Irradiation of 2N5339 n-p-n bipolar junction transistors (BJTs) with either 250-MeV protons or 10-keV X-rays shifts the input characteristics to lower values of <inline-formula> <tex-math ...notation="LaTeX">V_{\mathrm {BE}} </tex-math></inline-formula> while degrading the current gain and drive current. The degradation is consistent with increased recombination in the neutral base and emitter-base (E-B) depletion region. A decrease in collector current following proton irradiation suggests that recombination in the neutral base is significant. At a given ionizing dose, degradation is worse for proton irradiation than for X-ray irradiation due to the presence of displacement damage and a higher charge yield. A comparison of degradation produced by the two radiation sources suggests that ~40% of the excess base current resulting from 250-MeV proton irradiation is due to ionization damage. When compared with previous results for other devices, these results suggest that ionization-to-displacement damage ratios in bipolar devices may increase with proton energy in a way that is consistent with trends in charge yield and non-ionizing energy loss (NIEL).
Autonomic dysfunction has been implicated as a consequence of traumatic brain injury (TBI). Heart rate variability (HRV) may be a viable measure of autonomic dysfunction that could enhance ...rehabilitative interventions for individuals with TBI. This pilot study sought to assess the feasibility and validity of using the Zeriscope™ platform system in a real-world clinical setting to measure HRV in active-duty service members with TBI who were participating in an intensive outpatient program.
Twenty-five service members with a history of mild, moderate, or severe TBI were recruited from a military treatment facility. A baseline assessment was conducted in the cardiology clinic where point validity data were obtained by comparing a 5-min recording of a standard 12-lead electrocardiogram (ECG) output against the Zeriscope platform data.
Compared with the ECG device, the Zeriscope device had a concordance coefficient (
) of 0.16, falling below the standard deemed to represent acceptable accuracy in HR measurement (i.e., 0.80). Follow-up analyses excluding outliers did not significantly improve the concordance coefficient to an acceptable standard for the total participant sample. System Usability Survey responses showed that participants rated the Zeriscope system as easy to use and something that most people would learn to use quickly.
This study demonstrated promise in ambulatory HRV measurement in a representative military TBI sample. Future research should include further refinement of such ambulatory devices to meet the specifications required for use in a military active-duty TBI population.
•Overview of positive displacement pumps in portable analytical systems.•Discussion on factors that influence pressure/flow stability.•Overview of the use of closed-loop control of positive ...displacement pumps.•Discussion of recent developments in control systems that can enhance fluidic control.
The demand for accurate control of the flowrate/pressure in chemical analytical systems has given rise to the adoption of mechatronic approaches in analytical instruments. A mechatronic device is a synergistic system which combines mechanical, electronic, computer and control components. In the development of portable analytical devices, considering the instrument as a mechatronic system can be useful to mitigate compromises made to decrease space, weight, or power consumption. Fluid handling is important for reliability, however, commonly utilized platforms such as syringe and peristaltic pumps are typically characterized by flow/pressure fluctuations and slow responses. Closed loop control systems have been used effectively to decrease the difference between desired and realized fluidic output. This review discusses the way control systems have been implemented for enhanced fluidic control, categorized by pump type. Advanced control strategies used to enhance the transient and the steady state responses are discussed, along with examples of their implementation in portable analytical systems. The review is concluded with the outlook that the challenge in adequately expressing the complexity and dynamics of the fluidic network as a mathematical model has yielded a trend towards the adoption of experimentally informed models and machine learning approaches.
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Whether patients with monoclonal protein are at a higher risk for progression of kidney disease is not known. The goal of this study was to measure the association of monoclonal protein with ...progression to ESKD.
This was a retrospective cohort study of 2,156,317 patients who underwent serum creatinine testing between October 1, 2000 and September 30, 2001 at a Department of Veterans Affairs medical center, among whom 21,898 had paraprotein testing within 1 year before or after cohort entry. Progression to ESKD was measured using linked data from the US Renal Data System.
Overall, 1,741,707 cohort members had an eGFR≥60 ml/min per 1.73 m
, 283,988 had an eGFR of 45-59 ml/min per 1.73 m
, 103,123 had an eGFR of 30-44 ml/min per 1.73 m
and 27,499 had an eGFR of 15-29 ml/min per 1.73 m
. The crude incidence of ESKD ranged from 0.7 to 80 per 1000 person-years from the highest to lowest eGFR category. Patients with low versus preserved eGFR were more likely to be tested for monoclonal protein but no more likely to have a positive test result. In adjusted analyses, a positive versus negative test result was associated with a higher risk of ESKD among patients with an eGFR≥60 ml/min per 1.73 m
(hazard ratio, 1.67; 95% confidence interval, 1.22 to 2.29) and those with an eGFR of 15-29 ml/min per 1.73 m
(hazard ratio, 1.38; 95% confidence interval, 1.07 to 1.77), but not among those with an eGFR of 30-59 ml/min per 1.73 m
Progression to ESKD was attributed to a monoclonal process in 21 out of 76 versus seven out of 174 patients with monoclonal protein and preserved versus severely reduced eGFR at cohort entry.
The detection of monoclonal protein provides little information on ESKD risk for most patients with a low eGFR. Further study is required to better understand factors contributing to a positive association of monoclonal protein with ESKD risk in patients with preserved and severely reduced levels of eGFR.
Melanoma incidence continues to increase across many populations globally and there is significant mortality associated with advanced disease. However, if detected early, patients have a very ...promising prognosis. The methods that have been utilized for early detection include clinician and patient skin examinations, dermoscopy (static and sequential imaging), and total body photography via 2D imaging. Total body photography has recently witnessed an evolution from 2D imaging with the ability to now create a 3D representation of the patient linked with dermoscopy images of individual lesions. 3D total body photography is a particularly beneficial screening tool for patients at high risk due to their personal or family history or those with multiple dysplastic naevi-the latter can make monitoring especially difficult without the assistance of technology. In this perspective, we discuss clinical examples utilizing 3D total body photography, associated advantages and limitations, and future directions of the technology. The optimal system for melanoma screening should improve diagnostic accuracy, be time and cost efficient, and accessible to patients across all demographic and socioeconomic groups. 3D total body photography has the potential to address these criteria and, most importantly, optimize crucial early detection.
ObjectivesIdiopathic inflammatory myopathies (IIM) are a spectrum of rare autoimmune diseases characterised clinically by muscle weakness and heterogeneous systemic organ involvement. The strongest ...genetic risk is within the major histocompatibility complex (MHC). Since autoantibody presence defines specific clinical subgroups of IIM, we aimed to correlate serotype and genotype, to identify novel risk variants in the MHC region that co-occur with IIM autoantibodies.MethodsWe collected available autoantibody data in our cohort of 2582 Caucasian patients with IIM. High resolution human leucocyte antigen (HLA) alleles and corresponding amino acid sequences were imputed using SNP2HLA from existing genotyping data and tested for association with 12 autoantibody subgroups.ResultsWe report associations with eight autoantibodies reaching our study-wide significance level of p<2.9×10–5. Associations with the 8.1 ancestral haplotype were found with anti-Jo-1 (HLA-B*08:01, p=2.28×10–53 and HLA-DRB1*03:01, p=3.25×10–9), anti-PM/Scl (HLA-DQB1*02:01, p=1.47×10–26) and anti-cN1A autoantibodies (HLA-DRB1*03:01, p=1.40×10–11). Associations independent of this haplotype were found with anti-Mi-2 (HLA-DRB1*07:01, p=4.92×10–13) and anti-HMGCR autoantibodies (HLA-DRB1*11, p=5.09×10–6). Amino acid positions may be more strongly associated than classical HLA associations; for example with anti-Jo-1 autoantibodies and position 74 of HLA-DRB1 (p=3.47×10–64) and position 9 of HLA-B (p=7.03×10–11). We report novel genetic associations with HLA-DQB1 anti-TIF1 autoantibodies and identify haplotypes that may differ between adult-onset and juvenile-onset patients with these autoantibodies.ConclusionsThese findings provide new insights regarding the functional consequences of genetic polymorphisms within the MHC. As autoantibodies in IIM correlate with specific clinical features of disease, understanding genetic risk underlying development of autoantibody profiles has implications for future research.
A recently reported crystal structure of an intact bacterial group I self-splicing intron in complex with both its exons provided the first molecular view into the mechanism of RNA splicing. This ...intron structure, which was trapped in the state prior to the exon ligation reaction, also reveals the architecture of a complex RNA fold. The majority of the intron is contained within three internally stacked, but sequence discontinuous, helical domains. Here the tertiary hydrogen bonding and stacking interactions between the domains, and the single-stranded joiner segments that bridge between them, are fully described. Features of the structure include: (1) A pseudoknot belt that circumscribes the molecule at its longitudinal midpoint; (2) two tetraloop-tetraloop receptor motifs at the peripheral edges of the structure; (3) an extensive minor groove triplex between the paired and joiner segments, P6-J6/6a and P3-J3/4, which provides the major interaction interface between the intron's two primary domains (P4-P6 and P3-P9.0); (4) a six-nucleotide J8/7 single stranded element that adopts a mu-shaped structure and twists through the active site, making critical contacts to all three helical domains; and (5) an extensive base stacking architecture that realizes 90% of all possible stacking interactions. The intron structure was validated by hydroxyl radical footprinting, where strong correlation was observed between experimental and predicted solvent accessibility. Models of the pre-first and pre-second steps of intron splicing are proposed with full-sized tRNA exons. They suggest that the tRNA undergoes substantial angular motion relative to the intron between the two steps of splicing.
In spite of its central role in biology and disease, protein turnover is a largely understudied aspect of most proteomic studies due to the complexity of computational workflows that analyze in vivo ...turnover rates. To address this need, we developed a new computational tool, TurnoveR, to accurately calculate protein turnover rates from mass spectrometric analysis of metabolic labeling experiments in Skyline, a free and open-source proteomics software platform. TurnoveR is a straightforward graphical interface that enables seamless integration of protein turnover analysis into a traditional proteomics workflow in Skyline, allowing users to take advantage of the advanced and flexible data visualization and curation features built into the software. The computational pipeline of TurnoveR performs critical steps to determine protein turnover rates, including isotopologue demultiplexing, precursor-pool correction, statistical analysis, and generation of data reports and visualizations. This workflow is compatible with many mass spectrometric platforms and recapitulates turnover rates and differential changes in turnover rates between treatment groups calculated in previous studies. We expect that the addition of TurnoveR to the widely used Skyline proteomics software will facilitate wider utilization of protein turnover analysis in highly relevant biological models, including aging, neurodegeneration, and skeletal muscle atrophy.
The social organization of the first fully sedentary societies that emerged during the Neolithic period in Southwest Asia remains enigmatic,1 mainly because material culture studies provide limited ...insight into this issue. However, because Neolithic Anatolian communities often buried their dead beneath domestic buildings,2 household composition and social structure can be studied through these human remains. Here, we describe genetic relatedness among co-burials associated with domestic buildings in Neolithic Anatolia using 59 ancient genomes, including 22 new genomes from Aşıklı Höyük and Çatalhöyük. We infer pedigree relationships by simultaneously analyzing multiple types of information, including autosomal and X chromosome kinship coefficients, maternal markers, and radiocarbon dating. In two early Neolithic villages dating to the 9th and 8th millennia BCE, Aşıklı Höyük and Boncuklu, we discover that siblings and parent-offspring pairings were frequent within domestic structures, which provides the first direct indication of close genetic relationships among co-burials. In contrast, in the 7th millennium BCE sites of Çatalhöyük and Barcın, where we study subadults interred within and around houses, we find close genetic relatives to be rare. Hence, genetic relatedness may not have played a major role in the choice of burial location at these latter two sites, at least for subadults. This supports the hypothesis that in Çatalhöyük,3–5 and possibly in some other Neolithic communities, domestic structures may have served as burial location for social units incorporating biologically unrelated individuals. Our results underscore the diversity of kin structures in Neolithic communities during this important phase of sociocultural development.
•Genetic kinship estimated from co-buried individuals’ genomes in Neolithic Anatolia•Close relatives are common among co-burials in Aşıklı and Boncuklu•Many unrelated infants found buried in the same building in Çatalhöyük and Barcın•Neolithic societies in Southwest Asia may have held diverse concepts of kinship
Yaka et al. use ancient genomes from Neolithic Anatolia and present evidence for diverse concepts of social kinship in Neolithic societies. In some communities, like Çatalhöyük, many genetically unrelated infants were buried together inside the same buildings, whereas in other sites, people buried together were frequently close biological kin.
Abstract Background The generative learning model posits that individuals remember content they have generated better than materials created by others. The goals of this study were to evaluate ...question generation as a study method for the American Board of Surgery In-Training Examination (ABSITE) and determine whether practice test scores and other data predict ABSITE performance. Methods Residents (n = 206) from 6 general surgery programs were randomly assigned to one of the two study conditions. One group wrote questions for practice examinations. All residents took 2 practice examinations. Results There was not a significant effect of writing questions on ABSITE score. Practice test scores, United States Medical Licensing Examination Step 1 scores, and previous ABSITE scores were significantly correlated with ABSITE performance. Conclusions The generative learning model was not supported. Performance on practice tests and other data can be used for early identification of residents at risk of performing poorly on the ABSITE.
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