bluuebunny/crossref_metadata_2025_split huggingface dataset:
MrkD
1P
from Klebsiella pneumoniae Strain IA565 Allows for Coexistence with Pseudomonas aeruginosa and Protection from Protease-Mediated Biofilm Detachment
Authors: Childers Brandon M. , Van Laar Tricia A. , You Tao , Clegg Steven , Leung Kai P. 
Published: August 2013

ABSTRACT

Biofilm formation and persistence are essential components for the continued survival of pathogens inside the host and constitute a major contributor to the development of chronic wounds with resistance to antimicrobial compounds. Understanding these processes is crucial for control of biofilm-mediated disease. Though chronic wound infections are often polymicrobial in nature, much of the research on chronic wound-related microbes has focused on single-species models.
Klebsiella pneumoniae
and
Pseudomonas aeruginosa
are microbes that are often found together in wound isolates and are able to form stable
in vitro
biofilms, despite the antagonistic nature of
P. aeruginosa
with other organisms. Mutants of the
K. pneumoniae
strain IA565 lacking the plasmid-borne
mrkD
1P
gene were less competitive than the wild type in an
in vitro
dual-species biofilm model with
P. aeruginosa
(PAO1). PAO1 spent medium inhibited the formation of biofilm of
mrkD
1P
-deficient mutants and disrupted preestablished biofilms, with no effect on IA565 and no effect on the growth of the wild type or mutants. A screen using a two-allele PAO1 transposon library identified the LasB elastase as the secreted effector involved in biofilm disruption, and a purified version of the protein produced results similar to those with PAO1 spent medium. Various other proteases had a similar effect, suggesting that the disruption of the
mrkD
1P
gene causes sensitivity to general proteolytic effects and indicating a role for MrkD
1P
in protection against host antibiofilm effectors. Our results suggest that MrkD
1P
allows for competition of
K. pneumoniae
with
P. aeruginosa
in a mixed-species biofilm and provides defense against microbial and host-derived proteases.
The Haemophilus ducreyi Fis Protein Is Involved in Controlling Expression of thelspB-lspA2Operon and Other Virulence Factors
Authors: Labandeira-Rey Maria , Dodd Dana A. , Brautigam Chad A. , Fortney Kate R. , Spinola Stanley M. , Hansen Eric J. 
Published: August 2013

ABSTRACTExpression of thelspB-lspA2operon encoding a virulence-related two-partner secretion system inHaemophilus ducreyi35000HP is directly regulated by the CpxRA regulatory system (M. Labandeira-Rey, J. R. Mock, and E. J. Hansen, Infect. Immun. 77:3402–3411, 2009). In the present study, we show that this secretion system is also regulated by the small nucleoid-associated protein Fis. Inactivation of theH. ducreyi fisgene resulted in a reduction in expression of both theH. ducreyiLspB and LspA2 proteins. DNA microarray experiments showed that aH. ducreyi fisdeletion mutant exhibited altered expression levels of genes encoding other importantH. ducreyivirulence factors, including DsrA and Flp1, suggesting a possible global role for Fis in the control of virulence in this obligate human pathogen. While theH. ducreyiFis protein has a high degree of sequence and structural similarity to the Fis proteins of other bacteria, its temporal pattern of expression was very different from that of enterobacterial Fis proteins. The use of alacZ-based transcriptional reporter provided evidence which indicated that theH. ducreyiFis homolog is a positive regulator ofgyrB, a gene that is negatively regulated by Fis in enteric bacteria. Taken together, the Fis protein expression data and the observed regulatory effects of Fis inH. ducreyisuggest that this small DNA binding protein has a regulatory role inH. ducreyiwhich may differ in substantial ways from that of other Fis proteins.
Secreted Pyomelanin of Legionella pneumophila Promotes Bacterial Iron Uptake and Growth under Iron-Limiting Conditions
Authors: Zheng Huaixin , Chatfield Christa H. , Liles Mark R. , Cianciotto Nicholas P. 
Published: August 2013

ABSTRACT

Iron acquisition is critical to the growth and virulence of
Legionella pneumophila
. Previously, we found that
L. pneumophila
uses both a ferrisiderophore pathway and ferrous iron transport to obtain iron. We now report that two molecules secreted by
L. pneumophila
, homogentisic acid (HGA) and its polymerized variant (HGA-melanin, a pyomelanin), are able to directly mediate the reduction of various ferric iron salts. Furthermore, HGA, synthetic HGA-melanin, and HGA-melanin derived from bacterial supernatants enhanced the ability of
L. pneumophila
and other species of
Legionella
to take up radiolabeled iron. Enhanced iron uptake was not observed with a ferrous iron transport mutant. Thus, HGA and HGA-melanin mediate ferric iron reduction, with the resulting ferrous iron being available to the bacterium for uptake. Upon further testing of
L. pneumophila
culture supernatants, we found that significant amounts of ferric and ferrous iron were associated with secreted HGA-melanin. Importantly, a pyomelanin-containing fraction obtained from a wild-type culture supernatant was able to stimulate the growth of iron-starved legionellae. That the corresponding supernatant fraction obtained from a nonpigmented mutant culture did not stimulate growth demonstrated that HGA-melanin is able to both promote iron uptake and enhance growth under iron-limiting conditions. Indicative of a complementary role in iron acquisition, HGA-melanin levels were inversely related to the levels of siderophore activity. Compatible with a role in the ecology and pathogenesis of
L. pneumophila
, HGA and HGA-melanin were effective at reducing and releasing iron from both insoluble ferric hydroxide and the mammalian iron chelates ferritin and transferrin.
Short-Lived Effector CD8 T Cells Induced by Genetically Attenuated Malaria Parasite Vaccination Express CD11c
Authors: Cooney Laura A. , Gupta Megha , Thomas Sunil , Mikolajczak Sebastian , Choi Kimberly Y. , Gibson Claire , Jang Ihn K. , Danziger Sam , Aitchison John , Gardner Malcolm J. , Kappe Stefan H. I. , Wang Ruobing 
Published: August 2013

ABSTRACTVaccination with a single dose of genetically attenuated malaria parasites can induce sterile protection against sporozoite challenge in the rodentPlasmodium yoeliimodel. Protection is dependent on CD8+T cells, involves perforin and gamma interferon (IFN-γ), and is correlated with the expansion of effector memory CD8+T cells in the liver. Here, we have further characterized vaccine-induced changes in the CD8+T cell phenotype and demonstrated significant upregulation of CD11c on CD3+CD8b+T cells in the liver, spleen, and peripheral blood. CD11c+CD8+T cells are predominantly CD11ahiCD44hiCD62L−, indicative of antigen-experienced effector cells. Followingin vitrorestimulation with malaria-infected hepatocytes, CD11c+CD8+T cells expressed inflammatory cytokines and cytotoxicity markers, including IFN-γ, tumor necrosis factor alpha (TNF-α), interleukin-2 (IL-2), perforin, and CD107a. CD11c−CD8+T cells, on the other hand, expressed negligible amounts of all inflammatory cytokines and cytotoxicity markers tested, indicating that CD11c marks multifunctional effector CD8+T cells. Coculture of CD11c+, but not CD11c−, CD8+T cells with sporozoite-infected primary hepatocytes significantly inhibited liver-stage parasite development. Tetramer staining for the immunodominant circumsporozoite protein (CSP)-specific CD8+T cell epitope demonstrated that approximately two-thirds of CSP-specific cells expressed CD11c at the peak of the CD11c+CD8+T cell response, but CD11c expression was lost as the CD8+T cells entered the memory phase. Further analyses showed that CD11c+CD8+T cells are primarily KLRG1+CD127−terminal effectors, whereas all KLRG1−CD127+memory precursor effector cells are CD11c−CD8+T cells. Together, these results suggest that CD11c marks a subset of highly inflammatory, short-lived, antigen-specific effector cells, which may play an important role in eliminating infected hepatocytes.
Neuroanatomical Basis for Acupuncture Point Pc8 in the Rat: Neural Tracing Study with Cholera Toxin Subunit B
Authors: Cui Jing-Jing , Ha Li-Juan , Zhu Xin-Long , Shi Hong , Wang Fu-Chun , Jing Xiang-Hong , Bai Wan-Zhu 
Published: August 2013

Objectives This study was performed to investigate the innervations related to acupuncture point PC8 in rats using a neural tracing technique. Methods After 6 μL of 1% cholera toxin subunit B (CTB) was injected into the site between the second and third metacarpal bone in rats, a corresponding site to acupuncture point PC8 in the human body, CTB labelling was examined with immunofluorescence and immunohistochemistry in the dorsal root ganglia (DRG), spinal cord and brainstem. Results All CTB labelling appeared on the ipsilateral side of the injection. The labelled sensory neurons distributed from cervical (C)6 to thoracic (T)1 DRG, while the labelled motor neurons were located on the dorsolateral part of the spinal ventral horn ranging from the C6 to T1 segments. In addition, the transganglionically-labelled axonal terminals were found to be dense in the medial part of laminae 3–4 from C6 to the T1 spinal dorsal horn, as far as in the cuneate nucleus. Conclusions These results indicate that sensory and motor neurons associated with PC8 distribute in a distinct segmental pattern. The sensory information from PC8 could be transganglionically transported to the spinal dorsal horn and cuneate nucleus.
The efficacy of manual joint mobilisation/manipulation in treatment of lateral ankle sprains: a systematic review
Authors: Loudon Janice K , Reiman Michael P , Sylvain Jonathan 
Published: August 2013

BackgroundLateral ankle sprains are common and can have detrimental consequences to the athlete. Joint mobilisation/manipulation may limit these outcomes.ObjectiveSystematically summarise the effectiveness of manual joint techniques in treatment of lateral ankle sprains.MethodsThis review employed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A computer-assisted literature search of MEDLINE, CINHAL, EMBASE, OVID and Physiotherapy Evidence Database (PEDro) (January 1966 to March 2013) was used with the following keywords alone and in combination ‘ankle’, ‘sprain’, ‘injuries’, 'lateral’, ‘manual therapy’, and ‘joint mobilisation’. The methodological quality of individual studies was assessed using the PEDro scale.ResultsAfter screening of titles, abstracts and full articles, eight articles were kept for examination. Three articles achieved a score of 10 of 11 total points; one achieved a score of 9; two articles scored 8; one article scored a 7 and the remaining article scored a 5. Three articles examined joint techniques for acute sprains and the remainder examined subacute/chronic ankle sprains. Outcome measures included were pain level, ankle range of motion, swelling, functional score, stabilometry and gait parameters. The majority of the articles only assessed these outcome measures immediately after treatment. No detrimental effects from the joint techniques were revealed in any of the studies reviewed.ConclusionsFor acute ankle sprains, manual joint mobilisation diminished pain and increased dorsiflexion range of motion. For treatment of subacute/chronic lateral ankle sprains, these techniques improved ankle range-of-motion, decreased pain and improved function.
Near-duplicate video retrieval
Authors: Liu Jiajun , Huang Zi , Cai Hongyun , Shen Heng Tao , Ngo Chong Wah , Wang Wei 
Published: August 2013

The exponential growth of online videos, along with increasing user involvement in video-related activities, has been observed as a constant phenomenon during the last decade. User's time spent on video capturing, editing, uploading, searching, and viewing has boosted to an unprecedented level. The massive publishing and sharing of videos has given rise to the existence of an already large amount of near-duplicate content. This imposes urgent demands on near-duplicate video retrieval as a key role in novel tasks such as video search, video copyright protection, video recommendation, and many more. Driven by its significance, near-duplicate video retrieval has recently attracted a lot of attention. As discovered in recent works, latest improvements and progress in near-duplicate video retrieval, as well as related topics including low-level feature extraction, signature generation, and high-dimensional indexing, are employed to assist the process.
As we survey the works in near-duplicate video retrieval, we comparatively investigate existing variants of the definition of near-duplicate video, describe a generic framework, summarize state-of-the-art practices, and explore the emerging trends in this research topic.
Performance potential of optimization phase selection during dynamic JIT compilation
Authors: Jantz Michael R. , Kulkarni Prasad A. 
Published: August 2013

Phase selection is the process of customizing the applied set of compiler optimization phases for individual functions or programs to improve performance of generated code. Researchers have recently developed novel feature-vector based heuristic techniques to perform phase selection during online JIT compilation. While these heuristics improve program startup speed, steady-state performance was not seen to benefit over the default fixed single sequence baseline. Unfortunately, it is still not conclusively known whether this lack of steady-state performance gain is due to a failure of existing online phase selection heuristics, or because there is, indeed, little or no speedup to be gained by phase selection in online JIT environments. The goal of this work is to resolve this question, while examining the phase selection related behavior of optimizations, and assessing and improving the effectiveness of existing heuristic solutions.We conduct experiments to find and understand the potency of the factors that can cause the phase selection problem in JIT compilers. Next, using long-running genetic algorithms we determine that program-wide and method-specific phase selection in the HotSpot JIT compiler can produce ideal steady-state performance gains of up to 15% (4.3% average) and 44% (6.2% average) respectively. We also find that existing state-of-the-art heuristic solutions are unable to realize these performance gains (in our experimental setup), discuss possible causes, and show that exploiting knowledge of optimization phase behavior can help improve such heuristic solutions. Our work develops a robust open-source production-quality framework using the HotSpot JVM to further explore this problem in the future.
Towards verifiable resource accounting for outsourced computation
Authors: Chen Chen , Maniatis Petros , Perrig Adrian , Vasudevan Amit , Sekar Vyas 
Published: August 2013

Outsourced computation services should ideally only charge customers for the resources used by their applications. Unfortunately, no verifiable basis for service providers and customers to reconcile resource accounting exists today. This leads to undesirable outcomes for both providers and consumers-providers cannot prove to customers that they really devoted the resources charged, and customers cannot verify that their invoice maps to their actual usage. As a result, many practical and theoretical attacks exist, aimed at charging customers for resources that their applications did not consume. Moreover, providers cannot charge consumers precisely, which causes them to bear the cost of unaccounted resources or pass these costs inefficiently to their customers.
We introduce ALIBI, a first step toward a vision for verifiable resource accounting. ALIBI places a minimal, trusted reference monitor underneath the service provider's software platform. This monitor observes resource allocation to customers' guest virtual machines and reports those observations to customers, for verifiable reconciliation. In this paper, we show that ALIBI efficiently and verifiably tracks guests' memory use and CPU-cycle consumption.
Ligra
Authors: Shun Julian , Blelloch Guy E. 
Published: August 2013

There has been significant recent interest in parallel frameworks for processing graphs due to their applicability in studying social networks, the Web graph, networks in biology, and unstructured meshes in scientific simulation. Due to the desire to process large graphs, these systems have emphasized the ability to run on distributed memory machines. Today, however, a single multicore server can support more than a terabyte of memory, which can fit graphs with tens or even hundreds of billions of edges. Furthermore, for graph algorithms, shared-memory multicores are generally significantly more efficient on a per core, per dollar, and per joule basis than distributed memory systems, and shared-memory algorithms tend to be simpler than their distributed counterparts.
In this paper, we present a lightweight graph processing framework that is specific for shared-memory parallel/multicore machines, which makes graph traversal algorithms easy to write. The framework has two very simple routines, one for mapping over edges and one for mapping over vertices. Our routines can be applied to any subset of the vertices, which makes the framework useful for many graph traversal algorithms that operate on subsets of the vertices. Based on recent ideas used in a very fast algorithm for breadth-first search (BFS), our routines automatically adapt to the density of vertex sets. We implement several algorithms in this framework, including BFS, graph radii estimation, graph connectivity, betweenness centrality, PageRank and single-source shortest paths. Our algorithms expressed using this framework are very simple and concise, and perform almost as well as highly optimized code. Furthermore, they get good speedups on a 40-core machine and are significantly more efficient than previously reported results using graph frameworks on machines with many more cores.
Scheduling parallel programs by work stealing with private deques
Authors: Acar Umut A. , Chargueraud Arthur , Rainey Mike 
Published: August 2013

Work stealing has proven to be an effective method for scheduling parallel programs on multicore computers. To achieve high performance, work stealing distributes tasks between concurrent queues, called deques, which are assigned to each processor. Each processor operates on its deque locally except when performing load balancing via steals. Unfortunately, concurrent deques suffer from two limitations: 1) local deque operations require expensive memory fences in modern weak-memory architectures, 2) they can be very difficult to extend to support various optimizations and flexible forms of task distribution strategies needed many applications, e.g., those that do not fit nicely into the divide-and-conquer, nested data parallel paradigm.
For these reasons, there has been a lot recent interest in implementations of work stealing with non-concurrent deques, where deques remain entirely private to each processor and load balancing is performed via message passing. Private deques eliminate the need for memory fences from local operations and enable the design and implementation of efficient techniques for reducing task-creation overheads and improving task distribution. These advantages, however, come at the cost of communication. It is not known whether work stealing with private deques enjoys the theoretical guarantees of concurrent deques and whether they can be effective in practice.
In this paper, we propose two work-stealing algorithms with private deques and prove that the algorithms guarantee similar theoretical bounds as work stealing with concurrent deques. For the analysis, we use a probabilistic model and consider a new parameter, the branching depth of the computation. We present an implementation of the algorithm as a C++ library and show that it compares well to Cilk on a range of benchmarks. Since our approach relies on private deques, it enables implementing flexible task creation and distribution strategies. As a specific example, we show how to implement task coalescing and steal-half strategies, which can be important in fine-grain, non-divide-and-conquer algorithms such as graph algorithms, and apply them to the depth-first-search problem.
NSD2 Is Recruited through Its PHD Domain to Oncogenic Gene Loci to Drive Multiple Myeloma
Authors: Huang Zheng , Wu Haiping , Chuai Shannon , Xu Fiona , Yan Feng , Englund Nathan , Wang Zhaofu , Zhang Hailong , Fang Ming , Wang Youzhen , Gu Justin , Zhang Man , Yang Teddy , Zhao Kehao , Yu Yanyan , Dai Jingquan , Yi Wei , Zhou Shaolian , Li Qian , Wu Jing , Liu Jun , Wu Xu , Chan Homan , Lu Chris , Atadja Peter , Li En , Wang Yan , Hu Min 
Published: August 2013

Abstract
Histone lysine methyltransferase NSD2 (WHSC1/MMSET) is overexpressed frequently in multiple myeloma due to the t(4;14) translocation associated with 15% to 20% of cases of this disease. NSD2 has been found to be involved in myelomagenesis, suggesting it may offer a novel therapeutic target. Here we show that NSD2 methyltransferase activity is crucial for clonogenicity, adherence, and proliferation of multiple myeloma cells on bone marrow stroma in vitro and that NSD2 is required for tumorigenesis of t(4;14)+ but not t(4;14)− multiple myeloma cells in vivo. The PHD domains in NSD2 were important for its cellular activity and biological function through recruiting NSD2 to its oncogenic target genes and driving their transcriptional activation. By strengthening its disease linkage and deepening insights into its mechanism of action, this study provides a strategy to therapeutically target NSD2 in multiple myeloma patients with a t(4;14) translocation. Cancer Res; 73(20); 6277–88. ©2013 AACR.
Capillary Isoelectric-Focusing Immunoassays to Study Dynamic Oncoprotein Phosphorylation and Drug Response to Targeted Therapies in Non–Small Cell Lung Cancer
Authors: Chen Jin-Qiu , Lee Jih-Hsiang , Herrmann Michelle A. , Park Kang-Seo , Heldman Madeleine R. , Goldsmith Paul K. , Wang Yisong , Giaccone Giuseppe 
Published: August 2013

Abstract
Developing proteomic biomarkers is valuable for evaluating therapeutic effects of drugs and generating better treatment strategies. However, conventional protein analysis is often challenging due to inadequate sample size of clinical specimens, lack of assay reproducibility, accuracy, and sensitivity. A novel capillary isoelectricfocusing (IEF) immunoassay system (NanoPro) was used to study the dynamic phosphorylation status of signaling molecules in non–small cell lung cancer (NSCLC) cells treated with EGFR tyrosine kinase and MEK inhibitors. NanoPro showed the same dynamic ERK phosphorylation as Western blotting with good assay reproducibility using 1,000 times less protein. The IEF separation in NanoPro system enables multiple protein phosphorylation isoforms to be resolved and detected simultaneously. With NanoPro, we identified a specific on-target mitogen-activated protein/extracellular signal–regulated kinase (MEK) response pattern to MEK inhibitor PD325901, which was not detectable by Western blot analysis. We also revealed a MEK2 signal that may be associated with NSCLC cell sensitivity to the EGF receptor inhibitor erlotinib, and distinguished erlotinib-sensitive cells from intrinsic as well as acquired resistant cells to erlotinib. Moreover, NanoPro could differentiate human ERK1 isoforms from the mouse isoforms based on their isoelectric point differences and showed that erlotinib effectively inhibited ERK phosphorylation in targeted human xenograft cancer cells but not in surrounding mouse stromal cells. With 8 μg of tumor aspirates, we precisely quantified the response of 18 signaling molecules to erlotinib and MEK1 inhibitor treatments in an NSCLC patient. NanoPro's higher sensitivity, better resolution of protein phosphorylation status, and reduced tissue requirement warrant NanoPro's investigation for future drug development and evaluation of drug effects of targeted therapies. Mol Cancer Ther; 12(11); 2601–13. ©2013 AACR.