bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blockade of CD137 Signaling Counteracts Polymicrobial Sepsis Induced by Cecal Ligation and Puncture
Authors: Nguyen Quang-Tam , Ju Seong-A , Park Sang-Min , Lee Sang-Chul , Yagita Hideo , Lee In Hee , Kim Byung-Sam 
Published: June 2009

ABSTRACTSepsis, a leading cause of death worldwide, involves proinflammatory responses and inefficient bacterial clearance. Previously, we have shown that CD137 (4-1BB), a member of the tumor necrosis factor receptor superfamily, plays critical roles in eradicating infectiveListeria monocytogenes, a gram-positive bacterium, and that stimulation of CD137 protects mice from sepsis-induced death. In this study, we unexpectedly found that CD137 activation aggravated polymicrobial sepsis due to mixed gram-positive and gram-negative bacterial infection induced by cecal ligation and puncture (CLP). CD137-deficient (CD137−/−) mice showed significantly lower mortality than CD137-sufficient (CD137+/+) mice in the CLP model. Administration of an agonistic anti-CD137 monoclonal antibody (MAb) to CD137+/+mice decreased their survival in this infection model, while administration of a blocking anti-CD137 ligand MAb (TKS-1) to such mice increased their survival. CD137−/−mice and TKS-1-treated CD137+/+mice had lower levels of chemokines/proinflammatory cytokines (monocyte chemoattractant protein 1, interleukin-6 [IL-6], tumor necrosis factor alpha, IL-12) and an anti-inflammatory cytokine (IL-10), exhibited improved bacterial clearance in the peritoneum, liver, and blood, and had greater numbers of infiltrated peritoneal neutrophils and macrophages in the CLP model than control mice. Our data suggest that CD137 activation aggravates polymicrobial sepsis induced by CLP.
Bicarbonate InducesVibrio choleraeVirulence Gene Expression by Enhancing ToxT Activity
Authors: Abuaita Basel H. , Withey Jeffrey H. 
Published: June 2009

ABSTRACTVibrio choleraeis a gram-negative bacterium that is the causative agent of cholera, a severe diarrheal illness. The two biotypes ofV. choleraeO1 capable of causing cholera, classical and El Tor, require different in vitro growth conditions for induction of virulence gene expression. Growth under the inducing conditions or infection of a host initiates a complex regulatory cascade that results in production of ToxT, a regulatory protein that directly activates transcription of the genes encoding cholera toxin (CT), toxin-coregulated pilus (TCP), and other virulence genes. Previous studies have shown that sodium bicarbonate induces CT expression in theV. choleraeEl Tor biotype. However, the mechanism for bicarbonate-mediated CT induction has not been defined. In this study, we demonstrate that bicarbonate stimulates virulence gene expression by enhancing ToxT activity. Both the classical and El Tor biotypes produce inactive ToxT protein when they are cultured statically in the absence of bicarbonate. Addition of bicarbonate to the culture medium does not affect ToxT production but causes a significant increase in CT and TCP expression in both biotypes. Ethoxyzolamide, a potent carbonic anhydrase inhibitor, inhibits bicarbonate-mediated virulence induction, suggesting that conversion of CO2into bicarbonate by carbonic anhydrase plays a role in virulence induction. Thus, bicarbonate is the first positive effector for ToxT activity to be identified. Given that bicarbonate is present at high concentration in the upper small intestine whereV. choleraecolonizes, bicarbonate is likely an important chemical stimulus thatV. choleraesenses and that induces virulence during the natural course of infection.
Transcription Factor PrtT Controls Expression of Multiple Secreted Proteases in the Human Pathogenic Mold
Aspergillus fumigatus
Authors: Sharon Haim , Hagag Shelly , Osherov Nir 
Published: June 2009

ABSTRACT

The role of secreted proteases in the virulence of the pathogenic fungus
Aspergillus fumigatus
remains controversial. Recently, the
Aspergillus niger
transcription factor PrtT was shown to control the expression of multiple secreted proteases. In this work, the gene which encodes the PrtT homolog in
A. fumigatus
was cloned and its function analyzed using a deletion mutant strain. Deletion of
A. fumigatus prtT
resulted in the loss of secreted protease activity. The expression of six secreted proteases (ALP, MEP, Dpp4, CpdS, AFUA_2G17330, and AFUA_7G06220) was markedly reduced. Culture filtrates from the
prtT
deletion strain exhibited reduced killing of lung epithelial cells and lysis of erythrocytes. However, the
prtT
deletion strain did not exhibit altered virulence in lung-infected mice. These results suggest that PrtT is not a significant virulence factor in
A. fumigatus
.
Macrophage-Mediated Responses toCandida albicansin Mice Expressing the Human Immunodeficiency Virus Type 1 Transgene
Authors: Goupil Mathieu , Trudelle Émilie Bélanger , Dugas Véronique , Racicot-Bergeron Catherine , Aumont Francine , Sénéchal Serge , Hanna Zaher , Jolicoeur Paul , de Repentigny Louis 
Published: June 2009

ABSTRACTThe critical impairments of innate and adaptive immunity that cause susceptibility to mucosal candidiasis in human immunodeficiency virus (HIV) infection have not been fully determined. We therefore conducted an analysis of macrophage-mediated responses toCandida albicansin transgenic (Tg) mice expressing Nef, Env, and Rev of HIV type 1 (HIV-1) in CD4+T cells, dendritic cells, and macrophages and developing an AIDS-like disease (CD4C/HIVMutATg mice). Macrophages were successfully recruited to the oral and gastric mucosae of these Tg mice in response to chronic carriage ofC. albicansand displayed polarization toward an alternatively activated phenotype. Functionally, peritoneal macrophages from uninfected Tg mice exhibited increased phagocytosis ofC. albicansand enhanced production of interleukin 6 and monocyte chemoattractant protein 1, demonstrating that the HIV-1 transgene independently activates selected macrophage functions. Production of H2O2by macrophages from Tg mice primed with gamma interferon and treated with phorbol 12-myristate 13-acetate orC. albicanswas moderately reduced, but expression of the HIV-1 transgene did not alter production of nitric oxide or reduce killing ofC. albicans. A knockout of the inducible nitric oxide synthase (NOS2) gene in these Tg mice did not augment oral or gastrointestinal burdens during chronic carriage ofC. albicansor cause systemic dissemination, likely due to a redundancy provided by partially preserved production of H2O2and oxygen-independent candidacidal mechanisms. Thus, the macrophage response toC. albicansis largely preserved in these Tg mice, and no functional macrophage defect appears to primarily determine the susceptibility to mucosal candidiasis.
Protection against Intestinal Amebiasis by a Recombinant Vaccine Is Transferable by T Cells and Mediated by Gamma Interferon
Authors: Guo Xiaoti , Barroso Lisa , Becker Steven M. , Lyerly David M. , Vedvick Thomas S. , Reed Steven G. , Petri William A. , Houpt Eric R. 
Published: June 2009

ABSTRACTWe have previously shown that vaccination with purifiedEntamoeba histolyticaGal/GalNAc lectin or recombinant subunits can protect mice from intestinal amebiasis upon intracecal challenge. In this study, we demonstrated with adoptive-transfer experiments that this lectin vaccine protection is mediated by T cells but not serum. The cell-mediated immune (CMI) response was characterized by significant gamma interferon (IFN-γ), interleukin 12 (IL-12), IL-2, IL-10, and IL-17 production. To move toward a human vaccine, we switched to a recombinant protein and tested a range of adjuvants and routes appropriate for humans. We found that subcutaneous delivery of LecA with IDRI's adjuvant system EM014 elicited a potent Th1-type CMI profile and provided significant protection, as measured by culture negativity (79% efficacy); intranasal immunization with cholera toxin provided 56% efficacy; and alum induced a Th2-type response that protected 62 to 68% of mice. Several antibody and CMI cytokine responses were examined for correlates of protection, and prechallenge IFN-γ+or IFN-γ-, IL-2-, and tumor necrosis factor alpha-triple-positive CD4 cells in blood were statistically associated with protection. To test the role of IFN-γ in LecA-mediated protection, we neutralized IFN-γ in LecA-immunized mice and found that it abrogated the protection conferred by vaccination. These data demonstrate that CMI is sufficient for vaccine protection from intestinal amebiasis and reveal an important role for IFN-γ, even in the setting of alum.
Antibiotic Treatment of
Clostridium difficile
Carrier Mice Triggers a Supershedder State, Spore-Mediated Transmission, and Severe Disease in Immunocompromised Hosts
Authors: Lawley Trevor D. , Clare Simon , Walker Alan W. , Goulding David , Stabler Richard A. , Croucher Nicholas , Mastroeni Piero , Scott Paul , Raisen Claire , Mottram Lynda , Fairweather Neil F. , Wren Brendan W. , Parkhill Julian , Dougan Gordon 
Published: June 2009

ABSTRACT

Clostridium difficile
persists in hospitals by exploiting an infection cycle that is dependent on humans shedding highly resistant and infectious spores. Here we show that human virulent
C. difficile
can asymptomatically colonize the intestines of immunocompetent mice, establishing a carrier state that persists for many months.
C. difficile
carrier mice consistently shed low levels of spores but, surprisingly, do not transmit infection to cohabiting mice. However, antibiotic treatment of carriers triggers a highly contagious supershedder state, characterized by a dramatic reduction in the intestinal microbiota species diversity,
C. difficile
overgrowth, and excretion of high levels of spores. Stopping antibiotic treatment normally leads to recovery of the intestinal microbiota species diversity and suppresses
C. difficile
levels, although some mice persist in the supershedding state for extended periods. Spore-mediated transmission to immunocompetent mice treated with antibiotics results in self-limiting mucosal inflammation of the large intestine. In contrast, transmission to mice whose innate immune responses are compromised (Myd88
−/−
) leads to a severe intestinal disease that is often fatal. Thus, mice can be used to investigate distinct stages of the
C. difficile
infection cycle and can serve as a valuable surrogate for studying the spore-mediated transmission and interactions between
C. difficile
and the host and its microbiota, and the results obtained should guide infection control measures.
Landslide mapping in Seattle, Washington
Authors: Laprade William T. , Tubbs Donald W. 
Published: June 2009

Abstract
Seattle, Washington, has one of the most progressive landslide ordinances and mitigation programs in the United States. The necessity for this is driven by concentrated winter precipitation, steep slopes, and glacial soils that are susceptible to instability. Early in the European development, engineers recognized the vulnerability of Seattle hillsides to landslides, particularly when the hillsides were disturbed. In this paper, we trace the history of mapping of landslide-prone ground in Seattle, started by Miller (1973), detailed by Tubbs (1974, 1975), and most recently catalogued by Shannon & Wilson (2000, 2003).
Owing to the relative homogeneity of geology (glacial and other Pleistocene nonglacial soils), landsliding consists mainly of debris landslides, debris avalanches, and slumps. Debris avalanches that engage the shallow colluvial soils are by far the most common. Deep-seated slumps are not as common but can encompass a large area and affect many property owners. Several studies agree that ~80% of the landslides include one or more human influences.
To limit the amount of damage that landslides cause to private properties and City of Seattle infrastructure, rules were promulgated by the city in 1984. These rules have been revised three times, and they now serve as an example for the rest of the state of Washington. Following destructive, widespread slope instability in 1997 and the Shannon & Wilson studies in 2000 and 2003, Seattle Public Utilities instituted a state-of-the-industry landslide mitigation program that has already paid dividends for the city.
Numerical modeling of rainfall thresholds for shallow landsliding in the Seattle, Washington, area
Authors: Godt Jonathan W. , McKenna Jonathan P. 
Published: June 2009

Abstract
The temporal forecasting of landslide hazard has typically relied on empirical relations between rainfall characteristics and landslide occurrence to identify conditions that may cause shallow landslides. Here, we describe an alternate, deterministic approach to define rainfall thresholds for landslide occurrence in the Seattle, Washington, area. This approach combines an infinite slope-stability model with a variably saturated flow model to determine the rainfall intensity and duration that leads to shallow failure of hillside colluvium. We examine the influence of variation in particle-size distribution on the unsaturated hydraulic properties of the colluvium by performing capillary-rise tests on glacial outwash sand and three experimental soils with increasing amounts of fine-grained material. Observations of pore-water response to rainfall collected as part of a program to monitor the near-surface hydrology of steep coastal bluffs along Puget Sound were used to test the numerical model results and in an inverse modeling procedure to determine the in situ hydraulic properties. Modeling results are given in terms of a destabilizing rainfall intensity and duration, and comparisons with empirical observations of landslide occurrence and triggering rainfall indicate that the modeling approach may be useful for forecasting landslide occurrence.
Modeling rainfall Conditions for Shallow landsliding in Seattle, Washington
Authors: Godt Jonathan W. , Schulz William H. , Baum Rex L. , Savage William Z. 
Published: June 2009

Abstract
We describe the results from an application of a distributed, transient infiltration–slope-stability model for an 18 km2 area of southwestern Seattle, Washington, USA. The model (TRIGRS) combines an infinite slope-stability calculation and an analytic, one-dimensional solution for pore-pressure diffusion in a soil layer of finite depth in response to time-varying rainfall. The transient solution for pore-pressure response can be superposed on any steady-state groundwater-flow field that is consistent with model assumptions. Applied over digital topography, the model computes a factor of safety for each grid cell at any time during a rainstorm. Input variables may vary from cell to cell, and the rainfall rate can vary in both space and time. For Seattle, topographic slope derived from an airborne laser swath mapping (ALSM)–based 3 m digital elevation model (DEM), maps of soil and water-table depths derived from geotechnical borings, and hourly rainfall intensities were used as model inputs. Material strength and hydraulic properties used in the model were determined from field and laboratory measurements, and a tension-saturated initial condition was assumed. Results are given in terms of a destabilizing intensity and duration of rainfall, and they were evaluated by comparing the locations of 212 historical landslides with the area mapped as potentially unstable. Because the equations of groundwater flow are explicitly solved with respect to time, the results from TRIGRS simulations can be portrayed quantitatively to assess the potential landslide hazard based on rainfall conditions.
Peat flow in Mercer Slough, Lake Washington
Authors: Badger Thomas C. 
Published: June 2009

Abstract
Over the past four decades, ongoing deformation of an 18-m-thick peat deposit within the flat-lying Mercer Slough has resulted in damaging deflections, and near-collapse in three cases, of pile-supported Interstate 90 bridges and a major water line on the east side of the slough. The peat is partially underlain by a dense sand unit, which includes a highly pressurized aquifer that produces artesian flow 1–2.5 m above the ground surface. Inclinometers on the east side of the slough show the peat flowing toward the structures and then apparently directed west along the interstate centerline. Large displacements recorded in several inclinometers near the center of the slough suggest a length of deforming peat that approaches 600 m, which is likely initiating retrogressively. Potential causal mechanisms include poor engineering characteristics of the peat, presence of high hydrostatic pressure transmitted within and beneath the peat, seasonal water-level variations of Lake Washington and induced hydraulic gradients within the peat, dredging of the Mercer Slough channel, puncturing of the underlying aquifer by numerous pile foundations, and fill placement along the eastern margin of the slough. The peat is flowing around the pile/shaft foundations; however, excessive lateral loads are still being applied to the foundations in a poorly understood and unpredictable manner. The most severe deflections have occurred in the outermost structures where the peat is primarily flowing transverse to the structures.
The Ross Point landslide
Authors: Moses Lynn J. 
Published: June 2009

Abstract
In September 1998, a geotechnical investigation was initiated by the Washington State Department of Transportation (WSDOT) to assess stability of a slope in the vicinity of Ross Point, located along the State Route 166 (SR 166) corridor. The roadway lies at the base of a marine bluff composed of Pleistocene glacial and interglacial deposits, and it has a history of roadway closures associated with landslides and embankment failures. As part of the investigation, geotechnical test borings were drilled to define subsurface conditions, and inclinometer casing and open-standpipe piezometers were installed to monitor slope movement and groundwater levels. All drilling was completed and inclinometer and piezometer installations initialized by 30 December 1998.
The Ross Point landslide occurred on 29 January 1999. This landslide is unique in that the subsurface conditions had been thoroughly characterized in a geotechnical investigation prior to failure, and rainfall and groundwater levels were being frequently monitored at the time of the failure. Although slope failures are common in the landslide sequence of Esperance Sand overlying Lawton Clay, monitoring of rainfall and groundwater levels prior to and during landslide failure is unique. The groundwater levels monitored within the Ross Point landslide mass showed a rapid response to intense rainfall events, whereas the groundwater response measured in boreholes located outside of the failure was subdued. Excessive pore-water pressures rapidly developed within the landslide mass following significant rainfall events. This rapid increase in pore-water pressure, coupled with high antecedent groundwater levels, is considered to be the critical factor in triggering the Ross Point landslide. Wood sampled from the lowest nonglacial sediments exposed at Ross Point yielded a 14C date of 40,570 ± 700 yr B.P. and are considered to be the Olympia beds.
HIV testing of junior doctors: exploring their experiences, perspectives and accounts: Table 1
Authors: Salkeld L R , McGeehan S J , Chaudhuri E , Kerslake I M 
Published: June 2009

Objective:To explore the accounts and perspectives of junior doctors who were offered an HIV test by their employing National Health Service (NHS) trust and discuss ethical issues posed by this new policy.Design:Qualitative in-depth interview study.Setting:4 NHS hospital trusts.Participants:24 junior doctors who had been offered an HIV test as part of their pre-employment occupational health checks.Results:The manner in which HIV tests were offered to junior doctors varied both between and within the NHS trusts. Overall, the doctors were highly critical of the way the HIV test was offered. Recurrent themes surrounding a lack of discussion and information regarding the indications for the test and implications of a positive result influenced the the doctors’ perception of their experiences. As a consequence of the shortcomings of how the test was offered, most of the doctors held the misperception that HIV testing was mandatory and many felt unable to decline the test. The majority of doctors referred to patient protection as adequate justification for being offered an HIV test.Conclusions:Junior doctors offered an HIV test under new Department of Health occupational health guidance were disparaging about how the test was offered. The findings of this study affect thousands of junior doctors in the UK, and the impact of these results is extensive. Participants’ suggestions regarding how the process of offering an HIV test can be improved are discussed and ethical issues regarding the new Department of Health policy are highlighted.
Understanding respect: learning from patients
Authors: Dickert N W , Kass N E 
Published: June 2009

Background:The importance of respecting patients and participants in clinical research is widely recognised. However, what it means to respect persons beyond recognising them as autonomous is unclear, and little is known about what patients find to be respectful.Objective:To understand patients’ conceptions of respect and what it means to be respected by medical providers.Design:Qualitative study from an academic cardiology clinic, using semistructured interviews with 18 survivors of sudden cardiac death.Results:Patients believed that respecting persons incorporates the following major elements: empathy, care, autonomy, provision of information, recognition of individuality, dignity and attention to needs.Conclusions:Making patients feel respected, or valued as a person, is a multi-faceted task that involves more than recognising autonomy. While patients’ views of respect do not determine what respect means, these patients expressed important intuitions that may be of substantial conceptual relevance.
Vulnerability in palliative care research: findings from a qualitative study of black Caribbean and white British patients with advanced cancer: Table 1
Authors: Koffman J , Morgan M , Edmonds P , Speck P , Higginson I J 
Published: June 2009

Introduction:Vulnerability is a poorly understood concept in research ethics, often aligned to autonomy and consent. A recent addition to the literature represents a taxonomy of vulnerability developed by Kipnis, but this refers to the conduct of clinical trials rather than qualitative research, which may raise different issues.Aim:To examine issues of vulnerability in cancer and palliative care research obtained through qualitative interviews.Method:Secondary analysis of qualitative data from 26 black Caribbean and 19 white British patients with advanced cancer.Results:Four domains of vulnerability derived from Kipnis’s taxonomy were identified and included: (i) communicative vulnerability, represented by participants impaired in their ability to communicate because of distressing symptoms; (ii) institutional vulnerability, which referred to participants who existed under the authority of others—for example, in hospital; (iii) deferential vulnerability, which included participants who were subject to the informal authority or the independent interests of others; (iv) medical vulnerability, which referred to participants with distressing medical conditions; and (v) social vulnerability, which included participants considered to belong to an undervalued social group. Participants from both ethnic groups populated all these domains, but those who were black Caribbean were more present among the socially vulnerable.Conclusions:Current classifications of vulnerability require reinterpretation when applied to qualitative research at the end of life. We recommend that researchers and research ethics committees reconceptualise vulnerability using the domains identified in this study and consider the research context and interviewers’ skills.