bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimisation of the combined treatments of aqueous chlorine dioxide, fumaric acid and ultraviolet‐C for improving the microbial quality and maintaining sensory quality of common buckwheat sprout
Authors: Chun Ho Hyun , Song Kyung Bin
Published: July 2013

The effects of the combined treatments with aqueous chlorine dioxide (ClO2), fumaric acid and ultraviolet‐C (UV‐C) on the microbial quality of common buckwheat sprouts were examined using a response surface methodology. The populations of total aerobic bacteria, yeast and mould, and coliform decreased with increasing aqueous ClO2 and fumaric acid concentrations and increasing UV‐C irradiation dose. However, the increase in the UV‐C irradiation dose had a negative effect on the sensory quality. Therefore, the optimal combined treatment condition of 100 ppm aqueous ClO2, 0.31% fumaric acid and 1.9 kJ m−2 UV‐C was selected for the buckwheat sprouts by providing reductions of 3.9, 1.8 and 2.4 log CFU g−1 on the populations of total aerobic bacteria, yeast and mould, and coliform, respectively. The combined treatment also maintained an acceptable sensory quality. These results suggest that the optimised combined treatment can be used as a microbial inactivation method for buckwheat sprouts.
Antioxidant activities and functional properties of soy protein isolate hydrolysates obtained using microbial proteases
Authors: de Castro Ruann J. S. , Sato Hélia H.
Published: July 2013

Soy protein isolate (SPI) hydrolysates were prepared using microbial proteases to produce peptides with antioxidant activity. The process parameters (substrate and enzyme concentrations), hydrolysis time, functional properties and the effects of ultrafiltration were further investigated. The results showed that the soy protein isolate exhibited a 7.0‐fold increase in antioxidant activity after hydrolysis. The hydrolysis parameters, defined by the experimental design, were a substrate concentration of 90 mg mL−1 and the addition of 70.0 U of protease per mL of reaction. The maximum antioxidant activities were observed between 120 and 180 min of hydrolysis, where the degree of hydrolysis was approximately 20.0%. The hydrolysis increased solubility of the soy protein isolate; however, the hydrolysates exhibited a tendency to decrease in the interfacial activities and the heat stability. The SPI hydrolysates fractions obtained by ultrafiltration showed that the enzymatic hydrolysis resulted in samples with homogenous size and strong antioxidant activity.
Progress in the Western lowland gorilla Gorilla gorilla gorilla European Endangered Species Programme: a review of the decade 2002–2011
Authors: Vermeer J. , Abelló M. T. , Holtkötter M.
Published: July 2013

In the past decade, some major improvements have been achieved in the management of the European Endangered Species Programme (EEP) for the Western lowland gorilla Gorilla gorilla gorilla. To assess the achievements of the current management approach, data on 225 births, 96 deaths and 154 transfers were collected from the most recent international studbook and analysed. Compared with the preceding decade, neonatal mortality and hand‐rearing rates have decreased, resulting in a lower but acceptable birth rate. Transfers in most cases proved to be successful: almost all gorillas were integrated into their new groups and most animals introduced to a breeding group had their first offspring within 2 years. The results show that the current management approach is successful, and that the population is sustainable and has good genetic health. Several aspects of gorilla management are presented and discussed. One of the major challenges for both the Gorilla EEP Species Committee (GEEPC) and the holders is to find a solution for the increasing problem of ♂♂ not needed for the breeding programme at any given time.
Dynamics of predator and modular prey: effects of module consumption on stability of prey–predator system
Authors: Yamauchi Atsushi , Namba Toshiyuki
Published: July 2013

In traditional models of predator–prey population dynamics, it is usually assumed that consumed prey are immediately removed from the population. However, in plant–herbivore interactions, damaged plants are generally alive after attacks by herbivores. This can result in successive or simultaneous attacks by multiple predators on a single prey item (here, the term prey is expanded to include plants). We constructed a mathematical model with two time scales, taking into account predation processes within a generation, considering post‐predation survival and the modularity of prey. We assumed that a prey item can be divided into modules and that it can be fed on by multiple predators or parasitized by multiple parasites at the same time. The model includes two essential factors: the modularity of prey for predators (n) and the detaching/attaching ratio of predators to prey (ε). Based on the formulae, we revealed a general property of realistic dynamics in plant–herbivore and host–parasite interactions. The analysis showed that the model could be approximated by models with the type I, type II or Beddington–DeAngelis functional responses by taking appropriate limits to the situations. When modularity is low or the detaching/attaching ratio is high, population dynamics tend to be stabilized. These stabilizing effects may be related to interference competition among predator individuals or increases in free prey modules and free predator individuals. In the limit of high modularity, the ratio of the attached prey modules to the total prey modules becomes negligible and the dynamics tend to be destabilized. However, if quantity and quality of prey modules are negatively correlated, the equilibrium is likely to be stabilized at high modularity as long as it remains feasible. These results suggest that considering post‐predation survival and modularity of prey is crucial to understand predator–prey interactions.
Impact of pay‐for‐performance on management of diabetes: a systematic review
Authors: Huang Jin , Yin Senlin , Lin Yifei , Jiang Qian , He Yazhou , Du Liang
Published: July 2013

Objectives

To review and synthesize published evidence of pay‐for‐performance (P4P) effects on management of diabetes.

Methods

Databases including Ovid MEDLINE, EMbase, PubMed, The Cochrane Library (Issue 3, 2012) were comprehensively searched for the effects of P4P programs in terms of patient outcomes and physician behaviors. Studies covering detailed data were included and synthesized. The quality of the body of evidence for each quality indicator was determined using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system.

Results

Among 742 identified articles, 12 interrupted time series studies, 7 controlled before‐after studies, and 2 cross‐sectional studies were included. Additionally, 12 studies were further included for quantitative analysis. Results of meta‐analysis showed that P4P produced generally positive effects in most indicators (eg, patients with records of total cholesterol or blood pressure). However, these results were inconsistent. The percentage of patients with HbA1c ≤ 7% or 53 mmol/mol showed a pooled odds ratio of 0.98 in patients, but a pooled mean difference of 19.71% in the physician groups. The odds ratios of receiving tests/reaching an outcome level were also diverse in patients (odds ratios ranged from 0.98 to 3.32). Besides, process indicators had higher rates of improvement than outcome indicators.

Conclusions

P4P programs have variable impacts on patient outcomes of diabetes as well as physician behaviors, with various effects from negligible to strongly beneficial. Considering the low quality of the included studies, this conclusion should be cautiously interpreted.
An Exploration of Family Therapists' Beliefs about the Ethics of Conversion Therapy: The Influence of Negative Beliefs and Clinical Competence With Lesbian, Gay, and Bisexual Clients
Authors: McGeorge Christi R. , Carlson Thomas Stone , Toomey Russell B.
Published: July 2013

The majority of the literature on conversion therapy has focused on clients' experiences and rationales for seeking such therapy. This study sought to explore differences in the beliefs and clinical competence of therapists who practice and believe in the ethics of conversion therapy and those who do not. The sample for this study included 762 family therapists who were members of the American Association of Marriage and Family Therapy. Data were collected using electronic surveys that assessed participants' negative beliefs about and perceived clinical competence with lesbian, gay, and bisexual (LGB) individuals. Results indicate that those who believe in the ethics of and/or practice conversion therapy report statistically higher levels of negative beliefs about LGB individuals and lower levels of clinical competence working with LGB clients. Implications for clinical practice and organizational policy are discussed.
Amyloid beta1–42 (Aβ42) up‐regulates the expression of sortilin via the p75NTR/RhoA signaling pathway
Authors: Saadipour Khalil , Yang Miao , Lim Yoon , Georgiou Kristen , Sun Ying , Keating Damien , Liu Jia , Wang Ye‐Ran , Gai Wei‐ping , Zhong Jin‐hua , Wang Yan‐Jiang , Zhou Xin‐Fu
Published: July 2013

Sortilin, a Golgi sorting protein and a member of the VPS10P family, is the co‐receptor for proneurotrophins, regulates protein trafficking, targets proteins to lysosomes, and regulates low density lipoprotein metabolism. The aim of this study was to investigate the expression and regulation of sortilin in Alzheimer's disease (AD). A significantly increased level of sortilin was found in human AD brain and in the brains of 6‐month‐old swedish‐amyloid precursor protein/PS1dE9 transgenic mice. Aβ42 enhanced the protein and mRNA expression levels of sortilin in a dose‐ and time‐dependent manner in SH‐SY5Y cells, but had no effect on sorLA. In addition, proBDNF also significantly increased the protein and mRNA expression of sortilin in these cells. The recombinant extracellular domain of p75NTR (P75ECD‐FC), or the antibody against the extracellular domain of p75NTR, blocked the up‐regulation of sortilin induced by Amyloid‐β protein (Aβ), suggesting that Aβ42 increased the expression level of sortilin and mRNA in SH‐SY5Y via the p75NTR receptor. Inhibition of ROCK, but not Jun N‐terminal kinase, suppressed constitutive and Aβ42‐induced expression of sortilin. In conclusion, this study shows that sortilin expression is increased in the AD brain in human and mice and that Aβ42 oligomer increases sortilin gene and protein expression through p75NTR and RhoA signaling pathways, suggesting a potential physiological interaction of Aβ42 and sortilin in Alzheimer's disease.

image

Sortilin is the co‐receptor of p75NTR which signals the cell death induced by Aβ and proneurotrophins. We found that sortilin is increased in the AD brain and up‐regulated by Aβ and pro‐brain‐derived neurotrophic factor (proBDNF). Aβ‐induced upregulation of sortilin is mediated by p75NTR and the down‐streaming RhoA‐ROCK signaling pathway. The Aβ/Sortilinp/75NTR signaling may play a role in the pathogenesis of AD.
Effects of Gonadal Hormones on Cognitive Behaviour in Elderly Men and Women
Authors: Hogervorst E.
Published: July 2013

Over the last four decades, animal and cell culture studies have shown that sex steroids can have protective effects on the ageing brain. Limited short‐term positive effects (2–4 months) of oestrogen treatment were found in women without (as well as with) dementia. By contrast to these initial promising findings, several large treatment studies showed that longer‐term oestrogen treatment, particularly when given in combination with progesterone, could exert negative effects on cognitive function in women aged over 65 years. Several observational studies of older women and men also suggest that longer exposure to higher endogenous oestrogen levels at an older age might confer risk for accelerated cognitive decline and dementia. However, health of participants may modify this association and, in women closer to the age at the onset of menopause, positive associations of oestrogens with cognition were also found. The ‘healthy cell bias’ theory suggests that oestrogens have protective effects in healthy neurones, although cells undergoing pathological change show acceleration in their demise when exposed to oestrogens. In older men, most studies reported higher bioavailable testosterone levels to be associated with better cognitive function. Other studies have reported optimal testosterone levels for better global cognitive function and a reduced risk of cognitive decline. Variation in health status over time and the use of (in)sensitive cognitive tests and hormone assays may explain why this was not always found. In older women, this association (of testosterone with cognition) is less clear. Small studies reported some benefits of testosterone treatment in combination with oestrogen on cognition, although these were of short duration. Several observational studies, on the other hand, found negative associations between high testosterone levels and worse cognitive function in older women. Age, health status, duration of treatment and sex may thus modify effects of longer‐term elevated sex steroid levels on brain function.
Endocannabinoid Receptor Deficiency Affects Maternal Care and Alters the Dam's Hippocampal Oxytocin Receptor and Brain‐Derived Neurotrophic Factor Expression
Authors: Schechter M. , Weller A. , Pittel Z. , Gross M. , Zimmer A. , Pinhasov A.
Published: July 2013

Maternal care is the newborn's first experience of social interaction, and this influences infant survival, development and social competences throughout life. We recently found that postpartum blocking of the endocannabinoid receptor‐1 (CB1R) altered maternal behaviour. In the present study, maternal care was assessed by the time taken to retrieve pups, pups' ultrasonic vocalisations (USVs) and pup body weight, comparing CB1R deleted (CB1R KO) versus wild‐type (WT) mice. After culling on postpartum day 8, hippocampal expression of oxytocin receptor (OXTR), brain‐derived neurotrophic factor (BDNF) and stress‐mediating factors were evaluated in CB1R KO and WT dams. Comparisons were also performed with nulliparous (NP) CB1R KO and WT mice. Compared to WT, CB1R KO dams were slower to retrieve their pups. Although the body weight of the KO pups did not differ from the weight of WT pups, they emitted fewer USVs. This impairment of the dam–pup relationship correlated with a significant reduction of OXTR mRNA and protein levels among CB1R KO dams compared to WT dams. Furthermore, WT dams exhibited elevated OXTR mRNA expression, as well as increased levels of mineralocorticoid and glucocorticoid receptors, compared to WT NP mice. By contrast, CB1R KO dams showed no such elevation of OXTR expression, alongside lower BDNF and mineralocorticoid receptors, as well as elevated corticotrophin‐releasing hormone mRNA levels, when compared to CB1R KO NP. Thus, it appears that the disruption of endocannabinoid signalling by CB1R deletion alters expression of the OXTR, apparently leading to deleterious effects upon maternal behaviour.
Analysis of stress on mucosa and basal bone underlying complete dentures with different reliner material thicknesses: a three‐dimensional finite element study
Authors: Lima J. B. G. , Orsi I. A. , Borie E. , Lima J. H. F. , Noritomi P. Y.
Published: July 2013

The aim of this study was to determine the optimal thickness of reliner material that provides the least amount of stress on thin mucosa and supporting bone in patients with complete removable dentures using a three‐dimensional finite element analyses. The model was obtained from two CT scans of edentulous mandibles with dentures supported by the alveolar ridge. After virtual reconstruction, the three‐dimensional models were exported to the solidworks cad software and divided into six groups based on the thickness of the reliner material as follows: (i) without material, (ii) 0·5 mm, (iii) 1 mm, (iv) 1·5 mm, (v) 2 mm and (vi) 2·5 mm. The applied load was 60 N and perpendicular to the long axis of the alveolar ridge of all the prosthetic teeth, and the mucosal thickness used was 1 mm. The analyses were based on the maximum principal stress in the fibromucosa and the minimum principal stress in the basal bone. Stress concentration was observed in the anterior zone of the mandible in the mucosa and in the bone. The maximum and minimum principal stress in the mucosa and bone, respectively, decreased, whereas the thickness of the reliner material increased until 2 mm, which transmitted the lowest stress, compared with the control. Reliner materials with a thickness of 2·5 mm showed higher stress values than those with a thickness of 2 mm. In conclusion, reliner material with a thickness of 2 mm transmitted the lowest amount of stress to the mucosa and bone in 1 mm of mucosa thickness.
Impact of caffeic acid on aluminium chloride-induced dementia in rats
Authors: Khan Kafeel A , Kumar Nitesh , Nayak Pawan G , Nampoothiri Madhavan , Shenoy Rekha R , Krishnadas Nandakumar , Rao C Mallikarjuna , Mudgal Jayesh
Published: July 2013

Objective

Literature favours the in vitro neuroprotective role of caffeic acid, a naturally derived polyphenolic compound. This study was aimed to investigate the role of caffeic acid in experimental model of Alzheimer's disease.

Methods

Firstly, caffeic acid was tested for in vitro anticholinesterase potential using rat brain homogenate. Later, in vivo antidementia activity of caffeic acid was assessed against aluminium chloride (AlCl3)-induced dementia in rats. Behavioural (Morris water maze test) and brain biochemical parameters (acetylcholinesterase (AChE), catalase, glutathione-S-transferase (GST) activity, glutathione (GSH) and nitrite levels) were assessed to correlate the cognitive function with cholinergic transmission and oxidative stress.

Key findings

Rats administered with caffeic acid showed improved cognitive function in Morris water maze test. The antidementia activity of caffeic acid was confirmed by the reduction in brain AChE activity and nitrite levels. Further, caffeic acid corrected the diminished level of antioxidant enzymes such as catalase, GSH and GST in brain.

Conclusion

These findings suggest the antidementia activity of caffeic acid against AlCl3-induced dementia in rats. The outcome of present study offers a wider scope to screen caffeic acid against neurodegeneration associated disorders.
Perceptions of pediatric asthma in African American underserved families using metaphorical analysis
Authors: McClelland Molly , Wenz Cathy , Sood Kush , Yono Anita
Published: July 2013

Purpose

The purpose was to understand how African American children with asthma and their families living in underserved urban areas experience and perceive asthma.

Design and Methods

A narrative inquiry design with metaphorical analysis was used in this study with 20 African American children and their 10 families.

Results

Participants metaphorically viewed the family system as a functioning healthcare facility. Children didn't find their asthma abnormal but did use asthma symptoms to their advantage. Caregivers were viewed as first‐line medical responders but often made errors in delivering medical treatment. Lack of knowledge relating to appropriate asthma interventions led to insufficient asthma care.

Practice Implications

Results provide evidence to improve patient–nurse interactions for this vulnerable patient group.
Controlled attenuation parameter (CAP) for detection of hepatic steatosis in patients with chronic liver diseases: a prospective study of a native Korean population
Authors: Chon Young Eun , Jung Kyu Sik , Kim Seung Up , Park Jun Yong , Park Young Nyun , Kim Do Young , Ahn Sang Hoon , Chon Chae Yoon , Lee Hye Won , Park Yehyun , Han Kwang‐Hyub
Published: July 2013

Background

Controlled attenuation parameter (CAP) is a non‐invasive method of measuring hepatic steatosis using a process based on transient elastography. We investigated the diagnostic accuracy of CAP in detecting hepatic steatosis in patients with chronic liver disease (CLD).

Methods

A total of 135 patients with CLD who underwent liver biopsy and CAP were consecutively enrolled in this prospective study. The performance of CAP for detection of hepatic steatosis compared with liver biopsy was calculated using area under receiver operating characteristics curves (AUROC). Steatosis was categorized into S0 (<5%), S1 (5–33%), S2 (34–66%) and S3 (>66% of hepatocytes).

Results

Male gender predominated (n = 87, 64%) and the median age was 51 years. The aetiologies of CLD included non‐alcoholic fatty liver disease (n = 56, 41.5%) and chronic viral hepatitis because of hepatitis B (n = 47, 34.8%) and C (n = 12, 8.9%). Steatosis repartition was: S0 31.1% (n = 42), S1 43.7% (n = 59), S2 18.5% (n = 25) and S3 6.7% (n = 9) respectively. In the multivariate analysis, steatosis grade and body mass index were independently associated with CAP (all P < 0.001), whereas fibrosis stage and activity grade were not. The AUROCs of CAP were 0.885 for ≥S1 (sensitivity 73.1%, specificity 95.2%), 0.894 for ≥S2 (sensitivity 82.4%, specificity 86.1%) and 0.800 for S3 (sensitivity 77.8%, specificity 84.1%). The optimal cut‐off CAP values that maximized the Youden index were 250 dB/m (≥S1), 299 dB/m (≥S2), and 327 dB/m (=S3) respectively.

Conclusions

Our data showed that CAP had high diagnostic accuracy for detecting hepatic steatosis in patients with CLD and suggested that CAP is also applicable for Asian patients.
Improving immunotherapy of hepatocellular carcinoma (HCC) using dendritic cells (DC) engineered to express IL‐12 in vivo
Authors: Vogt Annabelle , Sievers Elisabeth , Lukacs‐Kornek Veronika , Decker Georges , Raskopf Esther , Meumann Nadja , Büning Hildegard , Sauerbruch Tilman , Strassburg Christian P. , Schmidt‐Wolf Ingo G. H. , Gonzalez‐Carmona Maria A.
Published: July 2013

Background

Interleukin 12 (IL‐12), one of the most potent Th1‐cytokines, has been used to improve dendritic cells (DC)‐based immunotherapy of cancer. However, it failed to achieve clinical response in patients with hepatocellular carcinoma (HCC). In this study, improved conditions of immunotherapy with DC engineered to express IL‐12 were studied in murine subcutaneous HCC.

Methods

Tumour‐lysate pulsed DC were transduced with IL‐12‐encoding adenoviruses or cultivated with recombinant (r)IL‐12. DC were injected intratumourally, subcutaneously or intravenously at different stages of tumour‐development.

Results

Dendritic cell overexpressing IL‐12 by adenoviruses showed enhanced expression of costimulatory molecules and stronger priming of HCC‐specific effector cells than DC cultured with rIL‐12. Intratumoural but not systemic injections of IL‐12‐DC induced the strongest antitumoural effects reaching complete regressions in 75% of early‐staged tumours and in 33% of advanced tumours. Importantly, antitumoural effects could be further enhanced through combination with sorafenib. Analysing the tumour‐environment, IL‐12‐DC increased the levels of Th1‐cytokines/chemokines and of CD4+‐, CD8+‐T‐ and NK‐cells. Induced immunity was tumour‐specific and sustained since all tumour‐free animals were protected towards hepatic tumour‐cell rechallenge. However, IL‐12‐DC also enhanced immunosuppressive cytokines, regulatory T cells and even myeloid‐derived suppressor cells within the tumours.

Conclusions

Induced IL‐12‐overexpression by adenoviral vectors can effectively immunostimulate DC. Intratumoural but not systemic injection of activated IL‐12‐DC was crucial for effective tumour regression. The mechanism of this approach seems to be the induction of a sufficient Th1 tumour‐environment allowing the recruitment of effector cells rather than the inhibition of tumour immunosuppression. Thus, improved immunotherapy with IL‐12‐DC represents a promising approach towards HCC.
Incidence of Early Postpartum Voiding Dysfunction in Primiparae: Comparison Between Vaginal Delivery and Cesarean Section
Authors: AL‐MANDEEL Hazem , AL‐BADR Ahmed , AL‐SHAIKH Ghadeer
Published: July 2013

Objectives

To compare the incidence of early postpartum voiding dysfunction (PPVD) in primiparae women delivered vaginally (VD) to those delivered by elective Caesarean section (CS).

Methods

A prospective study of primiparae in early postpartum period, were grouped into: VD group and CS group. Following the first 24 h from delivery, patients had uroflowmetry and post‐void residual urine (PVR) volume measurement.

Results

Two hundred and fifty six primiparae women recruited; 204 (81%) had VD and 48 (19%) had primary elective CS. Forty‐two women in the VD group (20.2%) diagnosed with PPVD compared to only four (8.3%) in the CS group (P = 0.05). Within VD group, women who had vaginal tear (86.4% vs. 44%, P < 0.001) or epidural analgesia (33.3% vs. 18.1%, P < 0.05) experienced higher incidence of PPVD.

Conclusion

Women who had normal VD are at higher risk of transient PPVD than those delivered by CS during their early postpartum period.
Monetary Policy Reaction Functions in Small Open Economies: a Quantile Regression Approach
Authors: Chevapatrakul Thanaset , Paez‐Farrell Juan
Published: July 2013

We use quantile regressions to model monetary policy reaction functions in three small open economies: Australia, Canada and New Zealand. Focusing on Taylor‐type rules, we find evidence of asymmetric interest rate responses for all the countries considered, with monetary policy reacting more strongly to inflation when interest rates are high than when they are low. This is consistent with previous research suggesting that central bankers place more weight on positive deviations of inflation from its target than negative ones. In contrast, the interest rate response to the output gap is largely symmetric and small.
EMPLOYMENT AND THE BUSINESS CYCLE
Authors: CHAUVET MARCELLE , PIGER JEREMY
Published: July 2013

This paper investigates the differences in the cyclical dynamics in employment on non‐agricultural payroll (ENAP) and total civilian employment (TCE), and the implications for monitoring US business cycles in real time. We find that employment measures have diverged considerably around the last three recessions and subsequent recoveries. This significantly impacts identification of turning points. Models that use TCE are more in line with the National Bureau of Economic Research (NBER) recession dating, and deliver faster call of troughs in real time, whereas models that include ENAP series yield delays in signaling troughs, especially the most recent ones.
Complete hydrothermal re‐equilibration of zircon in the Maniitsoq structure, West Greenland: A 3001 Ma minimum age of impact?
Authors: Scherstén Anders , Garde Adam A.
Published: July 2013

Zircon in five samples of variably comminuted, melted, and hydrothermally altered orthogneiss from the Maniitsoq structure of southern West Greenland yield a weighted mean 207Pb/206Pb age of 3000.9 ± 1.9 Ma (ion probe data, n = 37). The age data constitute a rare example of pervasive and nearly complete isotopic resetting of zircon during a regional hydrothermal event. Many zircon grains are homogeneous or display weak flame‐like patterns in backscattered electron images. Other grains show complex internal textures, where homogeneous, high‐U fronts commonly cut across relict igneous‐type oscillatory zonation. Inclusions of quartz, plagioclase, mica, and other Al ± Na ± Ca ± Fe‐bearing silicates are very common. In two samples, selective replacement of zircon with baddeleyite occurs along concentric zones with relict igneous zonation, and as specks a few microns large within recrystallized, high‐U areas. We interpret the 3000.9 ± 1.9 Ma date as the minimum age of the recently proposed impact structure at Maniitsoq. The great geographical extent and intensity of the hydrothermal event suggest massive invasion of water into the currently exposed crust, implying that the age of the hydrothermal alteration would closely approximate the age of the proposed impact at Maniitsoq. At the western margin of the Taserssuaq tonalite complex, which postdates the Maniitsoq event, a 207Pb/206Pb mean age of 2994.6 ± 3.4 Ma obtained from zircon has mostly retained igneous‐type oscillatory zonation. A subsequent thermal event at approximately 2975 Ma is recorded in several samples by zircon with baddeleyite replacement textures.
A respiratory nitrate reductase active exclusively in resting spores of the obligate aerobe Streptomyces coelicolor A3(2)
Authors: Fischer Marco , Falke Dörte , Sawers R. Gary
Published: July 2013

The Gram‐positive aerobe Streptomyces coelicolor undergoes a complex life cycle including growth as vegetative hyphae and the production of aerial hyphae and spores. Little is known about how spores retain viability in the presence of oxygen; however, nothing is known about this process during anaerobiosis. Here, we demonstrate that one of the three respiratory nitrate reductases, Nar‐1, synthesized by S. coelicolor is functional exclusively in spores. A tight coupling between nitrite production and the activity of the cytoplasmically oriented Nar‐1 enzyme was demonstrated. No exogenous electron donor was required to drive nitrate reduction, which indicates that spore storage compounds are used as electron donors. Oxygen reversibly inhibited nitrate reduction by spores but not by spore extracts, suggesting that nitrate transport might be the target of oxygen inhibition. Nar‐1 activity required no de novo protein synthesis indicating that Nar‐1 is synthesized during sporulation and remains in a latently active state throughout the lifetime of the spore. Remarkably, the rates of oxygen and of nitrate reduction by wetted spores were comparable. Together, these findings suggest that S. coelicolor spores have the potential to maintain a membrane potential using nitrate as an alternative electron acceptor.
In vitro susceptibility of chromoblastomycosis agents to five antifungal drugs and to the combination of terbinafine and amphotericin B
Authors: Daboit Tatiane C. , Massotti Magagnin Cibele , Heidrich Daiane , Czekster Antochevis Laura , Vigolo Suelen , Collares Meirelles Lúcia , Alves Karine , Scroferneker Maria L.
Published: July 2013

Chromoblastomycosis is a chronic mycosis that affects the skin and subcutaneous tissues caused by several genera of dematiaceous fungi. There is not a treatment of choice. Thus, tools that help guide clinical practice are fundamental. In this sense, antifungal activity tests in vitro could be useful. However, trials with chromoblastomycosis agents are scarce. The aim of this study was to evaluate both the in vitro susceptibility of 60 chromoblastomycosis agents to five antifungals and the combination of amphotericin B (AMB) and terbinafine (TRB). TRB, itraconazole (ITZ) and ketoconazole (KTZ) were, in this order, the drugs which showed better activity against the chromoblastomycosis agents. The less active drugs were voriconazole (VRZ) and AMB. The more differentiated group was Exophiala spinifera. Cladophialophora carrionii and Fonsecaea spp. are significantly more susceptible to KTZ than Phialophora verrucosa, whereas C. carrionii is significantly more sensitive to VRZ than P. verrucosa and E. spinifera. Assays in this direction allow the knowledge of the susceptibility of the causative agents which may help the management of patients with this disease. This study includes the largest number of these agents and of genera found in the literature.
Oral Fusobacterium nucleatum subsp. polymorphum binds to human salivary α‐amylase
Authors: Zulfiqar M. , Yamaguchi T. , Sato S. , Oho T.
Published: July 2013

Fusobacterium nucleatum acts as an intermediate between early and late colonizers in the oral cavity. In this study, we showed that F. nucleatum subsp. polymorphum can bind to a salivary component with a molecular weight of approximately 110 kDa and identified the protein and another major factor of 55 kDa, as salivary α‐amylase by time‐of‐flight mass spectrometry and immuno‐reactions. Salivary α‐amylase is present in both monomeric and dimeric forms and we found that formation of the dimer depends on copper ions. The F. nucleatum adhered to both monomeric and dimeric salivary α‐amylases, but the numbers of bacteria bound to the dimeric form were more than those bound to the monomeric form. The degree of adherence of F. nucleatum to four α‐amylases from different sources was almost the same, however its binding to β‐amylase was considerably decreased. Among four α‐amylase inhibitors tested, acarbose and type 1 and 3 inhibitors derived from wheat flour showed significant activity against the adhesion of F.nucleatum to monomeric and dimeric amylases, however voglibose had little effect. Moreover F. nucleatum cells inhibited the enzymatic activity of salivary α‐amylase in a dose‐dependent manner. These results suggest that F. nucleatum plays more important and positive role as an early colonizer for maturation of oral microbial colonization.
Feasibility of Local Stress Relaxation by Laser Annealing and X‐ray Measurement
Authors: Barile C. , Casavola C. , Pappalettera G. , Pappalettere C.
Published: July 2013

Most manufacturing processes generate residual stresses inside the materials and components. Stress relief heat treatments can be used to reduce the magnitude of the residual stresses: by uniformly heating a structure to a sufficiently high temperature, and then uniformly cooling it, residual stresses can be relaxed. This process generally requires the insertion of the entire component in a large furnace, for a fairly long period of time.

In this paper, the possibility of using a high power laser source to locally relieve residual stresses is studied; this has the advantage of calibrating and confining the relief process just to the laser affected area. An experimental set‐up was tested on an aluminium specimen, and the preliminary results are reported in this paper.
Belief and Motivation
Authors: Friedrich Daniel
Published: July 2013

Humeans claim that all motivation is by desire. Anti‐Humeans maintain that some beliefs can motivate all by themselves. This dispute, I argue, hinges on the question whether belief can rationalize motivation. Moreover, I argue belief can rationalize motivation since rationality requires that one be motivated to φ if one believes one has most reason to φ, and it is possible to be motivated to φ because one believes one has most reason to φ and one exercises one's capacity for rational agency.
A trs20 Mutation That Mimics an SEDT‐Causing Mutation Blocks Selective and Non‐Selective Autophagy: A Model for TRAPP III Organization
Authors: Brunet Stephanie , Shahrzad Nassim , Saint‐Dic Djenann , Dutczak Hartley , Sacher Michael
Published: July 2013

TRAPP is a multisubunit complex that functions in membrane traffic. Mutations in the mammalian TRAPP protein C2 are linked to the skeletal disorder spondyloepiphyseal dysplasia tarda (SEDT) that is thought to arise from an inability to secrete procollagen from the endoplasmic reticulum. Here, we show that C2 binds to the SNARE protein Syntaxin 5 and this interaction is weakened by an SEDT‐causing missense mutation (D47Y). Interestingly, the equivalent mutation (D46Y) in the yeast C2 homolog Trs20p does not block anterograde traffic but did affect endocytosis. The trs20D46Y mutation interfered with the interaction between Trs20p and Trs85p (TRAPP III‐specific subunit), Trs120p and Trs130p (TRAPP II‐specific subunits). Size exclusion chromatography suggested that this yeast mutation destabilized the TRAPP III complex that is involved in autophagy. We further show that this mutation blocks both the selective cytosol‐to‐vacuole (cvt) pathway as well as non‐selective autophagy. We demonstrate that the apparent molecular size of the TRAPP III complex is dependent upon membranes, and that the presence of TRAPP III is dependent upon Atg9p. Finally, we demonstrate that lipidated Bet3p is enriched in TRAPP III and that lipidation increases the efficiency of autophagy. Our study suggests that Trs20p acts as an adaptor for Trs85p and Trs120p and reveals complexities in TRAPP III assembly and function. The implications of C2D47Y in SEDT are discussed.
Using water industry data to assess the metaldehyde pollution problem
Authors: Kay Paul , Grayson Richard
Published: July 2013

The presence of metaldehyde in raw and treated water has become a recognised problem recently. The current study used water industry monitoring data collected over a two and a half‐year period (2008–2011) to quantify the presence of metaldehyde in rivers and finished waters. Measured surface water concentrations were then compared with catchment characteristics in an attempt to identify those factors driving losses of the pesticide to water. An assessment was also made of the robustness of the monitoring strategy used, which was assumed to represent typical water industry practice, and is currently being used to develop catchment management plans. It was found that exceedance of the European Union pesticide standard (0.1 μg/L) during the October–December slug pellet application period is commonplace. Peak concentrations were generally in the 0.4–0.6 μg/L range although sometimes were an order of magnitude higher.
Fatigue Crack Propagation Analysis of Plaque Rupture
Authors: Pei Xuan , Wu Baijian , Li Zhi-Yong
Published: July 2013

Rupture of atheromatous plaque is the major cause of stroke or heart attack. Considering that the cardiovascular system is a classic fatigue environment, plaque rupture was treated as a chronic fatigue crack growth process in this study. Fracture mechanics theory was introduced to describe the stress status at the crack tip and Paris' law was used to calculate the crack growth rate. The effect of anatomical variation of an idealized plaque cross-section model was investigated. The crack initiation was considered to be either at the maximum circumferential stress location or at any other possible locations around the lumen. Although the crack automatically initialized at the maximum circumferential stress location usually propagated faster than others, it was not necessarily the most critical location where the fatigue life reached its minimum. We found that the fatigue life was minimum for cracks initialized in the following three regions: the midcap zone, the shoulder zone, and the backside zone. The anatomical variation has a significant influence on the fatigue life. Either a decrease in cap thickness or an increase in lipid pool size resulted in a significant decrease in fatigue life. Comparing to the previously used stress analysis, this fatigue model provides some possible explanations of plaque rupture at a low stress level in a pulsatile cardiovascular environment, and the method proposed here may be useful for further investigation of the mechanism of plaque rupture based on in vivo patient data.
On the Fracture Toughness of Pseudoelastic Shape Memory Alloys
Authors: Baxevanis Theocharis , Landis Chad M. , Lagoudas Dimitris C.
Published: July 2013

A finite element analysis of quasi-static, steady-state crack growth in pseudoelastic shape memory alloys is carried out for plane strain, mode I loading. The crack is assumed to propagate at a critical level of the crack-tip energy release rate. Results pertaining to the influence of forward and reverse phase transformation on the near-tip mechanical fields and fracture toughness are presented for a range of thermomechanical parameters and temperature. The fracture toughness is obtained as the ratio of the far-field applied energy release rate to the crack-tip energy release rate. A substantial fracture toughening is observed, in accordance with experimental observations, associated with the energy dissipated by the transformed material in the wake of the growing crack. Reverse phase transformation, being a dissipative process itself, is found to increase the levels of toughness enhancement. However, higher nominal temperatures tend to reduce the toughening of an SMA alloy—although the material's tendency to reverse transform in the wake of the advancing crack tip increases—due to the higher stress levels required for initiation of forward transformation.
Stochastic Averaging of Quasi-Integrable and Resonant Hamiltonian Systems Under Combined Gaussian and Poisson White Noise Excitations
Authors: Jia Wantao , Zhu Weiqiu , Xu Yong , Liu Weiyan
Published: July 2013

A stochastic averaging method for quasi-integrable and resonant Hamiltonian systems subject to combined Gaussian and Poisson white noise excitations is proposed. The case of resonance with α resonant relations is considered. An (n + α)-dimensional averaged Generalized Fokker–Plank–Kolmogorov (GFPK) equation for the transition probability density of n action variables and α combinations of phase angles is derived from the stochastic integrodifferential equations (SIDEs) of original quasi-integrable and resonant Hamiltonian systems by using the jump-diffusion chain rule. The reduced GFPK equation is solved by using finite difference method and the successive over relaxation method to obtain the stationary probability density of the system. An example of two nonlinearly damped oscillators under combined Gaussian and Poisson white noise excitations is given to illustrate the proposed method. The good agreement between the analytical results and those from digital simulation shows the validity of the proposed method.
Not mTORCing
Authors: Ray L. Bryan
Published: July 2013

Inhibition of a protein kinase differentially affects its targets, depending on phosphorylation site characteristics.
Whence the “Eat Me” Signal?
Authors: Ray L. Bryan
Published: July 2013

An enzyme involved in the flipping of phospholipids in dying cells’ surfaces to mark the cells for removal is identified.
Macrolide-Resistant Mycoplasma pneumoniae Pneumonia in Adolescents and Adults: Clinical Findings, Drug Susceptibility, and Therapeutic Efficacy
Authors: Miyashita Naoyuki , Akaike Hiroto , Teranishi Hideto , Ouchi Kazunobu , Okimoto Niro
Published: July 2013

We investigated differences in the clinical findings between 30 patients with macrolide-resistant
Mycoplasma pneumoniae
pneumonia and 43 patients with macrolide-sensitive
M. pneumoniae
pneumonia in adolescents and adults. No differences in clinical presentation were observed between the two groups. Among patients with macrolide-resistant
Mycoplasma pneumoniae
pneumonia, treatment was more effective in the groups that received quinolones and minocycline than in the group that received macrolides (
P
= 0.0361 and
P
= 0.0237, respectively).
Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of GSK2336805, an Inhibitor of Hepatitis C Virus (HCV) NS5A, in Healthy Subjects and Subjects Chronically Infected with HCV Genotype 1
Authors: Wilfret D. A. , Walker J. , Adkison K. K. , Jones L. A. , Lou Y. , Gan J. , Castellino S. , Moseley C. L. , Horton J. , de Serres M. , Culp A. , Goljer I. , Spreen W.
Published: July 2013

GSK2336805 is an orally bioavailable hepatitis C virus (HCV) inhibitor working through an NS5A-mediated mechanism. This first-time-in-human study was conducted to assess the safety, tolerability, pharmacokinetics, metabolism, and efficacy of GSK2336805 in healthy subjects and subjects infected with HCV genotype 1. We performed a three-part, randomized, double-blind, placebo-controlled study in 46 healthy subjects and 23 HCV-infected subjects. After an overnight fast, healthy subjects received GSK2336805 as 10 mg, 30 mg, 30 mg plus food, and 60 mg in a single dose and 10 mg (7 days), 30 mg (7 days), and 75 mg (14 days) in a once-daily multiple dose. Subjects with HCV received GSK2336805 as a 1- to 120-mg single dose. In subjects with HCV, reductions in HCV RNA were observed within 4 h and a single dose of GSK2336805 of ≥10 mg resulted in a statistically significant ≥2-log reduction in HCV RNA compared with placebo at 24 h postdose. GSK2336805 was readily absorbed in all subjects, and the half-life (
t
1/2
) was suitable for once-daily dosing. Administration of GSK2336805 with food had no effect on plasma GSK2336805 exposure; however, absorption was delayed, with a median
t
max
(time to maximum concentration of drug in serum) of 4.5 versus 2.0 h. Twenty subjects who received GSK2336805 experienced mild to moderate adverse events; none were serious. GSK2336805 was well tolerated and exhibited rapid, significant antiviral activity after a single dose in HCV-infected subjects. These results support the conduct of further studies evaluating GSK2336805 administered once daily for longer durations in combination with peginterferon, ribavirin, and other direct-acting antivirals. (This study has been registered at ClinicalTrials.gov under registration no. NCT01277692.)
A Chimeric Plasmodium falciparum Merozoite Surface Protein Vaccine Induces High Titers of Parasite Growth Inhibitory Antibodies
Authors: Alaro James R. , Partridge Andrea , Miura Kazutoyo , Diouf Ababacar , Lopez Ana M. , Angov Evelina , Long Carole A. , Burns James M.
Published: July 2013

The C-terminal 19-kDa domain ofPlasmodium falciparummerozoite surface protein 1 (PfMSP119) is an established target of protective antibodies. However, clinical trials ofPfMSP142, a leading blood-stage vaccine candidate which contains the protective epitopes ofPfMSP119, revealed suboptimal immunogenicity and efficacy. Based on proof-of-concept studies in thePlasmodium yoeliimurine model, we produced a chimeric vaccine antigen containing recombinantPfMSP119(rPfMSP119) fused to the N terminus ofP. falciparummerozoite surface protein 8 that lacked its low-complexity Asn/Asp-rich domain, rPfMSP8 (ΔAsn/Asp). Immunization of mice with the chimeric rPfMSP1/8 vaccine elicited strong T cell responses to conserved epitopes associated with the rPfMSP8 (ΔAsn/Asp) fusion partner. While specific forPfMSP8, this T cell response was adequate to provide help for the production of high titers of antibodies to bothPfMSP119and rPfMSP8 (ΔAsn/Asp) components. This occurred with formulations adjuvanted with either Quil A or with Montanide ISA 720 plus CpG oligodeoxynucleotide (ODN) and was observed in both inbred and outbred strains of mice.PfMSP1/8-induced antibodies were highly reactive with two major alleles ofPfMSP119(FVO and 3D7). Of particular interest, immunization withPfMSP1/8 elicited higher titers ofPfMSP119-specific antibodies than a combined formulation of rPfMSP142and rPfMSP8 (ΔAsn/Asp). As a measure of functionality,PfMSP1/8-specific rabbit IgG was shown to potently inhibit thein vitrogrowth of blood-stage parasites of the FVO and 3D7 strains ofP. falciparum. These data support the further testing and evaluation of this chimericPfMSP1/8 antigen as a component of a multivalent vaccine forP. falciparummalaria.
Relationship between periparturient management, prevalence of MAP and preventable economic losses in UK dairy herds
Authors: Radia D. , Bond K. , Limon G. , van Winden S. , Guitian J.
Published: July 2013

Johne's disease (JD) is an infectious, progressive, gastrointestinal disease affecting ruminants. Calves are mostly infected in their first six months of life, or in utero. We investigated the impact of specific periparturient management practices on within‐herd JD prevalence and economic losses foregone in UK dairy herds by means of data synthesis (systematic appraisal of published evidence and expert elicitation) and use of a pre‐existing simulation model. Our results show the scarcity of accurate estimates of the impact of specific periparturient management practices on within‐herd JD prevalence, which could, in part, be explained by challenges associated with the chronic nature of JD. Management practices aiming to limit the faecal‐oral transmission route ofMycobacterium aviumsubspeciesparatuberculosis(MAP) were found to be most effective at reducing within‐herd prevalence of JD. Practices aiming to limit MAP transmission via colostrum and milk were found to be less effective. Losses foregone for a hypothetical herd of 200 milking cows were considerable; based on the assumptions, it is reasonable to expect between £7000 and £11,000 of losses foregone when management practices are implemented as a package of measures. The findings of this study are envisaged to enable farmers and veterinarians to make more informed decisions on changes to periparturient management to control JD.