bluuebunny/crossref_metadata_2025 huggingface dataset:
Best Practices in Docking and Activity Prediction
Authors: Rueda Manuel , Abagyan Ruben
Published: February 2016

During the last decade we witnessed how computational docking methods became a crucial tool in the search for new drug candidates. The ‘central dogma’ of small molecule docking is that compounds that dock correctly into the receptor are more likely to display biological activity than those that do not dock. This ‘dogma’, however, possesses multiple twists and turns that may not be obvious to novice dockers. The first premise is that the compounds must dock; this implies: (i) availability of data, (ii) realistic representation of the chemical entities in a form that can be understood by the computer and the software, and, (iii) exhaustive sampling of the protein-ligand conformational space. The second premise is that, after the sampling, all docking solutions must be ranked correctly with a score representing the physico-chemical foundations of binding. The third premise is that ‘correctness’ must be defined unambiguously, usually by comparison with ‘static’ experimental data (or lack thereof). Each of these premises involves some degree of simplification of reality, and overall loss in the accuracy of the docking predictions.

In this chapter we will revise our latest experiences in receptor-based docking when dealing with all three above-mentioned issues. First, we will explain the theoretical foundation of ICM docking, along with a brief explanation on how we measure performance. Second, we will contextualize ICM by showing its performance in single and multiple receptor conformation schemes with the Directory of Useful Decoys (DUD) and the Pocketome. Third, we will describe which strategies we are using to represent protein plasticity, like using multiple crystallographic structures or Monte Carlo (MC) and Normal Mode Analysis (NMA) sampling methods, emphasizing how to overcome the associated pitfalls (e.g., increased number of false positives). In the last section, we will describe ALiBERO, a new tool that is helping us to improve the discriminative power of X-ray structures and homology models in screening campaigns.
Intelligence and neuroticism in relation to depression and psychological distress: evidence of interaction using data from Generation Scotland: Scottish Family Health Study and UK Biobank
Authors: Navrady LB , Ritchie SJ , Chan SWY , Kerr DM , Adams MJ , Hawkins E , Porteous DJ , Deary IJ , Gale CR , Batty GD , McIntosh AM
Published: February 2016

Background

Neuroticism is a risk factor for selected mental and physical illnesses and is inversely associated with intelligence. Intelligence appears to interact with neuroticism and mitigate its detrimental effects on physical health and mortality. However, the inter-relationships of neuroticism and intelligence for major depressive disorder (MDD) and psychological distress has not been well examined.

Methods

Associations and interactions between neuroticism and general intelligence (g) on MDD and psychological distress were examined in two population-based cohorts: Generation Scotland: Scottish Family Health Study (GS:SFHS, N=19,200) and UK Biobank (N=90,529). The Eysenck Personality Scale Short Form-Revised measured neuroticism and g was extracted from multiple cognitive ability tests in each cohort. Family structure was adjusted for in GS:SFHS.

Results

Neuroticism was associated with MDD and psychological distress in both samples. A significant interaction between neuroticism and g in predicting MDD status was found in UK Biobank (OR = 0.96,p< .01), suggesting that higher g ameliorated the adverse effects of neuroticism on the likelihood of having MDD. This interaction was not found in GS:SFHS. In both samples, higher neuroticism and lower intelligence were associated with increased psychological distress. A significant interaction was also found in both cohorts (GS:SFHS: ß = -0.05,p< .01; UK Biobank: ß = -0.02,p< .01), such that intelligence protected against the deleterious effect of neuroticism on psychological distress.

Conclusions

From two large cohort studies, our findings suggest intelligence acts a protective factor in mitigating the effects of neuroticism on risk for depressive illness and psychological distress.
Biocompatibility of Subcutaneously Implanted Plant-Derived Cellulose Biomaterials
Authors: Modulevsky Daniel J. , Cuerrier Charles M. , Pelling Andrew E.
Published: February 2016

There is intense interest in developing novel biomaterials which support the invasion and proliferation of living cells for potential applications in tissue engineering and regenerative medicine. Decellularization of existing tissues have formed the basis of one major approach to producing 3D scaffolds for such purposes. In this study, we utilize the native hypanthium tissue of apples and a simple preparation methodology to create implantable cellulose scaffolds. To examine biocompatibility, scaffolds were subcutaneously implanted in wild-type, immunocompetent mice (males and females; 6-9 weeks old). Following the implantation, the scaffolds were resected at 1, 4 and 8 weeks and processed for histological analysis (H&E, Masson’s Trichrome, anti-CD31 and anti-CD45 antibodies). Histological analysis revealed a characteristic foreign body response to the scaffold 1 week post-implantation. However, the immune response was observed to gradually disappear by 8 weeks post-implantation. By 8 weeks, there was no immune response in the surrounding dermis tissue and active fibroblast migration within the cellulose scaffold was observed. This was concomitant with the deposition of a new collagen extracellular matrix. Furthermore, active blood vessel formation within the scaffold was observed throughout the period of study indicating the pro-angiogenic properties of the native scaffolds. Finally, while the scaffolds retain much of their original shape they do undergo a slow deformation over the 8-week length of the study. Taken together, our results demonstrate that native cellulose scaffolds are biocompatible and exhibit promising potential as a surgical biomaterial.
Using Field Experiments in Accounting and Finance
Authors: FLOYD ERIC , LIST JOHN A.
Published: February 2016

The gold standard in the sciences is uncovering causal relationships. A growing literature in economics utilizes field experiments as a methodology to establish causality between variables. Taking lessons from the economics literature, this study provides an “A‐to‐Z” description of how to conduct field experiments in accounting and finance. We begin by providing a user's guide into what a field experiment is, what behavioral parameters field experiments identify, and how to efficiently generate and analyze experimental data. We then provide a discussion of extant field experiments that touch on important issues in accounting and finance, and we also review areas that have ample opportunities for future field experimental explorations. We conclude that the time is ripe for field experimentation to deepen our understanding of important issues in accounting and finance.
Area reduction and trace element pollution in Nile Delta wetland ecosystems
Authors: El‐Shazly Mohamed M. , Omar Wael A. , Edmardash Yusuf A. , Ibrahim Mona Sayed , Elzayat Emad I. , El‐Sebeay Iman I.A. , Abdel Rahman Khaled M. , Soliman Mustafa M.
Published: February 2016

The three main Nile Delta wetland ecosystems, Manzala, Burullus and Edku lagoons, are among the most ecologically important and productive habitats in Egypt. We studied the area degradation and the human health risks associated with trace metal accumulation in Tilapia zillii harvested from these lakes. The area of Manzala lagoon has shrunken from about 3035 km2 in 1800 to about 288 km2 in 2015, the area of Edku has shrunken from about 336 km2 in 1824 to about 18 km2 in 2014, and the area of Burullus has shrunken from about 1116 km2 in 1949 to about 546 km2 in 2014. This area degradation is attributed to drying for housing, land reclamation and fish farming. As a result, the concentration of pollutants and nutrients has subsequently increased, and large parts of the lakes have been overgrown with aquatic vegetation, which increased the rate of degradation and land transformation. Metal pollution was detected in water, sediment and edible fish harvested from the lakes. The hazard index, an indicator of human health risks associated with fish consumption, showed adverse health effects of zinc and lead metals for habitual fish consumers. The impact of the high dam on the lakes was discussed.
Elevated plasma levels of vascular permeability factors in C1 inhibitor‐deficient hereditary angioedema
Authors: Loffredo S. , Bova M. , Suffritti C. , Borriello F. , Zanichelli A. , Petraroli A. , Varricchi G. , Triggiani M. , Cicardi M. , Marone G.
Published: February 2016

Background

Hereditary angioedema with C1 inhibitor deficiency (C1‐INH‐HAE) is a rare inherited genetic disease characterized by recurrent swelling episodes of the skin, gastrointestinal tract, and upper airways. Angioedema attacks result from increased vascular permeability due to the release of bradykinin from high molecular weight kininogen. Currently, there are no biomarkers predicting the frequency of angioedema attacks. Vascular permeability is modulated by several factors, including vascular endothelial growth factors (VEGFs) and angiopoietins (Angs). As increased circulating levels of VEGFs and Angs have been observed in diseases associated with higher vascular permeability (e.g., systemic capillary leak syndrome and sepsis), we sought to analyze plasma concentrations of VEGFs and Angs in patients with C1‐INH‐HAE.

Methods

Sixty‐eight healthy controls and 128 patients with C1‐INH‐HAE were studied. Concentrations of angiogenic (VEGF‐A, Ang1, Ang2), anti‐angiogenic (VEGF‐A165b) and lymphangiogenic (VEGF‐C) factors were evaluated by ELISA. C1‐INH functional activity was assessed by EIA.

Results

Plasma concentrations of VEGF‐A, VEGF‐C, Ang1, and Ang2 were higher in patients with C1‐INH‐HAE in remission than in healthy controls. Concentration of VEGF‐A was further increased in patients with lower C1‐INH functional activity. Patients with C1‐INH‐HAE experiencing more than 12 angioedema attacks per year were characterized by higher plasma levels of VEGF‐A, VEGF‐C, and Ang2 compared with the other patients.

Conclusions

We hypothesize that VEGFs and Angs induce a state of ‘vascular preconditioning’ that may predispose to angioedema attacks. In addition, the identification of increased plasma levels of VEGFs and Angs in patients with C1‐INH‐HAE may prompt the investigation of VEGFs and Angs as biomarkers of C1‐INH‐HAE severity.
Body fat measurement in adolescent girls with type 1 diabetes: a comparison of skinfold equations against dual‐energy X‐ray absorptiometry
Authors: Särnblad S , Magnuson A , Ekelund U , Åman J
Published: February 2016

Aim

Skinfold measurement is an inexpensive and widely used technique for assessing the percentage of body fat (%BF). This study assessed the accuracy of prediction equations for %BF based on skinfold measurements compared to dual‐energy X‐ray absorptiometry (DXA) in girls with type 1 diabetes and healthy age‐matched controls.

Methods

We included 49 healthy girls and 44 girls with diabetes aged 12–19 years old, comparing the predicted %BF based on skinfold measurements and the %BF values obtained by a Lunar DPX‐L scanner. The agreement between the methods was assessed using an Bland–Altman plot.

Results

The skinfold measurements were significantly higher in girls with diabetes (p = 0.003) despite a nonsignificant difference in total %BF (p = 0.1). A significant association between bias and %BF was found for all tested equations in the Bland–Altman plots. Regression analysis showed that the association between skinfold measurements and %BF measured by DXA differed significantly (p = 0.039) between the girls with diabetes and the healthy controls.

Conclusion

The accuracy of skinfold thickness equations for assessment of %BF in adolescent girls with diabetes is poor in comparison with DXA measurements as criterion. Our findings highlight the need for the development of new prediction equations for girls with type 1 diabetes.
Some Anticancer Agents Act on Human Serum Paraoxonase‐1 to Reduce Its Activity
Authors: Alim Zuhal , Beydemir Şükrü
Published: February 2016

Human serum paraoxonase (hPON1) is an important antioxidant enzyme. It protects low‐density lipoproteins against oxidative stress and prevents atherosclerosis development. Anticancer agents have cardiotoxic effects, and this situation can lead to significant complications. Our aim was to evaluate the in vitro effects of some of the anticancer agents such as cetuximab, paclitaxel, etoposide, docetaxel, and ifosfamide on the activity of hPON1 in this study. For this reason, PON1 was purified from human serum with a specific activity of 3654.2 EU/mg and 16.84% yield using simple chromatographic methods. The five chemotherapeutic agents dose dependently decreased in vitro hPON1 activity. IC50 values for cetuximab, paclitaxel, etoposide, docetaxel, and ifosfamide were 0.0111, 0.042, 0.226, 0.665, and 23.3 mm, respectively. Ki constants were 0.0194, 0.0165, 0.131, 0.291, and 8.973 mm, respectively. The inhibition mechanisms of cetuximab, etoposide, docetaxel, and ifosfamide were non‐competitive, and for paclitaxel was competitive. Consequently, inhibition of hPON1 by these anticancer agents may explain some of the cardiotoxic actions of these drugs.
Density dependence of herbivorous central stoneroller Campostoma anomalum in stream mesocosms
Authors: Pennock Casey A. , Gido Keith B.
Published: February 2016

Herbivorous fish can have strong effects on stream ecosystem function by consuming primary producers and excreting limiting nutrients, but it is unclear whether they are resource limited. Thus, understanding factors regulating abundance of these fish might help predict ecosystem function. We used stream mesocosms to test whether populations of central stoneroller Campostoma anomalum exhibit density dependence across a range of typical densities and resource abundance found in Great Plains streams. We predicted that incrementally increasing stocking biomass from 3·7 to 24·9 g·m−2 would reduce standing stocks of resources resulting in lower growth of stocked fish. Fish growth (over 41 days) was compared to initial stocking biomass and primary production as well as standing stocks of algae and invertebrates using regression analysis. Mean growth of individuals was negatively associated with stocking biomass ( = 0·55; P = 0·02), as predicted. Contrary to our prediction, increases in fish biomass led to increased primary productivity ( = 0·31, P = 0·07), but resulted in no relationship among algal filament lengths ( = 0·00; P = 0·34), algal biomass ( = 0·12; P = 0·19) or invertebrate biomass ( = 0·03; P = 0·30). Thus, density dependence occurred without an apparent reduction in food resources. We hypothesised that stoneroller growth was possibly limited by competition for high‐quality algae or invertebrates, or behavioural interactions causing interference competition.
Risk of skin cancer in multiple myeloma patients: a retrospective cohort study
Authors: Robinson Austin A. , Wang James , Vardanyan Suzie , Madden Erik K. , Hebroni Frank , Udd Kyle A. , Spektor Tanya M. , Nosrati Jason D. , Kitto Alex Z. , Zahab Michael , Cheema Simrin , Fors Darron H. , Norberg Adam , Diehl Joseph , Waterman Gabriel N. , Swift Regina A. , Crowley John , Berenson James R.
Published: February 2016

Immunosuppressed patients are known to have an increased incidence of skin cancer. Patients with multiple myeloma (MM) show impaired immune function. In the past, because of poor survival, the incidence of specific secondary primary malignancies such as skin cancer among these patients was difficult to establish. With more effective MM therapies that have emerged in recent years, these patients are living markedly longer, and therefore, it becomes of increasing importance to determine whether their risk of developing other medical problems such as skin cancer is increased. We performed a retrospective cohort study of 205 myeloma patients and 193 age‐, race‐, and gender‐matched control subjects to assess the incidence of skin cancers among patients with MM and determine the specific types of and risk factors for skin cancer. We found that there is an increased occurrence of skin cancer among patients with MM compared to control subjects (26.8% vs. 16.1% in controls; P = 0.009). Among specific types of skin cancer, the proportion of patients with squamous cell carcinoma (SCC) was higher than controls (P = 0.016). In addition to MM diagnosis, older age and Caucasian ethnicity were predictors of skin cancer of any type. Furthermore, older age was also a predictor of SCC.
A study of the prevalence of smear‐positive leprosy cases in a tertiary care center in the post‐elimination phase of leprosy
Authors: Pradeep Nair Sukumaran , Vidyadharan Suja
Published: February 2016

Background

India has declared leprosy to be eliminated in the country, according to the WHO criteria of attaining a prevalence of less than 1 in 10,000. However, smear‐positive leprosy cases are frequently being encountered.

Methods

This is an 18‐year retrospective study done in the Department of Dermatology and Venereology, Government Medical College, Trivandrum. Data were collected from the records of all cases in the study period, and the prevalence of smear‐positive cases was determined in the post‐elimination phase and this was compared to the pre‐elimination phase.

Results

A total of 901 cases were analyzed, which comprised 538 cases in the pre‐ and 363 cases in the post‐elimination phase. The male/female ratio in the pre and post phases was 2.61 : 1 and 2.45 : 1, respectively. Borderline tuberculoid accounted for the commonest type in both the pre and post phases comprising 45.54 and 50.69%, respectively. Type 2 lepra reactions were seen in 40.21% of the reaction cases in the post‐elimination phase. The smear‐positive cases in the post‐elimination phase accounted for 34.99% compared to 14.68% in the pre‐elimination phase. Lepromatous leprosy (LL) accounted for 67.71% of the smear‐positive cases in the post phase compared to 67.08% in the pre phase.

Conclusions

There was an increase of 20.30% of smear‐positive cases in the post‐elimination phase, which was statistically significant (P < 0.001), and the majority of them were LL (P < 0.001).
Ideal glycated hemoglobin cut‐off points for screening diabetes and prediabetes in a Chinese population
Authors: Liu Yujia , Xiao Xianchao , Sun Chenglin , Tian Suyan , Sun Zhonghua , Gao Ying , Li Yazhen , Cheng Jie , Lv You , Li Mei , Li Zhuo , Zhang Yumin , Wang Gang , Liu Yang , Gao Yuan , Zhu Liwen , Liu Yan , Wang Guixia
Published: February 2016

Aims/Introduction

The aims of the present study were to evaluate the diagnostic value of fasting plasma glucose, 2‐h postload plasma glucose and glycosylated hemoglobin (HbA1c) measurements in the screening of diabetes and prediabetes, and to determine the cut‐off point of HbA1c in the diagnosis of diabetes and prediabetes in a Chinese population.

Materials and Methods

A total of 7,611 individuals aged 40 years or older, who did not have a prior history of diabetes, were randomly selected in the Changchun area. For each participant, a questionnaire was completed, and a physical examination and an oral glucose tolerance test were carried out. The values of fasting plasma glucose, 2‐h postload plasma glucose and HbA1c were compared by area under the receiver operating characteristic curves. The Youden index was used to identify the optimal cut‐off point of HbA1c in the diagnosis of diabetes and prediabetes.

Results

The prevalence of newly diagnosed diabetes and prediabetes was 12.71% and 29.39%, respectively. In participants with newly diagnosed diabetes, the area under the receiver operating characteristic curve was 0.8368 for fasting plasma glucose, 0.9330 for 2‐h postload plasma glucose and 0.8064 for HbA1c; whereas for prediabetes, these values were 0.8022, 0.9288 and 0.6895, respectively. In addition, an HbA1c threshold of 6.3% showed the highest Youden index (0.4799) for detecting diabetes; furthermore, an HbA1c threshold of 5.8% showed the highest Youden index (0.2866) for detecting prediabetes.

Conclusions

HbA1c ≥6.3% (45 mmol/mol) and between 5.8% and 6.2% (40–44 mmol/mol) were the optimal cut‐off values for the diagnosis of diabetes and prediabetes, respectively, in a Chinese population.
Long‐term safety and efficacy of a novel once‐weekly oral trelagliptin as monotherapy or in combination with an existing oral antidiabetic drug in patients with type 2 diabetes mellitus: A 52‐week open‐label, phase 3 study
Authors: Inagaki Nobuya , Sano Hiroki , Seki Yoshifumi , Kuroda Shingo , Kaku Kohei
Published: February 2016

Aims/Introduction

Trelagliptin is a novel once‐weekly oral dipeptidyl peptidase‐4 inhibitor for type 2 diabetes mellitus that was first approved in Japan. We evaluated long‐term safety and efficacy of trelagliptin in Japanese patients with type 2 diabetes mellitus.

Materials and Methods

This was a phase 3, multicenter, open‐label study to evaluate long‐term safety and efficacy of trelagliptin. Patients with type 2 diabetes mellitus inadequately controlled despite diet/exercise or treatment with one of the existing oral antidiabetic drugs along with diet/exercise received trelagliptin 100 mg orally once weekly for 52 weeks as monotherapy or combination therapies. The primary end‐points were the safety variables, and the secondary end‐points were glycosylated hemoglobin and fasting plasma glucose.

Results

A total of 680 patients received the following antidiabetic therapies: trelagliptin monotherapy (n = 248), combination with a sulfonylurea (n = 158), a glinide (n = 67), an α‐glucosidase inhibitor (n = 65), a biguanide (n = 70), or a thiazolidinedione (n = 72). During the study, 79.8% of the patients experienced at least one adverse event for monotherapy, 87.3% for combination with a sulfonylurea, 77.6% for a glinide, 81.5% for an α‐glucosidase inhibitor, 64.3% for a biguanide, and 84.7% for a thiazolidinedione, respectively. Most of the adverse events were mild or moderate. The change in glycosylated hemoglobin from baseline at the end of the treatment period was −0.74 to −0.25% for each therapy.

Conclusions

Once‐weekly oral trelagliptin provides well‐tolerated long‐term safety and efficacy in both monotherapy and combination therapies in Japanese patients with type 2 diabetes mellitus.
The influence of space and time on the evolution of altruistic defence: the case of ant slave rebellion
Authors: Metzler D. , Jordan F. , Pamminger T. , Foitzik S.
Published: February 2016

How can antiparasite defence traits evolve even if they do not directly benefit their carriers? An example of such an indirect defence is rebellion of enslavedTemnothorax longispinosusant workers against their social parasiteTemnothorax americanus, a slavemaking ant. Ant slaves have been observed to kill their oppressors' offspring, a behaviour from which the sterile slaves cannot profit directly. Parasite brood killing could, however, reduce raiding pressure on related host colonies nearby. We analyse with extensive computer simulations for theTemnothoraxslavemaker system under what conditions a hypothetical rebel allele could invade a host population, and in particular, how host–parasite dynamics and population structure influence the rebel allele's success. Exploring a wide range of model parameters, we only found a small number of parameter combinations for which kin selection or multilevel selection could allow a slave rebellion allele to spread in the host population. Furthermore, we did not detect any cases in which the reduction of raiding pressure in the close vicinity of the slavemaker nest would substantially contribute to the inclusive fitness of rebels. This suggests that slave rebellion is not costly and perhaps a side‐effect of some other beneficial trait. In some of our simulations, however, even a costly rebellion allele could spread in the population. This was possible when host–parasite interactions led to a metapopulation dynamic with frequent local extinctions and recolonizations of demes by the offspring of few immigrants.
The potential forEntomophaga maimaigato regulate gypsy mothLymantria dispar(L.) (Lepidoptera: Erebidae) in Europe
Authors: Zúbrik M. , Hajek A. , Pilarska D. , Špilda I. , Georgiev G. , Hrašovec B. , Hirka A. , Goertz D. , Hoch G. , Barta M. , Saniga M. , Kunca A. , Nikolov C. , Vakula J. , Galko J. , Pilarski P. , Csóka G.
Published: February 2016

Gypsy moth,Lymantria disparL., is one of the most important pests of deciduous trees in Europe. In regular cycles, it causes large‐scale defoliation mostly of oak,Quercusspp., forests. Government authorities in the most infested countries in Europe conduct large‐scale applications of pesticides against gypsy moth. In 1999, a new natural enemy, the entomopathogenic fungusEntomophaga maimaiga, was successfully introduced into a gypsy moth population in Bulgaria. Recent investigations suggest that nowE. maimaigais quickly spreading in Europe. Herein, past studies are reviewed regarding this fungus with special emphasis on its potential for becoming an important factor regulating gypsy moth populations in Europe, focusing on the host's population dynamics in relation to the fungus, the influence of environmental conditions on fungal activity, the influence ofE. maimaigaon the native entomofauna, including other gypsy moth natural enemies, and spread of the fungus. Based on this analysis, the potential ofE. maimaigafor providing control in European gypsy moth populations is estimated.
Idiopathic non‐cirrhotic portal hypertension: the tip of the obliterative portal venopathies iceberg?
Authors: Elkrief Laure , Rautou Pierre‐Emmanuel
Published: February 2016

See Article on Page 454
Ni/S/Cl systematics and the origin of impact‐melt glasses in Martian meteorite Elephant Moraine 79001
Authors: Schrader Christian M. , Cohen Barbara A. , Donovan John J. , Vicenzi Edward P.
Published: February 2016

Martian meteorite Elephant Moraine A79001 (EET 79001) has received considerable attention for the unusual composition of its shock melt glass, particularly its enrichment in sulfur relative to the host shergottite. It has been hypothesized that Martian regolith was incorporated into the melt or, conversely, that the S‐enrichment stems from preferential melting of sulfide minerals in the host rock during shock. We present results from an electron microprobe study of EET 79001 including robust measurements of major and trace elements in the shock melt glass (S, Cl, Ni, Co, V, and Sc) and minerals in the host rock (Ni, Co, and V). We find that both S and major element abundances can be reconciled with previous hypotheses of regolith incorporation and/or excess sulfide melt. However, trace element characteristics of the shock melt glass, particularly Ni and Cl abundances relative to S, cannot be explained either by the incorporation of regolith or sulfide minerals. We therefore propose an alternative hypothesis whereby, prior to shock melting, portions of EET 79001 experienced acid‐sulfate leaching of the mesostasis, possibly groundmass feldspar, and olivine, producing Al‐sulfates that were later incorporated into the shock melt, which then quenched to glass. Such activity in the Martian near‐surface is supported by observations from the Mars Exploration Rovers and laboratory experiments. Our preimpact alteration model, accompanied by the preferential survival of olivine and excess melting of feldspar during impact, explains the measured trace element abundances better than either the regolith incorporation or excess sulfide melting hypothesis does.
A service evaluation comparing CVVH and CVVHDF in minimising circuit failure
Authors: Ede Jody , Dale Andrea
Published: February 2016

Background

A significant problem during continuous renal replacement therapy is premature circuit failure, affecting efficacy and molecular clearance. Techniques to improve circuit failure are anticoagulation, access site and modality. A modality change was introduced, moving from continuous veno‐venous haemofiltration to continuous veno‐venous haemodiafiltration as a result of existing issues with failing circuit times and failure rates.

Aim

The aim of this service evaluation was to ascertain if the use of continuous veno‐venous haemodiafiltration compared to continuous veno‐venous haemofiltration had affected failed circuit survival times and rates.

Methods

A service evaluation was chosen because the focus was to ascertain what effect a practice change had had on a particular service. The service evaluation was registered with the local trust's audit department and gained university ethical approval. It was anticipated that the data generated would be used to inform, question and improve practices. Patients who received renal replacement therapy (RRT) from May 2012 to January 2013 were retrospectively identified. Patients received continuous veno‐venous haemofiltration for the duration of their treatment before September 2012 and continuous veno‐venous haemodiafiltration after. A total of 78 patients were identified as receiving RRT; 41 of these patients had failed circuits.

Results

A total of 182 failed circuits were analysed. The median duration of failed circuits during continuous veno‐venous haemofiltration was shorter (2·75 h, standard deviation (SD) = 13·82) when compared to continuous veno‐venous haemodiafiltration (11 h, SD = 15·26, p < 0·001, 95% confidence interval (CI) 2·5–10). Circuit failure rate in continuous veno‐venous haemofiltration was 56% compared to 43% in continuous veno‐venous haemodiafiltration. After performing a Cox regression analysis, continuous veno‐venous haemofiltration appeared to have a 1·87 times (CI 1·18–2·82, p > 0·007) more likely chance of failure.

Conclusion

The use of continuous veno‐venous haemodiafiltration has had an overall positive effect on the haemofiltration service by reducing the number of failed circuits and increasing circuit survival times, which may have improved the efficacy of the service. Continuous veno‐venous haemodiafiltration may be a more appropriate modality of choice in non‐septic patients requiring prolonged continuous RRT episodes.
Expression of Arabidopsis Bax Inhibitor‐1 in transgenic sugarcane confers drought tolerance
Authors: Ramiro Daniel Alves , Melotto‐Passarin Danila Montewka , Barbosa Mariana de Almeida , Santos Flavio dos , Gomez Sergio Gregorio Perez , Massola Júnior Nelson Sidnei , Lam Eric , Carrer Helaine
Published: February 2016

The sustainability of global crop production is critically dependent on improving tolerance of crop plants to various types of environmental stress. Thus, identification of genes that confer stress tolerance in crops has become a top priority especially in view of expected changes in global climatic patterns. Drought stress is one of the abiotic stresses that can result in dramatic loss of crop productivity. In this work, we show that transgenic expression of a highly conserved cell death suppressor, Bax Inhibitor‐1 from Arabidopsis thaliana (AtBI‐1), can confer increased tolerance of sugarcane plants to long‐term (>20 days) water stress conditions. This robust trait is correlated with an increased tolerance of the transgenic sugarcane plants, especially in the roots, to induction of endoplasmic reticulum (ER) stress by the protein glycosylation inhibitor tunicamycin. Our findings suggest that suppression of ER stress in C4 grasses, which include important crops such as sorghum and maize, can be an effective means of conferring improved tolerance to long‐term water deficit. This result could potentially lead to improved resilience and yield of major crops in the world.
Biomanufacturing of protective antibodies and other therapeutics in edible plant tissues for oral applications
Authors: Juarez Paloma , Virdi Vikram , Depicker Ann , Orzaez Diego
Published: February 2016

Although plant expression systems used for production of therapeutic proteins have the advantage of being scalable at a low price, the downstream processing necessary to obtain pure therapeutic molecules is as expensive as for the traditional Chinese hamster ovary (CHO) platforms. However, when edible plant tissues (EPTs) are used, there is no need for exhaustive purification, because they can be delivered orally as partially purified formulations that are safe for consumption. This economic benefit is especially interesting when high doses of recombinant proteins are required throughout the treatment/prophylaxis period, as is the case for antibodies used for oral passive immunization (OPI). The secretory IgA (SIgA) antibodies, which are highly abundant in the digestive tract and mucosal secretions, and thus the first choice for OPI, have only been successfully produced in plant expression systems. Here, we cover most of the up‐to‐date examples of EPT‐produced pharmaceuticals, including two examples of SIgA aimed at oral delivery. We describe the benefits and drawbacks of delivering partially purified formulations and discuss a number of practical considerations and criteria to take into account when using plant expression systems, such as subcellular targeting, protein degradation, glycosylation patterns and downstream strategies, all crucial for improved yield, high quality and low cost of the final product.
Unexplained subfertility: diagnosis and management
Authors: Nandi Anupa , Homburg Roy
Published: February 2016

Key content

Unexplained subfertility is diagnosed when standard investigations (tests for ovulation, tubal patency and semen analysis) are all normal. Between 30% and 40% of subfertile couples fall into this category.

In some couples, unexplained subfertility may result from subtle undetectable factors; in other couples, it may be associated with a genuine absence of any abnormality.

There is currently much controversy about the selection of appropriate management options for such couples, especially following the National Institute for Health and Care Excellence (NICE) guideline published in 2013. Therefore, a clear understanding of the available evidence is essential for the management of couples with unexplained subfertility.

The potential contributing factors, diagnosis and management of unexplained subfertility are discussed.

Learning objectives

To summarise the available recent evidence and help the reader obtain a clear understanding of the continuing debates in this field.

To help clinicians in counselling couples with unexplained subfertility.

Ethical issues

Should couples be advised to try to conceive naturally for 2 years (regardless of their age) before they are offered treatment, even though fecundity declines with age?

What does the evidence suggest should be the first line of management for couples with unexplained subfertility: intrauterine insemination or in vitro fertilisation?
Sarcocystid organisms found in bile from a dog with acute hepatitis: a case report and review of intestinal and hepatobiliary Sarcocystidae infections in dogs and cats
Authors: Irvine Katherine L. , Walker Julie M. , Friedrichs Kristen R.
Published: February 2016

Sarcocystidae is a family of coccidian protozoa from the phylum Apicomplexa that includesToxoplasma,Neospora,Sarcocystis,Hammondia, andBesnoitiaspp. All species undergo a 2‐host sexual and asexual cycle. In the definitive host, replication is enteroepithelial, and infection is typically asymptomatic or less commonly causes mild diarrhea. Clinical disease is most frequently observed in the intermediate host, often as an aberrant infection, and is mostly associated with neurologic, muscular, or hepatic inflammation. Here, we review the literature regarding intestinal Sarcocystidae infections in dogs and cats, with emphasis on the life cycle stages and the available diagnostic assays and their limitations. We also report the diagnostic findings for an 11‐year‐old dog with acute neutrophilic hepatitis, biliary protozoa, and negative biliary culture. AlthoughToxoplasmaandNeosporaIgG titers were both high,PCRfor these 2 organisms was negative for bile. The organisms were identified by 18SrDNA PCRas most consistent withHammondia, eitherH heydorniorH triffittae. This is the first report of presumedHammondiaorganisms being found in canine bile.
Extracellular vesicles in cardiovascular disease: are they Jedi or Sith?
Authors: Osteikoetxea Xabier , Németh Andrea , Sódar Barbara W , Vukman Krisztina V , Buzás Edit Irén
Published: February 2016

In the recent past, extracellular vesicles have become recognized as important players in cell biology and biomedicine. Extracellular vesicles, including exosomes, microvesicles and apoptotic bodies, are phospholipid bilayer‐enclosed structures found to be secreted by most if not all cells. Extracellular vesicle secretion represents a universal and highly conserved active cellular function. Importantly, increasing evidence supports that extracellular vesicles may serve as biomarkers and therapeutic targets or tools in human diseases. Cardiovascular disease undoubtedly represents one of the most intensely studied and rapidly growing areas of the extracellular vesicle field. However, in different studies related to cardiovascular disease, extracellular vesicles have been shown to exert diverse and sometimes discordant biological effects. Therefore, it might seem a puzzle whether these vesicles are in fact beneficial or detrimental to cardiovascular health. In this review we provide a general introduction to extracellular vesicles and an overview of their biological roles in cardiovascular diseases. Furthermore, we aim to untangle the various reasons for the observed discrepancy in biological effects of extracellular vesicles in cardiovascular diseases. To this end, we provide several examples that demonstrate that the observed functional diversity is in fact due to inherent differences among various types of extracellular vesicles.

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An Enhanced Primary Reference Fuel Mechanism Considering Conventional Fuel Chemistry in Engine Simulation
Authors: Zhou Dezhi , Yang Wenming , An Hui , Li Jing , Kraft Markus
Published: February 2016

A compact and accurate primary reference fuel (PRF) mechanism which consists of 46 species and 144 reactions was developed and validated to consider the fuel chemistry in combustion simulation based on a homogeneous charged compression ignition (HCCI) mechanism. Some significant reactions were updated to ensure its capabilities for predicting combustion characteristics of PRFs. To better predict the laminar flame speed, the relevant C2–C3 carbon reactions were coupled in. This enhanced PRF mechanism was validated by available experimental data references including ignition delay times, laminar flame speed, premixed flame species concentrations in jet stirred reactor (JSR), rapid compression machine (RCM), and shock tube. The predicted data was calculated by chemkin-ii codes. All the comparisons between experimental and calculated data indicated high accuracy of this mechanism to capture combustion characteristics. Also, this mechanism was integrated into kiva4–chemkin. The engine simulation data (including in-cylinder pressure and apparent heat release rate (HRR)) was compared with experimental data in PRF HCCI, partially premixed compression ignition (PCCI), and diesel/gasoline dual-fuel engine combustion data. The comparison results implied that this mechanism could predict PRF and gasoline/diesel combustion in computational fluid dynamic (CFD) engine simulations. The overall results show this PRF mechanism could predict the conventional fuel combustion characteristics in engine simulation.
Propagation of In-Plane Shear Waves in Magnetically Affected Highly Conductive Nanofilms by Considering Both Surface and Nonlocality Effects
Authors: Kiani Keivan
Published: February 2016

To study the size and surface effects on characteristics of in-plane shear waves in magnetically affected nanofilms, a novel model is developed. Using nonlocal and surface continuum theories, the governing equations are established and appropriate boundary conditions are imposed at the bottom and top surfaces of the nanofilm. The dispersion relations associated with symmetric and asymmetric modes are obtained. The effects of the surface energy, small-scale parameter, nanofilm's thickness, and magnetic field strength on dispersion curves are addressed. The limitations of the classical theory of elasticity are discussed. The obtained results show that the phase velocity of the propagated in-plane shear waves magnifies by an increase of the thickness as well as magnetic field strength. However, the phase velocity commonly decreases as the effect of the surface energy or nonlocality increases. Such a fact is more obvious for higher modes of vibration. Generally, the cutoff frequency reaches a lower value as the nanofilm's thickness reduces or the small-scale parameter increases. Additionally, variation of the magnetic field strength has fairly no influence on the cutoff frequency.
A Flexoelectric Double-Curvature Nonlinear Shell Energy Harvester
Authors: Tzou H. S. , Zhang X. F.
Published: February 2016

Flexoelectricity possesses two gradient-dependent electromechanical coupling effects: the direct flexoelectric effect and the converse flexoelectric effect. The former can be used for sensing and energy generation; the latter can be used for ultraprecision actuation and control applications. Due to the direct flexoelectricity and large deformations, theoretical fundamentals of a generic nonlinear distributed flexoelectric double-curvature shell energy harvester are proposed and evaluated in this study. The generic flexoelectric shell energy harvester is made of an elastic double-curvature shell laminated with flexoelectric patches and the shell experiences large oscillations, such that the von Karman geometric nonlinearity occurs. Flexoelectric output voltages and energies across a resistive load are evaluated using the current model in the closed-circuit condition when the shell is subjected to harmonic excitations and its steady-state voltage and power outputs are also calculated. The generic flexoelectric shell energy harvesting theory can be simplified to shell (e.g., cylindrical, conical, spherical, paraboloidal, etc.) and nonshell (beam, plate, ring, arch, etc.) distributed harvesters and the simplification procedures are demonstrated in three cases, i.e., a cylindrical shell, a circular ring and a beam harvester. Other shell and nonshell flexoelectric energy harvesters with standard geometries can also be defined using their distinct two Lamé parameters and two curvature radii.
Time-Dependent Reliability Analysis of Vibratory Systems With Random Parameters
Authors: Mourelatos Zissimos P. , Majcher Monica , Geroulas Vasileios
Published: February 2016

The field of random vibrations of large-scale systems with millions of degrees-of-freedom (DOF) is of significant importance in many engineering disciplines. In this paper, we propose a method to calculate the time-dependent reliability of linear vibratory systems with random parameters excited by nonstationary Gaussian processes. The approach combines principles of random vibrations, the total probability theorem, and recent advances in time-dependent reliability using an integral equation involving the upcrossing and joint upcrossing rates. A space-filling design, such as optimal symmetric Latin hypercube (OSLH) sampling, is first used to sample the input parameter space. For each design point, the corresponding conditional time-dependent probability of failure is calculated efficiently using random vibrations principles to obtain the statistics of the output process and an efficient numerical estimation of the upcrossing and joint upcrossing rates. A time-dependent metamodel is then created between the input parameters and the output conditional probabilities allowing us to estimate the conditional probabilities for any set of input parameters. The total probability theorem is finally applied to calculate the time-dependent probability of failure. The proposed method is demonstrated using a vibratory beam example.
Darwinian sex roles confirmed across the animal kingdom
Authors: Janicke Tim , Häderer Ines K. , Lajeunesse Marc J. , Anthes Nils
Published: February 2016

Consistent with Darwin’s ideas, this meta-analysis reveals that males experience stronger sexual selection than females.
A new phase diagram of water under negative pressure: The rise of the lowest-density clathrate s-III
Authors: Huang Yingying , Zhu Chongqin , Wang Lu , Cao Xiaoxiao , Su Yan , Jiang Xue , Meng Sheng , Zhao Jijun , Zeng Xiao Cheng
Published: February 2016

Researchers predict a new ice clathrate structure as the most stable ice polymorph with the lowest density in a negative-pressure region.
Ion transport in complex layered graphene-based membranes with tuneable interlayer spacing
Authors: Cheng Chi , Jiang Gengping , Garvey Christopher J. , Wang Yuanyuan , Simon George P. , Liu Jefferson Z. , Li Dan
Published: February 2016

A combination of experiments and simulations unveils unusual nanoconfined ion transport in layered graphene membranes.
The Histone-Like Nucleoid Structuring Protein (H-NS) Is a Negative Regulator of the Lateral Flagellar System in the Deep-Sea Bacterium Shewanella piezotolerans WP3
Authors: Jian Huahua , Xu Guanpeng , Gai Yingbao , Xu Jun , Xiao Xiang
Published: February 2016

Although the histone-like nucleoid structuring protein (H-NS) is well known for its involvement in the adaptation of mesophilic bacteria, such as
Escherichia coli
, to cold environments and high-pressure stress, an understanding of the role of H-NS in the cold-adapted benthic microorganisms that live in the deep-sea ecosystem, which covers approximately 60% of the earth's surface, is still lacking. In this study, we characterized the function of H-NS in
Shewanella piezotolerans
WP3, which was isolated from West Pacific sediment at a depth of 1,914 m. An
hns
gene deletion mutant (WP3Δ
hns
) was constructed, and comparative whole-genome microarray analysis was performed. H-NS had a significant influence (fold change, >2) on the expression of a variety of WP3 genes (274 and 280 genes were upregulated and downregulated, respectively), particularly genes related to energy production and conversion. Notably, WP3Δ
hns
exhibited higher expression levels of lateral flagellar genes than WP3 and showed enhanced swarming motility and lateral flagellar production compared to those of WP3. The DNA gel mobility shift experiment showed that H-NS bound specifically to the promoter of lateral flagellar genes. Moreover, the high-affinity binding sequences of H-NS were identified by DNase I protection footprinting, and the results support the “binding and spreading” model for H-NS functioning. To our knowledge, this is the first attempt to characterize the function of the universal regulator H-NS in a deep-sea bacterium. Our data revealed that H-NS has a novel function as a repressor of the expression of genes related to the energy-consuming secondary flagellar system and to swarming motility.