Evaluation of the Indian Migration Study Physical Activity Questionnaire (IMS-PAQ): a cross-sectional study.
Socio-cultural differences for country-specific activities are rarely addressed in physical activity questionnaires. We examined the reliability and validity of the Indian Migration Study Physical Activity Questionnaire (IMS-PAQ) in urban and rural groups in India. A sub-sample of IMS participants (n = 479) was used to examine short term (≤ 1 month [n = 158]) and long term (> 1 month [n = 321]) IMS-PAQ reliability for levels of total, sedentary, light and moderate/vigorous activity (MVPA) intensity using intraclass correlation (ICC) and kappa coefficients (k). Criterion validity (n = 157) was examined by comparing the IMS-PAQ to a uniaxial accelerometer (ACC) worn ≥ 4 days, via Spearman's rank correlations (ρ) and k, using Bland-Altman plots to check for systematic bias. Construct validity (n = 7,000) was established using linear regression, comparing IMS-PAQ against theoretical constructs associated with physical activity (PA): BMI [kg/m2], percent body fat and pulse rate. IMS-PAQ reliability ranged from ICC 0.42-0.88 and k = 0.37-0.61 (≤ 1 month) and ICC 0.26 to 0.62; kappa 0.17 to 0.45 (> 1 month). Criterion validity was ρ = 0.18-0.48; k = 0.08-0.34. Light activity was underestimated and MVPA consistently and substantially overestimated for the IMS-PAQ vs. the accelerometer. Criterion validity was moderate for total activity and MVPA. Reliability and validity were comparable for urban and rural participants but lower in women than men. Increasing time spent in total activity or MVPA, and decreasing time in sedentary activity were associated with decreasing BMI, percent body fat and pulse rate, thereby demonstrating construct validity. IMS-PAQ reliability and validity is similar to comparable self-reported instruments. It is an appropriate tool for ranking PA of individuals in India. Some refinements may be required for sedentary populations and women in India.


Small-Group Activity to Reinforce the Impact of Valvular Defects and Heart Failure on Cardiac Pressure-Volume Relationships.
An important topic in cardiac physiology is the relationship between changes in intracardiac pressures and volumes during the cardiac cycle. This topic lends itself well to utilizing active learning principles to facilitate student understanding of pressure and volume changes in normal cardiac physiology and in the pathophysiology of valve disease and heart failure. We describe an active learning exercise regarding this topic that engages and facilitates student learning in a small-group setting. Following an overview lecture on the normal cardiac physiology, small groups of students under the guidance of a facilitator were provided with a worksheet consisting of questions related to background knowledge of cardiac physiology. Additional questions related to five valve disease and heart failure cases were also provided to promote the application of basic physiology principles to clinically relevant problems. The facilitator was provided with a guide to help facilitate the student interactions. Following the group worksheet activity, an animated slide presentation was shown to further engage student learning through active discussion of their worksheet answers. Students were assessed by written examination, and were found to have a higher performance on the subset of questions related to this learning activity compared to the overall exam. Of the 175 students completing the exercise, 23 voluntarily provided feedback via a survey. Student surveys provided overwhelmingly positive feedback on the benefits of this active learning exercise. Small group, active learning exercises benefited student learning by providing a framework for analysis, synthesis, and application of clinically relevant cardiac physiology concepts.


The prognostic value of β-catenin and LEF-1 expression in patients with operable gastric carcinoma.
The aim of this study is to evaluate the prognostic value of β-catenin and LEF-1 expression in patients with operable gastric cancer that receive adjuvant treatment and the relationship between demographic and histopathological variables. In this study, 82 gastric cancer patients treated with adjuvant treatment after surgery and followed in the Medical Oncology Department of Kocaeli University were included. β-catenin and LEF-1 expression were examined by immunuhistochemical analysis in paraffin embedded tumor tissues of the patients. Median age was 56 (26-81) and follow up was 19 months (4-61). Performance status (ECOG) were 0-1 in all patients. Male/female ratio was 53/29 (64.6/35.4%). The median disease free survival (DFS) time was 17 months (SE: 3 95% CI: 11-23) and 3 years DFS rate was 39.7%. The median overall survival (OS) time was 28 months (SE: 4 95% CI: 20-36) and 3 years OS rate was 41.2%. There was no statistical correlation between β-catenin and LEF-1 expression and age, gender, performance status, tumor localization, T and N stage, lymphovascular, perinoral invasion, grade and operation type (>0.005). According to univariate analysis, we did not find significant effect of age, gender, T stage, lymphovascular, perinoral invasion, grade and operation type on overall survival (p>0.005). Good performance status (ECOG 0), tumor infiltration without diffuse type like linitis plastica, and lower N stage had positive effect on survival respectively (p=0.04, 0.033 and 0.005). In this study group, we found that only N stage was an independent prognostic factor (<0.005). Demographic features of the patients, histopathological characteristics other than N stage, β-catenin and LEF-1 prognostic effects have not been shown.


Relationships of physical performance tests to military-relevant tasks in women.
This investigation sought to determine the most predictive measures of performance on a repetitive box lifting task (RBLT) and load bearing task (LBT) among 123 women (aged ±4 years, height 165±7 cm, body mass 64±10 kg). To determine the relationship of various predictors to performance on the RBLT and LBT, multiple regression analysis was conducted on body mass, height, leg cross-sectional area, upper and lower body muscular strength, lower body explosive power, upper and lower body local muscular endurance, and aerobic capacity. The mean±SD (range) number of repetitions for the RBLT was 86±23 (20-159). The mean±SD (range) time to complete the LBT was 2,054±340 seconds (1,307-3,447). The following equations were generated: RBLT (number of repetitions)=57.4+0.2(peak jump power)+0.4(number of pushups in 2 minutes)+0.15(number of repetitions during the squat endurance test)+1.39(one repetition maximal strength boxlift (kg))-0.04(2-mile run time (2MR) in seconds), R=0.81; standard error of the estimate (SEE)=14; LBT (in seconds)=1,831-4.28(number of repetitions during the squat endurance test)+0.95(2MR in seconds)-13.4(body mass), R=0.73; SEE=232. We found that the 2MR and squat endurance test were significant predictive factors for performance on both load carriage tasks. These data also imply that women's performance in combat-related tasks can be improved with training that targets muscular strength, power, and local muscular endurance in addition to aerobic capacity.


US secondary schools and food outlets.
We examined the availability of fast food restaurants and convenience stores within walking distance (0.5 miles or 805 m) of US public secondary schools. We found that one-third of schools nationwide have at least one fast food restaurant or convenience store within walking distance. In multivariate analyses, schools in the lowest-income versus the highest-income neighborhoods have more fast food restaurants and convenience stores, while schools in African-American versus White neighborhoods generally have fewer food outlets. Furthermore, urban neighborhoods with a high school versus no secondary school have more food outlets. Curbing the obesity epidemic among adolescents requires addressing the food environment surrounding schools.


A thaumarchaeal provirus testifies for an ancient association of tailed viruses with archaea.
Archaeal viruses, or archaeoviruses, display a wide range of virion morphotypes. Whereas the majority of those morphotypes are unique to archaeal viruses, some are more widely distributed across different cellular domains. Tailed double-stranded DNA archaeoviruses are remarkably similar to viruses of the same morphology (order Caudovirales) that infect many bacterial hosts. They have, so far, only been found in one phylum of the archaea, the Euryarchaeota, which has led to controversial hypotheses about their origin. In the present paper, we describe the identification and analysis of a putative provirus present in the genome of a mesophilic thaumarchaeon. We show that the provirus is related to tailed bacterial and euryarchaeal viruses and encodes a full complement of proteins that are required to build a tailed virion. The recently discovered wide distribution of tailed viruses in Euryarchaeota and the identification of a related provirus in Thaumarchaeota, an archaeal phylum which might have branched off before the separation of Crenarchaeota and Euryarchaeota, suggest that an association of these viruses with Archaea might be more ancient than previously anticipated.


Hearing loss prevention for carpenters: part 1 - using health communication and health promotion models to develop training that works.
In phase 1 of a large multiyear effort, health communication and health promotion models were used to develop a comprehensive hearing loss prevention training program for carpenters. Additionally, a survey was designed to be used as an evaluation instrument. The models informed an iterative research process in which the authors used key informant interviews, focus groups, and early versions of the survey tool to identify critical issues expected to be relevant to the success of the hearing loss prevention training. Commonly held attitudes and beliefs associated with occupational noise exposure and hearing losses, as well as issues associated with the use or non-use of hearing protectors, were identified. The training program was then specifically constructed to positively shape attitudes, beliefs, and behavioral intentions associated with healthy hearing behaviors - especially those associated with appropriate hearing protector use. The goal was to directly address the key issues and overcome the barriers identified during the formative research phase. The survey was finalized using factor analysis methods and repeated pilot testing. It was designed to be used with the training as an evaluation tool and thus could indicate changes over time in attitudes, beliefs, and behavioral intentions regarding hearing loss prevention. Finally, the training program was fine tuned with industry participation so that its delivery would integrate seamlessly into the existing health and safety training provided to apprentice carpenters. In phase 2, reported elsewhere in this volume, the training program and the survey were tested through a demonstration project at two sites.


Tokamak magnetohydrodynamic equilibrium states with axisymmetric boundary and a 3D helical core.
Magnetohydrodynamic (MHD) equilibrium states with imposed axisymmetric boundary are computed in which a spontaneous bifurcation develops to produce an internal three-dimensional (3D) configuration with a helical structure in addition to the standard axisymmetric system. Equilibrium states with similar MHD energy levels are shown to develop very different geometric structures. The helical equilibrium states resemble saturated internal kink mode structures.


Comparison of the effects of mizoribine with those of azathioprine, 6-mercaptopurine, and mycophenolic acid on T lymphocyte proliferation and purine ribonucleotide metabolism.
The immunosuppressive drug mizoribine has been demonstrated to inhibit T lymphocyte proliferation by depleting these cells of guanine ribonucleotides as a consequence of inhibiting the enzyme inosine monophosphate (IMP) dehydrogenase. Because the immunosuppressive agents azathioprine and 6-mercaptopurine (6MP) are both converted to the IMP analog 6-thio-IMP, we postulated that these drugs might inhibit T cell activation and/or proliferation by a similar mechanism. Incubation of isolated peripheral blood T cells with either mizoribine or the selective IMP dehydrogenase inhibitor mycophenolic acid caused a dose-dependent inhibition of T cell proliferation, which was reversible with the addition of 50 microM guanosine to replete guanine ribonucleotide pools. In contrast, guanosine exacerbated the inhibition of proliferation induced by azathioprine and restored proliferation at IC50 concentrations of 6MP by only 10%. Complete restoration of proliferation in the presence of 6MP, but not azathioprine, was achieved with the addition of adenine. The inhibitory effects of azathioprine, as well as those of mizoribine, 6MP, and mycophenolic acid, were identical in cells stimulated with antibody to the T cell receptor and in cells stimulated with phorbol ester and ionomycin. We conclude from these studies that mizoribine selectively inhibits guanine ribonucleotide formation in purified T cells, whereas the effect of 6MP appears to be more dependent on adenine ribonucleotide depletion. Azathioprine, on the other hand, inhibits proliferation by a mechanism independent of purine ribonucleotide depletion. None of these agents inhibits T cell proliferation by interfering with signal transduction mediated by the T cell receptor. Inhibition of guanine ribonucleotide biosynthesis appears to be a novel and perhaps more selective mechanism of inhibiting T cell proliferative responses after T cell activation.


Observation of 54Ni: cross-conjugate symmetry in f7/2 mirror energy differences.
Gamma decays from excited states up to Jpi=6+ in the N=Z-2 nucleus 54Ni have been identified for the first time. Level energies are compared with those of the isobars 54Co and 54Fe and of the cross-conjugate nuclei of mass A=42. The good but puzzling f7/ cross-conjugate symmetry in mirror and triplet energy differences is analyzed. Shell model calculations reproduce the new data but the necessary nuclear charge-dependent phenomenology is not fully explained by modern nucleon-nucleon potentials.


Data-driven analysis of immune infiltrate in a large cohort of breast cancer and its association with disease progression, ER activity, and genomic complexity.
The tumor microenvironment is now widely recognized for its role in tumor progression, treatment response, and clinical outcome. The intratumoral immunological landscape, in particular, has been shown to exert both pro-tumorigenic and anti-tumorigenic effects. Identifying immunologically active or silent tumors may be an important indication for administration of therapy, and detecting early infiltration patterns may uncover factors that contribute to early risk. Thus far, direct detailed studies of the cell composition of tumor infiltration have been limited; with some studies giving approximate quantifications using immunohistochemistry and other small studies obtaining detailed measurements by isolating cells from excised tumors and sorting them using flow cytometry. Herein we utilize a machine learning based approach to identify lymphocyte markers with which we can quantify the presence of B cells, cytotoxic T-lymphocytes, T-helper 1, and T-helper 2 cells in any gene expression data set and apply it to studies of breast tissue. By leveraging over 2,100 samples from existing large scale studies, we are able to find an inherent cell heterogeneity in clinically characterized immune infiltrates, a strong link between estrogen receptor activity and infiltration in normal and tumor tissues, changes with genomic complexity, and identify characteristic differences in lymphocyte expression among molecular groupings. With our extendable methodology for capturing cell type specific signal we systematically studied immune infiltration in breast cancer, finding an inverse correlation between beneficial lymphocyte infiltration and estrogen receptor activity in normal breast tissue and reduced infiltration in estrogen receptor negative tumors with high genomic complexity.


New structural insights into mechanically interlocked polymers revealed by ion mobility mass spectrometry.
Mechanically interlocked polymers can possess significant additional physical properties, in comparison to those associated with their constituent parts. Their unique properties make them attractive for a range of potential applications, such as as biomaterials and molecular machines. Their efficient and reproducible synthesis is therefore of much interest. Both their synthesis and subsequent characterization are intriguing yet demanding. The properties of mechanically interlocked polymeric systems depend not only on the properties of their individual components but also on the topology of the subsequent product. Here traveling wave ion mobility mass spectrometry has been used to investigate the structural properties of a polyrotaxane system. Ion mobility studies reveal that this system remains linear in form with increase in size. Both ion mobility studies and tandem mass spectrometry studies indicate that the macrocycle preferentially remains associated with the ammonium moiety of the polymeric repeat unit and is impeded from moving freely along the axle. This is consistent with NMR observations of the average structure. Analysis of mechanically interlocked polymers by ion mobility mass spectrometry provides additional structural insights into these systems relating to dynamics, heterogeneity, and topology. This molecule-specific information is vital in order to understand the origin of a system's functional properties.


Intravenous ibandronate injections in postmenopausal women with osteoporosis: one-year results from the dosing intravenous administration study.
Although oral bisphosphonates are effective treatments for postmenopausal women with osteoporosis, oral dosing may be unsuitable for some patients. An efficacious intravenously administered bisphosphonate could be beneficial for such patients. Ibandronate, a potent nitrogen-containing bisphosphonate, can be administered using extended dosing intervals, either orally or by rapid intravenous injection. The aim of this study was to identify the optimal intravenous dosing regimen for ibandronate in postmenopausal women with osteoporosis. In a randomized, double-blind, double-dummy, phase III, noninferiority study, we compared 2 regimens of intermittent intravenous injections of ibandronate (2 mg every 2 months and 3 mg every 3 months) with a regimen of 2.5 mg of oral ibandronate daily, the latter of which has proven antifracture efficacy. The study group comprised 1,395 women (ages 55-80 years) who were at least 5 years postmenopausal. All patients had osteoporosis (lumbar spine [L2-L4] bone mineral density [BMD] T score less than -2.5). Participants also received daily calcium (500 mg) and vitamin D (400 IU). The primary end point was change from baseline in lumbar spine BMD at 1 year. Changes in hip BMD and in the level of serum C-telopeptide of type I collagen (CTX) were also measured, as were safety and tolerability. At 1 year, mean lumbar spine BMD increases were as follows: 5.1% among 353 patients receiving 2 mg of ibandronate every 2 months, 4.8% among 365 patients receiving 3 mg of ibandronate every 3 months, and 3.8% among 377 patients receiving 2.5 mg of oral ibandronate daily. Both of the intravenous regimens not only were noninferior, but also were superior (P < 0.001) to the oral regimen. Hip BMD increases (at all sites) were also greater in the groups receiving medication intravenously than in the group receiving ibandronate orally. Robust decreases in the serum CTX level were observed in all arms of the study. Both of the intravenous regimens were well tolerated and did not compromise renal function. As assessed by BMD, intravenous injections of ibandronate (2 mg every 2 months or 3 mg every 3 months) are at least as effective as the regimen of 2.5 mg orally daily, which has proven antifracture efficacy, and are well tolerated.


Expression of parathyroid hormone-related protein and the parathyroid hormone/parathyroid hormone-related protein receptor in rat thymic epithelial cells.
Thymic epithelial cells are an important source of cytokines and other regulatory peptides which guide thymocyte proliferation and maturation. Parathyroid hormone-related protein (PTHrP), a cytokine-like peptide, has been reported to affect the proliferation of lymphocytes in vitro. The studies presented here were undertaken to test the hypotheses that PTHrP is produced locally within the thymus where it could influence thymocyte maturation and, more specifically, that thymic epithelial cells (TEC) could be the intrathymic source of PTHrP expression. To this end, immunohistochemical studies were performed to localise PTHrP and the PTH/PTHrP receptor within the adult rat thymus. Antibodies directed against 2 different PTHrP epitopes, PTHrP(1-34) and PTHrP(34-53), demonstrated prominent specific PTHrP immunoreactivity in both subcapsular and medullary TEC. In addition, faint but specific staining for PTHrP was seen in the cortex, interdigitating between cortical lymphocytes while sparing epithelial-free subcapsular areas, thus suggesting that cortical TEC could also be a source of PTHrP immunoreactivity. In contrast, PTH/PTHrP receptor immunoreactivity was only seen in medullary and occasional septal TEC; no evidence of cortical or lymphocytic PTH/PTHrP receptor immunoreactivity was detected. Immunohistochemical studies of cultured cytokeratin-positive rat TEC confirmed the results of these in situ studies as cultured TEC were immunoreactive both for PTHrP and the PTH/PTHrP receptor. Thus these results demonstrate that PTHrP is produced by the epithelial cells of the mature rat thymus. This suggests that PTHrP, a peptide with known cytokine, growth factor and neuroendocrine actions, could exert important intrathymic effects mediated by direct interactions with TEC, or indirect effects on PTH/PTHrP receptor-negative thymocytes.


Polyploidy and failed fertilization in in-vitro fertilization are related to patient's age and gamete quality.
A review of 392 cycles of in-vitro fertilization (IVF) was carried out in order to identify whether any factors such as sperm concentration at insemination, sperm motility or morphology, oocyte grading, number of oocytes retrieved, patient age, follicular stimulation protocols or duration of follicular growth, could be associated with the incidence of polyploidy or completely failed fertilization. The majority of polypronuclear fertilizations occurred in mature oocytes and in patients < 37 years of age and the incidence of polyploidy was strongly associated with fertilization and pregnancy rates. Fertilization rates were highest with mature oocytes. A significant linear trend was observed with failed fertilization and sperm concentration, morphology and motility. High rates of failed fertilization were found in patients > 37 years of age and with one to five oocytes retrieved. No significant difference was seen in stimulation protocols and oocyte grading between oocytes that fertilized and those that did not. Cycles with good sperm morphology and motility, the presence of mature oocytes, the retrieval of a large number of oocytes and younger maternal age seem to provide the best chance for IVF success.


Quantification of the effects of VRN1 and Ppd-D1 to predict spring wheat (Triticum aestivum) heading time across diverse environments.
Heading time is a major determinant of the adaptation of wheat to different environments, and is critical in minimizing risks of frost, heat, and drought on reproductive development. Given that major developmental genes are known in wheat, a process-based model, APSIM, was modified to incorporate gene effects into estimation of heading time, while minimizing degradation in the predictive capability of the model. Model parameters describing environment responses were replaced with functions of the number of winter and photoperiod (PPD)-sensitive alleles at the three VRN1 loci and the Ppd-D1 locus, respectively. Two years of vernalization and PPD trials of 210 lines (spring wheats) at a single location were used to estimate the effects of the VRN1 and Ppd-D1 alleles, with validation against 190 trials (~4400 observations) across the Australian wheatbelt. Compared with spring genotypes, winter genotypes for Vrn-A1 (i.e. with two winter alleles) had a delay of 76.8 degree days (°Cd) in time to heading, which was double the effect of the Vrn-B1 or Vrn-D1 winter genotypes. Of the three VRN1 loci, winter alleles at Vrn-B1 had the strongest interaction with PPD, delaying heading time by 99.0 °Cd under long days. The gene-based model had root mean square error of 3.2 and 4.3 d for calibration and validation datasets, respectively. Virtual genotypes were created to examine heading time in comparison with frost and heat events and showed that new longer-season varieties could be heading later (with potential increased yield) when sown early in season. This gene-based model allows breeders to consider how to target gene combinations to current and future production environments using parameters determined from a small set of phenotyping treatments.


Outcome of Noninvasive Ventilation in Acute Respiratory Failure.
Noninvasive ventilation (NIV) represents the delivery of positive pressure to the lungs without inserting an endotracheal tube. Noninvasive ventilation has been successfully used in patients with acute respiratory failure. There is a tremendous increase in usage of NIV in clinical settings aiming to reduce complications due to invasive ventilation and to improve resource utilization. It is imperative to watch for outcome of NIV in patients with acute respiratory failure. A total of 50 patients were included in this prospective longitudinal study and divided into two groups: type I and type II respiratory failure. All patients were administered bilevel positive airway pressure (BIPAP) ventilator support system using full-face mask or nasal mask depending on the status of the patient. Dyspnea quantitated by modified Borg dyspnea score, heart rate (HR), respiratory rate (RR), blood pressure, and arterial blood gas analysis were assessed at the end of 4, 12, and 24 hours. Respiratory rate and HR were significantly improved at the end of 4, 12, and 24 hours with NIPPV compared with baseline (0 hour) in both groups (p < 0.01). Statistically significant improvements in pH and PaO2 was seen with NIPPV at the end of 12 hours and 24 hours (p < 0.001) compared with the baseline in both type I and type II respiratory failure patients. Dryness of mouth and nose was noted in 3 (6.81%) patients with NIPPV. Study indicates that a trial of BIPAP is effective in improving gas exchange, reducing intubation, and length of stay in hospital in patients with acute respiratory failure. Arsude S, Sontakke A, Jire A. Outcome of Noninvasive Ventilation in Acute Respiratory Failure. Indian J Crit Care Med 2019;23(12):556-561.


Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors.
Traditional treatment of infectious diseases is based on compounds that kill or inhibit growth of bacteria. A major concern with this approach is the frequent development of resistance to antibiotics. The discovery of communication systems (quorum sensing systems) regulating bacterial virulence has afforded a novel opportunity to control infectious bacteria without interfering with growth. Compounds that can override communication signals have been found in the marine environment. Using Pseudomonas aeruginosa PAO1 as an example of an opportunistic human pathogen, we show that a synthetic derivate of natural furanone compounds can act as a potent antagonist of bacterial quorum sensing. We employed GeneChip microarray technology to identify furanone target genes and to map the quorum sensing regulon. The transcriptome analysis showed that the furanone drug specifically targeted quorum sensing systems and inhibited virulence factor expression. Application of the drug to P.aeruginosa biofilms increased bacterial susceptibility to tobramycin and SDS. In a mouse pulmonary infection model, the drug inhibited quorum sensing of the infecting bacteria and promoted their clearance by the mouse immune response.


A simple and convenient approach for preparing core-shell-like silica@nickel species nanoparticles: highly efficient and stable catalyst for the dehydrogenation of 1,2-cyclohexanediol to catechol.
A simple and convenient approach denoted as gel-deposition-precipitation (G-D-P) for the preparation of core-shell-like silica@nickel species nanoparticles was studied systematically. Core-shell-like silica@nickel species nanoparticles consisted of a Si-rich core and a Ni-rich shell. The G-D-P process included two steps: one was the deposition-precipitation of nickel over the gelled colloidal silica particle, generating core-shell-like silica@nickel species nanoparticles, and the other was the aging period. It was found that the nickel phyllosilicate layer was formed mainly during the aging period and served as the protective cover to resist against aggregation of the nanoparticles, which could be utilized for regulating the dispersion of nickel over the silica@nickel species nanoparticles. In the present paper, the silica@nickel species nanoparticles were used as the catalysts for preparing catechol via dehydrogenation of 1,2-cyclohexanediol. Their catalytic activity and long-term stability were compared to those of a catalyst prepared by a conventional deposition-precipitation (D-P) approach. The higher activity and better stability of the title reaction over the silica@nickel species nanoparticles catalyst prepared by G-D-P than those over the catalyst prepared by D-P could be due to the higher dispersion of metallic nickel stabilized by the layers of nickel phyllosilicates. Moreover, it was found that the dehydrogenation of 1,2-cyclohexanediol to catechol was a structurally sensitive reaction.


Planting sentinel European trees in eastern Asia as a novel method to identify potential insect pest invaders.
Quarantine measures to prevent insect invasions tend to focus on well-known pests but a large proportion of the recent invaders were not known to cause significant damage in their native range, or were not even known to science before their introduction. A novel method is proposed to detect new potential pests of woody plants in their region of origin before they are introduced to a new continent. Since Asia is currently considered to be the main supplier of insect invaders to Europe, sentinel trees were planted in China during 2007-2011 as an early warning tool to identify the potential for additional Asian insect species to colonize European trees. Seedlings (1-1.5 m tall) of five broadleaved (Quercus petraea, Q. suber, Q. ilex, Fagus sylvatica, and Carpinus betulus) and two conifer species (Abies alba and Cupressus sempervirens) were planted in blocks of 100 seedlings at two widely separated sites (one in a nursery near Beijing and the other in a forest environment near Fuyang in eastern China), and then regularly surveyed for colonization by insects. A total of 104 insect species, mostly defoliators, were observed on these new hosts, and at least six species were capable of larval development. Although a number of the insects observed were probably incidental feeders, 38 species had more than five colonization events, mostly infesting Q. petraea, and could be considered as being capable of switching to European trees if introduced to Europe. Three years was shown to be an appropriate duration for the experiment, since the rate of colonization then tended to plateau. A majority of the identified species appeared to have switched from agricultural crops and fruit trees rather than from forest trees. Although these results are promising, the method is not appropriate for xylophagous pests and other groups developing on larger trees. Apart from the logistical problems, the identification to species level of the specimens collected was a major difficulty. This situation could be improved by the development of molecular databases.


The Efficacy of Flutter® and Active Cycle of Breathing Techniques in Patients with Bronchiectasis: A Prospective, Randomized, Comparative Study.
The objective of the study was to compare the efficacy of an oscillating positive expiratory device and the active cycle of breathing techniques (ACBT) in patients with bronchiectasis. A home-based study that lasted for 4 weeks was designed to compare the oscillating physiotherapy device Flutter® and the ACBT in 40 patients, who were randomly assigned into two groups containing 20 patients each. The effect of the two methods of physiotherapy on sputum production, pulmonary functions, and the quality of life was compared. The results of the present study indicate that both the methods were associated with a reduced number of patients complaining of cough and fatigue and increased sputum production (p=0.000, p=0.004, and p=0.002, respectively). In addition, statistically significant reductions were determined by the Medical Research Council and Borg Dyspnea scores (p=0.001 and 0.002, respectively). The Flutter® device caused a more significant effect on the perception of dyspnea. Overall, there was an improvement in the physical sub-scale of the Short Form (SF)-36 Quality of Life Questionnaire scores of 36 patients who completed the study (p=0.001). During the physiotherapy period, no changes in pulmonary functions were observed. Exacerbations were recorded in 3 patients in the ACBT group and in 1 patient in the Flutter® group. The Flutter® device and ACBT represent effective home-based physiotherapeutic methods. The Flutter® device appears to be more effective with regard to sputum production.


The leukemia associated nuclear corepressor ETO homologue genes MTG16 and MTGR1 are regulated differently in hematopoietic cells.
MTG16, MTGR1 and ETO are nuclear transcriptional corepressors of the human ETO protein family. MTG16 is implicated in hematopoietic development and in controlling erythropoiesis/megakaryopoiesis. Furthermore, ETO homologue genes are 3'participants in leukemia fusions generated by chromosomal translocations responsible of hematopoietic dysregulation. We tried to identify structural and functional promoter elements of MTG16 and MTGR1 genes in order to find associations between their regulation and hematopoiesis. 5' deletion examinations and luciferase reporter gene studies indicated that a 492 bp sequence upstream of the transcription start site is essential for transcriptional activity by the MTG16 promoter. The TATA- and CCAAT-less promoter with a GC box close to the start site showed strong reporter activity when examined in erythroid/megakaryocytic cells. Mutation of an evolutionary conserved GATA -301 consensus binding site repressed promoter function. Furthermore, results from in vitro antibody-enhanced electrophoretic mobility shift assay and in vivo chromatin immunoprecipitation indicated binding of GATA-1 to the GATA -301 site. A role of GATA-1 was also supported by transfection of small interfering RNA, which diminished MTG16 expression. Furthermore, expression of the transcription factor HERP2, which represses GATA-1, produced strong inhibition of the MTG16 promoter reporter consistent with a role of GATA-1 in transcriptional activation. The TATA-less and CCAAT-less MTGR1 promoter retained most of the transcriptional activity within a -308 to -207 bp region with a GC-box-rich sequence containing multiple SP1 binding sites reminiscent of a housekeeping gene with constitutive expression. However, mutations of individual SP1 binding sites did not repress promoter function; multiple active SP1 binding sites may be required to safeguard constitutive MTGR1 transcriptional activity. The observed repression of MTG16/MTGR1 promoters by the leukemia associated AML1-ETO fusion gene may have a role in hematopoietic dysfunction of leukemia. An evolutionary conserved GATA binding site is critical in transcriptional regulation of the MTG16 promoter. In contrast, the MTGR1 gene depends on a GC-box-rich sequence for transcriptional regulation and possible ubiquitous expression. Our results demonstrate that the ETO homologue promoters are regulated differently consistent with hematopoietic cell-type- specific expression and function.


Mathematical Modeling of RNA-Based Architectures for Closed Loop Control of Gene Expression.
Feedback allows biological systems to control gene expression precisely and reliably, even in the presence of uncertainty, by sensing and processing environmental changes. Taking inspiration from natural architectures, synthetic biologists have engineered feedback loops to tune the dynamics and improve the robustness and predictability of gene expression. However, experimental implementations of biomolecular control systems are still far from satisfying performance specifications typically achieved by electrical or mechanical control systems. To address this gap, we present mathematical models of biomolecular controllers that enable reference tracking, disturbance rejection, and tuning of the temporal response of gene expression. These controllers employ RNA transcriptional regulators to achieve closed loop control where feedback is introduced via molecular sequestration. Sensitivity analysis of the models allows us to identify which parameters influence the transient and steady state response of a target gene expression process, as well as which biologically plausible parameter values enable perfect reference tracking. We quantify performance using typical control theory metrics to characterize response properties and provide clear selection guidelines for practical applications. Our results indicate that RNA regulators are well-suited for building robust and precise feedback controllers for gene expression. Additionally, our approach illustrates several quantitative methods useful for assessing the performance of biomolecular feedback control systems.


Effect of chest wall vibration on breathlessness in normal subjects.
This study evaluated the effect of chest wall vibration (115 Hz) on breathlessness. Breathlessness was induced in normal subjects by a combination of hypercapnia and an inspiratory resistive load; both minute ventilation and end-tidal CO2 were kept constant. Cross-modality matching was used to rate breathlessness. Ratings during intercostal vibration were expressed as a percentage of ratings during the control condition (either deltoid vibration or no vibration). To evaluate their potential contribution to any changes in breathlessness, we assessed several aspects of ventilation, including chest wall configuration, functional residual capacity (FRC), and the ventilatory response to steady-state hypercapnia. Intercostal vibration reduced breathlessness ratings by 6.5 +/- 5.7% compared with deltoid vibration (P less than 0.05) and by 7.0 +/- 8.3% compared with no vibration (P less than 0.05). The reduction in breathlessness was accompanied by either no change or negligible change in minute ventilation, tidal volume, frequency, duty cycle, compartmental ventilation, FRC, and the steady-state hypercapnic response. We conclude that chest wall vibration reduces breathlessness and speculate that it may do so through stimulation of receptors in the chest wall.


Risk perception, risk communication, and stakeholder involvement for biosolids management and research.
An individual's perception of risk develops from his or her values, beliefs, and experiences. Social scientists have identified factors that affect perceptions of risk, such as whether the risk is knowable (uncertainty), voluntary (can the individual control exposure?), and equitable (how fairly is the risk distributed?). There are measurable differences in how technical experts and citizen stakeholders define and assess risk. Citizen knowledge and technical expertise are both relevant to assessing risk; thus, the 2002 National Research Council panel on biosolids recommended stakeholder involvement in biosolids risk assessments. A survey in 2002 identified some of the factors that influence an individual's perception of the risks involved in a neighbor's use of biosolids. Risk communication was developed to address the gap between experts and the public in knowledge of technical topics. Biosolids management and research may benefit from applications of current risk communication theory that emphasizes (i) two-way communications (dialogue); (ii) that the public has useful knowledge and concerns that need to be acknowledged; and (iii) that what may matter most is the credibility of the purveyor of information and the levels of trustworthiness, fairness, and respect that he or she (or the organization) demonstrates, which can require cultural change. Initial experiences in applying the dialogue and cultural change stages of risk communication theory--as well as consensus-building and joint fact-finding--to biosolids research suggest that future research outcomes can be made more useful to decision-makers and more credible to the broader public. Sharing control of the research process with diverse stakeholders can make research more focused, relevant, and widely understood.


Distinguishing species of European sturgeons Acipenser spp. using microsatellite allele sequences.
Five microsatellite markers were analysed and their alleles were sequenced for the three sturgeon species that lived in western Europe: the European sturgeon Acipenser sturio, the Atlantic sturgeon Acipenser oxyrinchus and the Adriatic sturgeon Acipenser naccarii. A total of 94 different allele sequences were obtained. Fixed mutations in the flanking regions or in the core repeat of microsatellites provided a clear distinction between the different species. Comparison of allele sequences also provided some insights into microsatellites and the evolution of Acipenser species. These nuclear markers can be used to solve species determination problems, and combined with mitochondrial markers, will be useful to identify introgression and hybridization among the three species. Moreover, because they are short and with a limited allele size range, they are particularly suited for analysis of museum specimens or archaeological remains.


A wearable airbag to prevent fall injuries.
We have developed a wearable airbag that incorporates a fall-detection system that uses both acceleration and angular velocity signals to trigger inflation of the airbag. The fall-detection algorithm was devised using a thresholding technique with an accelerometer and gyro sensor. Sixteen subjects mimicked falls, and their acceleration waveforms were monitored. Then, we developed a fall-detection algorithm that could detect signals 300 ms before the fall. This signal was used as a trigger to inflate the airbag to a capacity of 2.4 L. Although the proposed system can help to prevent fall-related injuries, further development is needed to miniaturize the inflation system.


The presence of extra chromosomes leads to genomic instability.
Aneuploidy is a hallmark of cancer and underlies genetic disorders characterized by severe developmental defects, yet the molecular mechanisms explaining its effects on cellular physiology remain elusive. Here we show, using a series of human cells with defined aneuploid karyotypes, that gain of a single chromosome increases genomic instability. Next-generation sequencing and SNP-array analysis reveal accumulation of chromosomal rearrangements in aneuploids, with break point junction patterns suggestive of replication defects. Trisomic and tetrasomic cells also show increased DNA damage and sensitivity to replication stress. Strikingly, we find that aneuploidy-induced genomic instability can be explained by the reduced expression of the replicative helicase MCM2-7. Accordingly, restoring near-wild-type levels of chromatin-bound MCM helicase partly rescues the genomic instability phenotypes. Thus, gain of chromosomes triggers replication stress, thereby promoting genomic instability and possibly contributing to tumorigenesis.


Treatment of Depression From a Self-Regulation Perspective: Basic Concepts and Applied Strategies in Self-System Therapy.
Self-regulation models of psychopathology provide a theory-based, empirically supported framework for developing psychotherapeutic interventions that complement and extend current cognitive-behavioral models. However, many clinicians are only minimally familiar with the psychology of self-regulation. The aim of the present manuscript is twofold. First, we provide an overview of self-regulation as a motivational process essential to well-being and introduce two related theories of self-regulation which have been applied to depression. Second, we describe how self-regulatory concepts and processes from those two theories have been translated into psychosocial interventions, focusing specifically on self-system therapy (SST), a brief structured treatment for depression that targets personal goal pursuit. Two randomized controlled trials have shown that SST is superior to cognitive therapy for depressed clients with specific self-regulatory deficits, and both studies found evidence that SST works in part by restoring adaptive self-regulation. Self-regulation-based psychotherapeutic approaches to depression hold significant promise for enhancing treatment efficacy and ultimately may provide an individualizable framework for treatment planning.


Hypodontia in hemifacial microsomia.
The purpose of this study was twofold: (1) to describe the patterns of missing teeth in patients with hemifacial microsomia (HFM) and (2) to compare the prevalence of missing teeth in subjects with HFM with a group of unaffected subjects. A descriptive study was conducted comparing HFM subjects with a group of patients selected from an orthodontic clinic. The prevalence of missing teeth was assessed by evaluation of panoramic radiographs. At the time of the study, records of 125 patients with HFM were available from the Craniofacial Center at Boston's Children's Hospital. Seventy-six met inclusion criteria for radiographic analysis of hypodontia. Fifty-two patients met inclusion criteria into the comparison study in which the prevalence of hypodontia was compared with a group of patients from the Department of Orthodontics at Harvard School of Dental Medicine. A Fisher's exact test was conducted to test the hypothesis that HFM patients have a greater prevalence of missing teeth than individuals without the anomaly. A chi-square test for trend was conducted to determine whether hypodontia was more prevalent with increasing severity of the mandibular deformity in HFM. Hypodontia was more common among HFM patients (26.9%) versus the comparison group in which no missing teeth were recorded (p < .0001). Additionally, the degree of hypodontia was correlated with the grade of mandibular hypoplasia (p = .024). Hypodontia was found to be more prevalent in patients with HFM than in comparison subjects, possibly indicating an etiologic link between the two conditions.


Temporal judgments of immediate and delayed consequences of self-initiated movements.
This study was designed to examine the impact of a delay between a self-initiated movement and a subsequent auditory event on temporal judgements of movement or sound onset. Participants watched a red dot move in a clockwise direction around a circle displayed on a computer screen and reported when they had pressed the spacebar or heard a tone. In other conditions, the movement and tone both occurred. Specifically, the tone followed the button press either immediately or after delays of 100, 250, or 400 ms. On some trial blocks, participants were asked to judge the time of the button press and on other blocks the time of the tone. When the tone occurred alone, participants' judgements were accurate. When the movement occurred alone participants exhibited an anticipatory bias. Although a delayed tone had a modest impact on judgements movement initiation, button press judgements were anticipatory in all tone delay conditions. Thusly temporal judgements associated with event binding are affected more by voluntary action than the auditory consequences of that action.


Characteristics of the HIV cascade of care and unsuppressed viral load among gay, bisexual and other men who have sex with men living with HIV across Canada's three largest cities.
Treatment as prevention strategies have been variously applied across provinces in Canada. We estimated HIV care cascade indicators and correlates of unsuppressed viral load (VL) among gay, bisexual and other men who have sex with men (GBM) recruited in Vancouver, Toronto and Montreal. Sexually active GBM, aged ≥16 years, were recruited through respondent-driven sampling (RDS) from February 2017 to August 2019. Participants completed a Computer-Assisted Self-Interview and tests for HIV and other sexually transmitted infections (STIs). We conducted bivariate analyses comparing RDS-adjusted proportions across cities. We used multivariable logistic regression to examine factors associated with having a measured VL ≥ 200 copies/mL with data pooled from all three cities. We recruited 1179 participants in Montreal, 517 in Toronto and 753 in Vancouver. The RDS-adjusted HIV prevalence was 14.2% (95% CI 11.1 to 17.2) in Montreal, 22.1% (95% CI 12.4 to 31.8) in Toronto and 20.4% (95% CI 14.5 to 26.3) in Vancouver (p < 0.001). Of participants with confirmed HIV infection, 3.3% were previously undiagnosed in Montreal, 3.2% undiagnosed in Toronto and 0.2% in Vancouver (p = 0.154). In Montreal, 87.6% of GBM living with HIV were receiving antiretroviral therapy (ART) and 10.6% had an unsuppressed VL; in Toronto, 82.6% were receiving ART and 4.0% were unsuppressed; in Vancouver, 88.5% were receiving ART and 2.6 % were unsuppressed (p < 0.001 and 0.009 respectively). Multivariable modelling demonstrated that participants in Vancouver (adjusted odds ratio [AOR]=0.23; 95% CI 0.06 to 0.82), but not Toronto (AOR = 0.27; 95% CI 0.07 to 1.03), had lower odds of unsuppressed VL, compared to Montreal, as did older participants (AOR 0.93 per year; 95% CI 0.89 to 0.97), those at high-risk for hazardous drinking (AOR = 0.19; 95% CI 0.05 to 0.70), those with a primary care provider (AOR = 0.11; 95% CI 0.02 to 0.57), and those ever diagnosed with other STIs (AOR = 0.12; 95% CI 0.04 to 0.32). GBM living in Montreal, Toronto and Vancouver are highly engaged in HIV testing and treatment and all three cities have largely achieved the 90-90-90 targets for GBM. Nevertheless, we identified disparities which can be used to identify GBM who may require additional interventions, in particular younger men and those who are without a regular primary care provider.


Vasoactive intestinal peptide binding sites and fibers in the brain of the pigeon Columba livia: an autoradiographic and immunohistochemical study.
The distribution of vasoactive intestinal peptide (VIP) binding sites in the pigeon brain was examined by in vitro autoradiography on slide-mounted sections. A fully characterized monoiodinated form of VIP, which maintains the biological activity of the native peptide, was used throughout this study. The highest densities of binding sites were observed in the hyperstriatum dorsale, archistriatum, auditory field L of neostriatum, area corticoidea dorsolateralis and temporo-parieto-occipitalis, area parahippocampalis, tectum opticum, nucleus dorsomedialis anterior thalami, and in the periventricular area of the hypothalamus. Lower densities of specific binding occurred in the neostriatum, hyperstriatum ventrale and nucleus septi lateralis, dorsolateral area of the thalamus, and lateral and posteromedial hypothalamus. Very low to background levels of VIP binding were detected in the ectostriatum, paleostriatum primitivum, paleostriatum augmentatum, lobus parolfactorius, nucleus accumbens, most of the brainstem, and the cerebellum. The distribution of VIP-containing fibers and terminals was examined by indirect immunofluorescence using a polyclonal antibody against porcine VIP. Fibers and terminals were observed in the area corticoidea dorsolateralis, area parahippocampalis, hippocampus, hyperstriatum accessorium, hyperstriatum dorsale, archistriatum, tuberculum olfactorium, nuclei dorsolateralis and dorsomedialis of the thalamus, and throughout the hypothalamus and the median eminence. Long projecting fibers were visualized in the tractus septohippocampalis. In the brainstem VIP immunoreactive fibers and terminals were observed mainly in the substantia grisea centralis, fasciculus longitudinalis medialis, lemniscus lateralis, and in the area surrounding the nuclei of the 7th, 9th, and 10th cranial nerves. The correlation between the distribution of VIP binding sites and immunoreactive fibers and terminals was assessed in a restricted number of regions. A qualitatively good matching was found in the area corticoidea dorsolateralis, hyperstriatum dorsale, hyperstriatum accessorium, nucleus septi lateralis, nuclei dorsomedialis and dorsolateralis thalami, and in some hypothalamic areas. A striking mismatch occurred in the hyperstriatum ventrale, neostriatum, tectum opticum (high to moderate density of binding sites but only few immunoreactive profiles), and in the tuberculum olfactorium, median eminence, and spinal cord (lower density of binding sites but abundant immunoreactive profiles). The paleostriatum, lobus parolfactorius, and ectostriatum were virtually devoid of both binding sites and immunoreactive profiles. The results are discussed in relation to the known actions of VIP in the rodent and avian brain and are compared with previous observations on the distribution of VIP binding sites in the central nervous system of other vertebrates.


Solvent-Triggered Long-Range Proton Transport in 7-Hydroxyquinoline Using a Sulfonamide Transporter Group.
The ability of long-range proton transport by substitution of 7-hydroxyquinoline at the eighth position with sulfonamide and sulfonylhydrazone rotor units to act as a crane-arm has been studied. Different proton transport pathways triggered by different stimuli have been established depending on the structure of the crane-arms. Solvent-driven proton switching from OH to the quinoline nitrogen (Nquin) site, facilitated by a sulfonamide transporter group in polar protic and aprotic solvents, has been confirmed by optical (absorption and fluorescence) and NMR spectroscopies as well as by single-crystal X-ray structure analysis. Photoinduced long-range proton transport to the Nquin site upon 340 nm UV light irradiation has been estimated in sulfonylhydrazone, which is not sensitive to solvent-driven switching. Both compounds have exhibited acid-triggered switching by trifluoroacetic acid due to the formation of a stable six-membered intramolecular hydrogen bonding interaction between the protonated Nquin and crane-arm. The structures of acid-switched form were confirmed by NMR spectroscopy and single-crystal X-ray structure analysis. The behavior of the compounds suggests a big step forward in the advanced proton pump-switching architecture because they cover three distinct driving forces in the switching process: solvent, light, and acid.


Asthma and immunoglobulin E antibodies after respiratory syncytial virus bronchiolitis: a prospective cohort study with matched controls.
To study the occurrence of bronchial obstructive symptoms and immunoglobulin (Ig) E antibodies after respiratory syncytial virus (RSV) bronchiolitis in infancy. Previous studies of this subject have mostly been retrospective or without controls, or the controls have not been followed prospectively. This was a prospective cohort study with matched controls. Forty-seven infants had experienced RSV bronchiolitis severe enough to cause hospitalization at a mean age of 3 1/2 months. For each child with RSV infection, two controls were acquired from the local Child Health Center and matched for date of birth, sex, and residence. Only one control was obtained for one RSV child, and the control group thus contained 93 children. All the children underwent two follow-up examinations, the first one at a mean age of 1 year and the second at a mean age of 3 years. At the first follow-up, a skin-prick test against egg white was performed, and serum IgG antibodies against RSV were measured. At the second follow-up, serum IgE antibodies were measured using screening tests for common food and inhalant antibodies, and skin-prick tests against egg white, cat, birch, and mite allergen were performed. Hereditary and environmental factors (passive smoking, indoor furred animals) and duration of breast-feeding were recorded. At the first follow-up, 89% in the RSV group and 27% in the control group had IgG antibodies against RSV (P < .001). At the second follow-up, asthma, defined as three episodes of bronchial obstruction verified by a physician, was found in 11 of 47 children (23%) in the RSV group and in 1 of 93 children (1%) in the control group (P < .001). A positive test for IgE antibodies was noted in 14 of 44 (32%) RSV children and in 8 of 92 (9%) children in the control group (P = .002). An analysis of risk factors for the development of asthma and IgE antibodies on the whole group of 140 children showed that RSV bronchiolitis was the most important risk factor, and a family history of atopy or asthma further increased the risk. Respiratory syncytial virus bronchiolitis during the first year of life apparently is an important risk factor for the development of asthma and sensitization to common allergens during the subsequent 2 years, particularly in children with hereditary for atopy/asthma.


Phase-coded microwave signal generation based on a single electro-optical modulator and its application in accurate distance measurement.
A novel scheme for photonic generation of a phase-coded microwave signal is proposed and its application in one-dimension distance measurement is demonstrated. The proposed signal generator has a simple and compact structure based on a single dual-polarization modulator. Besides, the generated phase-coded signal is stable and free from the DC and low-frequency backgrounds. An experiment is carried out. A 2 Gb/s phase-coded signal at 20 GHz is successfully generated, and the recovered phase information agrees well with the input 13-bit Barker code. To further investigate the performance of the proposed signal generator, its application in one-dimension distance measurement is demonstrated. The measurement accuracy is less than 1.7 centimeters within a measurement range of ~2 meters. The experimental results can verify the feasibility of the proposed phase-coded microwave signal generator and also provide strong evidence to support its practical applications.


An observational study of the 'isolated forearm technique' in unparalysed, spontaneously breathing patients.
The isolated forearm technique enables a patient, otherwise paralysed by neuromuscular blockade, to communicate by movement if wakeful during surgery. The positive response rate to verbal command is high (~32%). The 5th National Audit Project recommended that this monitoring technique should become more widely taught and considered, so this study was designed to assess its utility as a standard of care in unparalysed patients. A positive response rate as high as in the paralysed would justify local adoption. Therefore, 100 consecutive patients undergoing urology surgery were given verbal commands to move at two-minute intervals from induction of anaesthesia (fentanyl and propofol) to full emergence and extubation of the supraglottic airway. Anaesthesia was maintained with isoflurane in oxygen/nitrous oxide. Although 24 patients moved during surgery (and therefore needed additional anaesthetic), none moved to verbal command. Even at extubation, when patients moved to expel the airway, there was no response to command until after wakening. These results suggest that in contrast to its use in paralysed patients, the isolated forearm technique does not yield useful information about the patient's state of wakefulness in the unparalysed. Another interpretation is that unparalysed patients are less prone to wakefulness than the paralysed.


The influence of coherent waves on the remotely sensed reflectance.
Oceanic waves have been found to contribute enhanced back-scattering in the direction of the illumination source in studies that assumed the ocean surface to be a random sum of waves. Here we investigate enhanced back-scattering by coherent capillary-gravity wave trains that co-exist near the crests of short gravity waves in the ocean. We find that the enhanced back-scattering effect is intensified relative to that of a random surface and that the effect is observed at larger angles. This effect may not only affect active sensors such as lidar, which have a viewing angle close to that of the source but possibly passive sensors as well. This effect is likely to result in biases when attempting closure between radiative transfer models that do not include realistic representation of the ocean surface and observed water leaving radiance.


Treatment outcome of smear-positive pulmonary tuberculosis patients in Tigray Region, Northern Ethiopia.
Monitoring the outcome of tuberculosis treatment and understanding the specific reasons for unsuccessful treatment outcome are important in evaluating the effectiveness of tuberculosis control program. This study investigated tuberculosis treatment outcomes and predictors for unsuccessful treatment outcome in the Tigray region of Ethiopia. Medical records of smear-positive pulmonary tuberculosis (PTB) patients registered from September 2009 to June 2011 in 15 districts of Tigray region, Northern Ethiopia, were reviewed. Additional data were collected using a structured questionnaire administered through house-to-house visits by trained nurses. Tuberculosis treatment outcomes were assessed according to WHO guidelines. The association of unsuccessful treatment outcome with socio-demographic and clinical factors was analyzed using logistic regression model. Out of the 407 PTB patients (221 males and 186 females) aged 15 years and above, 89.2% had successful and 10.8% had unsuccessful treatment outcome. In the final multivariate logistic model, the odds of unsuccessful treatment outcome was higher among patients older than 40 years of age (adj. OR=2.50, 95% CI: 1.12-5.59), family size greater than 5 persons (adj. OR=3.26, 95% CI: 1.43-7.44), unemployed (adj. OR=3.10, 95% CI: 1.33-7.24) and among retreatment cases (adj. OR=2.00, 95% CI: 1.37-2.92) as compared to their respective comparison groups. Treatment outcome among smear-positive PTB patients was satisfactory in the Tigray region of Ethiopia. Nonetheless, those patients at high risk of an unfavorable treatment outcome should be identified early and given additional follow-up and social support.


Synthetic Biology Open Language (SBOL) Version 2.2.0.
Synthetic biology builds upon the techniques and successes of genetics, molecular biology, and metabolic engineering by applying engineering principles to the design of biological systems. The field still faces substantial challenges, including long development times, high rates of failure, and poor reproducibility. One method to ameliorate these problems would be to improve the exchange of information about designed systems between laboratories. The synthetic biology open language (SBOL) has been developed as a standard to support the specification and exchange of biological design information in synthetic biology, filling a need not satisfied by other pre-existing standards. This document details version 2.2.0 of SBOL that builds upon version 2.1.0 published in last year's JIB special issue. In particular, SBOL 2.2.0 includes improved description and validation rules for genetic design provenance, an extension to support combinatorial genetic designs, a new class to add non-SBOL data as attachments, a new class for genetic design implementations, and a description of a methodology to describe the entire design-build-test-learn cycle within the SBOL data model.


National responsibilities in European species conservation: a methodological review.
One particular challenge in reducing the loss of biodiversity by 2010, as agreed on at the Earth Summit in 2002, is to assign conservation tasks to geographic or administrative entities (e.g., countries or regions) on different geographical scales. To identify conservation tasks, it is imperative to determine the importance of a specific area for the global survival of a species. So far, these national or subnational responsibilities for the conservation of species have been included differently in methods prioritizing conservation. We reviewed how 12 European and 3 non-European methods determined national conservation responsibilities and evaluated the international importance of a biological population. Different countries used different methodologies, which made a direct comparison of assessments of national responsibilities among countries extremely difficult. Differences existed in the importance criteria used. Criteria included population decline, range reduction, rarity status, degree of isolation of a population, endemism, proportional distribution, and geographic location. To increase comparability, it is imperative to develop criteria for which data are generally available and to standardize the methodology among countries. A standardized method would allow conservation decisions to be based on the conservation status of a species and on the responsibility of a geographic or administrative entity for the survival of a species. We suggest that such a method should use a scalable index of proportional distribution, taxonomic status, and the distribution pattern of a taxon or species as key elements. Such a method would allow for the creation of hierarchical lists and would be highly relevant for parts of the world with multiple political jurisdictions or state unions and for nations with regional governmental structures. Conservation priorities could then be reasonably set by combining national responsibility assessments with the international conservation status of a species.


Endemism predicts intrinsic vulnerability to nonindigenous species on islands.
While numerous efforts have been made to identify and quantify factors controlling invasibility of biological communities, less attention has been given to analyzing the expressions of vulnerability to nonindigenous species (NIS). Using the International Union for the Conservation of Nature and Natural Resources Red List database for birds, mammals, and amphibians and the Invasive Species Specialist Group global invasive species database as sources of information, we developed a new indicator for the relative intrinsic vulnerability of islands to NIS. It was calculated from the residuals to the global relationship between the impact of NIS and their exposure to the islands. The impact of NIS was expressed as the proportion of indigenous species threatened by NIS, and the exposure was the number of invasive NIS per number of native species. The residuals corresponded to the variability in impact, about 60%, that was not explained by exposure. The proportion of endemic species on the islands was positively correlated with the relative intrinsic vulnerability and explained about 60% of its variability. The robust relationship between endemism and intrinsic vulnerability reinforces the role of long-term isolation for the fate of island indigenous species to biological invasions and is useful in identifying vulnerable environments without having a specific invader in mind.


Surface exposure of outer membrane protein and lipopolysaccharide epitopes in Brucella species studied by enzyme-linked immunosorbent assay and flow cytometry.
Seven surface-exposed outer membrane proteins (OMPs) in Brucella supp. have been previously described (A. Cloeckaert, P. de Wergifosse, G. Dubray, and J. N. Limet, Infect. Immun. 58:3980-3987, 1990). OMPs were shown to be more accessible to monoclonal antibodies (MAbs) on rough (R) Brucella melitensis and B. abortus strains than to MAbs on their smooth (S) counterparts. In this work, we have extended this study to representatives of the main Brucella species, using MAbs specific for OMPs and S and R lipopolysaccharides (S-LPS and R-LPS). Enzyme-linked immunosorbent assay (ELISA), flow cytometry, and immunoelectron microscopy showed important differences between strains in the binding of OMP- and R-LPS-specific MAbs which were in part related to the particular expression of S-LPS, irrespective of the species. Results indicated that both the amount and the length of O polysaccharide on S-LPS greatly influenced the accessibility of OMP and R-LPS epitopes to MAbs. S-R B. melitensis EP and S B. suis 40, for instance, which express O-polysaccharide chains in small amounts and with short mean length, respectively, bound a greater number of OMP- and R-LPS-specific MAbs than the other S Brucella strains. The major 31- to 34-kDa OMP was the most exposed OMP on S strains of B. melitensis and B. suis. In most cases, flow cytometry results agreed with those of ELISA and supplied additional data, such as the homogeneity or heterogeneity of OMP expression at the strain level. However, there were some discordances between flow cytometry and ELISA results concerning the surface exposure of the 25- to 27-kDa and 31- to 34-kDa OMPs on S strains and that of minor OMPs in vaccine strain B. melitensis Rev.1. Immunoelectron microscopy confirmed the poor accessibility of OMPs to MAbs on the surface of S Brucella strains. The naturally R pathogenic species B. ovis and B. canis bound the majority of OMP-specific MAbs as well as the R-LPS-specific MAbs. Therefore, the conserved OMP and R-LPS epitopes could play a role as targets of protective antibody-mediated immunity in infections caused by naturally R B. ovis and B. canis.


Effect of timing of dialysis commencement on clinical outcomes of patients with planned initiation of peritoneal dialysis in the IDEAL trial.
Since the mid-1990s, early dialysis initiation has dramatically increased in many countries. The Initiating Dialysis Early and Late (IDEAL) study demonstrated that, compared with late initiation, planned early initiation of dialysis was associated with comparable clinical outcomes and increased health care costs. Because residual renal function is a key determinant of outcome and is better preserved with peritoneal dialysis (PD), the present pre-specified subgroup analysis of the IDEAL trial examined the effects of early-compared with late-start dialysis on clinical outcomes in patients whose planned therapy at the time of randomization was PD. Adults with an estimated glomerular filtration rate (eGFR) of 10 - 15 mL/min/1.73 m(2) who planned to be treated with PD were randomly allocated to commence dialysis at an eGFR of 10 - 14 mL/min/1.73 m(2) (early start) or 5 - 7 mL/min/1.73 m(2) (late start). The primary outcome was all-cause mortality. Of the 828 IDEAL trial participants, 466 (56%) planned to commence PD and were randomized to early start (n = 233) or late start (n = 233). The median times from randomization to dialysis initiation were, respectively, 2.03 months [interquartile range (IQR):1.67 - 2.30 months] and 7.83 months (IQR: 5.83 - 8.83 months). Death occurred in 102 early-start patients and 96 late-start patients [hazard ratio: 1.04; 95% confidence interval (CI): 0.79 - 1.37]. No differences in composite cardiovascular events, composite infectious deaths, or dialysis-associated complications were observed between the groups. Peritonitis rates were 0.73 episodes (95% CI: 0.65 - 0.82 episodes) per patient-year in the early-start group and 0.69 episodes (95% CI: 0.61 - 0.78 episodes) per patient-year in the late-start group (incidence rate ratio: 1.19; 95% CI: 0.86 - 1.65; p = 0.29). The proportion of patients planning to commence PD who actually initiated dialysis with PD was higher in the early-start group (80% vs 70%, p = 0.01). Early initiation of dialysis in patients with stage 5 chronic kidney disease who planned to be treated with PD was associated with clinical outcomes comparable to those seen with late dialysis initiation. Compared with early-start patients, late-start patients who had chosen PD as their planned dialysis modality were less likely to commence on PD.


Centrosomes and cancer: lessons from a TACC.
The recent discovery that many cancer cells have centrosomal abnormalities suggests a link between centrosomes and cancer. Members of the transforming acidic coiled-coil (TACC) family of proteins have been implicated in cancer and are concentrated at centrosomes, where they regulate microtubule stability. I discuss a model of how the TACC proteins might contribute to cancer. This model predicts that defects in TACC function can make important contributions to the development of cancer but are unlikely to be the primary cause of cancer. The model might also apply to several other centrosomal proteins that have been linked to cancer.


The potential impact of an HIV vaccine with rapidly waning protection on the epidemic in Southern Africa: examining the RV144 trial results.
The prime-boost HIV vaccine regimen used in the recent RV144 trial resulted in modest efficacy of 31% over 3.5 years, but was substantially higher in the first year post-vaccination. We sought to explore the potential impact of a vaccine with rapidly waning efficacy in a South African population. We explored two strategies using a dynamic compartmental epidemic model for heterosexual transmission of HIV: [1] vaccination of a single cohort (30%, 60% or 90% of the initial population), with exponentially waning efficacy, but booster vaccinations at 5- or 2-year intervals, and [2] continuous vaccination of the unvaccinated population at the same coverage levels (30%, 60% or 90%) but with a constant efficacy vaccine of short duration. We also examined potential changes in post-vaccination condom use. The single cohort vaccination strategies did not have a substantial impact on HIV prevalence, although without boosters they still prevented 2-6% of the expected infections at 20 years, depending on the population coverage. The 5-year and 2-year booster strategies prevented 8-24% and 17-45% of the expected infections, respectively. Continuous vaccination to maintain population coverage levels resulted in more substantial reductions in population HIV prevalence and greater numbers of infections prevented: HIV prevalence at 20 years was reduced from 23% to 8-14% and the number of expected infections was decreased by 34-59%, depending on the population coverage level. Moderate changes in post-vaccination condom use did not substantially affect these outcomes. An HIV vaccine with partial efficacy and declining protection similar to the RV144 vaccine could prevent a substantial proportion of HIV infections if booster vaccinations were effective and available. Our estimates of the population impact of vaccination would be improved by further understanding of the duration of protection, the effectiveness of booster vaccination, and whether the vaccine efficacy varies between subpopulations at higher and lower risk of exposure.


[A study on the effect of waiting time for operations in the operating room on preoperative patients].
This study was attempted to provide us with basic information on how to improve understanding with patients for operation, and to offer them better nursing and treatment. This kind of study will help scientific application to nursing practice and operating room. The data was collected by interviewing 29 patients who underwent the elective surgery under the general anesthesia at Y hospital in Seoul. The interview ran from October 15 to December 15, 1989. The research instrument was a anxiety measurement device (SAAI) originally developed by Spielberger, et al and modified by Jung-Tack Kim. 1. Hypothesis Testing Hypothesis one was that there would be a difference in state anxiety level according to a time difference in waiting for operation. This hypothesis was rejected (state anxiety level one hour before operation P greater than .05, r = .747, State anxiety level half an hour before operation P greater than .05, r = .1550, state anxiety level just before operation, P greater than .05, r = .1099). However, state anxiety level appeared to be associated with a longer waiting period, like one day before operation (P less than .05, r = .4628). Hypothesis two was that there would be a difference according to state anxiety level of patients for operation. This was rejected. (Change of blood pressure in systolic P greater than .05, r = -.1082. Change of blood pressure in diastolic P greater than .05, r = -.088, Change of pulse rate, P less than .05, r = 1.909) 2. Examining trait anxiety and state anxiety levels, the average level of trait anxiety was 42.034, and the average level of state anxiety one day before operation was 43,000. The average level of state anxiety was averaged 42.356 in a waiting room for operation. 3. Examining the state anxiety level by time period, the level one hour before was 42.379, the level half an hour before 42.276, and the level just before operation 42.414. The low level of state anxiety was due to the fact that premedication was not eliminated. 4. Age and time period like one day before operation was related to state anxiety level (F = 5.271, P less than .001) and blood pressure in waiting room for operation. That is, state anxiety level and blood pressure of patients one day before operation appeared high. Sex was related to changes of blood pressure; the blood pressure of male patients appeared higher than that of female patients.(ABSTRACT TRUNCATED AT 400 WORDS)


Phenotype anchoring in zebrafish reveals a potential role for matrix metalloproteinases (MMPs) in tamoxifen's effects on skin epithelium.
The zebrafish is a powerful alternative model used to link phenotypes with molecular effects to discover drug mode of action. Using a zebrafish embryo-larval toxicity bioassay, we evaluated the effects of tamoxifen--a widely used anti-estrogen chemotherapeutic. Zebrafish exposed to ≥ 10 μM tamoxifen exhibited a unique necrotic caudal fin phenotype that was rapidly induced regardless of developmental life-stage when treatment was applied. To define tamoxifen's bioactivity resulting in this phenotype, targeted gene expression was used to evaluate 100 transcripts involved in tissue remodeling, calcium signaling, cell cycle and cell death, growth factors, angiogenesis and hypoxia. The most robustly misregulated transcripts in the tail were matrix metalloproteinases mmp9 and mmp13a, induced 127 and 1145 fold, respectively. Expression of c-fos, c-jun, and ap1s1 were also moderately elevated (3-7 fold), consistent with AP-1 activity--a transcription factor that regulates MMP expression. Immunohistochemistry confirmed high levels of induction for MMP13a in affected caudal fin skin epithelial tissue. The necrotic caudal fin phenotype was significantly attenuated or prevented by three functionally unique MMP inhibitors: EDTA (metal chelator), GM 6001 (broad MMP inhibitor), and SR 11302 (AP-1 transcription factor inhibitor), suggesting MMP-dependence. SR 11302 also inhibited induction of mmp9, mmp13a, and a putative MMP target, igfbp1a. Overall, our studies suggest that tamoxifen's effect is the result of perturbation of the MMP system in the skin leading to ectopic expression, cytotoxicity, and the necrotic caudal fin phenotype. These studies help advance our understanding of tamoxifen's non-classical mode of action and implicate a possible role for MMPs in tissues such as skin.


Further delineation of the KAT6B molecular and phenotypic spectrum.
KAT6B sequence variants have been identified previously in both patients with the Say-Barber-Biesecker type of blepharophimosis mental retardation syndromes (SBBS) and in the more severe genitopatellar syndrome (GPS). We report on the findings in a previously unreported group of 57 individuals with suggestive features of SBBS or GPS. Likely causative variants have been identified in 34/57 patients and were commonly located in the terminal exons of KAT6B. Of those where parental samples could be tested, all occurred de novo. Thirty out of thirty-four had truncating variants, one had a missense variant and the remaining three had the same synonymous change predicted to affect splicing. Variants in GPS tended to occur more proximally to those in SBBS patients, and genotype/phenotype analysis demonstrated significant clinical overlap between SBBS and GPS. The de novo synonymous change seen in three patients with features of SBBS occurred more proximally in exon 16. Statistical analysis of clinical features demonstrated that KAT6B variant-positive patients were more likely to display hypotonia, feeding difficulties, long thumbs/great toes and dental, thyroid and patella abnormalities than KAT6B variant-negative patients. The few reported patients with KAT6B haploinsufficiency had a much milder phenotype, though with some features overlapping those of SBBS. We report the findings in a previously unreported patient with a deletion of the KAT6B gene to further delineate the haploinsufficiency phenotype. The molecular mechanisms giving rise to the SBBS and GPS phenotypes are discussed.


Developing a dancer wellness program employing developmental evaluation.
Wellness programs are being increasingly employed with performing artists. Given their aim of reducing injuries, injury tracking is commonly employed as an outcome measure. Evaluating the development and process of a wellness program can also enhance its effectiveness. Developmental evaluation offers one methodological framework within which to conduct such investigations. This paper reports on a 2-year process involving feedback from professional ballet dancers, management and artistic staff, and healthcare providers at a ballet company in order to develop a dancer screening and wellness program. Following a consultation phase, an initial program composed of an expanded medical team and annual injury prevention screen was proposed. Alongside implementation with 30 professional ballet dancers, formal and informal feedback was sought from stakeholders and members across all levels of the ballet company to facilitate ongoing development, evaluation, and revision of the wellness program. The use of a process informed by developmental evaluation helped identify strengths and limitations within the screening process. The collective expertise of the assessors was used to modify the components and process of the screen to strive for ecological appropriateness. The process also fostered buy-in from all involved. Participant feedback helped refine the medical team available to the dancers and influenced the treatment and referral pathways via which dancers are able to access each member of the medical team. Furthermore, reflective discussions with artistic and management staff brought to light potential interactions between repertoire programming, fitness, and injury patterns. This prompted a reconsideration of how artists are trained and supported. Evaluation methods that focus on experiences and insight gained during program development stand to result in more efficient screening programs and health-promotion models and, ultimately, healthier performing artists.


Common factors associated with choking in psychiatric patients.
Choking is common among psychiatric patients and represents one of the main causes of death in this patient population. We aimed to identify common factors associated with choking among psychiatric patients. The demographic information and medical history of 250 psychiatric patients living in an acute psychiatric ward were retrieved from medical charts, interview records, and check lists. Coughing while eating and swallowing difficulties were assessed based on patient self-reports. The main outcomes were choking while taking drugs (CTD) as observed by nursing staffs and choking experiences during hospitalization (CEH) as reported by the patients. Chi-square tests were used to examine the potential associations among the independent variables. Multiple logistic regression was used to further examine those independent variables found to be significantly associated with CTD to estimate their relative contributions. CEH was reported in 50.8%, and CTD was observed in 17.6% of study participants. Use of anxiolytics, consuming a semiliquid or liquid diet, coughing while eating, and swallowing difficulties were found to be associated with CTD. Coughing while eating was the only independent variable associated with CEH. Further logistic regression on the relationships between CTD and variables including the use of anxiolytics, coughing while eating, and swallowing difficulties showed the independent contributions of these variables in the model. The odds ratios were 12.8 (p = .003), 16.7 (p < .001), and 21.7 (p = .001) for each of the three respective variables. The use of anxiolytics, coughing while eating, and swallowing difficulties all potentially contributed to the choking events in our sample. Additional precautions should thus be taken in caring for psychiatric patients who use anxiolytics, who have a history of coughing while eating, or who exhibit swallowing difficulties to prevent choking events.


A randomized, controlled trial of tea tree topical preparations versus a standard topical regimen for the clearance of MRSA colonization.
Two topical MRSA eradication regimes were compared in hospital patients: a standard treatment included mupirocin 2% nasal ointment, chlorhexidine gluconate 4% soap, silver sulfadiazine 1% cream versus a tea tree oil regimen, which included tea tree 10% cream, tea tree 5% body wash, both given for five days. One hundred and fourteen patients received standard treatment and 56 (49%) were cleared of MRSA carriage. One hundred and ten received tea tree oil regimen and 46 (41%) were cleared. There was no significant difference between treatment regimens (Fisher's exact test; P = 0.0286). Mupirocin was significantly more effective at clearing nasal carriage (78%) than tea tree cream (47%; P = 0.0001) but tea tree treatment was more effective than chlorhexidine or silver sulfadiazine at clearing superficial skin sites and skin lesions. The tea tree preparations were effective, safe and well tolerated and could be considered in regimens for eradication of MRSA carriage.


Polypharmacy and falls in the middle age and elderly population.
Falls in the elderly are common and often serious. We studied the association between multiple drug use (polypharmacy) and falls in the elderly. This was a population-based cross-sectional study, part of the Rotterdam Study. The participants were 6928 individuals aged > or = 55 years. The prevalence of falls in the previous year was assessed. Medication use was determined with an interviewer-administered questionnaire with verification of use. Polypharmacy was defined as the use of four or more drugs per day. The prevalence of falls strongly increased with age. Falls were more common in women than in men. Fall risk increased with increasing disability, presence of joint complaints, use of a walking aid and fracture history. The risk of falling increased significantly with the number of drugs used per day (P for trend < 0.0001). After adjustment for a large number of comorbid conditions and disability, polypharmacy remained a significant risk factor for falling. Stratification for polypharmacy with or without at least one drug which is known to increase fall risk (notably CNS drugs and diuretics) disclosed that only polypharmacy with at least one risk drug was associated with an increased risk of falling. Fall risk is associated with the use of polypharmacy, but only when at least one established fall risk-increasing drug was part of the daily regimen.


From stem cells to comparative corticogenesis: a bridge too far?
It has been hypothesized that the higher number of neurons in human cortex compared to the chimpanzee and other primate species is key to high cognitive function. Are human cortical precursors endowed with specific properties that drive greater neuronal expansion than in other non-human primates? Otani et al. 2016 addressed this issue taking advantage of comparative in vitro corticogenesis models based on human, chimpanzee and macaque pluripotent stem cells. Clonal analysis revealed a heterochrony of early developmental events possibly leading to a relatively higher expansion of human cortical precursor population. In absence of evidence going beyond putative correlation, the claim that stem cell models of cortical development indicate mechanism of cortical size regulation needs to be further examined notably with respect to in vivo observations of cortical precursor lineages.


Apolipoprotein M in patients with chronic kidney disease.
Plasma apolipoprotein M (APOM) is bound to HDL-particles and has anti-atherogenic effects. The present study explored whether plasma APOM is reduced in patients with chronic kidney disease (CKD), and associated with cardiovascular disease (CVD). In addition, we tested the hypothesis that the excretion of APOM into the urine is increased in patients with kidney disease. Plasma samples were collected from a cohort of patients with CKD stages 1 to 5D (N = 409) and controls (N = 35). Urine was collected from 47 subjects. Plasma APOM was measured with sandwich ELISA and urine APOM with competitive ELISA. Plasma APOM levels were reduced in patients with CKD stages 3-5D as compared to patients with CKD stages 1 + 2 and controls (p < 0.01). CKD patients with known CVD displayed even further reduction in plasma APOM levels than CKD patients without known CVD (p < 0.001). Fast-phase liquid chromatography showed that plasma APOM was primarily associated with HDL-cholesterol (HDL-C) across CKD stages. Accordingly, when plasma APOM values were corrected for HDL-C, a significant difference only persisted between patients with CKD stage 3 and stages 1 + 2 (p < 0.05), and the difference between CKD patients with and without known CVD disappeared. Urine APOM/creatinine ratio was not significantly increased in patients with kidney disease. The results show that the difference in plasma APOM levels observed between patients with mild and advanced CKD may mainly be due to differences in plasma HDL-C. Whether APOM plays a role in human uremic atherogenesis warrants further experimental studies.


Ancient plant DNA in lake sediments.
Contents 924 I. 925 II. 925 III. 927 IV. 929 V. 930 VI. 930 VII. 931 VIII. 933 IX. 935 X. 936 XI. 938 938 References 938 SUMMARY: Recent advances in sequencing technologies now permit the analyses of plant DNA from fossil samples (ancient plant DNA, plant aDNA), and thus enable the molecular reconstruction of palaeofloras. Hitherto, ancient frozen soils have proved excellent in preserving DNA molecules, and have thus been the most commonly used source of plant aDNA. However, DNA from soil mainly represents taxa growing a few metres from the sampling point. Lakes have larger catchment areas and recent studies have suggested that plant aDNA from lake sediments is a more powerful tool for palaeofloristic reconstruction. Furthermore, lakes can be found globally in nearly all environments, and are therefore not limited to perennially frozen areas. Here, we review the latest approaches and methods for the study of plant aDNA from lake sediments and discuss the progress made up to the present. We argue that aDNA analyses add new and additional perspectives for the study of ancient plant populations and, in time, will provide higher taxonomic resolution and more precise estimation of abundance. Despite this, key questions and challenges remain for such plant aDNA studies. Finally, we provide guidelines on technical issues, including lake selection, and we suggest directions for future research on plant aDNA studies in lake sediments.


Genetic associations of short- and long-term aggressiveness identified by skin lesion with growth, feed efficiency, and carcass characteristics in growing pigs.
The objective of this study was to investigate the genetic relationships between skin lesion traits in group housed growing pigs as a measure of short- (in a newly mixed group) and long- (in a socially stable group) term aggression and commonly used commercial performance measures: growth, feed intake, feed efficiency, and carcass traits. Data on 2,413 growing pigs (138 groups) were available. Pigs were mixed into new social groups of 18 animals, and skin lesions were counted 24 h (SL24h) and 5 wk (SL5wk) postmixing. The animal model was used to estimate genetic parameters for skin lesion traits, test daily gain, lifetime daily gain, daily feed intake, feed efficiency (calculated as test daily gain divided by daily feed intake), loin depth, back fat, and HCW. Skin lesions had a heritable component, ranging from 0.08 for anterior SL24h to 0.22 for central SL5wk and would, therefore, be suitable as a method of phenotyping aggression for selection purposes. Significant positive genetic correlations were found between SL24h and SL5wk (0.46 to 0.81). Positive genetic correlations were also found between SL24h (central and posterior body regions) or SL5wk (all body regions) and the production traits lifetime daily gain, test daily gain, and HCW (0.29 to 0.54). Central SL24h, anterior SL5wk, and posterior SL5wk were found to correlate positively with feed efficiency (0.39 to 0.50), suggesting that pigs with more lesions convert feed more efficiently. Where significant, the magnitude of phenotypic correlations was low but positive (0.07 to 0.10). These results suggest that, genetically, animals that receive many lesions show improved performance compared to those with few lesions, except for anterior SL24h, which had previously been shown to be genetically positively correlated with the initiation of nonreciprocal attacks. It may, therefore, be possible, via selection against anterior skin lesions at mixing, to reduce this form of 1-sided aggression without adversely affecting production traits.


Experimental demonstration of continuously variable optical encoding in a hybrid imaging system.
We demonstrate an experimental method to obtain a continuously variable hybrid imaging system that uses two generalized cubic phase masks, to enable real-time optimization of the trade between extended depth-of-field and noise gain. We obtain point-spread functions as a function of the rotation angle and show an example of optimization based on recovered image quality.


Solution NMR characterization of WT CXCL8 monomer and dimer binding to CXCR1 N-terminal domain.
Chemokine CXCL8 and its receptor CXCR1 are key mediators in combating infection and have also been implicated in the pathophysiology of various diseases including chronic obstructive pulmonary disease (COPD) and cancer. CXCL8 exists as monomers and dimers but monomer alone binds CXCR1 with high affinity. CXCL8 function involves binding two distinct CXCR1 sites - the N-terminal domain (Site-I) and the extracellular/transmembrane domain (Site-II). Therefore, higher monomer affinity could be due to stronger binding at Site-I or Site-II or both. We have now characterized the binding of a human CXCR1 N-terminal domain peptide (hCXCR1Ndp) to WT CXCL8 under conditions where it exists as both monomers and dimers. We show that the WT monomer binds the CXCR1 N-domain with much higher affinity and that binding is coupled to dimer dissociation. We also characterized the binding of two CXCL8 monomer variants and a trapped dimer to two different hCXCR1Ndp constructs, and observe that the monomer binds with ∼10- to 100-fold higher affinity than the dimer. Our studies also show that the binding constants of monomer and dimer to the receptor peptides, and the dimer dissociation constant, can vary significantly as a function of pH and buffer, and so the ability to observe WT monomer peaks is critically dependent on NMR experimental conditions. We conclude that the monomer is the high affinity CXCR1 agonist, that Site-I interactions play a dominant role in determining monomer vs. dimer affinity, and that the dimer plays an indirect role in regulating monomer function.


Zinc metalloproteinase ProA directly activates Legionella pneumophila PlaC glycerophospholipid:cholesterol acyltransferase.
Enzymes secreted by Legionella pneumophila, such as phospholipases A (PLAs) and glycerophospholipid:cholesterol acyltransferases (GCATs), may target host cell lipids and therefore contribute to the establishment of Legionnaires disease. L. pneumophila possesses three proteins, PlaA, PlaC, and PlaD, belonging to the GDSL family of lipases/acyltransferases. We have shown previously that PlaC is the major GCAT secreted by L. pneumophila and that the zinc metalloproteinase ProA is essential for GCAT activity. Here we characterized the mode of PlaC GCAT activation and determined that ProA directly processes PlaC. We further found that not only cholesterol but also ergosterol present in protozoa was palmitoylated by PlaC. Such ester formations were not induced by either PlaA or PlaD. PlaD was shown here to possess lysophospholipase A activity, and interestingly, all three GDSL enzymes transferred short chain fatty acids to sterols. The three single putative catalytic amino acids (Ser-37, Asp-398, and His-401) proved essential for all PlaC-associated PLA, lysophospholipase A, and GCAT activities. A further four cysteine residues are important for the PLA/GCAT activities as well as their oxidized state, and we therefore conclude that PlaC likely forms at least one disulfide loop. Analysis of cleavage site and loop deletion mutants suggested that for GCAT activation deletion of several amino acids within the loop is necessary rather than cleavage at a single site. Our data therefore suggest a novel enzyme inhibition/activation mechanism where a disulfide loop inhibits PlaC GCAT activity until the protein is exported to the external space where it is ProA-activated.