bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chitin Accelerates Activation of a Novel Haloarchaeal Serine Protease That Deproteinizes Chitin-Containing Biomass
Authors: Zhang Yaoxin , Wang Mengxin , Du Xin , Tang Wei , Zhang Li , Li Moran , Wang Jian , Tang Bing , Tang Xiao-Feng 
Published: July 2014

ABSTRACT

The haloarchaeon
Natrinema
sp. strain J7-2 has the ability to degrade chitin, and its genome harbors a chitin metabolism-related gene cluster that contains a halolysin gene,
sptC
. The
sptC
gene encodes a precursor composed of a signal peptide, an N-terminal propeptide consisting of a core domain (N*) and a linker peptide, a subtilisin-like catalytic domain, a polycystic kidney disease domain (PkdD), and a chitin-binding domain (ChBD). Here we report that the autocatalytic maturation of SptC is initiated by
cis
-processing of N* to yield an autoprocessed complex (N*-I
WT
), followed by
trans
-processing/degradation of the linker peptide, the ChBD, and N*. The resulting mature form (M
WT
) containing the catalytic domain and the PkdD showed optimum azocaseinolytic activity at 3 to 3.5 M NaCl, demonstrating salt-dependent stability. Deletion analysis revealed that the PkdD did not confer extra stability on the enzyme but did contribute to enzymatic activity. The ChBD exhibited salt-dependent chitin-binding capacity and mediated the binding of N*-I
WT
to chitin. ChBD-mediated chitin binding enhances SptC maturation by promoting activation of the autoprocessed complex. Our results also demonstrate that SptC is capable of removing proteins from shrimp shell powder (SSP) at high salt concentrations. Interestingly, N*-I
WT
released soluble peptides from SSP faster than did M
WT
. Most likely, ChBD-mediated binding of the autoprocessed complex to chitin in SSP not only accelerates enzyme activation but also facilitates the deproteinization process by increasing the local protease concentration around the substrate. By virtue of these properties, SptC is highly attractive for use in preparation of chitin from chitin-containing biomass.
Development of Primary Invasive Pneumococcal Disease Caused by Serotype 1 Pneumococci Is Driven by Early Increased Type I Interferon Response in the Lung
Authors: Hughes Catherine E. , Harvey Richard M. , Plumptre Charles D. , Paton James C. 
Published: July 2014

ABSTRACT

The pneumococcus is the world's foremost respiratory pathogen, but the mechanisms allowing this pathogen to proceed from initial asymptomatic colonization to invasive disease are poorly understood. We have examined the early stages of invasive pneumococcal disease (IPD) by comparing host transcriptional responses to an invasive strain and a noninvasive strain of serotype 1
Streptococcus pneumoniae
in the mouse lung. While the two strains were present in equal numbers in the lung 6 h after intranasal challenge, only the invasive strain (strain 1861) had invaded the pleural cavity at that time point; this correlated with subsequent development of bacteremia in mice challenged with strain 1861 but not the noninvasive strain (strain 1). Progression beyond the lung was associated with stronger induction of the type I interferon (IFN-I) response in the lung at 6 h. Suppression of the IFN-I response through administration of neutralizing antibody to IFNAR1 (the receptor for type I interferons) led to significantly reduced invasion of the pleural cavity by strain 1861 at 6 h postchallenge. Our data suggest that strong induction of the IFN-I response is a key factor in early progression of invasive serotype 1 strain 1861 beyond the lung during development of IPD.
Optimizing the Block I/O Subsystem for Fast Storage Devices
Authors: Yu Young Jin , Shin Dong In , Shin Woong , Song Nae Young , Choi Jae Woo , Kim Hyeong Seog , Eom Hyeonsang , Yeom Heon Young 
Published: July 2014

Fast storage devices are an emerging solution to satisfy data-intensive applications. They provide high transaction rates for DBMS, low response times for Web servers, instant on-demand paging for applications with large memory footprints, and many similar advantages for performance-hungry applications. In spite of the benefits promised by fast hardware, modern operating systems are not yet structured to take advantage of the hardware’s full potential. The software overhead caused by an OS, negligible in the past, adversely impacts application performance, lessening the advantage of using such hardware. Our analysis demonstrates that the overheads from the traditional storage-stack design are significant and cannot easily be overcome without modifying the hardware interface and adding new capabilities to the operating system.
In this article, we propose six optimizations that enable an OS to fully exploit the performance characteristics of fast storage devices. With the support of new hardware interfaces, our optimizations minimize per-request latency by streamlining the I/O path and amortize per-request latency by maximizing parallelism inside the device. We demonstrate the impact on application performance through well-known storage benchmarks run against a Linux kernel with a customized SSD. We find that eliminating context switches in the I/O path decreases the software overhead of an I/O request from 20 microseconds to 5 microseconds and a new request merge scheme called Temporal Merge enables the OS to achieve 87% to 100% of peak device performance, regardless of request access patterns or types. Although the performance improvement by these optimizations on a standard SATA-based SSD is marginal (because of its limited interface and relatively high response times), our sensitivity analysis suggests that future SSDs with lower response times will benefit from these changes. The effectiveness of our optimizations encourages discussion between the OS community and storage vendors about future device interfaces for fast storage devices.
Type II collagen antibody response is enriched in the synovial fluid of rheumatoid joints and directed to the same major epitopes as in collagen induced arthritis in primates and mice
Authors: Lindh Ingrid , Snir Omri , Lönnblom Erik , Uysal Hüseyin , Andersson Ida , Nandakumar Kutty Selva , Vierboom Michel , 't Hart Bert , Malmström Vivianne , Holmdahl Rikard 
Published: July 2014

Abstract
Introduction
Antibodies towards type II collagen (CII) are detected in patients with rheumatoid arthritis (RA) and in non-human primates and rodents with collagen induced arthritis (CIA). We have previously shown that antibodies specific for several CII-epitopes are pathogenic using monoclonal antibodies from arthritic mice, although the role of different anti-CII epitopes has not been investigated in detail in other species. We therefore performed an inter-species comparative study of the autoantibody response to CII in patients with RA versus monkeys and mice with CIA.

Methods
Analysis of the full epitope repertoire along the disease course of CIA was performed using a library of CII triple-helical peptides. The antibody responses to the major CII epitopes were analyzed in sera and synovial fluid from RA patients, and in sera from rhesus monkeys (Macaca mulatta), common marmosets (Callithrix jacchus) and mice.

Results
Many CII epitopes including the major C1, U1, and J1 were associated with established CIA and arginine residues played an important role in the anti-CII antibody interactions. The major epitopes were also recognized in RA patients, both in sera and even more pronounced in synovial fluid: 77% of the patients had antibodies to the U1 epitope. The anti-CII immune response was not restricted to the anti-citrulline protein antibodies (ACPA) positive RA group.

Conclusion
CII conformational dependent antibody responses are common in RA and are likely to originate from rheumatoid joints but did not show a correlation with ACPA response. Importantly, the fine specificity of the anti-CII response is similar with CIA in monkeys and rodents where the recognized epitopes are conserved and have a major pathogenic role. Thus, anti-CII antibodies may both contribute to, as well as be the consequence of, local joint inflammation.
Parity-related molecular signatures and breast cancer subtypes by estrogen receptor status
Authors: Rotunno Melissa , Sun Xuezheng , Figueroa Jonine , Sherman Mark E , Garcia-Closas Montserrat , Meltzer Paul , Williams Tyisha , Schneider Sallie Smith , Jerry D Joseph , Yang Xiaohong R , Troester Melissa A 
Published: July 2014

Abstract
Introduction
Relationships of parity with breast cancer risk are complex. Parity is associated with decreased risk of postmenopausal hormone receptor–positive breast tumors, but may increase risk for basal-like breast cancers and early-onset tumors. Characterizing parity-related gene expression patterns in normal breast and breast tumor tissues may improve understanding of the biological mechanisms underlying this complex pattern of risk.

Methods
We developed a parity signature by analyzing microRNA microarray data from 130 reduction mammoplasty (RM) patients (54 nulliparous and 76 parous). This parity signature, together with published parity signatures, was evaluated in gene expression data from 150 paired tumors and adjacent benign breast tissues from the Polish Breast Cancer Study, both overall and by tumor estrogen receptor (ER) status.

Results
We identified 251 genes significantly upregulated by parity status in RM patients (parous versus nulliparous; false discovery rate = 0.008), including genes in immune, inflammation and wound response pathways. This parity signature was significantly enriched in normal and tumor tissues of parous breast cancer patients, specifically in ER-positive tumors.

Conclusions
Our data corroborate epidemiologic data, suggesting that the etiology and pathogenesis of breast cancers vary by ER status, which may have implications for developing prevention strategies for these tumors.
Early adaptive immune suppression in children with septic shock: a prospective observational study
Authors: Muszynski Jennifer A , Nofziger Ryan , Greathouse Kristin , Steele Lisa , Hanson-Huber Lisa , Nateri Jyotsna , Hall Mark W 
Published: July 2014

Abstract
Introduction
Innate immune suppression occurs commonly in pediatric critical illness, in which it is associated with adverse outcomes. Less is known about the adaptive immune response in critically ill children with sepsis. We designed a single-center prospective, observational study to test the hypothesis that children with septic shock would have decreased adaptive immune function compared with healthy children and that among children with sepsis, lower adaptive immune function would be associated with the development of persistent infection or new nosocomial infection.

Methods
Children (18 years or younger) who were admitted to the pediatric intensive care unit with septic shock (by International Consensus Criteria) were enrolled in the study. Blood samples were taken within 48 hours of sepsis onset and again on Day 7 of illness. Adaptive immune function was assessed with ex vivo phytohemagglutinin (PHA)-induced cytokine production capacity of isolated CD4+ T cells. Percentage of regulatory T cells was measured with flow cytometry. Absolute lymphocyte counts were recorded when available.

Results
In total, 22 children with septic shock and eight healthy controls were enrolled. Compared with those from healthy children, CD4+ T cells isolated from septic shock children on Days 1 to 2 of illness and stimulated with PHA produced less of the pro-inflammatory cytokine interferon gamma (IFN-γ) (P = 0.002), and the antiinflammatory cytokines interleukin (IL)-4 (P = 0.03) and IL-10 (P = 0.02). Among septic shock children, those who went on to develop persistent or nosocomial infection had decreased T-cell ex vivo PHA-induced production of IFN-γ (P = 0.01), IL-2 (P = 0.01), IL-4 (P = 0.008), and IL-10 (P = 0.001) compared with septic shock children who did not. Percentage of regulatory T cells (CD4+CD25+CD127lo) did not differ among groups.

Conclusions
Adaptive immune suppression may occur early in the course of pediatric septic shock and is associated with adverse infection-related outcomes.
SIRT1 inhibition during the hypoinflammatory phenotype of sepsis enhances immunity and improves outcome
Authors: Vachharajani Vidula T , Liu Tiefu , Brown Candice M , Wang Xianfeng , Buechler Nancy L , Wells Jonathan David , Yoza Barbara K , McCall Charles E 
Published: July 2014

ABSTRACTMechanism-based sepsis treatments are unavailable, and their incidence is rising worldwide. Deaths occur during the early acute phase of hyperinflammation or subsequent postacute hypoinflammatory phase with sustained organ failure. The acute sepsis phase shifts rapidly, and multiple attempts to treat early excessive inflammation have uniformly failed. We reported in a sepsis cell model and human sepsis blood leukocytes that nuclear NAD+ sensor SIRT1 deacetylase remodels chromatin at specific gene sets to switch the acute-phase proinflammatory response to hypoinflammatory. Importantly, SIRT1 chromatin reprogramming is reversible, suggesting that inhibition of SIRT1 might reverse postacute-phase hypoinflammation. We tested this concept in septic mice, using the highly specific SIRT1 inhibitor EX-527, a small molecule that closes the NAD+ binding site of SIRT1. Strikingly, when administered 24 h after sepsis, all treated animals survived, whereas only 40% of untreated mice survived. EX-527 treatment reversed the inability of leukocytes to adhere at the small intestine MVI, reversed in vivo endotoxin tolerance, increased leukocyte accumulation in peritoneum, and improved peritoneal bacterial clearance. Mechanistically, the SIRT1 inhibitor restored repressed endothelial E-selectin and ICAM-1 expression and PSGL-1 expression on the neutrophils. Systemic benefits of EX-527 treatment included stabilized blood pressure, improved microvascular blood flow, and a shift toward proimmune macrophages in spleen and bone marrow. Our findings reveal that modifying the SIRT1 NAD+ axis may provide a novel way to treat sepsis in its hypoinflammatory phase.
Quality Assessment of Implementation of the System of Protection, Information, and Notification of People in Natural and Man-made Transport Emergencies
Authors: Алымов  , Alymov Aleksandr , Лукьянович  , Lukyanovich Aleksey , Пашков  , Pashkov Andrey 
Published: July 2014

«All-Russian Research Institute on Problems of Civil Defense and Emergencies of Emergency Control Ministry of Russia» of the Ministry of the Russian Federation for Civil Defense, Emergencies and Elimination of Consequences of Natural Disasters
The article reviews creation (2010-2013) of the System of protection, information, and notification of people in natural and man-made transport emergencies, presents a methodological approach to evaluation of the System elements’ quality and the results of its application, and suggests schemes for its further development and improvement.
NUMERICAL ANALYSIS OF CAVITATION SUSCEPTIBILITY FOR STEAM GENERATOR INTEGRAL PREHEATER TUBES
Authors: Laroche S. , Sun L. , Pietralik J. 
Published: July 2014

A new tube degradation mechanism was observed in a recirculating steam generator (SG) with an integral preheater tube at the clearance gap between the tube and the preheater baffle. The general pattern of the damage and material composition in the degraded region suggested that the degradation was cavitation erosion. Cavitation erosion occurs when vapour bubbles exist or form in the flowing liquid and then these bubbles collapse violently in the vicinity of a solid wall. The bubbles collapse when they contact water that is sufficiently subcooled, i.e., below the saturation temperature. In the clearance gap between the tube and the preheater baffle, secondary fluid flow exists due to the pressure difference across the baffle plate. Meanwhile, heat transfer occurs from the primary-side fluid to the secondary-side fluid within this clearance gap, driven by the primary-to-secondary temperature difference. Factors such as the tube position in the baffle hole and fouling may influence the local flow and heat transfer conditions and can cause subcooled boiling that results in cavitation. This paper presents a numerical analysis of flow and heat transfer phenomena to determine the factors contributing to cavitation erosion of tubes in the preheater of a recirculating SG. The analysis used the THIRST code for a 3-dimensional thermalhydraulic simulation of steam generator and the ANSYS Fluent® code for detailed calculations of flow and heat transfer in the clearance gaps. A detailed temperature distribution in the gap was obtained using this analysis to determine the regions where subcooled boiling could occur by comparing the local fluid temperature with its saturation temperature. The susceptibility to cavitation was found to increase with increased inclination (i.e., tilt) and eccentricity (i.e., off-centre) of the tube in the baffle plate gap, and increased fouling on baffle plate surfaces. This methodology could be applied to analyze the cavitation susceptibility for other preheater types with this “tube to baffle plate” gap, as these preheaters might have conditions where boiling followed by the rapid condensation of the steam bubbles are present.
Correlating structure and ligand affinity in drug discovery: a cautionary tale involving second shell residues
Authors: Tziridis Anastasia , Rauh Daniel , Neumann Piotr , Kolenko Petr , Menzel Anja , Bräuer Ulrike , Ursel Christian , Steinmetzer Peter , Stürzebecher Jörg , Schweinitz Andrea , Steinmetzer Torsten , Stubbs Milton T. 
Published: July 2014

Abstract
A high-resolution crystallographic structure determination of a protein–ligand complex is generally accepted as the ‘gold standard’ for structure-based drug design, yet the relationship between structure and affinity is neither obvious nor straightforward. Here we analyze the interactions of a series of serine proteinase inhibitors with trypsin variants onto which the ligand-binding site of factor Xa has been grafted. Despite conservative mutations of only two residues not immediately in contact with ligands (second shell residues), significant differences in the affinity profiles of the variants are observed. Structural analyses demonstrate that these are due to multiple effects, including differences in the structure of the binding site, differences in target flexibility and differences in inhibitor binding modes. The data presented here highlight the myriad competing microscopic processes that contribute to protein–ligand interactions and emphasize the difficulties in predicting affinity from structure.
Insights into Supplements with Tribulus Terrestris used by Athletes
Authors: Pokrywka Andrzej , Obmiński Zbigniew , Malczewska-Lenczowska Jadwiga , Fijatek Zbigniew , Turek-Lepa Ewa , Grucza Ryszard 
Published: July 2014

Abstract
Herbal and nutritional supplements are more and more popular in the western population. One of them is an extract of an exotic plant, named Tribulus terrestris (TT). TT is a component of several supplements that are available over-the-counter and widely recommended, generally as enhancers of human vitality. TT is touted as a testosterone booster and remedy for impaired erectile function; therefore, it is targeted at physically active men, including male athletes. Based on the scientific literature describing the results of clinical trials, this review attempted to verify information on marketing TT with particular reference to the needs of athletes. It was found that there are few reliable data on the usefulness of TT in competitive sport. In humans, a TT extract used alone without additional components does not improve androgenic status or physical performance among athletes. The results of a few studies have showed that the combination of TT with other pharmacological components increases testosterone levels, but it was not discovered which components of the mixture contributed to that effect. TT contains several organic compounds including alkaloids and steroidal glycosides, of which pharmacological action in humans is not completely explained. One anti-doping study reported an incident with a TT supplement contaminated by a banned steroid. Toxicological studies regarding TT have been carried out on animals only, however, one accidental poisoning of a man was described. The Australian Institute of Sport does not recommend athletes’ usage of TT. So far, the published data concerning TT do not provide strong evidence for either usefulness or safe usage in sport.
Prediction of Rowing Ergometer Performance from Functional Anaerobic Power, Strength and Anthropometric Components
Authors: Akça Firat 
Published: July 2014

Abstract
The aim of this research was to develop different regression models to predict 2000 m rowing ergometer performance with the use of anthropometric, anaerobic and strength variables and to determine how precisely the prediction models constituted by different variables predict performance, when conducted together in the same equation or individually. 38 male collegiate rowers (20.17 ± 1.22 years) participated in this study. Anthropometric, strength, 2000 m maximal rowing ergometer and rowing anaerobic power tests were applied. Multiple linear regression procedures were employed in SPSS 16 to constitute five different regression formulas using a different group of variables. The reliability of the regression models was expressed by R2 and the standard error of estimate (SEE). Relationships of all parameters with performance were investigated through Pearson correlation coefficients. The prediction model using a combination of anaerobic, strength and anthropometric variables was found to be the most reliable equation to predict 2000 m rowing ergometer performance (R2 = 0.92, SEE= 3.11 s). Besides, the equation that used rowing anaerobic and strength test results also provided a reliable prediction (R2 = 0.85, SEE= 4.27 s). As a conclusion, it seems clear that physiological determinants which are affected by anaerobic energy pathways should also get involved in the processes and models used for performance prediction and talent identification in rowing.