bluuebunny/crossref_metadata_2025 huggingface dataset:
Atf6α deficiency suppresses microglial activation and ameliorates pathology of experimental autoimmune encephalomyelitis
Authors: Ta Hieu Minh , Le Thuong Manh , Ishii Hiroshi , Takarada‐Iemata Mika , Hattori Tsuyoshi , Hashida Koji , Yamamoto Yasuhiko , Mori Kazutoshi , Takahashi Ryosuke , Kitao Yasuko , Hori Osamu
Published: June 2016

Accumulating evidence suggests a critical role for the unfolded protein response in multiple sclerosis (MS) and in its animal model, experimental autoimmune encephalomyelitis (EAE). In this study, we investigated the relevance of activating transcription factor 6α (ATF6α), an upstream regulator of part of the unfolded protein response, in EAE. The expressions of ATF6α‐target molecular chaperones such as glucose‐regulated protein 78 (GRP78) and glucose‐regulated protein 94 (GRP94) were enhanced in the acute inflammatory phase after induction of EAE. Deletion of Atf6α suppressed the accumulation of T cells and microglia/macrophages in the spinal cord, and ameliorated the clinical course and demyelination after EAE induction. In contrast to the phenotypes in the spinal cord, activation status of T cells in the peripheral tissues or in the culture system was not different between two genotypes. Bone marrow transfer experiments and adoptive transfer of autoimmune CD4+ T cells to recipient mice (passive EAE) also revealed that CNS‐resident cells are responsible for the phenotypes observed in Atf6α−/− mice. Further experiments with cultured cells indicated that inflammatory response was reduced in Atf6α−/− microglia, but not in Atf6α−/− astrocytes, and was associated with proteasome‐dependent degradation of NF‐κB p65. Thus, our results demonstrate a novel role for ATF6α in microglia‐mediated CNS inflammation.

image

We investigated the relevance of ATF6α, an upstream regulator of part of the UPR, in EAE. Deletion of Atf6α suppressed inflammation, and ameliorated demyelination after EAE. Bone marrow transfer experiments and adoptive transfer of autoimmune CD4+ T cells revealed that CNS‐resident cells are responsible for the phenotypes in Atf6α−/− mice. Furthermore, inflammatory response was reduced in Atf6α−/− microglia, and was associated with degradation of NF‐κB p65. Our results demonstrate a novel role for ATF6α in microglia‐mediated inflammation.

Cover image for this issue: doi: 10.1111/jnc.13346.
A training programme for Taiwan nurses to improve child abuse reporting
Authors: Lee Pei‐Yu , Chou Fan‐Hao
Published: June 2016

Aims and objectives

To design a training programme for nurses and evaluate the effectiveness of the training programme in improving the nurses’ self‐efficacy in reporting cases of child abuse and neglect.

Background

The problem of child abuse and neglect cases has become prevalent throughout numerous countries. Previous studies have found that more than 70% of Taiwanese nurses considered that they required child abuse and neglect training. Moreover, a training programme for child abuse and neglect reporting based on self‐efficacy theory in clinical practice has been developed previously.

Methods

A quasi‐experimental research design was implemented. The study participants comprised 80 clinical nurses: 40 in an experimental group and 40 in a control group; the pretest, post‐test and follow‐up results were compared between the groups. Moreover, an analysis of covariance was applied to test the effectiveness of a nurse child abuse and neglect training programme after controlling for the effects of age, marital status and working years. The experimental and control groups were compared according to their scores on each self‐efficacy subscale.

Results

The experimental and control groups differed significantly regarding the outcome measures of all six subscales of child abuse and neglect reporting self‐efficacy between the pretest and post‐test. Therefore, the results supported the hypothesis that nurse self‐efficacy in reporting child abuse and neglect cases would improve after completing the Child Abuse and Neglect Training Program for Nurses.

Conclusion

The Child Abuse and Neglect Training Program for Nurses is an appropriate training programme for improving nurse competence and confidence in reporting suspected child abuse and neglect cases.

Relevance to clinical practice

This study is relevant to clinical practice because it clarifies a relationship between nurses’ self‐efficacy and reporting behaviour. It also highlights the importance and effectiveness of the training programme Child Abuse and Neglect Training Program for Nurses in improving nurses’ reporting behaviour for child abuse and neglect cases.
Feeling Rushed: Gendered Time Quality, Work Hours, Nonstandard Work Schedules, and Spousal Crossover
Authors: Craig Lyn , Brown Judith E.
Published: June 2016

The authors investigated gender differences in couple parents' subjective time pressure, using detailed Australian time use data (n=756 couples with minor children). They examined how family demand, employment hours, and nonstandard work schedules of both partners relate to each spouse's non‐employment time quality (“pure” leisure, “contaminated” leisure, multitasking housework, and child care) and subjective feelings of being rushed or pressed for time. Mothers averaged more contaminated leisure and less pure leisure and did much more unpaid work multitasking than fathers. These results suggest that these differences in time quality do partially account for mothers feeling more rushed than fathers. Weekend work was associated with mothers having less pure leisure, but not contaminated leisure. The opposite was found for fathers. Spousal work characteristics also related to time use and feeling rushed in gendered ways, with male long work hours positively associated with higher time pressure for mothers as well as the fathers who worked them.
Simple Technique to Reorient Different Casts of Same Patient on a Dental Surveyor
Authors: Patil Pravinkumar G. , Nimbalkar‐Patil Smita P.
Published: June 2016

Accurate planning for the framework design of removable partial dentures requires careful analysis of the diagnostic cast with a dental surveyor to determine the optimal path of placement. Some techniques described in the literature are helpful in reorienting the same cast on the surveyor, including the tripod marking method; however, there is a possibility of introducing human errors during marking and repositioning of the tripod points on to the different casts at the same location. Other techniques, which do not require markings on the cast to reorient different casts of the same patient, need specific devices or trays. This article suggests the direct use of a putty‐elastomeric orientation index that can be preserved and used multiple times while reorienting different casts of the same patients at various laboratory steps. A putty elastomeric impression material is mixed and adapted on to the diagnostic cast, covering key teeth areas of the cast and incorporating the analyzing rod of the surveyor. Thus there is no need to use a special device or the tray to reorient different casts.
High-throughput sequencing reveals unprecedented diversities of Aspergillus species in outdoor air
Authors: Lee S. , An C. , Xu S. , Lee S. , Yamamoto N.
Published: June 2016

This study used the Illumina MiSeq to analyse compositions and diversities of Aspergillus species in outdoor air. The seasonal air samplings were performed at two locations in Seoul, South Korea. The results showed the relative abundances of all Aspergillus species combined ranging from 0·20 to 18% and from 0·19 to 21% based on the number of the internal transcribed spacer 1 (ITS1) and β-tubulin (BenA) gene sequences respectively. Aspergillus fumigatus was the most dominant species with the mean relative abundances of 1·2 and 5·5% based on the number of the ITS1 and BenA sequences respectively. A total of 29 Aspergillus species were detected and identified down to the species rank, among which nine species were known opportunistic pathogens. Remarkably, eight of the nine pathogenic species were detected by either one of the two markers, suggesting the need of using multiple markers and/or primer pairs when the assessments are made based on the high-throughput sequencing. Due to diversity of species within the genus Aspergillus, the high-throughput sequencing was useful to characterize their compositions and diversities in outdoor air, which are thought to be difficult to be accurately characterized by conventional culture and/or Sanger sequencing-based techniques.

Significance and Impact of the Study

Aspergillus is a diverse genus of fungi with more than 300 species reported in literature. Aspergillus is important since some species are known allergens and opportunistic human pathogens. Traditionally, growth-dependent methods have been used to detect Aspergillus species in air. However, these methods are limited in the number of isolates that can be analysed for their identities, resulting in inaccurate characterizations of Aspergillus diversities. This study used the high-throughput sequencing to explore Aspergillus diversities in outdoor, which are thought to be difficult to be accurately characterized by traditional growth-dependent techniques.
First insights into the demography of the rare gorgonian Spinimuricea klavereni in the Mediterranean Sea
Authors: Topçu Nur Eda , Öztürk Bayram
Published: June 2016

We present the results of the first study to highlight the demography, morphometry and growth rates of Spinimuricea klavereni, a rare Mediterranean endemic gorgonian exceptionally common in shallow depths of the Northeast Marmara Sea. In the study area, this species forms vast populations on rocks, boulders and attached to pebbles/stones/shells on soft substrates between 20 and 45 m depth, with a total average density of 0.3 colonies·m−2 but comprising patches up to 3 colonies·m−2. Colonies, which are on average 42.9 (±20.1) cm in height, can reach up to 110 cm. Unlike other Mediterranean gorgonians, the colonies studied here showed fast growth rates that decreased with increasing colony height, between 1.5–11.1 and 4.96 ± 3.01 cm·year−1 on average. The low necrosis and high growth rates displayed by this species in the Northeast Marmara Sea confirm the previously hypothesized opportunistic behaviour of the species. The unique community consisting of S. klavereni and other rare gorgonian/soft corals has limited distribution in this area and should be considered to be a vulnerable marine ecosystem. Therefore we recommend that some conservation measures are taken, including the prohibition of all fisheries and anchoring over these assemblages.
The perilipin‐like PPE15 protein in Mycobacterium tuberculosis is required for triacylglycerol accumulation under dormancy‐inducing conditions
Authors: Daniel Jaiyanth , Kapoor Nidhi , Sirakova Tatiana , Sinha Rajesh , Kolattukudy Pappachan
Published: June 2016

Mycobacterium tuberculosis (Mtb) causes latent tuberculosis infection in one‐third of the world population and remains quiescent in the human body for decades. The dormant pathogen accumulates lipid droplets containing triacylglycerol (TAG). In mammals, perilipin regulates lipid droplet homeostasis but no such protein has been identified in Mtb. We identified an Mtb protein (PPE15) that showed weak amino acid sequence identities with mammalian perilipin‐1 and was upregulated in Mtb dormancy. We generated a ppe15 gene‐disrupted mutant of Mtb and examined its ability to metabolically incorporate radiolabeled oleic acid into TAG, accumulate lipid droplets containing TAG and develop phenotypic tolerance to rifampicin in two in vitro models of dormancy including a three‐dimensional human granuloma model. The mutant showed a significant decrease in the biosynthesis and accumulation of lipid droplets containing TAG and in its tolerance of rifampicin. Complementation of the mutant with a wild‐type copy of the ppe15 gene restored the lost phenotypes. We designate PPE15 as mycobacterial perilipin‐1 (MPER1). Our findings suggest that the MPER1 protein plays a critical role in the homeostasis of TAG ‐containing lipid droplets in Mtb and influences the entry of the pathogen into a dormant state.
Trypanosomatid parasites rescue heme from endocytosed hemoglobin through lysosomal HRG transporters
Authors: Cabello‐Donayre María , Malagarie‐Cazenave Sophie , Campos‐Salinas Jenny , Gálvez Francisco J. , Rodríguez‐Martínez Alba , Pineda‐Molina Estela , Orrego Lina M. , Martínez‐García Marta , Sánchez‐Cañete María P. , Estévez Antonio M. , Pérez‐Victoria José M.
Published: June 2016

Pathogenic trypanosomatid parasites are auxotrophic for heme and they must scavenge it from their human host. Trypanosoma brucei (responsible for sleeping sickness) and Leishmania (leishmaniasis) can fulfill heme requirement by receptor‐mediated endocytosis of host hemoglobin. However, the mechanism used to transfer hemoglobin‐derived heme from the lysosome to the cytosol remains unknown. Here we provide strong evidence that HRG transporters mediate this essential step. In bloodstream T. brucei, TbHRG localizes to the endolysosomal compartment where endocytosed hemoglobin is known to be trafficked. TbHRG overexpression increases cytosolic heme levels whereas its downregulation is lethal for the parasites unless they express the Leishmania orthologue LmHR1. LmHR1, known to be an essential plasma membrane protein responsible for the uptake of free heme in Leishmania, is also present in its acidic compartments which colocalize with endocytosed hemoglobin. Moreover, LmHR1 levels modulated by its overexpression or the abrogation of an LmHR1 allele correlate with the mitochondrial bioavailability of heme from lysosomal hemoglobin. In addition, using heme auxotrophic yeasts we show that TbHRG and LmHR1 transport hemoglobin‐derived heme from the digestive vacuole to the cytosol. Collectively, these results show that trypanosomatid parasites rescue heme from endocytosed hemoglobin through endolysosomal HRG transporters, which could constitute novel drug targets.
Cognitive dysfunction and regional cerebral blood flow changes in Japanese females after human papillomavirus vaccination
Authors: Matsudaira Takashi , Takahashi Yukitoshi , Matsuda Kazumi , Ikeda Hitoshi , Usui Keiko , Obi Tomokazu , Inoue Yushi
Published: June 2016

Background

Human papillomavirus vaccination is used to prevent cervical cancer in adolescent females; however, few vaccinated individuals show long‐lasting symptoms.

Aim

We investigated cognitive dysfunction and regional cerebral blood flow changes in human papillomavirus‐vaccinated patients to estimate their pathological condition.

Methods

We retrospectively included patients with cognitive dysfunction after human papillomavirus vaccination. N‐isopropyl‐(123I)‐p‐iodoamphetamine single‐photon emission computed tomography images of patients were compared with those of 10 healthy unvaccinated females (19.6 ± 0.5 years) using 3‐D stereotactic surface projection and stereotactic extraction estimation methods. We also investigated the correlation between the Wechsler Adult Intelligence Scale‐Third edition score and anatomical region with decreased regional cerebral blood flow.

Results

A total of 17 females (age 17.7 ± 1.4 years) showed cognitive dysfunction, including memory impairment (17 patients, 100%), acalculia (4, 23.5%), transient prosopagnosia‐like symptoms (3, 17.6%), and topographical impairment and hemispatial neglect (2, 11.8%). Significantly decreased regional cerebral blood flow was found in the right medial frontal, subcallosal, anterior cingulate, orbital, rectal, parahippocampal, fusiform gyrus, left angular and superior occipital gyrus, and bilateral thalamus. Significant negative correlations were found between the full scale intelligence quotient and extent of decreased regional cerebral blood flow in the right medial frontal and rectal gyrus, verbal intelligence quotient and right subcallosal, rectal gyrus and left thalamus, and performance intelligence quotient and the right medial frontal gyrus.

Conclusion

In patients with cognitive dysfunction after human papillomavirus vaccination, regional cerebral blood flow was decreased mainly in the regions connected to the limbic system. Hypoperfusion in the limbic system might reflect cognitive dysfunction, mainly memory impairment, after human papillomavirus vaccination.
Interventions that cause weight loss and the impact on cardiovascular risk factors: a systematic review and meta‐analysis
Authors: Zomer E. , Gurusamy K. , Leach R. , Trimmer C. , Lobstein T. , Morris S. , James W.P.T. , Finer N.
Published: June 2016

Overweight and obesity increase the risks of diabetes and cardiovascular disease (CVD). This has been shown to be reversed with weight loss. A systematic review and meta‐analysis were performed to determine the effect of weight loss in the primary prevention of CVD. PubMed, Embase and the Cochrane Library databases were searched electronically through to May 2013. Randomized controlled trials assessing weight loss and cardiovascular risk factors and outcomes were included. A random effects meta‐analysis, with sub‐group analyses for degree of weight loss, and age were performed. Because few studies reported clinical outcomes of CVD, analyses were limited to cardiovascular risk factors (83 studies). Interventions that caused any weight loss significantly reduced systolic blood pressure (−2.68 mmHg, 95% CI −3.37, −2.11), diastolic blood pressure (−1.34 mmHg, 95% CI −1.71, −0.97), low‐density lipoprotein cholesterol (−0.20 mmol L−1, 95% CI −0.29, −0.10), triglycerides (−0.13 mmol L−1, 95% CI −0.22, −0.03), fasting plasma glucose (−0.32 mmol L−1, 95% CI −0.43, −0.22) and haemoglobin A1c(−0.40%, 95% CI −0.52, −0.28) over 6–12 months. Significant changes remained after 2 years for several risk factors. Similar results were seen in sub‐group analyses. Interventions that cause weight loss are effective at improving cardiovascular risk factors at least for 2 years. © 2016 World Obesity
Residual FDG‐PET metabolic activity in metastatic melanoma patients with prolonged response to anti‐PD‐1 therapy
Authors: Kong Benjamin Y. , Menzies Alexander M. , Saunders Catherine A. B. , Liniker Elizabeth , Ramanujam Sangeetha , Guminski Alex , Kefford Richard F. , Long Georgina V. , Carlino Matteo S.
Published: June 2016

18‐Fluorodeoxyglucose positron emission tomography (FDG‐PET) scans were performed on 27 patients with unresectable stage IIIC or IV melanoma after prolonged treatment with anti‐PD‐1 antibodies to examine the hypothesis that patients with prolonged response to treatment may have metabolically inactive lesions by FDG‐PET. Scans were performed at a median of 15.2 months (range 12–29 months) after starting treatment. Overall, 15 of 27 (56%) patients had a positive FDG‐PET scan. Eight patients with positive scans underwent biopsy; 5 of 8 (62%) were melanoma and 3 of 8 (38%) were immune cell infiltrates. Of the 12 patients with negative FDG‐PET scans, six had residual computerized tomography‐visible lesions, five have ceased treatment, and none have recurred with follow‐up of 6–10 months. Patients with residual metastases after a prolonged period without progression on anti‐PD‐1 therapy may have metabolically inactive lesions. Isolated metabolically active lesions in clinically well patients may reveal immune cell infiltrates rather than melanoma.
Genetic variability of Fusarium fujikuroi populations associated with bakanae of rice in Italy
Authors: Valente M. T. , Desiderio F. , Infantino A. , Valè G. , Abbruscato P. , Aragona M.
Published: June 2016

The heterothallic ascomycete Fusarium fujikuroi (teleomorph: Gibberella fujikuroi) is the causal agent of bakanae of rice, a disease of increasing economic importance in the major rice‐producing areas in the world and a serious threat for Italian rice cultivation. A few studies have characterized F. fujikuroi isolates in America and the Philippines but no data are available on the genetic structure of Italian pathogen populations. Microsatellite SSRs are useful tools to study the intraspecific diversity at population level. In this study, 19 polymorphic SSRs have been identified and applied to characterize the genetic variation of 334 isolates of F. fujikuroi coming from eight Italian rice‐growing areas. A high degree of diversity at haplotype level has emerged: in the eight populations, 107 unique haplotypes were scored. Analysis of molecular variance (amova) showed that 98% of genetic variability occurred within F. fujikuroi Italian populations, as confirmed by the allelic Shannon index ranging from 0.56 to 1.06. The presence of a 1:1 ratio of mating type alleles in six out of eight of the Italian fungal populations suggests a potential for sexual reproduction in the field. However, the high fraction of clonality (43%), confirmed by neighbour‐joining clustering analysis, and the high level of linkage disequilibrium observed, indicates that reproduction of F. fujikuroi is mostly clonal in Italy. All data suggest that the observed genetic variability was probably mediated by human activity and transmission by rice seeds.
The Legal Character of the Paris Agreement
Authors: Bodansky Daniel
Published: June 2016

From start to finish, the question of legal form or character was central to the Paris negotiations. The Paris Agreement is a treaty within the definition of the Vienna Convention on the Law of Treaties, but not every provision of the agreement creates a legal obligation. It contains a mix of mandatory and non‐mandatory provisions relating to parties’ mitigation contributions, as well as to the other elements of the Durban Platform, including adaptation and finance. One cannot definitively say how much the legally binding character of the Paris Agreement matters. Making the agreement legally binding may provide a greater signal of commitment and greater assurance of compliance. But transparency, accountability and precision can also make a significant difference, and legal bindingness can be a double‐edged sword if it leads States not to participate or to make less ambitious commitments. Thus, the issue of legal character, though important, is only one factor in assessing the significance of the Paris outcome.
Age‐Structured Within‐Host HIV Dynamics with Multiple Target Cells
Authors: Wang Xia , Lou Yijun , Song Xinyu
Published: June 2016

Human immunodeficiency virus (HIV) can infect various types of cell populations such as CD4+ T cells and macrophages. The heterogeneity of these target cells implies different birth, death, infection rates, and so on. To investigate the within‐host dynamics of HIV which can infect n different types of target cells, a theoretical model with infection‐age structure for each type of target cells and a general nonlinear incidence rate is proposed in this manuscript. The model, in the form of a hyperbolic system of partial differential equations (PDE) for infected target cells coupled with several ordinary differential equations, is shown to be biologically reasonable with the establishment of existence, positivity, and boundedness of solutions. Although the PDE form poses novel challenges to theoretical investigation, rigorous analysis is performed to show the uniform persistence of the virus when the basic reproduction number is greater than one. Furthermore, by constructing suitable Lyapunov functionals, we show that the infection‐free steady state is globally asymptotically stable when the basic reproduction number is less than unity, while the positive steady state is globally asymptotically stable when the basic reproduction number is greater than one.
Prevalence of constipation among persons living in institutional geriatric‐care settings – a cross‐sectional study
Authors: Lämås Kristina , Karlsson Stig , Nolén Anna , Lövheim Hugo , Sandman Per‐Olof
Published: June 2016

Rational

The current state of knowledge about the prevalence of constipation among persons living in institutional geriatric‐care settings is limited.

Aim

The aim was to investigate the prevalence of constipation among institutional geriatric‐care residents and identify resident characteristics related to constipation.

Methodological design

In a cross‐sectional study of all the institutional geriatric‐care settings in a county in northern Sweden, 2970 residents were assessed. The member of staff who knew each resident best used the Multi‐Dimensional Dementia Assessment Scale and the resident's records of prescribed medication to monitor cognitive function, activities in daily life, behavioural and psychological symptoms, physical restraints, speech ability, nutrition and pharmacologic agents. The study was approved by the Regional Ethical Review Board.

Result

The prevalence of constipation was 67%. The mean age was higher among those with constipation. A significantly higher proportion of the constipated had cognitive and/or physical impairments, physical restraints, impaired speech, problems with nutrition, and higher numbers of drugs for regular use. Of those with constipation, 68% were prescribed laxatives for regular use. Twenty‐three per cent of the constipated residents were prescribed opioid analgesics (n = 465), and 29% (n = 134) of these were not prescribed any laxatives.

Study limitation

Due to the cross‐sectional design, the results should be interpreted with caution in terms of causal reasoning, generalisation and conclusions about risk factors. Another limitation is the use of proxy assessments of constipation.

Conclusion

The results show that constipation is common among residents in institutional geriatric‐care settings in Sweden, which is in line with previous studies from other Western countries. Despite being constipated when having prescribed opioid analgesics, a large number did not have prescribed laxatives. The results indicate the urgency of finding strategies and implementing suitable interventions to improve bowel management in residents in institutional geriatric‐care settings.
The role of religion and spirituality in coping with kidney disease and haemodialysis in Thailand
Authors: Yodchai Kantaporn , Dunning Trisha , Savage Sally , Hutchinson Alison M.
Published: June 2016

Background

People with chronic kidney disease (CKD) face various problems including psychological, socioeconomic and physical effects associated with CKD and its treatment. They need to develop strategies to help them cope with CKD and life challenges. Religion and spirituality are important coping strategies, but their role in helping people cope with CKD and haemodialysis (HD) in Thailand is relatively unknown.

Aims

To investigate the role of religion and spirituality in coping with CKD and its treatment in Thailand.

Design

An exploratory, qualitative approach was undertaken using semistructured individual interviews.

Method

Purposive sampling was used to recruit participants. Face‐to‐face, in‐depth individual interviews using open questions were conducted during January and February 2012. Interviews were audio‐recorded and transcribed verbatim. Data were analysed using the framework method of qualitative data analysis.

Findings

Twenty people receiving HD participated: age range 23–77 years, mean 53.7 (±16.38 SD). Ten were women. Participants reported use of religious and spiritual practices to cope with CKD and its treatment, including religious and spiritual explanations for developing CKD, karmic disease, making merit, reading Dharma books, praying and chanting to save life and making a vow to Pran‐Boon.

Conclusion

Religion and spirituality provide powerful coping strategies that can help Thai people with CKD overcome the associated distress and difficulties. Religion and spirituality cannot be separated in Thai culture because Thai people are both religious and spiritual.
Rab35 GTPase: A Central Regulator of Phosphoinositides and F‐actin in Endocytic Recycling and Beyond
Authors: Klinkert Kerstin , Echard Arnaud
Published: June 2016

Rab35 is one of the first discovered members of the large Rab GTPase family, yet it received little attention for 10 years being considered merely as a Rab1‐like GTPase. In 2006, Rab35 was recognized as a unique Rab GTPase localized both at the plasma membrane and on endosomes, playing essential roles in endocytic recycling and cytokinesis. Since then, Rab35 has become one of the most studied Rabs involved in a growing number of cellular functions, including endosomal trafficking, exosome release, phagocytosis, cell migration, immunological synapse formation and neurite outgrowth. Recently, Rab35 has been acknowledged as an oncogenic GTPase with activating mutations being found in cancer patients. In this review, we provide a comprehensive summary of known Rab35‐dependent cellular functions and detail the few Rab35 effectors characterized so far. We also review how the Rab35 GTP/GDP cycle is regulated, and emphasize a newly discovered mechanism that controls its tight activation on newborn endosomes. We propose that the involvement of Rab35 in such diverse and apparently unrelated cellular functions can be explained by the central role of this GTPase in regulating phosphoinositides and F‐actin, both on endosomes and at the plasma membrane.
Differential impact of acute and prolonged cAMP agonist exposure on protein kinase A activation and human myometrium contractile activity
Authors: Lai Pei F. , Tribe Rachel M. , Johnson Mark R.
Published: June 2016

Key points

Over 15 million babies are born prematurely each year with approximately 1 million of these babies dying as a direct result of preterm delivery.

β2‐Adrenoreceptor agonists that act via cAMP can reduce uterine contractions to delay preterm labour, but their ability to repress uterine contractions lasts ≤ 48 h and their use does not improve neonatal outcomes.

Previous research has suggested that cAMP inhibits myometrial contractions via protein kinase A (PKA) activation, but this has yet to be demonstrated with PKA‐specific agonists.

We investigated the role of PKA in mediating cAMP‐induced human myometrial relaxation, and the impact of prolonged cAMP elevation on myometrial contractility.

Our findings suggest that PKA is not the sole mediator of cAMP‐induced myometrial relaxation and that prolonged prophylactic elevation of cAMP alone is unlikely to prevent preterm labour (PTL).

Acute cAMP elevation inhibits myometrial contractility, but the mechanisms responsible are not fully elucidated and the long‐term effects are uncertain. Both need to be defined in pregnant human myometrium before the therapeutic potential of cAMP‐elevating agents in the prevention of preterm labour can be realised. In the present study, we tested the hypotheses that PKA activity is necessary for cAMP‐induced myometrial relaxation, and that prolonged cAMP elevation can prevent myometrial contractions. Myometrial tissues obtained from term, pre‐labour elective Caesarean sections were exposed to receptor‐independent cAMP agonists to determine the relationship between myometrial contractility (spontaneous and oxytocin‐induced), PKA activity, HSP20 phosphorylation and expression of contraction‐associated and cAMP signalling proteins. Acute (1 h) application of cAMP agonists promoted myometrial relaxation, but this was weakly related to PKA activation. A PKA‐specific activator, 6‐Bnz‐cAMP, increased PKA activity (6.8 ± 2.0 mean fold versus vehicle; P = 0.0313) without inducing myometrial relaxation. Spontaneous myometrial contractility declined after 24 h but was less marked when tissues were constantly exposed to cAMP agonists, especially for 8‐bromo‐cAMP (4.3 ± 1.2 mean fold versus vehicle; P = 0.0043); this was associated with changes to calponin, cofilin and HSP20 phosphorylated/total protein levels. Oxytocin‐induced contractions were unaffected by pre‐incubation with cAMP agonists despite treatments being able to enhance PKA activity and HSP20 phosphorylation. These data suggest that cAMP‐induced myometrial relaxation is not solely dependent on PKA activity and the ability of cAMP agonists to repress myometrial contractility is lost with prolonged exposure. We conclude that cAMP agonist treatment alone may not prevent preterm labour.
Modifications to Improve Fuel Consumption in the Remanufacture of Spark-Ignition Engines for Electric Generators
Authors: Swain Matthew Neill , Jordan Oliver Patrick , Mackey Travis Jamal , Seemann Patrick Shannon , Samarajeewa Hasitha , Swain Michael Robert
Published: June 2016

This paper describes the development of a water-cooled, lean burn, gaseous fueled engine designed for distributed power installations. Electric generators have become popular because they provide a portable supply of electrical power at consumer demand. They are used in critical need areas such as hospitals and airports, and have found their way into homes frequented with power outages or homes in remote locations. Gensets are available in a wide variety of sizes ranging from 1 kilowatt (kW) to thousands of kilowatts. In the midrange, the power sources are typically spark-ignition, automotive type internal combustion engines. Since engines designed for automotive use are subject to different emission regulations, and are optimized for operation at revolutions per minute (RPM) and brake mean effective pressures (BMEPs) above that of electric generator engines, modifications can be made to optimize them for gensets. This work describes modifications which can be made during remanufacturing an automotive engine to optimize it for use as a generator engine. While the work recognizes the potential for cost savings from the use of remanufactured automotive engines over that of using new automotive engines and the majority of the design constraints were adopted to reduce engine cost, the main focus of the work is quantifying the increase in fuel efficiency that can be achieved while meeting the required EPA emission requirements. This paper describes the seven combustion chamber designs that were developed and tested during this work. Friction reduction was obtained in both valve train and journal bearing design. The engine optimized for fuel efficiency produced a maximum brake thermal efficiency (BTE) of 37.5% with λ = 1.63. This yielded an EPA test cycle average brake specific fuel consumption (BSFC) of 325 g/kW hr. Modification of the spark advance and low load equivalence ratio to meet EPA Phase III emission standards resulted in an EPA test cycle average BSFC of 330 g/kW hr. When the engine used in this research was tested in its unmodified, automotive configuration under the EPA compliant test cycle, its EPA test cycle average BSFC was 443.4 g/kW hr. This is a 34% increase in fuel consumption compared to the modified engine.
Heat Transfer Across Nanoparticle–Liquid Interfaces
Authors: Nair Anjan R. , Sathian Sarith P.
Published: June 2016

A better understanding of submicron-scale heat transfer is rapidly gaining interest due to the complex phenomena involved in nanometer scales. We discuss the role of interfacial resistance, in particular that of curvature effects, and the possibility of achieving high temperatures inside the particles without creating a phase transition in the surrounding fluid. The heat transfer from a heated nanoparticle into surrounding fluid is studied using molecular dynamics (MD) simulations. The results show that the particle size and wetting strength between the nanoparticle–liquid influence the heat transfer characteristics. The interfacial conductance and Kapitza length for a model solid–liquid interface were calculated. Both quantities are found to be strongly dependent on particle size and temperature. Smaller nanoparticles are observed to have a stronger bonding with the interfacial fluid when the temperature of the particle is higher, while larger nanoparticles have better affinity with the liquid at lower temperatures.
Deflection Compensations for Tool Path to Enhance Accuracy During Double-Sided Incremental Forming
Authors: Rakesh Lingam , Amit Srivastava , Reddy N. V.
Published: June 2016

Incremental sheet forming (ISF) is a flexible sheet metal forming process that enables forming of complex three-dimensional components by successive local deformations without using component-specific tooling. ISF is also regarded as a die-less manufacturing process in the absence of part-specific die. Geometric accuracy of formed components is inferior to that of their conventional counterparts. In single-point incremental forming (SPIF), the simplest variant of ISF, bending near component opening region is unavoidable due to lack of support. The bending in the component opening region can be reduced to a larger extent by another variant of ISF, namely, double-sided incremental forming (DSIF) in which a moving tool is used to support the sheet locally at the deformation zone. However, the overall geometry of formed components still has unacceptable deviation from the desired geometry. Experimental observation and literature indicate that the supporting tool loses contact with the sheet after forming certain depth. This work demonstrates a methodology to enhance geometric accuracy of formed components by compensating for tool and sheet deflections due to forming forces. Forming forces necessary to predict compensations are obtained using force equilibrium method along with thickness calculation methodology developed using overlap of deformation zone that occurs during forming (instead of using sine law). A number of examples are presented to show that the proposed methodology works for a variety of geometries (axisymmetric, varying wall angle, free-forms, features above and below initial sheet plane, and multiple features). Results indicate that there is significant improvement in accuracy of the components produced using compensated tool paths using DSIF, and support tool maintains contact with sheet throughout the forming process.
Design and Analysis of Lattice Structures for Additive Manufacturing
Authors: Beyer Christiane , Figueroa Dustin
Published: June 2016

Additive manufacturing (AM) enables time and cost savings in the product development process. It has great potential in the manufacturing of lighter parts or tools by the embedding of cellular/lattice structures that consume less material while still distributing the necessary strength. Less weight and less material consumption can lead to enormous energy and cost savings. Although AM has come a long way over the past 25–30 years since the first technology was invented, the design of parts and tools that capitalize on the technology do not yet encompass its full potential. Designing for AM requires departing from traditional design guidelines and adopting new design considerations and thought structures. Where previous manufacturing techniques (computer numerical control (CNC) machining, casting, etc.) often necessitated solid parts, AM allows for complex parts with cellular and lattice structure implementation. The lattice structure geometry can be manipulated to deliver the level of performance required of the part. The development and research of different cell and lattice structures for lightweight design is of significant interest for realizing the full potential of AM technologies. The research not only includes analysis of existing software tools to design and optimize cell structures, but it also involves design consideration of different unit cell structures. This paper gives a solid foundation of an experimental analysis of additive manufactured parts with diverse unit cell structures in compression and flexural tests. Although the research also includes theoretical finite element analysis (FEA) of the models, the results are not considered here. As an introduction, the paper briefly explains the basics of stress and strain relationship and summarizes the test procedure and methods. The tests concentrate primarily on the analysis of 3D printed polymer parts manufactured using PolyJet technology. The results show the behavior of test specimens with different cell structures under compression and bending load. However, the research has been extended and is still ongoing with an analysis of selective laser melted test specimens in aluminum alloy AlSi10Mg.
von Neumann Stability Analysis of a Segregated Pressure-Based Solution Scheme for One-Dimensional and Two-Dimensional Flow Equations
Authors: Konangi Santosh , Palakurthi Nikhil K. , Ghia Urmila
Published: June 2016

The goal of this paper is to derive the von Neumann stability conditions for the pressure-based solution scheme, semi-implicit method for pressure-linked equations (SIMPLE). The SIMPLE scheme lies at the heart of a class of computational fluid dynamics (CFD) algorithms built into several commercial and open-source CFD software packages. To the best of the authors' knowledge, no readily usable stability guidelines appear to be available for this popularly employed scheme. The Euler equations are examined, as the inclusion of viscosity in the Navier–Stokes (NS) equation serves to only soften the stability limits. First, the one-dimensional (1D) Euler equations are studied, and their stability properties are delineated. Next, a rigorous stability analysis is carried out for the two-dimensional (2D) Euler equations; the analysis of the 2D equations is considerably more challenging as compared to analysis of the 1D form of equations. The Euler equations are discretized using finite differences on a staggered grid, which is used to achieve equivalence to finite-volume discretization. Error amplification matrices are determined from the stability analysis, stable and unstable regimes are identified, and practical stability limits are predicted in terms of the maximum allowable Courant–Friedrichs–Lewy (CFL) number as a function of Mach number. The predictions are verified using the Riemann problem, and very good agreement is obtained between the analytically predicted and the “experimentally” observed CFL values. The successfully tested stability limits are presented in graphical form, as compared to complicated mathematical expressions often reported in published literature. Since our analysis accounts for the solution scheme along with the full system of flow equations, the conditions reported in this paper offer practical value over the conditions that arise from analysis of simplified 1D model equations.
Characterization of Vortex Dynamics in the Near Wake of an Oscillating Flexible Foil
Authors: Siala Firas F. , Totpal Alexander D. , Liburdy James A.
Published: June 2016

An experimental study was conducted to explore the effect of surface flexibility at the leading and trailing edges on the near-wake flow dynamics of a sinusoidal heaving foil. Midspan particle image velocimetry (PIV) measurements were taken in a closed-loop wind tunnel at a Reynolds number of 25,000 and at a range of reduced frequencies (k = fc/U) from 0.09 to 0.20. Time-resolved and phase-locked measurements are used to describe the mean flow characteristics and phase-averaged vortex structures and their evolution. Large-eddy scale (LES) decomposition and swirling strength analysis are used to quantify the vortical structures. The results demonstrate that trailing edge flexibility has minimal influence on the mean flow characteristics. The mean velocity deficit for the flexible trailing edge and rigid foils remains constant for all reduced frequencies tested. However, the trailing edge flexibility increases the swirling strength of the small-scale structures, resulting in enhanced cross-stream dispersion. Flexibility at the leading edge is shown to generate a large-scale leading edge vortex (LEV) for k ≥ 0.18. This results in a reduction in the swirling strength due to vortex interactions when compared to the flexible trailing edge and rigid foils. Furthermore, it is shown that the large-scale LEV is responsible for extracting a significant portion of energy from the mean flow, reducing the mean flow momentum in the wake. The kinetic energy loss in the wake is shown to scale with the energy content of the LEV.
On the accurate determination of absorption coefficient from reflectanceand transmittance measurements: Application to Fe-doped GaN
Authors: Look David C. , Leach Jacob H.
Published: June 2016

For light impinging normally on the surface of a double-side-polished sample of thickness d, the sample's absorption coefficient α can be determined from the well-known formula for fractional transmittance: Tmeas = (1 − R)2exp(−αd)/[1 − R2exp(−2αd)]. Here, R is a fundamental property of the air/sample interface and is known as the “reflectance coefficient.” Often R in this equation is equated to the measured top-surface reflectance Rmeas, but such an approximation can lead to serious error. In fact, the authors explicitly show that Rmeas = R + R(1 − R)2exp(−2αd)/[1 − R2exp(−2αd)] and then further develop an easily solvable transcendental equation that determines both R and α from Tmeas and Rmeas. In strongly absorptive regions (αd ≫ 1), it turns out that R ≈ Rmeas, but in the opposite limit (αd ≪ 1), R ≈ Rmeas/(2 − Rmeas). Formulation by the authors enables accurate determinations of: (1) ε∞, the high-frequency dielectric constant; and (2) relatively weak absorbances, such as those related to defects or impurities with energy levels in the bandgap. The authors also compare the exact calculations of α in semi-insulating GaN:Fe with those obtained from commonly used approximations.
Nearly lattice-matched Zn1-zCdzSe/Zn1-xCdxSe/Zn1-yMgySe (z > x) quantum wells for yellow emission
Authors: Villa-Martínez Gerardo , Banthí-Barcenas Juan Carlos , Bahena Daniel , Sutara Frantisek , Hernández-Calderón Isaac
Published: June 2016

The authors present the results of the modeling and epitaxial growth of a nearly lattice matched Zn1-zCdzSe/Zn1-xCdxSe/Zn1-yMgySe quantum well (QW) heterostructure with yellow emission. The ZnCdSe QW is composed of regions with two different Cd content: in the center, seven monolayers of Zn1-zCdzSe with z Cd content are surrounded on each side by eight Zn1-xCdxSe monolayers with x Cd content (z > x). These last regions are lattice matched to the Zn1-yMgySe barrier. The quantum well design and modeling was based on calculations employing the transfer matrix method. The ZnCdSe quantum well layers were grown in a layer-by-layer mode by submonolayer pulsed beam epitaxy within ZnMgSe barriers grown by molecular beam epitaxy. The low temperature photoluminescence spectrum presented yellow excitonic emission at 2.176 eV, which is in very good agreement with the model calculations. At room temperature, the emission shifted to 2.112 eV, a deep yellow color.