bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potency of SMP-601, a Novel Carbapenem, in Hematogenous Murine Bronchopneumonia Caused by Methicillin-Resistant and Vancomycin-Intermediate
Staphylococcus aureus
Authors: Kihara Rie , Yanagihara Katsunori , Morinaga Yoshitomo , Araki Nobuko , Nakamura Shigeki , Seki Masafumi , Izumikawa Koichi , Kakeya Hiroshi , Yamamoto Yoshihiro , Tsukamoto Kazuhiro , Kamihira Shimeru , Kohno Shigeru 
Published: April 2008

ABSTRACT

We compared the potency of SMP-601, a novel carbapenem, with that of vancomycin in a murine model of hematogenous bronchopneumonia infection caused by methicillin-resistant
Staphylococcus aureus
(MRSA) and vancomycin-intermediate
S. aureus
(VISA). The MICs of SMP-601 and vancomycin against MRSA were 2 and 1 μg/ml, respectively, while those against VISA were 2 and 8 μg/ml, respectively. Treatment with SMP-601 resulted in a significant decrease in the number of viable bacteria in the MRSA infection model (control, 100 mg/kg vancomycin, and 100 mg/kg SMP-601, 8.42 ± 0.50, 5.29 ± 0.71, and 5.50 ± 0.58 log CFU/lung, respectively,) and in the VISA infection model (control, 100 mg/kg vancomycin, and 100 mg/kg SMP-601, 9.64 ± 0.63, 8.72 ± 0.45, 7.42 ± 0.14 log CFU/lung) (mean ± standard error of the mean). The survival rate in the VISA infection model treated with SMP-601 (70%) was significantly higher than those in the other two groups (20% for vancomycin and 0% for control;
P
< 0.05). Histopathological examination revealed that inflammatory changes in the SMP-601-treated group were less marked than in the other two groups. The results of pharmacokinetic-pharmacodynamic analysis supported the results of the bacteriological, histopathological and survival studies. Our results demonstrate the potency of SMP-601 against MRSA and VISA in murine hematogenous pulmonary infection.
Nasal Immunization with
Lactococcus lactis
Expressing the Pneumococcal Protective Protein A Induces Protective Immunity in Mice
Authors: Medina Marcela , Villena Julio , Vintiñi Elisa , Hebert Elvira María , Raya Raúl , Alvarez Susana 
Published: April 2008

ABSTRACT

Nisin-controlled gene expression was used to develop a recombinant strain of
Lactococcus lactis
that is able to express the pneumococcal protective protein A (PppA) on its surface. Immunodetection assays confirmed that after the induction with nisin, the PppA antigen was predictably and efficiently displayed on the cell surface of the recombinant strain, which was termed
L. lactis
PppA. The production of mucosal and systemically specific antibodies in adult and young mice was evaluated after mice were nasally immunized with
L. lactis
PppA. Immunoglobulin M (IgM), IgG, and IgA anti-PppA antibodies were detected in the serum and bronchoalveolar lavage fluid of adult and young mice, which showed that PppA expressed in
L. lactis
was able to induce a strong mucosal and systemic immune response. Challenge survival experiments demonstrated that immunization with
L. lactis
PppA was able to increase resistance to systemic and respiratory infection with different pneumococcal serotypes, and passive immunization assays of naïve young mice demonstrated a direct correlation between anti-PppA antibodies and protection. The results presented in this study demonstrate three major characteristics of the effectiveness of nasal immunization with PppA expressed as a protein anchored to the cell wall of
L. lactis
: it elicited cross-protective immunity against different pneumococcal serotypes, it afforded protection against both systemic and respiratory challenges, and it induced protective immunity in mice of different ages.
Extracellular Signal-Regulated Kinase Activation by
Neisseria gonorrhoeae
Downregulates Epithelial Cell Proapoptotic Proteins Bad and Bim
Authors: Howie Heather L. , Shiflett Shelly L. , So Magdalene 
Published: April 2008

ABSTRACT

Neisseria gonorrhoeae
expressing type IV pili (Tfp) activates extracellular signal-regulated kinase (ERK) and induces a cytoprotective state in the epithelial cell in a manner that is enhanced by
pilT
. As the ERK signaling pathway is well-known for its role in cytoprotection and cell survival, we tested the hypothesis that ERK is involved in producing this cytoprotective effect. Inhibiting ERK activation prior to infection attenuated the ability of these bacteria to induce cytoprotection. Activated ERK specifically targeted two proapoptotic Bcl-2 homology domain 3 (BH3)-only proteins, Bim and Bad, for downregulation at the protein level. Bim downregulation occurred through the proteasome. ERK, in addition, inactivated Bad by triggering its phosphorylation at Ser112. Finally, reducing the level of either Bad or Bim alone by small interfering RNA was sufficient to protect uninfected cells from staurosporine-induced apoptosis. We conclude that Tfp-induced cytoprotection is due in part to ERK-dependent modification and/or downregulation of proapoptotic proteins Bad and Bim.
Highly Conserved Surface Proteins of Oral Spirochetes as Adhesins and Potent Inducers of Proinflammatory and Osteoclastogenic Factors
Authors: Jun Hye-Kyoung , Kang Young-Mi , Lee Hae-Ri , Lee Sung-Hoon , Choi Bong-Kyu 
Published: April 2008

ABSTRACTOral spirochetes include enormously heterogeneousTreponemaspecies, and some have been implicated in the etiology of periodontitis. In this study, we characterized highly conserved surface proteins in four representative oral spirochetes (Treponema denticola, T. lecithinolyticum, T. maltophilum, andT. socranskiisubsp.socranskii) that are homologs ofT. pallidumTp92, with opsonophagocytic potential and protective capacity against syphilis. Tp92 homologs of oral spirochetes had predicted signal peptides (20 to 31 amino acids) and molecular masses of 88 to 92 kDa for mature proteins. They showed amino acid sequence identities of 37.9 to 49.3% and similarities of 54.5 to 66.9% to Tp92. The sequence identities and similarities of Tp92 homologs of oral treponemes to one another were 41.6 to 71.6% and 59.9 to 85.6%, respectively. Thetp92gene homologs were successfully expressed inEscherichia coli, and the recombinant proteins were capable of binding to KB cells, an epithelial cell line, and inhibited the binding of the whole bacteria to the cells. Antiserum (the immunoglobulin G fraction) raised against a recombinant form of theT. denticolaTp92 homolog cross-reacted with homologs from three other species of treponemes. The Tp92 homologs stimulated various factors involved in inflammation and osteoclastogenesis, like interleukin-1β (IL-1β), tumor necrosis factor alpha, IL-6, prostaglandin E2, and matrix metalloproteinase 9, in host cells like monocytes and fibroblasts. Our results demonstrate that Tp92 homologs of oral spirochetes are highly conserved and may play an important role in cell attachment, inflammation, and tissue destruction. The coexistence of variousTreponemaspecies in a single periodontal pocket and, therefore, the accumulation of multiple Tp92 homologs may amplify the pathological effect in periodontitis.
Borrelia burgdorferi
Surface-Localized Proteins Expressed during Persistent Murine Infection Are Conserved among Diverse
Borrelia
spp
Authors: Hughes Jessica L. , Nolder Christi L. , Nowalk Andrew J. , Clifton Dawn R. , Howison Rebekah R. , Schmit Virginia L. , Gilmore Robert D. , Carroll James A. 
Published: April 2008

ABSTRACT

Borrelia burgdorferi
, the causative agent of Lyme disease in the United States, regulates numerous genes encoding lipoproteins on linear plasmid 54 in response to environmental cues. We analyzed a subset of these genes/proteins that were historically categorized as paralogous gene family 54 (BBA64, BBA65, BBA66, BBA68, BBA69, BBA70, BBA71, and BBA73) and found that the expression of several genes was influenced by the σ
N
-σ
S
regulatory cascade at the level of transcription and protein synthesis. Moreover, we established in this and a previous study that BBA65, BBA66, BBA69, BBA71, and BBA73 are temporally expressed during persistent infection of immunocompetent mice, as determined by quantitative real time-PCR of ear tissue, by enzyme-linked immunosorbent assay, and by immunoblotting. Correspondingly, BBA65, BBA66, BBA71, and BBA73 proteins were detectable in infectious
B. burgdorferi
B31 isolates but undetectable in noninfectious isolates. BBA65, BBA66, BBA71, and BBA73 proteins were also found to partition into the Triton X-114 detergent phase and were sensitive to protease treatment of intact cells, indicating that they are membrane associated and surface localized. Lastly, Southern blotting and PCR with specific gene primer/probes for BBA64, BBA65, BBA66, BBA71, and BBA73 suggest that many of these genes are conserved among the
B. burgdorferi
sensu lato isolates and the relapsing-fever
Borrelia
species. Together, the data presented suggest that these genes may play a part in
Borrelia
infection and/or pathogenicity that could extend beyond the sensu lato group.
In LipL32, the Major Leptospiral Lipoprotein, the C Terminus Is the Primary Immunogenic Domain and Mediates Interaction with Collagen IV and Plasma Fibronectin
Authors: Hauk Pricila , Macedo Felipe , Romero Eliete Caló , Vasconcellos Sílvio Arruda , de Morais Zenaide Maria , Barbosa Angela Silva , Ho Paulo Lee 
Published: April 2008

ABSTRACT
LipL32 is the major leptospiral outer membrane lipoprotein expressed during infection and is the immunodominant antigen recognized during the humoral immune response to leptospirosis in humans. In this study, we investigated novel aspects of LipL32. In order to define the immunodominant domains(s) of the molecule, subfragments corresponding to the N-terminal, intermediate, and C-terminal portions of the LipL32 gene were cloned and the proteins were expressed and purified by metal affinity chromatography. Our immunoblot results indicate that the C-terminal and intermediate domains of LipL32 are recognized by sera of patients with laboratory-confirmed leptospirosis. An immunoglobulin M response was detected exclusively against the LipL32 C-terminal fragment in both the acute and convalescent phases of illness. We also evaluated the capacity of LipL32 to interact with extracellular matrix (ECM) components. Dose-dependent, specific binding of LipL32 to collagen type IV and plasma fibronectin was observed, and the binding capacity could be attributed to the C-terminal portion of this molecule. Both heparin and gelatin could inhibit LipL32 binding to fibronectin in a concentration-dependent manner, indicating that the 30-kDa heparin-binding and 45-kDa gelatin-binding domains of fibronectin are involved in this interaction. Taken together, our results provide evidence that the LipL32 C terminus is recognized early in the course of infection and is the domain responsible for mediating interaction with ECM proteins.
Heart rate and exercise intensity during training: observations from the DREW Study
Authors: Mikus C R , Earnest C P , Blair S N , Church T S 
Published: April 2008

Objective:Cardiovascular drift (CVdrift) is characterised by a continuous, gradual increase in heart rate (HR) after ∼10 min of moderate-intensity aerobic exercise, despite maintenance of a constant work rate. This has important implications for trials that employ HR to monitor exercise intensity, as reducing work rate in order to keep HR constant could result in participants exercising below the intended intensity. Utilising the Dose Response to Exercise in Women (DREW) database, we sought to determine if increases in HR during exercise (CVdrift) resulted in clinically significant reductions in exercise work rate in order to keep HR within a target range.Design:Randomised, prospective study.Setting:DREW clinical exercise trail, The Cooper Institute, Dallas, Texas.Participants:Overweight (body mass index 25–43 kg/m2), previously sedentary postmenopausal women (n  =  326).Intervention:Treadmill and cycling exercise (30–90 min, three to five times per week) at a HR corresponding to 50% of peak oxygen uptake (Vo2peak).Main outcome measure:Changes in exercise intensity (metabolic equivalents (METS)) during exercise in response to CVdrift.Results:We observed small increases in HR (1–4 beats per minute, p<0.001) combined with small increases in intensity (0.01–0.03 METS, p<0.03) during the combined 12 963 exercise training sessions. Further, we identified only 101 (0.78%) sessions in which intensity was reduced during the course of the exercise session, potentially in response to CVdrift.Conclusions:We conclude that CVdrift did not contribute to significant reductions in exercise intensity in the DREW study.
Effect of proprioception training on knee joint position sense in female team handball players
Authors: Pánics G , Tállay A , Pavlik A , Berkes I 
Published: April 2008

Background:A number of studies have shown that proprioception training can reduce the risk of injuries in pivoting sports, but the mechanism is not clearly understood.Aim:To determine the contributing effects of propioception on knee joint position sense among team handball players.Study design:Prospective cohort study.Methods:Two professional female handball teams were followed prospectively for the 2005–6 season. 20 players in the intervention team followed a prescribed proprioceptive training programme while 19 players in the control team did not have a specific propioceptive training programme. The coaches recorded all exposures of the individual players. The location and nature of injuries were recorded. Joint position sense (JPS) was measured by a goniometer on both knees in three angle intervals, testing each angle five times. Assessments were performed before and after the season by the same examiner for both teams. In the intervention team a third assessment was also performed during the season. Complete data were obtained for 15 subjects in the intervention team and 16 in the control team. Absolute error score, error of variation score and SEM were calculated and the results of the intervention and control teams were compared.Results:The proprioception sensory function of the players in the intervention team was significantly improved between the assessments made at the start and the end of the season (mean (SD) absolute error 9.78–8.21° (7.19–6.08°) vs 3.61–4.04°(3.71–3.20°), p<0.05). No improvement was seen in the sensory function in the control team between the start and the end of the season (mean (SD) absolute error 6.31–6.22°(6.12–3.59°) vs 6.13–6.69°(7.46–6.49°), p>0.05).Conclusion:This is the first study to show that proprioception training improves the joint position sense in elite female handball players. This may explain the effect of neuromuscular training in reducing the injury rate.
Consequences of dramatic reductions in state tobacco control funds: Florida, 1998–2000
Authors: Niederdeppe J , Farrelly M C , Hersey J C , Davis K C 
Published: April 2008

Objective:This study assessed whether dramatic funding reductions to the Florida Tobacco Control Program (FTCP) influenced trends in recall of the Florida “truth” anti-smoking media campaign, anti-industry attitudes and non-smoking intentions among Florida teens.Methods:We used an interrupted time series technique to test for differences in the rates of change in Florida “truth” recall, anti-industry beliefs and non-smoking intentions before and after the FTCP budget cuts using the Florida Anti-tobacco Media Evaluation (FAME) survey, a repeated cross-sectional telephone survey of Florida teens.Results:Recall of the Florida “truth” anti-smoking campaign, anti-industry attitudes, and non-smoking intentions increased dramatically between April 1998 and May 1999. Florida “truth” recall declined after FTCP budget cuts in June 1999. Anti-industry beliefs and non-smoking intentions plateaued or began to decline after the budget cuts. The launch of the national “truth” campaign in February 2000 may have offset otherwise deleterious effects of the budget cuts on anti-industry beliefs, but not smoking intentions.Conclusion:Reductions in tobacco control funding have immediate effects on programme exposure and cognitive precursors to smoking initiation. There is a critical need to maintain and enhance funding for state tobacco control programmes to continue nationwide progress in preventing youth from initiating cigarette smoking.
COST CONTAINMENT AND ACCESS TO CARE: THE SHANGHAI HEALTH CARE FINANCING MODEL
Authors: DONG WEIZHEN 
Published: April 2008

The medical savings account (MSA) model of health care financing is viewed as a health care cost containment strategy. Yet, health care expenditure in Shanghai has increased sharply since the adoption of the MSA system. This paper looks into the health care reforms in Shanghai, especially since the introduction of the MSA scheme. From the Labor Insurance Scheme and Government Insurance Scheme to the Medical Savings Account scheme, ordinary Shanghai residents have not benefited from the most recent health care reforms. They have found medical care much less affordable. Disparity in access to health care access has become more evident than ever. Meanwhile, health care cost has increased sharply. China has benefited from an emphasis on prevention and primary care, but the government's recent policies give a high priority to catastrophic disease. This is not a cost-effective approach. Shanghai's health care system needs to break socioeconomic class boundaries if it is to construct a harmonious society. Shanghai's decision makers and various stakeholders have the resources and wisdom to face the challenge.
GreenFS
Authors: Joukov Nikolai , Sipek Josef 
Published: April 2008

Hard disks contain data - frequently an irreplaceable asset of high monetary and non-monetary value. At the same time, hard disks are mechanical devices that consume power, are noisy, and fragile when their platters are rotating.
In this paper we demonstrate that hard disks cause different kinds of problems for different types of computer systems and demystify several common misconceptions. We show that solutions developed to date are incapable of solving the power consumption, noise, and data reliability problems without sacrificing hard disk life-time, data reliability, or user convenience.
We considered data reliability, recovery, performance, user convenience, and hard disk-caused problems together at the enterprise scale. We have designed GreenFS: a fan-out stackable file system that offers all-time all-data run-time data protection, improves performance under typical user workloads, and allows hard disks to be kept off most of the time. As a result, GreenFS improves enterprise data protection, minimizes disk drive-related power consumption and noise and increases the chances of disk drive survivability in case of unexpected external impacts.
VPFS
Authors: Weinhold Carsten , Härtig Hermann 
Published: April 2008

In this paper we present the lessons we learned when developing VPFS, a virtual private file system that is based on both a small amount of trusted storage and an untrusted legacy file system residing on the same machine. VPFS' purpose is to provide secure and reliable storage to highly sensitive applications running on top of a microkernel, which may concurrently execute untrusted software. The confidentiality and integrity guarantees of VPFS do not only apply to file contents, but also to all meta data including integrity of the directory structure.
We explored design alternatives that allow us to securely reuse untrusted infrastructure and thereby minimize the complexity that a file-system implementation adds to the trusted computing base. VPFS is split into two isolated components. A small trusted component implements all security-critical functionality, whereas the untrusted part reuses an existing file-system implementation provided by a virtualized legacy operating system that can be untrusted. In our VPFS prototype, alternative configurations of the trusted component comprise only between 4,000 and 4,600 lines of code, which is at least an order of magnitude smaller than existing commodity file-system stacks.
BorderPatrol
Authors: Koskinen Eric , Jannotti John 
Published: April 2008

Causal request traces are valuable to developers of large concurrent and distributed applications, yet difficult to obtain. Traces show how a request is processed, and can be analyzed by tools to detect performance or correctness errors and anomalous behavior.
We present BorderPatrol, which obtains precise request traces through suystems built from a litany of unmodified modules. Traced components include Apache, thttpd, PostgreSQL, TurboGears, BIND and notably Zeus, a closed-source event-driven web server. BorderPatrol obtains traces using active observation which carefully modifies the event stream observed by modules, simplifying precise observation. Protocol processors leverage knowledge about standard protocols, avoiding application-specific instrumentation.
BorderPatrol obtains precise traces for black-box systems that cannot be traced by any other technique. We confirm the accuracy of BorderPatrol's traces by comparing to manual instrumentation, and compare the developer effort required for each kind of trace. BorderPatrol imposes limited overhead on real systems (approximately 10-15%) and it may be enabled or disabled in at run-time, making it a viable option for deployment in production environments.
Documenting and automating collateral evolutions in linux device drivers
Authors: Padioleau Yoann , Lawall Julia , Hansen René Rydhof , Muller Gilles 
Published: April 2008

The internal libraries of Linux are evolving rapidly, to address new requirements and improve performance. These evolutions, however, entail a massive problem of collateral evolution in Linux device drivers: for every change that affects an API, all dependent drivers must be updated accordingly. Manually performing such collateral evolutions is time-consuming and unreliable, and has lead to errors when modifications have not been done consistently.
In this paper, we present an automatic program transformation tool Coccinelle, for documenting and automating device driver collateral evolutions. Because Linux programmers are accustomed to manipulating program modifications in terms of patch files, this tool uses a language based on the patch syntax to express transformations, extending patches to semantic patches. Coccinelle preserves the coding style of the original driver, as would a human programmer.
We have evaluated our approach on 62 representative collateral evolutions that were previously performed manually in Linux 2.5 and 2.6. On a test suite of over 5800 relevant driver files, the semantic patches for these collateral evolutions update over 93% of the files completely. In the remaining cases, the user is typically alerted to a partial match against the driver code, identifying the files that must be considered manually. We have additionally identified over 150 driver files where the maintainer made an error in performing the collateral evolution, but Coccinelle transforms the code correctly. Finally, several patches derived from the use of Coccinelle have been accepted into the Linux kernel.