bluuebunny/crossref_metadata_2025 huggingface dataset:
Yield randomness, cost tradeoffs, and diversification in the EOQ model
Authors: Gerchak Yigal , Parlar Mahmut
Published: December 2013

Existing production/inventory models with random (variable) yield take the yield distribution as given. This work takes a step towards selecting the optimal yield randomness, jointly with lot sizing decisions. First, we analyze an EOQ model where yield variance and lot size are to be selected simultaneously. Two different cost structures are considered. Secondly, we consider source diversification (‘second sourcing’) as a means of reducing effective yield randomness, and trade its benefits against its costs. Conditions for the superiority of diversification between two sources with distinct yield distributions over a single source are derived. The optimal number of identical sources is also analyzed. Some comments on the congruence of the results with recent JIT practices are provided.
On ruckle's game of ambush
Authors: Lee K. T.
Published: December 2013

This article considers a two‐person ambush game in which a traveler chooses his point within a given line so as to minimize the probability of being ambushed by two obstacles placed there by his adversary. We obtain some results which complement and extend those given by Ruckle, Baston, and Bostock.
Laplacian of the electron density: a hole–lump interaction as a tool to study stereoelectronic control of chemical reactions
Authors: Fernanda Zalazar María , Peruchena Nélida M.
Published: December 2013

In this work, we applied the theory of Atoms in Molecules to the study of carbocationic transition states involved in two different reaction mechanisms, using the proposed mechanism of ethylene dimerization over Brønsted‐acid site of zeolite catalyst as a study case. We report the main results of the analysis of the Laplacian of electron density distribution and Bader's atomic charges to increase our understanding of stereoelectronic aspects of these chemical reactions. At B3LYP/6–31++G(d,p)//B3LYP/6–3G(d,p) level, our results show that the envelopes of Laplacian distribution provide valuable information about the relative orientation of the species involved in the reaction, their interaction with the catalyst surface, and its stability. The stabilization and formation of these transition states depend on the availability of electrons in the environment. Such availability plays a key role to stabilize the positive charge on the carbocationic center and, thus, to stabilize the formed carbocation. The analysis of envelopes of Laplacian could be used to study different organic and inorganic chemical reactions and provide new insights to increase our understanding of these chemical reactions. Copyright © 2013 John Wiley & Sons, Ltd.
New results on global stabilization for time‐delay nonlinear systems with low‐order and high‐order growth conditions
Authors: Sun Zong‐Yao , Liu Zhen‐Guo , Zhang Xing‐Hui
Published: December 2013

This paper investigates the global stabilization for a class of high‐order time‐delay nonlinear systems. Compared with the existing references, a distinct characteristic of this paper rests in time‐delay entering high‐order, low‐order, and linear growth parts of system nonlinearities. Based on Lyapunov–Krasovskii theorem and necessary improvement of the adding a power integrator method, a continuous global state‐feedback controller is constructed to preserve the equilibrium at the origin and guarantees the global asymptotic stability of the resulting closed‐loop system. Finally, a simple example is provided to demonstrate the validness of the proposed approach. Copyright © 2013 John Wiley & Sons, Ltd.
Data integration using service composition in data service middleware
Authors: Gannouni Sofien , Beraka Mutaz , Mathkour Hassan
Published: December 2013

Service‐oriented computing has emerged as the state‐of‐the‐art distributed computing model for loosely coupled service‐centric business applications. Specifically, service‐oriented computing techniques allow organizations to compose Web services. Indeed, the organizational capacity to compose Web services has received much interest, particularly with respect to supporting business‐to‐business or enterprise application integration. In this paper, we present a system that proposes to adopt service composition as a new approach to integrate data from various data sources. We specify the business process description language as well as the service composition engine that supports the proposed language. We also present different strategies for executing a composite data service call. Copyright © 2013 John Wiley & Sons, Ltd.
Data integrity verification scheme with designated verifiers for dynamic outsourced databases
Authors: Wang Xiaoming , Lin Yanchun , Yao Guoxiang
Published: December 2013

In order to verify the integrity of the query results in outsourced database model, we first present a new authenticated data structure by combining skip lists with polynomial functions and accumulators and then construct a data integrity verification scheme for range query. Our scheme can verify the integrity of the query results with constant time verification and constant size proof and support dynamic maintenance with constant computational cost. Compared with that of previous schemes, the communication cost in our scheme is independent of the size of the authenticated dataset and is lower. When dataset size gets larger enough, our scheme outperforms previous schemes in terms of the computational cost and verification cost. In addition, we introduce the designated verifier idea into our scheme, so our scheme achieves the result that none but subscribers can verify the integrity of the query results and then meets the practical demands such as the payment service. The proof of security and analysis of experiment performance show that our scheme is secure and efficient for larger outsourced databases. Copyright © 2013 John Wiley & Sons, Ltd.
XML development with plug‐ins as a service
Authors: Karus S.
Published: December 2013

Extensible Markup Language (XML) has quickly become a mainstream language in software development. Not only is it used for message and document interchange, it is also used to define application logic and interfaces. However, modern general purpose integrated development environments have rather limited support for XML development. The wide variety of XML‐based languages makes it a challenge to build tools for comprehensive support of XML development. In this paper, we present extensions to a library exposed as an add‐in for Microsoft Visual Studio and a command line tool to improve the development experience by providing access to subscribable service‐based pluggable helper tools. The architecture of the solution allows easier publishing and deployment of the tools, minimising the exposure of development data to third parties and providing service providers with much needed tool usage and development process data. The tools offer developers new means to check their files against good and bad practices, automatically fix errors in XML or improve the files’ conformance with development guidelines, current state of project with other projects, or run service queries to estimate their projects future progress. Copyright © 2013 John Wiley & Sons, Ltd.
A venues‐aware message routing scheme for delay‐tolerant networks
Authors: Niu Jianwei , Liu Mingzhu , Liu Yazhi , Shu Lei , Wu Dapeng
Published: December 2013

With their proliferation and increasing capabilities, mobile devices with local wireless interfaces can be organized into delay‐tolerant networks (DTNs) that exploit communication opportunities arising out of the movement of their users. As the mobile devices are usually carried by people, these DTNs can also be viewed as social networks. Unfortunately, most existing routing algorithms for DTNs rely on relatively simple mobility models that rarely consider these social network characteristics, and therefore, the mobility models in these algorithms cannot accurately describe users’ real mobility traces. In this paper, we propose two predict and spread (PreS) message routing algorithms for DTNs. We employ an adapted Markov chain to model a node's mobility pattern and capture its social characteristics. A comparison with state‐of‐the‐art algorithms demonstrates that PreS can yield better performance in terms of delivery ratio and delivery latency, and it can provide a comparable performance with the epidemic routing algorithm with lower resource consumption. Copyright © 2013 John Wiley & Sons, Ltd.
Activating secondary metabolism with stress and chemicals
Authors: Yoon Vanessa , Nodwell Justin R
Published: December 2013

The available literature on the secondary or nonessential metabolites of the streptomycetes bacteria suggests that there may be poorly expressed or “cryptic” compounds that have yet to be identified and that may have significant medical utility. In addition, it is clear that there is a large and complex regulatory network that controls the production of these molecules in the laboratory and in nature. Two approaches that have been taken to manipulating the yields of secondary metabolites are the use of various stress responses and, more recently, the use of precision chemical probes. Here, we review the status of this work and outline the challenges and opportunities afforded by each of them.
Deleterious Cognitive and Motoric Effects of Haloperidol in an Adolescent With Cerebral Palsy: A Case Report
Authors: Mortimer Diane , Gelfius Carl D. , Potts Michelle A.
Published: December 2013

This case report describes a 15‐year‐old male patient with spastic diplegic cerebral palsy, Gross Motor Function Classification System Level III, who developed severe new cognitive and motoric impairments after the administration of haloperidol. He received this dopamine antagonist and typical antipsychotic medication for an acute postoperative episode of agitation. He improved when he received the dopamine agonists amantadine and carbidopa/levodopa. This case suggests that dopamine blockade may be deleterious for individuals with cerebral palsy. Potential explanations for the events observed in this case are also presented.
Conscientious objection to provision of legal abortion care
Authors: Johnson Brooke R. , Kismödi Eszter , Dragoman Monica V. , Temmerman Marleen
Published: December 2013

Despite advances in scientific evidence, technologies, and human rights rationale for providing safe abortion, a broad range of cultural, regulatory, and health system barriers that deter access to abortion continues to exist in many countries. When conscientious objection to provision of abortion becomes one of these barriers, it can create risks to women's health and the enjoyment of their human rights. To eliminate this barrier, states should implement regulations for healthcare providers on how to invoke conscientious objection without jeopardizing women's access to safe, legal abortion services, especially with regard to timely referral for care and in emergency cases when referral is not possible. In addition, states should take all necessary measures to ensure that all women and adolescents have the means to prevent unintended pregnancies and to obtain safe abortion.
The Struggle to Remake Politics: Liberal Reform and the Limits of Policy Feedback in the Contemporary American State
Authors: Patashnik Eric M. , Zelizer Julian E.
Published: December 2013

President Barack Obama's two signature first-term legislative victories—the Affordable Care Act and the Dodd-Frank Act—are the law of the land, but the political battle over their entrenchment continues. The question now is whether these landmark reforms will be consolidated and create a new politics going forward. We develop an argument about the limits of policy feedback to illuminate the obstacles to durable liberal reform in the contemporary American state. We argue that political scientists have paid insufficient attention to the fragility of inherited policy commitments, and that the capacity of reforms to remake politics is contingent, conditional, and contested. Feedbacks are shaped not only by the internal attributes of policies, but also by the interaction between policy-specific characteristics, the strategic goals of officeholders and clientele groups, and the political forces arising from a contentious and uncertain political environment.
Whither the Resource Curse?
Authors: Morrison Kevin M.
Published: December 2013

What is it about oil? Whereas one might think that countries that produce the world's energy have it good, much scholarship has come to the conclusion that countries that produce oil have it bad: they are worse off economically and politically than they would otherwise be. This counter-intuitive idea has become so widespread that the “resource curse” is often discussed in popular outlets, from Thomas Friedman to Stephen Colbert. And yet scholarship is increasingly questioning whether this curse actually exists. After several decades of research on the topic, we still do not have a clear idea what it is about oil—if anything—that causes problems.
Response to Aaron Schneider's review ofCapital, Coercion, and Postcommunist States
Authors: Easter Gerald M.
Published: December 2013

This dialogue might strike some readers as more amicable than critical, as the two books concur on core assumptions about the comparative politics of taxation and state building. They both prefer a macrosocial analytical framework to explain political institutional outcomes, focus on elite motives and actions as the main causal factor, and provide a historically grounded analysis. Also, both books advance recent scholarship on a neofiscal sociology in comparative state-building theory. Aaron Schneider's review, however, does note two underdeveloped themes in my study of postcommunist tax states, which rightly deserve response.
Nano-graphene oxide as a novel platform for monitoring the effect of LNA modification on nucleic acid interactions
Authors: Rana Muhit , Balcioglu Mustafa , Robertson Neil , Yigit Mehmet V.
Published: December 2013

Graphene oxide serves as a stable nano-platform for adsorption of nucleic acids with or without LNA base modification while providing kinetic and spectroscopic information about the interaction.
A small molecule that displays marked reactivity toward copper– versus zinc–amyloid-β implicated in Alzheimer's disease
Authors: Savelieff Masha G. , Liu Yuzhong , Senthamarai Russell R. P. , Korshavn Kyle J. , Lee Hyuck Jin , Ramamoorthy Ayyalusamy , Lim Mi Hee
Published: December 2013

A small molecule was designed for reactivity toward Cu(ii)–amyloid-β over Zn(ii)–amyloid-β, which will expand on the development of chemical tools to uncover the role of metal–Aβ species in Alzheimer's disease.
Rapid identification of phosphorus containing proteins in electrophoresis gel spots by Laser-Induced Breakdown Spectroscopy, LIBS
Authors: Aras Nadir , Yalçın Şerife
Published: December 2013

We describe a methodology for the rapid identification of phosphorus containing proteins in the polyacrylamide gel matrix by Laser-Induced Breakdown Spectroscopy, LIBS.
Rhodium-catalyzed three-component reaction of 3-diazooxindoles with indoles and isatin-derived ketimines: a facile and versatile approach to functionalized 3,3′,3′′-trisindoles
Authors: Mei Liang-Yong , Tang Xiang-Ying , Shi Min
Published: December 2013

A variety of functionalized 3,3′,3′′-trisindoles could be produced in high yields with moderate to excellent diastereoselectivities via Rh2(OAc)4-catalyzed three-component reaction of 3-diazooxindoles with indoles and isatin-derived N-Boc ketimines.
Non-close-packed pore arrays through one-step breath figure self-assembly and reversal
Authors: Thong Aaron Zhenghui , Wei Lim Daniel Soon , Ahsan Aniq , Wei Goh Glen Tai , Xu Jianwei , Chin Jia Min
Published: December 2013

Non-close-packed breath figure arrays were observed to form at the periphery of close-packed arrays. We propose a mechanism for their formation and show a proof-of-concept that these non-close-packed pore arrays are formed due to a reversal of breath figure formation, and hence introduce a novel route to the self-assembly of such non-close-packed structures.
Physiological expression of the PI3K-activating mutation Pik3caH1047R combines with Apc loss to promote development of invasive intestinal adenocarcinomas in mice
Authors: Hare Lauren M. , Phesse Toby J. , Waring Paul M. , Montgomery Karen G. , Kinross Kathryn M. , Mills Kevin , Roh Vincent , Heath Joan K. , Ramsay Robert G. , Ernst Matthias , Phillips Wayne A.
Published: December 2013

PIK3CA, the gene encoding the p110α catalytic subunit of PI3K (phosphoinositide 3-kinase), is mutated in approximately 20% of sporadic CRCs (colorectal cancers), but the role of these mutations in the pathogenesis of CRC remains unclear. In the present study we used a novel mouse model to investigate the role of the Pik3caH1047R mutation, the most common PIK3CA mutation in CRC, during the development and progression of intestinal cancer. Our results demonstrate that Pik3caH1047R, when expressed at physiological levels, is insufficient to initiate intestinal tumorigenesis; however, in the context of Apc (adenomatous polyposis coli) loss, which is observed in 80% of CRCs and by itself results in benign intestinal adenomas, the Pik3caH1047R mutation promotes the development of highly aggressive and invasive adenocarcinomas in both the small and large intestines. The results of the present study show that an activating Pik3ca mutation can act in tandem with Apc loss to drive the progression of gastrointestinal cancer and thus this disease may be susceptible to therapeutic targeting using PI3K pathway inhibitors.
Design of broadband microstrip‐to‐CPW transition
Authors: Tao Ziwen , Wang Jianpeng , Dou Yan
Published: December 2013

A broadband microstrip‐to‐CPW transition is presented. In the proposed structure, the upper microstrip ring is vertically coupled to the central conductor of the lower circular CPW via electromagnetic coupling. To obtain a wide bandwidth of operation, a short‐ended stub is introduced. The introduced short‐ended stub combined with the open‐ended microstrip ring constructs a quarter‐wavelength resonator. A sample transition has been designed and measured. Experimental results indicate that over 129% bandwidth with better than 10 dB return loss and below 1.7 dB insertion loss can be obtained.
Power amplifier linearisation scheme to mitigate superfluous radiations and suppress adjacent channel interference
Authors: Varahram Pooria , Ali Borhanuddin Mohd , Mohammady Somayeh , Sulaiman Nasri
Published: December 2013

Power amplifiers are one of the costly devices in wireless communication systems and exhibit non‐linearity. The problem of non‐linearity in the power amplifier categorises in two disturbance impacts, output distortion and in‐band distortion which lead to adjacent channel interference and constellation deviation, respectively. In order to gain maximum efficiency of the power amplifier and reduce interference, the authors propose a new digital pre‐distortion scheme called complex gain convergence (CGC). The proposed scheme is compared with indirect learning architecture and validated against an laterally diffused metal oxide semiconductor (LDMOS) power amplifier. The outcome of applying CGC scheme shows enhancement in adjacent channel leakage ratio and error vector magnitude performance while the complexity is even lower. An experimental demonstration with the actual power amplifier is also presented.
State‐of‐charge estimation of the lithium‐ion battery system with time‐varying parameter for hybrid electric vehicles
Authors: Zhang Yun , Zhang Chenghui , Zhang Xianfu
Published: December 2013

This study addresses the state‐of‐charge (SOC) estimation problem for a lithium‐ion battery system with time‐varying parameter. Although many methods have been proposed for the SOC estimation, the time‐varying parameter problem has not been solved perfectly up to now. In this study, by introducing a novel physical meaning for that the battery terminal current is ℒ2 ‐norm bounded and solving one linear matrix inequality, a robust H∞ filter is proposed for the first time to estimate the SOC of the lithium‐ion battery of hybrid electric vehicles. The proposed method is evaluated by the sequence of urban dynamometer driving schedule test. The experimental results show that the filter proposed here is more accurate and reliable than that without considering the time‐varying parameter.
Correlation analysis between SF6 decomposed components and charge magnitude of partial discharges initiated by free metal particles
Authors: Tang Ju , Pan Jianyu , Zhang Xiaoxing , Zeng Fuping , Yao Qiang , Hou Xingzhe
Published: December 2013

To obtain the inner correlation feature between SF6 decomposition characteristics caused by the partial discharge (PD) of the free metal particle insulation fault and charge magnitude, a series of experiments are conducted on the designed experimental system. Three methods, namely, gas chromatograph, chromatography‐mass spectrometry and Fourier infrared spectroscopy, are used to quantitatively measure the decomposed components. Their content relation under different PD magnitudes is obtained and determined as SOF2 > SiF4 > SOF4 > SO2F2 > SO2 > S2F10 > CO2 > CF4, where the content of highly toxic S2F10 greatly exceeds its safe threshold. The study also discusses the correlation feature between each component of the free metal particle insulation fault and charge magnitude, which is found only when the charge magnitude reaches the point where it promotes the obvious formation of the components. Each component formation is found positively related to PD quantity. Based on a stability analysis of the produced components, five components are proposed to represent PD strength and the diagnosis table to recognise the severity of the metal particle insulation fault. This study attempts to lay a solid foundation for the conditional assessment of SF6 insulated equipment.
Electrochemical quantification of fluoxetine in pharmaceutical formulation using carbon nanoparticles
Authors: Mohammadi Ali , Moghaddam Abdolmajid Bayandori , Alikhani Elham , Eilkhanizadeh Kordestan , Mozaffari Shahla
Published: December 2013

A sensitive electrochemical sensor is formed by a carbon nanoparticles (CNPs)/glassy carbon electrode for the determination of antidepressant drug fluoxetine in pharmaceutical formulation. The dependence of fluoxetine electro‐oxidation currents and potentials on pH concentration and the potential scan rate was studied. Scanning electron microscopy was used for characterisation of the CNPs. The porous layer of the CNPs improved the electroactive surface area and led to a significant increasing in the peak currents, based on the diffusion within a nanoporous film. The best electrochemical response was obtained from differential pulse voltammograms in the buffer solution (pH 9.0). Linear calibration graphs were obtained in 1–25 µM with %RSD values from 0.3 to 5.7 and the detection limit of 0.4 µM (S/N = 3). The CNPs modified electrode was successfully applied for fluoxetine determination in capsules and the results showed sufficient precision and achieved a mean recovery accuracy of 99.06%.
Evolutionary genomics of epidemic and nonepidemic strains of
Pseudomonas aeruginosa
Authors: Dettman Jeremy R. , Rodrigue Nicolas , Aaron Shawn D. , Kassen Rees
Published: December 2013

Significance

The bacterium
Pseudomonas aeruginosa
is an opportunistic pathogen of humans and is the leading cause of death in patients with cystic fibrosis (CF). We sequenced the genomes of
P. aeruginosa
isolated from respiratory tracts of patients with CF to investigate general patterns of adaptation associated with chronic infection. Selection imposed by the CF lung environment has had a major influence on genomic evolution and the genetic characteristics of isolates causing contemporary infection. Many of the genes and pathways implicated in adaptive evolution within the host had obvious roles in the pathogenic lifestyle of this bacteria. Genome sequence data indicated that an epidemic strain, with increased virulence and multidrug resistance, has spread between clinics in the United Kingdom and North America.
Evidence for soft bounds in Ubuntu package sizes and mammalian body masses
Authors: Gherardi Marco , Mandrà Salvatore , Bassetti Bruno , Cosentino Lagomarsino Marco
Published: December 2013

Significance

Not unlike a big city, a large software project grows in a complex way, involving many developers and even more users, but a predictive framework to understand these temporal patterns is lacking. We focus on software size and analyze the changes of the Ubuntu open source operating system, finding two quantitative laws. First, growth is driven by changes in scale rather than by addition–subtraction; second, evolution toward larger sizes between two consecutive releases is limited by bounds that depend on the starting size of a package. Strikingly, a stochastic model that implements these two laws is predictive. Finally, we provide evidence that similar principles could be in place for the evolution of body mass in mammals.
Whole chromosome gain does not in itself confer cancer-like chromosomal instability
Authors: Valind Anders , Jin Yuesheng , Baldetorp Bo , Gisselsson David
Published: December 2013

Significance

Aneuploidy, denoting cells with an abnormal number of chromosomes, is a common phenomenon in cancer. Another common finding in cancer cells is chromosomal instability, a condition in which cells change their chromosomal content at a high rate. It is clear that chromosomal instability can lead to aneuploidy, but whether the opposite is true has been much debated in the field of cancer biology. The concept that aneuploidy automatically triggers chromosomal instability has been propagated in the scientific literature in recent years. Here, we show that aneuploidy does not, on its own, lead to chromosomal instability, even when cells acquire chromosome alterations typical of cancer. This has important implications for understanding the role of aneuploidy in cancer development.
Long-term effect of September 11 on the political behavior of victims’ families and neighbors
Authors: Hersh Eitan D.
Published: December 2013

Significance

This study sheds light on how 9/11 catalyzed long-term changes in the political behaviors of victims’ families and neighbors. Political changes among associates of victims are important because system shocks like 9/11 can lead to rapid policy shifts, and relatives of victims often become leaders advocating for such shifts. I build upon prior research on the behavioral effects of tragic events by using a unique method of analysis. Rather than utilizing surveys, I link together individual-level government databases from before and after 9/11, and I measure the changes in the affected populations relative to similar populations that did not lose a relative or neighbor. The method I outline may prove useful in future studies of human behavior.
Resolution doubling in fluorescence microscopy with confocal spinning-disk image scanning microscopy
Authors: Schulz Olaf , Pieper Christoph , Clever Michaela , Pfaff Janine , Ruhlandt Aike , Kehlenbach Ralph H. , Wouters Fred S. , Großhans Jörg , Bunt Gertrude , Enderlein Jörg
Published: December 2013

Significance

Fluorescence microscopy is an enormously powerful tool for investigating structural organization and dynamical processes on the cellular level because of its noninvasiveness, sensitivity, and specificity. However, classical fluorescence microscopy is limited in resolution by the diffraction of light. In recent years, structural illumination microscopy has succeeded in doubling this resolution without requiring any special sample preparation or labeling dyes. However, it is technically very challenging and complex. Here, we present an alternative that achieves the same resolution enhancement by using a standard confocal spinning-disk microscope with minimal modifications. This method, in principle, allows one to double the resolution of any existing confocal microscope.
HPr antagonizes the anti-σ
70
activity of Rsd in
Escherichia coli
Authors: Park Young-Ha , Lee Chang-Ro , Choe Mangyu , Seok Yeong-Jae
Published: December 2013

Significance

Promoter recognition and specific transcription initiation depend on the binding of a sigma factor to the core RNA polymerase in bacteria. The activity of sigma factors is often regulated through sequestration by cognate anti-sigma factors. Although Rsd is known as the anti-sigma factor for the housekeeping sigma factor σ
70
, which is responsible for most of the gene expression in exponentially growing
Escherichia coli
cells, the mechanism for the sequestration of Rsd from σ
70
during the exponential phase of growth has not been investigated previously. In this study, we demonstrate that regulation of Rsd activity is achieved by the binding partner switch from σ
70
to the dephosphorylated histidine-containing phosphocarrier protein HPr of the bacterial phosphoenolpyruvate:sugar phosphotransferase system in
Escherichia coli
.
Transition state and ground state properties of the helix–coil transition in peptides deduced from high-pressure studies
Authors: Neumaier Sabine , Büttner Maren , Bachmann Annett , Kiefhaber Thomas
Published: December 2013

Significance

High pressure unfolds proteins due to a larger volume of the native state compared with the unfolded state, but the molecular origin of the volume changes is still under debate. Virtually no information is available on volume changes associated with secondary structure formation. We reveal that α-helices become stabilized with increasing pressure, which explains the commonly observed residual helical structure in pressure-unfolded proteins. The transition state for the helix–coil transition has a larger volume than both the helical and the coil state. Thus, addition or removal of a helical residue proceeds through a transitory high-energy state with a large volume, possibly due to the presence of unsatisfied hydrogen bonds, although steric effects may also be involved.
KIT oncogene inhibition drives intratumoral macrophage M2 polarization
Authors: Cavnar Michael J. , Zeng Shan , Kim Teresa S. , Sorenson Eric C. , Ocuin Lee M. , Balachandran Vinod P. , Seifert Adrian M. , Greer Jonathan B. , Popow Rachel , Crawley Megan H. , Cohen Noah A. , Green Benjamin L. , Rossi Ferdinand , Besmer Peter , Antonescu Cristina R. , DeMatteo Ronald P.
Published: December 2013

Tumor-associated macrophages (TAMs) are a major component of the cancer microenvironment. Modulation of TAMs is under intense investigation because they are thought to be nearly always of the M2 subtype, which supports tumor growth. Gastrointestinal stromal tumor (GIST) is the most common human sarcoma and typically results from an activating mutation in the KIT oncogene. Using a spontaneous mouse model of GIST and 57 freshly procured human GISTs, we discovered that TAMs displayed an M1-like phenotype and function at baseline. In both mice and humans, the KIT oncoprotein inhibitor imatinib polarized TAMs to become M2-like, a process which involved TAM interaction with apoptotic tumor cells leading to the induction of CCAAT/enhancer binding protein (C/EBP) transcription factors. In human GISTs that eventually developed resistance to imatinib, TAMs reverted to an M1-like phenotype and had a similar gene expression profile as TAMs from untreated human GISTs. Therefore, TAM polarization depends on tumor cell oncogene activity and has important implications for immunotherapeutic strategies in human cancers.
IRF4 controls the positioning of mature B cells in the lymphoid microenvironments by regulating NOTCH2 expression and activity
Authors: Simonetti Giorgia , Carette Amanda , Silva Kathryn , Wang Haowei , De Silva Nilushi S. , Heise Nicole , Siebel Christian W. , Shlomchik Mark J. , Klein Ulf
Published: December 2013

The transcription factor interferon regulatory factor-4 (IRF4) is expressed in B cells at most developmental stages. In antigen-activated B cells, IRF4 controls germinal center formation, class-switch recombination, and the generation of plasma cells. Here we describe a novel function for IRF4 in the homeostasis of mature B cells. Inducible deletion of irf4 specifically in B cells in vivo led to the aberrant accumulation of irf4-deleted follicular B cells in the marginal zone (MZ) area. IRF4-deficient B cells showed elevated protein expression and activation of NOTCH2, a transmembrane receptor and transcriptional regulator known to be required for MZ B cell development. Administration of a NOTCH2-inhibitory antibody abolished nuclear translocation of NOTCH2 in B cells within 12 h and caused a rapid and progressive disintegration of the MZ that was virtually complete 48 h after injection. The disappearance of the MZ was accompanied by a transient increase of MZ-like B cells in the blood rather than increased B cell apoptosis, demonstrating that continued NOTCH2 activation is critical for the retention of B cells in the MZ. Our results suggest that IRF4 controls the positioning of mature B cells in the lymphoid microenvironments by regulating NOTCH2 expression. These findings may have implications for the understanding of B cell malignancies with dysregulated IRF4 and NOTCH2 activity.
Foxp3+ Treg cells in humoral immunity
Authors: Wing James B. , Sakaguchi Shimon
Published: December 2013

Treg cells are essential for the maintenance of immune homeostasis and prevention of autoimmunity. In humoral immune responses, loss of Treg cell function causes increased levels of serum autoantibodies, hyper-IgE, spontaneous generation of germinal centres, and enhanced numbers of specialised T follicular helper cells (Tfh cells) controlled by the lineage-defining transcription factor BCL-6 (B-cell lymphoma 6). Recent studies have demonstrated that a subset of Treg cells [T follicular regulatory (Tfreg) cells] are able to co-opt the follicular T-cell program by gaining expression of BCL-6 and travelling to the follicle where they have an important role in the control of expansion of Tfh cells and the germinal centre reaction. However, the mechanisms by which they exert this control are still under investigation. In this review, we discuss the effects of Treg cells on humoral immunity and the mechanisms by which they exert their regulatory function.
Is Endoscopic Therapy Safe for Upper Gastrointestinal Bleeding in Anticoagulated Patients With Supratherapeutic International Normalized Ratios?
Authors: Shim Choong Nam , Chung Hyun Soo , Park Jun Chul , Shin Sung Kwan , Lee Sang Kil , Lee Yong Chan , Kim Ha Yan , Kim Dong Wook , Lee Hyuk
Published: December 2013

The management of upper gastrointestinal bleeding (UGIB) in anticoagulated patients with supratherapeutic international normalized ratios (INRs) presents a challenge. The purpose of the study was to evaluate the safety of endoscopic therapy for UGIB in anticoagulated patients with supratherapeutic INR in terms of rebleeding and therapeutic outcomes. One hundred ninety-two anticoagulated patients who underwent endoscopic treatment for UGIB were enrolled in the study. Patients were divided into 2 groups based on the occurrence of rebleeding within 30 days of the initial therapeutic endoscopy: no-rebleeding group (n = 168) and rebleeding group (n = 24). The overall rebleeding rate was 12.5%. Bleeding from gastric cancer and bleeding at the duodenum were significantly related to rebleeding in a univariate analysis. Multivariate analysis determined that presenting symptoms other than melena (hematemesis, hematochezia, or others) (odds ratio, 3.93; 95% confidence interval, 1.44–10.76) and bleeding from gastric cancer (odds ratio, 6.10; 95% confidence interval, 1.27–29.25) were significant factors predictive of rebleeding. Supratherapeutic INR at the time of endoscopic therapy was not significantly associated with rebleeding in either univariate or multivariate analysis. Significant differences in bleeding-related mortality, additional intervention to control bleeding, length of hospital stay, and transfusion requirements were revealed between the rebleeding and no-rebleeding groups. There were no significant differences in therapeutic outcomes between patients with INR within the therapeutic range and those with supratherapeutic INR. Supratherapeutic INR at the time of endoscopic therapy did not change rebleeding and therapeutic outcomes. Thus, we should consider endoscopic therapy for UGIB in anticoagulated patients, irrespective of INR at the time of endoscopic therapy.
Neurocognitive insights on conceptual knowledge and its breakdown
Authors: Lambon Ralph Matthew A.
Published: December 2013

Conceptual knowledge reflects our multi-modal ‘semantic database’. As such, it brings meaning to all verbal and non-verbal stimuli, is the foundation for verbal and non-verbal expression and provides the basis for computing appropriate semantic generalizations. Multiple disciplines (e.g. philosophy, cognitive science, cognitive neuroscience and behavioural neurology) have striven to answer the questions of how concepts are formed, how they are represented in the brain and how they break down differentially in various neurological patient groups. A long-standing and prominent hypothesis is that concepts are distilled from our multi-modal verbal and non-verbal experience such that sensation in one modality (e.g. the smell of an apple) not only activates the intramodality long-term knowledge, but also reactivates the relevant intermodality information about that item (i.e. all the things you know about and can do with an apple). This multi-modal view of conceptualization fits with contemporary functional neuroimaging studies that observe systematic variation of activation across different modality-specific association regions dependent on the conceptual category or type of information. A second vein of interdisciplinary work argues, however, that even a smorgasbord of multi-modal features is insufficient to build coherent, generalizable concepts. Instead, an additional process or intermediate representation is required. Recent multidisciplinary work, which combines neuropsychology, neuroscience and computational models, offers evidence that conceptualization follows from a combination of modality-specific sources of information plus a transmodal ‘hub’ representational system that is supported primarily by regions within the anterior temporal lobe, bilaterally.
Patients with impaired verb-tense processing: do they know that yesterday is past?
Authors: Patterson Karalyn , Holland Rachel
Published: December 2013

This paper begins with a focus on the task of stem inflection, where participants are given a verb stem and asked to produce the verb's past-tense form, which can produce a neuropsychological double dissociation with respect to regular versus irregular verbs. Two differing theoretical interpretations are outlined: one is based on specifically morphological and separate brain mechanisms for processing regular versus irregular verbs; the other argues that the two sides of the dissociation can arise from one procedure, which is not specifically morphological, and which relies to differing extents on phonological versus semantic information for regular versus irregular verbs. We then present data from a different version of the task, in which patients were given past-tense forms and asked to produce the present-tense or stem forms (talked → talk and ate → eat). This change yielded a very different pattern of performance in four non-fluent aphasic patients as a function of the regular–irregular manipulation, an outcome which is argued to be more compatible with the single- than the dual-mechanism account. Finally, we present a small amount of data from a task in which the patient was asked to judge whether spoken regular and irregular verb stems and past-tense forms indicated actions occurring
today
or
yesterday
. This task produced an even more different and intriguing pattern of performance suggesting a deficit in morpho-syntactic knowledge: not how to produce past-tense forms but what such forms mean and how that understanding interacts with verb regularity. The paper concludes with a discussion of how the research field of acquired disorders of tense processing might advance as a result of new approaches, in particular those informed by studies of developmental disorders.
Developmental disorders: what can be learned from cognitive neuropsychology?
Authors: Castles Anne , Kohnen Saskia , Nickels Lyndsey , Brock Jon
Published: December 2013

The discipline of cognitive neuropsychology has been important for informing theories of cognition and describing the nature of acquired cognitive disorders, but its applicability in a developmental context has been questioned. Here, we revisit this issue, asking whether the cognitive neuropsychological approach can be helpful for exploring the nature and causes of developmental disorders and, if so, how. We outline the key features of the cognitive neuropsychological approach, and then consider how some of the major challenges to this approach from a developmental perspective might be met. In doing so, we distinguish between challenges to the methods of cognitive neuropsychology and those facing its deeper conceptual underpinnings. We conclude that the detailed investigation of patterns of both associations and dissociations, and across both developmental and acquired cases, can assist in describing the cognitive deficits within developmental disorders and in delineating possible causal pathways to their acquisition.
Brucella ceti from two striped dolphins stranded on the Apulia coastline, Italy
Authors: Garofolo Giuliano , Zilli Katiuscia , Troiano Pasquale , Petrella Antonio , Marotta Francesca , Di Serafino Gabriella , Ancora Massimo , Di Giannatale Elisabetta
Published: December 2013

Since 1994, when Brucella ceti was first isolated from an aborted dolphin fetus, several cases have been reported worldwide. The first case of B. ceti in the Mediterranean (and in Italy), however, was recorded only in 2012, off the coast of Tuscany. Extensive studies, using serological and microbiological methods, have documented this bacterium in dolphins and demonstrated its zoonotic potential. We describe the typing of two B. ceti strains isolated from striped dolphins (Stenella coeruleoalba) stranded on the southern Apulia coastline. B. ceti isolates were conventionally typed, and then genotyped by both the multilocus sequence typing (MLST) and the multilocus variable number of tandem repeats typing (MLVA) methodologies to infer phylogeny and potential epidemiological links between the two cases. The two isolates were identified through MLST analysis as belonging to the common sequence type 26 (ST26), while MLVA analysis, having established that the two isolates have identical profiles, assigned them to a novel genotype within cluster A – a unique representative of a new Mediterranean subcluster. The results thus revealed a link between the two cases studied, demonstrating the usefulness of MLST and MLVA for the epidemiological investigation of brucellae among marine mammals.
Detection of enterovirus 68 as one of the commonest types of enterovirus found in patients with acute respiratory tract infection in China
Authors: Lu Qing-Bin , Wo Ying , Wang Hong-Yu , Wei Mao-Ti , Zhang Lei , Yang Hong , Liu En-Mei , Li Ting-Yu , Zhao Zhong-Tang , Liu Wei , Cao Wu-Chun
Published: December 2013

Human enterovirus 68 (HEV-68) is an enterovirus associated with respiratory illness. In China, no information about HEV-68 is available for children yet. This study aimed to investigate the presence of HEV-68 in mainland China between 2009 and 2012 and to explore the migration events of HEV-68 across the world. Among 1565 samples tested from children, 41 (2.6 %) were positive for HEV and 223 (14.3 %) for human rhinovirus (HRV). Seven (17.1 %) of 41 HEVs were HEV-68. Two HEV-68- and five HRV-positive samples were detected in 585 adult samples. HEV-68 is the predominant type of enterovirus in children with acute respiratory tract infection (ARTI), followed by HEV-71 and coxsackievirus A6. Three HEV-68-infected children presented with severe pneumonia and one presented with a severe asthma attack. The viruses were attributed to two novel distinct sublineages of HEV-68 based on phylogenetic analysis of partial VP1 gene sequences. Migration events analysis showed that the USA and the Netherlands were possible geographical sources of HEV-68, from where three strains migrated to China. In conclusion, HEV-68 may play a predominant role among the enteroviruses associated with ARTI in children. Additional surveillance is needed to clarify the reason why HEV-68 causes such a wide spectrum of disease, from asymptomatic to severe respiratory disease and even death.
A unique megaplasmid contributes to stress tolerance and pathogenicity of an emergent Salmonella enterica serovar Infantis strain
Authors: Aviv Gili , Tsyba Katherine , Steck Natalie , Salmon‐Divon Mali , Cornelius Antje , Rahav Galia , Grassl Guntram A, , Gal‐Mor Ohad
Published: December 2013

Of all known Salmonella enterica serovars, S. Infantis is one of the most commonly isolated and has been recently emerging worldwide. To understand the recent emergence of S. Infantis in Israel, we performed extensive comparative analyses between pre‐emergent and the clonal emergent S. Infantis populations. We demonstrate the fixation of adaptive mutations in the DNA gyrase (gyrA) and nitroreductase (nfsA) genes, conferring resistance to quinolones and nitrofurans, respectively, and the carriage of an emergent‐specific plasmid, designated pESI. This self‐transferred episome is a mosaic megaplasmid (∼280 kb), which increases bacterial tolerance to environmental mercury (mer operon) and oxidative stress, and provides further resistance to tetracycline, sulfamethoxazole and trimethoprim, most likely due to the presence of tetRA, sulI and dfrA genes respectively. Moreover, pESI carries the yersiniabactin siderophore system and two novel chaperone‐usher fimbriae. In vitro studies established that pESI conjugation into a plasmidless S. Infantis strain results in superior biofilm formation, adhesion and invasion into avian and mammalian host cells. In vivo mouse infections demonstrated higher pathogenicity and increased intestinal inflammation caused by an S. Infantis strain harboring pESI compared with the plasmidless parental strain. Our results indicate that the presence of pESI that was found only in the emergent population of S. Infantis in Israel contributes significantly to antimicrobials tolerance and pathogenicity of its carrier. It is highly likely that pESI plays a key role in the successful spread of the emergent clone that replaced the local S. Infantis community in the short time of only 2–3 years.