Search

Background: Ancestry is often viewed as a more objective and less objectionable population descriptor than race or ethnicity. Perhaps reflecting this, usage of the term “ancestry” is rapidly growing in genetics research, with ancestry groups referenced in many situations. The appropriate usage of population descriptors in genetics research is an ongoing source of debate. Sound normative guidance should rest on an empirical understanding of current usage; in the case of ancestry, questions about how researchers use the concept, and what they mean by it, remain unanswered.Methods: Systematic literature analysis of 205 articles at least tangentially related to human health from diverse disciplines that use the concept of ancestry, and semi-structured interviews with 44 lead authors of some of those articles.Results: Ancestry is relied on to structure research questions and key methodological approaches. Yet researchers struggle to define it, and/or offer diverse definitions. For some ancestry is a genetic concept, but for many—including geneticists—ancestry is only tangentially related to genetics. For some interviewees, ancestry is explicitly equated to ethnicity; for others it is explicitly distanced from it. Ancestry is operationalized using multiple data types (including genetic variation and self-reported identities), though for a large fraction of articles (26%) it is impossible to tell which data types were used. Across the literature and interviews there is no consistent understanding of how ancestry relates to genetic concepts (including genetic ancestry and population structure), nor how these genetic concepts relate to each other. Beyond this conceptual confusion, practices related to summarizing patterns of genetic variation often rest on uninterrogated conventions. Continental labels are by far the most common type of label applied to ancestry groups. We observed many instances of slippage between reference to ancestry groups and racial groups.Conclusion: Ancestry is in practice a highly ambiguous concept, and far from an objective counterpart to race or ethnicity. It is not uniquely a “biological” construct, and it does not represent a “safe haven” for researchers seeking to avoid evoking race or ethnicity in their work. Distinguishing genetic ancestry from ancestry more broadly will be a necessary part of providing conceptual clarity.

We demonstrate that a neural network pre-trained on text and fine-tuned on code solves mathematics course problems, explains solutions, and generates new questions at a human level. We automatically synthesize programs using few-shot learning and OpenAI's Codex transformer and execute them to solve course problems at 81% automatic accuracy. We curate a new dataset of questions from MIT's largest mathematics courses (Single Variable and Multivariable Calculus, Differential Equations, Introduction to Probability and Statistics, Linear Algebra, and Mathematics for Computer Science) and Columbia University's Computational Linear Algebra. We solve questions from a MATH dataset (on Prealgebra, Algebra, Counting and Probability, Intermediate Algebra, Number Theory, and Precalculus), the latest benchmark of advanced mathematics problems designed to assess mathematical reasoning. We randomly sample questions and generate solutions with multiple modalities, including numbers, equations, and plots. The latest GPT-3 language model pre-trained on text automatically solves only 18.8% of these university questions using zero-shot learning and 30.8% using few-shot learning and the most recent chain of thought prompting. In contrast, program synthesis with few-shot learning using Codex fine-tuned on code generates programs that automatically solve 81% of these questions. Our approach improves the previous state-of-the-art automatic solution accuracy on the benchmark topics from 8.8% to 81.1%. We perform a survey to evaluate the quality and difficulty of generated questions. This work is the first to automatically solve university-level mathematics course questions at a human level and the first work to explain and generate university-level mathematics course questions at scale, a milestone for higher education., Comment: 181 pages, 8 figures, 280 tables

It is often believed that for open source software (OSS) projects the faster the release, the better for attracting user interest in the software. Whether this is true, however, is still open to question. There is considerable information asymmetry between OSS projects and potential users as project quality is unobservable to users. We suggest that innovation speed of OSS project can signal the unobservable project quality and attract users’ interest in downloading and using the software. We contextualize innovation speed of OSS projects as initial release speed and update speed and examine their impacts on user interest. Drawing on the signaling theory, we propose a signaling effect through which a higher initial release speed or update speed increases user interest, while the effect diminishes as initial release or update speed increases. Using a large-scale panel data set from 7442 OSS projects on SourceForge between 2007 and 2010, our results corroborate the inverted U-shaped relationships between initial release speed and user downloads and between update speed and user downloads.

Pathology is practiced by visual inspection of histochemically stained tissue slides. While the hematoxylin and eosin (H&E) stain is most commonly used, special stains can provide additional contrast to different tissue components. Here, we demonstrate the utility of supervised learning-based computational stain transformation from H&E to special stains (Masson’s Trichrome, periodic acid-Schiff and Jones silver stain) using kidney needle core biopsy tissue sections. Based on the evaluation by three renal pathologists, followed by adjudication by a fourth pathologist, we show that the generation of virtual special stains from existing H&E images improves the diagnosis of several non-neoplastic kidney diseases, sampled from 58 unique subjects (P = 0.0095). A second study found that the quality of the computationally generated special stains was statistically equivalent to those which were histochemically stained. This stain-to-stain transformation framework can improve preliminary diagnoses when additional special stains are needed, also providing significant savings in time and cost., Performing multiple histological stains on a biopsy can be costly and time consuming. Here the authors present a method for the digital transformation of H&E stained tissue into special stains (e.g., PAS, Masson’s Trichrome and Jones silver stain), and demonstrate that it improves diagnoses over the use of H&E only.

The use of legal technology (legal tech) and the lawtech ecosystem of legal start-ups has experienced tremendous growth in recent years. To provide a structured approach of analysing IT innovations in the legal sector, we propose a framework for lawtech applications, classifying them into three groups: internal, B2C and B2B applications. In the context of this framework, we examine technological trends in lawtech and their potential to support and transform processes in specific areas of business or personal law. We acknowledge that within lawtech there is a gap between the areas of interest of legal practitioners, IT professionals and academic researchers, and that some areas have received considerable attention by these groups, while other areas have been left relatively unexplored by one or more of these groups. However, the growing interest by legal practitioners in advanced technology such as artificial intelligence (AI) and natural language processing (NLP) is further closing the gap between academic research, IT professionals and legal practice.

By using hydrogen quench continuous annealing technology, Stelco Inc. has developed a suite of Advanced High Strength Steel (AHSS) grades with tensile strength greater than 1000MPa to meet standard automotive specifications and for unique customer requirements. These grades were optimized by correlating chemical composition and processing parameters with microstructures and mechanical properties. Dual-Phase 980 (Stelco trademarked STELMAXTM 980DP), Multi-Phase 1180 (STELMAXTM 1180MP), Martensitic Steel 1300 (STELMAXTM 1300M) and 1500 (STELMAXTM 1500M) products met strength and formability requirements with excellent flatness and surface quality. Hydrogen quench continuous annealing technology not only ensures all developed AHSS grades have consistent mechanical properties across the entire strip length (from strip head to tail) and width (from edge to edge), but also produces high product yield compared with other continuous annealing processes.

Register of Chinese Immigrants to Canada, 1886-1949 is a historical dataset openly available to the public. Drawing on the previous studies based on the data and employing computational tools, this study aims to lower the barriers to the data use, as well as to reveal substantive potential of the data that has not been leveraged by scholars.

Using NASDAQ trade and Reuters news data, I show that the response of aggressive non‐high‐frequency traders (nHFTs) to news is stronger than that of aggressive high‐frequency traders (HFTs). Classifying news into quantitative (“hard”) and less quantitative (“softer”) news, the trading response of aggressive nHFTs to softer news exceeds HFTs’ response. Positive news elicits greater return and nHFT responses than negative news during the 2008 financial crisis period. As this phenomenon persists even after excluding the 2008 short‐sale ban, the results support the hypothesis of nHFTs exhibiting stronger asymmetric responses during crisis periods.

Organisms use various strategies to cope with fluctuating environmental conditions. In diversified bet-hedging, a single genotype exhibits phenotypic heterogeneity with the expectation that some individuals will survive transient selective pressures. To date, empirical evidence for bet-hedging is scarce. Here, we observe that individual Drosophila melanogaster flies exhibit striking variation in light- and temperature-preference behaviors. With a modeling approach that combines real world weather and climate data to simulate temperature preference-dependent survival and reproduction, we find that a bet-hedging strategy may underlie the observed interindividual behavioral diversity. Specifically, bet-hedging outcompetes strategies in which individual thermal preferences are heritable. Animals employing bet-hedging refrain from adapting to the coolness of spring with increased warm-seeking that inevitably becomes counterproductive in the hot summer. This strategy is particularly valuable when mean seasonal temperatures are typical, or when there is considerable fluctuation in temperature within the season. The model predicts, and we experimentally verify, that the behaviors of individual flies are not heritable. Finally, we model the effects of historical weather data, climate change, and geographic seasonal variation on the optimal strategies underlying behavioral variation between individuals, characterizing the regimes in which bet-hedging is advantageous.

Klotho plays an important role in the pathogenesis of cardiovascular disease in chronic kidney disease (CKD). Klotho is highly expressed in the kidney and parathyroid glands, but its presence in the vasculature is debated. Renal Klotho is decreased in CKD, but the effect of uremia on Klotho in other tissues is not defined. The effect of vitamin D receptor activator therapy in CKD on the expression of Klotho in various tissues is also in debate. In uremic rats (surgical 5/6th nephrectomy model), we compared 3 months of treatment with and without paricalcitol on Klotho immunostaining in the kidney, parathyroid glands, and aorta. With uremia, Klotho was unchanged in the parathyroid, significantly decreased in the kidney (66%) and the intimal-medial area of the aorta (69%), and significantly increased in the adventitial area of the aorta (67%) compared with controls. Paricalcitol prevented the decrease of Klotho in the kidney, increased expression in the parathyroid (31%), had no effect in the aortic media, but blunted the increase of Klotho in the aortic adventitia. We propose that fibroblasts are responsible for the expression of Klotho in the adventitia. In hyperplastic human parathyroid tissue from uremic patients, Klotho was higher in oxyphil compared with chief cells. Thus, under our conditions of moderate CKD and mild-to-moderate hyperphosphatemia in rats, the differential expression of Klotho and its regulation by paricalcitol in uremia is tissue-dependent.

I study the role of high-frequency traders (HFTs) and non-high-frequency traders (nHFTs) in transmitting hard price information from the futures market to the stock market using an index arbitrage strategy. Using intraday transaction data with HFT identification, I find that HFTs process hard information faster and trade on it more aggressively than nHFTs. In terms of liquidity supply, HFTs are better at avoiding adverse selection than nHFTs. Consequently, HFTs enhance the linkage between the futures and stock markets, and significantly contribute to information efficiency in the stock market by reducing the delay between the stock and the futures markets.

The role of hyperphosphatemia in the pathogenesis of secondary hyperparathyroidism, cardiovascular disease, and progression of renal failure is widely known. Here we studied effects of dietary phosphate restriction on mortality and vascular calcification in uremic rats. Control and uremic rats were fed a high-phosphate diet and at 3 months a portion of rats of each group were killed. Serum phosphate and the calcium phosphate product increased in uremic rats, as did aortic calcium. Of the rats, 56% had positive aortic staining for calcium (von Kossa), RUNX2, and osteopontin. The remaining uremic rats were continued on diets containing high phosphate without and with sevelamer, or low phosphate, and after 3 more months they were killed. Serum phosphate was highest in uremic rats on high phosphate. Serum PTH and FGF-23 were markedly lower in rats on low phosphate. Mortality on high phosphate was 71.4%, with sevelamer reducing this to 37.5% and phosphate restriction to 5.9%. Positive aortic staining for von Kossa, RUNX2, and osteopontin was increased, but phosphate restriction inhibited this. Kidneys from low-phosphate and sevelamer-treated uremic rats had less interstitial fibrosis, glomerulosclerosis, and inflammation than those of uremic rats on high phosphate. Importantly, kidneys from rats on low phosphate showed improvement over kidneys from high-phosphate rats at 3 months. Left ventricles from rats on low phosphate had less perivascular fibrosis and smaller cardiomyocyte size compared to rats on high phosphate. Thus, intensive phosphate restriction significantly reduces mortality in uremic rats with severe vascular calcification.

Objectives/Hypothesis To examine the sinus-related sequelae of free flap reconstruction for complex orbitofacial defects. Study Design Retrospective chart review. Methods Demographic, clinical, and radiographic data on a series of 55 patients who had undergone free tissue transfer for orbitofacial reconstruction was retrospectively reviewed. Follow-up of ≥ 3 months was available for 49 patients. Outcome measures studied included clinical or radiographic evidence of sinusitis and the need for sinus surgery. Results The most commonly involved sinuses were the ethmoid (n = 40) and maxillary (n = 38) sinuses, and the anterolateral thigh was the most common flap used (n = 41). Clinical and/or radiographic sinusitis was evident in 21 patients (43%), and 10 patients (20%) required sinus surgery at some point during follow-up. Involvement of multiple sinuses in the initial orbitofacial surgery was associated with a significantly increased need for subsequent sinus surgery (P = 0.009). Adjuvant radiotherapy and adjuvant chemoradiotherapy were associated with a significantly increased risk for the development of rhinosinusitis (P = 0.045 and 0.016, respectively). Conclusion Rhinosinusitis and the need for operative management of sinus obstruction are common in patients having undergone complex orbitofacial reconstruction. Careful management of the paranasal sinuses is an important component of the multidisciplinary treatment of such patients. Level of Evidence 4. Laryngoscope, 124:1059–1065, 2014

Transient receptor potential (TRP) channels are nonselective cation channels, several of which are expressed in striated muscle. Because the scaffolding protein Homer 1 has been implicated in TRP channel regulation, we hypothesized that Homer proteins play a significant role in skeletal muscle function. Mice lacking Homer 1 exhibited a myopathy characterized by decreased muscle fiber cross-sectional area and decreased skeletal muscle force generation. Homer 1 knockout myotubes displayed increased basal current density and spontaneous cation influx. This spontaneous cation influx in Homer 1 knockout myotubes was blocked by reexpression of Homer 1b, but not Homer 1a, and by gene silencing of TRPC1. Moreover, diminished Homer 1 expression in mouse models of Duchenne's muscular dystrophy suggests that loss of Homer 1 scaffolding of TRP channels may contribute to the increased stretch-activated channel activity observed in mdx myofibers. These findings provide direct evidence that Homer 1 functions as an important scaffold for TRP channels and regulates mechanotransduction in skeletal muscle.

Organisms use various strategies to cope with fluctuating environmental conditions. In diversified bet-hedging, a single genotype exhibits phenotypic heterogeneity with the expectation that some individuals will survive transient selective pressures. To date, empirical evidence for bet-hedging is scarce. Here, we observe that individual Drosophila melanogaster flies exhibit striking variation in light- and temperature-preference behaviors. With a modeling approach that combines real world weather and climate data to simulate temperature preference-dependent survival and reproduction, we find that a bet-hedging strategy may underlie the observed inter-individual behavioral diversity. Specifically, bet-hedging outcompetes strategies in which individual thermal preferences are heritable. Animals employing bet-hedging refrain from adapting to the coolness of spring with increased warm-seeking that inevitably becomes counterproductive in the hot summer. This strategy is particularly valuable when mean seasonal temperatures are typical, or when there is considerable fluctuation in temperature within the season. The model predicts, and we experimentally verify, that the behaviors of individual flies are not heritable. Finally, we model the effects of historical weather data, climate change, and geographic seasonal variation on the optimal strategies underlying behavioral variation between individuals, characterizing the regimes in which bet-hedging is advantageous.

Treatment halts recurrence of Clostridium difficile bacteria, but a commercial pill is still far off.

Living near livestock farms and manure-treated fields associated with higher rates of antibiotic-resistant infection.

Capitalizing on the potential for Mg alloys to reduce vehicle weight, a multi-national Mg-intensive front end research and development (MFERD) initiative has been established to identify and address the processing, joining and corrosion protection challenges that need to be overcome to support the fabrication of a complete Mg-intensive automotive front end assembly. The initiative identified high pressure die-cast (HPDC) AM60B and linear friction stir welding (FSW) as the preferred structural casting and joining technology, respectively, to be used for the fabrication of demonstrator sub-assemblies for component-level testing. A key fundamental aspect underpinning the successful implementation friction stir welded HPDC AM60B joints is a well-developed understanding of the extent of atmospheric corrosion damage expected to occur across the joint when boldly-exposed. The susceptibility of HPDC AM60B to localized corrosion arises from the heterogeneous microstructure and the formation of galvanic couples between the Mg matrix and the secondary intermetallic phases. Friction stir welding has been reported to significantly alter this heterogeneous microstructure across the welded joint. However definitive links between microstructure and localized corrosion susceptibility remain elusive. Electrochemical polarization and scanning vibrating probe (SVP) measurements were made to establish links between the localized corrosion susceptibility observed across the FSW joint and the resultant variations in microstructure, as revealed by scanning electron microscopy (SEM). Microstructural parameters of interest included microhardness, grain size and the size and spacial distribution of Al-Mn intermetallic particles and the secondary Mg17Al12(β) phase. The corrosive environment used was a near-neutral 5 wt.% NaCl solution. Complementary surface analyses by X-ray photoelectron spectroscopy (XPS) of the starting surface films were made to delineate the role played by the native oxide film on the subsequent localized corrosion susceptibility. The findings based on the bulk immersion testing were subsequently validated by continuous salt fog atmospheric corrosion testing. Of the microstructural parameters studied, only the grain size and spacial distribution of the secondary Mg17Al12 (β) phase were significantly affected across the friction stir welded joint. The stir zone exhibited a finer grain size relative to the unaffected base material, but did not exhibit a secondary Mg17Al12 (β) phase network. The combined set of electrochemical measurements (open-circuit potential, potentiodynamic polarization and SVP) consistently revealed that the stir zone was more susceptible to localized corrosion than the unaffected base material. SVP measurements on both the original topography and a flat-polished surface demonstrated that the stir zone striations had little effect on this tendency (see Figure 1). The findings thus far point to a combined alloy chemistry and structure link (centering on the fate of the secondary Mg17Al12 (β) phase network) between the localized corrosion susceptibility observed across the friction stir welded joint and the resultant variations in microstructure. Figure 1

In this study, we examined the hypothesis that stretch-induced (nitric oxide) NO modulates the mechanical properties of skeletal muscles by increasing accumulation of protein levels of talin and vinculin and by inhibiting calpain-induced proteolysis, thereby stabilizing the focal contacts and the cytoskeleton. Differentiating C2C12myotubes were subjected to a single 10% step stretch for 0–4 days. The apparent elastic modulus of the cells, Eapp, was subsequently determined by atomic force microscopy. Static stretch led to significant increases ( P < 0.01) in Eappbeginning at 2 days. These increases were correlated with increases in NO activity and neuronal NO synthase (nNOS) protein expression. Expression of talin was upregulated throughout, whereas expression of vinculin was significantly increased only on days 3 and 4. Addition of the NO donor l-arginine onto stretched cells further enhanced Eapp, NOS activity, and nNOS expression, whereas the presence of the NO inhibitor Nω-nitro-l-arginine methyl ester (l-NAME) reversed the effects of mechanical stimulation and of l-arginine. Overall, viscous dissipation, as determined by the value of hysteresis, was not significantly altered. For assessment of the role of vinculin and talin stability, cells treated with l-NAME showed a significant decrease in Eapp, whereas addition of a calpain inhibitor abolished the effect. Thus our results show that NO inhibition of calpain-initiated cleavage of cytoskeleton proteins was correlated with the changes in Eapp. Together, our data suggest that NO modulates the mechanical behavior of skeletal muscle cells through the combined action of increased talin and vinculin levels and a decrease in calpain-mediated talin proteolysis.

The effect of differentiation on the transverse mechanical properties of mammalian myocytes was determined by using atomic force microscopy. The apparent elastic modulus increased from 11.5 ± 1.3 kPa for undifferentiated myoblasts to 45.3 ± 4.0 kPa after 8 days of differentiation ( P< 0.05). The relative contribution of viscosity, as determined from the normalized hysteresis area, ranged from 0.13 ± 0.02 to 0.21 ± 0.03 and did not change throughout differentiation. Myosin expression correlated with the apparent elastic modulus, but neither myosin nor β-tubulin were associated with hysteresis. Microtubules did not affect mechanical properties because treatment with colchicine did not alter the apparent elastic modulus or hysteresis. Treatment with cytochalasin D or 2,3-butanedione 2-monoxime led to a significant reduction in the apparent elastic modulus but no change in hysteresis. In summary, skeletal muscle cells exhibited viscoelastic behavior that changed during differentiation, yielding an increase in the transverse elastic modulus. Major contributors to changes in the transverse elastic modulus during differentiation were actin and myosin.

Geologists, engineers and social scientists are poised to swoop in before reconstruction gets under way.

not Available.