In silicoAnalysis of the Structural Properties of PSMA and its Energetic Relationship with Zn as Cofactor

The prostate-specific membrane antigen (PSMA) is a 100 kDa type II transmembrane glycoprotein with enzymatic activity similar to the family of zinc-dependent exopeptidases. This protein is of great medical and pharmacological interest as overexpression in prostate cells is related to the progression of prostate cancer; therefore, it represents an important target for the design of radiopharmaceuticals. The presence of two Zn2+ ions in the active site is crucial to the enzymatic activity and the design of high-affinity inhibitors. The amino acid residues coordinating these ions are highly conserved in PSMA orthologs from plants to mammals, and site-mutagenesis assays of these residues show a loss of enzymatic function or reduction of the kinetic parameters. In the present work, we performed molecular dynamics simulation of PSMA with the purpose of characterizing it energetically and structurally. We elucidated the differences of PSMA with its two Zn+2 ions as cofactors and without them in the free energy profile, and in four structural parameters: root mean square deviations and root mean square fluctuations by atom and amino acid residue, radius of gyration, and solvent accessible surface area

The TechEdSat-N Series: A Collaborative Technology Development Platform in the Nano-Satellite Form Factor

The TechEdSat-1 (TES-1) was the first U.S. CubeSat to be deployed from the ISS (International Space Station). This permitted the initiation of a flight series that has recently de-orbited the 6th nano-satellite with subsequent numbers 7-10 under development. The nano-satellites range from 1U (1 unit) to 6U (TechEdSat-8) but have the critical ISS Safety design features standardized in order to focus on the particular experiment objectives. Incremental experimental development has included unique communication subsystems such as command/control of the nanosatellite through email commands -as well as a recent record for Wifi transmission. Also, the thermophysics of controlled drag devices (Exo-Brake) has been developed which will prelude sample return and planetary exploration applications. The successful "rapid incremental experiment" approach has also been incorporated into collaborations with academia, permitting professors/student interns to be exposed to the rigors of space mission hardware design and execution. The TechEdSat-8, a linear 6U configuration, allows for 5 different groups to contribute an "experiment, sensor, or sub-system" through a well-defined common interface. Lastly, the flying laboratory concept is helpful in developing future interplanetary nano-satellite subsystems which will advance exploration goals by allowing rapid demonstration/validation first in LEO (Low Earth Orbit)

TES-8: Advanced Exo-Brake, VR and COM Experiments

The TES-8 was jettisoned from the International Space Station on January 31, 2019. As an orbital laboratory and 8th in on-going series, the design makes use of a standard set of interfaces and safety features that permit rapid re-flight. On this flight, an advanced Exo-Brake is flown with de-orbit targeting capability that will engender sample return capability from LEO platforms. A Virtual Reality data recording system uses stereo imaging and efficient data-compression with an NVIDIA GPU (Graphics Processing Unit) to permit compression and transmission of very large data files. An SDR (Software Defined Radio) will download data to the NEN (Near Earth Network) for the first time - demonstrating potential use in cis-lunar space using S-band. For the first time, a comparison will be made regarding the functionality of the Iridium and Globalstar short burst data modems - as essential communication tools for future nano-sat projects. Lastly, the 7 micro-processors and 4 cameras provide an excellent learning platform for university students and NASA young professionals

Providing Small Satellite Communications Using the NOAA GOES Satellite

The results of a LEO to GEO communication system using the NOAA GOES (Geostationary Operational Environmental Satellite) DCS (Data Collection System) are presented. The DCS system was designed to collect climate-related data from remote unmanned stations. Data are uplinked to one of the two operational satellites via an aggregated link to the NASA Wallops Facility. The modified LEO transmitter, one of the 7 transmitters flown on the TechEdSat-8 nano-satellite, is designed to compensate for the Doppler effects to ensure the communication link. Though a slow data rate initially, the system may offer another convenient means of transmitting data from LEO to ground stations any time during an orbit. The experiment will allow for an assessment of this as a future communication system development path - as well as the very interesting extension of the system for a comparable system at Mars for climatic surveys from ground stations (hence, a Mars radio)

Frequency of CYP2C9 (*2, *3 and IVS8‑109A>T) allelic variants, and their clinical implications, among Mexican patients with diabetes mellitus type 2 undergoing treatment with glibenclamide and metformin

The majority of Mexican patients with diabetes mellitus type 2 (DMT2) (67.9-85.0%) are prescribed sulpho nylureas (SUs), which are metabolized by cytochrome P450 2C9 (abbreviated as CYP2C9). SUs are a type of oral anti-diabetic compound which inhibit ATP-sensitive potas sium channels, thus inducing glucose-independent insulin release by the β-pancreatic cells. The wide variability reported in SU responses has been attributed to the polymorphisms of CYP2C9. The present study aimed to describe CYP2C9 polymorphisms (*2, *3 and IVS8‑109T) within a sample of Mexican patients with DMT2, while suggesting the potential clinical implications in terms of glibenclamide response vari ability. From a sample of 248 patients with DMT2 who initially consented to be studied, those ultimately included in the study were treated with glibenclamide (n=11), glibenclamide combined with metformin (n=112) or metformin (n=76), and were subsequently genotyped using a reverse transcrip tion-quantitative polymerase chain reaction (PCR), end-point allelic discrimination and PCR amplifying enzymatic restric tion fragment long polymorphism. Clinical data were gathered through medical record revision. The frequencies revealed were as follows: CYP2C9*1/*1, 87.5%; *1/*2, 6.5%; *1/*3, 5.2%; and CYP2C9, IVS8‑109A>T, 16.1%. Glibenclamide significantly reduced the level of pre‑prandial glucose (P<0.01) and the percentage of glycated hemoglobin (%HbA1c; P<0.01) for IVS8‑109A>T compared with combined glibenclamide and metformin treatment. Concerning the various treatments with respect to the different genotypes, the percentages obtained were as follows: Glibenclamide A/A, HbA1c<6.5=33.3%; glibenclamide + metformin A/A, HbA1c<6.5=24.6%; gliben clamide A/T, HbA1c<6.5=33.3%; glibenclamide + metformin A/T, HbA1c<6.5=25%; glibenclamide T/T, HbA1c<6.5=100%; and glibenclamide + metformin T/T, HbA1c<6.5=12.5%. Altogether, these results revealed that, although genetically customized prescriptions remain a desirable goal to increase the chances of therapeutic success, within the studied popu lation neither allelic variants nor dosages demonstrated a clear association with biomarker levels. A key limitation of the present study was the lack of ability to quantify either the plasma concentrations of SU or their metabolites; therefore, further, precise experimental and observational studies are required

Factors of the epidemiological triad that influence the persistence of human papilloma virus infection in women with systemic lupus erythematosus

We studied the epidemiologic triad-related factors influencing human papilloma virus (HPV) persistence in Mexican women with systemic lupus erythematosus (SLE). Patients aged ?18 years with SLE (American College of Rheumatology criteria), with and without HPV persistence, were selected. Groups were analyzed by (1) host: clinical disease characteristics; (2) agent: (I) infectious (prevalence, incidence, HPV genotype and co-infections (?2 HPV genotypes or mycoplasmas)), (II) chemical (contraceptives and immunosuppressive drugs) and (III) physical (vitamin D deficiency) and (3) environment. A total of 121 SLE patients were selected over a two-year period. (1) Host: mean age 45.8 years and disease duration 12.7 years. (2) Agent: (I) infectious. HPV infection prevalence in the second sample was 26.4%, high-risk HPV genotypes 21.5% and co-infections 7.4%. HPV infection incidence was 13.2%, persistence 13.2% and clearance 15.7%. (II) Chemical: use of oral hormonal contraceptives 5% and immunosuppressive treatment 97.5%. (III) Physical: Vitamin D levels were similar in both groups. (3) Environment: (I) natural. A total of 60.6% of patients were residents of Puebla City. (II) Social: The mean education level was 10.9. Poverty levels were: III degree 52.4%, IV degree 28% and II degree 17%. (III) Cultural behavioral: Onset of sexual life was 20.5 years, 10% had ?3 sexual partners and 51.2% were postmenopausal. In conclusion, no factor of the epidemiologic triad was associated with HPV infection prevalence. © The Author(s) 2018

Modeling the Exo-Brake and the Development of Strategies for De-Orbit Drag Modulation

The Exo-Brake is a simple, non-propulsive means of de-orbiting small payloads from orbital platforms such as the International Space Station (ISS). Two de-orbiting experiments with fixed surface area Exo-Brakes have been successfully conducted in the last two years on the TechEdSat-3 and -4 nano-satellite missions. The development of the free molecular flow aerodynamic data-base is presented in terms of angle of attack, projected front surface area variation, and altitude. Altitudes are considered ranging from the 400km ISS jettison altitude to 90km. Trajectory tools are then used to predict de-orbit/entry corridors with the inclusion of the key atmospheric and geomagnetic uncertainties. Control system strategies are discussed which will be applied to the next two planned TechEdSat-5 and -6 nano-satellite missions - thus increasing the targeting accuracy at the Von Karman altitude through the proposed drag modulation technique

Pharmacogenetics of Metformin Transporters Suggests No Association with Therapeutic Inefficacy among Diabetes Type 2 Mexican Patients

Mexico has been under official epidemiological alert due to diabetes since 2016. This study presents new information on the frequency and variants of metformin transporters OCT1, OCT2, OCT3, ABCB1, and CYP2C9 variants as well. It also reports the association with HbA1c control on 103 DMT2 patients. They were genotyped through real-time PCR (TaqMan assays) and grouped according to treatment: metformin and metformin + glibenclamide. Metformin plasmatic levels were determined through mass spectrometry. The analysis of HbA1c showed statistical significance across genotypes in polymorphisms rs72552763 (p = 0.022), rs622342 (p = 0.009), rs1128503 (p = 0.021), and rs2032582 (p = 0.009) within the monotherapy group. Bivariate analysis found no association between any polymorphism and HbA1c control. Two logistic regression models accounted for two diplotypes in OCT1 and ABCB1, including statistically significant covariates. The first model yielded significance in age (p = 0.026), treatment period [p = 0.001], BMI ≥ 25 kg/m2 (p = 0.043), and combined therapy (p < 0.001). There was no association with GAT/GAT of rs72552763 or A/A rs622342 in OCT1. The second model yielded significance in age (p = 0.017), treatment period (p = 0.001), BMI ≥ 25 kg/m2 (p = 0.042), and combined therapy (p < 0.001), finding no association with C/C of rs1128503 or G/G of rs2032582 in ABCB1. Our multinomial logistic regression results may benefit future predictive analyses in diabetic populations