Space-Based Capstone: Public-Private-Academic Partnership in the Making

The Electronic Systems Engineering Technology (ESET) Program at Texas A&M University provides a recognized undergraduate program with an emphasis in electronics, communication, embedded systems, testing, instrumentation and control systems. The program combines engineering and industrial knowledge and methods to develop, design, and implement new innovative products through a two-semester long Senior Capstone Project. Capstone is designed to prepare future engineers by bridging the gap between the classroom and industry. Students are required to form teams of two to six members which allows them to develop the skills necessary to succeed in a diverse industry setting. Each team is required to use their knowledge and skills to design, develop, document, and deliver a real-world project equivalent to the assignments they will soon receive as professional engineers. Following NASA’s approval for funding the development of a research facility named Hermes, a Capstone team, named Microgravity Automated Research Systems (MARS), was sponsored by T STAR, a local space commercialization company, to develop the electronics portion of the facility. Hermes will reside on the International Space Station for five years in the hopes of streamlining the development of experiments that require extended periods of time in microgravity environments. The Hermes facility will host and manage up to four experiments at a time while allowing for the downlink of experiment data to an Earth station, and the uplink of commands to change experiment parameters. Experiments will adhere to a power budget and communication standard established by MARS so that experiments can be swapped out during the facility’s lifetime. MARS will work with the Mobile Integrated Solutions Laboratory (MISL), an undergraduate applied research lab, in order to prepare them to maintain support for Hermes in the future.Cockrell School of Engineerin

Insight into the palladium catalyzed oxidative arylation of benzofuran: Heteropoly acid oxidants evoke a Pd(II)/Pd(IV) mechanism

The effects of oxidant and organic acid additives on the oxidative cross-coupling reactions of electron rich heterocycles such as benzofuran with benzene were studied. Both regioselectivity and reaction rate could be controlled by varying the condition parameters. Furthermore, mechanistic insight was achieved via kinetic studies which indicate that reactions that are oxidized by the heteropoly acid H4PMo11VO40 operate via a Pd(II)/Pd(IV) mechanisms, while reactions oxidized by either AgOAc or Cu(OAc)2 operate by a Pd(II)/Pd(0) mechanism

Natural Categorization: Electrophysiological Responses to Viewing Natural Versus Built Environments

Environments are unique in terms of structural composition and evoked human experience. Previous studies suggest that natural compared to built environments may increase positive emotions. Humans in natural environments also demonstrate greater performance on attention-based tasks. Few studies have investigated cortical mechanisms underlying these phenomena or probed these differences from a neural perspective. Using a temporally sensitive electrophysiological approach, we employ an event-related, implicit passive viewing task to demonstrate that in humans, a greater late positive potential (LPP) occurs with exposure to built than natural environments, resulting in a faster return of activation to pre-stimulus baseline levels when viewing natural environments. Our research thus provides new evidence suggesting natural environments are perceived differently from built environments, converging with previous behavioral findings and theoretical assumptions from environmental psychology

lentiglobin gene therapy for transfusion dependent β thalassemia outcomes from the phase 1 2 northstar and phase 3 northstar 2 studies

Introduction Transfusion-dependent β-thalassemia (TDT) is a severe genetic disease characterized by anemia, iron overload and serious comorbidities for which gene therapy may be an effective treatment option. LentiGlobin gene therapy contains autologous CD34+ hematopoietic stem cells (HSCs) transduced ex vivo with the BB305 lentiviral vector (LVV) encoding β-globin with a T87Q substitution. Objective Evaluate the efficacy and safety of LentiGlobin in patients with TDT in the phase 1/2 Northstar (HGB-204; NCT01745120) and phase 3 Northstar-2 (HGB-207; NCT02906202) studies. Methods Patients with TDT (≥100 mL/kg/yr of red blood cells [RBCs] or ≥8 RBC transfusions/yr) received G-CSF and plerixafor for mobilization and HSCs were transduced with the BB305 LVV. Patients underwent single agent busulfan myeloablative conditioning, were infused with transduced cells, and were followed for engraftment, safety, and efficacy. Statistics are presented as median (min – max). Results As of March 7, 2018, 18 patients (12 – 35 yrs) were treated in Northstar (follow-up 32.1 [23.1 – 41.9] months) and as of May 15, 2018, 11 patients (12 – 24 yrs) were treated in Northstar-2 (follow-up 8.5 [0.3 – 16.2] months). Patients received a median cell dose of 8.0 (5.0 – 19.4) CD34+ cells × 106/kg in both studies. The median time to neutrophil and platelet engraftment in both studies was 19 (14 – 30) days and 44 (19 – 191) days, respectively; 1 patient in Northstar-2 (0.3 months follow-up) had not engrafted at time of analysis. Of 6 patients with platelet engraftment ≥ Day 60, 4 had non-serious bleeding events prior to engraftment. All 6 had intact spleens and 3/6 received G-CSF between Days 0 – 21. Both factors appeared associated with time to platelet engraftment. In Northstar, 8/10 patients with non-β0/β0 genotypes and 2/8 patients with β0/β0 genotypes achieved transfusion independence (TI; weighted average hemoglobin [Hb] ≥ 9 g/dL without RBC transfusions for ≥ 12 months). Median Hb during TI was 10.0 (9.3 – 13.1) g/dL. In Northstar-2, 7/8 patients with non-β0/β0 genotypes and ≥ 6 months follow-up stopped RBC transfusions with Hb of 11.1 – 13.3 g/dL at last visit; the first patient treated achieved TI. Non-hematologic grade ≥ 3 adverse events post-infusion in ≥ 5/29 (15%) patients were stomatitis, febrile neutropenia, and pharyngeal inflammation. Veno-occlusive liver disease attributed to busulfan occurred in 4/29 patients (Table 1). There was no transplant-related mortality, vector-mediated replication competent lentivirus, or clonal dominance. Conclusion In Northstar, 80% of patients with non-β0/β0 genotypes achieved TI and early Northstar-2 data suggest that patients can achieve near-normal Hb without transfusions. The safety profile of LentiGlobin is consistent with myeloablative busulfan conditioning. Longer time to platelet engraftment was observed in few patients, but no graft failure or deaths were reported

Rpl13a small nucleolar RNAs regulate systemic glucose metabolism

Small nucleolar RNAs (snoRNAs) are non-coding RNAs that form ribonucleoproteins to guide covalent modifications of ribosomal and small nuclear RNAs in the nucleus. Recent studies have also uncovered additional non-canonical roles for snoRNAs. However, the physiological contributions of these small RNAs are largely unknown. Here, we selectively deleted four snoRNAs encoded within the introns of the ribosomal protein L13a (Rpl13a) locus in a mouse model. Loss of Rpl13a snoRNAs altered mitochondrial metabolism and lowered reactive oxygen species tone, leading to increased glucose-stimulated insulin secretion from pancreatic islets and enhanced systemic glucose tolerance. Islets from mice lacking Rpl13a snoRNAs demonstrated blunted oxidative stress responses. Furthermore, these mice were protected against diabetogenic stimuli that cause oxidative stress damage to islets. Our study illuminates a previously unrecognized role for snoRNAs in metabolic regulation

Plasma sterols and vitamin D are correlates and predictors of ozone-induced inflammation in the lung: A pilot study

BACKGROUND: Ozone (O3) exposure causes respiratory effects including lung function decrements, increased lung permeability, and airway inflammation. Additionally, baseline metabolic state can predispose individuals to adverse health effects from O3. For this reason, we conducted an exploratory study to examine the effect of O3 exposure on derivatives of cholesterol biosynthesis: sterols, oxysterols, and secosteroid (25-hydroxyvitamin D) not only in the lung, but also in circulation. METHODS: We obtained plasma and induced sputum samples from non-asthmatic (n = 12) and asthmatic (n = 12) adult volunteers 6 hours following exposure to 0.4ppm O3 for 2 hours. We quantified the concentrations of 24 cholesterol precursors and derivatives by UPLC-MS and 30 cytokines by ELISA. We use computational analyses including machine learning to determine whether baseline plasma sterols are predictive of O3 responsiveness. RESULTS: We observed an overall decrease in the concentration of cholesterol precursors and derivatives (e.g. 27-hydroxycholesterol) and an increase in concentration of autooxidation products (e.g. secosterol-B) in sputum samples. In plasma, we saw a significant increase in the concentration of secosterol-B after O3 exposure. Machine learning algorithms showed that plasma cholesterol was a top predictor of O3 responder status based on decrease in FEV1 (>5%). Further, 25-hydroxyvitamin D was positively associated with lung function in non-asthmatic subjects and with sputum uteroglobin, whereas it was inversely associated with sputum myeloperoxidase and neutrophil counts. CONCLUSION: This study highlights alterations in sterol metabolites in the airway and circulation as potential contributors to systemic health outcomes and predictors of pulmonary and inflammatory responsiveness following O3 exposure

In vivo evaluation of different formulation strategies for sustained release injectables of a poorly soluble HIV protease inhibitor

At present no scientific rationale exists for selecting a particular enabling strategy to formulate a poorly water-soluble drug, although this is crucial as it will influence the in vivo performance of the resulting formulation. This study provides an insight into this complicated decision making process for a poorly soluble human immunodeficiency virus (HIV) protease inhibitor based upon in vivo test results. A formulation strategy based on the molecular dispersion of this active pharmaceutical ingredient (API) into a biphasic matrix consisting of water-insoluble poly(lactic-co-glycolic acid) (PLGA) and water-soluble polyvinylpyrrolidone (PVP) was evaluated. The long-term in vivo performance of this strategy was compared to that of other solubility enhancing approaches by evaluating the exposure in male Beagle dogs. Solid dispersions, based on a PLGA/PVP matrix, were compared to solid dispersions in a pure water-insoluble PLGA matrix. Additionally these solid dispersion strategies were compared to the strategy of particle size reduction by means of an API microsuspension. The in vivo performance of the various formulations over a period of 28 days after intramuscular injection was evaluated by the observed initial burst release, plasma concentration-time profiles, time at which maximum plasma levels were reached (tmax,obs) and the estimated bioavailability. Compared to the other formulation strategies assessed, it was concluded that the addition of PVP in a PLGA matrix resulted in vivo in a more sustained release as well as a higher amount of drug released from the polymeric matrix. This was explained based on the structure of these binary PLGA/PVP matrices where the pore network originating from rapidly dissolving PVP plays a crucial role. Moreover, the results suggest that the release of this type of formulations could be delayed by increasing the amount of PLGA in the formulation

Increasing follow-up questionnaire response rates in a randomized controlled trial of telehealth for depression: three embedded controlled studies

Background: Attrition is problematic in trials, and may be exacerbated in longer studies, telehealth trials and participants with depression – three features of The Healthlines Study. Advance notification, including a photograph and using action-oriented email subject lines might increase response rates, but require further investigation. We examined the effectiveness of these interventions in three embedded Healthlines studies. Methods: Based in different trial sites, participants with depression were alternately allocated to be pre-called or not ahead of the 8-month follow-up questionnaire (Study 1), randomized to receive a research team photograph or not with their 12-month questionnaire (Study 2), and randomized to receive an action-oriented (‘ACTION REQUIRED’) or standard (‘Questionnaire reminder’) 12-month email reminder (Study 3). Participants could complete online or postal questionnaires, and received up to five questionnaire reminders. The primary outcome was completion of the Patient Health Questionnaire (PHQ-9). Secondary outcome measures were the number of reminders and time to questionnaire completion. Results: Of a total of 609 Healthlines depression participants, 190, 251 and 231 participants were included in Studies 1–3 (intervention: 95, 126 and 115), respectively. Outcome completion was ≥90 % across studies, with no differences between trial arms (Study 1: OR 0.38, 95 % CI 0.07–2.10; Study 2: OR 0.84, 95 % CI 0.26–2.66; Study 3: OR 0.53 95 % CI 0.19–1.49). Pre-called participants were less likely to require a reminder (48.4 % vs 62.1 %, OR 0.41, 95 % CI 0.21–0.78), required fewer reminders (adjusted difference in means −0.67, 95 % CI −1.13 to −0.20), and completed follow-up quicker (median 8 vs 15 days, HR 1.35, 95 % CI 1.00–1.82) than control subjects. There were no significant between-group differences in Studies 2 or 3. Conclusions: Eventual response rates in this trial were high, with no further improvement from these interventions. While the photograph and email interventions were ineffective, pre-calling participants reduced time to completion. This strategy might be helpful when the timing of study completion is important. Researchers perceived a substantial benefit from the reduction in reminders with pre-calling, despite no overall decrease in net effort after accounting for pre-notification