bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of deleobuvir, a potent hepatitis C virus polymerase inhibitor, and its major metabolites labeled with carbon‐13 and carbon‐14
Authors: Latli Bachir , Hrapchak Matt , Chevliakov Maxim , Li Guisheng , Campbell Scot , Busacca Carl A. , Senanayake Chris H.
Published: May 2015

Deleobuvir, (2E)‐3‐(2‐{1‐[2‐(5‐bromopyrimidin‐2‐yl)‐3‐cyclopentyl‐1‐methyl‐1H‐indole‐6‐carboxamido]cyclobutyl}‐1‐methyl‐1H‐benzimidazol‐6‐yl)prop‐2‐enoic acid (1), is a non‐nucleoside, potent, and selective inhibitor of hepatitis C virus NS5B polymerase. Herein, we describe the detailed synthesis of this compound labeled with carbon‐13 and carbon‐14. The synthesis of its three major metabolites, namely, the reduced double bond metabolite (2) and the acyl glucuronide derivatives of (1) and (2), is also reported. Aniline‐13C6 was the starting material to prepare butyl (E)‐3‐(3‐methylamino‐4‐nitrophenyl‐13C6)acrylate [13C6]‐(11) in six steps. This intermediate was then used to obtain [13C6]‐(1) and [13C6]‐(2) in five and four more steps, respectively. For the radioactive synthesis, potassium cyanide‐14C was used to prepare 1‐cylobutylaminoacid [14C]‐(23) via Buchrer–Bergs reaction. The carbonyl chloride of this acid was then used to access both [14C]‐(1) and [14C]‐(2) in four steps. The acyl glucuronide derivatives [13C6]‐(3), [13C6]‐(4) and [14C]‐(3) were synthesized in three steps from the acids [13C6]‐(1), [13C6]‐(2) and [14C]‐(1) using known procedures.
MYB rearrangement and clinicopathologic characteristics in head and neck adenoid cystic carcinoma
Authors: Rettig Eleni M. , Tan Marietta , Ling Shizhang , Yonescu Raluca , Bishop Justin A. , Fakhry Carole , Ha Patrick K.
Published: May 2015

Objectives

Salivary gland adenoid cystic carcinoma (ACC) is rare, aggressive, and challenging to treat. Many ACCs have a t(6;9) chromosomal translocation resulting in a MYB‐NFIB fusion gene, but the clinical significance is unclear. The purposes of this study were to describe the clinicopathologic factors impacting survival and to determine the prevalence and clinical significance of MYB‐NFIB fusion.

Study Design

Case series.

Methods

Medical records of patients treated for ACC of the head and neck from 1974 to 2011 were reviewed and clinicopathologic data recorded. Fluorescence in situ hybridization (FISH) was used to detect MYB rearrangement in archival tumor tissue as a marker of MYB‐NFIB fusion.

Results

One hundred fifty‐eight patients were included, with median follow‐up 75.1 months. Median overall survival was 171.5 months (95% confidence interval [CI] = 131.9–191.6), and median disease‐free survival was 112.0 months (95% CI = 88.7–180.4). Advanced stage was associated with decreased overall survival (adjusted ptrend < 0.001), and positive margins were associated with decreased disease‐free survival (adjusted hazard ratio [aHR] = 8.80, 95% CI = 1.25–62.12, P = 0.029). Ninety‐one tumors were evaluable using FISH, and 59 (65%) had evidence of a MYB‐NFIB fusion. MYB‐NFIB positive tumors were more likely than MYB‐NFIB negative tumors to originate in minor salivary glands (adjusted prevalence ratios = 1.51, 95% CI = 1.07–2.12, P = 0.019). MYB‐NFIB tumor status was not significantly associated with disease‐free or overall survival (hazard ratio [HR] = 1.53, 95% CI = 0.77–3.02, P = 0.22 and HR = 0.91, 95% CI = 0.46–1.83, P = 0.80, respectively, for MYB‐NFIB positive compared with MYB‐NFIB negative tumors).

Conclusion

Stage and margin status were important prognostic factors for ACC. Tumors with evidence of MYB‐NFIB fusion were more likely to originate in minor salivary glands, but MYB‐NFIB tumor status was not significantly associated with prognosis.

Level of Evidence

4. Laryngoscope, 125:E292–E299, 2015
Differential mobility spectrometry/mass spectrometry history, theory, design optimization, simulations, and applications
Authors: Schneider Bradley B. , Nazarov Erkinjon G. , Londry Frank , Vouros Paul , Covey Thomas R.
Published: May 2015

This review of differential mobility spectrometry focuses primarily on mass spectrometry coupling, starting with the history of the development of this technique in the Soviet Union. Fundamental principles of the separation process are covered, in addition to efforts related to design optimization and advancements in computer simulations. The flexibility of differential mobility spectrometry design features is explored in detail, particularly with regards to separation capability, speed, and ion transmission. 2015 Wiley Periodicals, Inc. Mass Spec Rev 35:687–737, 2016
Intermittent stretching induces fibrosis in denervated rat muscle
Authors: Faturi Fernanda M. , Franco Rúbia C. , Gigo‐Benato Davilene , Turi Andriette C. , Silva‐Couto Marcela A. , Messa Sabrina P. , Russo Thiago L.
Published: May 2015

Introduction: Stretching (St) has been used for treating denervated muscles. However, its effectiveness and safety claims require further study. Methods: Rats were divided into: (1) those with denervated (D) muscles, evaluated 7 or 15 days after sciatic nerve crush injury; (2) those with D muscles submitted to St during 7 or 15 days; and (3) those with normal muscles. Muscle fiber cross‐sectional area, serial sarcomere number, sarcomere length, and connective tissue density were measured. MMP‐2, MMP‐9, TIMP‐1, TGF‐β1, and myostatin mRNAs were determined by real‐time polymerase chain reaction. MMP‐2 and MMP‐9 activity was evaluated by zymography. Collagen I was localized using immunofluorescence. Results: St did not prevent muscle atrophy due to denervation, but it increased fibrosis and collagen I deposition at day 15. St also upregulated MMP‐9 and TGF‐β1 gene expressions at day 7, and myostatin at day 15. Conclusions: Stretching denervated muscle does not prevent atrophy, but it increases fibrosis via temporal modulation of TGF‐β1/myostatin and MMP‐9 cascades. Muscle Nerve 53: 118–126, 2016
An economic mechanism for request routing and resource allocation in hybrid CDN–P2P networks
Authors: Garmehi Mehran , Analoui Morteza , Pathan Mukaddim , Buyya Rajkumar
Published: May 2015

Hybrid content delivery networks (HCDN) benefit from the complementary advantages of P2P (Peer to Peer) networks and CDNs (Content Delivery Network). In order to extend a traditional CDN and enable it to offer hybrid content delivery service, we have modified a traditional domain name system‐based request routing mechanism. The proposed scheme relies on an oligopolistic mechanism to balance the load on the edge servers and employs a truthful profit‐maximizing auction to maximize the contribution of users in the P2P content delivery. In particular, economics of content delivery in HCDNs is studied, and it is shown that through our request routing mechanism, it is possible to deliver higher quality of service to majority of end‐users, increase the net profit of the HCDN provider and decrease the content distribution cost at the same time. Copyright © 2015 John Wiley & Sons, Ltd.
The Role of Reward Systems in Product Innovations: An Examination of New Product Development Projects
Authors: Chen Yi-Jen
Published: May 2015

Focusing on new product development projects, this study suggests that the effect of a market orientation on innovation performance relationships may differ depending on whether the market orientation is responsive or proactive. This study also argues that process-based and outcome-based rewards moderate the effect. Based on a survey of 186 new product development projects in 122 high-tech firms, this study found that responsive and proactive market orientations have positive influences on incremental innovation performance and radical innovation performance, respectively. In addition, the positive effect of a proactive market orientation on performance is strengthened by process-based rewards, whereas the positive effect of a responsive market orientation on performance is positively moderated by outcome-based rewards. This study provides practical implications and directions for future research.
Vedolizumab for ulcerative colitis and Crohn's disease
Authors: Chaplin Steve , Goel Rishi , Patel Kamal , Irving Peter
Published: May 2015

Vedolizumab (Entyvio) is licensed for the treatment of moderate to active ulcerative colitis and Crohn's disease. Here we present the clinical data relating to its efficacy and adverse events and comment on its place in therapy.
Progestogen‐only oral contraceptives
Authors: Chaplin Steve , MacGregor Anne
Published: May 2015

Progestogen‐only oral contra ceptives are a useful alternative to combined oral contraceptives but adherence is more important.
Cystine‐knot peptides targeting cancer‐relevant human cytotoxic T lymphocyte‐associated antigen 4 (CTLA‐4)
Authors: Maaß Franziska , Wüstehube‐Lausch Joycelyn , Dickgießer Stephan , Valldorf Bernhard , Reinwarth Michael , Schmoldt Hans‐Ulrich , Daneschdar Matin , Avrutina Olga , Sahin Ugur , Kolmar Harald
Published: May 2015

Cystine‐knot peptides sharing a common fold but displaying a notably large diversity within the primary structure of flanking loops have shown great potential as scaffolds for the development of therapeutic and diagnostic agents. In this study, we demonstrated that the cystine‐knot peptide MCoTI‐II, a trypsin inhibitor from Momordica cochinchinensis, can be engineered to bind to cytotoxic T lymphocyte‐associated antigen 4 (CTLA‐4), an inhibitory receptor expressed by T lymphocytes, that has emerged as a target for the treatment of metastatic melanoma. Directed evolution was used to convert a cystine‐knot trypsin inhibitor into a CTLA‐4 binder by screening a library of variants using yeast surface display. A set of cystine‐knot peptides possessing dissociation constants in the micromolar range was obtained; the most potent variant was synthesized chemically. Successive conjugation with neutravidin, fusion to antibody Fc domain or the oligomerization domain of C4b binding protein resulted in oligovalent variants that possessed enhanced (up to 400‐fold) dissociation constants in the nanomolar range. Our data indicate that display of multiple knottin peptides on an oligomeric scaffold protein is a valid strategy to improve their functional affinity with ramifications for applications in diagnostics and therapy. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.
Peculiarities of defect generation under injection current in LEDs based on group‐III nitride3N nanostructures
Authors: Shmidt Natalia , Shabunina Evgeniia , Usikov Alexander , Chernyakov Anton , Kurin Sergey , Helava Hikki , Makarov Yuri
Published: May 2015

It has been demonstrated that, along with well‐known mechanisms of defect generation (DG) under injection current in fabricated UV‐ and commercial blue‐LED chips based on A3N nanostructures, other defect generation mechanisms are possible in local regions. Aging experiments performed simultaneously with analysis of evolution of I‐V characteristics at U < 2 V and spectral noise density dependences on current density, revealed DG with participation of multi‐phonon recombination of carriers in an extended defect system and local regions of random alloy fluctuations enriched by metallic atoms (Ga or In). (© 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Materials characterization and device analysis for evaluation of semiconductor processes by highly‐sophisticated photoelastic stress measurement technique
Authors: Herms Martin , Wagner Matthias , Molchanov Alexander , Lin Pinyen , Wolf Ingrid De , Zhao Ming
Published: May 2015

SIRD (Scanning Infrared Depolarization Imager) and SIREX (Scanning Infrared Stress Explorer) are measurement systems to evaluate and visualize the stress distribution in semiconductor materials and devices. Some main fields of application are crystal growth, high temperature processing of silicon wafers as well as the 3D‐structuring of silicon‐based microelectronic devices. The used strategies of measurement are different. SIRD and SIREX are equipped with versatile software packages that allow to separate defect‐related stress states of interest, for instance slip‐lines in GaN‐overgrown silicon. Micro‐holes fabricated for wafer marking and 3D TSV (through silicon vias) structures have been analyzed with micrometer resolution. (© 2015 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
First step towards preserving the privacy of cloud‐based IDS security policies
Authors: Kurek Tytus , Lason Artur , Niemiec Marcin
Published: May 2015

Traditional intrusion detection systems, managed by organizations themselves, have already evolved towards cloud architectures. While benefitting from all the advantages of the cloud computing paradigm, they are also suffering from one of its main drawbacks—privacy issues. As intrusion detection system security policies expose critical information regarding the organization such as vulnerabilities, sharing this information with cloud service providers raises serious privacy concerns. The following paper proposes and presents three novel solutions as a first step towards preserving the privacy of cloud‐based intrusion detection system security policies. All the solutions utilize hybrid cloud architecture, as this is a leading trend in the cloud‐based intrusion detection systems market, and share the concept of performing the most computationally expensive operations, which are pattern‐matching operations, in the public cloud. By taking the final decision regarding network packets in the private cloud on customer premises, the desired level of privacy is provided. Experimental results, received as an output from the performed simulations, confirm that all the presented solutions are efficient enough for the deployment of cloud‐based intrusion detection systems. Copyright © 2015 John Wiley & Sons, Ltd.
Morphological and functional carotid vessel wall properties in relation to cerebral white matter lesions in myocardial infarction patients
Authors: Kröner E.S.J. , van der Grond J. , Westenberg J.J.M. , van der Wall E.E. , Siebelink H.-M.J. , Lamb H.J.
Published: May 2015

Objective

Atherosclerotic large vessel disease is potentially involved in the pathogenesis of cerebral small vessel disease related to occurrence of white matter lesions (WMLs) in the brain. We aimed to assess morphological and functional carotid vessel wall properties in relation to WML using magnetic resonance imaging (MRI) in myocardial infarction (MI) patients.

Materials and methods

A total of 20 MI patients (90 % male, 61 ± 11 years) underwent carotid artery and brain MRI. Carotid vessel wall thickness (VWT) was assessed, by detecting lumen and outer wall contours. Carotid pulse wave velocity (PWV), a measure of elasticity, was determined using the transit-time method. Patients were divided according to the median VWT into two groups. Brain MRI allowed for the WML score.

Results

Mean VWT was 1.41 ± 0.29 mm and mean carotid PWV was 7.0 ± 2.2 m/s. A significant correlation (Pearson r = 0.45, p = 0.046) between VWT and PWV was observed. Furthermore, in the group of high VWT, the median WML score was higher as compared with the group with lower VWT (4.0 vs 3.0, p = 0.035).

Conclusions

Carotid artery morphological and functional alterations are correlated in MI patients. Patients with high VWT showed a higher amount of periventricular WMLs. These findings support the hypothesis that atherosclerotic large vessel disease is potentially involved in the pathogenesis of cerebral small vessel disease.
Bayesian Population Forecasting: Extending the Lee-Carter Method
Authors: Wiśniowski Arkadiusz , Smith Peter W. F. , Bijak Jakub , Raymer James , Forster Jonathan J.
Published: May 2015

In this article, we develop a fully integrated and dynamic Bayesian approach to forecast populations by age and sex. The approach embeds the Lee-Carter type models for forecasting the age patterns, with associated measures of uncertainty, of fertility, mortality, immigration, and emigration within a cohort projection model. The methodology may be adapted to handle different data types and sources of information. To illustrate, we analyze time series data for the United Kingdom and forecast the components of population change to the year 2024. We also compare the results obtained from different forecast models for age-specific fertility, mortality, and migration. In doing so, we demonstrate the flexibility and advantages of adopting the Bayesian approach for population forecasting and highlight areas where this work could be extended.
The rationale for and use of assessment frameworks: improving assessment and reporting quality in medical education
Authors: Pearce Jacob , Edwards Daniel , Fraillon Julian , Coates Hamish , Canny Benedict J. , David Wilkinson David
Published: May 2015

An assessment framework provides a structured conceptual map of the learning outcomes of a programme of study along with details of how achievement of the outcomes can be measured. The rationale for using frameworks to underpin the targeting of essential content components is especially relevant for the medical education community. Frameworks have the capacity to improve validity and reliability in assessment, allowing test developers to more easily create robust assessment instruments. The framework used by the Australian Medical Assessment Collaboration (AMAC) is an interesting and relevant case study for the international community as it draws and builds on established processes in higher education assessment. The AMAC experience offers an insight into important considerations for designing assessment frameworks and implementing frameworks in differing contexts. There are lessons which have the potential to improve assessment and reporting practice and quality in not only medical education, but in other domains of assessment. Prior to implementing any programme of assessment, the framework considerations outlined here will hopefully improve the quality of assessment and reporting practice by making implicit assumptions explicit, and allowing more critical reflection and evaluation throughout assessment processes.
Regularity of solutions to fully nonlinear elliptic and parabolic free boundary problems
Authors: Indrei Emanuel , Minne Andreas
Published: May 2015

We consider fully nonlinear obstacle-type problems of the form

\begin{cases}
F(D^{2}u,x) = f(x) & \text{a.e. in}B_{1} \cap \mathrm{\Omega }, \\
|D^{2}u| \leq K & \text{a.e. in}B_{1}\backslash \mathrm{\Omega },
\end{cases}

where Ω is an open set and

K > 0

. In particular, structural conditions on
F
are presented which ensure that

W^{2,n}(B_{1})

solutions achieve the optimal

C^{1,1}(B_{1/ 2})

regularity when
f
is Hölder continuous. Moreover, if
f
is positive on

\overline B_{1}

, Lipschitz continuous, and

\{u \neq 0\} \subset \mathrm{\Omega }

, we obtain interior

C^{1}

regularity of the free boundary under a uniform thickness assumption on

\{u = 0\}

. Lastly, we extend these results to the parabolic setting.

Highlights
THE CONGO OF EUROPE: THE BALKANS AND EMPIRE IN EARLY TWENTIETH-CENTURY BRITISH POLITICAL CULTURE
Authors: PERKINS JAMES
Published: May 2015

This article explores early twentieth-century British political and humanitarian engagement with the Balkans. It focuses on the Balkan Committee, a liberal pressure group that served as the main hub for British interest in the region in the decade before the First World War. Whilst drawing attention to the specific challenges presented by the Balkans to the British liberal mind, it is argued that the Balkan Committee was part of a wider movement of humanitarianism and political activism that encompassed both continental and colonial questions. The issues around which the committee campaigned are related to humanitarian protests against the use of forced labour in Africa, in particular the Congo Reform Association, as well as to the Persia Committee, formed in protest against the 1907 Anglo-Russian agreement. This approach highlights how ‘Europe’ and empire were interconnected agendas within an overarching liberal-internationalist worldview and reformist conscience, despite the different cultural lenses through which humanitarian questions in different parts of the globe were viewed. It is suggested that research into British interaction with the Balkans offers a fruitful means by which to integrate historical analysis of the continental and imperial aspects of Britain's external relations in the ‘age of empire’.
BORDERING AND FRONTIER-MAKING IN NINETEENTH-CENTURY BRITISH INDIA
Authors: SIMPSON THOMAS
Published: May 2015

From the 1820s to the 1850s, the British Indian state undertook its final major phase of expansion to assume the approximate geographical extent it retained until its demise in 1947. It confronted at its north-eastern and north-western outskirts seemingly intractable mountains, deserts, and jungles inhabited by apparently stateless ‘tribal’ peoples. In its various attempts to comprehend and deal with these human and material complexities, the colonial state undertook projects of spatial engagement that were often confused and ineffective. Efforts to produce borders and frontier areas to mark the limits of administered British India were rarely authoritative and were reworked by colonial officials and local inhabitants alike. Bringing together diverse examples of bordering and territory-making from peripheral regions of South Asia that are usually treated separately lays bare the limits of the colonial state's power and its ambivalent attitude towards spatial forms and technologies that are conventionally taken to be key foundations of modern states. These cases also intervene in the burgeoning political geography literature on boundary-making, suggesting that borders and the territories they delimit are not stable objects but complex and fragmented entities, performed and contested by dispersed agencies and therefore prone to endless fluctuation.
POLICING PEDDLERS: THE PROSECUTION OF ILLEGAL STREET TRADE IN EIGHTEENTH-CENTURY DUTCH TOWNS
Authors: VAN DEN HEUVEL DANIELLE
Published: May 2015

Street vending was a common feature in many towns in early modern Europe. However, peddlers and hawkers often operated outside the official framework, lacking permission from governments and guilds. The impact of their informal status has hitherto not featured very extensively in historical studies. This article assesses the impact of policing of street vendors by looking at familiar source materials in a new way. Rather than solely focusing on those people who were ultimately punished, this article investigates the full process of policing and prosecution of street traders in eighteenth-century Dutch towns. It exposes that apart from those receiving a formal punishment, many more traders could suffer from policing activities, and that particular groups of street vendors were more vulnerable than others due to the specific dynamics of local power relations. As such, this article provides new insights into policing and social control, while also offering wider lessons for our understanding of the relationship between the formal and informal economy in pre-industrial Europe.
Digestive flexibility in a euryhaline crab from a SW Atlantic coastal lagoon: alkaline phosphatase activity sensitive to salinity in the hepatopancreas
Authors: Pinoni Silvina Andrea , Méndez Eugenia , López Mañanes Alejandra Antonia
Published: May 2015

We studied biochemical characteristics and the response to low salinity at short and long-term after feeding of alkaline phosphatase (AP) activity in hepatopancreas of the osmoregulator crabNeohelice granulatafrom Mar Chiquita coastal lagoon (Buenos Aires Province, Argentina) (37°32′–37°45′S 57°19′–57°26′W). The hepatopancreas exhibited a levamisole-insensitive and a levamisole-sensitive AP activity with distinct characteristics. Levamisole-insensitive activity was similar within the range of pH 7.4–9.0 and exhibited a Michaelis–Menten kinetics. Levamisole-sensitive AP activity appeared to be maximal at pH 8.5 and appeared to exhibit an allosteric kinetics. In crabs acclimated to 10 psu (hyper-regulation conditions) levamisole-insensitive and levamisole-sensitive AP activity increased (about 16-fold) over time from short term (2–4 h) to long term (120 h) after feeding while no changes occurred in crabs acclimated to 35 psu (osmoconforming conditions). The changes of AP activity along with the higher values at 120 h after feeding in 10 psu compared with those in 35 psu, and the concomitant changes in proteolytic activity, suggest a role of AP in digestive and metabolic adjustments at the biochemical level upon hyper-regulatory conditions.
The formation of public-private partnerships in China: an institutional perspective
Authors: Zhang Yanlong
Published: May 2015

This study offers a sociopolitical perspective on the worldwide diffusion of liberalisation reforms in infrastructure industries. It unpacks the heterogeneity in the extent to which the private sector is allowed to participate in these industries through an analysis of the formation of public-private partnerships in Chinese cities. This study considers the effects of horizontal and vertical diffusion mechanisms on the adoption of different types of public-private partnerships in different infrastructure sectors. An analysis of projects with private participation in 333 Chinese cities between 1992 and 2008 reveals that the spatial effects appear to be significantly modulated when the influence from structurally equivalent peer cities are considered; moreover, the effects of the vertical diffusion mechanisms are moderated by the liberalisation index of the contract forms, and the horizontal diffusion mechanisms are moderated by the marketability of the infrastructure segments.
A defence of participation income
Authors: Pérez-Muñoz Cristian
Published: May 2015

This article offers a novel defence of participation income (PI). It claims that there are pragmatic and normative reasons to prefer PI over alternative redistributive policies, such as an unconditional basic income and workfare programmes. In particular, it argues that PI should be conceived as a particular type of civic service programme designed to address a large number of unmet social needs that are not met by entrepreneurs in the marketplace. The article ends by addressing five objections that can be raised against its argument.
Associations between quality of relationships and life satisfaction of older mothers in Estonia, Germany, Russia and China
Authors: WU JING , KASEARU KAIRI , VÄRNIK AIRI , TOODING LIINA-MAI , TROMMSDORFF GISELA
Published: May 2015

The aim of the current study is to examine the associations between the quality of relationships and life satisfaction of older mothers in Estonia, Germany, Russia and the People's Republic of China, based on the assumptions of the Family Change Theory. The role of satisfaction with family life as the probable mediating factor is considered. Estonian older mothers reported the least admiration and intimacy in their relationships with their adult daughters, and the least satisfaction with family life compared to German, Russian and Chinese mothers. German older mothers perceived the most admiration from their adult daughters and were the most satisfied with both their family and general life. Russian older mothers were the least satisfied with their general life compared to their counterparts in Estonia, Germany and China. The results from the Structural Equation Modelling showed that the relationship between satisfaction with family life and general life satisfaction was statistically significant in all countries except Russia. The satisfaction with family life as a mediating factor might strengthen the positive and negative aspects of intergenerational relationships on the life satisfaction of older mothers. The findings indicated that the emotional closeness and intergenerational relationships in families during the process of transition and globalisation play an important role in the life satisfaction of older mothers in these four countries.
Fast circular dictionary-matching algorithm
Authors: ATHAR TANVER , BARTON CARL , BLAND WIDMER , GAO JIA , ILIOPOULOS COSTAS S. , LIU CHANG , PISSIS SOLON P.
Published: May 2015

Circular string matching is a problem which naturally arises in many contexts. It consists in finding all occurrences of the rotations of a pattern of lengthmin a text of lengthn. There exist optimal worst- and average-case algorithms for circular string matching. Here, we present a suboptimal average-case algorithm for circular string matching requiring time$\mathcal{O}$(n) and space$\mathcal{O}$(m). The importance of our contribution is underlined by the fact that the proposed algorithm can be easily adapted to deal with circular dictionary matching. In particular, we show how the circular dictionary-matching problem can be solved in average-case time$\mathcal{O}$(n+M) and space$\mathcal{O}$(M), whereMis the total length of the dictionary patterns, assuming that the shortest pattern is sufficiently long. Moreover, the presented average-case algorithms and other worst-case approaches were also implemented. Experimental results, using real and synthetic data, demonstrate that the implementation of the presented algorithms can accelerate the computations by more than a factor of two compared to the corresponding implementation of other approaches.
Psychosocial approaches to violence and aggression: contextually anchored and trauma-informed interventions
Authors: Horowitz Deborah , Guyer Margaret , Sanders Kathy
Published: May 2015

Psychosocial interventions are part of the complex understanding and treatment of violent behavior in our state mental health hospitals. A comprehensive assessment of violence and aggression includes attention to all 3 domains of prevention and assessment (primary-institutional, secondary-structural, and tertiary-direct). Trauma experiences and their consequences may include behavioral violence and aggression. The authors’ premise is that trauma is a universal component in the individual assessment of violent behavior. Therapeutic interventions must include a trauma-informed formulation to be effective. Organizational commitment to trauma-informed, person-centered, recovery-oriented (TPR) care is crucial to the efficacy of any of the interventions discussed. Thus, the dynamic nature of the individual, interpersonal, environmental, and cultural factors associated with the daily operations of the inpatient unit need to be assessed through the lens of primary and secondary violence prevention, building on the recognition that the majority of persons served and staff have significant trauma histories. Once a compassionate, respectful, empathic, and empowering approach is embraced by leadership and staff, the work with individuals can proceed more effectively. Interventions used include a variety of cognitive-behavioral, interpersonal, and somatosensory therapies. These interventions, when effectively applied, result in more self-esteem, self-mastery, self-control for the person served, and diminished behavioral violence.
Bill Dixon's Voice (Letter)
Authors: PORTER ERIC
Published: May 2015

In November 1966 composer and improviser Bill Dixon recorded a seventeen-minute-long “voice letter” to jazz writer Frank Kofsky. This letter may be analyzed as a critical intervention by Dixon, an attempt to change the context of interpretation around improvised music. But the voice letter may also be heard and analyzed as a kind of performance. As Dixon speaks, one can hear the rumbling and roar of the city as well as the staccato sounds of car and truck horns unfolding in dynamic counterpoint to his words. In this essay, I put the voice letter into dialogue with Dixon's personal history, his writings and interview statements, and some of his contemporaneous musical and multi-generic projects, especially his collaboration with dancer and choreographer Judith Dunn. I show how the letter maps Dixon's and Dunn's positions within a geography of intellectual circles, experimental artistic communities, and low-wage employment networks. By extension, I examine how the voice letter, as critical intervention and performance, points us to a nuanced understanding of black experimental music of the 1960s as a socially inflected, self-conscious and, ultimately, serious engagement with various modes of artistic production and thought, carried out under conditions of both precarity and inspiration.
First distributional record of Nitokra affinis Gurney, 1927 (Copepoda: Harpacticoida: Ameiridae) from Vellar estuary (south-east India): structural and molecular evidence
Authors: Rajthilak C. , Santhanam P. , Raja M. , Suman T.Y. , Rajasree S.R. Radhika , Ramkumar R. , Perumal P.
Published: May 2015

The harpacticoid copepod,Nitokra affinisGurney, 1927 was recorded from Vellar estuary (south-east India) for the first time. This species was consistently found in plankton samples collected during June and July, 2010. The samples were collected by the horizontal towing of a plankton net for 20 min. In this paper, we provide drawings and descriptions ofNitokra affinisand discuss the possible mechanisms of its introduction. We also compare a 769 bp sequence of its 18S ribosomal (r) DNA with already publicly available sequences, which is characterized as a meaningful barcode for the subspecies identification ofNitokra affinisin the future.
Maternal nutrition in pregnancy and metabolic risks among neonates in a Pakistani population, a pilot study
Authors: Shaikh F. , Basit A. , Hakeem R. , Fawwad A. , Hussain A.
Published: May 2015

The aim of this study was to observe the association between maternal undernutrition and metabolic risk indicators in newborns at birth. Fifty-nine expectant mothers between 28 and 40 weeks of gestation were included after obtaining their informed consent. Mothers were divided into undernourished, normally nourished and overnourished groups. A total of 54 deliveries were followed-up, and cord blood samples were collected. Metabolic status at birth was assessed by determining the cord blood concentrations of glucose, insulin and lipids and by measuring insulin resistance through homeostasis model assessment. Metabolic risk indicators in the offspring were compared following mothers’ nutrition status (under and normal nourished groups). We found that concentrations of glucose (5.31±2.01 v. 4.69±2.22 mmol/l, P=0.01), total cholesterol (2.51±1.52 v. 1.84±0.66 mmol/l, P=0.04), triglycerides (0.85±1.12 v. 0.34±0.24 mmol/l, P=0.00) and low-density lipoprotein (LDL)-cholestrol (1.26±0.93 v. 1.02±0.50 mmol/l, P=0.04) were significantly high in the offspring born to undernourished mothers. LDL-cholestrol remained significantly high in the undernourished group even after adjustment for potential confounders. Furthermore, a weak association was observed between maternal body fat mass with serum leptin (r=0.272, P=0.05) and maternal body mass Index with LDL-cholestrol in the cord blood (r=0.285, P=0.05). Our results showed that offspring of undernourished mothers had a relatively higher metabolic risk profile including LDL-cholestrol compared with normal nourished group, suggesting that maternal undernutrition may influence metabolic risk markers of the newborn at birth. We recommend that these results should be confirmed by a longitudinal study with a larger sample size.
Histological variant as the significant predictor of survival in patients with lymph node positive urothelial carcinoma of the bladder
Authors: Kim Hyung Suk , Moon Kyung Chul , Jeong Chang Wook , Kwak Cheol , Kim Hyeon Hoe , Ku Ja Hyeon
Published: May 2015

The aim of this study was to evaluate the impact of histological variants of urothelial carcinoma (UC) on survival outcomes in patients with lymph node (LN) positive UC of the bladder. We reviewed and analyzed the clinical data from 424 patients who underwent radical cystectomy (RC) with pelvic lymph node dissection (PLND) for UC of the bladder and who did not receive neoadjuvant chemotherapy in our institution between 1991 and 2012. In total, 92 patients (21.7%) had histologically confirmed LN positive disease. In the LN negative group (332 patients), histological variants of UC were not a significant predictor in univariate analysis. However, in the LN positive group, histological variants of UC were a significant independent prognostic factor of overall survival (hazard ratio (HR) 3.54; 95% confidence interval (CI) 1.77–7.08, p < 0.001) and cancer specific survival (HR 3.66; 95% CI 1.69–7.90, p = 0.001) in both uni-variate and multivariate Cox regression analyses. The presence of histological variants of UC may indicate a worse prognosis in LN positive patients after RC with PLND for UC of the bladder and more aggressive adjuvant therapy may be required for the improvement of postoperative survival.
Odd-parity magnetoresistance in pyrochlore iridate thin films with broken time-reversal symmetry
Authors: Fujita T. C. , Kozuka Y. , Uchida M. , Tsukazaki A. , Arima T. , Kawasaki M.
Published: May 2015

A new class of materials termed topological insulators have been intensively investigated due to their unique Dirac surface state carrying dissipationless edge spin currents. Recently, it has been theoretically proposed that the three dimensional analogue of this type of band structure, the Weyl Semimetal phase, is materialized in pyrochlore oxides with strong spin-orbit coupling, accompanied by all-in-all-out spin ordering. Here, we report on the fabrication and magnetotransport of Eu2Ir2O7 single crystalline thin films. We reveal that one of the two degenerate all-in-all-out domain structures, which are connected by time-reversal operation, can be selectively formed by the polarity of the cooling magnetic field. Once formed, the domain is robust against an oppositely polarised magnetic field, as evidenced by an unusual odd field dependent term in the magnetoresistance and an anomalous term in the Hall resistance. Our findings pave the way for exploring the predicted novel quantum transport phenomenon at the surfaces/interfaces or magnetic domain walls of pyrochlore iridates.
Tail-scope: Using friends to estimate heavy tails of degree distributions in large-scale complex networks
Authors: Eom Young-Ho , Jo Hang-Hyun
Published: May 2015

Many complex networks in natural and social phenomena have often been characterized by heavy-tailed degree distributions. However, due to rapidly growing size of network data and concerns on privacy issues about using these data, it becomes more difficult to analyze complete data sets. Thus, it is crucial to devise effective and efficient estimation methods for heavy tails of degree distributions in large-scale networks only using local information of a small fraction of sampled nodes. Here we propose a tail-scope method based on local observational bias of the friendship paradox. We show that the tail-scope method outperforms the uniform node sampling for estimating heavy tails of degree distributions, while the opposite tendency is observed in the range of small degrees. In order to take advantages of both sampling methods, we devise the hybrid method that successfully recovers the whole range of degree distributions. Our tail-scope method shows how structural heterogeneities of large-scale complex networks can be used to effectively reveal the network structure only with limited local information.
Three-Dimensional Image of Cleavage Bodies in Nuclei Is Configured Using Gas Cluster Ion Beam with Time-of-Flight Secondary Ion Mass Spectrometry
Authors: Masaki Noritaka , Ishizaki Itsuko , Hayasaka Takahiro , Fisher Gregory L. , Sanada Noriaki , Yokota Hideo , Setou Mitsutoshi
Published: May 2015

Structural variations of DNA in nuclei are deeply related with development, aging and diseases through transcriptional regulation. In order to bare cross sections of samples maintaining sub-micron structures, an Ar2500+-gas cluster ion beam (GCIB) sputter was recently engineered. By introducing GCIB sputter to time-of-flight secondary ion mass spectrometry (TOF-SIMS), we analyzed the 3D configuration and chemical composition of subnuclear structures of pyramidal cells in the CA2 region in mouse brain hippocampus. Depth profiles of chemicals were analyzed as 3D distributions by combining topographic analyses. Signals corresponding to anions such as CN− and PO3− were distributed characteristically in the shape of cell organelles. CN− signals overlapped DAPI fluorescence signals corresponding to nuclei. The clusters shown by PO3− and those of adenine ions were colocalized inside nuclei revealed by the 3D reconstruction. Taking into account their size and their number in each nucleus, those clusters could be in the cleavage bodies, which are a kind of intranuclear structure.
Hypermethylated Epidermal growth factor receptor (EGFR) promoter is associated with gastric cancer
Authors: Weng Xiaoling , Zhang Hong , Ye Junyi , Kan Mengyuan , Liu Fatao , Wang Ting , Deng Jiaying , Tan Yanfang , He Lin , Liu Yun
Published: May 2015

Epidermal growth factor receptor (EGFR) is a member of the receptor tyrosine kinases ErbB family and it is found to be overexpressed in gastric cancer. However, the mechanism of the regulation of the EGFR expression is still unknown. We used the Sequenom EpiTYPER assay to detect the methylation status of the EGFR promoter in normal and tumour tissues of 30 patients with gastric cancer. We also carried out quantitative real time PCR (qPCR) to detect the expression level of EGFR in our 30 patients. Notably, increased methylation level at EGFR promoter was found in tumour tissues than the corresponding adjacent noncancerous. In both Region I DMR and Region II DMR detected in our study, tumor tissues were significantly hypermethylated (P = 2.7743E−10 and 2.1703E−05, respectively). Region I_⊿CpG_2 was also found to be associated with the presence of distant metastasis (P = 0.0323). Furthermore, the results showed a strongly significant association between the relative EGFR expression and the EGFR methylation changes in both Region I and Region II (P = 0.0004 and 0.0001, respectively). Our findings help to indicate the hypermethylation at EGFR promoter in gastric cancer and it could be a potential epigenetic biomarker for gastric cancer status and progression.
Simple metal under tensile stress: layer-dependent herringbone reconstruction of thin potassium films on graphite
Authors: Yin Feng , Kulju Sampo , Koskinen Pekka , Akola Jaakko , Palmer Richard E.
Published: May 2015

While understanding the properties of materials under stress is fundamentally important, designing experiments to probe the effects of large tensile stress is difficult. Here tensile stress is created in thin films of potassium (up to 4 atomic layers) by epitaxial growth on a rigid support, graphite. We find that this “simple” metal shows a long-range, periodic “herringbone” reconstruction, observed in 2- and 3- (but not 1- and 4-) layer films by low-temperature scanning tunneling microscopy (STM). Such a pattern has never been observed in a simple metal. Density functional theory (DFT)simulations indicate that the reconstruction consists of self-aligned stripes of enhanced atom density formed to relieve the tensile strain. At the same time marked layer-dependent charging effects lead to substantial variation in the apparent STM layer heights.
Four-pole galvanic vestibular stimulation causes body sway about three axes
Authors: Aoyama Kazuma , Iizuka Hiroyuki , Ando Hideyuki , Maeda Taro
Published: May 2015

Galvanic vestibular stimulation (GVS) can be applied to induce the feeling of directional virtual head motion by stimulating the vestibular organs electrically. Conventional studies used a two-pole GVS, in which electrodes are placed behind each ear, or a three-pole GVS, in which an additional electrode is placed on the forehead. These stimulation methods can be used to induce virtual head roll and pitch motions when a subject is looking upright. Here, we proved our hypothesis that there are current paths between the forehead and mastoids in the head and show that our invented GVS system using four electrodes succeeded in inducing directional virtual head motion around three perpendicular axes containing yaw rotation by applying different current patterns. Our novel method produced subjective virtual head yaw motions and evoked yaw rotational body sway in participants. These results support the existence of three isolated current paths located between the mastoids and between the left and right mastoids and the forehead. Our findings show that by using these current paths, the generation of an additional virtual head yaw motion is possible.
Targets of drugs are generally and targets of drugs having side effects are specifically good spreaders of human interactome perturbations
Authors: Perez-Lopez Áron R. , Szalay Kristóf Z. , Türei Dénes , Módos Dezső , Lenti Katalin , Korcsmáros Tamás , Csermely Peter
Published: May 2015

Network-based methods are playing an increasingly important role in drug design. Our main question in this paper was whether the efficiency of drug target proteins to spread perturbations in the human interactome is larger if the binding drugs have side effects, as compared to those which have no reported side effects. Our results showed that in general, drug targets were better spreaders of perturbations than non-target proteins and in particular, targets of drugs with side effects were also better spreaders of perturbations than targets of drugs having no reported side effects in human protein-protein interaction networks. Colorectal cancer-related proteins were good spreaders and had a high centrality, while type 2 diabetes-related proteins showed an average spreading efficiency and had an average centrality in the human interactome. Moreover, the interactome-distance between drug targets and disease-related proteins was higher in diabetes than in colorectal cancer. Our results may help a better understanding of the network position and dynamics of drug targets and disease-related proteins and may contribute to develop additional, network-based tests to increase the potential safety of drug candidates.
Evaluation and integration of cancer gene classifiers: identification and ranking of plausible drivers
Authors: Liu Yang , Tian Feng , Hu Zhenjun , DeLisi Charles
Published: May 2015

The number of mutated genes in cancer cells is far larger than the number of mutations that drive cancer. The difficulty this creates for identifying relevant alterations has stimulated the development of various computational approaches to distinguishing drivers from bystanders. We develop and apply an ensemble classifier (EC) machine learning method, which integrates 10 classifiers that are publically available and apply it to breast and ovarian cancer. In particular we find the following: (1) Using both standard and non-standard metrics, EC almost always outperforms single method classifiers, often by wide margins. (2) Of the 50 highest ranked genes for breast (ovarian) cancer, 34 (30) are associated with other cancers in either the OMIM, CGC or NCG database (P < 10−22). (3) Another 10, for both breast and ovarian cancer, have been identified by GWAS studies. (4) Several of the remaining genes--including a protein kinase that regulates the Fra-1 transcription factor which is overexpressed in ER negative breast cancer cells; and Fyn, which is overexpressed in pancreatic and prostate cancer, among others--are biologically plausible. Biological implications are briefly discussed. Source codes and detailed results are available at http://www.visantnet.org/misi/driver_integration.zip.