bluuebunny/crossref_metadata_2025 huggingface dataset:
Accurate Classification of Chronic Migraine via Brain Magnetic Resonance Imaging
Authors: Schwedt Todd J. , Chong Catherine D. , Wu Teresa , Gaw Nathan , Fu Yinlin , Li Jing
Published: June 2015

Background

The International Classification of Headache Disorders provides criteria for the diagnosis and subclassification of migraine. Since there is no objective gold standard by which to test these diagnostic criteria, the criteria are based on the consensus opinion of content experts. Accurate migraine classifiers consisting of brain structural measures could serve as an objective gold standard by which to test and revise diagnostic criteria. The objectives of this study were to utilize magnetic resonance imaging measures of brain structure for constructing classifiers: (1) that accurately identify individuals as having chronic vs episodic migraine vs being a healthy control; and (2) that test the currently used threshold of 15 headache days/month for differentiating chronic migraine from episodic migraine.

Methods

Study participants underwent magnetic resonance imaging for determination of regional cortical thickness, cortical surface area, and volume. Principal components analysis combined structural measurements into principal components accounting for 85% of variability in brain structure. Models consisting of these principal components were developed to achieve the classification objectives. Tenfold cross validation assessed classification accuracy within each of the 10 runs, with data from 90% of participants randomly selected for classifier development and data from the remaining 10% of participants used to test classification performance. Headache frequency thresholds ranging from 5‐15 headache days/month were evaluated to determine the threshold allowing for the most accurate subclassification of individuals into lower and higher frequency subgroups.

Results

Participants were 66 migraineurs and 54 healthy controls, 75.8% female, with an average age of 36 +/− 11 years. Average classifier accuracies were: (1) 68% for migraine (episodic + chronic) vs healthy controls; (2) 67.2% for episodic migraine vs healthy controls; (3) 86.3% for chronic migraine vs healthy controls; and (4) 84.2% for chronic migraine vs episodic migraine. The classifiers contained principal components consisting of several structural measures, commonly including the temporal pole, anterior cingulate cortex, superior temporal lobe, entorhinal cortex, medial orbital frontal gyrus, and pars triangularis. A threshold of 15 headache days/month allowed for the most accurate subclassification of migraineurs into lower frequency and higher frequency subgroups.

Conclusions

Classifiers consisting of cortical surface area, cortical thickness, and regional volumes were highly accurate for determining if individuals have chronic migraine. Furthermore, results provide objective support for the current use of 15 headache days/month as a threshold for dividing migraineurs into lower frequency (ie, episodic migraine) and higher frequency (ie, chronic migraine) subgroups.
Linear ubiquitination signals in adaptive immune responses
Authors: Ikeda Fumiyo
Published: June 2015

Ubiquitin can form eight different linkage types of chains using the intrinsic Met 1 residue or one of the seven intrinsic Lys residues. Each linkage type of ubiquitin chain has a distinct three‐dimensional topology, functioning as a tag to attract specific signaling molecules, which are so‐called ubiquitin readers, and regulates various biological functions. Ubiquitin chains linked via Met 1 in a head‐to‐tail manner are called linear ubiquitin chains. Linear ubiquitination plays an important role in the regulation of cellular signaling, including the best‐characterized tumor necrosis factor (TNF)‐induced canonical nuclear factor‐κB (NF‐κB) pathway. Linear ubiquitin chains are specifically generated by an E3 ligase complex called the linear ubiquitin chain assembly complex (LUBAC) and hydrolyzed by a deubiquitinase (DUB) called ovarian tumor (OTU) DUB with linear linkage specificity (OTULIN). LUBAC linearly ubiquitinates critical molecules in the TNF pathway, such as NEMO and RIPK1. The linear ubiquitin chains are then recognized by the ubiquitin readers, including NEMO, which control the TNF pathway. Accumulating evidence indicates an importance of the LUBAC complex in the regulation of apoptosis, development, and inflammation in mice. In this article, I focus on the role of linear ubiquitin chains in adaptive immune responses with an emphasis on the TNF‐induced signaling pathways.
The E3 ligase Itch in immune regulation and beyond
Authors: Aki Daisuke , Zhang Wen , Liu Yun‐Cai
Published: June 2015

Itch or itchy E3 ubiquitin ligase was initially discovered by genetic studies on the mouse coat color changes, and its deletion results in an itchy phenotype with constant skin scratching and multi‐organ inflammation. It is a member of the homologous to E6‐associated protein C‐terminus (HECT)‐type family of E3 ligases, with the protein‐interacting WW‐domains for the recruitment of substrate and the HECT domain for the transfer of ubiquitin to the substrate. Since its discovery, numerous studies have demonstrated that Itch is involved in the control of many aspects of immune responses including T‐cell activation and tolerance and T‐helper cell differentiation. Itch is also implicated in other biological contexts such as tumorigenesis, development, and stress responses. Many signaling pathways are regulated by Itch‐promoted ubiquitylation of diverse target proteins. Itch is also involved in human diseases. Here, we discuss the major progress in understanding the biological significance of Itch‐promoted protein ubiquitylation in the immune and other systems and in Itch‐mediated regulation of signal transduction.
Kinase inhibition, competitive binding and proteasomal degradation: resolving the molecular function of the suppressor of cytokine signaling (SOCS) proteins
Authors: Linossi Edmond M. , Nicholson Sandra E.
Published: June 2015

The suppressor of cytokine signaling (SOCS) family of proteins are key negative regulators of cytokine and growth factor signaling. They act at the receptor complex to modulate the intracellular signaling cascade, preventing excessive signaling and restoring homeostasis. This regulation is critical to the normal cessation of signaling, highlighted by the complex inflammatory phenotypes exhibited by mice deficient in SOCS1 or SOCS3. These two SOCS proteins remain the best characterized of the eight family members (CIS, SOCS1‐7), and in particular, we now possess a sound understanding of the mechanism of action for SOCS3. Here, we review the mechanistic role of the SOCS proteins and identify examples where clear, definitive data have been generated and discuss areas where the information is less clear. From this functional viewpoint, we discuss how the SOCS proteins achieve exquisite and specific regulation of cytokine signaling and highlight outstanding questions regarding the function of the less well‐studied SOCS family members.
Roles of linear ubiquitinylation, a crucial regulator of NF‐κB and cell death, in the immune system
Authors: Sasaki Katsuhiro , Iwai Kazuhiro
Published: June 2015

Linear ubiquitinylation, a newly identified post‐translational modification, is catalyzed by the linear ubiquitin assembly complex (LUBAC), which is composed of three different subunits, HOIL‐1L (heme‐oxidized IRP2 ligase 1L), HOIP (HOIL‐1 interacting protein), and SHARPIN (SHANK‐associated RH domain‐interacting protein). LUBAC plays a critical role in the activation of nuclear factor‐κB (NF‐κB) signaling triggered by a variety of stimuli, including tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), and pathogen‐derived components, and in the protection from cell death. Loss of function of SHARPIN in mice triggers chronic inflammation in multiple organs including the skin, as well as immunodeficiency. In humans, mutations in the gene encoding HOIL‐1L cause chronic hyperinflammation and immunodeficiency, which are both associated with decreased levels of LUBAC. The linear ubiquitinylation activity of LUBAC is indispensable for B‐cell function in mice, and hyperactivation of LUBAC is associated with oncogenesis in certain forms of B‐cell lymphoma. In this review, the current understanding of the biochemistry of LUBAC‐mediated linear ubiquitinylation and its involvement in the immune system are discussed.
Linear ubiquitination in immunity
Authors: Shimizu Yutaka , Taraborrelli Lucia , Walczak Henning
Published: June 2015

Linear ubiquitination is a post‐translational protein modification recently discovered to be crucial for innate and adaptive immune signaling. The function of linear ubiquitin chains is regulated at multiple levels: generation, recognition, and removal. These chains are generated by the linear ubiquitin chain assembly complex (LUBAC), the only known ubiquitin E3 capable of forming the linear ubiquitin linkage de novo. LUBAC is not only relevant for activation of nuclear factor‐κB (NF‐κB) and mitogen‐activated protein kinases (MAPKs) in various signaling pathways, but importantly, it also regulates cell death downstream of immune receptors capable of inducing this response. Recognition of the linear ubiquitin linkage is specifically mediated by certain ubiquitin receptors, which is crucial for translation into the intended signaling outputs. LUBAC deficiency results in attenuated gene activation and increased cell death, causing pathologic conditions in both, mice, and humans. Removal of ubiquitin chains is mediated by deubiquitinases (DUBs). Two of them, OTULIN and CYLD, are constitutively associated with LUBAC. Here, we review the current knowledge on linear ubiquitination in immune signaling pathways and the biochemical mechanisms as to how linear polyubiquitin exerts its functions distinctly from those of other ubiquitin linkage types.
Targeting signaling factors for degradation, an emerging mechanism for TRAF functions
Authors: Yang Xiao‐Dong , Sun Shao‐Cong
Published: June 2015

Tumor necrosis factor receptor (TNFR)‐associated factors (TRAFs) form a family of proteins that are best known as signaling adapters of TNFRs. However, emerging evidence suggests that TRAF proteins, particularly TRAF2 and TRAF3, also regulate signal transduction by controlling the fate of intracellular signaling factors. A well‐recognized function of TRAF2 and TRAF3 in this aspect is to mediate ubiquitin‐dependent degradation of nuclear factor‐κB (NF‐κB)‐inducing kinase (NIK), an action required for the control of NIK‐regulated non‐canonical NF‐κB signaling pathway. TRAF2 and TRAF3 form a complex with the E3 ubiquitin ligase cIAP (cIAP1 or cIAP2), in which TRAF3 serves as the NIK‐binding adapter. Recent evidence suggests that the cIAP‐TRAF2‐TRAF3 E3 complex also targets additional signaling factors for ubiquitin‐dependent degradation, thereby regulating important aspects of immune and inflammatory responses. This review provides both historical aspects and new insights into the signaling functions of this ubiquitination system.
Sensor‐Based Electromagnetic Navigation (Mediguide®): How Accurate Is It? A Phantom Model Study
Authors: BOURIER FELIX , REENTS TILKO , AMMAR‐BUSCH SONIA , BUIATTI ALESSANDRA , GREBMER CHRISTIAN , TELISHEVSKA MARTA , BRKIC AMIR , SEMMLER VERENA , LENNERZ CARSTEN , KAESS BERNHARD , KOTTMAIER MARC , KOLB CHRISTOF , DEISENHOFER ISABEL , HESSLING GABRIELE
Published: June 2015

Accuracy of MediGuide® Navigation

Background

Data about localization reproducibility as well as spatial and visual accuracy of the new MediGuide® sensor‐based electroanatomic navigation technology are scarce. We therefore sought to quantify these parameters based on phantom experiments.

Methods and Results

A realistic heart phantom was generated in a 3D‐Printer. A CT scan was performed on the phantom. The phantom itself served as ground‐truth reference to ensure exact and reproducible catheter placement. A MediGuide® catheter was repeatedly tagged at selected positions to assess accuracy of point localization. The catheter was also used to acquire a MediGuide®‐scaled geometry in the EnSite Velocity® electroanatomic mapping system. The acquired geometries (MediGuide®‐scaled and EnSite Velocity®‐scaled) were compared to a CT segmentation of the phantom to quantify concordance. Distances between landmarks were measured in the EnSite Velocity®‐ and MediGuide®‐scaled geometry and the CT dataset for Bland–Altman comparison. The visualization of virtual MediGuide® catheter tips was compared to their corresponding representation on fluoroscopic cine‐loops. Point localization accuracy was 0.5 ± 0.3 mm for MediGuide® and 1.4 ± 0.7 mm for EnSite Velocity®. The 3D accuracy of the geometries was 1.1 ± 1.4 mm (MediGuide®‐scaled) and 3.2 ± 1.6 mm (not MediGuide®‐scaled). The offset between virtual MediGuide® catheter visualization and catheter representation on corresponding fluoroscopic cine‐loops was 0.4 ± 0.1 mm.

Conclusions

The MediGuide® system shows a very high level of accuracy regarding localization reproducibility as well as spatial and visual accuracy, which can be ascribed to the magnetic field localization technology. The observed offsets between the geometry visualization and the real phantom are below a clinically relevant threshold.
The impact of inflammatory cells in malignant ascites on small intestinal ICCs' morphology and function
Authors: Li Jing , Kong Dan , He Yan , Wang Xiuli , Gao Lei , Li Jiade , Yan Meisi , Liu Duanyang , Wang Yufu , Zhang Lei , Jin Xiaoming
Published: June 2015

Malignant ascites is one of the common complication at the late stage of abdominal cancers, which may deteriorate the environment of abdominal cavity and lead to potential damage of functional cells. Interstitial cells of Cajal (ICCs) are mesoderm‐derived mesenchymal cells that function normal gastrointestinal motility. The pathological changes of ICCs or the reduced number may lead to the motility disorders of gastrointestinal tract. In this study, through analysis of malignant ascites which were obtained from cancer patients, we found that inflammatory cells, including tumour‐infiltrating lymphocytes, accounted for 17.26 ± 1.31% and tumour‐associated macrophages, occupied 19.06 ± 2.27% of total cells in the ascites, suggesting these inflammatory cells, in addition to tumour cells, may exert important influence on the tumour environment of abdominal cavity. We further demonstrated that the number of mice ICCs were significant decreased, as well as morphological and functional damage when ICCs were in the simulated tumour microenvironment in vitro. Additionally, we illustrated intestinal myoelectrical activity reduced and irregular with morphological changes of ICCs using the mice model of malignant ascites. In conclusion, our data suggested that inflammatory cells in malignant ascites may damage ICCs of the small intestine and lead to intestinal motility disorders.
Effects of immune challenge on the oviposition strategy of a noctuid moth
Authors: Staudacher H. , Menken S. B. J. , Groot A. T.
Published: June 2015

Infections can have detrimental effects on the fitness of an animal. Reproducing females may therefore be sensitive to cues of infection and be able to adaptively change their oviposition strategy in the face of infection. As one possibility, females could make a terminal investment and shift reproductive effort from future to current reproduction as life expectancy decreases. We hypothesized that females of the noctuid moth Heliothis virescens make a terminal investment and adapt their oviposition timing as well as their oviposition site selectivity in response to an immune challenge. We indeed found that females that were challenged with the bacterial entomopathogen Serratia entomophila laid more eggs than control females one night after the challenge. Additionally, bacteria‐challenged females were less discriminating between oviposition sites than control females. Whereas control females preferred undamaged over damaged plants, immune‐challenged females did not differentiate between the two. These results indicate that terminal investment is part of the life history of H. virescens females. Moreover, our results suggest that the strategy of terminal investment in H. virescens oviposition represents a fitness trade‐off for females: in the face of infection, an increase in oviposition rate enhances female fitness, whereas low oviposition site selectivity reduces female fitness.
Evolution of the Dynein Heavy Chain Family in Ciliates
Authors: Rajagopalan Vidyalakshmi , Wilkes David E.
Published: June 2015

Dynein heavy chains are motor proteins that comprise a large gene family found across eukaryotes. We have investigated this gene family in four ciliate species: Ichthyophthirius, Oxytricha, Paramecium, and Tetrahymena. Ciliates appear to encode more dynein heavy chain genes than most eukaryotes. Phylogenetic comparisons demonstrated that the last common ancestor of the ciliates that were examined expressed at least 14 types of dynein heavy chains with most of the expansion coming from the single‐headed inner arm dyneins. Each of the dyneins most likely performed different functions within the cell.
Plant–herbivorous beetle networks: molecular characterization of trophic ecology within a threatened steppic environment
Authors: Kajtoch Ł. , Kubisz D. , Heise W. , Mazur M. A. , Babik W.
Published: June 2015

DNA barcoding facilitates many evolutionary and ecological studies, including the examination of the dietary diversity of herbivores. In this study, we present a survey of ecological associations between herbivorous beetles and host plants from seriously threatened European steppic grasslands. We determined host plants for the majority (65%) of steppic leaf beetles (55 species) and weevils (59) known from central Europe using two barcodes (trnL and rbcL) and two sequencing strategies (Sanger for mono/oligophagous species and Illumina for polyphagous taxa). To better understand the ecological associations between steppic beetles and their host plants, we tested the hypothesis that leaf beetles and weevils differ in food selection as a result of their phylogenetic relations (within genera and between families) and interactions with host plants. We found 224 links between the beetles and the plants. Beetles belonging to seven genera feed on the same or related plants. Their preferences were probably inherited from common ancestors and/or resulted from the host plant's chemistry. Beetles from four genera feed on different plants, possibly reducing intrageneric competition and possibly due to an adaptation to different plant chemical defences. We found significant correlations between the numbers of leaf beetle and weevil species feeding on particular plants for polyphagous taxa, but not for nonpolyphagous beetles. Finally, we found that the previous identifications of host plants based on direct observations are generally concordant with host plant barcoding from insect gut. Our results expand basic knowledge about the trophic relations of steppic beetles and plants and are immediately useful for conservation purposes.
Interpreting Performance Information: Motivated Reasoning or Unbiased Comprehension
Authors: Baekgaard Martin , Serritzlew Søren
Published: June 2015

A main rationale of performance information is to empower citizens to make informed decisions by presenting them with unambiguous information about the performance of institutions. However, even objective, clear, and unambiguous performance information is subject to biased interpretation depending on whether the information is consistent with the prior beliefs held by those who receive the information. Integrating the theory of motivated reasoning with the literature on performance information, the authors hypothesize that performance information that is inconsistent with prior beliefs is less likely to be interpreted correctly than belief‐consistent information. Using randomized survey experiments in which respondents were presented with quantitative performance data, the authors show that subjects systematically interpret performance information in ways that conform with their prior beliefs. The findings question the assumption that providing performance information automatically increases knowledge about government performance, let alone improves political decisions.
Low melting temperature for calcite at 1000 bars on the join CaCO3‐H2O – some geological implications
Authors: Durand Cyril , Baumgartner Lukas P. , Marquer Didier
Published: June 2015

Melting experiments of calcite were performed on the join CaCO3‐H2O at a pressure of 1000 bars. The system evolves to the ternary CaO‐H2O‐CO2 system during melting experiments. Our experiments show that partial melting of calcite begins at a low temperature, below 650 °C. Such a low partial melting temperature for carbonates revives the debate about the presence of carbonate melts in the upper crust. More specifically, the conditions for carbonate partial melting are present in carbonate host rocks undergoing contact metamorphism at high temperatures in the presence of water‐rich fluid. The presence of carbonate melts influences physical parameters such as viscosity and permeability in contact aureoles, and, furthermore, decarbonation reactions release massive amounts of CO2.
Design of an In-Pile SCWR Fuel Qualification Test Loop
Authors: Vojacek Ales , Ruzickova Mariana , Schulenberg Thomas
Published: June 2015

In the development of the supercritical water-cooled reactor (SCWR), an in-pile fuel assembly test loop has been designed within the framework of the joint Chinese–European project, called SCWR-FQT (Fuel Qualification Test). This paper presents the basic design of the loop with its auxiliary and safety systems, which has been examined in detail by thermal-hydraulic analyses in order to achieve operation of the loop above the thermodynamic critical point of water (374°C, 22.1 MPa) and checked by stress analyses to assure safe operation. The designed experimental loop for fuel qualification in supercritical water consists of a closed pressurized water circuit with forced circulation of the coolant through the test section—the active channel which is intended to be installed into the existing research pool-type reactor LVR-15. The active channel will be operated at temperatures and pressures which are typical for the high-performance light water reactor (HPLWR). A thick-walled pressure tube made from austenitic stainless steel, which is able to withstand the high system pressure, encloses the active channel. It contains four fuel rods with UO2 (enrichment of 19.7% U235) with a total heating power of ∼64  kW and a recuperator in order to achieve hot channel conditions as they are expected to occur in the evaporator of the HPLWR. The internal flow is realized so as to prevent the creep condition of the pressure tube. An internal U-tube cooler serves as heat sink and is connected to the secondary circuit. The entire active channel is isolated from water of the reactor pool by an air gap between the pressure tube and an aluminum displacer. The test section with fuel is connected to a 300°C closed loop and to a primary pump located outside the reactor building as well as safety systems and auxiliary systems, such as purification and measurement circuits, which are all connected with the primary circuit.
Pulmonary imaging using respiratory motion compensated simultaneous PET/MR
Authors: Dutta Joyita , Huang Chuan , Li Quanzheng , El Fakhri Georges
Published: June 2015

Purpose:

Pulmonary positron emission tomography (PET) imaging is confounded by blurring artifacts caused by respiratory motion. These artifacts degrade both image quality and quantitative accuracy. In this paper, the authors present a complete data acquisition and processing framework for respiratory motion compensated image reconstruction (MCIR) using simultaneous whole body PET/magnetic resonance (MR) and validate it through simulation and clinical patient studies.

Methods:

The authors have developed an MCIR framework based on maximum a posteriori or MAP estimation. For fast acquisition of high quality 4D MR images, the authors developed a novel Golden‐angle RAdial Navigated Gradient Echo (GRANGE) pulse sequence and used it in conjunction with sparsity‐enforcing k‐t FOCUSS reconstruction. The authors use a 1D slice‐projection navigator signal encapsulated within this pulse sequence along with a histogram‐based gate assignment technique to retrospectively sort the MR and PET data into individual gates. The authors compute deformation fields for each gate via nonrigid registration. The deformation fields are incorporated into the PET data model as well as utilized for generating dynamic attenuation maps. The framework was validated using simulation studies on the 4D XCAT phantom and three clinical patient studies that were performed on the Biograph mMR, a simultaneous whole body PET/MR scanner.

Results:

The authors compared MCIR (MC) results with ungated (UG) and one‐gate (OG) reconstruction results. The XCAT study revealed contrast‐to‐noise ratio (CNR) improvements for MC relative to UG in the range of 21%–107% for 14 mm diameter lung lesions and 39%–120% for 10 mm diameter lung lesions. A strategy for regularization parameter selection was proposed, validated using XCAT simulations, and applied to the clinical studies. The authors’ results show that the MC image yields 19%–190% increase in the CNR of high‐intensity features of interest affected by respiratory motion relative to UG and a 6%–51% increase relative to OG.

Conclusions:

Standalone MR is not the traditional choice for lung scans due to the low proton density, high magnetic susceptibility, and low relaxation time in the lungs. By developing and validating this PET/MR pulmonary imaging framework, the authors show that simultaneous PET/MR, unique in its capability of combining structural information from MR with functional information from PET, shows promise in pulmonary imaging.
Assessment of performance and reproducibility of applying a content‐based image retrieval scheme for classification of breast lesions
Authors: Gundreddy Rohith Reddy , Tan Maxine , Qiu Yuchen , Cheng Samuel , Liu Hong , Zheng Bin
Published: June 2015

Purpose:

To develop a new computer‐aided diagnosis (CAD) scheme using a content‐based image retrieval (CBIR) approach for classification between the malignant and benign breast lesions depicted on the digital mammograms and assess CAD performance and reproducibility.

Methods:

An image dataset including 820 regions of interest (ROIs) was used. Among them, 431 ROIs depict malignant lesions and 389 depict benign lesions. After applying an image preprocessing process to define the lesion center, two image features were computed from each ROI. The first feature is an average pixel value of a mapped region generated using a watershed algorithm. The second feature is an average pixel value difference between a ROI's center region and the rest of the image. A two‐step CBIR approach uses these two features sequentially to search for ten most similar reference ROIs for each queried ROI. A similarity based classification score was then computed to predict the likelihood of the queried ROI depicting a malignant lesion. To assess the reproducibility of the CAD scheme, we selected another independent testing dataset of 100 ROIs. For each ROI in the testing dataset, we added four randomly queried lesion center pixels and examined the variation of the classification scores.

Results:

The area under the ROC curve (AUC) = 0.962 ± 0.006 was obtained when applying a leave‐one‐out validation method to 820 ROIs. Using the independent testing dataset, the initial AUC value was 0.832 ± 0.040, and using the median classification score of each ROI with five queried seeds, AUC value increased to 0.878 ± 0.035.

Conclusions:

The authors demonstrated that (1) a simple and efficient CBIR scheme using two lesion density distribution related features achieved high performance in classifying breast lesions without actual lesion segmentation and (2) similar to the conventional CAD schemes using global optimization approaches, improving reproducibility is also one of the challenges in developing CAD schemes using a CBIR based regional optimization approach.
Self-Talk of Marathon Runners
Authors: Van Raalte Judy L. , Morrey Ruth Brennan , Cornelius Allen E. , Brewer Britton W.
Published: June 2015

Much of the research on self-talk in sport has focused on the effects of assigned self-talk (e.g., instructional self-talk, motivational self-talk) on the performance of laboratory tasks and/or tasks of short duration (Hatzigeorgiadis, Zourbanos, Galanis, & Theodorakis, 2011; Tod, Hardy, & Oliver, 2011). The purpose of this study was to explore more fully the self-talk of athletes involved in competition over an extended period of time. Marathon runners (N = 483) were surveyed. The majority (88%) of runners, those who indicated that they use self-talk during marathons, completed open-ended items describing their self-talk while competing. Runners reported using a rich variety of motivational self-talk as well as spiritual self-talk and mantras, types of self-talk less widely studied in the literature. Given the findings of this research, future studies exploring self-talk use during competition in sporting events of long duration seems warranted.
Respiratory Infections in the U.S. Military: Recent Experience and Control
Authors: Sanchez Jose L. , Cooper Michael J. , Myers Christopher A. , Cummings James F. , Vest Kelly G. , Russell Kevin L. , Sanchez Joyce L. , Hiser Michelle J. , Gaydos Charlotte A.
Published: June 2015

This comprehensive review outlines the impact of military-relevant respiratory infections, with special attention to recruit training environments, influenza pandemics in 1918 to 1919 and 2009 to 2010, and peacetime operations and conflicts in the past 25 years. Outbreaks and epidemiologic investigations of viral and bacterial infections among high-risk groups are presented, including (i) experience by recruits at training centers, (ii) impact on advanced trainees in special settings, (iii) morbidity sustained by shipboard personnel at sea, and (iv) experience of deployed personnel. Utilizing a pathogen-by-pathogen approach, we examine (i) epidemiology, (ii) impact in terms of morbidity and operational readiness, (iii) clinical presentation and outbreak potential, (iv) diagnostic modalities, (v) treatment approaches, and (vi) vaccine and other control measures. We also outline military-specific initiatives in (i) surveillance, (ii) vaccine development and policy, (iii) novel influenza and coronavirus diagnostic test development and surveillance methods, (iv) influenza virus transmission and severity prediction modeling efforts, and (v) evaluation and implementation of nonvaccine, nonpharmacologic interventions.
Blood Groups in Infection and Host Susceptibility
Authors: Cooling Laura
Published: June 2015

Blood group antigens represent polymorphic traits inherited among individuals and populations. At present, there are 34 recognized human blood groups and hundreds of individual blood group antigens and alleles. Differences in blood group antigen expression can increase or decrease host susceptibility to many infections. Blood groups can play a direct role in infection by serving as receptors and/or coreceptors for microorganisms, parasites, and viruses. In addition, many blood group antigens facilitate intracellular uptake, signal transduction, or adhesion through the organization of membrane microdomains. Several blood groups can modify the innate immune response to infection. Several distinct phenotypes associated with increased host resistance to malaria are overrepresented in populations living in areas where malaria is endemic, as a result of evolutionary pressures. Microorganisms can also stimulate antibodies against blood group antigens, including ABO, T, and Kell. Finally, there is a symbiotic relationship between blood group expression and maturation of the gastrointestinal microbiome.
Structural Analysis of the Roles of Influenza A Virus Membrane-Associated Proteins in Assembly and Morphology
Authors: Chlanda Petr , Schraidt Oliver , Kummer Susann , Riches James , Oberwinkler Heike , Prinz Simone , Kräusslich Hans-Georg , Briggs John A. G.
Published: June 2015

The assembly of influenza A virus at the plasma membrane of infected cells leads to release of enveloped virions that are typically round in tissue culture-adapted strains but filamentous in strains isolated from patients. The viral proteins hemagglutinin (HA), neuraminidase (NA), matrix protein 1 (M1), and M2 ion channel all contribute to virus assembly. When expressed individually or in combination in cells, they can all, under certain conditions, mediate release of membrane-enveloped particles, but their relative roles in virus assembly, release, and morphology remain unclear. To investigate these roles, we produced membrane-enveloped particles by plasmid-derived expression of combinations of HA, NA, and M proteins (M1 and M2) or by infection with influenza A virus. We monitored particle release, particle morphology, and plasma membrane morphology by using biochemical methods, electron microscopy, electron tomography, and cryo-electron tomography. Our data suggest that HA, NA, or HANA (HA plus NA) expression leads to particle release through nonspecific induction of membrane curvature. In contrast, coexpression with the M proteins clusters the glycoproteins into filamentous membrane protrusions, which can be released as particles by formation of a constricted neck at the base. HA and NA are preferentially distributed to differently curved membranes within these particles. Both the budding intermediates and the released particles are morphologically similar to those produced during infection with influenza A virus. Together, our data provide new insights into influenza virus assembly and show that the M segment together with either of the glycoproteins is the minimal requirement to assemble and release membrane-enveloped particles that are truly virus-like.

IMPORTANCEInfluenza A virus is a major respiratory pathogen. It assembles membrane-enveloped virus particles whose shapes vary from spherical to filamentous. Here we examine the roles of individual viral proteins in mediating virus assembly and determining virus shape. To do this, we used a range of electron microscopy techniques to obtain and compare two- and three-dimensional images of virus particles and virus-like particles during and after assembly. The virus-like particles were produced using different combinations of viral proteins. Among our results, we found that coexpression of one or both of the viral surface proteins (hemagglutinin and neuraminidase) with the viral membrane-associated proteins encoded by the M segment results in assembly and release of filamentous virus-like particles in a manner very similar to that of the budding and release of influenza virions. These data provide novel insights into the roles played by individual viral proteins in influenza A virus assembly.
An Enhanced Synthetic Multiclade DNA Prime Induces Improved Cross-Clade-Reactive Functional Antibodies when Combined with an Adjuvanted Protein Boost in Nonhuman Primates
Authors: Wise Megan C. , Hutnick Natalie A. , Pollara Justin , Myles Devin J. F. , Williams Constance , Yan Jian , LaBranche Celia C. , Khan Amir S. , Sardesai Niranjan Y. , Montefiori David , Barnett Susan W. , Zolla-Pazner Susan , Ferrari Guido , Weiner David B.
Published: June 2015

The search for an efficacious human immunodeficiency virus type 1 (HIV-1) vaccine remains a pressing need. The moderate success of the RV144 Thai clinical vaccine trial suggested that vaccine-induced HIV-1-specific antibodies can reduce the risk of HIV-1 infection. We have made several improvements to the DNA platform and have previously shown that improved DNA vaccines alone are capable of inducing both binding and neutralizing antibodies in small-animal models. In this study, we explored how an improved DNA prime and recombinant protein boost would impact HIV-specific vaccine immunogenicity in rhesus macaques (RhM). After DNA immunization with either a single HIV Env consensus sequence or multiple constructs expressing HIV subtype-specific Env consensus sequences, we detected both CD4+and CD8+T-cell responses to all vaccine immunogens. These T-cell responses were further increased after protein boosting to levels exceeding those of DNA-only or protein-only immunization. In addition, we observed antibodies that exhibited robust cross-clade binding and neutralizing and antibody-dependent cellular cytotoxicity (ADCC) activity after immunization with the DNA prime-protein boost regimen, with the multiple-Env formulation inducing a more robust and broader response than the single-Env formulation. The magnitude and functionality of these responses emphasize the strong priming effect improved DNA immunogens can induce, which are further expanded upon protein boost. These results support further study of an improved synthetic DNA prime together with a protein boost for enhancing anti-HIV immune responses.

IMPORTANCEEven with effective antiretroviral drugs, HIV remains an enormous global health burden. Vaccine development has been problematic in part due to the high degree of diversity and poor immunogenicity of the HIV Env protein. Studies suggest that a relevant HIV vaccine will likely need to induce broad cellular and humoral responses from a simple vaccine regimen due to the resource-limited setting in which the HIV pandemic is most rampant. DNA vaccination lends itself well to increasing the amount of diversity included in a vaccine due to the ease of manufacturing multiple plasmids and formulating them as a single immunization. By increasing the number of Envs within a formulation, we were able to show an increased breadth of responses as well as improved functionality induced in a nonhuman primate model. This increased breadth could be built upon, leading to better coverage against circulating strains with broader vaccine-induced protection.
The ORF61 Protein Encoded by Simian Varicella Virus and Varicella-Zoster Virus Inhibits NF-κB Signaling by Interfering with IκBα Degradation
Authors: Whitmer Travis , Malouli Daniel , Uebelhoer Luke S. , DeFilippis Victor R. , Früh Klaus , Verweij Marieke C.
Published: June 2015

Varicella-zoster virus (VZV) causes chickenpox upon primary infection and establishes latency in ganglia. Reactivation from latency causes herpes zoster, which may be complicated by postherpetic neuralgia. Innate immunity mediated by interferon and proinflammatory cytokines represents the first line of immune defense upon infection and reactivation. VZV is known to interfere with multiple innate immune signaling pathways, including the central transcription factor NF-κB. However, the role of these inhibitory mechanisms
in vivo
is unknown. Simian varicella virus (SVV) infection of rhesus macaques recapitulates key aspects of VZV pathogenesis, and this model thus permits examination of the role of immune evasion mechanisms
in vivo
. Here, we compare SVV and VZV with respect to interference with NF-κB activation. We demonstrate that both viruses prevent ubiquitination of the NF-κB inhibitor IκBα, whereas SVV additionally prevents IκBα phosphorylation. We show that the ORF61 proteins of VZV and SVV are sufficient to prevent IκBα ubiquitination upon ectopic expression. We further demonstrate that SVV ORF61 interacts with β-TrCP, a subunit of the SCF ubiquitin ligase complex that mediates the degradation of IκBα. This interaction seems to inactivate SCF-mediated protein degradation in general, since the unrelated β-TrCP target Snail is also stabilized by ORF61. In addition to ORF61, SVV seems to encode additional inhibitors of the NF-κB pathway, since SVV with ORF61 deleted still prevented IκBα phosphorylation and degradation. Taken together, our data demonstrate that SVV interferes with tumor necrosis factor alpha (TNF-α)-induced NF-κB activation at multiple levels, which is consistent with the importance of these countermechanisms for varicella virus infection.

IMPORTANCE
The role of innate immunity during the establishment of primary infection, latency, and reactivation by varicella-zoster virus (VZV) is incompletely understood. Since infection of rhesus macaques by simian varicella virus (SVV) is used as an animal model of VZV infection, we characterized the molecular mechanism by which SVV interferes with innate immune activation. Specifically, we studied how SVV prevents activation of the transcription factor NF-κB, a central factor in eliciting proinflammatory responses. The identification of molecular mechanisms that counteract innate immunity might ultimately lead to better vaccines and treatments for VZV, since overcoming these mechanisms, either by small-molecule inhibition or by genetic modification of vaccine strains, is expected to reduce the pathogenic potential of VZV. Moreover, using SVV infection of rhesus macaques, it will be possible to study how increasing the vulnerability of varicella viruses to innate immunity will impact viral pathogenesis.
Health trajectories in regeneration areas in England: the impact of the New Deal for Communities intervention
Authors: Walthery Pierre , Stafford Mai , Nazroo James , Whitehead Margaret , Dibben Christopher , Halliday Emma , Povall Sue , Popay Jennie
Published: June 2015

Background

A large body of evidence documents the adverse relationship between concentrated deprivation and health. Among the evaluations of regeneration initiatives to tackle these spatial inequalities, few have traced the trajectories of individuals over time and fewer still have employed counterfactual comparison. We investigate the impact of one such initiative in England, the New Deal for Communities (NDC), which ran from 1999 to 2011, on socioeconomic inequalities in health trajectories.

Methods

Latent Growth Curve modelling of within-person changes in self-rated health, mental health and life satisfaction between 2002 and 2008 of an analytical cohort of residents of 39 disadvantaged areas of England in which the NDC was implemented, compared with residents of comparator, non-intervention areas, focusing on: (1) whether differences over time in outcomes can be detected between NDC and comparator areas and (2) whether interventions may have altered socioeconomic differences in outcomes.

Results

No evidence was found for an overall improvement in the three outcomes, or for significant differences in changes in health between respondents in NDC versus comparator areas. However, we found a weakly significant gap in life satisfaction and mental health between high and low socioeconomic status individuals in comparator areas which widened over time to a greater extent than in NDC areas. Change over time in the three outcomes was non-linear: individual improvements among NDC residents were largest before 2006.

Conclusions

There is limited evidence that the NDC moderated the impact of socioeconomic factors on mental health and life satisfaction trajectories. Furthermore, any NDC impact was strongest in the first 6 years of the programmes.
STUDY ON CONVERSION BETWEEN MOMENTUM AND CONTRARIAN BASED ON FRACTAL GAME
Authors: WU XU , SONG GUANGHUI , DENG YAN , XU LIN
Published: June 2015

Based on the fractal game which is performed by the majority and the minority, the fractal market theory (FMT) is employed to describe the features of investors' decision-making. Accordingly, the process of fractal games is formed in order to analyze the statistical features of conversion between momentum and contrarian. The result shows that among three fractal game mechanisms, the statistical feature of simulated return rate series is much more similar to log returns on actual series. In addition, the conversion between momentum and contrarian is also extremely similar to real situation, which can reflect the effectiveness of using fractal game in analyzing the conversion between momentum and contrarian. Moreover, it also provides decision-making reference which helps investors develop effective investment strategy.
Multilingual Topic Models for Bilingual Dictionary Extraction
Authors: Liu Xiaodong , Duh Kevin , Matsumoto Yuji
Published: June 2015

A machine-readable bilingual dictionary plays a crucial role in many natural language processing tasks, such as statistical machine translation and cross-language information retrieval. In this article, we propose a framework for extracting a bilingual dictionary from comparable corpora by exploiting a novel combination of topic modeling and word aligners such as the IBM models. Using a multilingual topic model, we first convert a comparable
document
-aligned corpus into a parallel
topic
-aligned corpus. This novel topic-aligned corpus is similar in structure to the
sentence
-aligned corpus frequently employed in statistical machine translation and allows us to extract a bilingual dictionary using a word alignment model.

The main advantages of our framework is that (1) no seed dictionary is necessary for bootstrapping the process, and (2) multilingual comparable corpora in more than two languages can also be exploited. In our experiments on a large-scale Wikipedia dataset, we demonstrate that our approach can extract higher precision dictionaries compared to previous approaches and that our method improves further as we add more languages to the dataset.
Effects of chronic dietary nitrate supplementation on the hemodynamic response to dynamic exercise
Authors: Lee Jae-Suk , Stebbins Charles L. , Jung Eunji , Nho Hosung , Kim Jong-Kyung , Chang Myoung-Jei , Choi Hyun-Min
Published: June 2015

While acute treatment with beetroot juice (BRJ) containing nitrate (NO3−) can lower systolic blood pressure (SBP), afterload, and myocardial O2 demand during submaximal exercise, effects of chronic supplementation with BRJ (containing a relatively low dose of NO3−, 400 mg) on cardiac output (CO), SBP, total peripheral resistance (TPR), and the work of the heart in response to dynamic exercise are not known. Thus, in 14 healthy males (22 ± 1 yr), we compared effects of 15 days of both BRJ and nitrate-depleted beetroot juice (NDBRJ) supplementation on plasma concentrations of NOx (NO3−/NO2−), SBP, diastolic blood pressure (DBP), mean arterial pressure (MAP), CO, TPR, and rate pressure product (RPP) at rest and during progressive cycling exercise. Endothelial function was also assessed via flow-mediated dilation (FMD). BRJ supplementation increased plasma NOx from 83.8 ± 13.8 to 167.6 ± 13.2 μM. Compared with NDBRJ, BRJ reduced SBP, DBP, MAP, and TPR at rest and during exercise ( P < 0.05). In addition, RPP was decreased during exercise, while CO was increased, but only at rest and the 30% workload ( P < 0.05). BRJ enhanced FMD-induced increases in brachial artery diameter (pre: 12.3 ± 1.6%; post: 17.8 ± 1.9%). We conclude that 1) chronic supplementation with BRJ lowers blood pressure and vascular resistance at rest and during exercise and attenuates RPP during exercise and 2) these effects may be due, in part, to enhanced endothelium-induced vasodilation in contracting skeletal muscle. Findings suggest that BRJ can act as a dietary nutraceutical capable of enhancing O2 delivery and reducing work of the heart, such that exercise can be performed at a given workload for a longer period of time before the onset of fatigue.
Feature-based and object-based attention orientation during short-term memory maintenance
Authors: Ku Yixuan
Published: June 2015

Top-down attention biases the short-term memory (STM) processing at multiple stages. Orienting attention during the maintenance period of STM by a retrospective cue (retro-cue) strengthens the representation of the cued item and improves the subsequent STM performance. In a recent article, Backer et al. (Backer KC, Binns MA, Alain C. J Neurosci 35: 1307–1318, 2015) extended these findings from the visual to the auditory domain and combined electroencephalography to dissociate neural mechanisms underlying feature-based and object-based attention orientation. Both event-related potentials and neural oscillations explained the behavioral benefits of retro-cues and favored the theory that feature-based and object-based attention orientation were independent.