bluuebunny/crossref_metadata_2025 huggingface dataset:
Seeking Humanizing Care in Patient-Centered Care Process
Authors: Cheraghi Mohammad Ali , Esmaeili Maryam , Salsali Mahvash
Published: October 2017

Patient-centered care is both a goal in itself and a tool for enhancing health outcomes. The application of patient-centered care in health care services globally however is diverse. This article reports on a study that sought to introduce patient-centered care. The aim of this study is to explore the process of providing patient-centered care in critical care units. The study used a grounded theory method. Data were collected on 5 critical care units in Tehran University of Medical Sciences. Purposive and theoretical sampling directed the collection of data using 29 semistructured interviews with 27 participants (nurses, patients, and physician). Data obtained were analyzed according to the analysis stages of grounded theory and constant comparison to identify the concepts, context, and process of the study. The core category of this grounded theory is “humanizing care,” which consisted of 4 interrelated phases, including patient acceptance, purposeful patient assessment and identification, understanding patients, and patient empowerment. A core category of humanizing care integrated the theory. Humanizing care was an outcome and process. Patient-centered care is a dynamic and multifaceted process provided according to the nurses' understanding of the concept. Patient-centered care does not involve repeating routine tasks; rather, it requires an all-embracing understanding of the patients and showing respect for their values, needs, and preferences.
HYPERREFLECTIVE DEPOSITION IN THE BACKGROUND OF ADVANCED STARGARDT DISEASE
Authors: Ciccone Lyam , Lee Winston , Zernant Jana , Tanaka Koji , Schuerch Kaspar , Tsang Stephen H. , Allikmets Rando
Published: October 2017

Purpose:

To describe an unusual manifestation of hyperreflective deposits in the subretinal space in a group of patients with clinically and genetically confirmed Stargardt disease.

Methods:

Retrospective review of color fundus, autofluorescence, infrared reflectance, red-free images, and spectral domain optical coherence tomography in 296 clinically diagnosed and genetically confirmed (2 expected disease-causing mutations in ABCA4) patients with Stargardt disease. Full-field electroretinogram (ffERG), medical history, and genotype data (in silico predictions) were further analyzed from the selected cohort.

Results:

Eight of 296 patients (2.7%) were found to exhibit small crystalline deposits that were detectable on certain imaging modalities, such as color, infrared reflectance and red-free images, but not autofluorescence. The deposits were most prevalent in the superior region of the macula, and spectral domain optical coherence tomography revealed their presence in the subretinal space. All patients presented with these findings at a notably advanced disease stage with abnormal ffERG and a high proportion of highly deleterious ABCA4 alleles.

Conclusion:

Hyperreflective subretinal deposits may be a manifestation of advanced ABCA4 disease, particularly in regions susceptible to disease-related changes, such as lipofuscin accumulation.
Surgical Outcomes of Gonioscopy-assisted Transluminal Trabeculotomy (GATT) in Patients With Open-angle Glaucoma
Authors: Rahmatnejad Kamran , Pruzan Noelle L. , Amanullah Sarah , Shaukat Bilal A. , Resende Arthur F. , Waisbourd Michael , Zhan Tingting , Moster Marlene R.
Published: October 2017

Purpose:

To evaluate the efficacy and safety of gonioscopy-assisted transluminal trabeculotomy (GATT) in patients with open-angle glaucoma.

Participants and Methods:

A retrospective chart review of adult patients who underwent GATT due to inadequately controlled intraocular pressure (IOP) or intolerance to medication. Main outcome measures were success rate, IOP, and number of glaucoma medications. Success was defined as IOP reduction >20% from baseline or IOP between 5 to 21 mm Hg, and no need for further glaucoma surgery. When success criteria were not met for any postoperative visit >3 months after surgery, failure was determined.

Results:

In total, 66 patients, average age 62.9±14.9 years (50.8% female) were included in the analysis. Average follow-up was 11.9 months (range, 3 to 30 mo) and overall success rate was 63.0%. Mean IOP was 26.1±9.9 mm Hg preoperatively and 14.6±4.7 mm Hg at 12 months (44% IOP decrease; P<0.001). Mean number of medications decreased from 3.1±1.1 preoperatively to 1.2±0.9 at 12 months (P<0.001). No significant differences between patients with primary open-angle glaucoma and other types of glaucoma were found.

The rate of hyphema at 1 week and 1 month postoperatively was 38% and 6%, respectively. Overall GATT success rate among white and black patients was 69% and 42%, respectively, which was statistically significant (P<0.05).

Conclusions:

The future of GATT as a minimally invasive glaucoma surgery in adults seems promising. This position is supported by its low rate of long-term complications and the conjunctiva-sparing nature of the surgery.
Rapid Deployment Aortic Valves Deliver Superior Hemodynamic Performance in Vitro
Authors: Ai Lisong , Chen Harvey , Lin Virginia , Bapat Vinayak N.
Published: October 2017

Objective

Clinical studies have demonstrated excellent hemodynamic performance of rapid deployment aortic valves; however, few studies have directly compared the performance of these valves with conventional bioprosthetic valves. Thus, the hemodynamic function of the EDWARDS INTUITY valve (rapid deployment valve) was compared with the Edwards Magna Ease valve in vitro (Edwards Lifesciences Corp, Irvine, CA USA).

Methods

Elastomeric material was used to create an aortic root model that included a left ventricular outflow tract and aortic annulus. The model was based on reconstructions from 3-dimensional multislice computed tomography images in patients with aortic stenosis; the aortic root was scaled to a 21-mm effective annulus diameter. EDWARDS INTUITY valves (21-mm diameter) were deployed by stent frame expansion within the aortic root; Edwards Magna Ease valves (21-mm diameter) were sutured to the annulus. The left ventricular outflow tract area index (left ventricular outflow tract area/baseline area) and ellipticity or noncircularity as indexed by Dmax/Dmin were measured under a video microscope after valve placement. Hemodynamic data were collected under pulsatile flow with saline (70 beats per minute, 5 L/min, 100 mm Hg aortic pressure).

Results

Compared with the Edwards Magna Ease valve (n = 4), the EDWARDS INTUITY valve (n = 4) had a greater effective orifice area (1.56 ± 0.01 vs 1.85 ± 0.06 cm2, P < 0.001) and a lower transvalvular pressure gradient (23.4 ± 0.51 vs 16.8 ± 1.3 mm Hg, P < 0.001). Multiple regression analysis showed that 93% of the variation in the effective orifice area and transvalvular pressure gradient was due to variation in the left ventricular outflow tract area index and ellipticity index.

Conclusions

A clinically relevant aortic root model was developed to evaluate aortic valve performance. The superior performance of the EDWARDS INTUITY valve seemed to be related to both a greater inflow area and a more circular left ventricular outflow tract.
The Development of Pulmonary Hypertension Results in Decreased Post-Transplant Survival
Authors: Schumer Erin M. , Gallo Michele , Rogers Michael P. , Trivedi Jaimin R. , Black Matthew C. , Massey H. Todd , Slaughter Mark S.
Published: October 2017

The effects of pulmonary hypertension (PAH) on survival after heart transplantation are debated, especially for patients with left ventricular assist devices (LVAD). The United Network of Organ Sharing database was retrospectively queried from January 2005 to June 2015 to identify adult patients who underwent heart transplantation. Four groups were defined: patients without PAH, persistent PAH, resolved PAH, and developed PAH between listing and transplant. A total of 15,914 patients underwent heart transplant of which 4,662 (29%) were implanted with an LVAD. Of the total population, 10,872 (68%) had PAH at time of listing and 9,661 (61%) had PAH at time of transplant. Long-term survival was significantly worse for patients with an LVAD than for those without who had PAH at time of transplant (p = 0.010). Kaplan–Meier analysis showed a trend of worse long-term survival for patients with an LVAD who developed PAH by the time of transplant but improved survival for patients with resolved PAH while on LVAD therapy (p = 0.052). PAH at time of transplant results in worse long-term survival for patients with an LVAD. Furthermore, the development of PAH while on LVAD therapy may negatively impact long-term post-transplant survival, while resolution of PAH improves long-term survival.
Biomarkers of drug-induced kidney injury
Authors: Redahan Lynn , Murray Patrick T.
Published: October 2017

Purpose of review

Drug-induced kidney injury (DIKI) is an important and potentially modifiable cause of acute kidney injury (AKI). The reliance on traditional markers of kidney injury to diagnose DIKI impedes early detection. Biomarkers of DIKI that facilitate early diagnosis and the identification of high-risk patients are essential to ameliorate the clinical burden of this complication.

Recent findings

Recent progress in this area supports the potential utility of several biomarkers for the diagnosis of DIKI, for the prediction of outcomes and also for monitoring responses to potential nephrotoxic or beneficial therapies. Data regarding the impact of clinically relevant factors, such as chronic kidney disease, on biomarker levels represents a further recent advancement. Emerging novel biomarkers include microRNAs, which are showing promise as markers of drug-induced tubular damage. They may also have a role in elucidating the molecular mechanisms of AKI.

There is compelling evidence to support the use of biomarkers for the early detection of DIKI. Ongoing research is required to delineate their role in prognostication and for the prediction of outcomes. The inclusion of biomarkers in more clinical studies of DIKI would be a welcome advance, which may accelerate their integration into clinical diagnostics.
Exchangeable Zinc Pool Size at Birth in Pakistani Small for Gestational Age and Appropriate for Gestational Age Infants Do Not Differ But Are Lower Than in US Infants
Authors: Ariff Shabina , Krebs Nancy F. , Westcott Jamie E. , Hambidge Michael , Miller Leland V. , Rizvi Arjumand , Soofi Sajid B. , Bhutta Zulfiqar A.
Published: October 2017

Objectives:

Small for gestational age (SGA) infants are more susceptible to infectious morbidity and growth faltering compared to their appropriate for gestational age (AGA) counterparts. Zinc supplementation of SGA infants may be beneficial but the underlying susceptibility to zinc deficiency of SGA infants has not been examined.

Methods:

In a community‐based, observational, longitudinal study in a peri‐urban settlement of Karachi, Pakistan, we compared the size of the exchangeable zinc pools (EZPs) in term SGA and AGA infants at birth and at 6 months of age, hypothesizing that the EZP would be lower in the SGA group. To measure EZP size, a zinc stable isotope was intravenously administered within 48 hours of birth (n = 17 and 22) at 6 months (n = 11 and 14) in SGA and AGA infants, respectively. Isotopic enrichment in urine was used to determine EZP.

Results:

No significant difference was detected in the mean (±standard deviation) EZP between SGA and AGA infants at birth, with values of 9.8 ± 3.5 and 10.1 ± 4.1 mg/kg, respectively (P = 0.86), or at 6 months. Longitudinal EZP measurements demonstrated a significant decline in EZP relative to body weight in both groups at 6 months (P < 0.001). Mean EZP (adjusted for body weight) size at birth for the combined Pakistani groups was significantly lower than AGA infants at birth in the United States (P = 0.017).

Conclusions:

These results did not support a difference in zinc endowment between SGA and AGA Pakistani infants. They, however, do suggest lower in utero zinc transfer to the fetus in a setting where poor maternal nutritional status may confer a high susceptibility to postnatal zinc deficiency.
Psychometric Properties and Factor Structure of a Long and Shortened Version of the Cognitive and Behavioural Responses Questionnaire
Authors: Ryan Elizabeth G. , Vitoratou Silia , Goldsmith Kimberley A. , Chalder Trudie
Published: October 2017

Objective

Symptoms of chronic fatigue syndrome (CFS) can be perpetuated by cognitive and behavioral responses to the illness. We aimed to determine the factor structure, reliability, and validity of the 40-item Cognitive and Behavioural Responses Questionnaire (CBRQ) using data gathered from CFS patients. We also propose a short-version CBRQ for greater clinical utility.

Methods

The psychometric analysis was performed on data sets drawn from two sources: a clinical service for CFS patients (n = 576) and the PACE randomized controlled trial of CFS treatments (n = 640). An exploratory factor analysis was conducted on the clinical data set and a confirmatory factor analysis was performed on the randomized controlled trial data set. Using these results, a short version of the CBRQ was proposed. Reliability, metric invariance across age and sex, and construct validity were assessed.

Results

The exploratory factor analysis (relative χ2 = 2.52, root mean square error of approximation = 0.051, comparative fit index = 0.964, Taylor-Lewis Index = 0.942) and confirmatory factor analysis (relative χ2 = 4.029, root mean square error of approximation = 0.069, comparative fit index = 0.901, Taylor-Lewis Index = 0.892) revealed that eight-factor models fitted the data well. Satisfactory Cronbach's α values were obtained for the final subscales (≥0.76). The shortened CBRQ was obtained by removing items that cross-loaded onto other factors and/or were the lowest loading items in each factor. The shortened CBRQ contained 18 items that had high factor loadings, good face validity, and reliability (Cronbach's α = 0.67–0.88).

Conclusions

The CBRQs, long and short versions, are reliable and valid scales for measuring cognitive and behavioral responses of patients with CFS. Further research is needed to examine the utility of the CBRQ in other long-term conditions.
Multiple interactions are involved in a highly specific association of the Mod(mdg4)-67.2 isoform with the Su(Hw) sites inDrosophila
Authors: Melnikova Larisa , Kostyuchenko Margarita , Molodina Varvara , Parshikov Alexander , Georgiev Pavel , Golovnin Anton
Published: October 2017

The best-studiedDrosophilainsulator complex consists of two BTB-containing proteins, the Mod(mdg4)-67.2 isoform and CP190, which are recruited to the chromatin through interactions with the DNA-binding Su(Hw) protein. It was shown previously that Mod(mdg4)-67.2 is critical for the enhancer-blocking activity of the Su(Hw) insulators and it differs from more than 30 other Mod(mdg4) isoforms by the C-terminal domain required for a specific interaction with Su(Hw) only. The mechanism of the highly specific association between Mod(mdg4)-67.2 and Su(Hw) is not well understood. Therefore, we have performed a detailed analysis of domains involved in the interaction of Mod(mdg4)-67.2 with Su(Hw) and CP190. We found that the N-terminal region of Su(Hw) interacts with the glutamine-rich domain common to all the Mod(mdg4) isoforms. The unique C-terminal part of Mod(mdg4)-67.2 contains the Su(Hw)-interacting domain and the FLYWCH domain that facilitates a specific association between Mod(mdg4)-67.2 and the CP190/Su(Hw) complex. Finally, interaction between the BTB domain of Mod(mdg4)-67.2 and the M domain of CP190 has been demonstrated. By using transgenic lines expressing different protein variants, we have shown that all the newly identified interactions are to a greater or lesser extent redundant, which increases the reliability in the formation of the protein complexes.
Detection of functional protein domains by unbiased genome-wide forward genetic screening
Authors: Herzog Mareike , Puddu Fabio , Coates Julia , Geisler Nicola , Forment Josep V , Jackson Stephen P.
Published: October 2017

Genetic and chemo-genetic interactions have played key roles in elucidating the molecular mechanisms by which certain chemicals perturb cellular functions. Many studies have employed gene knockout collections or gene disruption/depletion strategies to identify routes for evolving resistance to chemical agents. By contrast, searching for point-mutational genetic suppressors that can identify separation- or gain-of-function mutations, has been limited even in simpler, genetically amenable organisms such as yeast, and has not until recently been possible in mammalian cell culture systems. Here, by demonstrating its utility in identifying suppressors of cellular sensitivity to the drugs camptothecin or olaparib, we describe an approach allowing systematic, large-scale detection of spontaneous or chemically-induced suppressor mutations in yeast and in haploid mouse embryonic stem cells in a short timeframe, and with potential applications in essentially any other haploid system. In addition to its utility for molecular biology research, this protocol can be used to identify drug targets and to predict mechanisms leading to drug resistance. Mapping suppressor mutations on the primary sequence or three-dimensional structures of protein suppressor hits provides insights into functionally relevant protein domains, advancing our molecular understanding of protein functions, and potentially helping to improve drug design and applicability.
Development of a novelFrancisella tularensisLive Vaccine Strain expressing ovalbumin provides insight intoFrancisella tularensis-specific CD8+T cell responses
Authors: Place David E. , Williamson David R. , Yuzefpolskiy Yevgeniy , Katkere Bhuvana , Sarkar Surojit , Kalia Vandana , Kirimanjeswara Girish S.
Published: October 2017

Progress towards a safe and effective vaccine for the prevention of tularemia has been hindered by a lack of knowledge regarding the correlates of protective adaptive immunity and a lack of tools to generate this knowledge. CD8+T cells are essential for protective immunity against virulent strains ofFrancisella tularensis, but to-date, it has not been possible to study these cells in a pathogen-specific manner. Here, we report the development of a tool for expression of the model antigen ovalbumin (OVA) inF. tularensis, which allows for the study of CD8+T cell responses to the bacterium. We demonstrate that in response to intranasal infection with theF. tularensisLive Vaccine Strain, pathogen-specific CD8+T cells expand after the first week and produce IFN-γ but not IL-17. Effector and central memory subsets develop with disparate kinetics in the lungs, draining lymph node and spleen. Notably,F. tularensis-specific cells are poorly retained in the lungs after clearance of infection. We also show that intranasal vaccination leads to more pathogen-specific CD8+T cells in the lung-draining lymph node compared to scarification vaccination, but that an intranasal booster overcomes this difference. Together, our data show that this novel tool can be used to study multiple aspects of the CD8+T cell response toF. tularensis. Use of this tool will enhance our understanding of immunity to this deadly pathogen.
Practical computational reproducibility in the life sciences
Authors: Gruning Bjorn , Chilton John , Köster Johannes , Dale Ryan , Goecks Jeremy , Backofen Rolf , Nekrutenko Anton , Taylor James
Published: October 2017

Many areas of research suffer from poor reproducibility. This problem is particularly acute in computationally intensive domains where results rely on a series of complex methodological decisions that are not well captured by traditional publication approaches. Various guidelines have emerged for achieving reproducibility, but practical implementation of these practices remains difficult. This is because reproducing published computational analyses requires installing many software tools plus associated libraries, connecting tools together into the complete pipeline, and specifying parameters. Here we present a suite of recently emerged technologies which make computational reproducibility not just possible, but, finally, practical in both time and effort. By combining a system for building highly portable packages of bioinformatics software, containerization and virtualization technologies for isolating reusable execution environments for these packages, and an integrated workflow system that automatically orchestrates the composition of these packages for entire pipelines, an unprecedented level of computational reproducibility can be achieved.
Compensatory evolution via cryptic genetic variation: Distinct trajectories to phenotypic and fitness recovery
Authors: Chari Sudarshan , Marier Christian , Porter Cody , Northrop Emmalee , Belinky Alexandra , Dworkin Ian
Published: October 2017

Populations are constantly exposed to deleterious alleles, most of which are purged via natural selection. However, deleterious fitness effects of alleles can also be suppressed by compensatory adaptation. Compensatory mutations can act directly to reduce deleterious effects of an allele. Alternatively, compensation may also occur by altering other aspects of an organisms’ phenotype or performance, without suppressing the phenotypic effects of the deleterious allele. Moreover, the origin of allelic variation contributing to compensatory adaptation remains poorly understood. Compensatory evolution driven by mutations that arise during the selective process are well studied. However less is known about the role standing (cryptic) genetic variation plays in compensatory adaptation. To address these questions, we examined evolutionary trajectories of natural populations ofDrosophila melanogasterfixed for mutations that disrupt wing morphology, resulting in deleterious effects on several components of fitness. Lineages subjected only to natural selection, evolved modifications to courtship behavior and several life history traits without compensation in wing morphology. Yet, we observed rapid phenotypic compensation of wing morphology under artificial selection, consistent with segregating variation for compensatory alleles. We show that alleles contributing to compensation of wing morphology have deleterious effects on other fitness components. These results demonstrate the potential for multiple independent avenues for rapid compensatory adaptation from standing genetic variation, which ultimately may reveal novel adaptive trajectories.
Energetic costs, precision, and efficiency of a biological motor in cargo transport
Authors: Hwang Wonseok , Hyeon Changbong
Published: October 2017

Molecular motors play key roles in organizing the interior of cells. An efficient motor in cargo transport would travel with a high speed and a minimal error in transport time (or distance) while consuming minimal amount of energy. The travel distance and its variance of motor are, however, physically constrained by energy consumption, the principle of which has recently been formulated into thethermodynamic uncertainty relation. Here, we reinterpret the uncertainty measure (𝒬) defined in the thermodynamic uncertainty relation such that a motor efficient in cargo transport is characterized with a small 𝒬. Analyses on the motility data from several types of molecular motors show that 𝒬 is a nonmonotic function of ATP concentration and load (f). For kinesin-1, 𝒬 is locally minimized at [ATP] ≈ 200μM andf≈ 4 pN. Remarkably, for the mutant with a longer neck-linker this local minimum vanishes, and the energetic cost to achieve the same precision as the wild-type increases significantly, which underscores the importance of molecular structure in transport properties. For the biological motors studied here, their value of 𝒬 is semi-optimized under the cellular condition ([ATP] ≈ 1 mM,f= 0 − 1 pN). We find that among the motors, kinesin-1 at single molecule level is the most efficient in cargo transport.
Variants in RNA-Seq data show a continued mutation rate during strain preservation ofSchizophyllum commune
Authors: Gehrmann Thies , Pelkmans Jordi F. , Lugones Luis G. , Wösten Han A.B. , Abeel Thomas , Reinders Marcel J.T.
Published: October 2017

Background

Typical microorganism studies link genetic markers to physiological observations, like growth and survival. Experiments are carefully designed, comparing wildtype strains with knockout strains, and replications are conducted to capture biological variation. To maintain monoclonal strains, strain preservation systems are used to keep the number of generations between the primary stock and the experimental measurement low, to decrease the influence of spontaneous mutations on the experimental outcome. The impact of spontaneous mutations during the minimal number of growth cycles for the experimental design is, however, poorly studied.

Results

We set out to characterize the mutation landscape using a transcriptomic dataset ofSchizophyllum commune, a laboratory model for mushroom formation. We designed a methodology to detect SNPs from the RNA-seq data, and found a mutation rate of 1.923 10−8per haploid genome per base per generation, highly similar to the previously described mutation rate ofS. communein the wild. Our results imply that approximately 300 mutations are generated during growth of a colony on an agar plate, of which 5 would introduce stop codons. Knock-outs did not incur an increase of mutations and chromosomal recombination occurring at mating type loci was frequent. We found that missense and nonsense SNPs were selected against throughout the experiment. Also, most mutations show a low variant allele frequency and appear only in a small part of the population. Yet, we found 40 genes that gained a nonsense mutation affecting one of its annotated protein domains, and more than 400 genes having a missense mutation inside an annotated protein domain. Further, we found transcription factors, metabolic genes and cazymes having gained a mutation. Hence, the mutation landscape is wide-spread and has many functional annotations.

Conclusions

We have shown that spontaneous mutations accumulate in typical microorganism experiments, where one usually assumes that these do not happen. As these mutations possibly confound experiments they should be minimized as much as possible, or, at least, be trackable. Therefore, we recommend labs to ensure that biological replicates originate from different parental plates, as much as possible.
Bayesian Optimisation for Neuroimaging Pre-processing in Brain Age Prediction
Authors: Lancaster Jenessa , Lorenz Romy , Leech Rob , Cole James H
Published: October 2017

Neuroimaging-based age predictions using machine learning have been shown to relate to cognitive performance, health outcomes and progression of neurodegenerative disease. However, even leading age-prediction algorithms contain measurement error, motivating efforts to improve experimental pipelines. T1-weighted MRI is commonly used for age prediction, and the pre-processing of these scans involves normalisation to a common template and resampling to a common voxel size, followed by spatial smoothing. Resampling parameters are often selected arbitrarily. Here, we sought to improve brain-age prediction accuracy by optimising resampling parameters using Bayesian optimisation.

Using data on N=2001 healthy individuals (aged 16-90 years) we trained support vector machines to i) distinguish between young (<50 years) and old (>50 years) brains and ii) predict chronological age, with accuracy assessed using cross-validation. We also evaluated model generalisability to the Cam-CAN dataset (N=648, aged 18-88 years). Bayesian optimisation was used to identify optimal voxel size and smoothing kernel size for each task. This procedure adaptively samples the parameter space to evaluate accuracy across a range of possible parameters, using independent sub-samples to iteratively assess different parameter combinations to arrive at optimal values.

When distinguishing between young and old brains a classification accuracy of 96.25% was achieved, with voxel size = 11.5mm3and smoothing kernel = 2.3mm. For predicting chronological age, a mean absolute error (MAE) of 5.08 years was achieved, with voxel size = 3.73mm3and smoothing kernel = 3.68mm. This was compared to performance using default values of 1.5mm3and 4mm respectively, which gave a MAE = 5.48 years, a 7.3% improvement. When assessing generalisability, best performance was achieved when applying the entire Bayesian optimisation framework to the new dataset, out-performing the parameters optimised for the initial training dataset.

Our study demonstrates the proof-of-principle that neuroimaging models for brain age prediction can be improved by using Bayesian optimisation to select more appropriate pre-processing parameters. Our results suggest that different parameters are selected and performance improves when optimisation is conducted in specific contexts. This motivates use of optimisation techniques at many different points during the experimental process, which may result in improved statistical sensitivity and reduce opportunities for experimenter-led bias.
Specific cardiolipin-SecY interactions are required for proton-motive-force stimulation of protein secretion
Authors: Corey Robin A. , Pyle Euan , Allen William J. , Casiraghi Marina , Miroux Bruno , Arechaga Ignacio , Politis Argyris , Collinson Ian
Published: October 2017

The transport of proteins across or into membranes is a vital biological process, achieved in every cell by the conserved Sec machinery. In bacteria, SecYEG combines with the SecA motor protein for secretion of pre-proteins across the plasma membrane, powered by ATP hydrolysis and the trans-membrane proton-motive-force (PMF). The activities of SecYEG and SecA are modulated by membrane lipids, particularly by cardiolipin, a specialised phospholipid known to associate with a range of energy-transducing machines. Here, we identify two specific cardiolipin binding sites on theThermotoga maritimaSecA-SecYEG complex, through application of coarse-grained molecular dynamics simulations. We validate the computational data and demonstrate the conserved nature of the binding sites usingin vitromutagenesis, native mass spectrometry and biochemical analysis ofEscherichia coliSecYEG. The results show that the two sites account for the preponderance of functional cardiolipin binding to SecYEG, and mediate its roles in ATPase and protein transport activity. In addition, we demonstrate an important role for cardiolipin in the conferral of PMF-stimulation of protein transport. The apparent transient nature of the CL interaction might facilitate proton exchange with the Sec machinery and thereby stimulate protein transport, by an as yet unknown mechanism. This study demonstrates the power of coupling the high predictive ability of coarse-grained simulation with experimental analyses, towards investigation of both the nature and functional implications of protein-lipid interactions.

Significance Statement

Many proteins are located in lipid membranes surrounding cells and cellular organelles. The membrane can impart important structural and functional effects on the protein, making understanding of this interaction critical. Here, we apply computational simulation to the identification of conserved lipid binding sites on an important highly conserved bacterial membrane protein, the Sec translocase (SecA-SecYEG), which uses ATP and the proton motive force (PMF) to secrete proteins across the bacterial plasma membrane. We experimentally validate and reveal the conserved nature of these binding sites, and use functional analyses to investigate the biological significance of this interaction. We demonstrate that these interactions are specific, transient, and critical for both ATP- and PMF- driven protein secretion.
Ki-67 and condensins support the integrity of mitotic chromosomes through distinct mechanisms
Authors: Takagi Masatoshi , Ono Takao , Natsume Toyoaki , Sakamoto Chiyomi , Nakao Mitsuyoshi , Saitoh Noriko , Kanemaki Masato T. , Hirano Tatsuya , Imamoto Naoko
Published: October 2017

Although condensins play essential roles in mitotic chromosome assembly, Ki-67, a protein localizing to the periphery of mitotic chromosomes, had also been shown to make a contribution to the process. To examine their respective roles, we generated a set of HCT116-based cell lines expressing Ki-67 and/or condensin subunits that were fused with an auxin-inducible degron for their conditional degradation. Both the localization and the dynamic behavior of Ki-67 on mitotic chromosomes were not largely affected upon depletion of condensin subunits, and vice versa. When both Ki-67 and SMC2 (a core subunit of condensins) were depleted, ball-like chromosome clusters with no sign of discernible thread-like structures were observed. This severe defective phenotype was distinct from that observed in cells depleted of either Ki-67 or SMC2 alone. Our results show that Ki-67 and condensins, which localize to the external surface and the central axis of mitotic chromosomes, respectively, have independent yet cooperative functions in supporting the structural integrity of mitotic chromosomes.

List of Abbreviations used

AID

auxin-inducible degron

DOX

doxycycline

FRAP

fluorescence recovery after photobleaching

IAA

indol-3-acetic acid

mACl

mAID-mClover

mACh

mAID-mCherry

NEBD

nuclear envelope breakdown

SMC

structural maintenance of chromosomes

STLC

S-Trityl-L-cysteine

topo IIα

topoisomerase IIα
Inverse pole figure mapping of bulk crystalline grains in a polycrystalline steel plate by pulsed neutron Bragg-dip transmission imaging
Authors: Sato Hirotaka , Shiota Yoshinori , Morooka Satoshi , Todaka Yoshikazu , Adachi Nozomu , Sadamatsu Sunao , Oikawa Kenichi , Harada Masahide , Zhang Shuoyuan , Su Yuhua , Kamiyama Takashi , Ohnuma Masato , Furusaka Michihiro , Shinohara Takenao , Kiyanagi Yoshiaki
Published: October 2017

A new mapping procedure for polycrystals using neutron Bragg-dip transmission is presented. This is expected to be useful as a new materials characterization tool which can simultaneously map the crystallographic direction of grains parallel to the incident beam. The method potentially has a higher spatial resolution than neutron diffraction imaging. As a demonstration, a Bragg-dip neutron transmission experiment was conducted at J-PARC on beamline MLF BL10 NOBORU. A large-grained Si–steel plate was used. Since this specimen included multiple grains along the neutron beam transmission path, it was a challenging task for existing methods to analyse the direction of the crystal lattice of each grain. A new data-analysis method for Bragg-dip transmission measurements was developed based on database matching. As a result, the number of grains and their crystallographic direction along the neutron transmission path have been determined.
Stoichiometric and polymorphic salts of hexamethylenetetraminium and 2-chloro-4-nitrobenzoate
Authors: Lemmerer Andreas , Motlaung Xolani
Published: October 2017

Four molecular salts made from hexamethylenetetraminium and 2-chloro-4-nitrobenzoate have been synthesized and are reported, namely ammonium hexamethylenetetraminium bis(2-chloro-4-nitrobenzoate), NH4+·C6H13N4+·2C7H3ClNO4−, (I), hexamethylenetetraminium hydrogen bis(2-chloro-4-nitrobenzoate), 0.5C6H13N4+·C7H3.50ClNO4−, (II), hexamethylenetetraminium 2-chloro-4-nitrobenzoate, C6H13N4+·C7H3ClNO4−, (IIIa) and (IIIb). All four molecular salts show N+—H...O−hydrogen bonding. Salt (I) crystallized out with an NH4+counter-ion which came from decomposition of 50% of the hexamethylenetetraminium cation in solution. (II) shows an unusual asymmetric unit, with both a hexamethylenetetraminium cation and a partially deprotonated 2-chloro-4-nitrobenzoate anion. Salts (IIIa) and (IIIb) are polymorphs of each other. This work shows that hexamethylenetetramine only protonates once, even in the presence of excess acid.
Crystal structures and Hirshfeld surfaces of differently substituted (E)-N′-benzylidene-N-methyl-2-(thiophen-2-yl)acetohydrazides
Authors: Cardoso Laura N. F. , Noguiera Thais C. M. , Kaiser Carlos R. , Wardell James L. , Souza Marcus V. N. de , Harrison William T. A.
Published: October 2017

The syntheses and crystal structures of (E)-N′-(3-cyanobenzylidene)-N-methyl-2-(thiophen-2-yl)acetohydrazide, C15H13N3OS, (I), and (E)-N′-(4-methoxybenzylidene)-N-methyl-2-(thiophen-2-yl)acetohydrazide, C15H16N2O2S, (II), with different substituents in themetaandparaposition of the benzene ring are described. Compounds (I) and (II) both crystallize with two molecules in the asymmetric unit, with generally similar conformations [r.m.s. overlay fits for (I) and (II) of 0.334 and 0.280 Å, respectively] that approximate to L-shapes. The thiophene rings in (I) are well ordered, whereas those in (II) exhibit `flip' rotational disorder [occupancies 0.662 (2) and 0.338 (2) for molecule 1, and 0.549 (3) and 0.451 (3) for molecule 2]. The packing for (I) features short C—H...O interactions arising from the C—H grouping adjacent to the cyanide group and C—H...Nc(c = cyanide) links arising from the methine groups to generate [110] double chains. Weak C—H...π interactions interlink the chains into a three-dimensional network. The packing for (II) features numerous C—H...O and C—H...π interactions arising from different donor groups to generate a three-dimensional network. Hirshfeld fingerprint plots indicate significant differences in the percentage contact surfaces for (I) and (II).
Application of grey systems in predicting the degree of cotton spider mite infestations
Authors: Wang Shouhui , Dai Jianguo , Zhao Qingzhan , Cui Meina
Published: October 2017

Purpose

Many factors affect the emergence and development of crop diseases and insect pests. Traditional methods for investigating this subject are often difficult to employ and produce limited data with considerable uncertainty. The purpose of this paper is to predict the annual degree of cotton spider mite infestations by employing grey theory.

Design/methodology/approach

The authors established a GM(1,1) model to forecast mite infestation degree based on the analysis of historical data. To improve the prediction accuracy, the authors modified the grey model using Markov chain and BP neural network analyses. The prediction accuracy of the GM(1,1), Grey-Markov chain, and Grey-BP neural network models was 84.31, 94.76, and 96.84 per cent, respectively.

Findings

Compared with the single grey forecast model, both the Grey-Markov chain model and the Grey-BP neural network model had higher forecast accuracy, and the accuracy of the latter was highest. The improved grey model can be used to predict the degree of cotton spider mite infestations with high accuracy and overcomes the shortcomings of traditional forecasting methods.

Practical implications

The two new models were used to estimate mite infestation degree in 2015 and 2016. The Grey-Markov chain model yielded respective values of 1.27 and 1.15, whereas the Grey-BP neural network model yielded values 1.4 and 1.68; the actual values were 1.5 and 1.8.

Originality/value

The improved grey model can be used for medium- and long-term predictions of the occurrence of cotton spider mites and overcomes problems caused by data singularity and fluctuation. This research method can provide a reference for the prediction of similar diseases.
Research on an exponential distribution reliability function model based on multi-source heterogeneous data supplements
Authors: Shao Heng , Fang Zhigeng , Zhang Qin , Hu Qian , Cai Jiajia , Tao Liangyan
Published: October 2017

Purpose

As productions show characteristics of multi-varieties and small batch in a recent new product system, it is more difficult to acquire its failure rate data. With the help of expert experience information, the authors can get the interval estimation of failure rate data under different methods, so how to make the interval convergence with the new information is an important problem to be solved. The paper aims to discuss this issue.

Design/methodology/approach

In this paper, the concept of generalized standard grey number is used to characterize the multi-source heterogeneous uncertainty failure rate data into a unified framework. Then, the engineering construction method is used to calculate the average failure rate and build the grey exponential distribution reliability function, whose image is presented as the possible region of the two-curve envelope.

Findings

Further, according to the normal distribution assumption of the regional convergence based on the information supplement, the convergence problem of the reliability function is transformed into the convergence of the area of the curve envelope region, and construct the multi-objective programming model with the minimum envelope area and the lowest total cost of information acquisition, acquire the conclusion that the failure rate is equal to the nuclear of the average failure rate when the envelope region converges.

Originality/value

Through the case analysis of the equipment ejection system of the Harbinger system, five groups of results are obtained by Matlab simulation, which verify the rationality and feasibility of the model described in this paper.
Beginning teachers’ perceptions of mentors and access to communities of practice
Authors: Shields Samantha , Murray Megan
Published: October 2017

Purpose

The purpose of this paper is to explore beginning teachers’ perceptions of the role of the mentor in the early stages of developing a professional identity. The beginning teachers in the authors’ study are defined as having been awarded qualified teacher status at the end of an initial teacher education programme or having completed their first term as a new teacher with responsibility for a class of pupils.

Design/methodology/approach

The research design was a qualitative, inductive study. The concepts of communities of practice, legitimate peripheral participation and power dynamics within a community underpinned this study. The data set was collected over a period of 18 months, through six focus groups and 40 questionnaires with beginning teachers across 34 schools altogether. The data set was analysed using interpretive phenomenological analysis (IPA).

Findings

The findings indicated that the ways in which mentors use their power to recognise (or not) the legitimacy of beginning teachers as being part of the school community influences the development of beginning teachers’ professional identities. The thematic analysis of the data indicated the different types of support that mentors may provide: “belonging”, “emotional”, “pedagogical” and “space”.

Research limitations/implications

Further research into how mentors perceive their role in supporting new entrants into the profession is needed.

Originality/value

These findings are pertinent in England, as the increase in school-based initial teacher training provision will intensify the role of school mentors. These findings will be of value to other countries that are moving towards an increase in school-based teacher training.
The effect of round corner on lubrication of high speed cylindrical roller bearings considering skidding
Authors: Cao Wei , Wang Jiaxu , Pu Wei , Zhang Ying , Wu Jiqiang , Ren Si , Long Jianbing
Published: October 2017

Purpose

Previous studies were mainly focused on profile designation of bearing rollers and lubrication performance without considering roller-races skidding. However, the width of round corner, load, rotational speed and some other parameters have significant effects on the roller-races sliding speed. This paper aims to investigate the effect of round corner on lubricating characteristics between the heavily loaded roller and inner race considering skidding and roughness.

Design/methodology/approach

A mixed elastohydrodynamic lubrication (EHL) model which is capable of handling practical cases with 3D machined roughness is combined with the skidding model to investigate the effect of round corner on lubricating characteristics between the heavily loaded roller and inner race.

Findings

The width of round corner and round corner radius have a desirable range under certain operating condition, within which the maximum pressure, stress and maximum flash temperature remain low. The optimized range is sensitive to the operating condition. Roughness and skidding narrow the optimized range of round corner radius. Roughness increases the pressure peak, Mises stress and friction coefficient. At the same time, skidding and roughness have obvious effects on film thickness at the contact center area if the round radius is small.

Research limitations/implications

This paper uses the Harris skidding model that has a relatively bigger error, which is not accurate if the bearing load is less.

Practical implications

This paper unifies the skidding model and mixed EHL model which can be used as a tool for optimization design and lubricating performance analysis of cylindrical roller bearing.

Originality/value

Lubrication analyses for roller bearing are assumed to be pure rolling contact between roller and races in a previous study, which could not reflect the real contact characteristics. The skidding model is merged into a mixed EHL model which can be used as a dynamic tool to analyze the lubricating performance considering the round corner, skidding and roughness.
Investigation of slip/no-slip surface for two-dimensional large tilting pad thrust bearing
Authors: Song Zhixiang , Guo Fei , Liu Ying , Hu Songtao , Liu Xiangfeng , Wang Yuming
Published: October 2017

Purpose

This paper aims to present the slip/no-slip design in two-dimensional water-lubricated tilting pad thrust bearings (TPTBs) considering the turbulence effect and shifting of pressure centers.

Design/methodology/approach

A numerical model is established to analyze the slip condition and the effect of turbulence according to a Reynolds number defined in terms of the slip condition. Simulations are carried out for eccentrically and centrally pivoted bearings and the influence of different slip parameters is discussed.

Findings

A considerable enhancement in load capacity, as well as a reduction in friction, can be achieved by heterogeneous slip/no-slip surface designs for lubricated sliding contacts, especially for near parallel pad configurations. The optimized design largely depends on the pivot position. The load capacity increases by 174 per cent for eccentrically pivoted bearings and 159 per cent for centrally pivoted bearings for a suitable design. When slip zone locates at the middle of the radial direction or close to the inner edge, the performance of the TPTB is better.

Research limitations/implications

The simplification of slip effect on the turbulence (definition of Reynolds number) can only describe the trend of the increasing turbulence due to slip condition. The accurate turbulence expression considering the boundary slip needs further explorations.

Originality/value

The shifting of pressure center due to the slip/no-slip design for TPTBs is investigated in this study. The turbulence effect and influence of slip parameters is discussed for large water-lubricated bearings.