Formulation and performance of variational integrators for rotating bodies

Variational integrators are obtained for two mechanical systems whose configuration spaces are, respectively, the rotation group and the unit sphere. In the first case, an integration algorithm is presented for Euler’s equations of the free rigid body, following the ideas of Marsden et al. (Nonlinearity 12:1647–1662, 1999). In the second example, a variational time integrator is formulated for the rigid dumbbell. Both methods are formulated directly on their nonlinear configuration spaces, without using Lagrange multipliers. They are one-step, second order methods which show exact conservation of a discrete angular momentum which is identified in each case. Numerical examples illustrate their properties and compare them with existing integrators of the literature

Combining Path Integration and Remembered Landmarks When Navigating without Vision

This study investigated the interaction between remembered landmark and path integration strategies for estimating current location when walking in an environment without vision. We asked whether observers navigating without vision only rely on path integration information to judge their location, or whether remembered landmarks also influence judgments. Participants estimated their location in a hallway after viewing a target (remembered landmark cue) and then walking blindfolded to the same or a conflicting location (path integration cue). We found that participants averaged remembered landmark and path integration information when they judged that both sources provided congruent information about location, which resulted in more precise estimates compared to estimates made with only path integration. In conclusion, humans integrate remembered landmarks and path integration in a gated fashion, dependent on the congruency of the information. Humans can flexibly combine information about remembered landmarks with path integration cues while navigating without visual information.National Institutes of Health (U.S.) (Grant T32 HD007151)National Institutes of Health (U.S.) (Grant T32 EY07133)National Institutes of Health (U.S.) (Grant F32EY019622)National Institutes of Health (U.S.) (Grant EY02857)National Institutes of Health (U.S.) (Grant EY017835-01)National Institutes of Health (U.S.) (Grant EY015616-03)United States. Department of Education (H133A011903

Mycobacterium tuberculosis lineage 4 comprises globally distributed and geographically restricted sublineages

Generalist and specialist species differ in the breadth of their ecological niches. Little is known about the niche width of obligate human pathogens. Here we analyzed a global collection of Mycobacterium tuberculosis lineage 4 clinical isolates, the most geographically widespread cause of human tuberculosis. We show that lineage 4 comprises globally distributed and geographically restricted sublineages, suggesting a distinction between generalists and specialists. Population genomic analyses showed that, whereas the majority of human T cell epitopes were conserved in all sublineages, the proportion of variable epitopes was higher in generalists. Our data further support a European origin for the most common generalist sublineage. Hence, the global success of lineage 4 reflects distinct strategies adopted by different sublineages and the influence of human migration.We thank S. Lecher, S. Li and J. Zallet for technical support. Calculations were performed at the sciCORE scientific computing core facility at the University of Basel. This work was supported by the Swiss National Science Foundation (grants 310030_166687 (S.G.) and 320030_153442 (M.E.) and Swiss HIV Cohort Study grant 740 to L.F.), the European Research Council (309540-EVODRTB to S.G.), TB-PAN-NET (FP7-223681 to S.N.), PathoNgenTrace projects (FP7-278864-2 to S.N.), SystemsX.ch (S.G.), the German Center for Infection Research (DZIF; S.N.), the Novartis Foundation (S.G.), the Natural Science Foundation of China (91631301 to Q.G.), and the National Institute of Allergy and Infectious Diseases (5U01-AI069924-05) of the US National Institutes of Health (M.E.)

Lack of microbiological concordance between bone and non-bone specimens in chronic osteomyelitis: an observational study

BACKGROUND: Prognosis of chronic osteomyelitis depends heavily on proper identification and treatment of the bone-infecting organism. Current knowledge on selecting the best specimen for culture is confusing, and many consider that non-bone specimens are suitable to replace bone cultures. This paper compares the microbiology of non-bone specimens with bone cultures, taking the last as the diagnostic gold standard. METHODS: Retrospective observational analysis of 50 patients with bacterial chronic osteomyelitis in a 750-bed University-based hospital. RESULTS: Concordance between both specimens for all etiologic agents was 28%, for Staphylococcus aureus 38%, and for organisms other than S. aureus 19%. The culture of non-bone specimens to identify the causative organisms in chronic osteomyelitis produced 52% false negatives and 36% false positives when compared against bone cultures. CONCLUSIONS: Diagnosis and therapy of chronic osteomyelitis cannot be guided by cultures of non-bone specimens because their microbiology is substantially different to the microbiology of the bone

Comparison of risk patterns in carcinoma and melanoma of the skin in men: a multi-centre case–case–control study

We directly compared risk factors between 214 histologically confirmed melanomas (CMM), 215 basal-cell carcinomas (BCC) and 139 squamous-cell carcinomas (SCC) in a multiple case–case–control study with 349 controls from patients without dermatological disease admitted to the same hospitals. Subjects with fair hair had a significant risk increase for all types of tumours at a comparable level (ORadj for blonde hair: CMM 2.3; SCC 2.4; BCC 2.3). The effect of pale eyes was significant and similar for CMM and BCC (ORadj 2.6). Intermittent sun exposure measured in hours spent at beach during holidays was significant for both CMM (ORadj 2.6 for more than 7000 lifelong hours) and BCC (ORadj 2.1 for more than 7000 lifelong hours), while SCC exhibited a significant risk increase for chronic exposure to sunlight measured in hours of outdoor work (ORadj 2.2 for more than 6000 lifelong hours). In the case–case comparison using a multinomial logistic regression model, we found a statistically significant risk difference for pale eyes, and number of naevi in the CMM group, compared to other skin cancers. For intermittent sun exposure, there was a significant risk difference of BCC when compared to the risk of SCC. Factors influencing risk of SCC are different, with chronic exposure to sun playing a major role in causing this type of carcinoma

A comparison of methods for purification and concentration of norovirus GII-4 capsid virus-like particles

Noroviruses (NoVs) are one of the leading causes of acute gastroenteritis worldwide. NoV GII-4 VP1 protein was expressed in a recombinant baculovirus system using Sf9 insect cells. Several methods for purification and concentration of virus-like particles (VLPs) were evaluated. Electron microscopy (EM) and histo-blood group antigen (HBGA) binding assays showed that repeated sucrose gradient purification followed by ultrafiltration resulted in intact VLPs with excellent binding to H type 3 antigens. VLPs were stable for at least 12 months at 4°C, and up to 7 days at ambient temperature. These findings indicate that this method yielded stable and high-quality VLPs

Construct Validity in Cross-Cultural, Developmental Research: Challenges and Strategies for Improvement

Data Availability Statement: This manuscript does not rely on any data, code or other resources.This is a “preproof” accepted article for Evolutionary Human Sciences. This version may be subject to change during the production process.The recent expansion of cross-cultural research in the social sciences has led to increased discourse on methodological issues involved when studying culturally diverse populations. However, discussions have largely overlooked the challenges of construct validity- ensuring instruments are measuring what they are intended to- in diverse cultural contexts, particularly in developmental research. We contend that cross-cultural developmental research poses distinct problems for ensuring high construct validity, owing to the nuances of working with children and that the standard approach of transporting protocols designed and validated in one population to another risks low construct validity. Drawing upon our own and others’ work, we highlight several challenges to construct validity in the field of cross-cultural developmental research, including 1) lack of cultural and contextual knowledge, 2) dissociating developmental and cultural theory and methods, 3) lack of causal frameworks, 4) superficial and short- term partnerships and collaborations, and 5) culturally inappropriate tools and tests. We provide guidelines to address these challenges, including 1) using ethnographic and observational approaches, 2) developing evidence-based causal frameworks, 3) conducting community-engaged and collaborative research, and 4) culture-specific refinements and training. We discuss the need to balance methodological consistency with culture-specific refinements to improve construct validity in cross-cultural developmental research.This work was supported by a Cultural Evolution Society New Investigator Award and Society for Research in Child Development Early Career Scholars Grant to NJW, as well as a Cultural Evolution Society Workshop Fund to NJW. and BSR. BSR was also supported by a UKRI ESRC New Investigator Grant, number ES/Y005600/1

Arterial Embolization Hyperthermia Using As2O3 Nanoparticles in VX2 Carcinoma–Induced Liver Tumors

BACKGROUND: Combination therapy for arterial embolization hyperthermia (AEH) with arsenic trioxide (As(2)O(3)) nanoparticles (ATONs) is a novel treatment for solid malignancies. This study was performed to evaluate the feasibility and therapeutic effect of AEH with As(2)O(3) nanoparticles in a rabbit liver cancer model. The protocol was approved by our institutional animal use committee. METHODOLOGY/PRINCIPAL FINDINGS: In total, 60 VX(2) liver-tumor-bearing rabbits were randomly assigned to five groups (n = 12/group) and received AEH with ATONs (Group 1), hepatic arterial embolization with ATONs (Group 2), lipiodol (Group 3), or saline (Group 4), on day 14 after tumor implantation. Twelve rabbits that received AEH with ATONs were prepared for temperature measurements, and were defined as Group 5. Computed tomography was used to measure the tumors' longest dimension, and evaluation was performed according to the Response Evaluation Criteria in Solid Tumors. Hepatic toxicity, tumor necrosis rate, vascular endothelial growth factor level, and microvessel density were determined. Survival rates were measured using the Kaplan-Meier method. The therapeutic temperature (42.5°C) was obtained in Group 5. Hepatotoxicity reactions occurred but were transient in all groups. Tumor growth was delayed and survival was prolonged in Group 1 (treated with AEH and ATONs). Plasma and tumor vascular endothelial growth factor and microvessel density were significantly inhibited in Group 1, while tumor necrosis rates were markedly enhanced compared with those in the control groups. CONCLUSIONS: ATON-based AEH is a safe and effective treatment that can be targeted at liver tumors using the dual effects of hyperthermia and chemotherapy. This therapy can delay tumor growth and noticeably inhibit tumor angiogenesis

Oscillatory Dynamics of Cell Cycle Proteins in Single Yeast Cells Analyzed by Imaging Cytometry

Progression through the cell division cycle is orchestrated by a complex network of interacting genes and proteins. Some of these proteins are known to fluctuate periodically during the cell cycle, but a systematic study of the fluctuations of a broad sample of cell-cycle proteins has not been made until now. Using time-lapse fluorescence microscopy, we profiled 16 strains of budding yeast, each containing GFP fused to a single gene involved in cell cycle regulation. The dynamics of protein abundance and localization were characterized by extracting the amplitude, period, and other indicators from a series of images. Oscillations of protein abundance could clearly be identified for Cdc15, Clb2, Cln1, Cln2, Mcm1, Net1, Sic1, and Whi5. The period of oscillation of the fluorescently tagged proteins is generally in good agreement with the inter-bud time. The very strong oscillations of Net1 and Mcm1 expression are remarkable since little is known about the temporal expression of these genes. By collecting data from large samples of single cells, we quantified some aspects of cell-to-cell variability due presumably to intrinsic and extrinsic noise affecting the cell cycle

Running away experience and psychoactive substance use among adolescents in Taiwan: multi-city street outreach survey

<p>Abstract</p> <p>Background</p> <p>This study aimed to examine: 1) the relationship between being a runaway and the time since the first absconding event and adolescent substance use; 2) whether different kinds of psychoactive substances have a different temporal relationship to the first absconding event; and 3) whether the various reasons for the first absconding event are associated with different risks of substance use.</p> <p>Methods</p> <p>Participants were drawn from the 2004-2006 nationwide outreach programs across 26 cities/towns in Taiwan. A total of 17,133 participants, age 12-18 years, who completed an anonymous questionnaire on their experience of running away and substances use and who were now living with their families, were included in the analysis.</p> <p>Results</p> <p>The lifetime risk of tobacco, alcohol, betel nut, and illegal drug/inhalant use increased steadily from adolescents who had experienced a trial runaway episode (one time lasting ≤ 1 day), to those with extended runaway experience (≥ 2 times or lasting > 1 day), when compared to those who had never ran away. Adolescents who had their first running away experience > 6 months previously had a greater risk of betel nut or illegal drug/inhalant use over the past 6-months than those with a similar experience within the last 6 months. Both alcohol and tobacco use were most frequently initiated before the first running away, whereas both betel nut and illegal drug/inhalant use were most frequently initiated after this event. When adolescents who were fleeing an unsatisfactory home life were compared to those who ran away for excitement, the risk of alcohol use was similar but the former tended to have a higher risk of tobacco, betel nut, and illegal drug/inhalant use.</p> <p>Conclusions</p> <p>More significant running away and a longer time since the first absconding experience were associated with more advanced substance involvement among adolescents now living in a family setting. Once adolescents had left home, they developed additional psychoactive substance problems, regardless of their reasons for running away. These findings have implications for caregivers, teachers, and healthcare workers when trying to prevent and/or intervening in adolescent substance use.</p