Prediction Model for the Life of Nickel-cadmium Batteries in Geosynchronous Orbit Satellites

A mathematical model is described which predicts the service life of nickel-cadmium batteries designed for geosynchronous orbit satellites. Regression analysis technique is used to analyze orbital data on second generation trickle charged batteries. The model gives average cell voltage as a function of design parameters, operating parameters and time. The voltage model has the properties of providing a good fit to the data, good predictive capability, and agreement with known battery performance characteristics. Average cell voltage can be predicted to within 0.02 volts for up to 8 years. This modeling shows that these batteries will operate reliably for 10 years. Third-generation batteries are expected to operate even longer

Targeting Glutamate Uptake To Treat Alcohol Use Disorders

Alcoholism is a serious public health concern that is characterized by the development of tolerance to alcohol's effects, increased consumption, loss of control over drinking and the development of physical dependence. This cycle is often times punctuated by periods of abstinence, craving and relapse. The development of tolerance and the expression of withdrawal effects, which manifest as dependence, have been to a great extent attributed to neuroadaptations within the mesocorticolimbic and extended amygdala systems. Alcohol affects various neurotransmitter systems in the brain including the adrenergic, cholinergic, dopaminergic, GABAergic, glutamatergic, peptidergic, and serotonergic systems. Due to the myriad of neurotransmitter and neuromodulator systems affected by alcohol, the efficacies of current pharmacotherapies targeting alcohol dependence are limited. Importantly, research findings of changes in glutamatergic neurotransmission induced by alcohol self- or experimenter-administration have resulted in a focus on therapies targeting glutamatergic receptors and normalization of glutamatergic neurotransmission. Glutamatergic receptors implicated in the effects of ethanol include the ionotropic glutamate receptors (AMPA, Kainate, and NMDA) and some metabotropic glutamate receptors. Regarding glutamatergic homeostasis, ceftriaxone, MS-153, and GPI-1046, which upregulate glutamate transporter 1 (GLT1) expression in mesocorticolimbic brain regions, reduce alcohol intake in genetic animal models of alcoholism. Given the hyperglutamatergic/hyperexcitable state of the central nervous system induced by chronic alcohol abuse and withdrawal, the evidence thus far indicates that a restoration of glutamatergic concentrations and activity within the mesocorticolimbic system and extended amygdala as well as multiple memory systems holds great promise for the treatment of alcohol dependence

Caenorhabditis elegans as a model system to identify therapeutics for alcohol use disorders

Alcohol use disorders (AUDs) cause serious problems in society and few effective treatments are available. Caenorhabditis elegans (C. elegans) is an excellent invertebrate model to study the neurobiological basis of human behavior with a conserved, fully tractable genome, and a short generation time for fast generation of data at a fraction of the cost of other organisms. C. elegans demonstrate movement toward, and concentration-dependent self-exposure to various psychoactive drugs. The discovery of opioid receptors in C. elegans provided the impetus to test the hypothesis that C. elegans may be used as a medications screen to identify new AUD treatments. We tested the effects of naltrexone, an opioid antagonist and effective treatment for AUDs, on EtOH preference in C. elegans. Six-well agar test plates were prepared with EtOH placed in a target zone on one side and water in the opposite target zone of each well. Worms were treated with naltrexone before EtOH preference testing and then placed in the center of each well. Wild-type worms exhibited a concentration-dependent preference for 50, 70 and 95% EtOH. Naltrexone blocked acute EtOH preference, but had no effect on attraction to food or benzaldehyde in wild-type worms. Npr-17 opioid receptor knockout mutants did not display a preference for EtOH. In contrast, npr-17 opioid receptor rescue mutants exhibited significant EtOH preference behavior, which was attenuated by naltrexone. Chronic EtOH exposure induced treatment resistance and compulsive-like behavior. These data indicate that C. elegans can serve as a model system to identify compounds to treat AUDs

The Reinforcing Properties of Drugs of Abuse are Attenuated by Naltrexone in Caenorhabditis elegans

poster abstractDrug addiction is a chronic, relapsing disease premised on compulsive drug seeking. Previous work from our lab demonstrated that the nematode Caenorhabditis elegans (C. elegans) can be used to examine the reinforcing properties of drugs of abuse. A successful model for studying the reinforcing effects of drugs in C. elegans would greatly aid efforts to discover potential therapeutic interventions for drug addiction. The present study examined preference for morphine, ethanol, cocaine, and a cannabinoid agonist (CB agonist) in C. elegans and the effect of naltrexone, an opioid antagonist, on this behavior. Six-well agar test plates were utilized to test drug preference. Each well had two circular target zones equidistant from the center; 4μl of the targeted drug or water were placed in the center of one of the two target zones within each well. Worms in one group were pre-treated with 10mM naltrexone, while controls were pre-treated with 0.97 mM HCl for 30 min prior to testing. Worms in each treatment group were then placed in the center of each well and allowed to move freely for 30 minutes-images were captured at 10 and 30 minutes. Animals treated with vehicle displayed a significant preference for the aforementioned drugs relative to controls; naltrexone pretreatment significantly ameliorated this effect. Naltrexone had no effect on food or chemoatractant preference, indicating that the effects of naltrexone on drug preference are selective and not due to disruption in general behaviors. These findings suggest that the reinforcing properties of drugs of abuse can be examined in C. elegans and this model may be useful for screening potential pharmacotherapies for drug abuse

Nicotine is more addictive, not more cognitively therapeutic in a neurodevelopmental model of schizophrenia produced by neonatal ventral hippocampal lesions

Nicotine dependence is the leading cause of death in the United States. However, research on high rates of nicotine use in mental illness has primarily explained this co-morbidity as reflecting nicotine's therapeutic benefits, especially for cognitive symptoms, equating smoking with 'self-medication'. We used a leading neurodevelopmental model of mental illness in rats to prospectively test the alternative possibility that nicotine dependence pervades mental illness because nicotine is simply more addictive in mentally ill brains that involve developmental hippocampal dysfunction. Neonatal ventral hippocampal lesions (NVHL) have previously been demonstrated to produce post-adolescent-onset, pharmacological, neurobiological and cognitive-deficit features of schizophrenia. Here, we show that NVHLs increase adult nicotine self-administration, potentiating acquisition-intake, total nicotine consumed and drug seeking. Behavioral sensitization to nicotine in adolescence prior to self-administration is not accentuated by NVHLs in contrast to increased nicotine self-administration and behavioral sensitization documented in adult NVHL rats, suggesting periadolescent neurodevelopmental onset of nicotine addiction vulnerability in the NVHL model. Delivering a nicotine regimen approximating the exposure used in the sensitization and self-administration experiments (i.e. as a treatment) to adult rats did not specifically reverse NVHL-induced cortical-hippocampal-dependent cognitive deficits and actually worsened cognitive efficiency after nicotine treatment stopped, generating deficits that resemble those due to NVHLs. These findings represent the first prospective evidence demonstrating a causal link between disease processes in schizophrenia and nicotine addiction. Developmental cortical-temporal limbic dysfunction in mental illness may thus amplify nicotine's reinforcing effects and addiction risk and severity, even while producing cognitive deficits that are not specifically or substantially reversible with nicotine

Prescription drug monitoring program data tracking of opioid addiction treatment outcomes in integrated dual diagnosis care involving injectable naltrexone

BACKGROUND AND OBJECTIVES: Fourfold increases in opioid prescribing and dispensations over 2 decades in the U.S. has paralleled increases in opioid addictions and overdoses, requiring new preventative, diagnostic, and treatment strategies. This study examines Prescription Drug Monitoring Program (PDMP) tracking as a novel measure of opioid addiction treatment outcomes in a university-affiliated integrated mental health-addiction treatment clinic. METHODS: Repeated measure parametrics examined PDMP and urine drug screening (UDS) data before and after first injection for all patients (N = 68) who received at least one long-acting naltrexone injection (380 mg/IM) according to diagnostic groupings of having either (i) alcohol (control); (ii) opioid; or (iii) combined alcohol and opioid use disorders. RESULTS: There were no group differences post-injection in treatment days, injections delivered, or treatment service encounters. UDS and PDMP measures of opioid exposures were greater in opioid compared to alcohol-only patients. Post-first injection, UDS's positive for opioids declined (p < .05) along with PDMP measures of opioid prescriptions (p < .001), doses (p < .01), types (p < .001), numbers of dispensing prescribers (p < .001) and pharmacies (p < .001). Opioid patients without alcohol disorders showed the best outcomes with 50% to 80% reductions in PDMP-measures of opioids, down to levels of alcohol-only patients. CONCLUSIONS: This study shows PDMP utility for measuring opioid addiction treatment outcomes, supporting the routine use of PDMPs in clinical and research settings. SCIENTIFIC SIGNIFICANCE: These findings demonstrate that opioid addiction in patients with complex addictions and mental illnesses comorbidities can show effective treatment responses as measured by PDMP tracking of decreases in opioid prescriptions to those patients. (Am J Addict 2016;25:557-564)

Use of the Fluorescence-Activated Cell Sorter to Quantitate and Enrich for Subpopulations of Human Skin Cells

A variety of immunologic staining techniques were compared in a quantitative study of antigen expression by human epidermal cells. Virtually all nucleated epidermal cells express β2-microglobulin, which is associated with HLA-A, -B, and -C antigens, whereas only about 4% expressed T6, an antigen expressed by Langerhans cells but not other cells in the skin. With the fluorescence-activated cell sorter (FACS), epidermal cell suspensions were selectively enriched 10- to 15-fold for T6-positive Langerhans cells.An average of 6.5% of cells were specifically stained by anti-HLA-DR antibody. When dispersed cells stained with anti-DR plus peroxidase were examined with the technique of immunoelectron microscopy, only mononuclear leukocytes (probably Langerhans cells) were stained. After separating HLA-DR positive skin cells with the FACS, the DR-positive population but not the DR-negative population stimulated proliferation of allogeneic responder lymphocytes, indicating that sorted cells are metabolically active. We conclude that HLA-DR antigen is not expressed by keratinocytes in normal human skin cell suspensions and that the FACS can be used to selectively enrich or deplete skin cell suspensions of antigenically distinct subpopulations such as Langerhans cells

HD 65949: Rosetta Stone or Red Herring

HD 65949 is a late B star with exceptionally strong Hg II at 3984[A], but it is not a typical HgMn star. The Re II spectrum is of extraordinary strength. Abundances, or upper limits are derived here for 58 elements based on a model with Teff = 13100K, and log(g) = 4.0. Even-Z elements through nickel show minor deviations from solar abundances. Anomalies among the odd-Z elements through copper are mostly small. Beyond the iron peak, a huge scatter is found. The abundance pattern of the heaviest elements resembles the N=126 r-process peak of solar material, though not in detail. We find a significant correlation of the abundance excesses with second ionization potentials for elements with Z > 30. This indicates the relevance of photospheric or near-photospheric processes. We explore a model with mass accretion of exotic material followed by the more commonly accepted differentiation by diffusion. That model leads to a number of predictions which challenge future work. Likely primary and secondary masses are near 3.3 and 1.6 M(solar), with a separation of ca. 0.25 AU. New atomic structure calculations are presented in two appendices.Comment: Accepted by MNRAS: 16 pages, 5 figure

Systemic immunity is required for effective cancer immunotherapy

Immune responses involve coordination across cell types and tissues. However, studies in cancer immunotherapy have focused heavily on local immune responses in the tumor microenvironment. To investigate immune activity more broadly, we performed an organism-wide study in genetically engineered cancer models using mass cytometry. We analyzed immune responses in several tissues after immunotherapy by developing intuitive models for visualizing single-cell data with statistical inference. Immune activation was evident in the tumor and systemically shortly after effective therapy was administered. However, during tumor rejection, only peripheral immune cells sustained their proliferation. This systemic response was coordinated across tissues and required for tumor eradication in several immunotherapy models. An emergent population of peripheral CD4 T cells conferred protection against new tumors and was significantly expanded in patients responding to immunotherapy. These studies demonstrate the critical impact of systemic immune responses that drive tumor rejection