bluuebunny/crossref_metadata_2025 huggingface dataset:
Studying Yellowstone by Integrating Deep Carbon Science
Authors: Morrison Shaunna , Pistone Mattia , Kohl Lukas
Published: June 2017

Second Deep Carbon Observatory Summer School; Yellowstone National Park, Montana and Wyoming, 23–28 July 2016
γ-COPI mediates the retention of kAE1 G701D protein in Golgi apparatus – a mechanistic explanation of distal renal tubular acidosis associated with the G701D mutation
Authors: Duangtum Natapol , Junking Mutita , Phadngam Suratchanee , Sawasdee Nunghathai , Castiglioni Andrea , Charngkaew Komgrid , Limjindaporn Thawornchai , Isidoro Ciro , Yenchitsomanus Pa-thai
Published: June 2017

Mutations of the solute carrier family 4 member 1 (SLC4A1) gene encoding kidney anion (chloride/bicarbonate ion) exchanger 1 (kAE1) can cause genetic distal renal tubular acidosis (dRTA). Different SLC4A1 mutations give rise to mutant kAE1 proteins with distinct defects in protein trafficking. The mutant kAE1 protein may be retained in endoplasmic reticulum (ER) or Golgi apparatus, or mis-targeted to the apical membrane, failing to display its function at the baso-lateral membrane. The ER-retained mutant kAE1 interacts with calnexin chaperone protein; disruption of this interaction permits the mutant kAE1 to reach the cell surface and display anion exchange activity. However, the mechanism of Golgi retention of mutant kAE1 G701D protein, which is otherwise functional, is still unclear. In the present study, we show that Golgi retention of kAE1 G701D is due to a stable interaction with the Golgi-resident protein, coat protein complex I (COPI), that plays a role in retrograde vesicular trafficking and Golgi-based quality control. The interaction and co-localization of kAE1 G701D with the γ-COPI subunit were demonstrated in human embryonic kidney (HEK-293T) cells by co-immunoprecipitation and immunofluorescence staining. Small interference RNA (siRNA) silencing of COPI expression in the transfected HEK-293T cells increased the cell surface expression of transgenic kAE1 G701D, as shown by immunofluorescence staining. Our data unveil the molecular mechanism of Golgi retention of kAE1 G701D and suggest that disruption of the COPI-kAE1 G701D interaction could be a therapeutic strategy to treat dRTA caused by this mutant.
Convolutional recurrent neural networks with hidden Markov model bootstrap for scene text recognition
Authors: Wang Fenglei , Guo Qiang , Lei Jun , Zhang Jun
Published: June 2017

Text recognition in natural scene remains a challenging problem due to the highly variable appearance in unconstrained condition. The authors develop a system that directly transcribes scene text images to text without character segmentation. They formulate the problem as sequence labelling. They build a convolutional recurrent neural network (RNN) by using deep convolutional neural networks (CNN) for modelling text appearance and RNNs for sequence dynamics. The two models are complementary in modelling capabilities and so integrated together to form the segmentation free system. They train a Gaussian mixture model–hidden Markov model to supervise the training of the CNN model. The system is data driven and needs no hand labelled training data. Their method has several appealing properties: (i) It can recognise arbitrary length text images. (ii) The recognition process does not involve sophisticated character segmentation. (iii) It is trained on scene text images with only word‐level transcriptions. (iv) It can recognise both the lexicon‐based or lexicon‐free text. The proposed system achieves competitive performance comparison with the state of the art on several public scene text datasets, including both lexicon‐based and non‐lexicon ones.
Sixth harmonic‐based fault location for VSC‐DC distribution systems
Authors: Li Meng , Jia Ke , Bi Tianshu , Yang Qixun
Published: June 2017

Accurate fault location methods are of major significance to the line maintenance of voltage source converter (VSC)‐DC distribution systems. However, power electronics change the fault‐characteristics, and the new fault theory is not fully mature. In addition, rapid fault isolation leaves little information for fault location. Fault location for VSC‐DC distribution systems is still a big challenge. The proposed fault location method is developed based on an equivalent feeding‐stage circuit derived herein. The line quantities sixth‐harmonics are used, and an improved discrete Fourier transform algorithm (IDFT) is proposed to remove the influence of both decaying periodic and DC components. Simulation results on PSCAD/EMTDC verified the feasibility of the proposed fault location and IDFT algorithms. Using local measurements with the sampling frequency of 9.6 kHz, the method can locate fault position within 10 ms and with less than 2% error.
Optimisation of dynamic reactive power sources using mesh adaptive direct search
Authors: Huang Weihong , Sun Kai , Qi Junjian , Ning Jiaxin
Published: June 2017

Dynamic reactive power sources can be used to effectively mitigate the fault‐induced delayed voltage recovery and transient voltage instability issues. When many var sources need to be installed at planned locations, optimisation of their sizes is a complicated non‐linear optimisation problem due to its non‐convexity and the dependence of the constraint on time‐series trajectories of post‐fault voltages. Solving this optimal sizing problem needs to utilise both a non‐linear optimisation solver and a power system differential‐algebraic equation solver. This study proposes a new approach for solving this problem under both a single contingency and multiple contingencies by using the mesh adaptive direct search algorithm interfaced with a power system simulator. The proposed approach is validated by case studies on a North American Eastern Interconnection model to optimise the sizes of planned STATCOMs against critical contingencies.
Ambiguities in 3D target motion estimation for general radar measurements
Authors: Garren David Alan
Published: June 2017

A recent analysis reveals that any attempt to estimate the underlying two‐dimensional (2D) motion of a surface target via general bistatic synthetic aperture radar yields ambiguities, so that alternate target trajectories can give the same measurement data. These ambiguities are of a continuous nature and are fundamentally distinct from the discrete ambiguities that arise in pulse‐Doppler moving target indication radar. The current investigation relaxes the constraint that the mobile target lies on the surface of a ground plane, so that air targets with general 3D motion are considered. Specifically, the current paper develops methods for constructing alternate fictitious 3D target trajectory and speed profiles in time which yield identical radar measurements as that obtained from the true 3D target motion. These ambiguities are shown to remain even with the inclusion of bistatic range rate or Doppler measurements. Thus, the energy patterns of the radar transmission and reception beams determine the ability to localise and estimate the 3D target trajectory and speed profiles for general bistatic radar collections.
Synchronisation of two separate zones in a standalone microgrid
Authors: Hong Ying‐Yi , Liu Chun‐Yi , Chang Yung‐Ruei , Lee Yih‐Der , Ouyang Der‐Chuan
Published: June 2017

Standalone microgrids that comprise distributed generation sources (DGSs) or energy storage systems (ESSs) exist on off‐shore islands or remote areas. When a fault occurs in a standalone microgrid, the microgrid is separated into several zones with pre‐specified DGS or ESS supplying power to local loads. After the fault is cleared, the three‐phase voltages and frequencies may differ among these zones. To restore the original microgrid topology, these zones must be reconnected to each other by synchronisation. A synchronisation controller of the DGS/ESS that accounts for slightly different three‐phase voltages and frequencies in two separate zones is presented. The Clark transform and Mamdani fuzzy rules are used to implement the controller, providing fast and seamless synchronisation. Simulation results using a standalone microgrid show the practical applicability of the proposed method.
Symmetric switched diode multilevel inverter structure with minimised switch count
Authors: Ibrahim S.A. Ahamed , Palanimuthu Anbalagan , Sathik M.A. Jagabar
Published: June 2017

A new symmetric switched diode multilevel inverter with reduced power switches for medium‐voltage applications is presented. The proposed topology consists of several double‐source units to produce the synthesised stepped output voltage waveform with reduced total harmonic distortion. The required number of insulated bipolar junction transistors, power diode, and total power losses are compared between conventional and recent topologies. The seven‐level output voltage is simulated by using simulation software MATLAB/Simulink, and hardware prototype model has been developed to prove the superiority of the proposed topology. Finally, the advantage of the proposed topology is highlighted, and the topology for high‐voltage applications is suggested.
Blind evaluation of AFM tip shape by using optical glass surface with irregular nanostructures as a tip characteriser
Authors: Han Guoqiang , Cao Shuguang , Wang Xiumei , Lin Bo , Chen Yuqin
Published: June 2017

Atomic‐force microscopy (AFM) is a type of scanning probe microscopy. It possesses nano‐scale resolution which is >1000 times better than the optical diffraction limit. An image of AFM is the result of interaction between the tip and the sample. The AFM image is not accurate and distorted due to the finite size of the probe tip. To correct the AFM image and acquire accurate sample morphology information, it needs to evaluate the tip shape and status. The shape of the probe tip is calculated to determine the quality of the probe. The optical glass surface fabricated by free abrasive polishing (traditional mechanical polishing) technique is used as a new tip characteriser to calibrate the AFM probe tip. Meanwhile, an improved blind reconstruction algorithm is adopted to calculate the AFM tip shape and size. In the help of matrices, the blind reconstruction algorithm is elaborated clearly. The optical glass surface with irregular nanostructures ensures that the morphology of probe tip can be determined accurately. Without independent knowledge of the sample morphology, the three‐dimensional morphology of the AFM tip can be obtained.
Three-dimensional mapping of the local interstellar medium with composite data
Authors: Capitanio L. , Lallement R. , Vergely J. L. , Elyajouri M. , Monreal-Ibero A.
Published: June 2017

Context. Three-dimensional maps of the Galactic interstellar medium are general astrophysical tools. Reddening maps may be based on the inversion of color excess measurements for individual target stars or on statistical methods using stellar surveys. Three-dimensional maps based on diffuse interstellar bands (DIBs) have also been produced. All methods benefit from the advent of massive surveys and may benefit from Gaia data.

Aims. All of the various methods and databases have their own advantages and limitations. Here we present a first attempt to combine different datasets and methods to improve the local maps.

Methods. We first updated our previous local dust maps based on a regularized Bayesian inversion of individual color excess data by replacing Hipparcos or photometric distances with Gaia Data Release 1 values when available. Secondly, we complemented this database with a series of ≃5000 color excess values estimated from the strength of the λ15273 DIB toward stars possessing a Gaia parallax. The DIB strengths were extracted from SDSS/APOGEE spectra. Third, we computed a low-resolution map based on a grid of Pan-STARRS reddening measurements by means of a new hierarchical technique and used this map as the prior distribution during the inversion of the two other datasets.

Results. The use of Gaia parallaxes introduces significant changes in some areas and globally increases the compactness of the structures. Additional DIB-based data make it possible to assign distances to clouds located behind closer opaque structures and do not introduce contradictory information for the close structures. A more realistic prior distribution instead of a plane-parallel homogeneous distribution helps better define the structures. We validated the results through comparisons with other maps and with soft X-ray data.

Conclusions. Our study demonstrates that the combination of various tracers is a potential tool for more accurate maps. An online tool makes it possible to retrieve maps and reddening estimations.
Does the Surgical Correction of Tibial Torsion with Genu Varum Produce Outcomes Similar to Those in Varus Correction Alone?
Authors: Meade Matthew , Borst Eugene , Nguyen Joseph , Rozbruch S. , Fragomen Austin
Published: June 2017

The aim of this article is to study the relationship between tibia vara and external tibial torsion in adults. The following questions were asked: (1) what is the incidence of rotational deformity in patients with genu varum and (2) do patients who undergo correction of tibial torsion with genu varum have similar outcomes to those who undergo simple tibia vara correction? In this study, 69 patients (138 limbs) underwent bilateral proximal tibial osteotomy for the correction of genu varum. Patients with simple coronal plane deformity (varus alone) were treated with either a monolateral external fixator or a hexapod frame. Those with concomitant external tibial torsion were treated with circular external fixation. The primary outcome was the ability to achieve the desired correction of alignment in the coronal, sagittal, and axial planes. Secondary outcomes included a postoperative Knee Injury and Osteoarthritis Outcome Score (KOOS) and a routine patient satisfaction questionnaire. The incidence of tibial torsion among the entire group of patients with bilateral tibia vara was 46% and overwhelmingly external in direction. The two groups had some significant differences in demographics with torsion patients tending to be younger and thinner. The final mechanical axis deviation and medial proximal tibial angle values for both groups did not differ significantly (p = 0.956). The postcorrection thigh–foot axis was not significantly different between the two groups (p = 0.666). Time to union was not significant (p > 0.999). KOOS was not different between the two groups in symptoms, pain, activities of daily living, and return to sport. There was a difference in the quality of life score between the two groups (p = 0.044). There was no difference between the two groups regarding the patient questionnaire. Based on the finding of this analysis, the incidence of rotational malalignment with genu varum is close to 50%. The recognition of this close association with external tibial torsion deformity may allow for further insights into the role of rotation in varus deformity-related knee pathology and treatment. Patients can expect nearly identical outcomes from this surgery.
Bone Marrow Aspirate Concentrate versus Platelet Rich Plasma to Enhance Osseous Integration Potential for Osteochondral Allografts
Authors: Baumann Charles , Stannard James , Cook James , Stoker Aaron
Published: June 2017

Fresh osteochondral allograft (OCA) transplantation is an attractive treatment option for symptomatic articular cartilage lesions in young, healthy patients. Since a lack of OCA bone integration can be a cause of treatment failure, methods for speeding and enhancing OCA bone integration to mitigate this potential complication are highly desirable. This study sought to determine and compare the potential of bone marrow aspirate concentrate (BMC) and leukoreduced platelet rich plasma (PRP) to repopulate the osseous portion of an OCA with cells and deliver osteogenic proteins. It was hypothesized that BMC would have significantly higher colony forming units (CFUs)/mL and seed the osseous portion of OCA with more cells than PRP. Finally, we hypothesized that the media of BMC and PRP treated OCAs would have significantly higher concentrations of osteogenic proteins compared with negative control OCAs. Cylindrical OCAs (n = 36) created from tissue stored for 21 days were treated with BMC (n = 12) or PRP (n = 12) obtained for 6 dogs, or left untreated as a negative control (n = 12). After treatment, OCAs were cultured for 7 or 14 days. Media were collected for analysis of osteogenic biomarker concentration. Samples of each BMC and PRP were tested for CFU concentration. On day 7 or 14, the grafts were assessed for cell surface adhesion and penetration using fluorescent microscopy. Significant differences in CFU and media biomarker concentration between the groups were determined using one-way analysis of variance (ANOVA) and Tukey's post-hoc test with the significance set at p < 0.05. Only OCAs saturated with BMC had viable cells detectable on the osseous portion of the allografts at day 7 and 14 of culture. BMC samples had a significantly higher (p = 0.029) CFU/mL compared with PRP samples. At day 3 and/or 7 of culture, the concentration of several osteogenic proteins was significantly higher in both BMC and PRP samples. Autogenous BMC can be used to deliver both a cell population and osteogenic proteins that may improve healing of the osseous portion of the OCA clinically.
Multiparity improves outcomes after cerebral ischemia in female mice despite features of increased metabovascular risk
Authors: Ritzel Rodney M. , Patel Anita R. , Spychala Monica , Verma Rajkumar , Crapser Joshua , Koellhoffer Edward C. , Schrecengost Anna , Jellison Evan R. , Zhu Liang , Venna Venugopal Reddy , McCullough Louise D.
Published: June 2017

Significance

Stroke is an age-related disease that disproportionately affects women. Although experimental studies have identified several hormonal and genetic factors underlying these differences, little is known about how reproductive experience influences risk. This study examined the role of pregnancy and parturition on neurovascular function and behavior in both normal female mice and in females exposed to stroke. We found that reproductive experience increases systemic metabolic risk and results in significant behavioral deficits that are associated with CNS immunosuppression. After stroke, however, multiparous females exhibited smaller infarct volumes, attenuated inflammatory responses, enhanced angiogenesis, and improved behavioral recovery. Although the precise mechanisms underlying this paradoxical finding remain unknown, parity was associated with higher VEGF and improved postischemic vascular remodeling.
DNA–PK facilitates
piggyBac
transposition by promoting paired-end complex formation
Authors: Jin Yan , Chen Yaohui , Zhao Shimin , Guan Kun-Liang , Zhuang Yuan , Zhou Wenhao , Wu Xiaohui , Xu Tian
Published: June 2017

Significance

Transposons are usually functional only in their natural hosts, indicating the involvement of host factors during transposition. In contrast,
piggyBac
(
PB
)-based transposon systems are active in cells from yeast to human. We found that the evolutionarily conserved DNA–PK complex binds to the transposase of
PB
. DNA–PK promotes the formation of the transposition intermediate paired-end complex (PEC) and facilitates
PB
transposition.
PB
vectors with closer transposon ends help PEC formation and significantly promote
PB
transposition even in cells without functional DNA–PK. These results not only suggest a mechanistic explanation of the broad host spectrum of
PB
but also provide a simple practical approach to designing efficient transposon vectors.
Nucleotide-dependent farnesyl switch orchestrates polymerization and membrane binding of human guanylate-binding protein 1
Authors: Shydlovskyi Sergii , Zienert Anke Y. , Ince Semra , Dovengerds Christine , Hohendahl Annika , Dargazanli Julia M. , Blum Ailisa , Günther Saskia D. , Kladt Nikolay , Stürzl Michael , Schauss Astrid C. , Kutsch Miriam , Roux Aurélien , Praefcke Gerrit J. K. , Herrmann Christian
Published: June 2017

Significance

In the human organism, guanylate-binding proteins (GBPs) are involved in antimicrobial and antiviral activity, but the mechanism of GBPs’ action remains poorly understood. We have discovered that binding of a substrate molecule, GTP, to the enzyme triggers the release of an aforemasked lipid anchor, which results in GBP polymerization on the one hand and in the attachment of GBPs to lipid membranes on the other. Thus, membrane binding of GBPs competes with protein polymerization and, furthermore, leads to the membrane tethering, which could play a role in a clearance of engulfed pathogens from the cell. Altogether, our findings give deeper insights into GBPs’ molecular mechanism in the course of pathogen response.
Cumulative Intracranial Tumor Volume Augments the Prognostic Value of Diagnosis-Specific Graded Prognostic Assessment Model for Survival in Patients with Melanoma Cerebral Metastases
Authors: Hirshman Brian R , Wilson Bayard R , Ali Mir Amaan , Schupper Alexander J , Proudfoot James A , Goetsch Steven J , Carter Bob S , Sinclair Georges , Bartek Jiri , Chiang Veronica , Fogarty Gerald , Hong Angela , Chen Clark C
Published: June 2017

BACKGROUND

The diagnosis-specific graded prognostic assessment scale (ds-GPA) for patients with melanoma brain metastasis (BM) utilizes only 2 key prognostic variables: Karnofsky performance status and the number of intracranial metastases. We wished to determine whether inclusion of cumulative intracranial tumor volume (CITV) into the ds-GPA model for melanoma augmented its prognostic value.

OBJECTIVE

To determine whether or not CITV augments the ds-GPA prognostic scale for melanoma.

METHODS

We analyzed the survival pattern of 344 melanoma patients with BM treated with stereotactic radiosurgery (SRS) at separate institutions and validated our findings in an independent cohort of 201 patients. The prognostic value of ds-GPA for melanoma was quantitatively compared with and without the addition of CITV using the net reclassification index (NRI > 0) and integrated discrimination improvement (IDI) metrics.

RESULTS

The incorporation of CITV into the melanoma-specific ds-GPA model enhanced its prognostic accuracy. Addition of CITV to the ds-GPA model significantly improved its prognostic value, with NRI > 0 of 0.366 (95% CI: 0.125-0.607, P = .002) and IDI of 0.024 (95% CI: 0.008-0.040, P = .004). We validated these findings that CITV improves the prognostic utility of melanoma ds-GPA in an independent cohort of 201 melanoma cohort.

CONCLUSION

The prognostic value of the ds-GPA scale for melanoma BM is enhanced by the incorporation of CITV.
A correlation analysis framework for localization-based super-resolution microscopy
Authors: Schnitzbauer Joerg , Wang Yina , Bakalar Matthew , Chen Baohui , Nuwal Tulip , Zhao Shijie , Huang Bo
Published: June 2017

Super-resolution images reconstructed from single-molecule localizations can reveal cellular structures close to the macromolecular scale and are now being used routinely in many biomedical research applications. However, because of their coordinate-based representation, a widely applicable and unified analysis platform that can extract a quantitative description and biophysical parameters from these images is yet to be established. Here, we propose a conceptual framework for correlation analysis of coordinate-based super-resolution images using distance histograms. We demonstrate the application of this concept in multiple scenarios including image alignment, tracking of diffusing molecules, as well as for quantification of colocalization.

Significance statement

Correlation analysis is one of the most widely used image processing method. In the quantitative analysis of localization-based super-resolution images, there still lacks a generalized coordinate-based correlation analysis framework to take fully advantage of the super-resolution information. We show a coordinate-based correlation analysis framework for localization-based super-resolution microscopy. This framework is highly general and flexible in that it can be easily extended to model the effect of localization uncertainty, to the time domain and other distance definitions, enabling it to be adapted for a wide range of applications. Our work will greatly benefit the quantitative interpretation of super-resolution images and thus the biological application of super-resolution microscopy.
The decline of malaria in Vietnam, 1991-2014
Authors: Goldlust Sandra M , Thuan Phung Duc , Duy Hoang Giang Dang , Thang Ngo Duc , Thwaites Guy E , Farrar Jeremy , Thanh Ngo Viet , Nguyen Tran Dang , Grenfell Bryan T , Boni Maciej F , Hien Tran Tinh
Published: June 2017

A central component of malaria control initiatives throughout the world is the use of artemisinin-based combination therapies (ACTs) for treatment of uncomplicatedP. falcipariummalaria. Despite the well-documented clinical efficacy of ACTs, the population-level effects of ACT case management on malaria transmission have not been studied thoroughly until recently. An ideal case study for the population-level effects of artemisinin use can be found in Vietnam, where a major increase of malaria cases in the 1980s was followed by the gradual adoption of artemisinin-based clinical case management. We assembled annual data from Vietnam’s National Institutes for Malariology, Parasitology, and Entomology showing the degree to which artemisinin therapies were adopted in different provinces, the effort placed on vector control, and the funding available to provincial malaria control programs, from 1991 to 2014. Data on urbanization were also collected for this period. We found that a 10% increase in the artemisinin proportion of treatments procured by a provincial control program corresponded to a 32.8% (95% CI: 27.7 – 37.5%) decline in estimated malaria cases; the association persisted and the effect size was nearly unchanged if confirmed cases or suspected cases were used. There was no consistent effect of vector control on malaria cases in Vietnam as a whole, nor was any effect found when the data were broken up regionally. The association between urbanization and malaria was generally negative and sometimes statistically significant. This was most pronounced in the central region of Vietnam, where a 10% increase in urbanization corresponded to a 43.3% (95% CI: 21.6 – 58.9%) decrease in suspected malaria incidence; this association was not statistically significant if confirmed cases or estimated cases were used. The decline of malaria in Vietnam from 1991 to 2014 can largely be attributed to the rapid adoption of artemisinin-based drugs. Recent analyses of aggregated data from Africa have shown that insecticide-treated nets have had the greatest effect on lowering malaria prevalence over the past fifteen years, suggesting that the success of different types of malaria interventions is region specific. Continuing global efforts on malaria elimination should focus on both vector control measures and increased access to artemisinin-combination therapies.
In silicoidentification of non-coding RNAs inHalobacterium salinarum NRC-1, a model archeon organism
Authors: Fonseca M. A. S. , Vêncio R. Z. N.
Published: June 2017

Background

In addition to the regulatory elements already known, for instance, transcription factors or post-translation modifications, there is growing interest in the regulatory role played by non-coding RNA molecules (ncRNA), whose functions are performed at a different level of biological information processing. Model organisms provide a convenient way of working in the laboratory, and different research groups use these models to conduct studies on the cellular mechanisms present in these organisms. Although some ncRNAs elements have been found in theHalobacterium salinarummodel organism, we believe that not enough is known about these genomic regions.

Methods

Therefore, anin silicoanalysis for ncRNA identification was conducted onH. salinarumNRC-1. Considering a data integration perspective and some available methodologies, several machine learning models were built and used to designate candidate ncRNAs genome regions.

Results

A total of 42 new ncRNAs were identified. Combing analysis with other available tools, it had been observed that some suggested candidates also was found with different methodologies and thus, it highlights the proposed results.
Twelve Elements of Visualization and Analysis for Tertiary and Quaternary Structure of Biological Molecules
Authors: Youkharibache Philippe
Published: June 2017

During the last decades, 3D Molecular Graphics in Life Sciences has been used almost exclusively by experts through complex software and applications ranging from Structural Biology to Computer Aided Drug Design. The emergence of JavaScript and WebGL as a viable platform has enabled 3D visualization of biomolecular structures through Web browsers, without any need for specialized software. Although still in its infancy, Web Molecular Graphics opens new perspectives. This white paper, proposes a set of Twelve Elements to consider to enable 3D visualization and structural analyses of biological systems in Web molecular viewers. The Elements go beyond 3D graphics and propose an integrated approach to visualize and analyze molecular entities and their interactions in multiple dimensions, at multiple levels of details, for diverse users. The bridging of 1D sequence browsers and 3D structure viewers, possible under a Web browser, enables information flow where molecular biologists can use structural information directly at the sequence level. Given the tsunami of sequence information linked to diseases from next generation sequencing - in need for interpretation - making structural information readily available to research scientists is a tremendous opportunity for medical discovery. The Twelve Elements are conceptual and are intended to entice developers to architect software components and APIs, and to gather together as a community around common goals and open source software. A few features of emerging viewers, all available as open source, are highlighted. Speed and quality of 3D graphics for large molecular systems, the interoperability of Web components, and the instantaneous sharing of annotated visualizations through the Web, are some of the most amazing and promising capabilities of 3D Web viewing, opening bright perspectives for Life Sciences research.
Structural brain development: a review of methodological approaches and best practices
Authors: Vijayakumar Nandita , Mills Kathryn L. , Alexander-Bloch Aaron , Tamnes Christian K. , Whittle Sarah
Published: June 2017

Continued advances in neuroimaging technologies and statistical modelling capabilities have improved our knowledge of structural brain development in children and adolescents. While this has provided an increasingly nuanced understanding of brain development, the field is still plagued by inconsistent findings. This review highlights the methodological diversity in existing longitudinal magnetic resonance imaging (MRI) studies on structural brain development during childhood and adolescence, and addresses how such variation might contribute to inconsistencies in the literature. We discuss the impact of method choices at multiple decision points across the research process, from study design and sample selection, to image processing and statistical analysis. We also highlight the extent to which different methodological considerations have been empirically examined, drawing attention to specific areas that would benefit from future investigation. Where appropriate, we recommend certain best practices that would be beneficial for the field to adopt, including greater completeness and transparency in reporting methods, in order to ultimately develop an accurate and detailed understanding of normative child and adolescent brain development.
A National Estimate of the Health and Cost Burden ofEscherichia coliBacteraemia in the Hospital Setting: The Importance of Antibiotic Resistance
Authors: Naylor NR , Pouwels KB , Hope R , Green N , Henderson KL , Knight GM , Atun R , Robotham JV , Deeny SR
Published: June 2017

Background

Antibiotic resistance poses a threat to public health and a burden to healthcare systems.Escherichia colicauses more bacteraemia cases in England than any other bacterial species, these infections, in part due to their high incidence, also pose a significant antibiotic resistance burden. The main aim of this study was to estimate the impact ofE. colibacteraemia on patient in-hospital mortality and length of stay. Secondarily, this study also aimed to estimate the effect of antibiotic resistance on these outcomes.

Methods and Findings

Case patients were adultE. colibacteraemia patients infected between July 2011 and June 2012, as reported in an English national mandatory surveillance database, with susceptibility data taken from a national laboratory surveillance database. Control patients were all non-case, adult patients with an English hospital admission record. Case and control patient characteristics and admission information were taken from NHS Digital Datasets. ‘Resistance’ was defined as non-susceptible and intermediate isolates, whilst ‘susceptible’ was defined as susceptible and non-tested isolates. Time to in-hospital mortality and discharge was investigated through Cox proportional hazards models. To acquire estimates of excess length of stay, multistate models were constructed, with a unit bed day cost applied to estimate cost burden. The total number of case and control hospital spells was 14,051 and 8,919,275 respectively. Acquisition ofE. colibacteraemia was associated with a statistically significant increased daily risk of in-hospital mortality, especially for the first eight days of someone’s hospital admission [Hazard Ratio = 2.77 (95% confidence interval; 2.61-2.94)]. Antibiotic resistance did not seem to significantly increase this risk further, though did significantly reduce risk of experiencing a discharge event (dead or alive).E.colibacteraemia was estimated to cost £14,340,900 over the study period (rounded to the nearest £100), with resistance associated with excess costs per infection of £220 - £420 dependent on resistance type, for those where a significant impact was found (rounded to the nearest £10).

Conclusions

E. colibacteraemia places a significant burden on patient health and on the hospital sector in England. Resistance is an important factor on length of stay with regards to such infections.
A genetic investigation of sex bias in the prevalence of attention deficit hyperactivity disorder
Authors: Martin Joanna , Walters Raymond K. , Demontis Ditte , Mattheisen Manuel , Lee S. Hong , Robinson Elise , Brikell Isabell , Ghirardi Laura , Larsson Henrik , Lichtenstein Paul , Eriksson Nicholas , Werge Thomas , Mortensen Preben Bo , Giørtz Pedersen Marianne , Mors Ole , Nordentoft Merete , Hougaard David M. , Bybjerg-Grauholm Jonas , Wray Naomi , Franke Barbara , Faraone Stephen V. , O’Donovan Michael C. , Thapar Anita , Børglum Anders D. , Neale Benjamin M.
Published: June 2017

Attention-deficit/hyperactivity disorder (ADHD) shows substantial heritability and is 2-7 times more common in males than females. We examined two putative genetic mechanisms underlying this sex bias: sex-specific heterogeneity and higher burden of risk in female cases. We analyzed genome-wide common variants from the Psychiatric Genomics Consortium and iPSYCH Project (20,183 cases, 35,191 controls) and Swedish population-registry data (N=77,905 cases, N=1,874,637 population controls). We find strong genetic correlation for ADHD across sex and no mean difference in polygenic burden across sex. In contrast, siblings of female probands are at an increased risk of ADHD, compared to siblings of male probands. The results also suggest that females with ADHD are at especially high risk of comorbid developmental conditions. Overall, this study supports a greater familial burden of risk in females with ADHD and some clinical and etiological heterogeneity. However, autosomal common variants largely do not explain the sex bias in ADHD prevalence.
Genetic context and proliferation determine contrasting patterns of copy number amplification and loss for 5S and 45S ribosomal DNA arrays in cancer
Authors: Wang Meng , Lemos Bernardo
Published: June 2017

The multicopy 45S ribosomal DNA (45S rDNA) array gives origin to the nucleolus, the first discovered nuclear organelle, site of Poll I 45S rRNA transcription and key regulator of cellular metabolism, DNA repair response, genome stability, and global epigenetic states. The multicopy 5S ribosomal DNA array (5S rDNA) is located on a separate chromosome, encodes the 5S rRNA transcribed by Pol III, and exhibits concerted copy number variation (cCNV) with the 45S rDNA array in human blood. Here we combined genomic data from >700 tumors and normal tissues to provide a portrait of ribosomal DNA variation in human tissues and cancers of diverse mutational signatures. We show that most cancers undergo coupled 5S rDNA array amplification and 45S rDNA loss, with abundant inter-individual variation in rDNA copy number of both arrays, and concerted modulation of 5S-45S copy number in some but not all tissues. Analysis of genetic context revealed associations between the presence of specific somatic alterations, such as P53 mutations in stomach and lung adenocarcinomas, and coupled 5S gain / 45S loss. Finally, we show that increased proliferation rates along cancer lineages can partially explain contrasting copy number changes in the 5S and 45S rDNA arrays. We suggest that 5S rDNA amplification facilitates increased ribosomal synthesis in cancer, whereas 45S rDNA loss emerges as a byproduct of transcription-replication conflict in highly proliferating tumor cells. Our results highlight the tissue- specificity of concerted copy number variation and uncover contrasting changes in 5S and 45S rDNA copy number along rapidly proliferating cell lineages.

Lay Summary

The 45S and 5S ribosomal DNA (rDNA) arrays contain hundreds of rDNA copies, with substantial variability across individuals and species. Although physically unlinked, both arrays exhibit concerted copy number variation. However, whether concerted copy number is universally observed across all tissues is unknown. It also remains unknown if rDNA copy number may vary in tissues and cancer lineages. Here we showed that most cancers undergo coupled 5S rDNA array amplification and 45S rDNA loss, and concerted 5S-45S copy number variation in some but not all tissues. The coupled 5S amplification and 45S loss is associated with the presence of certain somatic genetic variations, as well as increased cancerous cell proliferation rate. Our research highlights the tissue- specificity of concerted copy number variation and uncover contrasting changes in rDNA copy number along rapidly proliferating cell lineages. Our observations raise the prospects of using 5S and 45S ribosomal DNA states as indicators of cancer status and targets in new strategies for cancer therapy.
Functional selectivity for face processing in the temporal voice area of early deaf individuals
Authors: Benetti Stefania , van Ackeren Markus J. , Rabini Giuseppe , Zonca Joshua , Foa Valentina , Baruffaldi Francesca , Rezk Mohamed , Pavani Francesco , Rossion Bruno , Collignon Olivier
Published: June 2017

Brain systems supporting face and voice processing both contribute to the extraction of important information for social interaction (e.g., person identity). How does the brain reorganize when one of these channels is absent? Here we explore this question by combining behavioral and multimodal neuroimaging measures (magneto-encephalography and functional imaging) in a group of early deaf humans. We show enhanced selective neural response for faces and for individual face coding in a specific region of the auditory cortex that is typically specialized for voice perception in hearing individuals. In this region, selectivity to face signals emerges early in the visual processing hierarchy, shortly following typical face-selective responses in the ventral visual pathway. Functional and effective connectivity analyses suggest reorganization in long-range connections from early visual areas to the face-selective temporal area in individuals with early and profound deafness. Altogether, these observations demonstrate that regions that typically specialize for voice processing in the hearing brain preferentially reorganize for face processing in born deaf people. Our results support the idea that cross-modal plasticity in case of early sensory deprivation relates to the original functional specialization of the reorganized brain regions.
Honey Bee Diversity is Swayed by Migratory Beekeeping and Trade Despite Conservation Practices: Genetic Evidences for the Impact of Anthropogenic Factors on Population Structure
Authors: Kükrer Mert , Kence Meral , Kence Aykut
Published: June 2017

Intense admixture of honey bee (Apis melliferaL.) populations is mostly attributed to migratory beekeeping practices and replacement of queens and colonies with non-native races or hybrids of different subspecies. These two practices are also heavily carried out in Anatolia and Thrace where 5 subspecies reside naturally.

Here, we carried out an analysis of population structure of honey bees sampled from six different regions (n = 250) in order to test the genetic impacts of migratory beekeeping, queen and colony trade and conservation efficacy of isolated regions. A total of 30 microsatellite markers were used in four multiplex reactions.

Direct genetic impact of migratory beekeeping was demonstrated first time based on a comparison of assignment of individuals to their geographically native populations where migratory colonies showed less fidelity. We found genetic evidence for them acting as a hybrid zone mobile in space and time, becoming vectors of otherwise local gene combinations.

The effects of honey bee trade were revealed by the presence of very high introgression levels from the highly commercial Caucasian bees naturally limited to a narrow range. We also measured the direction and magnitude of this gene flow connected with bee trade.

Comparison between regions that are either open to migratory beekeeping or not let us evaluate the status of isolated regions as centers of limited gene flow and showed the importance of establishing such regions.

Despite signs of gene flow, our findings confirm high levels of geographically structured genetic diversity of four subspecies of honey bees in Turkey and emphasize the need to develop policies to maintain this diversity.

Our overall results might potentially bear a wider interest to the community since they constitute an important attempt to quantify the effects of anthropogenic impacts on established patterns of honey bee diversity. Our measurable and justified findings on migratory beekeeping, queen and colony replacements as well as conservation implications will hopefully be of use for the decision makers and other stakeholders.
Can a red wood-ant nest be a trap for fault-related CH4 micro-seepage? A case study from continuous short-term in-situ sampling
Authors: Berberich G.M. , Ellison A.M. , Berberich M.B. , Grumpe A. , Becker A. , Wohler C.
Published: June 2017

Methane (CH4) is common on Earth, forms the major commercial natural gas reservoirs, and is a key component of the global carbon cycle, but its natural sources are not well-characterized. We present a geochemical dataset acquired from a red wood-ant (RWA; Formica polyctena) nest in the Neuwied Basin, a part of the East Eifel Volcanic Field (EEVF), focusing on methane (CH4), stable carbon isotope of methane (δ13C-CH4), RWA activity patterns, earthquakes, and earth tides. Nest gas and ambient air were continuously sampled in-situ and analyzed to detect microbial, thermogenic, and abiotic fault-related micro-seepage. Methane degassing was not synchronized with earth tides. Elevated CH4 concentrations in nest gas appear to result from a combination of microbial activity and fault-related emissions moving via through fault networks through the RWA nest. Two δ13C-CH4 signatures were identified in nest gas: −69‰ and −37‰. The −69‰ signature of δ13C-CH4 within the RWA nest is attributed to microbial decomposition of organic matter. This finding supports previous findings that RWA nests are hot-spots of microbial CH4. Additionally, the −37% δ13C-CH4 signature is the first evidence that RWA nests also serve as traps for fault-related emissions of CH4. The −37‰ δ13C-CH4 signature can be attributed either to thermogenic/fault-related or to abiotic/fault-related CH4 formation originating from e.g. low-temperature gas-water-rock reactions in a continental setting at shallow depths (microseepage). Sources of these micro-seeps could be Devonian schists (“Sphaerosiderith Schiefer”) with iron concretions (“Eisengallen”), sandstones, or the iron-bearing “Klerf Schichten”. We cannot exclude overlapping micro-seepage of magmatic CH4 from the Eifel plume. Given the abundance of RWA nests on the landscape, their role as sources of microbial CH4 and traps for abiotically-derived CH4 should be included in estimation of methane emissions that are contributing to climatic change.
A model-free method for measuring dimerization free energies of CLC-ec1 in lipid bilayers
Authors: Chadda Rahul , Cliff Lucy , Brimberry Marley , Robertson Janice L.
Published: June 2017

We previously reported the equilibrium dimerization reaction of the CLC-ec1 Cl-/H+transporter in 2:1 POPE/POPG membranes (Chadda et al. 2016). This was determined by measuring the probability distributions of subunit capture into extruded liposomes by single-molecule photobleaching analysis across a wide range of subunit/lipid mole fraction densities. In this approach, knowledge of the liposome size distribution is necessary in order to correct the data for random co-capture events and extract the underlying dimerization reaction. For this we used a previously reported cryo-electron microscopy (cryo-EM) measured size distribution of 400 nm extruded liposomes made ofE. colipolar lipids (Walden et al. 2007). While the model and data agreed at low densities, we observed systematic inaccuracies at higher densities limiting our ability to extractFDimerin this range. To address this issue, we measured the 400 nm extruded 2:1 POPE/POPG liposome size distribution by cryo-EM and found that there is a small, but significant amount of larger liposomes in the population. Re-analysis of the I201W/I422W ‘WW’ photobleaching data using this distribution shows that the protein is monomeric in the membrane and can serve as an experimental control. Dimer controls were constructed by glutaraldehyde cross-linking of C85A/H234C ‘WT’ or introducing R230C/L249C, which forms a spontaneous disulfide bond. Determination ofFDimerbased on the experimental controls yields improved fits and no change in the previously reportedΔG° values, providing an alternate model-free approach to measuring CLC-ec1 dimerization in membranes.