Evaluation of Separation Mechanism Design for the Orion/Ares Launch Vehicle

As a part of the preliminary design work being performed for the Orion vehicle, the Orion to Spacecraft Adaptor (SA) separation mechanism was analyzed and sized, with findings presented here. Sizing is based on worst case abort condition as a result of an anomaly driving the launch vehicle engine thrust vector control hard-over causing a severe vehicle pitch over. This worst case scenario occurs just before Upper Stage Main Engine Cut-Off (MECO) when the vehicle is the lightest and the damping effect due to propellant slosh has been reduced to a minimum. To address this scenario and others, two modeling approaches were invoked. The first approach was a detailed Simulink model to quickly assess the Service Module Engine nozzle to SA clearance for a given separation mechanism. The second approach involved the generation of an Automatic Dynamic Analysis of Mechanical Systems (ADAMS) model to assess secondary effects due to mass centers of gravity that were slightly off the vehicle centerline. It also captured any interference between the Solar Arrays and the Spacecraft Adapter. A comparison of modeling results and accuracy are discussed. Most notably, incorporating a larger SA flange diameter allowed for a natural separation of the Orion and it's engine nozzle even at relatively large pitch rates minimizing the kickoff force. Advantages and disadvantages of the Simulink model vs. a full geometric ADAMS model are discussed as well

Pharmacogenetics: CYPs, NAT2 and 5-HTT Related to Antidepressants

Pharmacogenetics (PGt), the study of a gene\u27s influence on patient response to a drug, shows strong potential for explaining issues with efficacy related to antidepressant medications. Each year, antidepressants are one of the most commonly prescribed medications due to the millions of Americans affected by depression. Importantly, it is recognized that there is wide interpatient variability in drug response to antidepressants caused by genetic mutations, which can alter the pharmacodynamic (PD) and pharmacokinetic (PK) properties of various drugs used to treat depression. Proteins that are mainly involved in how patients respond to medications include receptors, drug-targeted proteins, drug transport proteins and drug-metabolizing enzymes. Specifically in depression, variations in the serotonin reuptake transporter (SERT-1 or 5-HTT), N-acetyltransferase (NAT2), cytochrome P450 (CYP) 2C19, 2D6, and 1A2 can affect the outcomes of patients receiving certain antidepressant medications. Utilizing PGt can help prevent the trial and error in prescribing antidepressants and lead to better patient outcomes in the treatment of depression. Pharmacists can utilize genetic information to help primary care physicians choose drug regimens that are more likely to benefit their patients. Although advances are being made in this subject matter, some major efforts of future research will evaluate the efficacy of drug regimens and the dosing of drugs based on patient genetics

Quality Protein Maize Germplasm Characterized for Amino Acid Profiles and Endosperm Opacity

Quality protein maize (QPM) is improved over normal (non-QPM) maize in grain concentrations of the essential amino acids lysine and tryptophan. Quality protein maize has a long history as tropical adapted germplasm, but little effort has been made to incorporate temperate or sub-tropical germplasm for temperate adaptation and interactions between different modifier loci in these backgrounds are poorly understood. A design-II mating scheme including new temperate and subtropical lines produced 69 hybrids. Large hybrid genetic variation components resulted in substantial broad-sense heritability H2 estimates, specifically tryptophan (0.46) and endosperm opacity (0.82). A microbial assay for amino acid estimation proved robust across diverse environments with minimal genotype × environment (G×E) effects. Endosperm opacity had no G×E effects across both Texas and Iowa locations demonstrating stability for this trait. Endosperm opacity primarily followed an additive, midparent trend, with a few hybrids deviating from the trend (36%) suggesting a complex nature of multiple modifier loci across diverse germplasm. The top QPM hybrid outperformed the top commercial hybrid by 35 and 30% for lysine and tryptophan as a proportion of grain, respectively. QPM line Tx832 was a parent of top hybrids for lysine and tryptophan, and the highest noncommercial hybrids for methionine. Minimal correlations with yield and other traits suggest that future breeding should result in QPM hybrids with increasingly competitive yields

Combating Antibiotic Resistance in the 21st Century

Antibiotic resistance is one of the most significant challenges facing the medical community today. In response, the Centers for Disease Control and Prevention (CDC) created a list of the greatest antibiotic resistance threats, a number of which are gram-positive bacteria. The cell wall of these organisms has long been a favored target of antibiotic therapies, but the development of numerous resistance mechanisms has led to widespread resistance against nearly all major antibiotic compounds on the market. The medical community is faced with the task of developing better antibiotic compounds that preclude the spread of bacterial resistance and also increasing the screening of natural antimicrobials from organisms not readily cultured in the laboratory. The iChip is a novel in situ cultivation device that allows researchers to grow cultures of bacterial species that could not otherwise be cultured in a laboratory setting. This technology has already led to the discovery of several promising novel antimicrobial compounds, including teixobactin. This depsipeptide has excellent activity in vitro against gram-positive organisms including Clostridium difficille, Bacillus anthracis, Enterococcus strains (including vancomycin resistant enterococci), Mycobacterium tuberculosis and Staphylococcus aureus. Pharmacists have a significant impact in the education of patients receiving antibiotic therapy about the issue of drug resistance and how alternative courses of treatment may be needed if antibiotic therapy is unsuccessful

Trametinib and Dabrafenib: New Agents for Advanced Stage Melanoma

Melanoma, the deadliest form of skin cancer, is caused primarily by exposure to ultraviolet radiation. Tumor formation occurs early in disease progression and can easily metastasize. The development of the disease can be described by one of four stages, characterized by tumor size and risk of spreading. The B-rafprotein plays an important role in cell proliferation and has the ability to develop a mutation for continuous activation, resulting in uncontrolled cell growth. Sixty percent of melanomas possess a V600E mutation in the BRAF gene. Recently, drug developers have turned the focus of melanoma treatments toward preventing the activation of the mitogenactivated protein kinase (MAPK) pathway and, consequently, cell proliferation is decreased and leads to cell cycle arrest. Two of the newest U.S. Food and Drug Administration (FDA)approved medications for the treatment of melanoma are trametinib (Mekinist®) and dabrafenib (Taflinar®). It is important for pharmacists to understand the benefits, side effects and potential warnings involved with trametinib and dabrafenib so they are better able to educate their patients on these innovations in melanoma treatment

Cannabinoids for the Treatment of Chronic Headaches

Species of the Cannabis plant genus were among the earliest medicinal plants cultivated by man, with historical accounts of their medicinal uses dating back before the Common Era. Despite its current legal status, Cannabis has garnered nationwide attention as a therapeutic agent for various disease states, including chronic headaches, due to its medical indications as an antispastic, analgesic, antiemetic, neuroprotective and anti-inflammatory agent. Since headaches have a high prevalence in the American population and greatly impair simple daily aspects of living, chronic headaches have become a particular point of interest in regard to the therapeutic potential of Cannabis. Clinical trials and case reports have shown that Cannabis administration for headaches has greatly improved the quality of life and decreased the use of adjuvant medications for some patients. Studies are limited and conflicting, mostly due to the legal issues associated with Cannabis. Pharmacists play a major role in managing patients who are treating their chronic headaches and need to be able to educate patients about Cannabis. Patients may consider trying to treat their headaches with Cannabis even though it has legal restrictions regarding its use and is not U.S. Food and Drug Administration (FDA) approved. Pharmacists should understand federal and state restrictions, drug interactions, potential health risks, psychoactive effects and types of delivery systems for Cannabis use