well as in the workplace. In order to study the toxicity of such materials, a special technology relating to inhalation exposure systems has evolved. The purpose of this paper is to provide a description of the techniques which are used in exposing laboratory subjects to airborne particles and gases. The various modes of inhalation exposure (whole body, head only, nose or mouth only, etc.) are described at length, including the advantages and disadvantages inherent to each mode. Numerous literature citations are included for further reading. Among the topics briefly discussed are the selection of appropriate animal species for toxicological testing, and the types of inhalation studies performed (acute, chronic, etc.)

The Leptonic Higgs as a Messenger of Dark Matter

We propose that the leptonic cosmic ray signals seen by PAMELA and ATIC result from the annihilation or decay of dark matter particles via states of a leptonic Higgs doublet to $\tau$ leptons, linking cosmic ray signals of dark matter to LHC signals of the Higgs sector. The states of the leptonic Higgs doublet are lighter than about 200 GeV, yielding large $\bar{\tau} \tau$ and $\bar{\tau} \tau \bar{\tau} \tau$ event rates at the LHC. Simple models are given for the dark matter particle and its interactions with the leptonic Higgs, for cosmic ray signals arising from both annihilations and decays in the galactic halo. For the case of annihilations, cosmic photon and neutrino signals are on the verge of discovery.Comment: 34 pages, 9 figures, minor typos corrected, references adde