bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine learning based side‐channel‐attack countermeasure with hamming‐distance redistribution and its application on advanced encryption standard
Authors: Shan Weiwei , Zhang Shuai , He Yukun
Published: June 2017

Side channel analysis (SCA) is effective to reveal the key of crypto devices by applying statistical analysis to a number of power traces, thus hardware countermeasure is necessary to protect the crypto circuits. A SCA‐resistance methodology by machine learning trained power compensation module is proposed to compensate the probability of hamming distance (HD) of the intermediate data directly, to make it unable to be distinguished from correct and incorrect sub‐key, thus providing resistance to SCA. The machine learning algorithm is used to find out the best HD redistribution mapping by using neural dynamic programming. Implemented on an AES‐128 encryption algorithm circuit on a Xilinx Spartan‐6 FPGA mounted on a SAKURA‐G board, experimental SCA results show that it can provide more than 200 × measures to disclosure and still has no sign to reveal the advanced encryption standard (AES) sub‐key. In addition, it has low power and area overhead and zero frequency overhead, thus is appropriate for hardware implementation of SCA countermeasure.
Through‐wall detection and imaging of a vibrating target using synthetic aperture radar
Authors: Corbett B. , Andre D. , Finnis M.
Published: June 2017

The development of a through‐wall synthetic aperture radar (SAR) simulator, which is being used to investigate the SAR artefacts originating from vibrating target's, known as paired echoes is explained. The simulation and experimental results both show that paired echoes can be detected and imaged through a wall, with a noticeable reduction in intensity, resulting in the number of visible echoes to be reduced in brightness and appear shifted in location in a through‐wall SAR image.
Design of high‐performance microstrip diplexers with stub‐loaded parallel‐coupled lines
Authors: Chen Xun , Yu Xi , Sun Sheng
Published: June 2017

A compact and high‐performance microstrip diplexer is designed by using stub‐loaded parallel‐coupled lines and half‐wavelength resonators. First, the traditional equivalent circuit of the parallel‐coupled line is extended to consider the length effect of the loaded stub. Second, by choosing the length of the stub, the multiple transmission zeros can be introduced and allocated to reduce the coupling between two signal channels and improve the isolation between two out‐put ports. Finally, a prototype of the proposed microstrip diplexer is designed and fabricated. The simulated insertion losses are 1.34 dB at 1.8 GHz (first band) and 1.28 dB at 2.4 GHz (second band), while the measured ones achieve 1.54 and 1.47 dB, respectively. More than 40‐dB isolation level is obtained over the whole concerned frequency range.
Debugging experiment machinery through time‐course event sequence analysis
Authors: Reynolds Christopher R. , Exley Kealan , Bultelle Matthieu A. , Sainz de Murieta Inaki , Kitney Richard I.
Published: June 2017

This application note describes an open‐source web application software package for viewing and analysing time‐course event sequences in the form of log files containing timestamps. Web pages allow the visualisation of time‐course event sequences as time curves and the comparison of sequences against each other to visualise deviations between the timings of the sequences. A feature allows the analysis of the sequences by parsing selected sections with a support vector machine model that heuristically calculates a value for the likelihood of an error occurring based on the textual output in the log files. This allows quick analysis for errors in files with large numbers of log events. The software is written in ASP.NET with Visual Basic code‐behind to allow it to be hosted on servers and integrated into web application frameworks.
Islanding detection technique based on superimposed components of voltage
Authors: Makwana Yogesh M. , Bhalja Bhavesh R.
Published: June 2017

This study presents a new islanding detection technique based on islanding discrimination factor which is derived from the superimposed components of voltages. These voltages are calculated by utilising the acquired voltage signals from the terminal of distributed generators. Various islanding and non‐islanding events with varying power mismatches have been simulated on two different widely used networks namely (i) IEEE 34 bus network and (ii) IEC61850‐7‐420 Micro‐Grid model in real time digital simulator (RTDS/RSCAD) environment. The authenticity of the presented scheme has been verified on diversified islanding and non‐islanding cases, generated from the above two models. The results indicate that the proposed scheme is able to distinguish islanding situation with non‐islanding events accurately. Moreover, it senses islanding condition quickly (within one and half cycle) even with perfect power balance situation and hence, eliminates non‐detection zone. In addition, it also provides better stability against nuisance tripping which is initiated due to various types of non‐islanding events including reconfiguration of the network. In the end, comparative assessment of the presented scheme with the scheme just published in the literature shows its domination in distinguishing islanding condition with non‐islanding events.
Three‐level boost converter with zero voltage transition
Authors: Hwu Kuo‐Ing , Shieh Jenn‐Jong , Jiang Wen‐Zhuang
Published: June 2017

As compared with the traditional boost converter, the three‐level boost converter possesses several advantages, such as lower switch voltage stresses and lower inductor current ripple. To improve the efficiency, this paper proposes a zero voltage transition (ZVT) three‐level boost converter. With the proposed ZVT circuit, the switches can achieve soft switching. Moreover, by using the voltage balance control, the output voltage can be equally across the output capacitors. In this study, the effectiveness of the proposed topology is verified by the experimental results based on the field‐programmable gate array control.
Crystal structure of tubulin tyrosine ligase-like 3 reveals essential architectural elements unique to tubulin monoglycylases
Authors: Garnham Christopher P. , Yu Ian , Li Yan , Roll-Mecak Antonina
Published: June 2017

Significance

Tubulin is subject to diverse posttranslational modifications that constitute a code read by cellular effectors. Most of these modifications are catalyzed by tubulin tyrosine ligase-like (TTLL) family members. The functional specialization and biochemical interplay between TTLL enzymes remain largely unknown. Our X-ray structure of TTLL3, a tubulin glycylase, identifies two functionally essential architectural elements and illustrates how the common TTL scaffold was used to functionally diversify the TTLL family. We show that TTLL3 competes with the glutamylase TTLL7 for overlapping modification sites on tubulin, providing a molecular basis for the anticorrelation between these modifications observed in vivo. Our results illustrate how a combinatorial tubulin code can arise through the intersection of activities of TTLL enzymes.
BLOC-1 is required for selective membrane protein trafficking from endosomes to primary cilia
Authors: Monis William J. , Faundez Victor , Pazour Gregory J.
Published: June 2017

Primary cilia perceive the extracellular environment through receptors localized in the ciliary membrane, but mechanisms directing specific proteins to this domain are poorly understood. To address this question, we knocked down proteins potentially important for ciliary membrane targeting and determined how this affects the ciliary trafficking of fibrocystin, polycystin-2, and smoothened. Our analysis showed that fibrocystin and polycystin-2 are dependent on IFT20, GMAP210, and the exocyst complex, while smoothened delivery is largely independent of these components. In addition, we found that polycystin-2, but not smoothened or fibrocystin, requires the biogenesis of lysosome-related organelles complex-1 (BLOC-1) for ciliary delivery. Consistent with the role of BLOC-1 in sorting from the endosome, we find that disrupting the recycling endosome reduces ciliary polycystin-2 and causes its accumulation in the recycling endosome. This is the first demonstration of a role for BLOC-1 in ciliary assembly and highlights the complexity of pathways taken to the cilium.
Advancing the link between ocean connectivity, ecological function and management challenges
Authors: Hidalgo Manuel , Kaplan David M. , Kerr Lisa A. , Watson James R. , Paris Claire B. , Browman Howard I.
Published: June 2017

“Ocean connectivity” is a dynamic and rapidly evolving field of research in marine science, partly because there is an increasing demand for information on connectivity that informs effective assessment and management of marine resources. Achieving this will require a better alignment between ocean connectivity tools and developments and the needs and challenges of assessments and conservation. For these reasons, the ICES Journal of Marine Science solicited contributions to the article theme set (TS), “Beyond ocean connectivity.” We briefly summarize the nine articles that appear herein, grouping them into four general topics: methodological advances, population dynamics and assessment implications of connectivity, spatial and management implications, and connectivity in ecosystem processes. We also discuss the challenges facing ocean connectivity research if it is to effectively support advancing fisheries assessment frameworks and integrated ecosystem approaches. We hope that the contributions included in this TS serve to convince managers and fisheries scientists of the need to incorporate results from research on connectivity.
National Study of Excellence and Innovation in Physical Therapist Education: Part 2—A Call to Reform
Authors: Jensen Gail M. , Hack Laurita M. , Nordstrom Terrence , Gwyer Janet , Mostrom Elizabeth
Published: June 2017

This perspective shares recommendations that draw from (1) the National Study of Excellence and Innovation in Physical Therapist Education research findings and a conceptual model of excellence in physical therapist education, (2) the Carnegie Foundation's Preparation for the Professions Program (PPP), and (3) research in the learning sciences. The 30 recommendations are linked to the dimensions described in the conceptual model for excellence in physical therapist education: Culture of Excellence, Praxis of Learning, and Organizational Structures and Resources. This perspective proposes a transformative call for reform framed across 3 core categories: (1) creating a culture of excellence, leadership, and partnership, (2) advancing the learning sciences and understanding and enacting the social contract, and (3) implementing organizational imperatives. Similar to the Carnegie studies, this perspective identifies action items (9) that should be initiated immediately in a strategic and systematic way by the major organizational stakeholders in physical therapist education. These recommendations and action items provide a transformative agenda for physical therapist education, and thus the profession, in meeting the changing needs of society through higher levels of excellence.
The Growing Importance of Social Skills in the Labor Market*
Authors: Deming David J.
Published: June 2017

The labor market increasingly rewards social skills. Between 1980 and 2012, jobs requiring high levels of social interaction grew by nearly 12 percentage points as a share of the U.S. labor force. Math-intensive but less social jobs—including many STEM occupations—shrank by 3.3 percentage points over the same period. Employment and wage growth were particularly strong for jobs requiring high levels of both math skill and social skills. To understand these patterns, I develop a model of team production where workers “trade tasks” to exploit their comparative advantage. In the model, social skills reduce coordination costs, allowing workers to specialize and work together more efficiently. The model generates predictions about sorting and the relative returns to skill across occupations, which I investigate using data from the NLSY79 and the NLSY97. Using a comparable set of skill measures and covariates across survey waves, I find that the labor market return to social skills was much greater in the 2000s than in the mid-1980s and 1990s.
Ocular Surface Changes After Sulfur Mustard Exposure in Rabbits, Monitored by Impression Cytology
Authors: Dachir Shlomit , Gutman Hila , Gore Ariel , Cohen Liat , Cohen Maayan , Amir Adina , Horwitz Vered , Kadar Tamar
Published: June 2017

Purpose:

Ocular injuries after exposure to sulfur mustard (SM) are characterized by acute corneal erosion and inflammation of the anterior segment that may be followed by delayed corneal neovascularization and epithelial defects, associated with limbal stem cell deficiency in part of the exposed eyes. This study aimed to further clarify the mechanism of the late injury by monitoring SM-induced cytological alterations in the ocular surface, in relation to the clinical symptoms, using impression cytology (IC).

Methods:

Rabbit eyes were exposed to SM vapor (n = 20) and were clinically observed up to 4 weeks. Samples for IC were collected simultaneously from the upper bulbar conjunctiva, limbus, and cornea and then fixed and stained with periodic acid–Schiff and hematoxylin. At 1 month, animals were killed and eyes dissected and processed for histology.

Results:

Concomitant with clinical symptoms of SM ocular toxicity, IC showed significant long-term loss of conjunctival goblet cells shortly after exposure, followed by abnormal differentiation toward squamous metaplasia. Simultaneously with corneal erosion, apoptotic bodies and cellular debris were seen in the corneal epithelium, followed by regeneration at 1 week. Migration of conjunctival goblet cells toward the cornea was noted in neovascularized eyes, as early as 1 week, indicating limbal stem cell deficiency. The IC findings were supported by histological evaluation.

Conclusions:

Continuous monitoring of the ocular surface after SM exposure by IC enables earlier detection of pathology and therapeutic intervention, therefore, is recommended for routine follow-up of casualties. Prolonged loss of goblet cells may point toward the role of mucin in the pathogenesis.
Clinical Presentation and Anatomical Location of Orbital Plasmacytomas
Authors: Thuro Bradley A. , Sagiv Oded , Shinder Roman , Debnam J. Matthew , Ozgur Omar , Ng John D. , Rootman Daniel , Thomas Sheeba K. , Esmaeli Bita
Published: June 2017

Purpose:

To evaluate the clinical and anatomical location of orbital plasmacytomas and assess local control following therapy.

Methods:

The American Society of Ophthalmic Plastic and Reconstructive Surgery Oncology Database was queried to identify patients diagnosed with orbital plasmacytoma. These patients’ records were reviewed for demographic characteristics, clinical and radiologic findings, treatments, and outcomes.

Results:

Thirty patients from 4 institutions (24 from MD Anderson Cancer Center, 3 from SUNY Downstate Medical Center, 2 from University of California, Los Angeles, and 1 from Oregon Health and Science University) were identified. Eighteen patients (60%) were diagnosed with multiple myeloma (MM) before and 11 (37%) were diagnosed with MM immediately after orbital plasmacytoma. Based on imaging, 4 distinct anatomical patterns were identified: 1) bony plasmacytoma affecting the superotemporal orbit, epidural space, and temporal fossa (15 patients; 50%); 2) discrete orbital plasmacytoma (7 patients; 23%); 3) infiltrative plasmacytoma either originating from a sinus (4 patients; 13%); or 4) originating from the orbital floor and infiltrating facial soft tissue (4 patients; 13%). Of the 29 patients with available treatment data, 2 had radiation only, 3 had chemotherapy only, 6 had chemoradiation, and 18 had stem cell transplant following chemoradiation (n = 17) or only chemotherapy (n = 1). Following treatment, 10 patients achieved complete and 11 achieved partial responses.

Conclusion:

Orbital plasmacytomas were found exclusively in patients with MM diagnosed before or immediately after orbital plasmacytoma. Plasmacytomas can have 4 distinct anatomical patterns of origin. Following treatment, all patients had good to excellent local control of their orbital lesions.
Spontaneous Resolution of Optic Neuropathy in Sphenoid Wing Meningioma
Authors: Ramesh Sathyadeepak , Goldberg Robert Alan , Rootman Daniel Benson
Published: June 2017

The authors describe herein a case of optic neuropathy in progesterone receptor positive sphenoid wing meningioma of the greater wing which demonstrated spontaneous recovery with conservative management.
Health Behaviors Survey
Authors: Serowoky Mary L. , Kwasky Andrea N.
Published: June 2017

Objective

This study determined the prevalence of alcohol, drug, and nonmedical prescription drugs at a small private university. In addition, risk and protective factors are examined.

Method

The Core Institute (Southern Illinois University) was contracted to administer an anonymous, Web-based 49-item survey to matriculated undergraduate students, aged 18–23 years. Data were obtained on student behaviors, perceptions, consequences of substance use, risk factors, and coping strategies. Statistical analysis included descriptive measures, cross-tabs, t test, and chi-square.

Results

The response rate was 14%, which is consistent with other CORE Institute surveys. Almost half of the total respondents were from the college of nursing (46%), and most participants were female (82%). There was a significant association between heavy drinking and grades; the B students engaged in more binge drinking. Living on campus and being involved in Greek life confer a higher level of risk for sexual assault when alcohol was consumed. Most participants (57%) were unaware of campus resources for assistance with alcohol or drug problems.

Conclusion

Campus administrators now have a better awareness related to the extent of drug and alcohol use among the student body. A faculty engagement workshop was developed to provide tools to assess and communicate with students. Improvements are anticipated to enhance student relationships and decrease incidents of drug- and alcohol-related sexual assault or misconduct.
Effectiveness of the Sexual Health/Reproductive Health Education Given to Turkey Adolescents Who Use Alcohol or Substance
Authors: Ataman Hacer , Kömürcü Nuran
Published: June 2017

Objective

The research was conducted experimentally to evaluate the effectiveness of the sexual health/reproductive health (SH/RH) education given to Turkish adolescents who use alcohol or illicit substances.

Methods

The population was adolescents who use alcohol and substances and were inpatients at the Child and Adolescent Substance Addiction Research, Treatment and Education Center. The adolescents were grouped into the following three groups: Group 1 (control group), Group 2 (those who have received training once), and Group 3 (those who have received training twice). Data were collected between September 2011 and December 2012 using the forms Self-Introduction and Information on Sexual Health-Reproductive Health and Information on Sexual Health-Reproductive Health Education Modules.

Results

Upon studying the total SH/RH test scores of the groups individually, a statistically significant difference was observed in the scores of Groups 2 and 3 (p < .01). Upon studying the change in the posttest scores from the pretest ones for each group individually, the increase in the scores of Group 3 (34.57 ± 16.33) was observed to have a statistically highly significant difference from those of Groups 1 (2.73 ± 10.65) and 2 (20.23 ± 12.09; p < .01).

Conclusions and Practice Implications

Adolescents who abuse alcohol or substances should be given SH/RH education in a repetitive manner for prevention of risky sexual behavior.
Oxytocin and potential benefits for obesity treatment
Authors: Olszewski Pawel K. , Klockars Anica , Levine Allen S.
Published: June 2017

Purpose of review

Laboratory animal experiments have consistently shown that oxytocin causes early termination of food intake, thereby promoting a decrease in body weight in a long term. Recent studies have also assessed some of oxytocin's effects on appetite and energy balance in humans. The present study examines the findings of the key basic research and of the few clinical studies published thus far in the context of potential benefits and challenges stemming from the use of oxytocin in obese patients.

Recent findings

Basic research indicates the involvement of oxytocin in satiety, processing, in reducing a drive to eat for pleasure and because of psychosocial factors. Although the results of clinical studies are very scarce, they suggest that oxytocin administered intranasally in humans decreases energy-induced and reward-induced eating, supports cognitive control of food choices, and improves glucose homeostasis, and its effectiveness may be BMI dependent.

Despite the wealth of basic research showing broad anorexigenic effects of oxytocin, clinical studies on oxytocin's therapeutic potential in obesity, are still in their infancy. Future implementation of oxytocin-based pharmacological strategies in controlling energy balance will likely depend on our ability to integrate diverse behavioral and metabolic effects of oxytocin in obesity treatment regimens.
Novel imaging in advanced prostate cancer
Authors: Goldberg Hanan , Hamilton Robert J.
Published: June 2017

Purpose of review

Prostate cancer (PCa) is the most commonly diagnosed noncutaneous cancer and second leading cause of death in men. Imaging evaluation of PCa is challenging because of the prostate's deep pelvic location, its complex zonal anatomy and its multifocal nature. Novel imaging modalities are needed to improve detection, reassessment in biochemical relapse, and disease progression in advanced metastatic stages.

Recent findings

Current imaging modalities have distinct strengths. However, all lack the ability to diagnose micrometastases, differentiate high from low-grade disease and diagnose advanced disease, especially at low prostate specific antigen values. There is a need to combine the existing imaging methods with concepts utilizing tumor biology to differentiate biologically aggressive from indolent tumors. PET imaging with novel tracers facilitate improved imaging of PCa, but also usher in new compounds that could be useful for directing treatment as well. Most tracers have limited sensitivity, with the exception of prostate-specific membrane antigen (PSMA)-targeting tracers, that offer relatively higher sensitivity and specificity.

PSMA-PET appears promising in improving the imaging yield particularly in recurrent and advanced disease states. Incorporating PSMA-PET in these settings could open or prolong windows along the trajectory of the disease that could allow new treatments or more effective use of currently existing treatments. Prospective studies focusing on novel imaging enhancement and integration with therapeutic applications are needed.
Social dilemma in the external immune system of the red flour beetle? It is a matter of time
Authors: Gokhale Chaitanya S. , Traulsen Arne , Joop Gerrit
Published: June 2017

Sociobiology has revolutionized our understanding of interactions between organisms. Interactions may present a social dilemma where the interests of individual actors do not align with those of the group as a whole. Viewed through a sociobiological lens, nearly all interactions can be described in terms of their costs and benefits and a number of them then resemble a social dilemma. Numerous experimental systems, from bacteria to mammals, have been proposed as models for studying such dilemmas. Here we make use of the external immune system of the red flour beetle,Tribolium castaneum, to investigate how the experimental duration can affect whether the external secretion comprises a social dilemma or not. Some beetles (secretors) produce a costly quinone-rich external secretion that inhibits microbial growth in the surrounding environment, providing the secretors with direct personal benefits. However, since the antimicrobial secretion acts in the environment of the beetle it is potentially also advantageous to other beetles (non-secretors), who avoid the cost of producing the secretion. We test experimentally if the secretion qualifies as a public good. We find that in the short term, costly quinone secretion can be interpreted as a public good presenting a social dilemma where the presence of secretors increases the fitness of the group. In the long run, the benefit to the group of having more secretors vanishes and actually becomes detrimental to the group. Therefore, in such semi-natural environmental conditions, it turns out that qualifying a trait as social can be a matter of timing.
Reconstructing spatial transport distributions in the nuclear pore complex from 2D images—how reliable is it?
Authors: Tu Li-Chun , Huisman Maximiliaan , Chung Yu-Chieh , Smith Carlas , Grunwald David
Published: June 2017

Imaging single molecules in living cells and reconstituted cell systems has resulted in a new understanding of the dynamics of nuclear pore complex functions over the last decade. It does, however, fall short on providing insights into the functional relationships between the pore and nucleocytoplasmic cargo in three-dimensional space. This limited ability is the result of insufficient resolution of optical microscopes along the optical axis and limited fluorescent signal due to the short timescales involved in nuclear transport (fractions of a second). To bypass current technological limitations, it was suggested that highly time-resolved 2D single molecule data could be interpreted as projected cargo locations and could subsequently be transformed into a spatial cargo distribution by assuming cylindrical symmetry1. Such cargo distributions would provide valuable insights into the NPC-mediated transport in cells. This method, termed 3D-SPEED, has attracted large interest inside and beyond the nuclear pore field, but has also been sharply critiqued for a lack of critical evaluation. Here we present such an evaluation, testing the robustness, reconstruction quality and model-dependency.
Whole-ganglion imaging of voltage in the medicinal leech using a double-sided microscope
Authors: Tomina Yusuke , Wagenaar Daniel A.
Published: June 2017

Studies of neuronal network emergence during sensory processing and motor control are greatly promoted by technologies that allow us to simultaneously record the membrane potential dynamics of a large population of neurons in single cell resolution. To achieve whole-brain recording with the ability to detect both small synaptic potentials and action potentials, we developed a voltage-sensitive dye (VSD) imaging technique based on a double-sided microscope that can image two sides of a nervous system simultaneously. We applied this system to the segmental ganglia of the medicinal leech. Double-sided VSD imaging enabled simultaneous recording of membrane potential events from almost all of the identifiable neurons. Using data obtained from double-sided VSD imaging we analyzed neuronal dynamics in both sensory processing and generation of behavior and constructed functional maps for identification of neurons contributing to these processes.
Using connectivity to identify climatic drivers of local adaptation
Authors: Macdonald Stewart L. , Llewelyn John , Phillips Ben L.
Published: June 2017

This preprint has been reviewed and recommended by Peer Community In Evolutionary Biology (http://dx.doi.org/10.24072/pci.evolbiol.100034).Despite being able to conclusively demonstrate local adaptation, we are still often unable to objectively determine the climatic drivers of local adaptation. Given the rapid rate of global change, understanding the climatic drivers of local adaptation is vital. Not only will this tell us which climate axes matter most to population fitness, but such knowledge is critical to inform management strategies such as translocation and targeted gene flow. While simple assessments of geographic trait variation are useful, geographic variation (and its associations with environment) may represent plastic, rather than evolved, differences. Additionally, the vast number of trait–environment combinations makes it difficult to determine which aspects of the environment populations adapt to. Here we argue that by incorporating a measure of landscape connectivity as a proxy for gene flow, we can differentiate between trait–environment relationships underpinned by genetic differences versus those that reflect phenotypic plasticity. By doing so, we can rapidly shorten the list of trait–environment combinations that may be of adaptive significance. We demonstrate how this reasoning can be applied using data on geographic trait variation in a lizard species from Australia's Wet Tropics rainforest. Our analysis reveals an overwhelming signal of local adaptation for the traits and environmental variables we investigated. Our analysis also allows us to rank environmental variables by the degree to which they appear to be driving local adaptation. Although encouraging, methodological issues remain: we point to these issue in the hope that the community can rapidly hone the methods we sketch here. The promise is a rapid and general approach to identifying the environmental drivers of local adaptation.
Pair Matcher (PaM): fast model-based optimisation of treatment\case-control matches using demographic and genetic data
Authors: Ryan Desmond M , Elhaik Eran
Published: June 2017

In clinical trials, individuals are matched for demographic criteria, paired, and then randomly assigned to treatment and control groups to determine a drug’s efficacy. The successful completion of pilot trials is a prerequisite to larger and more expensive Phase III trials. One of the chief causes for the irreproducibility of results across pilot to Phase III trials is population stratification bias caused by the uneven distribution of ancestries in the treatment and control groups. Pair Matcher (PaM) addresses stratification bias by optimising pairing assignmentsa priori- and\orposteriorito the trial using both genetic and demographic criteria. Using simulated and real datasets, we show thatPaMidentifies ideal and near-ideal pairs that are more genetically homogeneous than those identified based on racial criteria or Principal Component Analysis (PCA) alone. Homogenising the treatment (or case) and control groups can be expected to improve the accuracy and reproducibility of the study.PaM’s ability to infer the ancestry of the participants further allows identifying subgroup of responders and developing a precision medicine approach to treatment.PaMis simple to execute, fast, and can be used for clinical trials and association studies.PaMis freely available via R scripts and a web interface.
Subharmonics and chaos in simple periodically-forced biomolecular models
Authors: Nikolaev Evgeni V. , Rahi Sahand Jamal , Sontag Eduardo D.
Published: June 2017

This paper uncovers a remarkable behavior in two biochemical systems that commonly appear as components of signal transduction pathways in systems biology. These systems have globally attracting steady states when unforced, so they might have been considered “uninteresting” from a dynamical standpoint. However, when subject to a periodic excitation, strange attractors arise via a period-doubling cascade. Quantitative analyses of the corresponding discrete chaotic trajectories are conducted numerically by computing largest Lyapunov exponents, power spectra, and autocorrelation functions. To gain insight into the geometry of the strange attractors, the phase portraits of the corresponding iterated maps are interpreted as scatter plots for which marginal distributions are additionally evaluated. The lack of entrainment to external oscillations, in even the simplest biochemical networks, represents a level of additional complexity in molecular biology, which has previously been insufficiently recognized but is plausibly biologically important.
Effective online Bayesian phylogenetics via sequential Monte Carlo with guided proposals
Authors: Fourment Mathieu , Claywell Brian C. , Dinh Vu , McCoy Connor , Matsen Frederick A. , Darling Aaron E.
Published: June 2017

Abstract

Modern infectious disease outbreak surveillance produces continuous streams of sequence data which require phylogenetic analysis as data arrives. Current software packages for Bayesian phy-logenetic inference are unable to quickly incorporate new sequences as they become available, making them less useful for dynamically unfolding evolutionary stories. This limitation can be addressed by applying a class of Bayesian statistical inference algorithms called sequential Monte Carlo (SMC) to conductonline inference, wherein new data can be continuously incorporated to update the estimate of the posterior probability distribution. In this paper we describe and evaluate several different online phylogenetic sequential Monte Carlo (OPSMC) algorithms. We show that proposing new phylogenies with a density similar to the Bayesian prior suffers from poor performance, and we develop ‘guided’ proposals that better match the proposal density to the posterior. Furthermore, we show that the simplest guided proposals can exhibit pathological behavior in some situations, leading to poor results, and that the situation can be resolved by heating the proposal density. The results demonstrate that relative to the widely-used MCMC-based algorithm implemented in MrBayes, the total time required to compute a series of phylogenetic posteriors as sequences arrive can be significantly reduced by the use of OPSMC, without incurring a significant loss in accuracy.
An intracellular pathogen response pathway promotes proteostasis inC. elegans
Authors: Reddy Kirthi C. , Dror Tal , Sowa Jessica N. , Panek Johan , Chen Kevin , Lim Efrem S. , Wang David , Troemel Emily R.
Published: June 2017

Maintenance of proteostasis is critical for organismal health. Here we describe a novel pathway that promotes proteostasis, identified through the analysis ofC. elegansgenes upregulated by intracellular infection. We named this distinct transcriptional signature the Intracellular Pathogen Response (IPR), and it includes upregulation of several predicted ubiquitin ligase complex components such as the cullincul-6. Through a forward genetic screen we foundpals-22, a gene of previously unknown function, to be a repressor of thecul-6/Cullin gene and other IPR gene expression. Interestingly,pals-22mutants have increased thermotolerance and reduced levels of stress-induced polyglutamine aggregates, likely due to upregulated IPR expression. We found the enhanced stress resistance ofpals-22mutants to be dependent oncul-6, suggesting thatpals-22mutants have increased activity of a CUL-6/Cullin-containing ubiquitin ligase complex. pals-22mutant phenotypes are distinct from the well-studied heat shock and insulin signaling pathways, indicating that the IPR is a novel pathway that protects animals from proteotoxic stress.
Driver pattern identification over the gene co-expression of drug response in ovarian cancer by integrating high throughput genomics data
Authors: Lu Xinguo , Lu Jibo , Liao Bo , Li Keqin
Published: June 2017

The multiple types of high throughput genomics data create a potential opportunity to identify driver pattern in ovarian cancer, which will acquire some novel and clinical biomarkers for appropriate diagnosis and treatment to cancer patients. However, it is a great challenging work to integrate omics data, including somatic mutations, Copy Number Variations (CNVs) and gene expression profiles, to distinguish interactions and regulations which are hidden in drug response dataset of ovarian cancer. To distinguish the candidate driver genes and the corresponding driving pattern for resistant and sensitive tumor from the heterogeneous data, we combined gene co-expression modules and mutation modulators and proposed the identification driver patterns method. Firstly, co-expression network analysis is applied to explore gene modules for gene expression profiles via weighted correlation network analysis (WGCNA). Secondly, mutation matrix is generated by integrating the CNVs and somatic mutations, and a mutation network is constructed from this mutation matrix. The candidate modulators are selected from the significant genes by clustering the vertex of the mutation network. At last, regression tree model is utilized for module networks learning in which the achieved gene modules and candidate modulators are trained for the driving pattern identification and modulator regulatory exploring. Many of the candidate modulators identified are known to be involved in biological meaningful processes associated with ovarian cancer, which can be regard as potential driver genes, such as CCL11, CCL16, CCL18, CCL23, CCL8, CCL5, APOB, BRCA1, SLC18A1, FGF22, GADD45B, GNA15, GNA11 and so on, which can help to facilitate the discovery of biomarkers, molecular diagnostics, and drug discovery.
KmerFinderJS: A client-server method for fast species typing of bacteria over slow Internet connections
Authors: Cineros Jose Luis Bellod , Lund Ole
Published: June 2017

Motivation

KmerFinder is a program based on K-mer statistics for identifying bacterial species in whole genome data, that as a web server that have been used more than 10.000 times. Kmer-FinderJS is a development of the KmerFinder that benefits from the downsampling of data using a prefix filtering used by KmerFinder, to minimize amount of data that needs to be transferred between the client and the server.

Results

KmerFinderJS replaces the python based hash structure for holding the databases with a true Key-value database. These improvements are shown to lead to a many-fold speed up of species identification with the internet transfer speeds that are realistic to expect today. It is also shown that the method can find the true content of an artificial metagenomic cocktail with no false positives.

Availability

The method is freely available athttps://cge.cbs.dtu.dk/services/KmerFinderJS/and as a source code athttps://bitbucket.org/genomicepidemiology/kmerfinderjs

Contact

cisneros@cbs.dtu.dk

Supplementary information

Supplementary data are available atbiorxivonline.
Energetic costs of cellular and therapeutic control of stochastic mtDNA populations
Authors: Hoitzing Hanne , Gammage Payam A. , Minczuk Michal , Johnston Iain G. , Jones Nick S.
Published: June 2017

Mitochondrial DNA (mtDNA) copy numbers fluctuate over time due to stochastic cellular dynamics. Understanding mtDNA dynamics and the accumulation of mutations is vital for understanding mitochondrial-related diseases. Here, we use stochastic modelling to derive general results for the impact of cellular control on mtDNA populations, the cost to the cell of different mtDNA states, and the optimisation of therapeutic control of mtDNA populations. We provide theoretical evidence that an increasing mtDNA variance can increase the energetic cost of maintaining a tissue, that intermediate levels of heteroplasmy can be more detrimental than ho-moplasmy even for a dysfunctional mutant, that het-eroplasmy distribution (not mean alone) is crucial for the success of gene therapies, and that long-term rather than short intense gene therapies are more likely to beneficially impact mtDNA populations. New experiments validate our predictions on heteroplasmy dependence of therapeutic outcomes.
Beyond brain size
Authors: Logan Corina J , Avin Shahar , Boogert Neeltje , Buskell Andrew , Cross Fiona R. , Currie Adrian , Jelbert Sarah , Lukas Dieter , Mares Rafael , Navarrete Ana F , Shigeno Shuichi , Montgomery Stephen H
Published: June 2017

Despite prolonged interest in comparing brain size and behavioral proxies of ‘intelligence’ across taxa, the adaptive and cognitive significance of brain size variation remains elusive. Central to this problem is the continued focus on hominid cognition as a benchmark, and the assumption that behavioral complexity has a simple relationship with brain size. Although comparative studies of brain size have been criticized for not reflecting how evolution actually operates, and for producing spurious, inconsistent results, the causes of these limitations have received little discussion. We show how these issues arise from implicit assumptions about what brain size measures and how it correlates with behavioral and cognitive traits. We explore how inconsistencies can arise through heterogeneity in evolutionary trajectories and selection pressures on neuroanatomy or neurophysiology across taxa. We examine how interference from ecological and life history variables complicates interpretations of brain-behavior correlations, and point out how this problem is exacerbated by the limitations of brain and cognitive measures. These considerations, and the diversity of brain morphologies and behavioral capacities, suggest that comparative brain-behavior research can make greater progress by focusing on specific neuroanatomical and behavioral traits within relevant ecological and evolutionary contexts. We suggest that a synergistic combination of the ‘bottom up’ approach of classical neuroethology and the ‘top down’ approach of comparative biology/psychology within closely related but behaviorally diverse clades can limit the effects of heterogeneity, interference, and noise. We argue this shift away from broad-scale analyses of superficial phenotypes will provide deeper, more robust insights into brain evolution.
Mycophenolate mofetil increases inflammation resolution in zebrafish via neutrophil apoptosis
Authors: Bojarczuk Aleksandra , Johnston Simon A.
Published: June 2017

Mycophenolate mofetil (MMF) is an immunosuppressive agent used in the treatment of autoimmune and inflammatory conditions, and following organ transplant. MMF treatment results in lymphopenia via the depletion of purines required for DNA synthesis. While the primary effect of MMF treatment is thought to be via the depletion of lymphocytes, MMF has also been associated with innate immune defects, including neutropenia and neutrophil dysplasia. Here, we address the question of MMF specific effects on neutrophils in anin vivomodel of neutrophil inflammation in zebrafish. We find that, following tissue injury, MMF increases resolution of neutrophilic inflammation via increased neutrophil apoptosis. Critically, we identify that the effect of MMF is distinct from DNA synthesis inhibition by using the competitive inhibitor of purine nucleotide incorporation, azathioprine. Therefore, we propose that increased neutrophil cell death during inflammatory insult may play a role in neutrophil defects associated with MMF treatment.
Modelling personality, plasticity and predictability in shelter dogs
Authors: Goold Conor , Newberry Ruth C.
Published: June 2017

Behavioural assessments of shelter dogs (Canis lupus familiaris) typically comprise standardised test batteries conducted at one time point but test batteries have shown inconsistent predictive validity. Longitudinal behavioural assessments offer an alternative. We modelled longitudinal observational data on shelter dog behaviour using the framework of behavioural reaction norms, partitioning variance into personality (i.e. inter-individual differences in behaviour), plasticity (i.e. individual differences in behavioural change) and predictability (i.e. individual differences in residual intra-individual variation). We analysed data on 3,263 dogs’ interactions (N = 19,281) with unfamiliar people during their first month after arrival at the shelter. Accounting for personality, plasticity (linear and quadratic trends) and predictability improved the predictive accuracy of the analyses compared to models quantifying personality and/or plasticity only. While dogs were, on average, highly sociable with unfamiliar people and sociability increased over days since arrival, group averages were unrepresentative of all dogs and predictions made at the individual level entailed considerable uncertainty. Effects of demographic variables (e.g. age) on personality, plasticity and predictability were observed. Behavioural repeatability was higher one week after arrival compared to arrival day. Our results highlight the value of longitudinal assessments on shelter dogs and identify measures that could improve the predictive validity of behavioural assessments in shelters.
Central amygdala circuits modulate food consumption through a positive valence mechanism
Authors: Douglass Amelia M. , Kucukdereli Hakan , Ponserre Marion , Markovic Milica , Gründemann Jan , Strobel Cornelia , Alcala Morales Pilar L. , Conzelmann Karl-Klaus , Lüthi Andreas , Klein Rüdiger
Published: June 2017

The complex behaviors underlying the pursuit and consumption of rewards are integral to an organism’s survival. The hypothalamus and mesolimbic dopamine system are key mediators of these behaviors, yet regulation of appetitive and consummatory behaviors outside of these regions is not well understood. The central nucleus of the amygdala (CeA) is implicated in feeding and reward behavior, but the specific neural players and circuit mechanisms that positively regulate these behaviors remain unclear. Here, we define the neuronal mechanisms by which the CeA promotes consumption of food. We show, usingin vivoactivity manipulations and Ca2+imaging, that CeA GABAergic neurons expressing the serotonin receptor 2a (Htr2a) modulate food consumption in multiple contexts, promote positive reinforcement and are activein vivoduring eating. We demonstrate using electrophysiology, anatomical tracing methods andin vivooptogenetics that both intra-CeA and long-range circuit mechanisms underlie these functional effects. Finally, we show that CeAHtr2aneurons are poised to regulate food consumption through inputs from feeding-relevant brain regions. Our study highlights a mechanism by which defined CeA neural circuits positively regulate food consumption.
Alkyl gallates display elicitor activities in tobacco plants
Authors: Goupil Pascale , Benouaret Razik , Richard Claire
Published: June 2017

Alkyl gallates showed elicitor activities on tobacco in both whole plants and cell suspensions. Methyl gallate (MG), ethyl gallate (EG) andn-propyl gallate (PG) infiltration into tobacco leaves induced hypersensitive reaction-like lesions and topical production of autofluorescent compounds revealed under UV light. When sprayed on tobacco plants at 5 mM, EG promoted upregulation of defence-related genes such as the antimicrobialPR1, β-1,3-glucanasePR2, chitinasePR3and osmotinPR5target genes. Tobacco BY-2 cells challenged with EG underwent cell death in 48 h, significantly reduced in the presence of the protease inhibitor aprotinin. The three alkyl gallates all caused alkalinisation of the BY-2 extracellular medium, whereas gallic acid did not trigger any pH variation. Using EGTA or LaCl3, we showed that Ca2+mobilisation occurred in BY-2 cells elicited with EG. Overall, our findings are the first evidence of alkyl gallate elicitor properties with early perception events on plasma membrane, potential hypersensitive reactions and PR-related downstream defence responses in tobacco.

Highlights

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Alkyl gallates elicited defence reactions in tobacco

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Alkyl gallates induced local biochemical changes in tobacco leaves

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Alkyl gallates caused modification of plasma membrane properties

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Ethyl gallate led to defence transcript accumulation and dose-dependent cell death associated with hypersensitive response

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Alkyl gallates are novel elicitor agents well-suited to crop protection schemes.