bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensitivity of Rhizoctonia solani AG-2-2 from Sugar Beet to Fungicides
Authors: Arabiat Sahar , Khan Mohamed F. R.
Published: August 2016

Rhizoctonia damping-off and crown and root rot caused by Rhizoctonia solani are major diseases of sugar beet (Beta vulgaris L.) worldwide, and growers in the United States rely on fungicides for disease management. Sensitivity of R. solani to fungicides was evaluated in vitro using a mycelial radial growth assay and by evaluating disease severity on R. solani AG 2-2 inoculated plants treated with fungicides in the greenhouse. The mean concentration that caused 50% mycelial growth inhibition (EC50) values for baseline isolates (collected before the fungicides were registered for sugar beet) were 49.7, 97.1, 0.3, 0.2, and 0.9 μg ml−1 and for nonbaseline isolates (collected after registration and use of fungicides) were 296.1, 341.7, 0.9, 0.2, and 0.6 μg ml−1 for azoxystrobin, trifloxystrobin, pyraclostrobin, penthiopyrad, and prothioconazole, respectively. The mean EC50 values of azoxystrobin, trifloxystrobin, and pyraclostrobin significantly increased in the nonbaseline isolates compared with baseline isolates, with a resistant factor of 6.0, 3.5, and 3.0, respectively. Frequency of isolates with EC50 values >10 μg ml−1 for azoxystrobin and trifloxystrobin increased from 25% in baseline isolates to 80% in nonbaseline isolates. Although sensitivity of nonbaseline isolates of R. solani to quinone outside inhibitors decreased, these fungicides at labeled rates were still effective at controlling the pathogen under greenhouse conditions.
Pea seed-borne mosaic virusin Field Pea: Widespread Infection, Genetic Diversity, and Resistance Gene Effectiveness
Authors: Congdon B. S. , Coutts B. A. , Renton M. , Banovic M. , Jones R. A. C.
Published: August 2016

From 2013 to 2015, incidences of Pea seed-borne mosaic virus (PSbMV) infection were determined in semi-leafless field pea (Pisum sativum) crops and trial plots growing in the Mediterranean-type environment of southwest Australia. PSbMV was found at incidences of 2 to 51% in 9 of 13 crops, 1 to 100% in 20 of 24 cultivar plots, and 1 to 57% in 14 of 21 breeding line plots. Crops and plots of ‘PBA Gunyah’, ‘Kaspa’, and ‘PBA Twilight’ were frequently PSbMV infected but none of PSbMV resistance gene sbm1-carrying ‘PBA Wharton’ plants were infected. In 2015, 14 new PSbMV isolates obtained from these various sources were sequenced and their partial coat protein (CP) nucleotide sequences analyzed. Sequence identities and phylogenetic comparison with 39 other PSbMV partial CP nucleotide sequences from GenBank demonstrated that at least three PSbMV introductions have occurred to the region, one of which was previously unknown. When plants of ‘Greenfeast’ and PBA Gunyah pea (which both carry resistance gene sbm2) and PBA Wharton and ‘Yarrum’ (which carry sbm1) were inoculated with PSbMV pathotype P-2 isolate W1, resistance was overcome in a small proportion of plants of each cultivar, showing that resistance-breaking variants were likely to be present. An improved management effort by pea breeders, advisors, and growers is required to diminish infection of seed stocks, avoid sbm gene resistance being overcome in the field, and mitigate the impact of PSbMV on seed yield and quality. A similar management effort is likely to be needed in field pea production elsewhere in the world.
Trends in the Nonmedical Use of OxyContin, United States, 2006 to 2013
Authors: Jones Christopher M. , Muhuri Pradip K. , Lurie Peter G.
Published: August 2016

Objectives:

The role of the opioid OxyContin in the opioid abuse epidemic has been well documented. In 2010, OxyContin was reformulated to make it more difficult to abuse. We assessed past-year OxyContin nonmedical use among a nationally representative population and among nonmedical users of opioid pain relievers in the United States between 2006 and 2013.

Materials and Methods:

Data are from the National Survey on Drug Use and Health. Prevalence estimates of past-year OxyContin nonmedical use overall and by sociodemographic, geographic, and substance use characteristics were calculated for each year, 2006 through 2013. Multivariable logistic regression was used to identify individual characteristics associated with past-year OxyContin nonmedical use before and after reformulation.

Results:

In 2013, the of past-year nonmedical use of OxyContin among people 12 years and older in the United States was 0.5%. This was significantly lower than the prevalence in 2010 (0.7%; P<0.05), but was similar to that in 2006 to 2009 and 2011 to 2012. Among past-year nonmedical users of pain relievers in 2013, the prevalence of OxyContin nonmedical use was 13.0%. This was significantly higher than the prevalence in 2006 (10.5%; P<0.05), and was similar to that in 2007 through 2012. Groups with increased odds of using OxyContin nonmedically in the past-year were similar before and after reformulation (2009-2010 and 2012-2013, respectively). For 2012-2013, odds for past-year OxyContin nonmedical use after reformulation were greatest for: people reporting ≥200 days of pain reliever nonmedical use, adjusted odds ratio (aOR)=3.61 (95% confidence interval [CI], 2.47-5.28); past-year heroin users, aOR=3.45 (95% CI, 2.22-5.37); and people with past-year pain reliever abuse or dependence, aOR=2.57 (95% CI, 1.88-3.51).

Discussion:

The prevalence of past-year OxyContin nonmedical use in 2013, 3 years after reformulation, was significantly lower than the prevalence in the reformulation year, but similar to other years before and after reformulation. The prevalence of OxyContin nonmedical use among nonmedical users of pain relievers was higher than or similar to historical prevalence rates before reformulation. Groups with increased odds of OxyContin nonmedical use were similar before and after reformulation.
Men in Nursing: Intention, Intentionality, Caring, and Healing
Authors: Zahourek Rothlyn P.
Published: August 2016

The purpose of this article is to amplify the results section of a grounded theory study on how men in nursing view and experience intention, intentionality, caring, and healing. This is the second grounded theory study addressing intentionality in healing. The first study included a female population. The theory that was generated—Intentionality: The Matrix of Healing (IMH)—is examined with these new data. The results are compared with issues generally faced by men in nursing and how they described their beliefs and experiences with intentionality and healing. The theory (IMH) is supported; the importance of action in this cohort was an additional emphasis. This article provides an expanded view of men in nursing and their experiences as nurses and with intentionality, caring, and healing and has implications for the development of holistic nursing theory as well.
Potential Blood-based Biomarkers for Concussion
Authors: Papa Linda
Published: August 2016

Mounting research in the field of sports concussion biomarkers has led to a greater understanding of the effects of brain injury from sports. A recent systematic review of clinical studies examining biomarkers of brain injury following sports-related concussion established that almost all studies have been published either in or after the year 2000. In an effort to prevent chronic traumatic encephalopathy and long-term consequences of concussion, early diagnostic and prognostic tools are becoming increasingly important; particularly in sports and in military personnel, where concussions are common occurrences. Early and tailored management of athletes following a concussion with biomarkers could provide them with the best opportunity to avoid further injury. Should blood-based biomarkers for concussion be validated and become widely available, they could have many roles. For instance, a point-of-care test could be used on the field by trained sport medicine professionals to help detect a concussion. In the clinic or hospital setting, it could be used by clinicians to determine the severity of concussion and be used to screen players for neuroimaging (computed tomography and/or magnetic resonance imaging) and further neuropsychological testing. Furthermore, biomarkers could have a role in monitoring progression of injury and recovery and in managing patients at high risk of repeated injury by being incorporated into guidelines for return to duty, work, or sports activities. There may even be a role for biomarkers as surrogate measures of efficacy in the assessment of new treatments and therapies for concussion.
Age, Sex, Health Insurance, and Race Associated With Increased Rate of Emergent Pediatric Gastrointestinal Procedures
Authors: Andrews Ashley , Franklin Linda , Rush Natasha , Witts Robin , Blanco David , Pall Harpreet
Published: August 2016

Objectives:

Few studies have examined the role health disparities play in pediatric gastrointestinal (GI) procedures. We hypothesized that health disparity factors affect whether patients undergo an emergent versus nonemergent GI procedure. The aims were to characterize the existing pediatric population undergoing GI procedures at our institution and assess specific risk factors associated with emergent versus nonemergent care.

Methods:

We retrospectively reviewed the medical records of 2110 patients undergoing GI procedures from January 2012 to December 2014. Emergent procedures were performed on an urgent inpatient basis. All other procedures were considered nonemergent. Health disparity factors analyzed included age, sex, insurance type, race, and language. Logistic regression analysis identified the odds of undergoing emergent procedures for each factor.

Results:

Most study patients were boys (58.2%), primarily insured by Medicaid (63.8%), white (44.0%), and spoke English (91.7%). Ten percent of all patients had an emergent procedure. Logistic regression analysis showed significant odds ratios (P value) for ages 18 years older (2.16, 0.003), females (0.62, 0.001), commercial insurance users (0.49, <0.0001), African Americans (1.94, <0.0001), and other race (1.72, 0.039).

Conclusions:

Health disparities in age, sex, insurance, and race appear to exist in this pediatric population undergoing GI procedures. Patients older than 18 years, African Americans, and other races were significantly more likely to have an emergent procedure. Girls and commercial insurance users were significantly less likely to have an emergent procedure. More research is necessary to understand why these relations exist and how to establish appropriate interventions.
Michael Elliott CBE. 30 September 1924 — 17 October 2007
Authors: Pickett John
Published: August 2016

Michael Elliott was the leader of work at Rothamsted that invented and subsequently commercially developed the pyrethroids, a new class of insecticides. Michael made probably the greatest individual contribution to the control of insect pests that not only constrain global food production but also affect the health of ourselves and our livestock. In one of the first pioneering structure–activity relationship studies, Michael led the multidisciplinary team that invented the major pyrethroid insecticides bioresmethrin, permethrin, cypermethrin and deltamethrin. In the 1980s these represented two-thirds of the global pyrethroid market; at that time pyrethroids captured more than 25% of the total insecticide market and were used on 33 million hectares of crops (Wirtz
et al
. 2009). In 2002 deltamethrin was the world's largest-selling pyrethroid, with annual sales worth $208 million (information from Cropnosis Ltd). In terms of human health, in 2009 it was estimated that pyrethroid-treated bednets significantly decreased the number of deaths due to malaria among children under five years of age by about one-fifth as well as reducing all incidents of malaria, and in 2011 the World Health Organization recommended its vastly expanded use.

Reference

Wirtz, K., Bala, S., Amann, A. & Elbert, A. 2009 A promise extended—future roles of pyrethroids in agriculture.
Bayer CropSci. J.
62
, 145–158.
Inhibition of Bcl-xL sensitizes cells to mitotic blockers, but not mitotic drivers
Authors: Bennett Ailsa , Sloss Olivia , Topham Caroline , Nelson Louisa , Tighe Anthony , Taylor Stephen S.
Published: August 2016

Cell fate in response to an aberrant mitosis is governed by two competing networks: the spindle assembly checkpoint (SAC) and the intrinsic apoptosis pathway. The mechanistic interplay between these two networks is obscured by functional redundancy and the ability of cells to die either in mitosis or in the subsequent interphase. By coupling time-lapse microscopy with selective pharmacological agents, we systematically probe pro-survival Bcl-xL in response to various mitotic perturbations. Concentration matrices show that BH3-mimetic-mediated inhibition of Bcl-xL synergises with perturbations that induce an SAC-mediated mitotic block, including drugs that dampen microtubule dynamics, and inhibitors targeting kinesins and kinases required for spindle assembly. By contrast, Bcl-xL inhibition does not synergize with drugs which drive cells through an aberrant mitosis by overriding the SAC. This differential effect, which is explained by compensatory Mcl-1 function, provides opportunities for patient stratification and combination treatments in the context of cancer chemotherapy.
Autophagy protects cardiomyocytes from the myocardial ischaemia-reperfusion injury through the clearance of CLP36
Authors: Li Shiguo , Liu Chao , Gu Lei , Wang Lina , Shang Yongliang , Liu Qiong , Wan Junyi , Shi Jian , Wang Fang , Xu Zhiliang , Ji Guangju , Li Wei
Published: August 2016

Cardiovascular disease (CVD) is the leading cause of the death worldwide. An increasing number of studies have found that autophagy is involved in the progression or prevention of CVD. However, the precise mechanism of autophagy in CVD, especially the myocardial ischaemia-reperfusion injury (MI/R injury), is unclear and controversial. Here, we show that the cardiomyocyte-specific disruption of autophagy by conditional knockout of
Atg7
leads to severe contractile dysfunction, myofibrillar disarray and vacuolar cardiomyocytes. A negative cytoskeleton organization regulator, CLP36, was found to be accumulated in
Atg7
-deficient cardiomyocytes. The cardiomyocyte-specific knockout of
Atg7
aggravates the MI/R injury with cardiac hypertrophy, contractile dysfunction, myofibrillar disarray and severe cardiac fibrosis, most probably due to CLP36 accumulation in cardiomyocytes. Altogether, this work reveals autophagy may protect cardiomyocytes from the MI/R injury through the clearance of CLP36, and these findings define a novel relationship between autophagy and the regulation of stress fibre in heart.
N-body dynamics on closed surfaces: the axioms of mechanics
Authors: Boatto Stefanella , Dritschel David G. , Schaefer Rodrigo G.
Published: August 2016

A major challenge for our understanding of the mathematical basis of particle dynamics is the formulation of N-body and N-vortex dynamics on Riemann surfaces. In this paper, we show how the two problems are, in fact, closely related when considering the role played by the intrinsic geometry of the surface. This enables a straightforward deduction of the dynamics of point masses, using recently derived results for point vortices on general closed differentiable surfaces
M
endowed with a metric
g
. We find, generally, that Kepler's Laws do not hold. What is more, even Newton's First Law (the law of inertia) fails on closed surfaces with variable curvature (e.g. the ellipsoid).
Evidence for water-mediated mechanisms in coral–algal interactions
Authors: Jorissen Hendrikje , Skinner Christina , Osinga Ronald , de Beer Dirk , Nugues Maggy M.
Published: August 2016

Although many coral reefs have shifted from coral-to-algal dominance, the consequence of such a transition for coral–algal interactions and their underlying mechanisms remain poorly understood. At the microscale, it is unclear how diffusive boundary layers (DBLs) and surface oxygen concentrations at the coral–algal interface vary with algal competitors and competitiveness. Using field observations and microsensor measurements in a flow chamber, we show that coral (massive
Porites
) interfaces with thick turf algae, macroalgae, and cyanobacteria, which are successful competitors against coral in the field, are characterized by a thick DBL and hypoxia at night. In contrast, coral interfaces with crustose coralline algae, conspecifics, and thin turf algae, which are poorer competitors, have a thin DBL and low hypoxia at night. Furthermore, DBL thickness and hypoxia at the interface with turf decreased with increasing flow speed, but not when thick turf was upstream. Our results support the importance of water-mediated transport mechanisms in coral–algal interactions. Shifts towards algal dominance, particularly dense assemblages, may lead to thicker DBLs, higher hypoxia, and higher concentrations of harmful metabolites and pathogens along coral borders, which in turn may facilitate algal overgrowth of live corals. These effects may be mediated by flow speed and orientation.
Host stress hormones alter vector feeding preferences, success, and productivity
Authors: Gervasi Stephanie S. , Burkett-Cadena Nathan , Burgan Sarah C. , Schrey Aaron W. , Hassan Hassan K. , Unnasch Thomas R. , Martin Lynn B.
Published: August 2016

Stress hormones might represent a key link between individual-level infection outcome, population-level parasite transmission, and zoonotic disease risk. Although the effects of stress on immunity are well known, stress hormones could also affect host–vector interactions via modification of host behaviours or vector-feeding patterns and subsequent reproductive success. Here, we experimentally manipulated songbird stress hormones and examined subsequent feeding preferences, feeding success, and productivity of mosquito vectors in addition to defensive behaviours of hosts. Despite being more defensive, birds with elevated stress hormone concentrations were approximately twice as likely to be fed on by mosquitoes compared to control birds. Moreover, stress hormones altered the relationship between the timing of laying and clutch size in blood-fed mosquitoes. Our results suggest that host stress could affect the transmission dynamics of vector-borne parasites via multiple pathways.
Palmitoylation of the oncogenic RhoGEF TGAT is dispensable for membrane localization and consequent activation of RhoA
Authors: van Unen Jakobus , Botman Dennis , Yin Taofei , Wu Yi I. , Hink Mark A. , Gadella Theodorus W.J. , Postma Marten , Goedhart Joachim
Published: August 2016

Rho guanine exchange factors (RhoGEFs) control many aspects of the cellular cytoskeleton, and thereby regulate and control processes such as cell migration, cell adhesion and proliferation. TGAT is a splice variant of the RhoGEF Trio, with oncogenic potential. Whether the subcellular location of TGAT is critical for its activity is unknown. Confocal microscopy of fluorescent protein tagged TGAT revealed co-localization with a Golgi marker. Because plasma membrane localized RhoGEFs are particularly effective at activating RhoA, plasma membrane localization of TGAT was studied. In order to quantitatively measure plasma membrane association we developed a novel, highly sensitive image analysis method. The method requires a cytoplasmic marker and a plasma membrane marker, which are co-imaged with the tagged protein of interest. Linear unmixing is performed to determine the plasma membrane and cytoplasmic component in the fluorescence signal of protein of interest. The analysis revealed that wild-type TGAT is partially co-localized with the plasma membrane. Strikingly, cysteine TGAT-mutants lacking one or more palmitoylation sites in the C-tail, still showed membrane association. In contrast, a truncated variant, lacking the last 15 amino acids, TGATΔ15, lost membrane association. The functional role of membrane localization was determined by measuring TGAT activity in single cells with a RhoA FRET-sensor and F-actin levels. Mutants of TGAT that still maintained membrane association showed similar activity as wild-type TGAT. In contrast, the activity was abrogated for the cytoplasmic TGATΔ15variant. Synthetic recruitment of TGATΔ15to membranes confirmed that TGAT effectively activates RhoA at the plasma membrane. Together, these results show that membrane association of TGAT is critical for its activity, but that palmitoylation is dispensable.
Bacterial invasion of the pancreas revealed after analyses of the pancreatic cyst fluids
Authors: Narayanan Vilvapathy , Utomo Wesley K. , Bruno Marco J. , Peppelenbosch Maikel P. , Konstantinov Sergey R.
Published: August 2016

The involvement of bacterial translocation (BT) in the promotion of carcinogenesis has gained a considerable attention in the last years. At this point however BT has not been studied in the context of pancreatic cystic lesions and their development into pancreatic ductal adenocarcinoma. The aim of the study was to analyze if bacteria are present in pancreatic cyst fluid (PCF) collected from patients with suspected pancreatic cysts. Total DNA was isolated from sixty nine PCF. The occurrence of bacteria in PCF was analyzed using bacterial 16S rRNA gene-specific PCR-based method followed by sequence identification and quantitative PCR assay tuned up to different pathogenic and commensal human bacteria. Forty-seven out of sixty-nine samples (68%) were found positive for harboring bacterial 16S rRNA gene. Follow up sequencing analyses of the PCR products revealed that bacterial species related toFusobacterium spp., Bacteroides spp.,andBacillus spp.were predominating the PCF samples. The results suggest that specific bacteria can translocate to the pancreas and become detectable in the PCF.
Fitness costs of noise in biochemical reaction networks and the evolutionary limits of cellular robustness
Authors: David Van Dyken J.
Published: August 2016

Gene expression is inherently noisy, but little is known about whether noise affects cell function or, if so, how and by how much. Here I present a theoretical framework to quantify the fitness costs of gene expression noise and identify the evolutionary and synthetic targets of noise control. I find that gene expression noise reduces fitness by slowing the average rate of nutrient uptake and protein synthesis. This is a direct consequence of the hyperbolic (Michaelis-Menten) kinetics of most biological reactions, which I show cause “hyperbolic filtering”, a process that diminishes both the average rate and noise propagation of stochastic reactions. Interestingly, I find that transcriptional noise directly slows growth by slowing the average translation rate. Perhaps surprisingly, this is the largest fitness cost of transcriptional noise since translation strongly filters mRNA noise, making protein noise largely independent of transcriptional noise, consistent with empirical data. Translation, not transcription, then, is the primary target of protein noise control. Paradoxically, selection for protein-noise control favors increased ribosome-mRNA binding affinity, even though this increases translational bursting. However, I find that the efficacy of selection to suppress noise decays faster than linearly with increasing cell size. This predicts a stark, cell-size-mediated taxonomic divide in selection pressures for noise control: small unicellular species, including most prokaryotes, face fairly strong selection to suppress gene expression noise, whereas larger unicells, including most eukaryotes, experience extremely weak selection. I suggest that this taxonomic discrepancy in selection efficacy contributed to the evolution of greater gene-regulatory complexity in eukaryotes.

ARTICLE SUMMARY

Gene expression is a probabilistic process, resulting in random variation in mRNA and protein abundance among cells called “noise”. Understanding how noise affects cell function is a major problem in biology. Here I present theory demonstrating that gene expression noise slows the average rate of cell division. Furthermore, by modeling stochastic gene expression with non-linearity, I identify novel mechanisms of cellular robustness. However, I find that the cost of noise, and therefore the strength of selection favoring robustness, decays faster than linearly with increasing cell size. This may help explain the vast differences in gene-regulatory complexity between prokaryotes and eukaryotes.
Development and Application of Equilibrium Thermodynamic Models Describing Coupled Protein Oligomerization and Ligand Binding
Authors: Rennie Martin L. , Kingston Richard L
Published: August 2016

The association and dissociation of protein oligomers is frequently coupled to the binding of ligands, facilitating the regulation of many biological processes. Equilibrium thermodynamic models are needed to describe the linkage between ligand binding and homo-oligomerization. These models must be parameterized in a way that makes physical interpretation straightforward, and allows elaborations or simplifications to be readily incorporated. We propose a systematic framework for the equilibrium analysis of ligand-linked oligomerization, treating in detail the case of a homo-oligomer with cyclic point group symmetry, where each subunit binds a ligand at a single site. Exploiting the symmetry of the oligomer, in combination with a nearest-neighbors approximation, we derive a class of site-specific ligand binding models involving only four parameters, irrespective of the size of the oligomer. The model parameters allow direct quantitative assessment of ligand binding cooperativity, and the influence of ligand binding on protein oligomerization, which are the key questions of biological interest. These models, which incorporate multiple types of linkage, are practically applicable, and we show how Markov Chain Monte Carlo (MCMC) methods can be used to characterize the agreement of the model with experimental data. Simplifications to the model emerge naturally, as its parameters take on extremal values. The nearest-neighbors approximation underpinning the model is transparent, and the model could be augmented in obvious fashion if the approximation were inadequate. The approach is generalizable, and could be used to treat more complex situations, involving more than a single kind of ligand, or a different protein symmetry.

Author Summary

The assembly and disassembly of protein complexes in response to the binding of ligands is a ubiquitous biological phenomenon. This is often linked, in turn, to the activation or deactivation of protein function. Methods are therefore needed to quantitate the linkage or coupling between protein assembly and effector binding, requiring the development of mathematical models describing the coupled binding processes. As proteins usually assemble in a symmetric fashion, the nature of any symmetry present has to be considered during model construction. We have developed a class of models than can effectively describe the coupling between effector binding and protein assembly into symmetric ring-like structures of any size. Despite the relatively complex mathematical form of the models, they are practically applicable. Markov Chain Monte Carlo methods, a form of Bayesian statistical analysis, can be used to analyze the fit of the models to experimental data, and recover the model parameters. This allows the direct assessment of the nature and magnitude of the coupling between effector binding and protein assembly, as well as other relevant characteristics of the system.
Common schizophrenia alleles are enriched in mutation-intolerant genes and maintained by background selection
Authors: Pardiñas Antonio F. , Holmans Peter , Pocklington Andrew J. , Escott-Price Valentina , Ripke Stephan , Carrera Noa , Legge Sophie E. , Bishop Sophie , Cameron Darren , Hamshere Marian L. , Han Jun , Hubbard Leon , Lynham Amy , Mantripragada Kiran , Rees Elliott , MacCabe James H. , McCarroll Steven A. , Baune Bernhard T. , Breen Gerome , Byrne Enda M. , Dannlowski Udo , Eley Thalia C. , Hayward Caroline , Martin Nicholas G. , McIntosh Andrew M. , Plomin Robert , Porteous David J. , Wray Naomi R. ,   GERAD Consortium, Collier David A. , Rujescu Dan , Kirov George , Owen Michael J. , O’Donovan Michael C. , Walters James T. R.
Published: August 2016

Schizophrenia is a debilitating psychiatric condition often associated with poor quality of life and decreased life expectancy. Lack of progress in improving treatment outcomes has been attributed to limited knowledge of the underlying biology, although large-scale genomic studies have begun to provide such insight. We report the largest single cohort genome-wide association study of schizophrenia (11,260 cases and 24,542 controls) and through meta-analysis with existing data we identify 50 novel GWAS loci. Using gene-wide association statistics we implicate an additional set of 22 novel associations that map onto a single gene. We show for the first time that the common variant association signal is highly enriched among genes that are intolerant to loss of function mutations and that variants in these genes persist in the population despite the low fecundity associated with the disorder through the process of background selection. Associations point to novel areas of biology (e.g. metabotropic GABA-B signalling and acetyl cholinesterase), reinforce those implicated in earlier GWAS studies (e.g. calcium channel function), converge with earlier rare variants studies (e.g.NRXN1, GABAergic signalling), identify novel overlaps with autism (e.g.RBFOX1,FOXP1,FOXG1), and support early controversial candidate gene hypotheses (e.g.ERBB4implicating neuregulin signalling). We also demonstrate the involvement of six independent central nervous system functional gene sets in schizophrenia pathophysiology. These findings provide novel insights into the biology and genetic architecture of schizophrenia, highlight the importance of mutation intolerant genes and suggest a mechanism by which common risk variants are maintained in the population.
An Analytic framework for stochastic binary biological switches
Authors: Innocentini Guilherme C.P. , Guiziou Sarah , Bonnet Jerome , Radulescu Ovidiu
Published: August 2016

We propose an analytic solution for the stochastic dynamics of a binary biological switch, defined as a DNA unit with two mutually exclusive configurations, each one triggering the expression of a different gene. Such a device could be used as a memory unit for biological computing systems designed to operate in noisy environments. We discuss a recent implementation of an exclusive switch in living cells, the recombinase addressable data (RAD) module. In order to understand the behavior of a RAD module we compute the exact time dependent distributions of the two expressed genes starting in one state and evolving to another asymptotic state. We consider two operating regimes of the RAD module: fast and slow stochastic switching. The fast regime is “aggregative” and produces unimodal distributions, whereas the slow regime is “separative” and produces bimodal distributions. Both regimes can serve to prepare pure memory states when all cells are expressing the same gene. The slow regime can also separate mixed states by producing two sub-populations each one expressing a different gene. Our model provides a simplified, general phenomenological framework for studying biological memory devices and our analytic solution can be further used to clarify theoretical concepts in bio-computation and for optimal design in synthetic biology.
Acceleratingk-nearest-neighbor searches
Authors: Bernstein Herbert J. , Andrews Lawrence C.
Published: August 2016

The search for whichkpoints are closest to a given probe point in a space ofNknown points, the `k-nearest-neighbor' or `KNN' problem, is a computationally challenging problem of importance in many disciplines, such as the design of numerical databases, analysis of multi-dimensional experimental data sets, multi-particle simulations and data mining. A standard approach is to preprocess the data into a tree and make use of the triangle inequality to prune the search time to the order of the logarithm ofNfor a single nearest point in a well balanced tree. All known approaches suffer from the `curse of dimensionality', which causes the search to explore many more branches of the tree than one might wish as the dimensionality of the problem increases, driving search times closer to the order ofN. Looking forknearest points can sometimes be done in approximately the time needed to search for one nearest point, but more often it requiresksearches because the results are distributed widely. The result is very long search times, especially when the search radius is large andkis large, and individual distance calculations are very expensive, because the same probe-to-data-point distance calculations need to be executed repeatedly as the top of the tree is re-explored. Combining two acceleration techniques was found to improve the search time dramatically: (i) organizing the search into nested searches in non-overlapping annuli of increasing radii, using an estimation of the Hausdorff dimension applicable to this data instance from the results of earlier annuli to help set the radius of the next annulus; and (ii) caching all distance calculations involving the probe point to reduce the cost of repeated use of the same distances. The result of this acceleration in a search of the combined macromolecular and small-molecule data in a combined six-dimensional database of nearly 900 000 entries has been an improvement in the overall time of the searches by one to two orders of magnitude.
The new NCPSS BL19U2 beamline at the SSRF for small-angle X-ray scattering from biological macromolecules in solution
Authors: Li Na , Li Xiuhong , Wang Yuzhu , Liu Guangfeng , Zhou Ping , Wu Hongjin , Hong Chunxia , Bian Fenggang , Zhang Rongguang
Published: August 2016

The beamline BL19U2 is located in the Shanghai Synchrotron Radiation Facility (SSRF) and is its first beamline dedicated to biological material small-angle X-ray scattering (BioSAXS). The electrons come from an undulator which can provide high brilliance for the BL19U2 end stations. A double flat silicon crystal (111) monochromator is used in BL19U2, with a tunable monochromatic photon energy ranging from 7 to 15 keV. To meet the rapidly growing demands of crystallographers, biochemists and structural biologists, the BioSAXS beamline allows manual and automatic sample loading/unloading. A Pilatus 1M detector (Dectris) is employed for data collection, characterized by a high dynamic range and a short readout time. The highly automated data processing pipeline SASFLOW was integrated into BL19U2, with help from the BioSAXS group of the European Molecular Biology Laboratory (EMBL, Hamburg), which provides a user-friendly interface for data processing. The BL19U2 beamline was officially opened to users in March 2015. To date, feedback from users has been positive and the number of experimental proposals at BL19U2 is increasing. A description of the new BioSAXS beamline and the setup characteristics is given, together with examples of data obtained.
BUSINESS MANAGEMENT DISTANCE EDUCATION RESEARCH ON YEAR MARK ASSESSMENT POLICY AT THE UNIVERSITY OF SOUTH AFRICA
Authors: Smith Marolee Beaumont
Published: August 2016

The current tuition policy of the Department of Business Management at the University of South Africa encourages, but does not compel students to submit assignments under the semester system. A relatively small percentage of students submit the voluntary assignment, thereby forfeiting the benefit of the learning experience and assessment feedback from the respective lecturers. The Department of Business Management is concerned that this voluntary assignment assessment policy impacts negatively on the standard of learning and assessment within the Department. It hence decided to implement, on a trial basis for 2003 and 2004, a year-mark option assignment policy for two of its undergraduate semester courses. The aim was to assess whether such an option contributed towards the improvement of examination results and the enhancement of the learning experience of students registered for the relevant courses. This paper reports on the findings of the year-mark option assignment policy for the second year degree course MNX202-J (marketing management) and the third year degree course MNF301-5 (financial management) for the trial period 2003 to 2004. The findings are in the form of (1) statistics on the percentage number of students who submitted assignments, average marks obtained and examination results statistics during the trial period: (2) the results of an opinion survey questionnaire sent to students to obtain their feedback on the value of compulsory year-mark option assignments; and (3) feedback and comments from facilitators involved in the year-mark option exercise. Finally recommendations are made on the way forward for future assessment in the Department of Business Management.
BUILDING BILINGUAL BI-CONTINENTAL E-LEARNING COURSES
Authors: Zhang Zhanyang , Klibaner Roberta Marsha , Chi Emile Chungtian , Yuan Ke-Ping
Published: August 2016

The authors have been actively engaged in E-learning starting in 1996, at the College of Staten Island, CUNY, a public university on the East coast and Shanghai Television University, an open university in Shanghai. We have reported on this work in [Chi, Klibaner, 1999, 2001, 2003]. This collaboration has been expanded to include a bilingual course offered simultaneously at both institutions. Of the many technical issues involved in such a simultaneous e-learning course, the time difference is the only one which remains immutable. This paper describes our experience with a hybrid course in Database Theory offered bilingually in Chinese and English and a Windows based terminal software laboratory.
EVALUATION STANDARD FOR INSTITUSIONAL EVALUATION OF OPEN UNIVERSITY
Authors: Kim Bowon , Yang Chang Yeul
Published: August 2016

This study is to develop the standards and indexes for evaluating the open university as an institution. Having successfully taken root in their societies since their launching, Asian open universities now need to further up their teaching and learning system which demands a rigid evaluation and assessment of a university as an institution. For the past ten years, Korea National Open University (KNOU) was evaluated twice by Korean Council for University Education (KCUE), which is in charge of the evaluation of the Korean universities; the result was not so satisfactory. It was because its evaluation standards and indexes were not appropriate for KNOU as an open university. They were primarily for the conventional universities. Thus KNOU needed its own assessment indexes, and this is a research looking for the proper ones for evaluating KNOU within the frame of university evaluation in Korea. Other open universities in Asia also have experienced or will face such problems in terms of the university evaluation. The result of this research will be helpful not only for KNOU but for other Asian open universities preparing for the university evaluation.
TOWARDS A MORE EFFECTIVE ENGAGEMENT OF LEARNERS AND TUTORS IN ONLINE DISCUSSION FORUMS
Authors: Abas Zoraini Wati , Fadzil Mansor
Published: August 2016

Online discussion forums have the potential to add value to the total learning environmental in open distance learning. A study analyzing more than a hundred online forums from twenty offered by four faculties was conducted at the Open University Malaysia (OUM). The study aimed to determine how effective online forums were in contributing to the blended learning pedagogies adopted by the university. Using the Community of Inquiry model to evaluate the effectiveness of the forum discourse, the forums were examined to determine the extent of social presence, cognitive presence and teaching presence in the forums. The study also looked at similarities and differences in interactions in the various forums. Several interesting observation were made as a result of the analysis. One major observation made was the need for tutors to be trained on how to field questions, pose questions and lead as well as moderate the discussions. The study was timely to ensure that online discussion forums contribute further to the blended learning environment at OUM.
Tutors and Learners Without Borders: In a Relationship but it's Complicated
Authors: Gervacio Juvy Lizette
Published: August 2016

Global tutoring and learning communities are composed of different people who share a common interest or a common goal. Learners aim to acquire knowledge and skills; while tutors aim to provide content support, coaching and motivation to learners. The interaction is done through the use of technology, specifically the Internet. Management of these communities can be a challenge because members are not only separated by space and time but they come from different cultures, contextual backgrounds and institutions. If managed well, global tutoring and learning communities can transcend barriers and be very effective, efficient and also inexpensive.

The paper looks into how online tutors and learners are effectively and efficiently managed and sustained. Specifically, it aims to: a) define global tutoring and learning communities and their rationale; b) describe the strategies and good practices employed in the planning, implementation, monitoring and evaluation; c)determine the effective communication tools used to manage and sustain global teams; and d) identify the challenges and lessons to maintain and sustain global tutoring and learning communities.

The paper is based on studies as well as actual experiences and written reports on managing global learning and tutoring communities. It will look into how teams are managed from planning, implementation to monitoring and evaluation. Specifically, it will provide a glimpse on how learners and tutors from different countries and nationalities are managed in the elearning Development and Implementation (eLDI) program and e-skills program. These courses are jointly offered by the University of the Philippines Open University (UPOU) and InWEnt, Capacity Building International, Germany and have learners and tutors from various countries not only from Asia, but from Africa and the Middle East. The paper also draws lessons on how to maintain tutors and learners without borders.
Augmenting the learning management system of UP Open University
Authors: Librero Al Francis D.
Published: August 2016

The University of the Philippines Open University (UPOU) has used Moodle, an open source course management system since 2007. While the application allowed the university to deploy all its courses online, Moodle still presents limitations. The compartmentalised nature of courses within the system inhibits the sharing of learning objects and resources across users. Furthermore, while it does have social networking capabilities to a certain degree (by many accounts more so than other learning management systems), Moodle provides little flexibility when it comes to collaborative learning. Technical issues also hampered the performance of a number of built-in functionalities, which in turn gets in the way of the learning experience. These limitations encouraged facilitators and students alike to opt for third party web applications to fulfil course requirements. This research project aimed to address these limitations by expanding upon the functionalities of Moodle. This was achieved through the installation of modules and plugins within Moodle itself and the integration of external web applications such as conferencing, blogging, e-portfolios and rich media content management through single sign on (SSO). This expansion brought about a number of achievements. First, learning activities were made available which were either new or improved upon what Moodle had by default. This expanded learning management system was piloted with two courses under the Bachelor of Arts in Multimedia Studies programme, which Moodle has been historically ill-equipped to accommodate on its own. Findings of this study were based on the analysis of performance as well as firsthand feedback from users, which in turn is to be used for the continual improvement of UPOU's online course deployment.
Comparative study on the usage of an online plagiarism detection service when presenting distance learning courses
Authors: Hong Loo Choo , Cheng Tung Lai
Published: August 2016

The Internet opens a library of wealth to the student and educator but it also makes it easy for students to copy when writing assignments. In this paper, we will look at how Wawasan Open University implemented plagiarism-detection software in its course delivery. In 2010, the university introduced the compulsory usage of an online plagiarism-detection software known as Turnitin (Turnitin TM). Students are required to scan their assignments using the service before submitting them for grading. In this study, we observed two different course clusters; one cluster is numerically-based and the other is narrative-based. We observed the Similarity Index Report on student assignments from four courses in two programmes from the 2011 cohort. The courses are Business Accounting II, Auditing and Assurance in Malaysia, Human Resource Management, and Organisational Behaviour. Our findings suggested that plagiarism detection software can be useful for courses that require a studentto demonstrate a strong sense of originality in their assignments. Essentially, the software would provide additional advantages in any narrative management course where it is the intention of the instructor to ensure that students demonstrate a high level of creativity. However, courses that require students to conform to any regimen should not be subjected to the anti-plagiarism process as this is futile, as in the case of many numerical and mathematical courses. Courses that require a high level of verbatim citation such as law, assurance, literature and divinity would not work very well with the software. The inability of current software to differentiate between patterns and strings of plagiarism and cited work makes this exercise futile.
How flexible do students prefer their learning to be?
Authors: LI Kam Cheong
Published: August 2016

The term 'flexible learning' has been used in the literature for decades in a rather general sense and has been closely associated with open and distance education. The notion of flexibility has been examined on various dimensions, such as admission criteria, students' control of learning time, commitment, content and tasks. There has recently been a tendency to use the term in a more defined or technical sense.One research focus has revolved around course design for effective learning in relation to the learner and dimensions of flexibility.

This paper offers an updated review of the literature on the approaches to understanding flexible learning and the dimensions of flexibility involved. It also reports a preliminary study on distancelearners' preferences for flexibility in the courses in which they are engaged. In the study, a questionnaire was administered to 162 distance learners in Hong Kongto determine their preferred levels of flexibility on a range of dimensions. The results suggest that learners' preferences vary across dimensions. Based on the findings, it is argued that the diversity of learners' preferences and learning styles should be incorporated as an integral part of the mechanism for designing and reviewing study programmes.