bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi-domain DDoS Mitigation Based on Blockchains
Authors: Rodrigues Bruno , Bocek Thomas , Stiller Burkhard
Published: June 2017

The exponential increase of the traffic volume makes Distributed Denial-of-Service (DDoS) attacks a top security threat to service providers. Existing DDoS defense mechanisms lack resources and flexibility to cope with attacks by themselves, and by utilizing other’s companies resources, the burden of the mitigation can be shared. Technologies as blockchain and smart contracts allow distributing attack information across multiple domains, while SDN (Software-Defined Networking) and NFV (Network Function Virtualization) enables to scale defense capabilities on demand for a single network domain. This proposal presents the design of a novel architecture combining these elements and introducing novel opportunities for flexible and efficient DDoS mitigation solutions across multiple domains.
A Blockchain-Based Architecture for Collaborative DDoS Mitigation with Smart Contracts
Authors: Rodrigues Bruno , Bocek Thomas , Lareida Andri , Hausheer David , Rafati Sina , Stiller Burkhard
Published: June 2017

The rapid growth in the number of insecure portable and stationary devices and the exponential increase of traffic volume makes Distributed Denial-of-Service (DDoS) attacks a top security threat to services provisioning. Existing defense mechanisms lack resources and flexibility to cope with attacks by themselves, and by utilizing other’s companies resources, the burden of the mitigation can be shared. Emerging technologies such as blockchain and smart contracts allows for the sharing of attack information in a fully distributed and automated fashion. In this paper, the design of a novel architecture is proposed by combining these technologies introducing new opportunities for flexible and efficient DDoS mitigation solutions across multiple domains. Main advantages are the deployment of an already existing public and distributed infrastructure to advertise white or blacklisted IP addresses, and the usage of such infrastructure as an additional security mechanism to existing DDoS defense systems, without the need to build specialized registries or other distribution mechanisms, which enables the enforcement of rules across multiple domains.
Towards a Software-Defined Security Framework for Supporting Distributed Cloud
Authors: Compastié Maxime , Badonnel Rémi , Festor Olivier , He Ruan , Kassi-Lahlou Mohamed
Published: June 2017

Cloud computing provides new facilities for building elaborated services hosted through various infrastructures over the Internet. In the meantime, these ones pose new important challenges in terms of security due to their intrinsic nature. We propose in this paper to detail a software-defined security framework supporting the protection of these services, in the context of distributed cloud. These ones require security mechanisms able to cope with their multi-tenancy and multi-cloud properties. The foundations of this framework rely on the software-defined logic to express and propagate security policies to the considered cloud resources, and on the autonomic paradigm to dynamically configure and adjust these mechanisms to distributed cloud constraints. In particular, we describe the main components and protocols of this software-defined security framework, evaluate this one and discuss implementation considerations, through the analysis of different realistic scenarios.
Hunting SIP Authentication Attacks Efficiently
Authors: Jansky Tomáš , Čejka Tomáš , Bartoš Václav
Published: June 2017

Extended flow records with application layer (L7) information allow for detection of various types of malicious traffic. Voice over IP (VoIP) is an example of technology that works on L7 and many attacks against it cannot be reliably detected using just basic flow information. Session Initiation Protocol (SIP), which is commonly used for VoIP signalling, is a frequent target of many types of attacks. This paper proposes and evaluates a novel algorithm for near real time detection of username scanning and password guessing attacks on SIP servers. The detection is based on analysis of L7 extended flow records.
Extraction of partonic transverse momentum distributions from semi-inclusive deep-inelastic scattering, Drell-Yan and Z-boson production
Authors: Bacchetta Alessandro , Delcarro Filippo , Pisano Cristian , Radici Marco , Signori Andrea
Published: June 2017

Abstract

We present an extraction of unpolarized partonic transverse momentum distributions (TMDs) from a simultaneous fit of available data measured in semi-inclusive deep-inelastic scattering, Drell-Yan andZboson production. To connect data at different scales, we use TMD evolution at next-to-leading logarithmic accuracy. The analysis is restricted to the low-transverse-momentum region, with no matching to fixed-order calculations at high transverse momentum. We introduce specific choices to deal with TMD evolution at low scales, of the order of 1 GeV2. This could be considered as a first attempt at a global fit of TMDs.
Recombinant 20.8-kDa protein of Mycobacterium avium subsp. paratuberculosis-based sero-diagnosis of paratuberculosis
Authors: Goswami P. P. , Chand Gokul , Prasad N. S. , Deb R. , Basagoudanavar S. H.
Published: June 2017

Johne’s disease or paratuberculosis is a chronic infectious enteric disease of ruminants caused by the intracellular pathogen. The control of the Johne’s disease is hampered by lack of specific diagnostic tests. In this study, we have cloned and expressed the N-terminal region of the locus tag Map 1637c encoding 20.8-kDa (r20.8) protein of Mycobacterium avium subsp. paratuberculosis. The recombinant protein r20.8 was expressed in high levels in Escherichia coli. The protein r20.8 was purified by single-step chromatography using Ni–NTA agarose. The protein r20.8 was reacted with anti-r20.8 antibodies as well as cattle sera infected with Map on Western blot. ELISA using well-characterized sera (both positive and negative; n = 60 each) Map-infected and non-infected cattle, respectively, yielded a sensitivity of 73.3% and a specificity of 98.3%. The 20.8 kDa protein expressed in the present study will prove useful as reagent in diagnostic test.
Bioremediation of palm industry wastes using vermicomposting technology: its environmental application as green fertilizer
Authors: Rupani Parveen Fatemeh , Embrandiri Asha , Ibrahim Mahamd Hakimi , Shahadat Mohammad , Hansen Sune Balle , Mansor Nur Naha Abu
Published: June 2017

Several technologies are being applied for treatment of palm oil mill wastes. Among them, the biological treatments (vermicomposting) have widely been recognized as one of the most efficient and eco-friendly methods for converting organic waste materials into valuable products. The present study focuses on vermicomposting of acidic palm oil mill effluent (POME) mixed with the palm pressed fibre (PPF) which are found difficult to decompose in the environment. The industrial waste (POME) was vermicomposted using Lumbricus rubellus under laboratory conditions for a period of 45 days. A significant improvement in nitrogen, phosphorus, and potassium content was monitored during vermicomposting process. In addition, the decline in C:N ratio of vermicompost (up to 17.20 ± 0.60) reflects the degree of stabilization of POME–PPF mixture. Different percentages of the vermicompost extract obtained from POME–PPF mixture were also examined for the germination of mung bean (Vigna radiata) seed. The results showed that 75% vermicompost extract demonstrated better performance for the seed germination. On the basis of significant findings, POME–PPF mixture can be successfully used as a feeding material for the earthworms, while on the other hand, it can also be used as a cost-effective fertilizer for the germination and the proper growth of mung bean.
Cognitive deficits in the first 24 hours after the onset of first unprovoked generalized Tonic and clonic seizure
Authors: Charmchi Zeinab , Sayadnasiri Mohammad
Published: June 2017

Background Many people with epilepsy suffer from cognitive deficits as a consequence of their seizure episodes. Relatively few researches have been undertaken to assess the short term impacts of seizure on cognitive function. This study aimed to evaluate changes in cognitive performance in adults with a new onset generalized seizure in the first 24 h after the onset of their attack.

Methods After having given informed consent, 40 patients with first episode of unprovoked generalized tonic-clonic seizure were investigated with a neuropsychological test battery (Wechsler Memory Scale III). Their performance was compared with 40 healthy individuals from the patients' companions.

Results Newly diagnosed patients had significantly worse performance in paired association recall which is a parameter of verbal memory; other memory parameters showed no significant changes after seizure attack.

Conclusion Our data suggested that even with a one-time seizure episode, patients are susceptible to verbal memory impairment.
Brain function and structure and risk for incident diabetes: The Atherosclerosis Risk in Communities Study
Authors: Bancks Michael P. , Alonso Alvaro , Gottesman Rebecca F. , Mosley Thomas H. , Selvin Elizabeth , Pankow James S.
Published: June 2017

Introduction

Diabetes is prospectively associated with cognitive decline. Whether lower cognitive function and worse brain structure are prospectively associated with incident diabetes is unclear.

Methods

We analyzed data for 10,133 individuals with cognitive function testing (1990–1992) and 1212 individuals with brain magnetic resonance imaging (1993–1994) from the Atherosclerosis Risk in Communities cohort. We estimated hazard ratios for incident diabetes through 2014 after adjustment for traditional diabetes risk factors and cohort attrition.

Results

Higher level of baseline cognitive function was associated with lower risk for diabetes (per 1 standard deviation, hazard ratio = 0.94; 95% confidence interval = 0.90, 0.98). This association did not persist after accounting for baseline glucose level, case ascertainment methods, and cohort attrition. No association was observed between any brain magnetic resonance imaging measure and incident diabetes.

Discussion

This is one of the first studies to prospectively evaluate the association between both cognitive function and brain structure and the incidence of diabetes.
Incidence of cognitively defined late‐onset Alzheimer's dementia subgroups from a prospective cohort study
Authors: Crane Paul K. , Trittschuh Emily , Mukherjee Shubhabrata , Saykin Andrew J. , Sanders R. Elizabeth , Larson Eric B. , McCurry Susan M. , McCormick Wayne , Bowen James D. , Grabowski Thomas , Moore Mackenzie , Bauman Julianna , Gross Alden L. , Keene C. Dirk , Bird Thomas D. , Gibbons Laura E. , Mez Jesse ,   Executive Prominent Alzheimer's Disease: Genetics and Risk Factors (EPAD:GRF) Investigators
Published: June 2017

Introduction

There may be biologically relevant heterogeneity within typical late‐onset Alzheimer's dementia.

Methods

We analyzed cognitive data from people with incident late‐onset Alzheimer's dementia from a prospective cohort study. We determined individual averages across memory, visuospatial functioning, language, and executive functioning. We identified domains with substantial impairments relative to that average. We compared demographic, neuropathology, and genetic findings across groups defined by relative impairments.

Results

During 32,286 person‐years of follow‐up, 869 people developed Alzheimer's dementia. There were 393 (48%) with no domain with substantial relative impairments. Some participants had isolated relative impairments in memory (148, 18%), visuospatial functioning (117, 14%), language (71, 9%), and executive functioning (66, 8%). The group with isolated relative memory impairments had higher proportions with ≥ APOE ε4 allele, more extensive Alzheimer's‐related neuropathology, and higher proportions with other Alzheimer's dementia genetic risk variants.

Discussion

A cognitive subgrouping strategy may identify biologically distinct subsets of people with Alzheimer's dementia.
Neuropathologic features of TOMM40 '523 variant on late‐life cognitive decline
Authors: Yu Lei , Lutz Michael W. , Farfel Jose M. , Wilson Robert S. , Burns Daniel K. , Saunders Ann M. , De Jager Philip L. , Barnes Lisa L. , Schneider Julie A. , Bennett David A.
Published: June 2017

Introduction

The study investigated the role of neuropathologies in the relationship between TOMM40 '523 genotype and late‐life cognitive decline.

Methods

Participants were community‐dwelling older persons who had annual cognitive assessments and brain autopsies after death. Genotyping used DNA from peripheral blood or postmortem brain tissue. Linear mixed models assessed the extent to which the association of '523 genotype with cognitive decline is attributable to neuropathologies.

Results

Relative to ε3/ε3 homozygotes with '523‐S/VL or '523‐VL/VL genotype, both '523‐L carriers and ε3/ε3 homozygotes with '523‐S/S genotype had faster cognitive decline. The association of '523‐L with cognitive decline was attenuated and no longer significant after controlling for Alzheimer's and other neuropathologies. By contrast, the association of '523‐S/S was unchanged.

Discussion

There are two distinct TOMM40 '523 signals in relation to late‐life cognitive decline. One signal primarily acts through AD and other common neuropathologies, whereas the other operates through a different mechanism.
Does the Severity of Overactive Bladder Symptoms Correlate with Risk for Female Sexual Dysfunction?
Authors: Juliato Cássia Raquel Teatin , Melotti Iane Glauce Ribeiro , Junior Luiz Carlos Santos , Britto Luiz Gustavo Oliveira , Riccetto Cássio Luiz Zanettini
Published: June 2017

Background

Several studies have associated overactive bladder (OAB) with female sexual dysfunction (FSD); however, there are no reports using a quantitative approach to measure OAB severity and to relate OAB to the risk of FSD.

Aim

To evaluate women with OAB and to correlate the severity of their urinary symptoms with their sexual function.

Methods

This cross-sectional study included 267 women older than 18 years with untreated OAB. All subjects completed the International Consultation on Incontinence Questionnaire Overactive Bladder (ICIQ-OAB) and the Female Sexual Function Index (FSFI).

Outcomes

Linear regression was used to analyze the association between variables and the numeric FSFI score, and categorical FSFI scores were analyzed using logistic regression. Spearman rank correlation coefficient was used to assess the correlation between ICIQ-OAB results and the different FSFI domains. The significance level was 5%.

Results

Subjects’ mean age was 50.2 ± 11.9 years. Most women were married, had at least three children, and were postmenopausal (54.3%). Mean FSFI total score was 19.2 ± 9.8. For menopausal status, 65.6% of premenopausal women had a risk for FSD vs 86.2% of postmenopausal women. Mean ICIQ-OAB score was 10 ± 3.17. Postmenopausal women had the following risk factors statistically associated with sexual dysfunction: age, ICIQ score, and marital status. For these women, greater OAB severity, especially those with urgency and/or urge incontinence, was associated with worse scores in the arousal, lubrication, orgasm, and sexual pain domains. However, there was no statistically significant association for premenopausal women.

Clinical Implications

Health professionals have to pay attention to OAB in women because of the greater risk for FSD in these patients.

Strengths and Limitations

The strength was using a quantitative approach to measure OAB severity in a larger population. Limitations include a convenience sample with no power calculation; exclusion of women who did not have sexual intercourse in the past month; unmeasured distress caused by sexual disorders; and the impossibility of establishing causality between OAB and sexual dysfunction.

Conclusion

Women with OAB frequently have a risk for sexual dysfunction. In the postmenopausal group, women with scores indicating severe OAB had worse sexual function, mainly in the arousal, lubrication, orgasm, pain, and total domains.
CEO inside debt and bank loan syndicate structure
Authors: Chen Liqiang , Fan Hong
Published: June 2017

This paper investigates the effects of a borrowing firm's CEO inside debt holdings on the structure of the firm's syndicated loans. When a borrowing firm's CEO has a higher level of inside debt holdings, syndicate loans have a larger number of lenders and are less concentrated, and lead arrangers will retain a smaller portion of loans. In addition, CEO inside debt holdings have a lesser effect on the syndicate structure when lead arrangers have a prior lending relationship with the borrowing firm or the CEOs are close to retirement, while CEO inside debt holdings have greater influence on the syndicate structure when the borrowing firm has low information transparency.
Randomized, double-blind, placebo-controlled, dose-escalation study: Investigation of the safety, pharmacokinetics, and antihyperalgesic activity of L-4-chlorokynurenine in healthy volunteers
Authors: Wallace Mark , White Alexander , Grako Kathy A. , Lane Randal , Cato Allen (Jo) , Snodgrass H. Ralph
Published: June 2017

Graphical Abstract
Transforming Traumatised Children within NSW Department of Education Schools: One School Counsellor's Model for Practise – REWIRE
Authors: Costa Deborah A.
Published: June 2017

Adequately supporting the needs of maltreated and traumatised children within New South Wales (NSW) public education system schools is often frustrated by poor perception of the impact of developmental trauma on children's school-based functioning and the need for additional, specialist support; the push for, and provision of, behaviour diagnoses for these children to fund basic assistance and supervision; competing demands on an overextended School Counselling resource impacting capacity for school-based trauma informed psychological services, and seemingly stretched capacity of government/non-government agencies to reliably provide effective support. This is accompanied by a lack of understanding of behavioural signals of distress children display and underreporting to agencies; persistent, simplistic behaviourist views of children's behaviours within schools and low-level collaboration between schools and external agencies. Facilitating a trauma sensitive environment within NSW schools can ameliorate these frustrations and attend to these inadequacies in a pragmatic, achievable way. This practice paper presents a School Counsellor-led model (REWIRE) for achieving this.
Wondering From the Womb: Antenatal Yarning In Rural Victoria
Authors: Crouch Kathy
Published: June 2017

This program development report describes the birth of ‘Wondering From the Womb’, a self-determined antenatal yarning resource created through a culturally respectful action research project undertaken in rural Victoria with Indigenous and non-Indigenous community members and professionals. The qualitative reviews completed within Community involved 40 participants who shared their wisdom and experiences regarding antenatal health, parenting and child-rearing practise and connection to Country. The resulting yarning resource, written from the perspective of a baby in the womb, has encouraged curiosity and wonder about what antenates can teach adults and community members regarding their life, learning and healing. Future uses for such a resource are identified with an aim to continue self-determined, culturally respectful service delivery for Indigenous babies, children and families across the Loddon Mallee region.
Optimal sensor placement for variational data assimilation of unsteady flows past a rotationally oscillating cylinder
Authors: Mons Vincent , Chassaing Jean-Camille , Sagaut Pierre
Published: June 2017

An optimal sensor placement procedure is proposed within the framework of variational data assimilation (DA) for unsteady flows, with the aim of maximizing the efficiency of the DA procedure. It is dedicated to the a priori design of a sensor network, and relies on a first-order adjoint approach. The proposed methodology first consists in identifying, via optimal control, the locations in the flow that have the greatest sensitivity with respect to a change in the initial condition, boundary conditions or model parameters. In a second step, sensors are placed at these locations for DA purposes. The use of this optimal sensor placement procedure does not require extra development in the case where a variational DA suite is available. The proposed methodology is applied to the reconstruction of unsteady bidimensional flows past a rotationally oscillating cylinder. More precisely, the possibilities of reconstructing the rotational speed of the cylinder and the initial flow, which here encompasses upstream conditions, from various types of observations are investigated via variational DA. Then, the observation optimization procedure is employed to identify optimal locations for placing velocity sensors downstream of the cylinder. Both reduction in the computational cost and improvement in the quality of the reconstructed flow are achieved through optimal sensor placement, encouraging the application of the proposed methodology to more complex and realistic flows.
Surfing surface gravity waves
Authors: Pizzo Nick E.
Published: June 2017

A simple criterion for water particles to surf an underlying surface gravity wave is presented. It is found that particles travelling near the phase speed of the wave, in a geometrically confined region on the forward face of the crest, increase in speed. The criterion is derived using the equation of John (Commun. Pure Appl. Maths, vol. 6, 1953, pp. 497–503) for the motion of a zero-stress free surface under the action of gravity. As an example, a breaking water wave is theoretically and numerically examined. Implications for upper-ocean processes, for both shallow- and deep-water waves, are discussed.
Yield, water productivity and economic return of dryland wheat in the Loess Plateau in response to conservation tillage practices
Authors: LI Z. , ZHANG Q. , YANG Q. , YANG X. , LI J. , CUI S. , SHEN Y.
Published: June 2017

Winter wheat (Triticum aestivum L.) production on the Loess Plateau in China has been threatened by water scarcity and climate change during the last decade. Sustainable crop production in this region requires managerial practices that can provide high yield and high water productivity (WP). A 7-year (2001–2008) study at the Loess Plateau Research Station of Lanzhou University investigated the effects of various conservation tillage practices on grain yield, soil water content (SWC), WP and economic return of winter wheat production. Tillage treatments included: conventional tillage (T), conventional tillage followed by stubble retention (TS), no-till (NT) and no-till followed by stubble retention (NTS). Over the entire experimental period, grain yield and WP of winter wheat ranged from 1279 to 4894 kg/ha and 0·32 to 2·41 kg/m3, respectively. Both were significantly affected by tillage treatment and year, while SWC was only affected by year. Grain yield and WP in TS was increased by 4·9, 12·1, 0·9% and 13·7, 20·4 and 3·9% compared with NTS, NT and T, respectively, over seven growing seasons. Additionally, a multiple linear regression analysis indicated that grain yield is mainly limited by SWC during planting. Despite its lower grain yield, the NTS treatment increased economic benefit by US$ 328, US$ 23 and US$ 87/ha compared with TS, NT and T, respectively. Therefore, it is suggested that increasing soil water storage at wheat sowing time and encouraging the use of NTS could improve economic returns in this region.
CHD and respiratory syncytial virus: global expert exchange recommendations
Authors: Tulloh Robert M. R. , Medrano-Lopez Constancio , Checchia Paul A. , Stapper Claudia , Sumitomo Naokata , Gorenflo Matthias , Jung Bae Eun , Juanico Antonio , Gil-Jaurena Juan M. , Wu Mei-Hwan , Farha Talal , Dodge-Khatami Ali , Tsang Rocky , Notario Gerard , Wegzyn Colleen
Published: June 2017

Background

Palivizumab is the standard immunoprophylaxis against serious disease due to respiratory syncytial virus infection. Current evidence-based prophylaxis guidelines may not address certain children with CHD within specific high-risk groups or clinical/management settings.

Methods

An international steering committee of clinicians with expertise in paediatric heart disease identified key questions concerning palivizumab administration; in collaboration with an additional international expert faculty, evidence-based recommendations were formulated using a quasi-Delphi consensus methodology.

Results

Palivizumab prophylaxis was recommended for children with the following conditions: <2 years with unoperated haemodynamically significant CHD, who are cyanotic, who have pulmonary hypertension, or symptomatic airway abnormalities; <1 year with cardiomyopathies requiring treatment; in the 1st year of life with surgically operated CHD with haemodynamically significant residual problems or aged 1–2 years up to 6 months postoperatively; and on heart transplant waiting lists or in their 1st year after heart transplant. Unanimous consensus was not reached for use of immunoprophylaxis in children with asymptomatic CHD and other co-morbid factors such as arrhythmias, Down syndrome, or immunodeficiency, or during a nosocomial outbreak. Challenges to effective immunoprophylaxis included the following: multidisciplinary variations in identifying candidates with CHD and prophylaxis compliance; limited awareness of severe disease risks/burden; and limited knowledge of respiratory syncytial virus seasonal patterns in subtropical/tropical regions.

Conclusion

Evidence-based immunoprophylaxis recommendations were formulated for subgroups of children with CHD, but more data are needed to guide use in tropical/subtropical countries and in children with certain co-morbidities.
Probleme evidenzbasierter bzw. -orientierter pädagogischer Praxis
Authors: Stark Robin
Published: June 2017

Zusammenfassung. Die Idee einer dezidierten wissenschaftlichen Orientierung der Lehramtsausbildung und der pädagogischen Praxis ist nicht neu. Relativ neu ist hingegen die Inanspruchnahme des Evidenzbegriffs und, oft im selben Atemzug, der Blick auf evidenzbasierte Medizin, der in Fragen evidenzbasierter Praxis eine Vorreiterrolle zugeschrieben wird. Der Evidenzbegriff ist schillernd und bringt einige Probleme mit sich. Zudem lassen sich in Bezug auf die Interpretation und Anwendung des Evidenzbegriffs verschiedene Paradigmen ausmachen. Im deutschsprachigen Raum überwiegt eine Evidenzperspektive, die im Vergleich zur vorherrschenden US-amerikanischen Variante einen liberalen Methodenpluralismus pflegt und evidenzbasierte Praxis als Spezialfall einer evidenzorientierten oder -informierten Praxis auffasst. In der Konsequenz werden pädagogischer und psychologischer Evidenz, um die es in diesem Beitrag geht, in Bezug auf pädagogische Praxis v.a. evaluative und reflexive Funktionen zugesprochen. Dennoch steht die Anwendung wissenschaftlichen Wissens in der pädagogischen Praxis vor Problemen, die nicht zuletzt durch die fragwürdige Qualität der wissenschaftlichen Wissensbasis bedingt sind. Zudem ergeben sich zwangsläufig Passungs- und Transferprobleme, die auch die elaborierte Technologiekonzeption von Theo Herrmann nicht überwinden konnte. Umso höher sind die Anforderungen, die evidenzorientiertes pädagogisches Handeln an bildungswissenschaftliche Forschungskompetenz sowie Kompetenzen der Integration von wissenschaftlichem Wissen und pädagogischem Erfahrungswissen an Lehrkräfte stellt. Diese Kompetenzen gilt es, bereits in der universitären Lehramtsausbildung systematisch zu fördern.
Male Smokers’ Behavioral and Brain Responses to Deviant Cigarette-Related Stimuli in a Two-Choice Oddball Paradigm
Authors: Zhao Xin , Liu Xiaoting , Maes Joseph H. R.
Published: June 2017

Abstract. Experimental studies on smoking and response-inhibition capacity have revealed inconsistent findings, which might be due to differences in sensitivity of the behavioral paradigms used. Here we aimed to replicate the impaired response inhibition in male smokers that was found in a previous study using a two-choice oddball task. This task enables the use of response times as index of inhibition capacity and equalizes the response requirement for the different trial types. In addition, we measured event-related brain potentials to explore the nature of the cognitive processes underlying the behavioral difference. Smokers (n = 19) and non-smokers (n = 19) were asked to make a different response to frequent standard stimuli (cigarette-unrelated pictures) than to infrequent deviant stimuli (cigarette-related pictures). Compared to non-smokers, smokers took a longer time to respond to deviant but not standard stimuli. In addition, smokers, but not non-smokers, displayed a smaller N2 amplitude to deviant than standard stimuli, and only the non-smokers showed larger P3 amplitudes to deviant compared to standard stimuli. Moreover, the response time (RT) measure was differentially correlated with N2 and P3 amplitudes in smokers and non-smokers. The joint results support the notion of deviant cognitive processes in smokers compared to non-smokers that are either directly or indirectly related to response-inhibition capacity.
Structural insights into the function of ZRANB3 in replication stress response
Authors: Sebesta Marek , Cooper Christopher D. O. , Ariza Antonio , Carnie Christopher J. , Ahel Dragana
Published: June 2017

Strategies to resolve replication blocks are critical for the maintenance of genome stability. Among the factors implicated in the replication stress response is the ATP-dependent endonuclease ZRANB3. Here, we present the structure of the ZRANB3 HNH (His-Asn-His) endonuclease domain and provide a detailed analysis of its activity. We further define PCNA as a key regulator of ZRANB3 function, which recruits ZRANB3 to stalled replication forks and stimulates its endonuclease activity. Finally, we present the co-crystal structures of PCNA with two specific motifs in ZRANB3: the PIP box and the APIM motif. Our data provide important structural insights into the PCNA-APIM interaction, and reveal unexpected similarities between the PIP box and the APIM motif. We propose that PCNA and ATP-dependency serve as a multi-layered regulatory mechanism that modulates ZRANB3 activity at replication forks. Importantly, our findings allow us to interpret the functional significance of cancer associated ZRANB3 mutations.
Optogenetic protein clustering through fluorescent protein tagging and extension of CRY2
Authors: Park Hyerim , Kim Na Yeon , Lee Sangkyu , Kim Nury , Kim Jihoon , Heo Won Do
Published: June 2017

Protein homo-oligomerization is an important molecular mechanism in many biological processes. Therefore, the ability to control protein homo-oligomerization allows the manipulation and interrogation of numerous cellular events. To achieve this, cryptochrome 2 (CRY2) from Arabidopsis thaliana has been recently utilized for blue light-dependent spatiotemporal control of protein homo-oligomerization. However, limited knowledge on molecular characteristics of CRY2 obscures its widespread applications. Here, we identify important determinants for efficient cryptochrome 2 clustering and introduce a new CRY2 module, named ‘‘CRY2clust’’, to induce rapid and efficient homo-oligomerization of target proteins by employing diverse fluorescent proteins and an extremely short peptide. Furthermore, we demonstrate advancement and versatility of CRY2clust by comparing against previously reported optogenetic tools. Our work not only expands the optogenetic clustering toolbox but also provides a guideline for designing CRY2-based new optogenetic modules.
Reverse engineering highlights potential principles of large gene regulatory network design and learning
Authors: Carré Clément , Mas André , Krouk Gabriel
Published: June 2017

Inferring transcriptional gene regulatory networks from transcriptomic datasets is a key challenge of systems biology, with potential impacts ranging from medicine to agronomy. There are several techniques used presently to experimentally assay transcription factors to target relationships, defining important information about real gene regulatory networks connections. These techniques include classical ChIP-seq, yeast one-hybrid, or more recently, DAP-seq or target technologies. These techniques are usually used to validate algorithm predictions. Here, we developed a reverse engineering approach based on mathematical and computer simulation to evaluate the impact that this prior knowledge on gene regulatory networks may have on training machine learning algorithms. First, we developed a gene regulatory networks-simulating engine called FRANK (Fast Randomizing Algorithm for Network Knowledge) that is able to simulate large gene regulatory networks (containing 104 genes) with characteristics of gene regulatory networks observed in vivo. FRANK also generates stable or oscillatory gene expression directly produced by the simulated gene regulatory networks. The development of FRANK leads to important general conclusions concerning the design of large and stable gene regulatory networks harboring scale free properties (built ex nihilo). In combination with supervised (accepting prior knowledge) support vector machine algorithm we (i) address biologically oriented questions concerning our capacity to accurately reconstruct gene regulatory networks and in particular we demonstrate that prior-knowledge structure is crucial for accurate learning, and (ii) draw conclusions to inform experimental design to performed learning able to solve gene regulatory networks in the future. By demonstrating that our predictions concerning the influence of the prior-knowledge structure on support vector machine learning capacity holds true on real data (Escherichia coli K14 network reconstruction using network and transcriptomic data), we show that the formalism used to build FRANK can to some extent be a reasonable model for gene regulatory networks in real cells.
A novel plant E3 ligase stabilizes Escherichia coli heat shock factor σ32
Authors: Niu Yulong , Xu Xibing , Liu Chengcheng , Wang Tao , Liang Ke , Wang Jianmei , Liu Zhibin , Li Xufeng , Yang Yi
Published: June 2017

The heat shock response is crucial for organisms against heat-damaged proteins and maintaining homeostasis at a high temperature. Heterologous expression of eukaryotic molecular chaperones protects Escherichia coli from heat stress. Here we report that expression of the plant E3 ligase BnTR1 significantly increases the thermotolerance of E. coli. Different from eukaryotic chaperones, BnTR1 expression induces the accumulation of heat shock factor σ32 and heat shock proteins. The active site of BnTR1 in E. coli is the zinc fingers of the RING domain, which interacts with DnaK resulting in stabilizing σ32. Our findings indicate the expression of BnTR1 confers thermoprotective effects on E. coli cells, and it may provide useful clues to engineer thermophilic bacterial strains.
Microbial Signatures Associated with Oropharyngeal and Oral Squamous Cell Carcinomas
Authors: Banerjee Sagarika , Tian Tian , Wei Zhi , Peck Kristen N. , Shih Natalie , Chalian Ara A. , O’Malley Bert W. , Weinstein Gregory S. , Feldman Michael D. , Alwine James , Robertson Erle S.
Published: June 2017

The microbiome is fundamentally one of the most unique organs in the human body. Dysbiosis can result in critical inflammatory responses and result in pathogenesis contributing to neoplastic events. We used a pan-pathogen array technology (PathoChip) coupled with next-generation sequencing to establish microbial signatures unique to human oral and oropharyngeal squamous cell carcinomas (OCSCC/OPSCC). Signatures for DNA and RNA viruses including oncogenic viruses, gram positive and negative bacteria, fungi and parasites were detected. Cluster and topological analyses identified 2 distinct groups of microbial signatures related to OCSCCs/OPSCCs. Results were validated by probe capture next generation sequencing; the data from which also provided a comprehensive map of integration sites and chromosomal hotspots for micro-organism genomic insertions. Identification of these microbial signatures and their integration sites may provide biomarkers for OCSCC/OPSCC diagnosis and prognosis as well as novel avenues for study of their potential role in OCSCCs/OPSCCs.
High-throughput Screening of Small Molecule Inhibitors of the Streptococcus Quorum-sensing Signal Pathway
Authors: Ishii Seiji , Fukui Kenji , Yokoshima Satoshi , Kumagai Kazuo , Beniyama Youko , Kodama Tetsuya , Fukuyama Tohru , Okabe Takayoshi , Nagano Tetsuo , Kojima Hirotatsu , Yano Takato
Published: June 2017

The main components of the quorum-sensing system are expected to be favorable targets for drug development to combat various chronic infectious diseases. ComA of Streptococcus is an ATP-binding cassette transporter containing a peptidase domain (PEP), which is essential for the quorum-sensing signal production. Using high-throughput screening, we found a potent small molecule that suppressed the S. mutans quorum-sensing pathway through inhibition of PEP activity. The compound effectively attenuated the biofilm formation and competence development of S. mutans without inhibiting cell growth. The kinetic and structural studies with this molecule and a related compound unexpectedly revealed an allosteric site of PEP. This relatively hydrophobic site is thought to undergo large structural changes during the catalytic process. These compounds inhibit PEP activity by binding to and suppressing the structural changes of this site. These results showed that PEP is a good target for inhibitors of the Streptococcus quorum-sensing system.
Physalins V-IX, 16,24-cyclo-13,14-seco withanolides from Physalis angulata and their antiproliferative and anti-inflammatory activities
Authors: Sun Cheng-Peng , Qiu Chong-Yue , Zhao Feng , Kang Ning , Chen Li-Xia , Qiu Feng
Published: June 2017

Five new physalins, including a novel 1,10-seco one, physalin V (1), a tricarboxylic acid cycle one, physalin VIII (5), a rare 11,15-cyclo one, physalin IX (6), and two new ones, physalins VI (2) and VII (4) were isolated from stems and leaves of Physalis angulata together with eleven known analogues (3 and 7–16). Their structures were established by MS, IR, UV, and NMR spectroscopic analysis, together with the X-ray diffraction analysis of neophysalin, physalin P (12), and the structure of physalin D1 (3) has been revised here. These isolated compounds were evaluated for their antiproliferative activities against human cancer cells (C4-2B, 22Rv1, 786-O, A-498, ACHN, and A375-S2) and inhibitory effects on nitric oxide production. Compounds 9 and 10 showed antiproliferative activities against all tested human cancer cells with IC50 values of 0.24–3.17 μM. Compounds 1, 3, 4, 9, 10, 13, 14, and 16 exhibited inhibitory activities against NO production. The IC50 values of compounds 9, 10, 13, and 16 were between 0.32 and 4.03 μM, while compounds 1, 3, 4, and 14 had IC50 values of 12.83–34.19 μM. Herein, plausible biosynthetic pathways for rare structures 1 and 6 and structure−activity relationships on the inhibition of NO production for all isolated compounds are discussed.
Deterministic radiative coupling of two semiconductor quantum dots to the optical mode of a photonic crystal nanocavity
Authors: Calic M. , Jarlov C. , Gallo P. , Dwir B. , Rudra A. , Kapon E.
Published: June 2017

A system of two site-controlled semiconductor quantum dots (QDs) is deterministically integrated with a photonic crystal membrane nano-cavity. The two QDs are identified via their reproducible emission spectral features, and their coupling to the fundamental cavity mode is established by emission co-polarization and cavity feeding features. A theoretical model accounting for phonon interaction and pure dephasing reproduces the observed results and permits extraction of the light-matter coupling constant for this system. The demonstrated approach offers a platform for scaling up the integration of QD systems and nano-photonic elements for integrated quantum photonics applications.
Cognitive and motor dual task gait training improve dual task gait performance after stroke - A randomized controlled pilot trial
Authors: Liu Yan-Ci , Yang Yea-Ru , Tsai Yun-An , Wang Ray-Yau
Published: June 2017

This study investigated effects of cognitive and motor dual task gait training on dual task gait performance in stroke. Participants (n = 28) were randomly assigned to cognitive dual task gait training (CDTT), motor dual task gait training (MDTT), or conventional physical therapy (CPT) group. Participants in CDTT or MDTT group practiced the cognitive or motor tasks respectively during walking. Participants in CPT group received strengthening, balance, and gait training. The intervention was 30 min/session, 3 sessions/week for 4 weeks. Three test conditions to evaluate the training effects were single walking, walking while performing cognitive task (serial subtraction), and walking while performing motor task (tray-carrying). Parameters included gait speed, dual task cost of gait speed (DTC-speed), cadence, stride time, and stride length. After CDTT, cognitive-motor dual task gait performance (stride length and DTC-speed) was improved (p = 0.021; p = 0.015). After MDTT, motor dual task gait performance (gait speed, stride length, and DTC-speed) was improved (p = 0.008; p = 0.008; p = 0.008 respectively). It seems that CDTT improved cognitive dual task gait performance and MDTT improved motor dual task gait performance although such improvements did not reach significant group difference. Therefore, different types of dual task gait training can be adopted to enhance different dual task gait performance in stroke.
Multiple origins and a narrow genepool characterise the African tea germplasm: concordant patterns revealed by nuclear and plastid DNA markers
Authors: Wambulwa Moses Cheloti , Meegahakumbura Muditha Kasun , Kamunya Samson , Muchugi Alice , Möller Michael , Liu Jie , Xu Jian-Chu , Li De-Zhu , Gao Lian-Ming
Published: June 2017

Despite the highly economic value of tea in Africa, its genetic and geographic origins remain largely unexplored. Here we address this by collecting 439 samples across 11 countries in Africa and Asia to investigate the origin and genepool composition of African tea based on 23 nuclear microsatellites loci (nSSRs) and three cpDNA intergenic spacer regions. Our results indicated that the African tea represents a potpourri originating from multiple introductions over time. The nSSR analysis revealed that the majority (79%) of tea accessions collected in Africa belong to Indian Assam tea which have likely originated from India and/or Sri Lanka. The patterns of nSSR variation also showed that Chinese Assam tea is genetically distinct from Indian Assam tea, and has rarely been used in African tea breeding efforts since only 4% of the African tea accessions possessed this genotype. We found a total of 22 cpDNA haplotypes, which grouped into three main geographic clades that were concordant with the distribution of microsatellite genotypes. Several private cpDNA haplotypes were identified in Chinese Assam tea in Southern Yunnan province of China. Therefore Chinese Assam tea will be important for the enrichment of African tea gene pools. Our results is a useful guide in future tea breeding programmes in Africa.
Genome-wide identification of Major Intrinsic Proteins in Glycine soja and characterization of GmTIP2;1 function under salt and water stress
Authors: Zhang Da-yong , Kumar Manoj , Xu Ling , Wan Qun , Huang Yi-hong , Xu Zhao-Long , He Xiao-Lan , Ma Jin-Biao , Pandey Girdhar K. , Shao Hong-Bo
Published: June 2017

In different plant species, aquaporins (AQPs) facilitate water movement by regulating root hydraulic conductivity under diverse stress conditions such as salt and water stresses. To improve survival and yield of crop plants, a detailed understanding of stress responses is imperative and required. We used Glycine soja genome as a tool to study AQPs, considering it shows abundant genetic diversity and higher salt environment tolerance features and identified 62 GsAQP genes. Additionally, this study identifies major aquaporins responsive to salt and drought stresses in soybean and elucidates their mode of action through yeast two-hybrid assay and BiFC. Under stress condition, the expression analysis of AQPs in roots and leaves of two contrasting ecotypes of soybean revealed diverse expression patterns suggesting complex regulation at transcriptional level. Based on expression analysis, we identify GmTIP2;1 as a potential candidate involved in salinity and drought responses. The overexpression of GmTIP2;1 in Saccharomyces cerevisiae as well as in-planta enhanced salt and drought tolerance. We identified that GmTIP2;1 forms homodimers as well as interacts with GmTIP1;7 and GmTIP1;8. This study augments our knowledge of stress responsive pathways and also establishes GmTIP2;1 as a new stress responsive gene in imparting salt stress tolerance in soybean.
Understanding the Unusual Response to High Pressure in KBe2BO3F2
Authors: Yu D. H. , Avdeev M. , Sun D. H. , Huston L. Q. , Shiell Thomas B. , Sun Q. B. , Lu T. , Gu Q. , Liu H. , Bradby J. E. , Yie N. , Liu Y. , Wang J. Y. , McIntyre G. J.
Published: June 2017

Strong anisotropic compression with pressure on the remarkable non-linear optical material KBe2BO3F2 has been observed with the linear compression coefficient along the c axis found to be about 40 times larger than that along the a axis. An unusual non-monotonic pressure response was observed for the a lattice parameter. The derived bulk modulus of 31 ± 1 GPa indicates that KBe2BO3F2 is a very soft oxide material yet with stable structure up to 45 GPa. A combination of high-pressure synchrotron powder X-ray diffraction, high-pressure Raman spectroscopy, and Density Functional Theory calculations points to the mechanism for the unusual pressure response being due to the competition between the K-F bond length and K-F-K bond angle and the coupling between the stretching and twisting vibration modes.
Cytokines regulate complement receptor immunoglobulin expression and phagocytosis of Candida albicans in human macrophages: A control point in anti-microbial immunity
Authors: Munawara Usma , Small Annabelle G. , Quach Alex , Gorgani Nick N. , Abbott Catherine A. , Ferrante Antonio
Published: June 2017

Complement Receptor Immunoglobulin (CRIg), selectively expressed by macrophages, plays an important role in innate immunity by promoting phagocytosis of bacteria. Thus modulation of CRIg on macrophages by cytokines can be an important mechanism by which cytokines regulate anti-microbial immunity. The effects of the cytokines, tumor necrosis factor, transforming growth factor-β1, interferon-γ, interleukin (IL)-4, IL-13, IL-10, IL-1β, IL-6, lymphotoxin-α, macrophage-colony stimulating factor (M-CSF) and GM-CSF on CRIg expression were examined in human macrophages. We demonstrated that cytokines regulated the CRIg expression on macrophages during their development from monocytes in culture at the transcriptional level using qPCR and protein by Western blotting. Both CRIg spliced forms (Long and Short), were similarly regulated by cytokines. Direct addition of cytokines to matured CRIg+ macrophages also changed CRIg mRNA expression, suggesting that cytokines control macrophage function via CRIg, at two checkpoints. Interestingly the classical complement receptors, CR3 and CR4 were differentially regulated by cytokines. The changes in CRIg but not CR3/CR4 mRNA expression correlated with ability to phagocytoseCandida albicansby macrophages. These findings suggest that CRIg is likely to be a control point in infection and immunity through which cytokines can mediate their effects, and is differentially regulated from CR3 and CR4 by cytokines.