The Effects of Glutathione and Its Derivatives on the Survival of Mycobacterium bovis-BCG Vegetative and Persistent Organisms

Mycobacterium tuberculosis is responsible for nearly 2 million deaths yearly. Upon inhalation,mycobacteria are engulfed by alveolar macrophages. These cells produce reactive oxygen and nitrogen intermediates (ROI’s and RNI’s), which normally kill pathogens, but are ineffective against invading mycobacteria. What ensues, is the formation of a tubercle to sequester the infected macrophages, and the initiation of a latent tuberculosis infection, in which the mycobacteria enter a state of non-replicative persistence (NRP). Glutathione (GSH), a host tripeptide thiol-based detoxification molecule, protects host cells from ROI/RNI toxicity.Recently, it has been demonstrated that GSH is toxic to in vitro and early infection mycobacteria, but no studies determined whether GSH is toxic to latent mycobacteria. To further elucidate the impact of GSH on mycobacteria, we exposed mid-logarithmic (mid-log) and NRP-induced M.bovis-BCG to glutathione in its reduced (GSH), oxidized (GSSG), and nitric oxide associated (GSNO) forms, for five days. We have demonstrated that the growth of mid-log M. bovis-BCG (BCG) is inhibited by 4 mM GSH, and killed by 8 mM GSH. The growth of NRP mycobacteria exposed to 4 mM GSH was inhibited similar to that of unexposed NRP mycobacteria. In contrast,the growth of NRP BCG is stimulated four fold following exposure to 8 mM GSH. We conclude that exposure of NRP BCG to 8 mM GSH stimulates exit from the NRP state into an actively metabolizing state. 4 and 8 mM GSSG and GSNO inhibited the growth of mid-log BCG; however, NRP BCG exposed to GSSG and GSNO inhibited growth similar to that of unexposed NRP BCG. These results were confirmed by performing viability studies, and analysis of freeintracellular cytoplasmic ATP concentrations. Initially hypothesized, the toxicity to GSH was due to redox potential imbalances within mycobacterial cytoplasm. Mycobacteria contain MSH detoxification system (5), to cope with GSH. However, the mechanism of interaction between the activation of the system and growth inhibition in mycobacteria is poorly understood. HPLC analyses on mid-log and NRP BCG cytoplasms exposed to 4 and 8 mM GSH demonstrated that the activation of the detoxification system and the oxidative stress of the mid-log and NRP cytoplasms were similar. This suggests that the activation of the detoxification system and the oxidative state of the mycobacterial cytoplasm may not play a direct role in mycobacterial growth inhibition and/or exit from the NRP state

Is the NCAA Finally Loosening Its Iron Grip On College Basketball By Allowing Underclassmen the Opportunity to Return to College After Declaring for the NBA Draft?

The National Collegiate Athletic Association (NCAA) Oversight Committee has proposed a new rule that allows undergraduate college basketball players to reject the National Basketball Association (NBA) and return to school after they have submitted their name for the draft. This rule represents a great change in the policies that regulate college sports, specifically college basketball. The NCAA has ruled college basketball with an iron fist, but with this new proposal, it seems that it is beginning to help our college athletes sustain some semblance of a normal life after their playing days are over. Importantly, the rule is merely a proposal. The NCAA will vote on the rule, and if passed, it will be immediately implemented for the 2016 NBA Draft. The objective of this Comment is to show the impact the proposed rule will have on the NCAA, universities, basketball players, and the NBA

THE ROLE OF AGULHAS LEAKAGE IN PLIOCENE CLIMATE CHANGE

The late Pliocene (2.6-3.3 Myr) was an epoch of gradual cooling, with expanding Antarctic ice sheets and sea ice preceding a general Northern Hemisphere glaciation. A decline in the strength of the Atlantic Meridional Circulation (AMOC) in the late Pliocene may have decreased Southern Hemisphere oceanic heat transport into the Northern Hemisphere; pre-conditioning it for glaciation. A common explanation for a weakening of the AMOC in paleoclimate is freshwater forcing into the North Atlantic. In this thesis, I posit that a northward shift in the Southern Hemisphere westerlies in the late Pliocene, due to an expanded Antarctic ice sheet, weakens the Agulhas Leakage — a narrow current flowing past the Cape of Good Hope that connects the Indian and Atlantic Ocean basins. Since the Agulhas Leakage transports relatively salty waters from the Indian Ocean into the South Atlantic, it could alter the AMOC by changing the density stratification in North Atlantic deep-water formation sites. To test this hypothesis, I use a high-resolution (1/6°) ocean model, the MITgcm, with passive and Lagrangian particle-based tracers to quantify changes in Agulhas Current leakage. Following a spin-up simulation, I run two experiments, an experiment with a prescribed 6° northward shift in the southern westerlies and a control experiment with unchanged winds, both run for 58 model-years. I found a quick (\u3c 10 year) decline in Agulhas Leakage volume in the northward wind perturbation experiment that, by the experiment end, led to changes in North Atlantic surface densities, including in areas of North Atlantic deep water formation (NADW), with an increase in vertical stratification in the perturbation experiment suggesting a weakening of the NADW. The findings from my research indicate that Agulhas Leakage water has a pathway into the North Atlantic and that the northward wind perturbation decreased the influx of Agulhas water into the North Atlantic, with corresponding implications for salt and heat transport. A northward shift in the southern westerlies is therefore a plausible mechanism for inter-hemisphere heat transport, altering the surface branch of the AMOC and inter-hemisphere heat transport and as such likely played a role in altering climate during the late Pliocene

The assessment of right ventricular function in infants with pulmonary hypertension

Pulmonary hypertension is a cause of significant morbidity and mortality in newborn infants. Right ventricular function, or dysfunction, is an important consequence of pulmonary hypertension and may be an important determinant of disease severity.This work aimed to improve the assessment and management of infants with pulmonary hypertension by:1. identifying non-invasive measures of right ventricular function in infants2. determining the mechanisms of right ventricular dysfunction3. demonstrating the variability of the relationship between RV function and PAPFive echocardiographic measures were selected to assess RV function; tricuspid valve Doppler inflow, right ventricular output (RVO), RV myocardial performance index (RVMpi), pulse wave tissue Doppler imaging (PWTDI) and colour tissue Doppler imaging (CTDI). Using a case-control design each measure was performed in a control group of infants with normal cardiovascular function, and a PHT group of infants with elevated pulmonary artery pressure. This design allowed assessment of each measure, and provided normative data for those measures (RVmpi, PWTDI and CWTDI) which had not previously been performed in infants.All measures were found to be technically feasible, and to provide some quantification of haemodynamic performance. However, the load-dependence of TV Doppler and the global nature of RVmpi and RVO meant that these measures could not be considered pure measures of RV myocardial function alone. By contrast, Tissue Doppler imaging measures allowed separate assessment of systolic and diastolic function. This study was an important first demonstration of the feasibility and application of TD1 in an infant disease state. Future studies are indicated to assess the load-dependence of TDI measures in infants, the repeatability of the technique and use of TDI in other infant diseases with myocardial dysfunction.The mechanisms of RV dysfunction in infants with PHT were investigated by comparison of RV function data between control and PHT groups. Accepting the limitations of the measures used, the results indicated the presence of impaired systolic and early diastolic function in infants with PHT. This finding highlighted the importance of diastolic dysfunction in the failing infant heart, and the usefulness of measures such as TDI which allow assessment of both systolic and diastolic dysfunction. There are also potential therapeutic implications, and the theoretical benefit of drugs with both inotropic and lusitropic actions in this setting was an important area identified for future research.Finally, no linear relationship was identified between RV function measures and PAP in the PHT group. It was concluded that pulmonary artery pressure should not be used as a proxy measure of RV function in infants and thus emphasised the importance of directly assessing RV function in infants with pulmonary hypertension

Textron Aviation Strategic Analysis

This paper is an analysis of current market conditions and issues that Textron Aviation faces. The analysis includes major competitors, suppliers, and the current fleet in production. The many other factors that affect Textron Aviation are also incorporated to provide courses of action. The other factors include economic, political/legal, sociocultural, global, demographic, and technology. The analytical tools to support the information collected are Porter’s Five Forces and SWOT analysis. Porter’s Five Forces provides the reader with a structured layout in terms of comparing Textron Aviation’s competition and the strength of its profitability. SWOT-analysis helps the reader understand the firm’s internal activities and provide insight into the performance of management. This also can show how effective Textron Aviation is in creating a competitive advantage in the business jet segment. This research is completed and complimented with thorough recommendations for Textron Aviation to improve and show which advantages they have

Cobalt Silicide Formation and Patterning Technology

The goal of this investigation was to develop a cobalt silicide formation process as a stepping stone to investigate a novel patterning technique known as, LOCOSI (LOCal Oxidation of Silicide). Cobalt suicide films were formed by sputter depositing cobalt onto silicon wafers then annealed at temperatures varying from 750 - 1000°C using two methods. The first method was a conventional anneal using a horizontal furnace using a forming gas ambient. The second method was a RTA (Rapid Thermal Anneal) using a nitrogen ambient. The RTA process for silicidation provided essentially a continuous film with minimal cracking, whereas the furnace anneals resulted in noncontinuous cobalt suicide films. The patterning of the films, which requires a patterned oxidation mask similar to the LOCOS (LOCal Oxidation of Silicon) process, was unsuccessful

Equity Allocation in Startups

For latest version: please go to https://academicentrepreneurship.pubpub.org/pub/ug7kijaq/release/5 Founders should not necessarily split equity evenly among cofounders; unequal splits can help prevent team dissonance and renegotiations as the company develops. The timing of equity splits is critical, with most experts favoring early discussions of own­ership. Companies should strive for capitalization tables that are simple in structure and easy to understand. Capitalization tables should have equity pools set aside to anticipate non-founder compen­sation of new hires. Equity dilution from future investors should be viewed in terms of the business’s overall financial strategy

Marketing in an Academic Institution

Mapping out key stakeholders at an institution and how they connect to each other can help strengthen one’s understanding of the ecosystem in which the company will start. Proactive marketing through targeted meetings and participation in on-campus events can help build one’s network. Becoming aware of the various marketing channels at an academic medical institution is critical for promoting one’s startup. Winning small grants can help build traction through an early reputation of success