bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of the Cre-
lox
Recombination System To Investigate the lp54 Gene Requirement in the Infectious Cycle of
Borrelia burgdorferi
Authors: Bestor Aaron , Stewart Philip E. , Jewett Mollie W. , Sarkar Amit , Tilly Kit , Rosa Patricia A. 
Published: March 2010

ABSTRACT

Borrelia burgdorferi
, the causative agent of Lyme disease, has a complex genome consisting of a linear chromosome and up to 21 linear and circular plasmids. These plasmids encode numerous proteins critical to the spirochete's infectious cycle and many hypothetical proteins whose functions and requirements are unknown. The conserved linear plasmid lp54 encodes several proteins important for survival in the mouse-tick infectious cycle, but the majority of the proteins are of unknown function and lack homologs outside the borreliae. In this study we adapted the Cre-
lox
recombination system to create large deletions in the
B. burgdorferi
genome. Using Cre-
lox
, we systematically investigated the contribution of 14 adjacent genes on the left arm of lp54 to the overall infectivity of
B. burgdorferi
. The deletion of the region of lp54 encompassing
bba07
to
bba14
had no significant effect on the infectious cycle of
B. burgdorferi
. The deletion of
bba01
to
bba07
resulted in a slight growth defect but did not significantly affect the ability of
B. burgdorferi
to complete the infectious cycle. This study demonstrated the utility of the Cre-
lox
system to efficiently explore gene requirements in
B. burgdorferi
and surprisingly revealed that a large number of the highly conserved proteins encoded on lp54 are not required to complete the infectious cycle.
The Levels of CD16/Fcγ Receptor IIIA on CD14+CD16+Monocytes Are Higher in Children with SeverePlasmodium falciparumAnemia than in Children with Cerebral or Uncomplicated Malaria
Authors: Ogonda Lilian A. , Orago Alloys S. S. , Otieno Michael F. , Adhiambo Christine , Otieno Walter , Stoute José A. 
Published: March 2010

ABSTRACTFc gamma receptor IIIA (CD16/FcγRIIIA) on monocytes/macrophages may play an important role in the pathogenesis of severe malarial anemia (SMA) by promoting phagocytosis of IgG-coated uninfected red cells and by allowing the production of tumor necrosis factor alpha (TNF-α) upon cross-linking by immune complexes (ICs). However, not much is known about the differential expression of this receptor on monocytes of children with severe malaria and uncomplicated malaria. Therefore, we investigated the expression of CD16/FcγRIIIA on monocytes of children with SMA, cerebral malaria (CM), and their age-matched uncomplicated malaria controls by flow cytometry. Since CD14low (CD14+) monocytes are considered more mature and macrophage-like than CD14high (CD14++) monocytes, we also compared the level of expression of CD16/FcγRIIIA according to the CD14 level and studied the relationship between CD16/FcγRIIIA expression and intracellular TNF-α production upon stimulation by ICs. CD16/FcγRIIIA expression was the highest overall on CD14+CD16+monocytes of children with SMA at enrollment. At convalescence, SMA children were the only ones to show a significant decline in the same parameter. In contrast, there were no significant differences among groups in the expression of CD16/FcγRIIIA on CD14++CD16+monocytes. A greater percentage of CD14+CD16+monocytes produced TNF-α upon stimulation than any other monocyte subset, and the amount of intracellular TNF-α correlated positively with CD16/FcγRIIIA expression. Furthermore, there was an inverse correlation between hemoglobin levels and CD16/FcγRIIIA expression in children with SMA and their controls. These data suggest that monocytes of children with SMA respond differently toPlasmodium falciparuminfection by overexpressing CD16/FcγRIIIA as they mature, which could enhance erythrophagocytosis and TNF-α production.
Anaerobic Metabolism Occurs in the Substratum of Gonococcal Biofilms and May Be Sustained in Part by Nitric Oxide
Authors: Falsetta Megan L. , McEwan Alastair G. , Jennings Michael P. , Apicella Michael A. 
Published: March 2010

ABSTRACT

Neisseria gonorrhoeae
is the etiologic agent of gonorrhea, which has been among the most frequently reported communicable diseases in the United States since 1960. Women frequently do not exhibit symptoms, which can lead to chronic infection.
N. gonorrhoeae
readily forms biofilms over abiotic surfaces, over primary and transformed cervical epithelial cells, and over cervical tissues
in vivo
. Biofilms are often associated with chronic infection, which suggests a link between biofilm formation and asymptomatic gonorrhea in women. Proteins involved in anaerobic metabolism and oxidative-stress tolerance are critical for normal biofilm formation of
N. gonorrhoeae
. Therefore, we examined the spatial profiles of anaerobic respiration in
N. gonorrhoeae
, using an
aniA
′-′
gfp
transcriptional fusion. Nitric oxide (NO) can elicit biofilm dispersal when present at sublethal concentrations in the surrounding medium. Some reports indicate that NO may also encourage biofilm formation at higher, potentially lethal concentrations. NO is produced by polymorphonuclear lymphocytes (PMNs) and cervical endothelial and epithelial cells. Thus, we also examined the effect of NO on
N. gonorrhoeae
biofilms. We found that anaerobic respiration occurs predominantly in the substratum of gonococcal biofilms and that expression of
aniA
is induced over time in biofilms. Treatment with high concentrations of a rapid-release NO donor prevents biofilm formation when supplied early in biofilm development but can also enhance biofilm formation once anaerobic respiration is initiated. NO treatment partially restores biofilm formation in an
aniA
::
kan
insertion mutant, which suggests that
N. gonorrhoeae
in biofilms may use NO as a substrate for anaerobic growth but prefer nitrite.
Impairment of Host Defense against Disseminated Candidiasis in Mice Overexpressing GATA-3
Authors: Haraguchi Norihiro , Ishii Yukio , Morishima Yuko , Yoh Keigyou , Matsuno Yosuke , Kikuchi Norihiro , Sakamoto Tohru , Takahashi Satoru , Hizawa Nobuyuki 
Published: March 2010

ABSTRACTCandidaspecies are the most common source of nosocomial invasive fungal infections. Previous studies have indicated that T-helper immune response is the critical host factor for susceptibility toCandidainfection. The transcription factor GATA-3 is known as the master regulator for T-helper type 2 (Th2) differentiation. We therefore investigated the role of GATA-3 in the host defense against systemicCandidainfection using GATA-3-overexpressing transgenic mice. The survival of GATA-3-overexpressing mice afterCandidainfection was significantly lower than that of wild-type mice.Candidaoutgrowth was significantly increased in the kidneys of GATA-3-overexpressing mice, compared with wild-type mice. The levels of various Th2 cytokines, including interleukin-4 (IL-4), IL-5, and IL-13, were significantly higher while the level of Th1 cytokine gamma interferon was significantly lower in the splenocytes of GATA-3-overexpressing mice afterCandidainfection. Recruitment of macrophages into the peritoneal cavity in response toCandidainfection and their phagocytic activity were significantly lower in GATA-3-overexpressing mice than in wild-type mice. Exogenous administration of gamma interferon to GATA-3-overexpressing mice significantly reducedCandidaoutgrowth in the kidney and thus increased the survival rate. Administration of gamma interferon also increased the recruitment of macrophages into the peritoneal cavity in response toCandidainfection. These results indicate that overexpression of GATA-3 modulates macrophage antifungal activity and thus enhances the susceptibility to systemicCandidainfection, possibly by reducing the production of gamma interferon in response toCandidainfection.
Rapid Identification of Bacteria from Positive Blood Culture Bottles by Use of Matrix-Assisted Laser Desorption-Ionization Time of Flight Mass Spectrometry Fingerprinting
Authors: Christner Martin , Rohde Holger , Wolters Manuel , Sobottka Ingo , Wegscheider Karl , Aepfelbacher Martin 
Published: March 2010

ABSTRACTEarly and adequate antimicrobial therapy has been shown to improve the clinical outcome in bloodstream infections (BSI). To provide rapid pathogen identification for targeted treatment, we applied matrix-assisted laser desorption-ionization time of flight (MALDI-TOF) mass spectrometry fingerprinting to bacteria directly recovered from blood culture bottles. A total of 304 aerobic and anaerobic blood cultures, reported positive by a Bactec 9240 system, were subjected in parallel to differential centrifugation with subsequent mass spectrometry fingerprinting and reference identification using established microbiological methods. A representative spectrum of bloodstream pathogens was recovered from 277 samples that grew a single bacterial isolate. Species identification by direct mass spectrometry fingerprinting matched reference identification in 95% of these samples and worked equally well for aerobic and anaerobic culture bottles. Application of commonly used score cutoffs to classify the fingerprinting results led to an identification rate of 87%. Mismatching mostly resulted from insufficient bacterial numbers and preferentially occurred with Gram-positive samples. The respective spectra showed low concordance to database references and were effectively rejected by score thresholds. Spiking experiments and examination of the respective study samples even suggested applicability of the method to mixed cultures. With turnaround times around 100 min, the approach allowed for reliable pathogen identification at the day of blood culture positivity, providing treatment-relevant information within the critical phase of septic illness.
Production of Infectious Hepatitis C Virus by Using RNA Polymerase I-Mediated Transcription
Authors: Masaki Takahiro , Suzuki Ryosuke , Saeed Mohsan , Mori Ken-ichi , Matsuda Mami , Aizaki Hideki , Ishii Koji , Maki Noboru , Miyamura Tatsuo , Matsuura Yoshiharu , Wakita Takaji , Suzuki Tetsuro 
Published: March 2010

ABSTRACTIn this study, we used an RNA polymerase I (Pol I) transcription system for development of a reverse genetics protocol to produce hepatitis C virus (HCV), which is an uncapped positive-strand RNA virus. Transfection with a plasmid harboring HCV JFH-1 full-length cDNA flanked by a Pol I promoter and Pol I terminator yielded an unspliced RNA with no additional sequences at either end, resulting in efficient RNA replication within the cytoplasm and subsequent production of infectious virions. Using this technology, we developed a simple replicontrans-packaging system, in which transient transfection of two plasmids enables examination of viral genome replication and virion assembly as two separate steps. In addition, we established a stable cell line that constitutively produces HCV with a low mutation frequency of the viral genome. The effects of inhibitors of N-linked glycosylation on HCV production were evaluated using this cell line, and the results suggest that certain step(s), such as virion assembly, intracellular trafficking, and secretion, are potentially up- and downregulated according to modifications of HCV envelope protein glycans. This Pol I-based HCV expression system will be beneficial for a high-throughput antiviral screening and vaccine discovery programs.
MODELING BIOLOGICAL CONTROL OF ALGAL BLOOM IN A LAKE CAUSED BY DISCHARGE OF NUTRIENTS
Authors: GHOSH MINI 
Published: March 2010

This paper proposes and analyzes a nonlinear model for the biological control of algal bloom in a lake. Algal bloom often occurs in a lake due to excessive flow of nutrients from domestic drainage, industrial and agricultural waste, and this causes the decrease in the concentration of dissolved oxygen in the lake. Hence, it threatens the survival of other species of the ecosystem indirectly, and it is also responsible for the degradation of water quality in the lake because of less oxygen content. In this work we study biological control which means the introduction of predatory fish, i.e. the release of algae-eating fish into the lake to control the rapid growth of algae. We formulate our model by assuming Michaelis-Menten type ratio-dependent prey-predator interaction. The equilibrium of the mathematical model is found and also the stability is discussed in detail. It is observed that the positive equilibria is locally asymptotically stable under certain conditions on the parameters. Also the system is simulated for various sets of parameters and it is found that system may oscillate for some realistic set of parameters. In fact we found that the parameter m, which is the half saturation constant, is very sensitive and with the decrease in this parameter steady state solution of the system changes to stable oscillation. On the practical side, it means that the method of biological control by introducing predatory fish is not always beneficial because outcome of this method depends upon the actual value of the parameter. Here we get the paradox of biological control, which says that it is not possible to have low level of steady state equilibrium of prey population.
Decoupling contention management from scheduling
Authors: Johnson F. Ryan , Stoica Radu , Ailamaki Anastasia , Mowry Todd C. 
Published: March 2010

Many parallel applications exhibit unpredictable communication between threads, leading to contention for shared objects. The choice of contention management strategy impacts strongly the performance and scalability of these applications: spinning provides maximum performance but wastes significant processor resources, while blocking-based approaches conserve processor resources but introduce high overheads on the critical path of computation. Under situations of high or changing load, the operating system complicates matters further with arbitrary scheduling decisions which often preempt lock holders, leading to long serialization delays until the preempted thread resumes execution.
We observe that contention management is orthogonal to the problems of scheduling and load management and propose to decouple them so each may be solved independently and effectively. To this end, we propose a load control mechanism which manages the number of active threads in the system separately from any contention which may exist. By isolating contention management from damaging interactions with the OS scheduler, we combine the efficiency of spinning with the robustness of blocking. The proposed load control mechanism results in stable, high performance for both lightly and heavily loaded systems, requires no special privileges or modifications at the OS level, and can be implemented as a library which benefits existing code.
Characterizing processor thermal behavior
Authors: Mesa-Martinez Francisco Javier , Ardestani Ehsan K. , Renau Jose 
Published: March 2010

Temperature is a dominant factor in the performance, reliability, and leakage power consumption of modern processors. As a result, increasing numbers of researchers evaluate thermal characteristics in their proposals. In this paper, we measure a real processor focusing on its thermal characterization executing diverse workloads.
Our results show that in real designs, thermal transients operate at larger scales than their performance and power counterparts. Conventional thermal simulation methodologies based on profile-based simulation or statistical sampling, such as Simpoint, tend to explore very limited execution spans. Short simulation times can lead to reduced matchings between performance and thermal phases. To illustrate these issues we characterize and classify from a thermal standpoint SPEC00 and SPEC06 applications, which are traditionally used in the evaluation of architectural proposals. This paper concludes with a list of recommendations regarding thermal modeling considerations based on our experimental insights.
Micro-pages
Authors: Sudan Kshitij , Chatterjee Niladrish , Nellans David , Awasthi Manu , Balasubramonian Rajeev , Davis Al 
Published: March 2010

Power consumption and DRAM latencies are serious concerns in modern chip-multiprocessor (CMP or multi-core) based compute systems. The management of the DRAM row buffer can significantly impact both power consumption and latency. Modern DRAM systems read data from cell arrays and populate a row buffer as large as 8 KB on a memory request. But only a small fraction of these bits are ever returned back to the CPU. This ends up wasting energy and time to read (and subsequently write back) bits which are used rarely. Traditionally, an open-page policy has been used for uni-processor systems and it has worked well because of spatial and temporal locality in the access stream. In future multi-core processors, the possibly independent access streams of each core are interleaved, thus destroying the available locality and significantly under-utilizing the contents of the row buffer. In this work, we attempt to improve row-buffer utilization for future multi-core systems.
The schemes presented here are motivated by our observations that a large number of accesses within heavily accessed OS pages are to small, contiguous "chunks" of cache blocks. Thus, the co-location of chunks (from different OS pages) in a row-buffer will improve the overall utilization of the row buffer contents, and consequently reduce memory energy consumption and access time. Such co-location can be achieved in many ways, notably involving a reduction in OS page size and software or hardware assisted migration of data within DRAM. We explore these mechanisms and discuss the trade-offs involved along with energy and performance improvements from each scheme. On average, for applications with room for improvement, our best performing scheme increases performance by 9% (max. 18%) and reduces memory energy consumption by 15% (max. 70%).
Power routing
Authors: Pelley Steven , Meisner David , Zandevakili Pooya , Wenisch Thomas F. , Underwood Jack 
Published: March 2010

Data center power infrastructure incurs massive capital costs, which typically exceed energy costs over the life of the facility. To squeeze maximum value from the infrastructure, researchers have proposed over-subscribing power circuits, relying on the observation that peak loads are rare. To ensure availability, these proposals employ power capping, which throttles server performance during utilization spikes to enforce safe power budgets. However, because budgets must be enforced locally -- at each power distribution unit (PDU) -- local utilization spikes may force throttling even when power delivery capacity is available elsewhere. Moreover, the need to maintain reserve capacity for fault tolerance on power delivery paths magnifies the impact of utilization spikes.
In this paper, we develop mechanisms to better utilize installed power infrastructure, reducing reserve capacity margins and avoiding performance throttling. Unlike conventional high-availability data centers, where collocated servers share identical primary and secondary power feeds, we reorganize power feeds to create shuffled power distribution topologies. Shuffled topologies spread secondary power feeds over numerous PDUs, reducing reserve capacity requirements to tolerate a single PDU failure. Second, we propose Power Routing, which schedules IT load dynamically across redundant power feeds to: (1) shift slack to servers with growing power demands, and (2) balance power draw across AC phases to reduce heating and improve electrical stability. We describe efficient heuristics for scheduling servers to PDUs (an NP-complete problem). Using data collected from nearly 1000 servers in three production facilities, we demonstrate that these mechanisms can reduce the required power infrastructure capacity relative to conventional high-availability data centers by 32% without performance degradation.
A real system evaluation of hardware atomicity for software speculation
Authors: Neelakantam Naveen , Ditzel David R. , Zilles Craig 
Published: March 2010

In this paper we evaluate the atomic region compiler abstraction by incorporating it into a commercial system. We find that atomic regions are simple and intuitive to integrate into an x86 binary-translation system. Furthermore, doing so trivially enables additional optimization opportunities beyond that achievable by a high-performance dynamic optimizer, which already implements superblocks.
We show that atomic regions can suffer from severe performance penalties if misspeculations are left uncontrolled, but that a simple software control mechanism is sufficient to reign in all detrimental side-effects. We evaluate using full reference runs of the SPEC CPU2000 integer benchmarks and find that atomic regions enable up to a 9% (3% on average) improvement beyond the performance of a tuned product.
These performance improvements are achieved without any negative side effects. Performance side effects such as code bloat are absent with atomic regions; in fact, static code size is reduced. The hardware necessary is synergistic with other needs and was already available on the commercial product used in our evaluation. Finally, the software complexity is minimal as a single developer was able to incorporate atomic regions into a sophisticated 300,000 line code base in three months, despite never having seen the translator source code beforehand.
Respec
Authors: Lee Dongyoon , Wester Benjamin , Veeraraghavan Kaushik , Narayanasamy Satish , Chen Peter M. , Flinn Jason 
Published: March 2010

Deterministic replay systems record and reproduce the execution of a hardware or software system. While it is well known how to replay uniprocessor systems, replaying shared memory multiprocessor systems at low overhead on commodity hardware is still an open problem. This paper presents Respec, a new way to support deterministic replay of shared memory multithreaded programs on commodity multiprocessor hardware. Respec targets online replay in which the recorded and replayed processes execute concurrently.
Respec uses two strategies to reduce overhead while still ensuring correctness: speculative logging and externally deterministic replay. Speculative logging optimistically logs less information about shared memory dependencies than is needed to guarantee deterministic replay, then recovers and retries if the replayed process diverges from the recorded process. Externally deterministic replay relaxes the degree to which the two executions must match by requiring only their system output and final program states match. We show that the combination of these two techniques results in low recording and replay overhead for the common case of data-race-free execution intervals and still ensures correct replay for execution intervals that have data races.
We modified the Linux kernel to implement our techniques. Our software system adds on average about 18% overhead to the execution time for recording and replaying programs with two threads and 55% overhead for programs with four threads.
Karl Popper and Pentecostal Historiography
Authors: Kay William K. 
Published: March 2010

AbstractKarl Popper argued that science proceeds not by induction but by offering explanatory theories that scientists then attempt to falsify. What cannot be falsified falls outside the realm of science. In applying his ideas to the writing of history, Popper was particularly scathing about Marxist predictions of future historical development. But he did believe history could be written by looking at the situations in which historical figures found themselves and the problems they attempted to solve. Pentecostal historiography has been divided into four main types: the providential, the historical roots, the multicultural, and the functional. When each of these types is analyzed and judged against Popper’s strictures against induction, we find, among other things, that the unfashionable providential account need not be ruled out.