Miracle-dz/UniFAR-FTUs huggingface dataset:
Kinematic Optimization in Birds, Bats and Ornithopters

Kinematic Optimization in Birds, Bats and Ornithopters Todd Reichert Doctor of Philosophy Institute for Aerospace Studies University of Toronto 2011 Birds and bats employ a variety of advanced wing motions in the efficient production of thrust. The purpose of this thesis is to quantify the benefit of these advanced wing motions, determine the optimal theoretical wing kinematics for a given flight condition, and to develop a methodology for applying the results in the optimal design of flapping-wing aircraft (ornithopters). To this end, a medium-fidelity, combined aero-structural model has been developed that is capable of simulating the advanced kinematics seen in bird flight, as well as the highly non-linear structural deformations typical of high-aspect ratio wings. Five unique methods of thrust production observed in natural species have been isolated, quantified and thoroughly investigated for their dependence on Reynolds number, airfoil selection, frequency, amplitude and relative phasing. A gradient-based optimization algorithm has been employed to determined the wing kinematics that result in the minimum required power for a generalized aircraft or species in any given flight condition. In addition to the theoretical work, with the help of an extended team, the methodology was applied to the design and construction of the world’s first successful human-powered ornithopter. The Snowbird Human-Powered Ornithopter is used as an example aircraft to show how additional design constraints can pose limits on the optimal kinematics. The results show significant trends that give insight into the kinematic operation of natural species. The general result is that additional complexity, whether it be larger twisting deformations or advanced wing-folding mechanisms, allows for the possibility of more efficient flight. At its theoretical optimum, the efficiency of flapping-wings exceeds that of current rotors and propellers, although these efficiencies are quite difficult to achieve in practice.
Human Endogenous Retrovirus (HERV-K) Reverse Transcriptase as a Breast Cancer Prognostic Marker 1,2,3

A reverse transcriptase (RT) cDNA, designated HERV-K-T47D-RT , was isolated from a hormonally treated human breast cancer cell line. The protein product putative sequence is 97% identical to the human endogenous HERV-K retroviral sequences. Recombinant T47D-RT protein was used to generate polyclonal antibodies. The expression of HERV-K-T47D-RT protein increased in T47D cells after treatment with estrogen and progesterone. The RT-associated DNA polymerase activity was substantially increased after over-expressing a chimeric YFP-HERV-K-T47D-RT protein in cells. This RT-associated polymerase activity was significantly reduced by mutating the active site sequence YIDD to SIAA. Moreover, the endogenous RT activity observed in T47D cells was decreased by HERV-K-T47D-RT – specific siRNA, confirming the dependence of the endogenous enzymatic activity. To assess HERV-K-T47D-RT expression in human breast tumors, 110 paraffin sections of breast carcinoma biopsies were stained and subjected to confocal analysis. Twenty-six percent (28/110) of the tumor tissues and 18% (15/85) of the adjacent normal tissue, from the same patients, expressed the RT. HERV-K-T47D-RT expression significantly correlates with poor prognosis for disease-free patients and their overall survival. These results imply that HERV-K-T47D-RT might be expressed in early malignancy and might serve as a novel prognostic marker for breast cancer. Furthermore, these results provide evidence for the possible involvement of endogenous retrovirus in human breast carcinoma. These results indicate that the HERV-K-T47D-RT is enzymatically active in mammalian cells and that the observed activity is specific to this RT enzyme. by the Human
Accuracy of Optimized Branched Algorithms to Assess Activity-Specific PAEE

PURPOSE— To assess the activity-specific accuracy achievable by branched algorithm (BA) analysis of simulated daily-living physical activity energy expenditure (PAEE) within a sedentary population. METHODS— Sedentary men (n=8) and women (n=8) first performed a treadmill calibration protocol, during which heart rate (HR), accelerometry (ACC), and PAEE were measured in 1-minute epochs. From these data, HR-PAEE, and ACC-PAEE regressions were constructed and used in each of six analytic models to predict PAEE from ACC and HR data collected during a subsequent simulated daily-living protocol. Criterion PAEE was measured during both protocols via indirect calorimetry. The accuracy achieved by each model was assessed by the root mean square of the difference between model-predicted daily–living PAEE and the criterion daily-living PAEE (expressed here as % of mean daily living PAEE). RESULTS— Across the range of activities an unconstrained post hoc optimized branched algorithm best predicted criterion PAEE. Estimates using individual calibration were generally more accurate than those using group calibration (14 vs. 16 % error, respectively). These analyses also performed well within each of the six daily-living activities, but systematic errors appeared for several of those activities, which may be explained by an inability of the algorithm to simultaneously accommodate a heterogeneous range of activities. Analyses of between mean square error by subject and activity suggest that optimization involving minimization of RMS for total daily-living PAEE is associated with decreased error between subjects but increased error between activities. CONCLUSION— The performance of post hoc optimized branched algorithms may be limited by heterogeneity in the daily-living activities being performed.
A Jackknife Empirical Likelihood Approach To Goodness Of Fit U-Statistic Testing With Side Information

Lin, Qun Ph.D., Purdue University, December 2013. A Jackknife Empirical Likelihood Approach To Goodness of Fit U-Statistic Testing With Side Information. Major Professor: Hanxiang Peng. Motivated by applications to goodness of fit U-statistic testing, the jackknife empirical likelihood (JEL) of Jing, et al. (2009) is justified with an alternative approach, and the Wilks theorem for vector U-statistics is proved. This generalizes Owen’s empirical likelihood from a vector mean to a vector U-statistic-based mean and Jing’s JEL for univariate U-statistics to vector U-statistics and includes the JEL for U-statistics with side information as a special case. The results are generalized to allow for the constraints to use estimated criteria functions and for the number of constraints to grow with the sample size. The latter is needed to handle naturally occurring nuisance parameters in semiparametric models. The developed theory is applied to derive the empirical-likelihood-based goodness-of-fit tests and confidence sets for U-quantiles with finite number and growing number of constraints in the Theil-estimator-based test about the slope in a simple linear regression; for the Wilcoxon signed rank test about symmetry with an unknown center; for Kendall’s tau and Goodman and Kruskal’s Gamma with side information; for the test about independence of two categorical outcomes; for the joint confidence sets of variances in a balanced random effects model and for the simplicial depth function with a finite number and growing number of constraints. Some of the proposed jackknife empirical likelihood based goodness of fit tests are asymptotically distribution free. A simulation study is conducted to evaluate the behaviors of the Theil test with finite number and growing number of constraints.
Developing Genome-wide Polygenic Risk Scores for Coronary Artery Disease in South Asians

Background: Genome-wide polygenic scores (GPS) integrate information from many common DNA variants into a single number. Because rates of coronary artery disease (CAD) are substantially higher among South Asians, a GPS to identify high-risk individuals may be particularly useful in this population. Objectives: We used summary statistics from a prior genome-wide association study to derive a new GPS CAD for South Asians. Methods: We validated this GPS CAD in 7,244 South Asian UK Biobank participants and tested it in 491 individuals from a case-control study in Bangladesh. Next, we built a static ancestry and GPS CAD reference distribution using whole genome sequencing from 1,522 Indian individuals, and tested a framework for projecting individuals onto this static ancestry and GPS CAD reference distribution using 1,800 CAD cases and 1,163 controls newly recruited in India. Results: The GPS CAD , containing 6,630,150 common DNA variants, had odds ratio per standard deviation (OR/SD) of 1.58 in South Asian UK Biobank participants and 1.60 in the Bangladeshi study (p < 0.001 for each). We next projected individuals of the Indian case-control study onto static reference distributions, observing an OR/SD of 1.66 (p < 0.001). Compared to the middle quintile, risk for CAD was most pronounced for those in the top 5% of the GPS CAD distribution ORs of 4.16, 2.46, and 3.22 in the South Asian UK Biobank, Bangladeshi, and Indian studies, respectively (p < 0.05 for each). Conclusions: We developed and tested a new GPS CAD using three distinct South Asian studies, and provide a generalizable framework for ancestry-specific GPS assessment. abstract: Genome-wide polygenic scores are a new approach to quantify inherited risk for a given disease using information from many common sites of DNA variation. The predictive capacity of a polygenic score for coronary artery disease in South Asians - a population that suffers from coronary artery disease at significantly higher rates - is largely unknown. Here, we build a polygenic score consisting of over 6.6 million common DNA variants and a workflow for ancestry-corrected risk quantification. Results confirm striking and consistent relationships with coronary artery disease in South Asian populations from the United Kingdom, Bangladesh, and India. Central illustration. Development and implementation of a framework for calculating genome- wide polygenic scores in South Asian individuals.
Hepatitis C and HIV Risk Behaviors in Polydrug Users on Methadone Maintenance

We examined the impact of methadone maintenance treatment (MMT) on risk behaviors for transmission of bloodborne diseases in polydrug users who had tested positive or negative for hepatitis C (HCV). At intake, HCV-positive participants (n = 362) engaged in more HIV risk behaviors (as measured by the HIV Risk-Taking Behaviour Scale; HRBS) than HCV-negative participants (n = 297) (p<.001). This difference was specific to injection-related behaviors and decreased significantly within the first few weeks of MMT (p<.0001). Where needles continued to be used, HCV-positive participants became more likely over time to engage in safer injecting practices. Furthermore HCV-positive participants became more likely to use condoms than HCV-negative participants. These findings demonstrate that both drug- and sex-related risk behaviors decrease during MMT, and emphasize the benefits of methadone programs for public health and HIV/HCV prevention.
Assessing Bioactivity-Exposure Profiles of Fruits and Vegetables in the BioMAP Profiling System

, Abstract The ToxCast program has generated in vitro screening data on over a thousand chemicals to assess potential disruption of important biological processes and assist in hazard identification and chemical testing prioritization. Few results have been reported for complex mixtures. To extend these ToxCast efforts to mixtures, we tested extracts from 30 organically grown fruits and vegetables in concentration-response in the BioMAP® assays. BioMAP systems use human primary cells primed with endogenous pathway activators to identify phenotypic perturbations related to proliferation, inflammation, immunomodulation, and tissue remodeling. Clustering of bioactivity profiles revealed separation of these produce extracts and ToxCast chemicals. Produce extracts elicited 87 assay endpoint responses per item compared to 20 per item for ToxCast chemicals. On a molar basis, the produce extracts were 10 to 50-fold less potent and when constrained to the maximum testing concentration of the ToxCast chemicals, the produce extracts did not show activity in as many assay endpoints. Using intake adjusted measures of dose, the bioactivity potential was higher for produce extracts than for agrichemicals, as expected based on the comparatively small amounts of agrichemical residues present on conventionally grown produce. The evaluation of BioMAP readouts and the dose responses for produce extracts showed qualitative and quantitative differences from results with single chemicals, highlighting challenges in the interpretation of bioactivity data and dose-response from complex mixtures.
Long-term NSAID use and Incident Urothelial Cell Carcinoma in the VITamins and Lifestyle Study

Purpose— Literature on the chemopreventive role of nonsteroidal anti-inflammatory drugs (NSAIDs) in urothelial carcinoma of the bladder (UC) is conflicting. A recent pooled analysis of three cohorts reported regular use of non-aspirin NSAIDs was associated with reduced risk of UC among non-smokers only; however, non-smokers are a group with a low risk of UC. We examine the association between NSAID use and UC risk. Materials and Methods— Study participants were members of the VITamins and Lifestyle (VITAL) cohort of 77,048 Washington State residents aged 50–76 years who completed a baseline questionnaire in 2000–2002 on NSAID use and cancer risk factors. Ten-year use of aspirin and other NSAIDs was categorized as none, low-use (1–3 days/week or <4 years), or high-use (≥4 days/week and ≥4 years). Incident UC cases were prospectively identified via linkage to a local cancer registry. Hazard ratios (HR) were estimated by multivariate Cox regression. Results— 385 incident cases of UC were diagnosed over a mean follow-up of 7 years. There was no association with NSAID use and risk of UC. However, the association of use of non-aspirin NSAIDs with UC risk differed by smoking status (p for interaction = 0.02). Specifically, among long-term former smokers (quit ≥10 years), non-aspirin NSAID use was associated with a 31% reduction in risk of UC in low-users (HR 0.69, 95% CI 0.46–1.04), and 48% reduction in risk for high-users (HR 0.52, 95% CI 0.24–1.11, p for trend=0.02). Conclusions— Our results show a risk reduction with non-aspirin NSAID use among long-term quitters, a group with significant risk of UC.
Moxifloxacin in the Initial Therapy of Tuberculosis: A Randomized, Phase 2 Trial

Background— New therapies are needed to shorten the time required to cure tuberculosis and to treat drug-resistant strains. The fluoroquinolone moxifloxacin is a promising new agent that may have additive activity to existing antituberculosis agents. We conducted a Phase 2 clinical trial to determine the activity and safety of moxifloxacin in the initial stage of tuberculosis treatment. Methods— We performed a randomized, double-blind trial of a moxifloxacin-containing regimen in patients with sputum smear-positive tuberculosis in Brazil. All participants received isoniazid, rifampin and pyrazinamide at standard doses and were randomized to receive either moxifloxacin or ethambutol and matching placebos five days per week for eight weeks. The primary endpoint was the proportion of patients whose sputum culture converted to negative by Week 8. Clinical trial identifier: NCT00082173. Results— One hundred seventy patients were enrolled, and 146 met all study eligibility criteria. In an intention to treat analysis where missing results were considered treatment failures, 59 patients (80%) assigned to moxifloxacin converted their 8-week sputum culture to negative vs. 45 (63%) of those assigned to ethambutol (p=0.03). Among patients with available cultures at Week 8, conversion rates were 92% (59/64) for moxifloxacin vs. 72% (45/61) for ethambutol (p=0.006). No differences in toxicity were observed. In a multivariate analysis, younger age (odds ratio 0.98, p=0.05), heavy baseline sputum smear positivity (OR 0.45, p <0.001) and treatment with moxifloxacin (OR 1.88, p<0.001) were significantly associated with sputum culture conversion. Conclusion— Moxifloxacin significantly improves culture conversion in the initial phase of tuberculosis treatment. Trials to assess whether moxifloxacin can be used to shorten the duration of tuberculosis therapy are justified. logistic regression as
Single-cell Transcriptomics Resolves Intermediate Glial Progenitors and Uncovers a Pivotal Determinant of Cell Fate and Gliomagenesis

The identity and heterogeneity of glial progenitors and their contributions to brain tumor malignancy remain elusive. By applying lineage-targeted single-cell transcriptomics, we uncover an unanticipated diversity of glial progenitor pools with unique molecular identities in developing brain. Our analysis identifies distinct transitional intermediate states and their divergent developmental trajectories in astroglial and oligodendroglial lineages. Moreover, intersectional analysis uncovers analogous intermediate progenitors during brain tumorigenesis, wherein oligodendrocyte-progenitor intermediates are abundant, hyper-proliferative and progressively reprogrammed towards a stem-like state susceptible to further malignant transformation. Similar actively cycling intermediate progenitors are prominent components in human gliomas with distinct driver mutations. We further unveil lineage-driving networks underlying glial fate specification and identify Zfp36l1 as necessary for oligodendrocyte-astrocyte lineage transition and glioma growth. Together, our results resolve the dynamic repertoire of common and divergent glial progenitors during development and tumorigenesis and highlight Zfp36l1 as a molecular nexus for balancing glial cell-fate decision and controlling gliomagenesis. By applying lineage-targeted single-cell transcriptomics analysis, Weng and colleagues uncover distinct intermediate glial progenitors in the neonatal brain, and their malignant counterparts in murine and human gliomas. Lineage-driving network analysis further identifies Zfp36l1 as a pivotal regulator for glial fate specification and glioma growth. brain tumor formation. Our findings demonstrate the importance of single-cell mapping and reconstructing fundamental processes of progenitor dynamics and plasticity during development and tumorigenesis. Identification of lineage-specific vulnerabilities for targeting malignant gliomas is an essential step toward a glioma treatment avenue.
Amyloid-beta imaging in older adults presenting to a memory clinic with subjective cognitive decline

, Abstract Background— Subjective cognitive decline (SCD) in otherwise normal aging may be identified via symptom inventories in a research setting (‘questionnaire-discovered complaints’) or via patients seeking evaluation / services in a clinical setting (‘presenting complainers’). Most studies of SCD and amyloid-beta (A β ) imaging to date have used the former approach, with inconsistent results. Objective— To test whether ‘presenting SCD’ participants in an academic memory clinic setting show increased brain A β deposition on imaging. Methods— Fourteen patients (mean age 68.1, SD 4.0 years) diagnosed with subjective cognitive complaints with normal neuropsychological testing were recruited into a Pittsburgh compound B (PiB)-PET study. Detailed self-report inventories and additional cognitive tests were administered. Results were compared to a reference cohort of cognitively normal (CN) volunteers from an independent neuroimaging study (mean age 73.6, SD 5.8 years) Results— 57% (8/14) of SCD participants were PiB-positive by a sensitive, regionally-based definition, compared to 31% (26/84) of the CN cohort. SCD participants had significantly higher PiB retention (SUVR) than CN in three of six regions of interest: frontal cortex (p=.02), lateral temporal cortex (p=.02) and parietal cortex (p=.04). Findings were suggestive that deficits on verbal associative binding may be specific to A β -positive vs. A β -negative SCD. Conclusion— Older participants with SCD presenting to a memory clinic have higher brain A β deposition compared to normal aging study volunteers unselected on complaints. Further study of presenting SCD are warranted to determine the prognostic significance of A β deposition in this context.
On Induced Subgraphs of Finite Graphs not Containing Large Empty and Complete Subgraphs

In their celebrated paper [Ramsey-Type Theorems, Discrete Appl. Math. 25 (1989) 37-52], Erd\H{o}s and Hajnal asked the following: is it true, that for any finite graph H there exists a constant c(H) such that for any finite graph G, if G does not contain complete or empty induced subgraphs of size at least |V(G)|^c(H), then H can be isomorphically embedded into G ? The positive answer has become known as the Erd\H{o}s-Hajnal conjecture. In Theorem 3.13 of the present paper we settle this conjecture in the affirmative. To do so, we are studying here the fine structure of ultraproducts of finite sets, so our investigations have a model theoretic character.
CORRIGENDUM: An empirical approach to K-shell ionisation cross section by electrons

The working out of an empirical expression for the cross section for production of atomic K-shell vacancies by electrons is described. The basis is a critical analysis of the existing experimental data. The ranges for which the function is evaluated are 6<or=Z<or=79 and 1<or=U<or=20 (U being the ratio between the incident electron energy and the binding energy of electrons in the K shell). The possible meanings of the various factors present in the expression are examined by comparison with the asymptotic Bethe expression. The results obtained by the empirical function can also be applied to both Z and U intervals even wider than those first considered.
HLA-DR alleles determine responsiveness to Borrelia burgdoferi antigens

Objective— Arthritis is a prominent manifestation of Lyme disease, caused upon infection with Borrelia burgdorferi (Bb) . Persistent chronic Lyme arthritis, even after antibiotic treatment, is linked to HLA-DRB1*0401 (DR4) and related alleles. On the contrary, Lyme patients who resolve arthritis within 3 months post-infection show an increased frequency of HLA-DRB1*1101 (DR11). The aim of this study was to analyze the underlying mechanism by which HLA-DR alleles confer genetic susceptibility or resistance to antibiotic-refractory Lyme arthritis. Methods— We generated DR11 transgenic (tg) mice on a murine class II − / − background and compared their immune response to Bb -antigens to that of DR4 tg mice after immunization with Bb outer surface protein (Osp)A or infection with live Bb . Results— We report that the T cells of OspA-immunized and Bb -infected DR11 tg mice were defective in IFN- γ production compared to those of DR4 mice. On the other hand, DR11 tg mice developed higher titers of anti-OspA and anti- Bb Abs, respectively, than DR4 mice. In accordance with this observation, we found that Bb -infected DR11 tg mice had decreased spirochetal burden compared to DR4 mice, measured by qPCR. Conclusion— This study provides direct evidence that in the presence of HLA-DR11 the immune response against Bb- antigens is directed towards a protective Ab response. In contrast, an inflammatory Th1 response is induced in the presence of DR4. These observations offer an explanation for the differential genetic susceptibility of DR4 + and DR11 + individuals for the development of chronic Lyme arthritis and eventually the progression to antibiotic-refractory Lyme arthritis.