bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical effectiveness of the pocket-creation method for colorectal endoscopic submucosal dissection
Authors: Kanamori Akira , Nakano Masakazu , Kondo Masayuki , Tanaka Takanao , Abe Keiichiro , Suzuki Tsunehiro , Kino Hitoshi , Kaneko Yoshihito , Tsuchida Chieko , Tsuchida Kouhei , Yoshitake Naoto , Tominaga Keiichi , Imai Yasuo , Hiraishi Hideyuki
Published: December 2017

Background and study aims Endoscopic submucosal dissection (ESD) is a technically advanced procedure for colorectal tumors. Hayashi et al. invented the “pocket-creation method (PCM),” and reported that Is-type lesions with fibrosis could be efficaciously and safely resected. However, only case studies have been published, and there are no previous reports on the usefulness of PCM in colorectal ESD for all lesions, as compared with the conventional method. This study aimed to evaluate the effectiveness and safety of PCM in colorectal ESD.

Patients and methods Ninety-six colorectal tumors were treated: 47 using the PCM and the other 49, considered the control group, using the conventional method. Therapeutic effectiveness and safety were retrospectively assessed.

Results The comparison between the PCM and control groups revealed higher rates of en bloc resection (100 % vs. 88 %, P = 0.015) and curative endoscopic resection (100 % vs. 84 %, P = 0.0030) with PCM. There was no significant difference in perforation as an adverse event (AE) between the two groups, though perforation was observed in only 6 % of the control group and none of the PCM group. Compared with the control group, the PCM group had lower incidences of perforation and post-ESD coagulation syndrome, and both AEs were associated with excessive thermal denaturation of the muscle layer (2 % vs. 16 %, P = 0.018).

Conclusions This study demonstrated the effectiveness and safety of ESD with PCM for colorectal tumors. Although there is a possible learning curve, PCM enables the endoscopist to safely perform ESD in most cases without encountering the difficulties associated with conventional ESD.
Factors associated with number of duodenal samples obtained in suspected celiac disease
Authors: Shamban Leonid , Sorser Serge , Naydin Stan , Lebwohl Benjamin , Shukr Mousa , Wiemann Charlotte , Yevsyukov Daniel , Piper Michael , Warren Bradley , Green Peter
Published: December 2017

Background and study aims Many people with celiac disease are undiagnosed and there is evidence that insufficient duodenal samples may contribute to underdiagnosis. The aims of this study were to investigate whether more samples leads to a greater likelihood of a diagnosis of celiac disease and to elucidate factors that influence the number of samples collected.

Patients and methods We identified patients from two community hospitals who were undergoing duodenal biopsy for indications (as identified by International Classification of Diseases code) compatible with possible celiac disease. Three cohorts were evaluated: no celiac disease (NCD, normal villi), celiac disease (villous atrophy, Marsh score 3), and possible celiac disease (PCD, Marsh score < 3). Endoscopic features, indication, setting, trainee presence, and patient demographic details were evaluated for their role in sample collection.

Results 5997 patients met the inclusion criteria. Patients with a final diagnosis of celiac disease had a median of 4 specimens collected. The percentage of patients diagnosed with celiac disease with one sample was 0.3 % compared with 12.8 % of those with six samples (P = 0.001). Patient factors that positively correlated with the number of samples collected were endoscopic features, demographic details, and indication (P = 0.001). Endoscopist factors that positively correlated with the number of samples collected were absence of a trainee, pediatric gastroenterologist, and outpatient setting (P < 0.001).

Conclusions Histological diagnosis of celiac disease significantly increased with six samples. Multiple factors influenced whether adequate biopsies were taken. Adherence to guidelines may increase the diagnosis rate of celiac disease.
Recurrent diffuse gastric bleeding as a leading symptom of gastrointestinal AL amyloidosis
Authors: Franck Caspar , Venerito Marino , Weigt Jochen , Roessner Albert , Malfertheiner Peter
Published: December 2017

Amyloidosis is a rare disease (incidence about 0.8/100 000) characterized by extracellular tissue deposition of fibrils composed of low molecular weight subunits of a variety of serum proteins. Clinical manifestations are largely determined by the type of precursor protein, the tissue distribution and the amount of amyloid deposition. Gastrointestinal (GI) manifestations of amyloidosis are even more uncommon (3 % of all amyloidosis patients). Symptoms of GI amyloidosis are nonspecific, heterogeneous, and include weight loss, GI bleeding, heartburn, early satiety, diarrhea and abdominal pain. The histopathological examination of biopsy specimens from the GI tract leads to the diagnosis.

Herein we report the case of a 63-year-old woman with recurrent diffuse gastric bleeding. Endoscopic biopsies revealed distinct amyloid deposits in the mucosa of the stomach. Further histochemical assessment confirmed systemic light chain (AL) amyloidosis with clinically predominant gastrointestinal manifestation. An induction therapy with bortezomib and dexamethasone was initiated.

Our report illustrates the importance of the multidisciplinary approach for diagnosis and management of AL amyloidosis. Current treatment of systemic AL amyloidosis is based on cytostatic targeting of immunoglobulin producing plasma cells. Therapeutic options are limited and highly toxic, making the development of novel treatment approaches an urgent need.
Photo-oxidative doping in π-conjugated zig-zag chain of carbon atoms with sulfur-functional group
Authors: Ikeura-Sekiguchi Hiromi , Sekiguchi Tetsuhiro
Published: December 2017

Photo-oxidative doping processes were studied for the trans-polyacetylene backbone with the –SCH3 side group as a chemically representative of the precisely controlled S-functionalized zig-zag graphene nanoribbon edge. Sulfur K-edge X-ray absorption near edge structure (XANES) spectroscopy indicates that photochemical reaction of S–CH3 with atmospheric O2 forms selectively oxidized products such as –S(O)CH3 and –SO3– bound to the polyacetylene (PA) backbone. Using the correlation between the oxidation states of sulfur and the XANES peak positions, the partial charge distribution of CH3Sδ+–PAδ– has been estimated. Such positively charged sulfur atoms can attract higher electronegative oxygen atoms and expect to enhance the photooxidization capabilities. The formation of the –SO3– side group is evidently responsible for hole doping into the PA backbone. The results can provide some strategy for area-selective and controllable doping processes of atomic-scale molecular systems with the assistance of UV light.
Gripping characteristics of an electromagnetically activated magnetorheological fluid-based gripper
Authors: Choi Young T. , Hartzell Christine M. , Leps Thomas , Wereley Norman M.
Published: December 2017

The design and test of a magnetorheological fluid (MRF)-based universal gripper (MR gripper) are presented in this study. The MR gripper was developed to have a simple design, but with the ability to produce reliable gripping and handling of a wide range of simple objects. The MR gripper design consists of a bladder mounted atop an electromagnet, where the bladder is filled with an MRF, which was formulated to have long-term stable sedimentation stability, that was synthesized using a high viscosity linear polysiloxane (HVLP) carrier fluid with a carbonyl iron particle (CIP) volume fraction of 35%. Two bladders were fabricated: a magnetizable bladder using a magnetorheological elastomer (MRE), and a passive (non-magnetizable) silicone rubber bladder. The holding force and applied (initial compression) force of the MR gripper for a bladder fill volume of 75% were experimentally measured, for both magnetizable and passive bladders, using a servohydraulic material testing machine for a range of objects. The gripping performance of the MR gripper using an MRE bladder was compared to that of the MR gripper using a passive bladder.
Facilitating dual careers by improving resistance to chronic stress: effects of an intervention programme for elite student athletes
Authors: Sallen Jeffrey , Hemming Karen , Richartz Alfred
Published: December 2017

The starting point of this contribution is the potential risk to health and performance from the combination of elite sporting careers with the pursuit of education. In European sport science and politics, structural measures to promote dual careers in elite sports have been discussed increasingly of late. In addition to organisational measures, there are calls for educational‐psychological intervention programmes supporting the successful management of dual careers at the individual level. This paper presents an appropriate intervention programme and its evaluation: stress‐resistance training for elite athletes (SRT‐EA). It comprises 10 units, each lasting 90 minutes. It is intended for athletes and aims to improve their resistance to chronic stress. The evaluation was carried out in a quasi‐experimental design, with three points of measurement (baseline, immediately after, and three months after) and two non‐randomised groups: an intervention group (n = 128) and an untreated control group (n = 117). Participants were between 13 and 20 years of age (53.5% male) and represented various Olympic sports. Outcome variables were assessed with questionnaires. Significant short‐ and mid‐term intervention effects were explored. The intervention increased stress‐related knowledge, general self‐efficacy, and stress sensitivity. Chronic stress level, stress symptoms, and stress reactivity were reduced. In line with the intention of the intervention, the results showed short‐ and mid‐term, small to medium‐sized effects. Accordingly, separate measurements at the end of the intervention and three months later showed mostly positive subjective experiences. Thus, the results reinforce the hope that educational‐psychological stress‐management interventions can support dual careers.
Preliminary phytochemical analysis, Antioxidant and cytotoxicity test of Carissa edulis Vahl dried fruits
Authors: Fowsiya J , Madhumitha G
Published: December 2017

Plants are the main source of medicine which is used in traditional as well as modern medicine in recent years for curing many diseases. Carissa edulis Vahl is one of the traditional plants which have healing property on diarrhea, toothache and chest pain. The present work aims on phytochemical, antioxidant and in vitro cytotoxicity test of C. edulis dried fruits. The different solvent extracts obtained from petroleum ether, ethyl acetate, chloroform, ethanol and water have been evaluated the presence of phytochemicals. Several assays were carried out like total antioxidant, DPPH, reducing power and thiobarbituric acid to investigate the free radical scavenging property. In addition, the cytotoxicity study also carried out on human lung cancer cells (A549). Among different solvent extract, ethanol exhibited strong antioxidant activity. Additionally, the in vitro cytotoxicity test of C. edulis on human lung cancer cell (A549) showed IC50 value 405.704 ± 2.42 μg/mL. Therefore, C. edulis could be useful as a potential preventive intervention for free radicals mediated diseases as well as an antioxidant drug in the pharmaceutical industry.
Bilayer tablets of Paliperidone for Extended release osmotic drug delivery
Authors: Sunil Chowdary K , Napoleon A A
Published: December 2017

The purpose of this study is to develop and optimize the formulation of paliperidone bilayer tablet core and coating which should meet in vitro performance of trilayered Innovator sample Invega. Optimization of core formulations prepared by different ratio of polyox grades and optimization of coating of (i) sub-coating build-up with hydroxy ethyl cellulose (HEC) and (ii).enteric coating build-up with cellulose acetate (CA). Some important influence factors such as different core tablet compositions and different coating solution ingredients involved in the formulation procedure were investigated. The optimization of formulation and process was conducted by comparing different in vitro release behaviours of Paliperidone. In vitro dissolution studies of Innovator sample (Invega) with formulations of different release rate which ever close release pattern during the whole 24 h test is finalized.
Synthesis of Novel Isochromen-1-one analogues of Etodolac
Authors: Napoleon A A , Sharma Vijay , Aggile Kadirappa
Published: December 2017

In the present work, anti-inflammatory drug based novel isochromen-1-one, their thio and N-methylated analogues were synthesized from the etodolac bulk drug, 1. All the synthesized compounds were purified and successfully characterized by FT-IR, 1H NMR, 13C NMR and Mass spectroscopy. All the derivatives procured are with remarkable yields from 67-72%.
RETRACTED: Spatial big data for disaster management
Authors: Shalini R , Jayapratha K , Ayeshabanu S , Chemmalar Selvi G
Published: December 2017

Big data is an idea of informational collections that depicts huge measure of information and complex that conventional information preparing application program is lacking to manage them. Presently, big data is a widely known domain used in research, academic, and industries. It is utilized to store substantial measure of information in a solitary brought together one. Challenges integrate capture, allocation, analysis, information precise, visualization, distribution, interchange, delegation, inquiring, updating and information protection. In this digital world, to put away the information and recovering the data is enormous errand for the huge organizations and some time information ought to be misfortune due to circulated information putting away. For this issue the organization individuals are chosen to actualize the huge information to put away every one of the information identified with the organization they are put away in one enormous database that is known as large information. Remote sensor is a science getting data used to distinguish the items or break down the range from a separation. It is anything but difficult to discover the question effortlessly with the sensor. It makes geographic data from satellite and sensor information so in this paper dissect what are the structures are utilized for remote sensor in huge information and how the engineering is vary from each other and how they are identify with our investigations. This paper depicts how the calamity happens and figuring consequence of informational collection. And applied a seismic informational collection to compute the tremor calamity in view of classification and clustering strategy. The classical data mining algorithms for classification used are k-nearest, naive bayes and decision table and clustering used are hierarchical, make density based and simple k_means using XLMINER and WEKA tool. This paper also helps to predicts the spatial dataset by applying the XLMINER AND WEKA tool and thus the big spatial data can be well suited to this paper.
6. Social revolution
Authors: Jeffrey Craig
Published: December 2017

Social revolution has provided people, elites in particular, with new economic and social aspirations. These have been brought about by a transformation in people’s access to communication technologies through mobile phones and the internet, as well as access to and enthusiasm for education. The educational revolution is in turn linked to a third key shift related to notions of citizenship and the state. ‘Social revolution’ also explains how cultural expression has been encouraged and civil society has increased. However, civil society and social production of hope are limited by three significant weaknesses in India’s political institutional infrastructure related to the law, policing, and the media.
4. Big data analytics
Authors: Holmes Dawn E.
Published: December 2017

‘Big data analytics’ argues that big data is only useful if we can extract useful information from it. It looks at some of the techniques used to discover useful information from big data, such as customer preferences or how fast an epidemic is spreading. Big data analytics is changing rapidly as the size of the datasets increases and classical statistics makes room for this new paradigm. An example of big data analytics is the algorithmic method called MapReduce, a distributed data processing system that forms part of the core functionality of the Hadoop Ecosystem. Amazon, Google, Facebook, and many others use Hadoop to store and process their data.
Therapeutic Effects of Lamellar Keratoplasty on Terrien Marginal Degeneration
Authors: Li Lin , Zhai Hualei , Xie Lixin , Cheng Jun , Liu Weiwei
Published: December 2017

Purpose:

To evaluate the therapeutic effects of lamellar keratoplasty (LK) on Terrien marginal degeneration (TMD).

Methods:

Retrospective interventional case series. Medical records of 63 patients (71 eyes) who received LK for TMD at Qingdao Eye Hospital, Shandong Eye Institute from December 1995 to March 2014 were reviewed. A total of 56 eyes were treated with partial LK and 15 eyes with total LK. Complications, visual acuity recovery, and graft status were evaluated.

Results:

Mean age of the patients was 50.4 ± 16.8 years. The follow-up period was 2.5 ± 0.9 years. The uncorrected distance visual acuity (UDVA) increased from preoperative 0.90 ± 0.44 logarithm of the minimum angle of resolution (logMAR) to 0.53 ± 0.27 logMAR at 1 year after surgery (t= 16.256,P< 0.001). The corrected distance visual acuity (CDVA) was 0.69 ± 0.30 logMAR preoperatively, and increased to postoperative 0.38 ± 0.22 logMAR (t= −19.982,P< 0.001). After surgery, mean astigmatism was 5.33 ± 2.44 diopters (D) compared with preoperative 10.19 ± 4.32 D (t= 7.351,P< 0.001), and the spherical equivalent decreased from preoperative −2.23 ± 2.34 D to −0.75 ± 2.04 D (t= −2.677,P= 0.012). There was a significant difference in UDVA, ΔUDVA, CDVA, ΔCDVA, and refractive astigmatism between the partial LK and total LK groups. The most common intraoperative complication was corneal perforation. The postoperative complications included double anterior chamber, persistent graft epithelium defects, corneal vascularization, immune rejection, graft ulcers, cataract, and recurrence of marginal degeneration.

Conclusions:

LK can effectively reduce refractive errors, improve visual acuity, and reduce the risk of corneal perforation for patients with TMD. The visual acuity after partial LK is superior to that after total LK.
Outcomes of Corneal Cross-Linking Correlate With Cone-Specific Lysyl Oxidase Expression in Patients With Keratoconus
Authors: Shetty Rohit , Rajiv Kumar Nimisha , Pahuja Natasha , Deshmukh Rashmi , Vunnava KrishnaPoojita , Abilash Valsala Gopalakrishnan , Roy Abhijit Sinha , Ghosh Arkasubhra
Published: December 2017

Purpose:

To evaluate the correlation of visual and keratometry outcomes after corneal cross-linking (CXL) in patients with keratoconus with cone epithelium–specific gene expression levels.

Methods:

Corneal epithelium was obtained from 35 eyes that underwent accelerated CXL (KXLII, 9 mW/cm2 for 10 min). Using corneal topography, epithelium over the cone and periphery was obtained separately from each subject. The ratio of gene expression for lysyl oxidase (LOX), matrix metalloproteinase 9 (MMP9), bone morphogenic protein 7, tissue inhibitor of metalloproteinase 1, collagen, type I, alpha 1, and collagen, type IV, alpha 1 (COL IVA1) from the cone and peripheral cornea was correlated with the outcome of cross-linking surgery. Patients were assessed for visual acuity, keratometry, refraction, and corneal densitometry before and 6 months after surgery. Based on the change in corneal flattening indicated by ΔKmax, the outcomes were classified as a higher response or lower response.

Results:

Reduction in keratometric indices correlated with improved spherical equivalent after CXL. Preoperative levels of cone-specific LOX expression in cases with a higher response were significant (P = 0.001). COL IVA1, bone morphogenic protein 7, and tissue inhibitor of metalloproteinase 1 gene expressions were reduced in the cones of the subjects with a lower response. MMP9 levels were relatively lower in cases with a higher response compared with those with a lower response.

Conclusions:

Our study demonstrates that preoperative levels of molecular factors such as LOX, MMP9, and COL IVA1 aid in understanding CXL outcomes at the tissue level.
Skeletal Muscle Mitochondrial Function is Determined by Burn Severity, Sex, and Sepsis, and is Associated With Glucose Metabolism and Functional Capacity in Burned Children
Authors: Rontoyanni Victoria G. , Malagaris Ioannis , Herndon David N. , Rivas Eric , Capek Karel D. , Delgadillo Anahi D. , Bhattarai Nisha , Elizondo Armando , Voigt Charles D. , Finnerty Celeste C. , Suman Oscar E. , Porter Craig
Published: December 2017

Background:

Restoring normal mitochondrial function represents a new target for strategies aimed at mitigating the stress response to severe burn trauma and hastening recovery. Our objective was to investigate the determinants of skeletal muscle mitochondrial respiratory capacity and function and its association with glucose metabolism and functional capacity in burned children.

Methods:

Data from burned children enrolled in the placebo arm of an ongoing prospective clinical trial were analyzed. Mitochondrial respiratory capacity was determined in permeabilized myofibers by high-resolution respirometry on at least one occasion per participant. In subsets of patients, glucose kinetics and cardiorespiratory fitness (VO2peak) were also determined. Mixed multiple regression models were used to identify the determinants of mitochondrial respiratory function and to assess the relationship between mitochondrial respiration and both glucose control and functional capacity (VO2peak).

Main results:

Increasing full-thickness burn size was associated with greater adjusted coupled (ATP-producing) respiration, adjusted for age, sex, sepsis, and time of testing (P < 0.01; n = 55, obs = 97). Girls had on average 23.3% lower coupled respiration (adjusted mean and 95% confidence of interval [CI], −7.1; −12.6 to −1.7 pmol/s/mg; P < 0.025) and 29.8% lower respiratory control than boys (adjusted mean and 95% CI, −0.66; −1.07 to −0.25; P < 0.01; n = 55, obs = 97). The presence of sepsis was associated with lower respiration coupled to ATP production by an average of 25.5% compared with nonsepsis (adjusted mean and 95% CI, −6.9; −13.0 to −0.7 pmol/s/mg; P < 0.05; n = 55, obs = 97), after adjustment for age, sex, full-thickness burn size, and time of testing. During a hyperinsulinemic euglycemic clamp, hepatic glucose release was associated with greater coupled respiration and respiratory control (P < 0.05; n = 42, obs = 73), independent of age, sepsis, full-thickness burn size, and time postinjury testing. Coupled respiration was positively associated with VO2peak after adjustment for age, full-thickness burn size, and time of exercise testing (P < 0.025; n = 18, obs = 25).

Conclusions:

Burn severity, sex, and sepsis influence skeletal muscle mitochondrial function in burned children. Glucose control and functional capacity are associated with altered mitochondrial respiratory function in muscle of burn survivors, highlighting the relationship of altered muscle bioenergetics with the clinical sequelae accompanying severe burn trauma.
Comprehensive, integrated, and phased whole-genome analysis of the primary ENCODE cell line K562
Authors: Zhou Bo , Ho Steve S. , Greer Stephanie U. , Zhu Xiaowei , Bell John M. , Arthur Joseph G. , Spies Noah , Zhang Xianglong , Byeon Seunggyu , Pattni Reenal , Ben-Efraim Noa , Haney Michael S. , Haraksingh Rajini R. , Ji Hanlee P. , Song Giltae , Perrin Dimitri , Wong Wing H. , Abyzov Alexej , Urban Alexander E.
Published: December 2017

K562 is widely used in biomedical research. It is one of three tier-one cell lines of ENCODE and also most commonly used for large-scale CRISPR/Cas9 screens. Although its functional genomic and epigenomic characteristics have been extensively studied, its genome sequence and genomic structural features have never been comprehensively analyzed. Such information is essential for the correct interpretation and understanding of the vast troves of existing functional genomics and epigenomics data for K562. We performed and integrated deep-coverage whole-genome (short-insert), mate-pair, and linked-read sequencing as well as karyotyping and array CGH analysis to identify a wide spectrum of genome characteristics in K562: copy numbers (CN) of aneuploid chromosome segments at high-resolution, SNVs and Indels (both corrected for CN in aneuploid regions), loss of heterozygosity, mega-base-scale phased haplotypes often spanning entire chromosome arms, structural variants (SVs) including small and large-scale complex SVs and non-reference retrotransposon insertions. Many SVs were phased, assembled, and experimentally validated. We identified multiple allele-specific deletions and duplications within the tumor suppressor geneFHIT. Taking aneuploidy into account, we re-analyzed K562 RNA-seq and whole-genome bisulfite sequencing data for allele-specific expression and allele-specific DNA methylation. We also show examples of how deeper insights into regulatory complexity are gained by integrating genomic variant information and structural context with functional genomics and epigenomics data. Furthermore, using K562 haplotype information, we produced an allele-specific CRISPR targeting map. This comprehensive whole-genome analysis serves as a resource for future studies that utilize K562 as well as a framework for the analysis of other cancer genomes.
Genetic architecture drives seasonal onset of hibernation in the 13-lined ground squirrel
Authors: Grabek Katharine R. , Cooke Thomas F. , Epperson L. Elaine , Spees Kaitlyn K. , Cabral Gleyce F. , Sutton Shirley C. , Merriman Dana K. , Martin Sandy L. , Bustamante Carlos D.
Published: December 2017

Hibernation is a highly dynamic phenotype whose timing, for many mammals, is controlled by a circannual clock and accompanied by rhythms in body mass and food intake. When housed in an animal facility, 13-lined ground squirrels exhibit individual variation in the seasonal onset of hibernation, which is not explained by environmental or biological factors, such as body mass and sex. We hypothesized that underlying genetic architecture instead drives variation in this timing. After first increasing the contiguity of the genome assembly, we therefore employed a genotype-by-sequencing approach to characterize genetic variation in 153 13-lined ground squirrels. Combining this with datalogger records, we estimated high heritability (61-100%) for the seasonal onset of hibernation. After applying a genome-wide scan with 46,996 variants, we also identified 21 loci significantly associated with hibernation immergence, which alone accounted for 54% of the variance in the phenotype. The most significant marker (SNP 15, p=3.81×10−6) was located near prolactin-releasing hormone receptor (PRLHR), a gene that regulates food intake and energy homeostasis. Other significant loci were located near genes functionally related to hibernation physiology, including muscarinic acetylcholine receptor M2 (CHRM2), involved in the control of heart rate, exocyst complex component 4 (EXOC4) and prohormone convertase 2 (PCSK2), both of which are involved in insulin signaling and processing. Finally, we applied an expression quantitative loci (eQTL) analysis using existing transcriptome datasets, and we identified significant (q<0.1) associations for 9/21 variants. Our results highlight the power of applying a genetic mapping strategy to hibernation and present new insight into the genetics driving its seasonal onset.
DNCON2: Improved protein contact prediction using two-level deep convolutional neural networks
Authors: Adhikari Badri , Hou Jie , Cheng Jianlin
Published: December 2017

Motivation

Significant improvements in the prediction of protein residue-residue contacts are observed in the recent years. These contacts, predicted using a variety of coevolution-based and machine learning methods, are the key contributors to the recent progress in ab initio protein structure prediction, as demonstrated in the recent CASP experiments. Continuing the development of new methods to reliably predict contact maps is essential to further improve ab initio structure prediction.

Results

In this paper we discuss DNCON2, an improved protein contact map predictor based on two-level deep convolutional neural networks. It consists of six convolutional neural networks – the first five predict contacts at 6, 7.5, 8, 8.5, and 10 Å distance thresholds, and the last one uses these five predictions as additional features to predict final contact maps. On the free-modeling datasets in CASP10, 11, and 12 experiments, DNCON2 achieves mean precisions of 35%, 50%, and 53.4%, respectively, higher than 30.6% by MetaPSICOV on CASP10 dataset, 34% by MetaPSICOV on CASP11 dataset, and 46.3% by Raptor-X on CASP12 dataset, when top L/5 long-range contacts are evaluated. We attribute the improved performance of DNCON2 to the inclusion of short- and medium-range contacts into training, two-level approach to prediction, use of the state-of-the-art optimization and activation functions, and a novel deep learning architecture that allows each filter in a convolutional layer to access all the input features of a protein of arbitrary length.

Availability

The web server of DNCON2 is at http://sysbio.rnet.missouri.edu/dncon2/ where training and testing datasets as well as the predictions for CASP10, 11, and 12 free-modeling datasets can also be downloaded. Its source code is available at https://github.com/multicom-toolbox/DNCON2/.

Contact

chengji@missouri.edu

Supplementary information

Supplementary data are available online.
A new analysis of resting state connectivity and graph theory reveals distinctive short-term modulations due to whisker stimulation in rats
Authors: Kreitz Silke , de Celis Alonso Benito , Uder Michael , Hess Andreas
Published: December 2017

Resting state (RS) connectivity has been increasingly studied in healthy and diseased brains in humans and animals. This paper presents a new method to analyze RS data from fMRI that combines multiple seed correlation analysis with graph-theory (MSRA). We characterize and evaluate this new method in relation to two other graph-theoretical methods and ICA. The graph-theoretical methods calculate cross-correlations of regional average time-courses, one using seed regions of the same size (SRCC) and the other using whole brain structure regions (RCCA). We evaluated the reproducibility, power, and capacity of these methods to characterize short term RS modulation to unilateral physiological whisker stimulation in rats. Graph-theoretical networks found with the MSRA approach were highly reproducible, and their communities showed large overlaps with ICA components. Additionally, MSRA was the only one of all tested methods that had the power to detect significant RS modulations induced by whisker stimulation that are controlled by family-wise error rate (FWE). Compared to the reduced resting state network connectivity during task performance, these modulations implied decreased connectivity strength in the bilateral sensorimotor and entorhinal cortex. Additionally, the contralateral ventromedial thalamus (part of the barrel field related lemniscal pathway) and the hypothalamus showed reduced connectivity. Enhanced connectivity was observed in the amygdala, especially the contralateral basolateral amygdala (involved in emotional learning processes). In conclusion, MSRA is a powerful analytical approach that can reliably detect tiny modulations of RS connectivity. It shows a great promise as a method for studying RS dynamics in healthy and pathological conditions.
CytoGAN: Generative Modeling of Cell Images
Authors: Goldsborough Peter , Pawlowski Nick , Caicedo Juan C , Singh Shantanu , Carpenter Anne E
Published: December 2017

We explore the application of Generative Adversarial Networks to the domain of morphological profiling of human cultured cells imaged by fluorescence microscopy. When evaluated for their ability to group cell images responding to treatment by chemicals of known classes, we find that adversarially learned representations are superior to autoencoder-based approaches. While currently inferior to classical computer vision and transfer learning, the adversarial framework enables useful visualization of the variation of cellular images due to their generative capabilities.
Analysis of archaic human haplotypes suggest 5-hmC to act as epigenetic guide for meiotic point recombination
Authors: Lee Bernett , Cyrill Samantha , Lee Wendy , Melchiotti Rosella , Andiappan Anand , Poidinger Michael , Rötzschke Olaf
Published: December 2017

Meiotic “point recombination” refers to homologue recombination events affecting only individual SNPs. Driven mostly by gene conversion, it is common process that allows for a gradual adaptation and maturation of haplotypes during genetic evolution. In contrast to crossover recombination it is not tied to predetermined recombination sites and therefore assumed to occur largely randomly. Our analysis of archaic human haplotypes however revealed striking differences in the local point recombination rate. A linkage-study of 1.9 million SNPs defined by the sequence of denisovan hominids revealed low rates in introns and quiescent intergenic regions but high rates in splice sites, exons, 5’- and 3’-UTRs, and CpG islands. Correlations with ChIP-Seq tracks from ENCODE and other public sources identified a number of epigenetic modifications, that associated directly with these recombination events. A particularly tight association was observed for 5-hydroxymethylcytosine marks (5hmC). The mark was enriched in virtually all of the functional regions associated with elevated point recombination rates, including CpG islands and ‘poised’ bivalent regions. As intermediate of oxidative demethylation, 5hmC is also a marker of recently opened gene loci. The data, thus, supports a model of ‘guided’ evolution, in which point recombination is directed by 5hmC marks towards the functionally relevant regions.
Natively Oxidized Amino Acid Residues in the Spinach Cytochromeb6fComplex
Authors: Taylor Ryan M. , Sallans Larry , Frankel Laurie K. , Bricker Terry M.
Published: December 2017

The cytochromeb6fcomplex of oxygenic photosynthesis produces substantial levels of reactive oxygen species (ROS). It has been observed that the ROS production rate byb6fis 10-20 fold higher than that observed for the analogous respiratory cytochromebc1complex. The types of ROS produced (O2•−,1O2, and, possibly, H2O2) and the site(s) of ROS production within theb6fcomplex has been the subject of some debate. Proposed sources of ROS have include the hemebp, PQp•−(possible sources for O2•−), the Rieske iron-sulfur cluster (possible source of O2•−and/or H2O2), Chla(possible source of1O2) and hemeCn(possible source of O2•−and/or H2O2). Our working hypothesis is that amino acid residues proximal to the ROS production sites will be more susceptible to oxidative modification than distant residues. In the current study, we have identified natively oxidized amino acid residues in the subunits of the spinach cytochromeb6fcomplex. The oxidized residues were identified by tandem mass spectrometry using the MassMatrix Program. Our results indicate that numerous residues, principally localized nearp-side cofactors and Chla, were oxidatively modified. We hypothesize that these sites are sources for ROS generation in the spinach cytochromeb6fcomplex.
Decoding the regulatory logic of theDrosophilamale stem cell system
Authors: Papagiannouli Fani , Tamirisa Srividya , Rempel Eugen , Ermakova Olga , Trost Nils , Zhou Jun , Mundorf Juliane , Brunel Samantha , Ruhland Naima , Boutros Michael , Lohmann Jan U. , Lohmann Ingrid
Published: December 2017

In the past decade, the importance of the niche to provide regulatory inputs to balance stem cell self-renewal and differentiation has become clear. However, the regulatory interplay between stem cells and their niche at the whole genome level is still poorly understood. To elucidate the mechanisms controlling stem cells and their progenies as they progress through their developmental program at the transcriptional level, we recorded the regulatory program of two independent cell lineages in theDrosophilatestis stem cell model. To this end, we identified genes active in the soma or germline as well as genome-wide binding profiles of two essential transcription factors, Zfh-1 and Abd-A, expressed in somatic support cells and crucial for fate acquisition of both cell lineages. Our data identified key roles for TOR signalling, signal processing V-ATPase proton pumps and the nuclear transport engaged nucleoporins and we demonstrate their importance in controlling germline maintenance, proliferation and differentiation from the support side. To make our dataset publicly available and support quick and intuitive data mining, we generated an interactive online analysis tool. Applying our tool for comparative analysis, we uncovered conserved core gene sets of adult stem cells across species boundaries. We have tested the functional relevance of these genes in theDrosophilatestis and intestine and find a striking overrepresentation of stem cell defects when the corresponding genes were depleted. In summary, our dataset and interactive platform represents a versatile tool for identifying novel gene networks active in diverse stem cell types and provides a valuable resource for elucidating the multifaceted regulatory inputs required to guide proper stem cell behaviour.
Cellular responses to reactive oxygen species can be predicted on multiple biological scales from molecular mechanisms
Authors: Yang Laurence , Mih Nathan , Anand Amitesh , Park Joon Ho , Tan Justin , Yurkovich James T. , Monk Jonathan M. , Lloyd Colton J. , Sandberg Troy E. , Seo Sang Woo , Kim Donghyuk , Sastry Anand V. , Phaneuf Patrick , Gao Ye , Broddrick Jared T. , Chen Ke , Heckmann David , Szubin Richard , Hefner Ying , Feist Adam M. , Palsson Bernhard O.
Published: December 2017

Catalysis using iron-sulfur clusters and transition metals can be traced back to the last universal common ancestor. The damage to metalloproteins caused by reactive oxygen species (ROS) can completely inhibit cell growth when unmanaged and thus elicits an essential stress response that is universal and fundamental in biology. We develop a computable multi-scale description of the ROS stress response in Escherichia coli. We show that this quantitative framework allows for the understanding and prediction of ROS stress responses at three levels: 1) pathways: amino acid auxotrophies, 2) networks: the systemic response to ROS stress, and 3) genetic basis: adaptation to ROS stress during laboratory evolution. These results show that we can now develop fundamental and quantitative genotype-phenotype relationships for stress responses on a genome-wide basis.
C-type lectin-like receptor 2 (CLEC-2)-dependent DC migration is controlled by tetraspanin CD37
Authors: de Winde Charlotte M , Matthews Alexandra L , van Deventer Sjoerd , van der Schaaf Alie , Tomlinson Neil D , Jansen Erik , Eble Johannes A , Nieswandt Bernhard , McGettrick Helen M , Figdor Carl G , Acton Sophie E , Tomlinson Michael G , van Spriel Annemiek B
Published: December 2017

Cell migration is central to evoke a potent immune response. Dendritic cell (DC) migration to lymph nodes is dependent on the interaction of C-type lectin-like receptor 2 (CLEC-2) expressed by DCs, with podoplanin expressed by lymph node stromal cells (LNSCs). However, the underlying molecular mechanisms by which CLEC-2 influences DC migration remain elusive. Here, we show that CLEC-2-dependent DC migration is tightly controlled by tetraspanin CD37, a membrane-organizing protein. Our findings demonstrate a specific molecular interaction between CLEC-2 and CD37. Myeloid cells lacking CD37 (Cd37-/-) expressed less CLEC-2 on their surface compared to wild-type cells, indicating that CD37 is required to stabilize membrane expression of CLEC-2. In addition, CLEC-2-expressing DCs lacking CD37 showed impaired adhesion, migration velocity and displacement on LNSCs. Moreover, Cd37-/- DCs failed to form actin protrusions in a 3D collagen matrix upon podoplanin-induced CLEC-2 stimulation, phenocopying CLEC-2-deficient DCs (CD11cΔCLEC-2). Microcontact printing experiments revealed that CD37 is required for CLEC-2 recruitment in the membrane to its ligand podoplanin. This study demonstrates that tetraspanin CD37 controls CLEC-2 membrane organization and provides new molecular insights underlying CLEC-2-dependent DC migration.
Exploring Drivers of Gene Expression in The Cancer Genome Atlas
Authors: Rau Andrea , Flister Michael , Rui Hallgeir , Auer Paul L.
Published: December 2017

The Cancer Genome Atlas (TCGA) has greatly advanced cancer research by generating, curating, and publicly releasing deeply measured molecular data from thousands of tumor samples. In particular, gene expression measures, both within and across cancer types, have been used to determine the genes and proteins that are active in tumor cells. To more thoroughly investigate the behavior of gene expression in TCGA tumor samples, we introduce a statistical framework for partitioning the variation in gene expression due to a variety of molecular variables including somatic mutations, transcription factors (TFs), microRNAs, copy number alternations, methylation, and germ-line genetic variation. As proof-of-principle, we identify and validate specific TFs that influence the expression ofPTPN14in breast cancer cells. We provide a freely available, user-friendly, browseable interactive web-based application for exploring the results of our transcriptome-wide analyses across 17 different cancers in TCGA athttp://ls-shiny-prod.uwm.edu/edge_in_tcga.
HOME: A histogram based machine learning approach for effective identification of differentially methylated regions
Authors: Srivastava Akanksha , Karpievitch Yuliya V , Eichten Steven R , Borevitz Justin O , Lister Ryan
Published: December 2017

Background

The development of whole genome bisulfite sequencing has made it possible to identify methylation differences at single base resolution throughout an entire genome. However, a persistent challenge in DNA methylome analysis is the accurate identification of differentially methylated regions (DMRs) between samples. Sensitive and specific identification of DMRs among different conditions requires accurate and efficient algorithms, and while various tools have been developed to tackle this problem, they frequently suffer from inaccurate DMR boundary identification and high false positive rate.

Results

We present a novel Histogram Of MEthylation (HOME) based method that takes into account the inherent difference in the distribution of methylation levels between DMRs and non-DMRs to discriminate between the two using a Support Vector Machine. We show that generated features used by HOME are dataset-independent such that a classifier trained on, for example, a mouse methylome training set of regions of differentially accessible chromatin, can be applied to any other organism’s dataset and identify accurate DMRs. We demonstrate that DMRs identified by HOME exhibit higher association with biologically relevant genes, processes, and regulatory events compared to the existing methods. Moreover, HOME provides additional functionalities lacking in most of the current DMR finders such as DMR identification in non-CG context and time series analysis. HOME is freely available at https://github.com/ListerLab/HOME.

Conclusion

HOME produces more accurate DMRs than the current state-of-the-art methods on both simulated and biological datasets. The broad applicability of HOME to identify accurate DMRs in genomic data from any organism will have a significant impact upon expanding our knowledge of how DNA methylation dynamics affect cell development and differentiation.
PET studies of the glial cell marker TSPO in psychosis patients - a meta-analysis using individual participant data
Authors: Plavén-Sigray Pontus , Matheson Granville J. , Collste Karin , Ashok Abhishekh H. , Coughlin Jennifer M. , Howes Oliver D. , Mizrahi Romina , Pomper Martin G. , Rusjan Pablo , Veronese Mattia , Wang Yuchuan , Cervenka Simon
Published: December 2017

Background:

Accumulating evidence suggests that the immune system may be an important target for new treatment approaches in schizophrenia. Positron emission tomography (PET) and radioligands binding to the translocator protein (TSPO), which is expressed in glial cells in brain including immune cells, represents a potential method for patient stratification and treatment monitoring. This study examined if patients with first episode psychosis and schizophrenia had altered TSPO levels as compared to healthy control subjects.

Methods:

PubMed was searched for studies comparing patients with psychosis to healthy controls using second-generation TSPO radioligands. The outcome measure was distribution volume (VT), an index of TSPO levels, in frontal cortex (FC), temporal cortex (TC) and hippocampus (HIP). Bayes factors (BF) were applied to examine the relative support for higher, lower or no-change of TSPO levels in patients as compared to healthy controls.

Results:

Five studies, with 75 patients with first-episode psychosis or schizophrenia and 77 healthy control subjects were included. BF showed strong support for lower patient VT relative to no-change (all BF>32) or relative to an increase (all BF>422) in all brain regions. From the posterior distributions, mean patient-control differences in standardized VT values were −0.48 for FC (95% credible interval (CredInt)=-0.88 to −0.09), −0.47 for TC (CredInt=−0.87 to −0.07) and −0.63 for HIP (CredInt=−1.00 to −0.25).

Discussion:

The observed reduction of TPSO in compared to control subjects in patients may correspond to altered function or lower density of brain immune cells. Future studies should focus on investigating the underlying biological mechanisms and their relevance for treatment.