Diversity and structure of human T-Cell receptor β-chain variable region genes

The nucleotide sequences of 27 T-cell receptor β cDNA clones isolated from a human peripheral lymphocyte library were determined and compared to five additional published sequences. These cDNA clones represent 22 distinct T-cell receptor β-chain variable region (Vβ) gene segment sequences, which fall into 15 different Vβ gene subfamilies, each containing six or fewer members. From this analysis, we estimate that the repertoire of expressed human Vβ genes is <59, apparently much smaller than the immunoglobulin heavy chain and light chain variable region (VH and VL) repertoires. Variability plots comparing these human Vβ regions with each other and with published mouse Vβ regions provide evidence for only four hypervariable regions homologous to those seen in comparisons of immunoglobulin V regions. Somatic hypermutation appears to be used infrequently, if at all, in these Vβ genes

Terminal deoxynucleotidyltransferase. Serological studies and radioimmunoassay

Mouse antisera against calf terminal deoxynucleotidyltransferase (terminal transferase) have been prepared. The sera have been used to characterize terminal transferase both by studying inhibition of enzyme activity and by developing a competition radioimmunoassay using highly purified 125I-labeled terminal transferase. By either assay, anti-terminal transferase serum did not cross-react significantly with calf DNA polymerases alpha and beta, Escherichia coli DNA polymerase I, or the reverse transcriptase of Moloney mouse leukemia virus. The calf terminal transferase did, however, share cross-reactive but not identical determinants with human and murine terminal transferase. The radioimmunoassay could detect as little as 2 ng of terminal transferase/mg of soluble protein in a tissue extract. Thymocytes were found to contain 280 ng of terminal transferase/mg of cell protein or about 1 X 10^(5) molecules/cell; bone marrow had about 1% of the level of enzyme found in thymus. Extracts of spleen, peripheral white blood cells, lymph nodes, liver, muscle, and kidney all lacked detectable antigenicity of terminal transferase. These data indicate that terminal transferase is a tissue-specific enzyme and is not related to other DNA polymerases

Murine terminal deoxynucleotidyl transferase: cellular distribution and response to cortisone

The mouse thymus contains two forms of terminal deoxynucleotidyl transferase (TdT) which are distinguishable by the salt concentration necessary to elute them from a phosphocellulose column, by their distrubtion among the thymocyte subpopulations, and by their sensitivity to cortisone treatment. In the whole thymus the later eluting peak (peak II) is the predominant one with about 3-10% of the total activity appearing in peak I. Both peak I and peak II activities are most sensitively assayed by the polymerization of dGMP onto an oligo(dA) primer. The minor population of thymocytes which is less dense and cortisone-resistant contains a higher specific activity of peak I TdT. The majority of TdT activity is, however, found in the major population of thymocytes which occurs in the center region of a bovine serum albumin gradient and is cortisone-sensitive. A very low level of an activity indistinguishable from peak II TdT activity is also detected in the mouse bone marrow. Other tissues, such as spleen, liver, heart, and brain lack detectable amounts of TdT activity

A model-based systems engineering approach to space mission education of a geographically disperse student workforce

The Alabama Burst Energetics eXplorer (ABEX) is a 12U CubeSat commissioned by the Alabama Space Grant Consortium; its astrophysics mission is to study the low energy, prompt emission of Gamma-ray Bursts in both gamma and X-ray spectra. The ABEX program is unique in that its workforce is comprised of individuals at seven colleges and universities around the state of Alabama. ABEX management releases Requests for Proposals (RFP) for Senior Design (SD) projects or university research groups to design and build spacecraft subsystems; university faculty with experience and facilities for the development of that subsystem respond to the RFPs to create a team. ABEX supports undergraduate SD students, graduate student mentors, and faculty technical advisors for all spacecraft subsystems in both ground and flight mission segments. Each team has between 5-15 undergraduate students, meaning ABEX teaches spacecraft design to ~85 undergraduate students at any given time; ABEX may be the largest collegiate CubeSat program in the world. The undergraduate labor force turns over, or cycles to new students, every 4-8 months, so ABEX can teach hands-on spacecraft design to over 100 students every year and has taught over 200 to date. Two features of ABEX create a difficult Systems Engineering (SE) environment: the undergraduate labor force turnover rate and the geographically disperse workforce. Most subsystem teams exist within two-semester SD courses, but some teams, like Flight Software, only exist for one semester before the undergraduate team turns over. This means the student onboarding process must be efficient and the material hand-off process effective if any substantive contribution to the spacecraft is to be made in their brief course period. A Model-Based Systems Engineering (MBSE) Integrated System Model (ISM) was created using SysML as a full-program organization of mission requirements, subsystem architectures, verification and validation procedures, and team interaction tracking methodologies for workforce turnover effect mitigation with ISM-exported artifacts as central objects of stage-gate reviews. An ABEX website was created with processes for first-time student onboarding, ISM artifact dissemination, and intercollegiate document transfer in addition to being a public relations arm for the program. With education at the forefront of ABEX, educational requirements and performance measures detailing onboarding efficiency, workforce preparedness, and alumni vocation results are defined within the ISM and used to evaluate program education proficiency. Program organization, ISM structure, and spacecraft design is presented with an emphasis on quantifying student education as a result of program involvemen

Predictive Models for Pulmonary Artery Size in Fontan Patients

We developed models of pulmonary artery (PA) size in Fontan patients as a function of age and body surface area (BSA) using linear regression and breakpoint analyses based on data from 43 Fontan patients divided into two groups: the extracardiac conduit (ECC) group (n = 24) and the non-ECC group (n = 19). Model predictions were compared against those of a non-Fontan control group (n = 18) and published literature. We observed strong positive correlations of the mean PA diameter with BSA (r = 0.9, p \u3c 0.05) and age (r = 0.88, p \u3c 0.05) in the ECC group. The absolute percentage differences between our BSA and age model predictions against published literature were less than 16% and 20%, respectively. Predicted PA size for Fontan patients was consistently smaller than the control group. These models may serve as useful references for clinicians and be utilized to construct 3D anatomic models that correspond to patient body size or age

Systematic Review and Regression Modeling of the Effects of Age, Body Size, and Exercise on Cardiovascular Parameters in Healthy Adults

Purpose Blood pressure, cardiac output, and ventricular volumes correlate to various subject features such as age, body size, and exercise intensity. The purpose of this study is to quantify this correlation through regression modeling. Methods We conducted a systematic review to compile reference data of healthy subjects for several cardiovascular parameters and subject features. Regression algorithms used these aggregate data to formulate predictive models for the outputs—systolic and diastolic blood pressure, ventricular volumes, cardiac output, and heart rate—against the features—age, height, weight, and exercise intensity. A simulation-based procedure generated data of virtual subjects to test whether these regression models built using aggregate data can perform well for subject-level predictions and to provide an estimate for the expected error. The blood pressure and heart rate models were also validated using real-world subject-level data. Results The direction of trends between model outputs and the input subject features in our study agree with those in current literature. Conclusion Although other studies observe exponential predictor-output relations, the linear regression algorithms performed the best for the data in this study. The use of subject-level data and more predictors may provide regression models with higher fidelity. Significance Models developed in this study can be useful to clinicians for personalized patient assessment and to researchers for tuning computational models

Breast cancer biomarker detection through the photoluminescence of epitaxial monolayer MoS2 fakes

The following article appeared in Scientific Reports 10 (2020): 16039 and may be found at https://www.nature.com/articles/s41598-020-73029-9In this work we report on the characterization and biological functionalization of 2D MoS2 fakes, epitaxially grown on sapphire, to develop an optical biosensor for the breast cancer biomarker miRNA21. The MoS2 fakes were modifed with a thiolated DNA probe complementary to the target biomarker. Based on the photoluminescence of MoS2, the hybridization events were analyzed for the target (miRNA21c) and the control non-complementary sequence (miRNA21nc). A specifc redshift was observed for the hybridization with miRNA21c, but not for the control, demonstrating the biomarker recognition via PL. The homogeneity of these MoS2 platforms was verifed with microscopic maps. The detailed spectroscopic analysis of the spectra reveals changes in the trion to excitation ratio, being the redshift after the hybridization ascribed to both peaks. The results demonstrate the benefts of optical biosensors based on MoS2 monolayer for future commercial devicesThe research is supported by the MINECO (CTQ2017-84309-C2-2-R, CTQ2017-84309-C2-1-R, ELECTROBIONET, RED2018-102412-T) and Comunidad de Madrid (TRANSNANOAVANSENS, P2018/NMT4349) projects. ARC acknowledges Ramón y Cajal program (under contract number RYC-2015-18047

Association of maternal levothyroxine use during pregnancy with offspring birth and neurodevelopmental outcomes: a population-based cohort study

BACKGROUND: The influence of maternal levothyroxine treatment during pregnancy remains unclear. This study aimed to evaluate the associations of maternal levothyroxine treatment during pregnancy with the birth and neurodevelopmental outcomes in offspring. METHODS: This population-based cohort study was conducted among pregnant women using the Hong Kong Clinical Data Analysis and Reporting System. Mother-child pairs in Hong Kong from 2001 to 2015 were included and children were followed up till 2020. We defined the exposure group as mothers who were exposed to levothyroxine during pregnancy. Preterm birth and small for gestational age (SGA) were included as birth outcomes. Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) were included as neurodevelopmental outcomes. Odds ratios (OR) or hazard ratios (HRs) with a 95% confidence interval (CI) were evaluated to assess the association of gestational levothyroxine use with offspring birth and neurodevelopmental outcomes respectively, using propensity score fine-stratification weighting and a Cox proportional hazards regression model. RESULTS: Among 422,156 mother-child pairs, 2125 children were born from mothers exposed to levothyroxine during pregnancy. A significantly increased risk of preterm birth was observed in children with maternal levothyroxine exposure during pregnancy, when compared to mothers who had no history of thyroid-related diagnoses or prescriptions (weighted OR [wOR]: 1.22, 95% CI: 1.07, 1.39). Similarly, an increased risk of preterm birth was found among children of gestational levothyroxine users, when compared to children of mothers who had used levothyroxine before but stopped during pregnancy (wOR: 2.16, 95% CI: 1.09, 4.25). Sensitivity analysis, by excluding mothers exposed to psychotropic or antiepileptic medications before or during pregnancy, also indicated a similar increased risk of preterm birth regarding the gestational use of levothyroxine (wOR: 1.26, 95% CI: 1.10, 1.45). No significant association was observed for the risk of SGA, ADHD, and ASD. CONCLUSIONS: There is no evidence that gestational use of levothyroxine is associated with SGA, ADHD, or ASD in offspring. Gestational levothyroxine treatment is associated with a higher risk of preterm birth. Such risk might be confounded by the underlying maternal thyroid disease itself, however, we cannot completely exclude the possible effect of gestational L-T4 treatment on offspring preterm birth. Our findings provided support to the current guidelines on the cautious use of levothyroxine treatment during pregnancy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-022-02586-9

Regenerative peripheral nerve interfaces for real-time, proportional control of a Neuroprosthetic hand

Abstract Introduction Regenerative peripheral nerve interfaces (RPNIs) are biological constructs which amplify neural signals and have shown long-term stability in rat models. Real-time control of a neuroprosthesis in rat models has not yet been demonstrated. The purpose of this study was to: a) design and validate a system for translating electromyography (EMG) signals from an RPNI in a rat model into real-time control of a neuroprosthetic hand, and; b) use the system to demonstrate RPNI proportional neuroprosthesis control. Methods Animals were randomly assigned to three experimental groups: (1) Control; (2) Denervated, and; (3) RPNI. In the RPNI group, the extensor digitorum longus (EDL) muscle was dissected free, denervated, transferred to the lateral thigh and neurotized with the residual end of the transected common peroneal nerve. Rats received tactile stimuli to the hind-limb via monofilaments, and electrodes were used to record EMG. Signals were filtered, rectified and integrated using a moving sample window. Processed EMG signals (iEMG) from RPNIs were validated against Control and Denervated group outputs. Results Voluntary reflexive rat movements produced signaling that activated the prosthesis in both the Control and RPNI groups, but produced no activation in the Denervated group. Signal-to-Noise ratio between hind-limb movement and resting iEMG was 3.55 for Controls and 3.81 for RPNIs. Both Control and RPNI groups exhibited a logarithmic iEMG increase with increased monofilament pressure, allowing graded prosthetic hand speed control (R2 = 0.758 and R2 = 0.802, respectively). Conclusion EMG signals were successfully acquired from RPNIs and translated into real-time neuroprosthetic control. Signal contamination from muscles adjacent to the RPNI was minimal. RPNI constructs provided reliable proportional prosthetic hand control.https://deepblue.lib.umich.edu/bitstream/2027.42/146521/1/12984_2018_Article_452.pd

Semantic IoT Solutions - A Developer Perspective

Semantic technologies have recently gained significant support in a number of communities, in particular the IoT community. An important problem to be solved is that, on the one hand, it is clear that the value of IoT increases significantly with the availability of information from a wide variety of domains. On the other hand, existing solutions target specific applications or application domains and there is no easy way of sharing information between the resulting silos. Thus, a solution is needed to enable interoperability across information silos. As there is a huge heterogeneity regarding IoT technologies on the lower levels, the semantic level is seen as a promising approach for achieving interoperability (i.e. semantic interoperability) to unify IoT device description, data, bring common interaction, data exploration, etc.This work has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreements No.732240 (SynchroniCity) and No. 688467 (VICINITY); from ETSI under Specialist Task Forces 534, 556, 566 and 578. This work is partially funded by Hazards SEES NSF Award EAR 1520870, and KHealth NIH 1 R01 HD087132-01