bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preserved Dendritic Cell HLA-DR Expression and Reduced Regulatory T Cell Activation in Asymptomatic Plasmodium falciparum and P. vivax Infection
Authors: Kho Steven , Marfurt Jutta , Noviyanti Rintis , Kusuma Andreas , Piera Kim A. , Burdam Faustina H. , Kenangalem Enny , Lampah Daniel A. , Engwerda Christian R. , Poespoprodjo Jeanne R. , Price Ric N. , Anstey Nicholas M. , Minigo Gabriela , Woodberry Tonia 
Published: June 2015

ABSTRACTClinical illness withPlasmodium falciparumorPlasmodium vivaxcompromises the function of dendritic cells (DC) and expands regulatory T (Treg) cells. Individuals with asymptomatic parasitemia have clinical immunity, restricting parasite expansion and preventing clinical disease. The role of DC and Treg cells during asymptomaticPlasmodiuminfection is unclear. During a cross-sectional household survey in Papua, Indonesia, we examined the number and activation of blood plasmacytoid DC (pDC), CD141+, and CD1c+myeloid DC (mDC) subsets and Treg cells using flow cytometry in 168 afebrile children (of whom 15 hadP. falciparumand 36 hadP. vivaxinfections) and 162 afebrile adults (of whom 20 hadP. falciparumand 20 hadP. vivaxinfections), alongside samples from 16 patients hospitalized with uncomplicated malaria. Unlike DC from malaria patients, DC from children and adults with asymptomatic, microscopy-positiveP. vivaxorP. falciparuminfection increased or retained HLA-DR expression. Treg cells in asymptomatic adults and children exhibited reduced activation, suggesting increased immune responsiveness. The pDC and mDC subsets varied according to clinical immunity (asymptomatic or symptomaticPlasmodiuminfection) and, in asymptomatic infection, according to host age and parasite species. In conclusion, active control of asymptomatic infection was associated with and likely contingent upon functional DC and reduced Treg cell activation.
Interleukin-1 (IL-1) Signaling in Intestinal Stromal Cells Controls KC/CXCL1 Secretion, Which Correlates with Recruitment of IL-22-Secreting Neutrophils at Early Stages of Citrobacter rodentium Infection
Authors: Lee Yong-Soo , Yang Hyungjun , Yang Jin-Young , Kim Yeji , Lee Su-Hyun , Kim Ji Heui , Jang Yong Ju , Vallance Bruce A. , Kweon Mi-Na 
Published: June 2015

ABSTRACTAttaching and effacing pathogens, including enterohemorrhagicEscherichia coliin humans andCitrobacter rodentiumin mice, raise serious public health concerns. Here we demonstrate that interleukin-1 receptor (IL-1R) signaling is indispensable for protection againstC. rodentiuminfection in mice. Four days after infection withC. rodentium, there were significantly fewer neutrophils (CD11b+Ly6C+Ly6G+) in the colons of IL-1R−/−mice than in wild-type mice. Levels of mRNA and protein of KC/CXCL1 were also significantly reduced in colon homogenates of infected IL-1R−/−mice relative to wild-type mice. Of note, infiltrated CD11b+Ly6C+Ly6G+neutrophils were the main source of IL-22 secretion afterC. rodentiuminfection. Interestingly, intestinal stromal cells isolated from IL-1R−/−mice secreted lower levels of KC/CXCL1 than stromal cells from wild-type mice duringC. rodentiuminfection. Similar effects were found when mouse intestinal stromal cells and human nasal polyp stromal cells were treated with IL-1R antagonists (i.e., anakinra)in vitro. These results suggest that IL-1 signaling plays a pivotal role in activating mucosal stromal cells to secrete KC/CXCL1, which is essential for infiltration of IL-22-secreting neutrophils upon bacterial infection.
Genetic and Proteomic Analyses of Pupylation in Streptomyces coelicolor
Authors: Compton Corey L. , Fernandopulle Michael S. , Nagari Rohith T. , Sello Jason K. 
Published: June 2015

ABSTRACT

Pupylation is a posttranslational modification peculiar to actinobacteria wherein proteins are covalently modified with a small protein called the prokaryotic ubiquitin-like protein (Pup). Like ubiquitination in eukaryotes, this phenomenon has been associated with proteasome-mediated protein degradation in mycobacteria. Here, we report studies of pupylation in a streptomycete that is phylogentically related to mycobacteria. We constructed mutants of
Streptomyces coelicolor
lacking PafA (Pup ligase), the proteasome, and the Pup-proteasome system. We found that these mutants share a high susceptibility to oxidative stress compared to that of the wild-type strain. Remarkably, we found that the
pafA
null mutant has a sporulation defect not seen in strains lacking the Pup-proteasome system. In proteomics experiments facilitated by an affinity-tagged variant of Pup, we identified 110 pupylated proteins in
S. coelicolor
strains having and lacking genes encoding the 20S proteasome. Our findings shed new light on this unusual posttranslational modification and its role in
Streptomyces
physiology.

IMPORTANCE
The presence of 20S proteasomes reminiscent of those in eukaryotes and a functional equivalent of ubiquitin, known as the prokaryotic ubiquitin-like protein (Pup), in actinobacteria have motivated reevaluations of protein homeostasis in prokaryotes. Though the Pup-proteasome system has been studied extensively in mycobacteria, it is much less understood in streptomycetes, members of a large genus of actinobacteria known for highly choreographed life cycles in which phases of morphological differentiation, sporulation, and secondary metabolism are often regulated by protein metabolism. Here, we define constituents of the pupylome in
Streptomyces coelicolor
for the first time and present new evidence that links pupylation and the oxidative stress response in this bacterium. Surprisingly, we found that the Pup ligase has a Pup-independent role in sporulation.
Individualised cognitive functional therapy compared with a combined exercise and pain education class for patients with non-specific chronic low back pain: study protocol for a multicentre randomised controlled trial
Authors: O'Keeffe Mary , Purtill Helen , Kennedy Norelee , O'Sullivan Peter , Dankaerts Wim , Tighe Aidan , Allworthy Lars , Dolan Louise , Bargary Norma , O'Sullivan Kieran 
Published: June 2015

IntroductionNon-specific chronic low back pain (NSCLBP) is a very common and costly musculoskeletal disorder associated with a complex interplay of biopsychosocial factors. Cognitive functional therapy (CFT) represents a novel, patient-centred intervention which directly challenges pain-related behaviours in a cognitively integrated, functionally specific and graduated manner. CFT aims to target all biopsychosocial factors that are deemed to be barriers to recovery for an individual patient with NSCLBP. A recent randomised controlled trial (RCT) demonstrated the superiority of individualised CFT for NSCLBP compared to manual therapy combined with exercise. However, several previous RCTs have suggested that class-based interventions are as effective as individualised interventions. Therefore, it is important to examine whether an individualised intervention, such as CFT, demonstrates clinical effectiveness compared to a relatively cheaper exercise and education class. The current study will compare the clinical effectiveness of individualised CFT with a combined exercise and pain education class in people with NSCLBP.Methods and analysisThis study is a multicentre RCT. 214 participants, aged 18–75 years, with NSCLBP for at least 6 months will be randomised to one of two interventions across three sites. The experimental group will receive individualised CFT and the length of the intervention will be varied in a pragmatic manner based on the clinical progression of participants. The control group will attend six classes which will be provided over a period of 6–8 weeks. Participants will be assessed preintervention, postintervention and after 6 and12 months. The primary outcomes will be functional disability and pain intensity. Non-specific predictors, moderators and mediators of outcome will also be analysed.Ethics and disseminationEthical approval has been obtained from the Mayo General Hospital Research Ethics Committee (MGH-14-UL). Outcomes will be disseminated through publication according to the SPIRIT statement and will be presented at scientific conferences.Trial registration number(ClinicalTrials.govNCT02145728).
How subduction broke up Pangaea with implications for the supercontinent cycle
Authors: Keppie Fraser 
Published: June 2015

Abstract
Mechanisms that can explain the Mesozoic motion of Pangaea in a palaeomagnetic mantle reference frame may also be able to explain its breakup. Calculations indicate that Pangaea moved along a non-rigid path in the mantle frame between the late Triassic and early Jurassic. The breakup of Pangaea may have happened as a response to this non-rigid motion. Tectonic forces applied to the margins of Pangaea as a consequence of subduction at its peripheries can explain both the motion and deformation of Pangaea with a single mechanism. In contrast, mantle forces applied to the base of Pangaea appear to be inconsistent with the kinematic constraints and do not explain the change in supercontinent motion that accompanied the breakup event. Top-down plate tectonics are inferred to have caused the breakup of Pangaea. Strong coupling between the mantle and lithosphere may not have been the case during the Phanerozoic eon when the Pangaean supercontinent formed and subsequently dispersed.
Chromatic Correlation Clustering
Authors: Bonchi Francesco , Gionis Aristides , Gullo Francesco , Tsourakakis Charalampos E. , Ukkonen Antti 
Published: June 2015

We study a novel clustering problem in which the pairwise relations between objects are
categorical
. This problem can be viewed as clustering the vertices of a graph whose edges are of different types (
colors
). We introduce an objective function that ensures the edges within each cluster have, as much as possible, the same color. We show that the problem is
NP
-hard and propose a randomized algorithm with approximation guarantee proportional to the maximum degree of the input graph. The algorithm iteratively picks a random edge as a pivot, builds a cluster around it, and removes the cluster from the graph. Although being fast, easy to implement, and parameter-free, this algorithm tends to produce a relatively large number of clusters. To overcome this issue we introduce a variant algorithm, which modifies how the pivot is chosen and how the cluster is built around the pivot. Finally, to address the case where a fixed number of output clusters is required, we devise a third algorithm that directly optimizes the objective function based on the
alternating-minimization
paradigm.

We also extend our objective function to handle cases where object’s relations are described by multiple labels. We modify our randomized approximation algorithm to optimize such an extended objective function and show that its approximation guarantee remains proportional to the maximum degree of the graph.
We test our algorithms on synthetic and real data from the domains of social media, protein-interaction networks, and bibliometrics. Results reveal that our algorithms outperform a baseline algorithm both in the task of reconstructing a ground-truth clustering and in terms of objective-function value.
Misbehavior in Bitcoin
Authors: Karame Ghassan O. , Androulaki Elli , Roeschlin Marc , Gervais Arthur , Čapkun Srdjan 
Published: June 2015

Bitcoin is a decentralized payment system that relies on Proof-of-Work (PoW) to resist double-spending through a distributed timestamping service. To ensure the operation and security of Bitcoin, it is essential that all transactions and their order of execution are available to all Bitcoin users.
Unavoidably, in such a setting, the security of transactions comes at odds with transaction privacy. Motivated by the fact that transaction confirmation in Bitcoin requires tens of minutes, we analyze the conditions for performing successful double-spending attacks against fast payments in Bitcoin, where the time between the exchange of currency and goods is short (in the order of a minute). We show that unless new detection techniques are integrated in the Bitcoin implementation, double-spending attacks on fast payments succeed with considerable probability and can be mounted at low cost. We propose a new and lightweight countermeasure that enables the detection of double-spending attacks in fast transactions.
In light of such misbehavior, accountability becomes crucial. We show that in the specific case of Bitcoin, accountability complements privacy. To illustrate this tension, we provide accountability and privacy definition for Bitcoin, and we investigate analytically and empirically the privacy and accountability provisions in Bitcoin.
Compiler Management of Communication and Parallelism for Quantum Computation
Authors: Heckey Jeff , Patil Shruti , JavadiAbhari Ali , Holmes Adam , Kudrow Daniel , Brown Kenneth R. , Franklin Diana , Chong Frederic T. , Martonosi Margaret 
Published: June 2015

Quantum computing (QC) offers huge promise to accelerate a range of computationally intensive benchmarks. Quantum computing is limited, however, by the challenges of decoherence: i.e., a quantum state can only be maintained for short windows of time before it decoheres. While quantum error correction codes can protect against decoherence, fast execution time is the best defense against decoherence, so efficient architectures and effective scheduling algorithms are necessary. This paper proposes the Multi-SIMD QC architecture and then proposes and evaluates effective schedulers to map benchmark descriptions onto Multi-SIMD architectures. The Multi-SIMD model consists of a small number of SIMD regions, each of which may support operations on up to thousands of qubits per cycle.
Efficient Multi-SIMD operation requires efficient scheduling. This work develops schedulers to reduce communication requirements of qubits between operating regions, while also improving parallelism.We find that communication to global memory is a dominant cost in QC. We also note that many quantum benchmarks have long serial operation paths (although each operation may be data parallel). To exploit this characteristic, we introduce Longest-Path-First Scheduling (LPFS) which pins operations to SIMD regions to keep data in-place and reduce communication to memory. The use of small, local scratchpad memories also further reduces communication. Our results show a 3% to 308% improvement for LPFS over conventional scheduling algorithms, and an additional 3% to 64% improvement using scratchpad memories. Our work is the most comprehensive software-to-quantum toolflow published to date, with efficient and practical scheduling techniques that reduce communication and increase parallelism for full-scale quantum code executing up to a trillion quantum gate operations.
PolyMage
Authors: Mullapudi Ravi Teja , Vasista Vinay , Bondhugula Uday 
Published: June 2015

This paper presents the design and implementation of PolyMage, a domain-specific language and compiler for image processing pipelines. An image processing pipeline can be viewed as a graph of interconnected stages which process images successively. Each stage typically performs one of point-wise, stencil, reduction or data-dependent operations on image pixels. Individual stages in a pipeline typically exhibit abundant data parallelism that can be exploited with relative ease. However, the stages also require high memory bandwidth preventing effective utilization of parallelism available on modern architectures. For applications that demand high performance, the traditional options are to use optimized libraries like OpenCV or to optimize manually. While using libraries precludes optimization across library routines, manual optimization accounting for both parallelism and locality is very tedious.
The focus of our system, PolyMage, is on automatically generating high-performance implementations of image processing pipelines expressed in a high-level declarative language. Our optimization approach primarily relies on the transformation and code generation capabilities of the polyhedral compiler framework. To the best of our knowledge, this is the first model-driven compiler for image processing pipelines that performs complex fusion, tiling, and storage optimization automatically. Experimental results on a modern multicore system show that the performance achieved by our automatic approach is up to 1.81x better than that achieved through manual tuning in Halide, a state-of-the-art language and compiler for image processing pipelines. For a camera raw image processing pipeline, our performance is comparable to that of a hand-tuned implementation.
Shared MPR Sets for Moderately Dense Wireless Multihop Networks
Authors: Kitasuka Teruaki , Tagashira Shigeaki 
Published: June 2015

Multipoint relays (MPRs) are used for flooding topology control messages and finding the shortest paths for unicast communications in the optimized link state routing protocol (OLSR). In this paper, we propose a method for achieving more efficient MPR selection in moderately dense wireless multihop networks (including sensor networks) than the conventional MPR selection. First, we analyze moderately dense networks to show that a node close to the two-hop border has little probability of being a two-hop neighbor. Second, we explain that there is a chance of the node's MPRs being shared with its neighbors. To maximize this chance, we propose using shared MPR sets. These sets minimize the MPR ratio, which is defined as the number of nodes selected as MPRs by at least one neighbor divided by the total number of nodes in the network. Simulations are used to confirm the efficiency of using shared MPR sets. A centralized heuristic algorithm shows an MPR ratio redundancy in moderately dense networks that is about 10% of that obtained through conventional MPR selection.
A Large Multiethnic Genome-Wide Association Study of Prostate Cancer Identifies Novel Risk Variants and Substantial Ethnic Differences
Authors: Hoffmann Thomas J. , Van Den Eeden Stephen K. , Sakoda Lori C. , Jorgenson Eric , Habel Laurel A. , Graff Rebecca E. , Passarelli Michael N. , Cario Clinton L. , Emami Nima C. , Chao Chun R. , Ghai Nirupa R. , Shan Jun , Ranatunga Dilrini K. , Quesenberry Charles P. , Aaronson David , Presti Joseph , Wang Zhaoming , Berndt Sonja I. , Chanock Stephen J. , McDonnell Shannon K. , French Amy J. , Schaid Daniel J. , Thibodeau Stephen N. , Li Qiyuan , Freedman Matthew L. , Penney Kathryn L. , Mucci Lorelei A. , Haiman Christopher A. , Henderson Brian E. , Seminara Daniela , Kvale Mark N. , Kwok Pui-Yan , Schaefer Catherine , Risch Neil , Witte John S. 
Published: June 2015

AbstractA genome-wide association study (GWAS) of prostate cancer in Kaiser Permanente health plan members (7,783 cases, 38,595 controls; 80.3% non-Hispanic white, 4.9% African-American, 7.0% East Asian, and 7.8% Latino) revealed a new independent risk indel rs4646284 at the previously identified locus 6q25.3 that replicated in PEGASUS (N = 7,539) and the Multiethnic Cohort (N = 4,679) with an overall P = 1.0 × 10−19 (OR, 1.18). Across the 6q25.3 locus, rs4646284 exhibited the strongest association with expression of SLC22A1 (P = 1.3 × 10−23) and SLC22A3 (P = 3.2 × 10−52). At the known 19q13.33 locus, rs2659124 (P = 1.3 × 10−13; OR, 1.18) nominally replicated in PEGASUS. A risk score of 105 known risk SNPs was strongly associated with prostate cancer (P &lt; 1.0 × 10−8). Comparing the highest to lowest risk score deciles, the OR was 6.22 for non-Hispanic whites, 5.82 for Latinos, 3.77 for African-Americans, and 3.38 for East Asians. In non-Hispanic whites, the 105 risk SNPs explained approximately 7.6% of disease heritability. The entire GWAS array explained approximately 33.4% of heritability, with a 4.3-fold enrichment within DNaseI hypersensitivity sites (P = 0.004).Significance: Taken together, our findings of independent risk variants, ethnic variation in existing SNP replication, and remaining unexplained heritability have important implications for further clarifying the genetic risk of prostate cancer. Our findings also suggest that there may be much promise in evaluating understudied variation, such as indels and ethnically diverse populations. Cancer Discov; 5(8); 878–91. ©2015 AACR.This article is highlighted in the In This Issue feature, p. 783
Through a Clear Cell, Darkly: HIF2α/PLIN2–Maintained Fat Droplets Protect ccRCCs from ER Stress
Authors: Sim Jingwei , Johnson Randall S. 
Published: June 2015

Abstract
Summary: Qiu and colleagues describe how a structural component of lipid droplets is markedly induced in pseudohypoxic renal tumors, where it maintains endoplasmic reticulum (ER) homeostasis. This adaptation is indispensable in tumor cells—where growth demands and a fluctuating blood supply place unnatural stresses on ER function—and is therefore an attractive therapeutic target. Cancer Discov; 5(6); 584–5. ©2015 AACR.
See related article by Qiu and colleagues, p. 652.
Interplay of male traits, male mating strategies and female mate choice in the Asian elephant, Elephas maximus
Authors: Chelliah Karpagam , Sukumar Raman 
Published: June 2015

Elaborate male traits with no apparent adaptive value may have evolved through female mate discrimination. Tusks are an elaborate male-only trait in the Asian elephant that could potentially influence female mate choice. We examined the effect of male body size, tusk possession and musth status on female mate choice in an Asian elephant population. Large/musth males received positive responses from oestrous females towards courtship significantly more often than did small/non-musth males. Young, tusked non-musth males attempted courtship significantly more often than their tuskless peers, and received more positive responses (though statistically insignificant) than did tuskless males. A positive response did not necessarily translate into mating because of mate-guarding by a dominant male. Female elephants appear to choose mates based primarily on traits such as musth that signal direct fertility benefits through increased sperm received than for traits such as tusks that may signal only indirect fitness benefits.
Patristic Exegesis
Authors: Ramelli Ilaria L.E. 
Published: June 2015

This essay will argue that in several – often unnoticed – respects patristic exegesis can be relevant to contemporary biblical hermeneutics and can be a source of fruitful inspiration for it. From several quarters, contemporary scholars have called for an integrative approach to biblical hermeneutics, especially one that conjoins the historico-critical method and theological hermeneutics. A similar integrative approach was already adopted by patristic exegetes in Origen’s line, with their integration of historical reading and noetic exegesis, and with their hermeneutics of multiplicity that is another respect in which patristic exegesis proves highly relevant to contemporary biblical hermeneutics. The present relevance of scriptural passages is also a core principle of both patristic exegesis and contemporary hermeneutics, as well as the tenet of the unity of Scripture, which was emphasised by patristic exegetes and is to be taken into account in contemporary biblical hermeneutics with respect to the Bible as supertext. Also, philosophical investigation applied to scriptural hermeneutics is one of the most remarkable features of Origen’s and his followers’ hermeneutics. A reflection will thus be devoted to the relationship between philosophy and biblical hermeneutics, as well as between theology and philosophy, and a parallel will be drawn with philosophy of religion.