bluuebunny/crossref_metadata_2025 huggingface dataset:
Design and optimization of a novel 3D detector: The 3D-open-shell-electrode detector
Authors: Liu Manwen , Tan Jian , Li Zheng
Published: April 2018

A new type of three-dimensional (3D) detector, namely 3D-Open-Shell-Electrode Detector (3DOSED), is proposed in this study. In a 3DOSED, the trench electrode can be etched all the way through the detector thickness, totally eliminating the low electric field region existed in the conventional 3D-Trench-Electrode detector. Full 3D technology computer-aided design (TCAD) simulations have been done on this novel silicon detector structure. Through comparing of the simulation results of the detector, we can obtain the best design of the 3SOSED. In addition, simulation results show that, as compared to the conventional 3D detector, the proposed 3DOSED can improve not only detector charge collection efficiency but also its radiation hardness with regard to solving the trapping problem in the detector bulk. What is more, it has been shown that detector full depletion voltage is also slightly reduced, which can improve the utility aspects of the detector. When compared to the conventional 3D detector, we find that the proposed novel 3DOSED structure has better electric potential and electric field distributions, and better electrical properties such as detector full depletion voltage. In 3DOSED array, each pixel cell is isolated from each other by highly doped trenches, but also electrically and physically connected with each other through the remaining silicon bulk between broken electrodes.
Phase-field modelling on effect of pressure on growth kinetics of Mg–Al–Sn alloy
Authors: Shang Shan , Han Zhiqiang , Luo Alan A.
Published: April 2018

The effects of pressure on dendritic growth kinetics of Mg–Al–Sn alloy were investigated using a ternary phase-field model coupled with thermodynamics with pressure effects and experiments. The results showed that the improved growth velocity and nucleation rate caused by pressure had the opposite effects on grain size. For one-grain growth, the dendrite was larger and more developed under pressure of 85 MPa than that under ambient pressure owing to larger thermodynamic driving force, and thus higher growth velocity. However, when nucleation was considered in multigrain growth case, the average grain size under pressure was smaller owing to less growth space. Growth velocity decreased with the increase in Sn content, on which pressure had no great influence.
Stranski–Krastanov growth of (Si)Ge/Si(001): Transmission electron microscopy compared with segregation theory
Authors: Norris D. J. , Walther T.
Published: April 2018

We performed transmission electron microscopy of SiGe/Si(001) and Ge/Si(001) samples that undergo the Stranski–Krastanov transition from flat layer to island growth. With the help of quantitative X-ray maps of those layers, we have determined the total amount of deposited germanium at which islanding commences. The maximum amount of Ge buried in a flat layer amounts to 2.3 monolayers. We show by modelling that it is the strain due to the total amount of Ge atoms deposited that drives the islanding process. At 600°C [400°C], 1.62 [1.74] monolayers of Ge are expected from simulations to segregate towards the surface, the strain of which is sufficient to trigger plastic relaxation by islanding, in agreement with our electron microscope observations.

This is part of a thematic issue on Nanoscale Materials Characterisation and Modeling by Advances Microscopy Methods - EUROMAT.
The latent geometry of the human protein interaction network
Authors: Alanis-Lobato Gregorio , Mier Pablo , Andrade-Navarro Miguel
Published: April 2018

Motivation

A series of recently introduced algorithms and models advocates for the existence of a hyperbolic geometry underlying the network representation of complex systems. Since the human protein interaction network (hPIN) has a complex architecture, we hypothesized that uncovering its latent geometry could ease challenging problems in systems biology, translating them into measuring distances between proteins.

Results

We embedded the hPIN to hyperbolic space and found that the inferred coordinates of nodes capture biologically relevant features, like protein age, function and cellular localization. This means that the representation of the hPIN in the two-dimensional hyperbolic plane offers a novel and informative way to visualize proteins and their interactions. We then used these coordinates to compute hyperbolic distances between proteins, which served as likelihood scores for the prediction of plausible protein interactions. Finally, we observed that proteins can efficiently communicate with each other via a greedy routing process, guided by the latent geometry of the hPIN. We show that these efficient communication channels can be used to determine the core members of signal transduction pathways and to study how system perturbations impact their efficiency.

Availability and implementation

An R implementation of our network embedder is available at https://github.com/galanisl/NetHypGeom. Also, a web tool for the geometric analysis of the hPIN accompanies this text at http://cbdm-01.zdv.uni-mainz.de/~galanisl/gapi.

Supplementary information

Supplementary data are available at Bioinformatics online.
Possible Neurobiological Underpinnings of Homosexuality and Gender Dysphoria
Authors: Manzouri A , Savic I
Published: April 2018

Although frequently discussed in terms of sex dimorphism, the neurobiology of sexual orientation and identity is unknown. We report multimodal magnetic resonance imaging data, including cortical thickness (Cth), subcortical volumes, and resting state functional magnetic resonance imaging, from 27 transgender women (TrW), 40 transgender men (TrM), and 80 heterosexual (40 men) and 60 homosexual cisgender controls (30 men). These data show that whereas homosexuality is linked to cerebral sex dimorphism, gender dysphoria primarily involves cerebral networks mediating self–body perception. Among the homosexual cisgender controls, weaker sex dimorphism was found in white matter connections and a partly reversed sex dimorphism in Cth. Similar patterns were detected in transgender persons compared with heterosexual cisgender controls, but the significant clusters disappeared when adding homosexual controls, and correcting for sexual orientation. Instead, both TrW and TrM displayed singular features, showing greater Cth as well as weaker structural and functional connections in the anterior cingulate-precuneus and right occipito-parietal cortex, regions known to process own body perception in the context of self.
Understanding the research landscape of major depressive disorder via literature mining: an entity-level analysis of PubMed data from 1948 to 2017
Authors: Zhu Yongjun , Kim Min-Hyung , Banerjee Samprit , Deferio Joseph , Alexopoulos George S , Pathak Jyotishman
Published: April 2018

Objective

To analyze literature-based data from PubMed to identify diseases and medications that have frequently been studied with major depressive disorder (MDD).

Materials and methods

Abstracts of 23 799 research articles about MDD that have been published since 1948 till 2017 were analyzed using data and text mining approaches. Methods such as information extraction, frequent pattern mining, regression, and burst detection were used to explore diseases and medications that have been associated with MDD.

Results

In addition to many mental disorders and antidepressants, we identified several nonmental health diseases and nonpsychotropic medications that have frequently been studied with MDD. Our results suggest that: (1) MDD has been studied with disorders such as Pain, Diabetes Mellitus, Wounds and Injuries, Hypertension, and Cardiovascular Diseases; (2) medications such as Hydrocortisone, Dexamethasone, Ketamine, and Lithium have been studied in terms of their side effects and off-label uses; (3) the relationships between nonmental disorders and MDD have gained increased attention from the scientific community; and (4) the bursts of Diabetes Mellitus and Cardiovascular Diseases explain the psychiatric and/or depression screening recommended by authoritative associations during the periods of the bursts.

Discussion and conclusion

This study summarized and presented an overview of the previous MDD research in terms of diseases and medications that are highly relevant to MDD. The reported results can potentially facilitate hypothesis generation for future studies. The approaches proposed in the study can be used to better understand the progress and advance of the field.
Outcomes of 40 Nonsyndromic Sagittal Craniosynostosis Patients as Adults: A Case-Control Study With 26 Years of Postoperative Follow-up
Authors: Salokorpi Niina , Savolainen Tuula , Sinikumpu Juha-Jaakko , Ylikontiola Leena , Sándor George K , Pirttiniemi Pertti , Serlo Willy
Published: April 2018

BACKGROUND

While sagittal synostosis is the most common craniosynostosis, long-term follow-up of these patients is lacking.

OBJECTIVE

To evaluate the results of surgical management of those patients with sagittal synostosis who attain adulthood.

METHODS

An outcome study of surgically treated isolated sagittal synostosis patients operated between 1977 and 1998 was conducted at the Craniofacial Center of Oulu University Hospital, Oulu, Finland with an average follow-up time of 26.5 yr. Patients’ socioeconomic situation, satisfaction with their own facial appearance and attractiveness as rated by 2 independent panels was evaluated and compared to controls.

RESULTS

The self-satisfaction with the patients’ own appearance scored a mean of 75 mm on a visual analog scale of 100 mm between the patients and 76 mm with the control group. The subjective satisfaction of the patients with their own appearance failed to correlate with the rating of their appearance by the panels. The panels rated the patients’ appearance to be on average 6 to 7 mm out of 100 mm visual analog scale less attractive than the controls. Data on socioeconomic situation, including marital status, housing, education, employment of the patients, and controls are presented.

CONCLUSION

Isolated sagittal synostosis patients treated surgically were as happy with their facial appearance as were individuals in an age and gender-matched control group. Two independent panels found the patients’ appearance to be only somewhat less attractive. Analysis of the socioeconomic situation and general health revealed that patients equaled that of controls.
Occipital Artery to Posterior Cerebral Artery Bypass Using Descending Branch of the Lateral Circumflex Femoral Artery Graft for Treatment of Fusiform, Unruptured Posterior Cerebral Artery Aneurysm: 3-Dimensional Operative Video
Authors: Ravina Kristine , Buchanan Ian A , Rennert Robert C , Strickland Ben A , Carey Joseph N , Russin Jonathan J
Published: April 2018

Posterior cerebral artery (PCA) aneurysms can be technically challenging lesions due to the intricacy of perforating branches and the relationship to cranial nerves and the brainstem. Fusiform aneurysms of the perimesencephalic segment of the PCA are a rare finding which does not favor direct clip occlusion or reconstruction. In such cases, proximal parent vessel occlusion is an option for aneurysm treatment. Extracranial-intracranial (EC-IC) bypass can be used to revascularize beyond the lesion when considering proximal occlusion. Based on previous literature for occipital artery (OA) bypass and the time-consuming dissection required for OA harvest, an interposition graft was chosen. The descending branch of the lateral circumflex femoral artery (DLCFA) is a good alternative interposition graft with a diameter that is favorable for revascularizing smaller, more distal vessels.

This 3-dimensional video presents the case of a 26-year-old female with severe headaches who was found to have unruptured, fusiform aneurysmal dilatations of the PCA. Given the patient's youth and the morphology of the aneurysms, an EC-IC bypass with proximal occlusion was recommended. The DLCFA was used as an interposition graft. The left OA was found to be a suitable donor. A subtemporal approach was used to access the PCA for proximal occlusion. An occipital interhemispheric approach was performed to isolate a suitable recipient segment of the ipsilateral PCA branch for microvascular end-to-side anastomosis. Postoperative catheter angiography showed significant thrombosis of the fusiform aneurysms and a patent EC-IC bypass. Postoperative magnetic resonance imaging showed no infarcts and the patient was discharged neurologically intact.

The patient was consented for inclusion in a prospective institutional review board (IRB) approved database from which this IRB approved retrospective report was performed. The consent for intraoperative video and picture use was also obtained.

Images in the video between 0:49 and 1:11, © University of Southern California Neurorestoration Center. Used with permission, all rights reserved.
Medical Care Costs Were Similar Across the Low-dose Computed Tomography and Chest X-Ray Arms of the National Lung Screening Trial Despite Different Rates of Significant Incidental Findings
Authors: Gareen Ilana F. , Black William C. , Tosteson Tor D. , Wang Qianfei , Sicks JoRean D. , Tosteson Anna N.A.
Published: April 2018

Background:

The National Lung Screening Trial (NLST) reported lung cancer and all-cause mortality reductions for low-dose computed tomography (LDCT) versus chest x-ray (CXR) screening. Although LDCT lung screening has received a grade B from the United States Preventive Services Task Force and is a covered service under most health plans, concerns remain on the costs engendered by screening, and the impact of the high rate of significant incidental finding (SIF) detection on those costs.

Methods:

We linked American College of Radiology Imaging Network NLST and Medicare fee-for-service claims data for participants from 23 sites for 2002–2009. We performed participant-level analyses using generalized linear regression models to estimate the adjusted annual mean of the 3-year total medical costs per person in each study arm and within screen outcome categories (ever positive with abnormalities suspicious for lung cancer, always negative for abnormalities suspicious for lung cancer, but with SIFs, and always negative without SIFs).

Results:

The adjusted annual mean total per person costs were not significantly different between screening arms [LDCT, $11,029 (95% confidence interval, $10,107–$11,951); CXR, $10,905 (95% confidence interval, $10,059–$11,751)], despite higher proportions of individuals with SIFs in the LDCT versus the CXR arm (18% vs. 4%; P<0.0001).

Conclusions:

We found little difference in total annual per person costs between LDCT-screened and CXR-screened Medicare participants, despite the higher number of SIFs in the LDCT arm of the study.
Pulmonary Function Tests Abnormalities in Children With Inflammatory Bowel Disease
Authors: El Amrousy Doaa Mohamed , Hassan Samir , El‐Ashry Heba , Yousef Mohamed , Sharshar Ragia
Published: April 2018

Objective:

The aim of the study was to evaluate the frequency and type of pulmonary dysfunction in newly diagnosed children with inflammatory bowel disease (IBD) and the correlation between pulmonary function tests (PFTs) and IBD activity.

Methods:

It is an observational case‐control study. One hundred newly diagnosed children with IBD were enrolled as the patient group, which was further subdivided into 52 with Crohn disease (CD) and 48 with ulcerative colitis (UC). Fifty healthy children matched for age, sex, height, and body mass index (BMI) served as the control group. PFTs in the form of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/FVC, residual volume (RV), total lung capacity (TLC), mid‐forced expiratory flow of 25% to 75% (FEF 25%–75%) and diffusing capacity of the lung for carbon monoxide (DLCO) were evaluated in all studied children. PFTs were measured at diagnosis, every 6 months for a period of 3 years, during remission and at least once during activity in patient group.

Results:

There was significant progressive deterioration in all PFTs in IBD patients compared with their PFTs at the start of the study (P < 0.05) except for FEV1/FVC, RV, and TLC (P > 0.05). There was significant deterioration during disease activity compared with remission state as regards FEV1, FVC, FEF 25% to 75%, and DLCO (P < 0.05). Significant negative correlation was found between disease activity in both UC and CD groups and FEV1, FVC, FEF 25% to 75%, and DLCO.

Conclusions:

Subclinical PFTs abnormalities are common in pediatric IBD even during remission period. So, periodic PFTs evaluation should be considered in the routine follow‐up of IBD children.
Pediatric Liver Transplant Teams Coping With Patient Death
Authors: Duncan Sarah E. , Arnon Ronen , DiPietrantonio Christie , Ehrlich Katie , Knight Christopher S. , Chu Jaime , Annunziato Rachel A.
Published: April 2018

Objectives:

Coping with patient death among pediatric liver transplant teams has received little attention despite general recognition of the potentially negative emotional consequences associated with such loss. The purpose of this study was to investigate the ways in which members of pediatric liver transplant teams cope with the death of patients on the waitlist and post‐transplant and the institutional resources available to facilitate this coping.

Methods:

Participants included 120 physicians, nurses, and mental health professionals from multiple transplant centers across the United States. Participants completed an online questionnaire that assessed the availability of formal coping resources at their institutions, informal sources of support used to cope with patient death, and as indices of coping, bereavement, and emotional exhaustion symptoms experienced.

Results:

Debriefing, the most commonly offered support, was available to about half (55.8%) of the sample; yet, nearly all respondents (98.3%) indicated that debriefing would be useful. On average, bereavement and emotional exhaustion levels were comparable to normative data, but patterns of coping varied based on participants’ position within the transplant team. For participants who reported that debriefing was available at their institutions, emotional exhaustion was lower.

Conclusions:

Overall, formal supports were inconsistently offered to pediatric transplant team members. Team members expressed high acceptability for debriefing, which has been associated with benefits in other populations, and findings indicated better coping in the transplant setting when it was offered.
Celiac Disease 30 Years After Diagnosis
Authors: Norsa Lorenzo , Branchi Federica , Bravo Marianna , Ferretti Francesca , Roncoroni Leda , Somalvico Francesco , Conte Dario , Bardella Maria Teresa , Fabiano Sabrina , Barigelletti Giulio , Elli Luca
Published: April 2018

Objectives:

Studies investigating patients with coeliac disease (CD) on very long‐term follow‐up are limited. We aimed to evaluate the characteristics of patients with CD diagnosed more than 30 years ago.

Methods:

Clinical, histologic, genetic, and demographic data of patients with CD diagnosis made before 1985 were collected and their standardised mortality ratio calculated. According to the gluten‐free diet (GFD) status, CD patients were divided into 3 groups and a specific questionnaire on GFD awareness and gluten‐free products was administered to patients and caregivers.

Results:

A total of 337 CD patients were included in the study. The standardised mortality ratio was 0.37 (confidence interval 0.10 to 0.94) compared with a matched population. A total of 197 patients were grouped according to GFD compliance, with 35 CD patients reporting chronic voluntary gluten ingestion. No significant differences were found between groups regarding family history of CD, symptoms and histology at diagnosis, autoimmune disorders. Follow‐up histology was performed in 63 patients. Twenty patients had normal histology on gluten‐containing diet (GCD). Questionnaire scores were lower in patients on GCD. Caregivers scores were not correlated with patients’ gluten consumption.

Conclusions:

Although poor adherence to GFD is the major predictor of persistence of mucosal lesions at follow‐up histology, a proportion of patients did not show a relapse of villous atrophy in spite chronic voluntary gluten ingestion, nor increase in mortality. Moreover, GFD knowledge and adherence could be partly lost during the transition between childhood and adulthood.
Malignant Pleural Mesothelioma: Are There Imaging Characteristics Associated With Different Histologic Subtypes on Computed Tomography?
Authors: Escalon Joanna G. , Harrington Kate A. , Plodkowski Andrew J. , Zheng Junting , Capanu Marinela , Zauderer Marjorie G. , Rusch Valerie W. , Ginsberg Michelle S.
Published: April 2018

Objectives

Determine imaging characteristics specific to epithelioid (eMPM), sarcomatoid (sMPM), and biphasic (bMPM) subtypes of malignant pleural mesothelioma (MPM) on computed tomography.

Methods

Preoperative computed tomography scans of patients with MPM were retrospectively assessed for numerous features including primary affected side, volume loss, pleural thickness, pleural calcifications, pleural effusion, and lymphadenopathy.

Results

One hundred twenty-five patients with MPM were included. Histologic subdivision was 97 eMPM (77%), 17 bMPM (14%), and 11 sMPM (9%). Nonepithelioid MPM (bMPM and sMPM) was more likely than eMPM to have calcified pleural plaques (P = 0.035). Analyzed separately, bMPM and sMPM each demonstrated calcified plaques more frequently than eMPM, and sMPM more often had internal mammary nodes; however, P values did not reach significance (P = 0.075 and 0.071, respectively).

Conclusions

Calcified plaques are significantly more common in nonepithelioid subtypes compared with eMPM. Given the different prognoses and management of MPM subtypes, accurate noninvasive subtype classification is clinically vital.
Whole-lesion Apparent Diffusion Coefficient First- and Second-Order Texture Features for the Characterization of Rectal Cancer Pathological Factors
Authors: Li Weifeng , Jiang Zhuoran , Guan Yue , Chen Ying , Huang Xiaolin , Liu Song , He Jian , Zhou Zhengyang , Ge Yun
Published: April 2018

Objective

The objective of this study was to explore the value of whole-volume apparent diffusion coefficient (ADC) features in characterizing pathologic features of rectal cancer.

Methods

A total of 50 patients who were diagnosed with rectal cancer via biopsy underwent 3-T pretreatment diffusion-weighted imaging. Apparent diffusion coefficient features, including mean, 10th–90th percentile, Entropy and Entropy(H), derived from whole-lesion volumes were compared between pathologic T1–2 and T3 stages, perineural invasion (PNI) present and absent, lymphangiovascular invasion present and absent, and pathological N0 and N+ stage groups.

Results

Entropy and Entropy(H) were significantly lower in rectal cancers at T1–2 stages than T3. The 90th percentile of rectal cancers with PNI was significantly lower than that of those without PNI. All P < 0.05.

Conclusions

Whole-lesion ADC Entropy and Entropy(H) have potential in evaluating different T stages, and 90th percentile can be helpful for determining PNI presence of rectal cancers.
Aquatic Exercise Program for Individuals With Osteoarthritis: Pain, Stiffness, Physical Function, Self-Efficacy
Authors: Kars Fertelli Tülay , Mollaoglu Mukadder , Sahin Ozlem
Published: April 2018

Purpose

This research was conducted to determine the effects of an aquatic exercise program on pain, stiffness, physical function, and self-efficacy in individuals with osteoarthritis.

Design

A randomized controlled trial.

Methods

Participants in the experimental group participated in the aquatic exercise program three times a week for 8 weeks; participants in the control group did not.

Findings

The mean scores of the experimental group on the pain, stiffness, and difficulty in carrying out physical functions subscales of the Western Ontario and McMaster Universities Osteoarthritis Index decreased significantly, whereas those of the control group decreased very little. The mean scores of the experimental group on the Arthritis Self-Efficacy Scale and the isokinetic muscle strength measurements increased, but those of the control group did not change in the final measurements. The difference between the groups was statistically significant.

Conclusions

Through the study, it was determined that the aquatic exercise program decreased pain, stiffness, and difficulty in carrying out physical functions and increased self-efficacy and muscle strength of individuals with osteoarthritis.

Clinical Relevance

The aquatic exercise program can be used by nurses as a reference in the management of osteoarthritic patients’ health status.
Immediate effects of blood donation on physical and cognitive performance—A randomized controlled double-blinded trial
Authors: Eliassen Håkon S. , Hervig Tor , Backlund Sebastian , Sivertsen Joar , Iversen Vegard Vereide , Kristoffersen Morten , Wengaard Eivind , Gramstad Arne , Fosse Theodor , Bjerkvig Christopher K. , Apelseth Torunn , Doughty Heidi , Strandenes Geir
Published: April 2018

BACKGROUND

The success of implementing damage control resuscitation principles pre-hospital has been at the expense of several logistic burdens including the requirements for resupply, and the question of donor safety during the development of whole blood programs. Previous studies have reported effects on physical performance after blood donation; however, none have investigated the effects of blood donation on cognitive performance.

METHOD

We describe a prospective double-blinded, randomized, controlled study comprised of a battery of tests: three cognitive tests, and VO2max testing on a cycle ergometer. Testing was performed 7 days before blinded donation (baseline day), immediately after donation (Day 0), and 7 days (Day 7) after donation. The inclusion criteria included being active blood donors at the Haukeland University Hospital blood bank, where eligibility requirements were met on the testing days, and providing informed consent. Participants were randomized to either the experimental (n = 26) or control group (n = 31). Control group participants underwent a "mock donation” in which a phlebotomy needle was placed but blood was not withdrawn.

RESULTS

In the experimental group, mean ± SEM VO2max declined 6% from 41.35 ± 1.7 mLO2/(min·kg) at baseline to 39.0 ± 1.6 mLO2/(min·kg) on Day 0 and increased to 40.51 ± 1.5 mLO2/(min·kg) on Day 7. Comparable values in the control group were 42.1 ± 1.8 mLO2/(min·kg) at baseline, 41.6 ± 1.8 mLO2/(min·kg)) on Day 1 (1% decline from baseline), and 41.8 ± 1.8 mLO2/(min·kg) on Day 7.

Comparing scores of all three cognitive tests on Day 0 and Day 7 showed no significant differences (p > 0.05).

CONCLUSION

Our main findings are that executive cognitive and physical performances were well maintained after whole blood donation in healthy blood donors. The findings inform postdonation guidance on when donors may be required to return to duty.

LEVEL OF EVIDENCE

Randomized, controlled, double-blinded prospective trial study, level 1.
Duration of Pupillary Unresponsiveness to Light
Authors: Venkataramaiah Sudhir , Umamaheswara Rao Ganne S. , Kamath Sriganesh , Jadhav Tanmay , Kumar Channaveerachari Naveen , Arumugham Shyam Sundar , Reddy Madhusudan , Philip Mariamma , Thirthalli Jagadisha
Published: April 2018

Background

During electroconvulsive therapy (ECT) sessions, we observed that the time taken for the return of pupillary response to light (ROPL) outlasted both the electroencephalography (EEG) and the motor seizure duration after the delivery of the electrical stimulus to produce convulsions.

Objective

The objective of this study was to investigate whether ROPL can be used as a marker of cessation of seizure activity in the brain after ECT and also to study the effect of atropine premedication on seizure activity during ECT.

Methods

Forty-one patients underwent 82 sessions of ECT in a cross-over design study. The duration of motor seizure, EEG seizure, and time for ROPL was observed and compared.

Results

The ROPL consistently outlasted EEG and motor seizures; the difference in their mean durations was statistically significantP< 0.05. There was good correlation among the 3 parameters. Atropine premedication did not alter the seizure activity and ROPL after ECT.

Conclusions

The ROPL after ECT stimulus is a good bedside monitor for termination of seizure activity and can be a valuable adjunct to surface EEG in monitoring the duration of epileptic activity after delivery of ECT.
Modulation of antibiotic sensitivity and biofilm formation in Pseudomonas aeruginosa by interspecies diffusible signal factor analogues
Authors: An Shi-qi , Murtagh Julie , Twomey Kate B. , Gupta Manoj K. , O’Sullivan Timothy P. , Ingram Rebecca , Valvano Miguel A. , Tang Ji-liang
Published: April 2018

The opportunistic pathogen Pseudomonas aeruginosa can participate in inter-species communication through signaling by cis-2-unsaturated fatty acids of the diffusible signal factor (DSF) family. Sensing these signals involves the histidine kinase PA1396 and leads to altered biofilm formation and increased tolerance to various antibiotics. Here, we show that the membrane-associated sensory input domain of PA1396 has five trans-membrane helices, two of which are required for DSF sensing. DSF binding is associated with enhanced auto-phosphorylation of PA1396 incorporated into liposomes. Further, we examined the ability of synthetic DSF analogues to modulate or inhibit PA1396 activity. Several of these analogues block the ability of DSF to trigger auto-phosphorylation and gene expression, whereas others act as inverse agonists reducing biofilm formation and antibiotic tolerance, both in vitro and in murine infection models. These analogues may thus represent lead compounds for novel adjuvants to improve the efficacy of existing antibiotics.
PDX Finder: A Portal for Patient-Derived tumor Xenograft Model Discovery
Authors: Conte Nathalie , Mason Jeremy , Halmagyi Csaba , Neuhauser Steven B. , Mosaku Abayomi , Begley Dale A. , Krupke Debra M. , Parkinson Helen , Meehan Terrence F. , Bult Carol J.
Published: April 2018

Patient-derived tumor xenograft (PDX) mouse models are a versatile oncology research platform for studying tumor biology and for testing chemotherapeutic approaches tailored to genomic characteristics of individual patient’s tumors. PDX models are generated and distributed by a diverse group of academic labs, research organizations, multi-institution consortia, and contract research organizations. The distributed nature of PDX repositories and the use of different standards in the associated metadata presents a significant challenge to finding PDX models relevant to specific cancer research questions. The Jackson Laboratory and EMBL-EBI are addressing these challenges by co-developing PDX Finder, a comprehensive open global catalog of PDX models and their associated datasets. Within PDX Finder, model attributes are harmonized and integrated using a previously developed community minimal information standard to support consistent searching across the originating resources. Links to repositories are provided from the PDX Finder search results to facilitate model acquisition and/or collaboration. The PDX Finder resource currently contains information for more than 1900 PDX models of diverse cancers including those from large resources such as the Patient-Derived Models Repository, PDXNet, and EurOPDX. Individuals or organizations that generate and distribute PDXs are invited to increase the “findability” of their models by participating in the PDX Finder initiative at www.pdxfinder.org.
A decisional space account of saccadic reaction times towards personally familiar faces
Authors: Ramon Meike , Sokhn Nayla , Caldara Roberto
Published: April 2018

Manual and saccadic reaction times (SRTs) have been used to determine the minimum time required for different types of visual categorizations. Such studies have demonstrated that faces can be detected within natural scenes within as little as 100ms (Crouzet, Kirchner & Thorpe, 2010), while increasingly complex decisions require longer processing times (Besson, Barragan-Jason, Thorpe, Fabre-Thorpe, Puma et al., 2017). Following the notion that facial representations stored in memory facilitate perceptual processing (Ramon & Gobbini, 2018), a recent study reported 180ms as the fastest speed at which “familiar face detection” based on expressed choice saccades (Visconti di Ollegio Castello & Gobbini, 2015). At first glance, these findings seem incompatible with the earliest neural markers of familiarity reported in electrophysiological studies (Barragan-Jason, Cauchoix & Barbeau, 2015; Caharel, Ramon & Rossion, 2014; Huang, Wu, Hu, Wang, Ding & Qu et al., 2017), which should temporally precede any overtly observed behavioral (oculomotor or manual) categorization. Here, we reason that this apparent discrepancy could be accounted for in terms of decisional space constraints, which modulate both manual RTs observed for different levels of visual processing (Besson et al., 2017), as well as saccadic RTs (SRTs) in both healthy observers and neurological patients (Ramon, in press; Ramon, Sokhn, Lao & Caldara, in press). In the present study, over 70 observers completed three different SRT experiments in which decisional space was manipulated through task demands and stimulus probability. Subjects performed a gender categorization task, or one of two familiar face “recognition” tasks, which differed with respect to the number of personally familiar identities presented (3 vs. 7). We observe an inverse relationship between visual categorization proficiency and decisional space. Observers were most accurate for categorization of gender, which could be achieved in as little as 140ms. Categorization of highly predictable targets was more error-prone and required an additional ~100ms processing time. Our findings add to increasing evidence that pre-activation of identity-information can modulate early visual processing in a top-down manner. They also emphasize the importance of considering procedural aspects as well as terminology when aiming to characterize cognitive processes.
A distributed neural code in the dentate gyrus and in CA1
Authors: Stefanini Fabio , Kheirbek Mazen A. , Kushnir Lyudmila , Jimenez Jessica , Jennings Joshua H. , Stuber Garret D. , Hen René , Fusi Stefano
Published: April 2018

The tuning properties of neurons in a given brain region have been traditionally viewed as the under-pinnings of computation in neural circuits. However, at the higher levels of processing, specialization is often elusive, instead a mix of sensory, cognitive and behavioural quantities drive neural activity. In such networks, ensembles of neurons, rather than single units with easily interpretable tuning properties, encode behaviourally relevant variables. Here we show that this is the case also in the dentate gyrus and CA1 subregions of the hippocampus. Using calcium imaging in freely moving mice, we decoded the instantaneous position, direction of motion and speed from the activity of hundreds of cells in the hippocampus of mice freely exploring an arena. For the vast majority of neurons in both regions, their response properties were not predictive of their importance for encoding position. Furthermore, we could decode position from populations of cells that were important for decoding direction of motion and vice versa, showing that these quantities are encoded by largely overlapping ensembles as in distributed neural code. Finally, we found that correlated activities had an impact on decoding performance in CA1 but not in dentate gyrus, suggesting different enconding strategies for these areas. Our analysis indicates that classical methods of analysis based on single cell response properties might be insufficient to accurately characterize the neural computation in a given area. In contrast, population analysis may help highlight previously overlooked properties of hippocampal circuits.
Integrated systems biology and imaging of the smallest free-living eukaryote Ostreococcus tauri
Authors: Smallwood Chuck R. , Chen Jian-Hua , Kumar Neeraj , Chrisler William , Purvine Samuel O. , Kyle Jennifer E. , Nicora Carrie D. , Boudreau Rosanne , Ekman Axel , Hixson Kim K. , Moore Ronald J. , McDermott Gerry , Cannon William R. , Evans James E.
Published: April 2018

Ostreococcus tauri is an ancient phototrophic microalgae that possesses favorable genetic and cellular characteristics for reductionist studies probing biosystem design and dynamics. Here multimodal bioimaging and multi-omics techniques were combined to interrogate O. tauri cellular changes in response to variations in bioavailable nitrogen and carbon ratios. Confocal microscopy, stimulated Raman scattering, and cryo-soft x-ray tomography revealed whole cell ultrastructural dynamics and composition while proteomic and lipidomic profiling captured changes at the molecular and macromolecular scale.

Despite several energy dense long-chain triacylglycerol lipids showing more than 40-fold higher abundance under N deprivation, only a few proteins directly associated with lipid biogenesis showed significant expression changes. However, the entire pathway for starch granule biosynthesis was highly upregulated suggesting much of the cellular energy is preferentially directed towards starch over lipid accumulation. Additionally, three of the five most downregulated and five of the ten most upregulated proteins during severe nitrogen depletion were unnamed protein products that warrant additional biochemical analysis and functional annotation to control carbon transformation dynamics in this smallest eukaryote.
Epigenetic prediction of complex traits and death
Authors: McCartney Daniel L , Stevenson Anna J , Ritchie Stuart J , Walker Rosie M , Zhang Qian , Morris Stewart W , Campbell Archie , Murray Alison D , Whalley Heather C , Gale Catharine R , Porteous David J , Haley Chris S , McRae Allan F , Wray Naomi R , Visscher Peter M , McIntosh Andrew M , Evans Kathryn L , Deary Ian J , Marioni Riccardo E
Published: April 2018

Background

Genome-wide DNA methylation (DNAm) profiling has allowed for the development of molecular predictors for a multitude of traits and diseases. Such predictors may be more accurate than the self-reported phenotypes, and could have clinical applications. Here, penalised regression models were used to develop DNAm predictors for body mass index (BMI), smoking status, alcohol consumption, and educational attainment in a cohort of 5,100 individuals. Using an independent test cohort comprising 906 individuals, the proportion of phenotypic variance explained in each trait was examined for DNAm-based and genetic predictors. Receiver operator characteristic curves were generated to investigate the predictive performance of DNAm-based predictors, using dichotomised phenotypes. The relationship between DNAm scores and all-cause mortality (n = 214 events) was assessed via Cox proportional-hazards models.

Results

The DNAm-based predictors explained different proportions of the phenotypic variance for BMI (12%), smoking (60%), alcohol consumption (12%) and education (3%). The combined genetic and DNAm predictors explained 20% of the variance in BMI, 61% in smoking, 13% in alcohol consumption, and 6% in education. DNAm predictors for smoking, alcohol, and education but not BMI predicted mortality in univariate models. The predictors showed moderate discrimination of obesity (AUC=0.67) and alcohol consumption (AUC=0.75), and excellent discrimination of current smoking status (AUC=0.98). There was poorer discrimination of college-educated individuals (AUC=0.59).

Conclusions

DNAm predictors correlate with lifestyle factors that are associated with health and mortality. They may supplement DNAm-based predictors of age to identify the lifestyle profiles of individuals and predict disease risk.

List of abbreviations

DNAm

DNA methylation

BMI

Body mass index

AUC

Area under the curve

CpG

Cytosine phosphate Guanine dinucleotide

EWAS

Epigenome-wide association study

GS:SFHS

Generation Scotland: The Scottish family health study

LBC1936

Lothian birth cohort 1936

LASSO

Least absolute shrinkage and selector operator

HR

Hazard ratio

CI

Confidence interval

STRADL

Stratifying resilience and depression longitudinally
Loss of E2F7 confers resistance to poly-ADP-ribose polymerase (PARP) inhibitors in BRCA2-deficient cells
Authors: Clements Kristen E. , Thakar Tanay , Nicolae Claudia M. , Liang Xinwen , Wang Hong-Gang , Moldovan George-Lucian
Published: April 2018

BRCA proteins are essential for Homologous Recombination DNA repair, and their germline or somatic inactivation is frequently observed in human tumors. Understanding the molecular mechanisms underlying the response to chemotherapy of BRCA-deficient tumors is paramount for developing improved personalized cancer therapies. While PARP inhibitors have been recently approved for treatment of BRCA-mutant breast and ovarian cancers, resistance to these novel drugs remains a major clinical problem. Several mechanisms of chemoresistance in BRCA2-deficient cells have been identified. Rather than restoring normal recombination, these mechanisms result in stabilization of stalled replication forks, which normally are subjected to degradation in BRCA2-mutated cells. Here, we show that the transcriptional repressor E2F7 controls chemoresistance in BRCA2-deficient cells. We found that E2F7 depletion restores PARP inhibitor and cisplatin resistance in BRCA2-depleted cells. Moreover, we show that the mechanism underlying this activity involves increased expression of RAD51, a target for E2F7-mediated transcriptional repression, which enhances both Homologous Recombination DNA repair, and replication fork stability in BRCA2-deficient cells. Our work describes a new mechanism of chemotherapy resistance in BRCA2-deficient cells, and identifies E2F7 as a novel biomarker for tumor response to PARP inhibitor therapy.
MX2: a high-flux undulator microfocus beamline serving both the chemical and macromolecular crystallography communities at the Australian Synchrotron
Authors: Aragão David , Aishima Jun , Cherukuvada Hima , Clarken Robert , Clift Mark , Cowieson Nathan Philip , Ericsson Daniel Jesper , Gee Christine L. , Macedo Sofia , Mudie Nathan , Panjikar Santosh , Price Jason Roy , Riboldi-Tunnicliffe Alan , Rostan Robert , Williamson Rachel , Caradoc-Davies Thomas Tudor
Published: April 2018

MX2 is an in-vacuum undulator-based crystallography beamline at the 3 GeV Australian Synchrotron. The beamline delivers hard X-rays in the energy range 4.8–21 keV to a focal spot of 22 × 12 µm FWHM (H × V). At 13 keV the flux at the sample is 3.4 × 1012 photons s−1. The beamline endstation allows robotic handling of cryogenic samplesviaan updated SSRL SAM robot. This beamline is ideal for weakly diffracting hard-to-crystallize proteins, virus particles, protein assemblies and nucleic acids as well as smaller molecules such as inorganic catalysts and organic drug molecules. The beamline is now mature and has enjoyed a full user program for the last nine years. This paper describes the beamline status, plans for its future and some recent scientific highlights.
Effects of soft X-ray radiation damage on paraffin-embedded rat tissues supported on ultralene: a chemical perspective
Authors: Bedolla Diana E. , Mantuano Andrea , Pickler Arissa , Mota Carla Lemos , Braz Delson , Salata Camila , Almeida Carlos Eduardo , Birarda Giovanni , Vaccari Lisa , Barroso Regina Cély , Gianoncelli Alessandra
Published: April 2018

Radiation damage is an important aspect to be considered when analysing biological samples with X-ray techniques as it can induce chemical and structural changes in the specimens. This work aims to provide new insights into the soft X-ray induced radiation damage of the complete sample, including not only the biological tissue itself but also the substrate and embedding medium, and the tissue fixation procedure. Sample preparation and handling involves an unavoidable interaction with the sample matrix and could play an important role in the radiation-damage mechanism. To understand the influence of sample preparation and handling on radiation damage, the effects of soft X-ray exposure at different doses on ultralene, paraffin and on paraffin-embedded rat tissues were studied using Fourier-transform infrared (FTIR) microspectroscopy and X-ray microscopy. Tissues were preserved with three different commonly used fixatives: formalin, glutaraldehyde and Karnovsky. FTIR results showed that ultralene and paraffin undergo a dose-dependent degradation of their vibrational profiles, consistent with radiation-induced oxidative damage. In addition, formalin fixative has been shown to improve the preservation of the secondary structure of proteins in tissues compared with both glutaraldehyde and Karnovsky fixation. However, conclusive considerations cannot be drawn on the optimal fixation protocol because of the interference introduced by both substrate and embedding medium in the spectral regions specific to tissue lipids, nucleic acids and carbohydrates. Notably, despite the detected alterations affecting the chemical architecture of the sample as a whole, composed of tissue, substrate and embedding medium, the structural morphology of the tissues at the micrometre scale is essentially preserved even at the highest exposure dose.
Advanced aircraft performance analysis
Authors: Immer Marc , Juretzko Philipp Georg
Published: April 2018

Purpose

The preliminary aircraft design process comprises multiple disciplines. During performance analysis, parameters of the design mission have to be optimized. Mission performance optimization is often challenging, especially for complex mission profiles (e.g. for unmanned aerial vehicles [UAVs]) or hybrid-electric propulsion. Therefore, the purpose of this study is to find a methodology that supports aircraft performance analysis and that is applicable to complex profiles and to novel designs.

Design/methodology/approach

As its core element, the developed method uses a computationally efficient C++ software “Aircraft Performance Program” (APP), which performs a segment-based mission computation. APP performs a time integration of the equations of motion of a point mass in the vertical plane. APP is called via a command line interface from a flexible scripting language (Python). On top of APP’s internal radius of action optimization, state-of-the-art optimization packages (SciPy) are used.

Findings

The application of the method to a conventional climb schedule shows that the definition of the top of climb has a significant influence on the resulting optimum. Application of the method to a complex UAV mission optimization, which included maximizing the radius of action, was successful. Low computation time enables to perform large parametric studies. This greatly improves the interpretation of the results.

Research limitations/implications

The scope of the paper is limited to the methodology that allows for advanced performance analysis at the conceptual and preliminary design stages with an emphasis on novel propulsion concepts. The methodology is developed using existing, validated methods, and therefore, this paper does not contain comprehensive validation. Other disciplines, such as cost analysis, life-cycle assessment or market analysis, are not considered.

Practical implications

With the proposed method, it is possible to obtain not only the desired optimum mission performance but also off-design performance of the investigated design. A thorough analysis of the mission performance provides insight into the design’s capabilities and shortcomings, ultimately aiding in obtaining a more efficient design.

Originality/value

Recent developments in the area of hybrid or hybrid-electric propulsion systems have shown the need for performance computation tools aiding the related design process. The presented method is especially valuable when novel design concepts with complex mission profiles are investigated.