bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational analysis of intersubject variability and thrombin generation in dilutional coagulopathy
Authors: Mitrophanov Alexander Y. , Rosendaal Frits R. , Reifman Jaques 
Published: March 2012

BACKGROUND: Blood dilution is a frequent complication of massive transfusion during trauma and surgery. This article investigates the quantitative effects of blood plasma dilution on thrombin generation in the context of intersubject variability.STUDY DESIGN AND METHODS: A thoroughly validated computational model was used to simulate thrombin generation curves for 472 healthy subjects in the Leiden Thrombophilia Study. Individual thrombin curves were calculated for undiluted blood and for different dilution scenarios. For every such curve, five standard quantitative parameters of thrombin generation were calculated and analyzed.RESULTS: Thrombin generation parameters in diluted blood plasma displayed significant intersubject variability (with a coefficient of variation up to approx. 28%). Nevertheless, dilutional effects in the majority (or all) of the subjects in the study group were characterized by persistent patterns. In particular, the largest dilution‐induced change typically occurred in the maximum slope (MS) of the thrombin curve, followed by a change in thrombin peak height (PH), whereas the smallest change often occurred in the area under the curve. The identified patterns demonstrated considerable robustness to variations in dilution scenario and tissue factor concentration.CONCLUSION: Dilutional effects on thrombin generation in a human population can be predicted from trends identified for the “average” subject and then refined by performing an analysis of actual subjects in the study group. The MS and PH are dilution indicators that are both sensitive and reliable across a large subject group and could potentially be used as disease markers in the diagnosis of coagulopathic conditions.
The Effects of Personality Type on Choices Made in Strategic Decision Situations*
Authors: Stumpf Stephen A. , Dunbar Roger L.M. 
Published: March 2012

ABSTRACTJung's personality‐theory typology is used as a framework for exploring the effects of cognitive style on the type and radicalness of choices made in strategic decision situations. Extending the work of Haley and Stumpf [23], it is proposed that individuals with different personality‐type preferences exhibit cognitive styles that are associated with specific biases in the pattern of choices they make. Through participation in an interactive behavioral simulation, 407 participants confronted over one hundred ill‐structured decision situations and proposed whatever actions they perceived appropriate. The results support the hypothesized relationships that individuals with different personality‐type preferences (i.e., sensing‐thinking, intuition‐thinking, sensing‐feeling, and intuition‐feeling) take patterns of actions that reflect specific biases (i.e., selective perception, positivity, social desirability, and reasoning‐by‐analogy, respectively). The implications of these findings for evaluating the likely effectiveness of strategic decisions and making senior‐level staffing decisions are discussed.
Lactobacillus and Pediococcus species richness and relative abundance in the vagina of rhesus monkeys (Macaca mulatta)
Authors: Gravett Michael G. , Jin Ling , Pavlova Sylvia I. , Tao Lin 
Published: March 2012

AbstractBackground  The rhesus monkey is an important animal model to study human vaginal health to which lactic acid bacteria play a significant role. However, the vaginal lactic acid bacterial species richness and relative abundance in rhesus monkeys is largely unknown.Methods  Vaginal swab samples were aseptically obtained from 200 reproductive‐aged female rhesus monkeys. Following Rogosa agar plating, single bacterial colonies representing different morphotypes were isolated and analyzed for whole‐cell protein profile, species‐specific polymerase chain reaction, and 16S rRNA gene sequence.Results  A total of 510 Lactobacillus strains of 17 species and one Pediococcus acidilactici were identified. The most abundant species was Lactobacillus reuteri, which colonized the vaginas of 86% monkeys. Lactobacillus johnsonii was the second most abundant species, which colonized 36% of monkeys. The majority of monkeys were colonized by multiple Lactobacillus species.Conclusions  The vaginas of rhesus monkeys are frequently colonized by multiple Lactobacillus species, dominated by L. reuteri.
Myoglobin‐Induced Apoptosis: Two Pathways Related to Endoplasmic Reticulum Stress
Authors: Zhou Jianhui , Kong Deyang , Zhang Xu , Wang Yuanda , Feng Zhe , Zhang Xueguang , Zhang Li , Wang Yan , Xie Yuansheng , Chen Xiangmei 
Published: March 2012

AbstractMyoglobin plays an important role in rhabdomyolysis‐induced acute kidney injury (AKI), but the underlying mechanisms are still unclear. The present study investigates myoglobin‐induced apoptosis in HK‐2 cells (human renal proximal tubule cells) to discover some of the mechanisms involved in rhabdomyolysis related AKI. Metmyoglobin is reduced to ferrous myoglobin by ascorbic acid, and then the HK‐2 cells are incubated with ferrous myoglobin. Cell viability is measured by 3‐(4,5)‐dimethylthiahiazo(‐z‐y1)‐3,5‐di‐phenytetrazoliumromide (MTT) assay, and cell injury is tested by supernatant lactose dehydrogenase (LDH). Cell apoptosis is evaluated by fluorescent microscopy of Hoechst staining and by flow cytometry of Annexin V/PI double staining. The apoptosis related protein expression is determined by Western blot. HK‐2 cells were incubated with 200 µM ferrous myoglobin for 24 h, the cell viability decreased and supernatant LDH release increased. Hoechst staining indicated more apoptosis after incubation. Molecular chaperone glucose‐related protein 78 (GRP78), cytochrome C, caspase‐9 started to increase within 3 h after incubation while caspase‐4, caspase‐8 showed no significant change. (iii) When the inositol triphosphate receptor (IP3R) calcium channel was blocked by 2‐aminoethoxydiphenyl‐borinate (2‐APB), caspase‐9 was completely inhibited, GRP78 and caspase‐4 increased dramatically, and caspase‐3 expression was not affected. The apoptosis in HK‐2 cells showed no significant change. Apoptosis in HK‐2 cells incubated with ferrous myoglobin is an endoplasmic reticulum stress induced, IP3R calcium channel mediated, caspase‐9 dependent intrinsic pathway. When the intrinsic pathway was inhibited using an IP3R calcium channel blocker, endoplasmic reticulum stress increased, resulting in the activation of caspase‐4 that cleaved caspase‐3 and generated a substitutive pathway of apoptosis.
Renal cortical and medullary blood flow during modest saline loading in humans
Authors: Damkjær M. , Vafaee M. , Braad P. E. , Petersen H. , Høilund‐Carlsen P. F. , Bie P. 
Published: March 2012

AbstractAimRenal medullary blood flow (RMBF) is considered an important element of sodium homeostasis, but the experimental evidence is incongruent. Studies in anaesthetized animals generally support the concept in contrast to measurements in conscious animals. We hypothesized that saline‐induced natriuresis is associated with changes in RMBF in humans.MethodsAfter 4 days of low‐sodium diet, healthy men were subjected to slow intravenous saline loading (12 μmol kg−1 min−1) for 4 h. Renal medullary and cortical blood flow was determined by positron emission tomography with H215O before and after saline infusion using two independent imaging processing methods. One based on a previously published algorithm (voxel peeling) and a novel method based on contrast‐enhanced computed tomography (CT). Blood pressure was measured oscillometrically every 10 min. Cardiac output, heart rate and total peripheral resistance were recorded continuously.ResultsSaline loading increased the urinary sodium excretion by 3.6‐fold (21–76 μmol min−1, P < 0.01). The RMBF was 2.6 ± 0.2 mL g−1 tissue min−1 before and 2.7 ± 0.1 mL g−1 tissue min−1 after saline (n.s.). Cortical blood flow was 3.6 ± 0.1 before and 3.4 ± 0.2 after saline (n.s.). Mean arterial blood pressure did not change measurably (90 vs. 90 mmHg). Bland–Altman analysis suggested agreement between results obtained with voxel peeling (2.6 ± 0.2 mL g−1 tissue min−1) and contrast‐enhanced CT (2.0 ± 0.1 mL g−1 tissue min−1).ConclusionIn normal humans, changes in RMBF are not necessarily involved in the natriuretic response to modest saline loading. This result is in line with data from conscious rodents.
Comparative genomics of bacteria from the genus Collimonas: linking (dis)similarities in gene content to phenotypic variation and conservation
Authors: Mela F. , Fritsche K. , de Boer W. , van den Berg M. , van Veen J. A. , Maharaj N. N. , Leveau J. H. J. 
Published: March 2012

SummaryCollimonas is a genus of soil bacteria comprising three recognized species: C. fungivorans, C. pratensis and C. arenae. Collimonads share the ability to degrade chitin (chitinolysis), feed on living fungal hyphae (mycophagy), and dissolve minerals (weathering), but vary in their inhibition of fungi (fungistasis). To better understand this phenotypic variability, we analysed the genomic content of four strains representing three Collimonas species (Ter14, Ter6, Ter91 and Ter10) by hybridization to a microarray based on reference strain C. fungivorans Ter331. The analysis revealed genes unique to strain Ter331 (e.g. those on the extrachromosomal element pTer331) and genes present in some but not all of the tested strains. Among the latter were several candidates that may contribute to fungistasis, including genes for the production and secretion of antifungals. We hypothesize that differential possession of these genes underlies the specialization of Collimonas strains towards different fungal hosts. We identified a set of 136 genes that were common in all tested Collimonas strains, but absent from the genomes of three other members of the family Oxalobacteraceae. Predicted products of these ‘Collimonas core’ genes include lytic, secreted enzymes such as chitinases, peptidases, nucleases and phosphatases with a putative role in mycophagy and weathering.
Randomized Trial of Entecavir plus Adefovir in Patients with Lamivudine-Resistant Chronic Hepatitis B Who Show Suboptimal Response to Lamivudine plus Adefovir
Authors: Lim Young-Suk , Lee Ji-Young , Lee Danbi , Shim Ju Hyun , Lee Han Chu , Lee Yung Sang , Suh Dong Jin 
Published: March 2012

ABSTRACTA substantial proportion of patients with lamivudine-resistant hepatitis B virus (HBV) show suboptimal virologic response during rescue combination treatment with lamivudine plus adefovir. In this randomized active-control trial, 90 patients with serum HBV DNA levels of >2,000 IU/ml after at least 24 weeks of treatment with lamivudine-plus-adefovir therapy for lamivudine-resistant HBV were randomized to combination treatment with entecavir plus adefovir (ETV+ADV,n= 45) or continuation of lamivudine plus adefovir (LAM+ADV,n= 45) for 52 weeks. At baseline, patients' mean serum HBV DNA level was 4.60 log10IU/ml (standard deviation [SD], 1.03). All 90 patients completed 52 weeks of treatment. At week 52, the proportion of patients with serum HBV DNA levels of <60 IU/ml, the primary endpoint, was significantly higher in the ETV+ADV group than in the LAM+ADV group (n= 13, 29%, versusn= 2, 4%, respectively;P= 0.004). The mean reduction in serum HBV DNA levels from baseline was significantly greater in the ETV+ADV group than in the LAM+ADV group (−2.2 log10IU/ml versus −0.6 log10IU/ml, respectively;P< 0.001). At week 52, additional mutations causing resistance to adefovir or entecavir were analyzed in all patients with detectable HBV DNA by restriction fragment mass polymorphism assays and detected in none of the ETV+ADV group but in 15% of patients in the LAM+ADV group (P= 0.018). Safety and adverse event profiles were similar in the two groups. In conclusion, entecavir-plus-adefovir combination therapy provides superior virologic response and favorable resistance profiles, compared with the continuing lamivudine-plus-adefovir combination, in patients with lamivudine-resistant HBV who fail to respond to lamivudine-plus-adefovir combination therapy.
Attenuated Virulence and Biofilm Formation in Staphylococcus aureus following Sublethal Exposure to Triclosan
Authors: Latimer Joe , Forbes Sarah , McBain Andrew J. 
Published: March 2012

ABSTRACT

Subeffective exposure of
Staphylococcus aureus
to the biocide triclosan can reportedly induce a small-colony variant (SCV) phenotype.
S. aureus
SCVs are characterized by low growth rates, reduced pigmentation, and lowered antimicrobial susceptibility. While they may exhibit enhanced intracellular survival, there are conflicting reports regarding their pathogenicity. The current study reports the characteristics of an SCV-like strain of
S. aureus
created by repeated passage on sublethal triclosan concentrations.
S. aureus
ATCC 6538 (the passage 0 [P0] strain) was serially exposed 10 times to concentration gradients of triclosan to generate strain P10. This strain was then further passaged 10 times on triclosan-free medium (designated strain ×10). The MICs and minimum bactericidal concentrations of triclosan for P0, P10, and ×10 were determined, and growth rates in biofilm and planktonic cultures were measured. Hemolysin, DNase, and coagulase activities were measured, and virulence was determined using a
Galleria mellonella
pathogenicity model. Strain P10 exhibited decreased susceptibility to triclosan and characteristics of an SCV phenotype, including a considerably reduced growth rate and the formation of pinpoint colonies. However, this strain also had delayed coagulase production, had impaired hemolysis (
P
< 0.01), was defective in biofilm formation and DNase activity, and displayed significantly attenuated virulence. Colony size, hemolysis, coagulase activity, and virulence were only partially restored in strain ×10, whereas the planktonic growth rate was fully restored. However, ×10 was at least as defective in biofilm formation and DNase production as P10. These data suggest that although repeated exposure to triclosan may result in an SCV-like phenotype, this is not necessarily associated with increased virulence and adapted bacteria may exhibit other functional deficiencies.
Action of Linezolid or Vancomycin on Biofilms in Ventriculoperitoneal Shunts
In Vitro
Authors: Bayston Roger , Ullas Gautham , Ashraf Waheed 
Published: March 2012

ABSTRACT

Cerebrospinal fluid (CSF) shunts used to treat hydrocephalus have an overall infection rate of about 10% of operations. The commonest causative bacteria are
Staphylococcus epidermidis
, followed by
Staphylococcus aureus
and enterococci. Major difficulties are encountered with nonsurgical treatment due to biofilm development in the shunt tubing and inability to achieve sufficiently high CSF drug levels by intravenous administration. Recently, three cases of
S. epidermidis
CSF shunt infection have been treated by intravenous linezolid without surgical shunt removal, and we therefore investigated vancomycin and linezolid against biofilms of these bacteria
in vitro
. A continuous-perfusion model of shunt catheter biofilms was used to establish mature (1-week) biofilms of
Staphylococcus aureus
,
Staphylococcus epidermidis
(both methicillin resistant [MRSA and MRSE]),
Enterococcus faecalis
, and
Enterococcus faecium
. They were then “treated” with either vancomycin or linezolid in concentrations achievable in CSF for 14 days. The biofilms were then monitored for 1 week for eradication and for regrowth. Enterococcal biofilms were not eradicated by either vancomycin or linezolid. Staphylococcal biofilms were eradicated by both antibiotics after 2 days and did not regrow. No resistance was seen. Linezolid at concentrations achievable by intravenous or oral administration was able to eradicate biofilms of both
S. epidermidis
(MRSE) and
S. aureus
(MRSA). Neither vancomycin at concentrations achievable by intrathecal administration nor linezolid was able to eradicate enterococcal biofilms. It is hoped that these
in vitro
results will stimulate further clinical trials with linezolid, avoiding surgical shunt removal.
Toll-Like Receptor 2 Ligand Pretreatment Attenuates Retinal Microglial Inflammatory Response but Enhances Phagocytic Activity toward Staphylococcus aureus
Authors: Kochan Travis , Singla Anuj , Tosi Joaquin , Kumar Ashok 
Published: March 2012

ABSTRACTStaphylococcus aureusis a leading cause of severe endophthalmitis, which often results in vision loss in some patients. Previously, we showed that Toll-like receptor 2 (TLR2) ligand pretreatment prevented the development of staphylococcal endophthalmitis in mice and suggested that microglia might be involved in this protective effect (Kumar A, Singh CN, Glybina IV, Mahmoud TH, Yu FS. J. Infect. Dis. 201:255–263, 2010). The aim of the present study was to understand how microglial innate response is modulated by TLR2 ligand pretreatment. Here, we demonstrate thatS. aureusinfection increased the CD11b+CD45+microglial/macrophage population in the C57BL/6 mouse retina. Using cultured primary retinal microglia and a murine microglial cell line (BV-2), we found that these cells express TLR2 and that its expression is increased upon stimulation with bacteria or an exclusive TLR2 ligand, Pam3Cys. Furthermore, challenge of primary retinal microglia withS. aureusand its cell wall components peptidoglycan (PGN) and lipoteichoic acid (LTA) induced the secretion of proinflammatory mediators (tumor necrosis factor alpha [TNF-α] and MIP-2). This innate response was attenuated by a function-blocking anti-TLR2 antibody or by small interfering RNA (siRNA) knockdown of TLR2. In order to assess the modulation of the innate response, microglia were pretreated with a low dose (0.1 or 1 μg/ml) of Pam3Cys and then challenged with liveS. aureus. Our data showed thatS. aureus-induced production of proinflammatory mediators is dramatically reduced in pretreated microglia. Importantly, microglia pretreated with the TLR2 agonist phagocytosed significantly more bacteria than unstimulated cells. Together, our data suggest that TLR2 plays an important role in retinal microglial innate response toS. aureus, and its sensitization inhibits inflammatory response while enhancing phagocytic activity.
Extrahepatic Exoerythrocytic Forms of Rodent Malaria Parasites at the Site of Inoculation: Clearance after Immunization, Susceptibility to Primaquine, and Contribution to Blood-Stage Infection
Authors: Voza Tatiana , Miller Jessica L. , Kappe Stefan H. I. , Sinnis Photini 
Published: March 2012

ABSTRACT

Plasmodium
sporozoites are inoculated into the skin of the mammalian host as infected mosquitoes probe for blood. A proportion of the inoculum enters the bloodstream and goes to the liver, where the sporozoites invade hepatocytes and develop into the next life cycle stage, the exoerythrocytic, or liver, stage. Here, we show that a small fraction of the inoculum remains in the skin and begins to develop into exoerythrocytic forms that can persist for days. Skin exoerythrocytic forms were observed for both
Plasmodium berghei
and
Plasmodium yoelii
, two different rodent malaria parasites, suggesting that development in the skin of the mammalian host may be a common property of plasmodia. Our studies demonstrate that skin exoerythrocytic stages are susceptible to destruction in immunized mice, suggesting that their aberrant location does not protect them from the host's adaptive immune response. However, in contrast to their hepatic counterparts, they are not susceptible to primaquine. We took advantage of their resistance to primaquine to test whether they could initiate a blood-stage infection directly from the inoculation site, and our data indicate that these stages are not able to initiate malaria infection.
Systematic variations in basement morphology and rifting geometry along the Nova Scotia and Morocco conjugate margins
Authors: Louden Keith , Wu Yue , Tari Gabor 
Published: March 2012

Abstract
The Nova Scotia and Morocco margins formed within a transition between volcanic margins to the south and non-volcanic margins to the north. We present deep seismic profiles to document the nature of this transition. Profiles on the Nova Scotia margin show two major transitions. The first transition represents a sharp reduction in syn-rift volcanism coincident with major changes in the East Coast Magnetic Anomaly and with the southern limit of the Slope Diapiric Province. The second transition represents a further restriction in syn- and post-rift volcanism leading to exposure of serpentinized mantle or the creation of highly tectonized oceanic crust. This transition is marked by highly extended and faulted continental crustal blocks. Revised plate reconstructions show similar transitions along the Moroccan margin. The southern transition occurs at a major change in the West Africa Coast Magnetic Anomaly and the southern limit of the Morocco Salt Basin. The second transition occurs at a major basement high (Tafelney Plateau), which is considered a high relief accommodation zone and contains highly extended faulted crustal blocks similar to those in a conjugate position off central Nova Scotia. This transition marks a major change in rifting asymmetry and separates the margins into two fundamentally distinct segments.
Firewall policy change-impact analysis
Authors: Liu Alex X. 
Published: March 2012

Firewalls are the cornerstones of the security infrastructure for most enterprises. They have been widely deployed for protecting private networks. The quality of the protection provided by a firewall directly depends on the quality of its policy (i.e., configuration). Due to the lack of tools for analyzing firewall policies, many firewalls used today have policy errors. A firewall policy error either creates security holes that will allow malicious traffic to sneak into a private network or blocks legitimate traffic and disrupts normal business processes, which in turn could lead to irreparable, if not tragic, consequences. A major cause of policy errors are policy changes. Firewall policies often need to be changed as networks evolve and new threats emerge. Users behind a firewall often request the firewall administrator to modify rules to allow or protect the operation of some services.
In this article, we first present the theory and algorithms for firewall policy change-impact analysis. Our algorithms take as input a firewall policy and a proposed change, then output the accurate impact of the change. Thus, a firewall administrator can verify a proposed change before committing it. We implemented our firewall change-impact analysis algorithms, and tested them on both real-life and synthetic firewall policies. The experimental results show that our algorithms are effective in terms of ensuring firewall policy correctness and efficient in terms of computing the impact of policy changes. Thus, our tool can be practically used in the iterative process of firewall policy design and maintenance. Although the focus of this article is on firewalls, the change-impact analysis algorithms proposed in this article are not limited to firewalls. Rather, they can be applied to other rule-based systems, such as router access control lists (ACLs), as well.