bluuebunny/crossref_metadata_2025 huggingface dataset:
Anthrax Edema Toxin Impairs Clearance in Mice
Authors: Sastalla Inka , Tang Shixing , Crown Devorah , Liu Shihui , Eckhaus Michael A. , Hewlett Indira K. , Leppla Stephen H. , Moayeri Mahtab
Published: November 2011

The anthrax edema toxin (ET) of
Bacillus anthracis
is composed of the receptor-binding component protective antigen (PA) and of the adenylyl cyclase catalytic moiety, edema factor (EF). Uptake of ET into cells raises intracellular concentrations of the secondary messenger cyclic AMP, thereby impairing or activating host cell functions. We report here on a new consequence of ET action
in vivo
. We show that in mouse models of toxemia and infection, serum PA concentrations were significantly higher in the presence of enzymatically active EF. These higher concentrations were not caused by ET-induced inhibition of PA endocytosis; on the contrary, ET induced increased PA binding and uptake of the PA oligomer
in vitro
and
in vivo
through upregulation of the PA receptors TEM8 and CMG2 in both myeloid and nonmyeloid cells. ET effects on protein clearance from circulation appeared to be global and were not limited to PA. ET also impaired the clearance of ovalbumin, green fluorescent protein, and EF itself, as well as the small molecule biotin when these molecules were coinjected with the toxin. Effects on injected protein levels were not a result of general increase in protein concentrations due to fluid loss. Functional markers for liver and kidney were altered in response to ET. Concomitantly, ET caused phosphorylation and activation of the aquaporin-2 water channel present in the principal cells of the collecting ducts of the kidneys that are responsible for fluid homeostasis. Our data suggest that
in vivo
, ET alters circulatory protein and small molecule pharmacokinetics by an as-yet-undefined mechanism, thereby potentially allowing a prolonged circulation of anthrax virulence factors such as EF during infection.
Interim analyses from a randomised controlled trial to improve visual processing speed in older adults: the Iowa Healthy and Active Minds Study
Authors: Wolinsky Fredric D , Vander Weg Mark W , Howren M Bryant , Jones Michael P , Martin Rene , Luger Tana M , Duff Kevin , Dotson Megan M
Published: November 2011

Objectives

The Iowa Healthy and Active Minds Study is a four-arm randomised controlled trial of a visual processing speed training programme (Road Tour). This article presents the preplanned interim results immediately after training (6–8 weeks post-randomisation) for the primary outcome.

Design

Within two age strata (50–64 vs ≥65), 681 men and women attending general internal and family medicine clinics were randomised to four training groups: (1) supervised, on-site standard (10 h) dose of Road Tour training; (2) supervised, on-site standard dose of Road Tour training with 4 h of subsequent booster training scheduled to occur at 11 months post-randomisation (ie, no booster training had occurred at the time of this interim analysis); (3) supervised, on-site standard dose of attention control (crossword puzzles) training and (4) self-administered, at-home standard dose of Road Tour training. The primary outcome was the Useful Field of View (UFOV) test. Three intent-to-treat interim analyses were conducted, including (1) multiple linear regression models of composite UFOV scores using Blom rank transformations, (2) general linear mixed effects models and (3) multiple logistic regression models among the 620 participants (91%) with complete data.

Results

In the linear regression analyses of both age strata, random assignment to any Road Tour training group versus the attention control group was significant (p<0.001), with an effect size of −0.558 (adjusted for the Blom rank transformed UFOV score at randomisation). Similar results were obtained for each Road Tour group and within each age stratum and from the general linear and logistic regression models.

Conclusions

Assignment to a standard dose of Road Tour training yielded medium-sized post-training improvements in visual processing speed. Road Tour was equally effective whether administered under laboratory supervision or self-administered in the patient's home and for participants in both age strata (50–64 vs ≥65).

Clinical trial registration number

NCT01165463.
The future role of rectal and vaginal microbicides to prevent HIV infection in heterosexual populations: implications for product development and prevention
Authors: Boily Marie-Claude , Dimitrov Dobromir , Abdool Karim Salim S , Mâsse Benoît
Published: November 2011

Objectives

To compare the potential impact of rectal (RMB), vaginal (VMB) and bi-compartment (RVMB) (applied vaginally and protective during vaginal and anal intercourse) microbicides to prevent HIV in various heterosexual populations. To understand when a RMB is as useful than a VMB for women practicing anal intercourse (AI).

Methods

Mathematical model was used to assess the population-level impact (cumulative fraction of new HIV infections prevented (CFP)) of the three different microbicides in various intervention scenarios and prevalence settings. We derived the break-even RMB efficacy required to reduce a female's cumulative risk of HIV infection by the same amount than a VMB.

Results

Under optimistic coverage (fast roll-out, 100% uptake), a 50% efficacious VMB used in 75% of sex acts in population without AI may prevent ∼33% (27, 42%) new total (men and women combined) HIV infections over 25 years. The 25-year CFP reduces to ∼25% (20, 32%) and 17% (13, 23%) if uptake decreases to 75% and 50%, respectively. Similar loss of impact (by 25%–50%) is observed if the same VMB is introduced in populations with 5%–10% AI and for RRRAI=4–20. A RMB is as useful as a VMB (ie, break-even) in populations with 5% AI if RRRAI=20 and in populations with 15%–20% AI if RRRAI=4, independently of adherence as long as it is the same with both products. The 10-year CFP with a RVMB is twofold larger than for a VMB or RMB when AI=10% and RRRAI=10.

Conclusions

Even low AI frequency can compromise the impact of VMB interventions. RMB and RVMB will be important prevention tools for heterosexual populations.
A METHOD FOR DISCOVERING COMMON PATTERNS FROM TWO RNA SECONDARY STRUCTURES AND ITS APPLICATION TO STRUCTURAL REPEAT DETECTION
Authors: HUA LEI , WANG JASON T. L. , JI XIANG , MALHOTRA ANKUR , KHALADKAR MUGDHA , SHAPIRO BRUCE A. , ZHANG KAIZHONG
Published: November 2011

We propose an ab initio method, named DiscoverR, for finding common patterns from two RNA secondary structures. The method works by representing RNA secondary structures as ordered labeled trees and performs tree pattern discovery using an efficient dynamic programming algorithm. DiscoverR is able to identify and extract the largest common substructures from two RNA molecules having different sizes without prior knowledge of the locations and topologies of these substructures. We also extend DiscoverR to find repeated regions in an RNA secondary structure, and apply this extended method to detect structural repeats in the 3′-untranslated region of a protein kinase gene. We describe the biological significance of a repeated hairpin found by our method, demonstrating the usefulness of the method. DiscoverR is implemented in Java; a jar file including the source code of the program is available for download at http://bioinformatics.njit.edu/DiscoverR.
COMPUTATIONAL FLUID DYNAMIC ANALYSIS OF A CELL-BASED MICROFLUIDIC DRUG SCREENING PLATFORM
Authors: MAGUIRE T. , USTA O. B. , YARMUSH M. L.
Published: November 2011

About 50% of all candidate drugs that make it past Phase-I clinical trials ultimately fail to receive U.S. Food and Drug Administration (FDA) marketing approval due to human toxicity or bioavailability problems that the drug develops. To remedy this state of affairs, in recent years, researchers have attempted to develop improved in vitro assays which can be applied pre-clinically to produce data with a higher degree of correlation to in vivo responses, and which circumvent the allometric limitations inherent in animal models. Such in vitro assays are intended to enable preclinical research and development groups to better predict the pharmacokinetic and pharmacodynamic action of candidate molecules prior to clinical trials, thereby reducing high late-stage failure rates. While most such in vitro systems comprise a static cell culture environment, microfluidic systems have been shown to provide better results. For example, experiments performed with the HμREL®microfluidics system demonstrated increased clearance rates and better in vitro–in vivo correlation (IVIVC) than that observed with static culture systems. Several hypotheses were suggested to account for these improvements: (1) enhanced mass transport resulting in better functional efficiency; (2) a flow-induced transduction of gene and protein expression and function; and (3) a flow-induced effect resulting in increased cellular uptake. In this paper, we describe a framework, utilizing computational fluid dynamics (CFD), that can be used to study culture systems with a level of scrutiny and spatial precision not offered using standard in vitro assays. Using this approach, we were able to successfully model experimental observations of increases in the clearance rates of high and medium clearance compounds in the microfluidics system. Based on these results we posit that the increase in clearance is most likely due to the addition of convective transport, and a thinning of the boundary layer present in static and mixed plate cultures systems.
STUDY OF NANOPOROUS MEMBRANES WITH APPLICATIONS IN THE ENHANCED DETECTION OF CADIOVASCULAR BIOMARKER PROTEINS
Authors: VATTIPALLI KRISHNA , FEIKERT PAIGE , BRANDIGAMPALA SAVINDRA , PRASAD SHALINI
Published: November 2011

The goal of this work is to understand the role of nanoconfinement in designing molecular biosensors. We have been investigating microdevices incorporated with nanoporous membranes as molecular biosensor platforms. Detection of ultra low concentration of biomolecules is the key expectation from the new class of molecular biosensors utilizing nanomaterial. In this paper we have evaluated the role of the physical attributes of nanoporous aluminum oxide membranes in nanoconfinement and enhancing sensitivity of detection of protein biomolecules. In this biosensor configuration we have generated a sandwich assay in a high density array of nanoscale confined spaces generated by overlaying the nanoporous alumina membrane over metallic microscale sensing sites. The binding of the biomolecules results in the perturbation of the electrical double layer due to the binding of the test protein (C-reactive protein). Using electrical impedance spectroscopy (EIS), the capacitance changes in the electrical double layer associated with specific protein binding has been evaluated. The sensor performance metrics of sensitivity and dynamic range have been analyzed with changes in the pore diameter.
ANALYTIC PROPERTIES OF MULTI-PARTON POLE MATRIX ELEMENTS AND UNIVERSALITY OF FRAGMENTATION FUNCTIONS
Authors: GAMBERG LEONARD , MUKHERJEE ASMITA , MULDERS P. J.
Published: November 2011

Gluonic pole matrix elements explain the appearance of single spin asymmetries (SSA) in high-energy scattering processes. They involve a combination of operators which are odd under time reversal (T-odd). Such matrix elements appear in principle both for parton distribution functions and parton fragmentation functions. We show that for parton fragmentation functions these gluonic pole matrix elements vanish as a consequence of the analytic structure of scattering amplitudes in Quantum Chromodynamics. We extend this analysis to the case of multi-partonic pole matrix elements. This result is important in the study of the universality of transverse momentum dependent (TMD) fragmentation functions.
USES OF Q2 EVOLUTION IN GPD PHENOMENOLOGY
Authors: MUELLER DIETER
Published: November 2011

We shortly review the status of perturbative corrections to hard exclusive processes, which were partially obtained by utilizing conformal symmetry. We outline the conformal partial wave expansion of generalized parton distributions (GPDs) and hard exclusive amplitudes, which can be used for a model dependent extraction of the two-dimensional momentum fraction shape of GPDs by means of evolution. We exemplify this method and point out it importance for the description of collider data in the small x Bj region.
Obstetric Thromboprophylaxis: The Swedish Guidelines
Authors: Lindqvist Pelle G. , Hellgren Margareta
Published: November 2011

Obstetric thromboprophylaxis is difficult. Since 10 years Swedish obstetricians have used a combined risk estimation model and recommendations concerning to whom, at what dose, when, and for how long thromboprophylaxis is to be administrated based on a weighted risk score. In this paper we describe the background and validation of the Swedish guidelines for obstetric thromboprophylaxis in women with moderate-high risk of VTE, that is, at similar or higher risk as the antepartum risk among women with history of thrombosis. The risk score is based on major risk factors (i.e., 5-fold increased risk of thromboembolism). We present data on the efficacy of the model, the cost-effectiveness, and the lifestyle advice that is given. We believe that the Swedish guidelines for obstetric thromboprophylaxis aid clinicians in providing women at increased risk of VTE with effective and appropriate thromboprophylaxis, thus avoiding both over- and under-treatment.
Coupling the BEM/TBEM and the MFS for the Numerical Simulation of Wave Propagation in Heterogeneous Fluid‐Solid Media
Authors: Tadeu António , Castro Igor
Published: November 2011

This paper simulates wave propagation in an elastic medium containing elastic, fluid, rigid, and empty heterogeneities, which may be thin. It uses a coupling formulation between the boundary element method (BEM)/the traction boundary element method (TBEM) and the method of fundamental solutions (MFS). The full domain is divided into subdomains, which are handled separately by the BEM/TBEM or the MFS, to overcome the specific limitations of each of these methods. The coupling is enforced by applying the prescribed boundary conditions at all medium interfaces. The accuracy, efficiency, and stability of the proposed algorithms are verified by comparing the results with reference solutions. The paper illustrates the computational efficiency of the proposed coupling formulation by computing the CPU time and the error. The transient analysis of wave propagation in the presence of a borehole driven in a cracked medium is used to illustrate the potential of the proposed coupling formulation.
Adrenal Failure due to Adrenal Metastasis of Lung Cancer: A Case Report
Authors: Faulhaber Gustavo Adolpho Moreira , Borges Flavia Kessler , Ascoli Aline Maria , Seligman Renato , Furlanetto Tania Weber
Published: November 2011

We report a case of a patient with adrenal failure due to bilateral adrenal metastasis of lung cancer. This is a rare presentation of lung cancer. We review the differential diagnosis of weight loss and how to make diagnosis of adrenal insufficiency.
Sample‐Path Large Deviations in Credit Risk
Authors: Leijdekker V. J. G. , Mandjes M. R. H. , Spreij P. J. C.
Published: November 2011

The event of large losses plays an important role in credit risk. As these large losses are
typically rare, and portfolios usually consist of a large number of positions, large deviation theory is
the natural tool to analyze the tail asymptotics of the probabilities involved. We first derive a sample‐path
large deviation principle (LDP) for the portfolio′s loss process, which enables the computation
of the logarithmic decay rate of the probabilities of interest. In addition, we derive exact asymptotic
results for a number of specific rare‐event probabilities, such as the probability of the loss process
exceeding some given function.
A Recent Development of Computer Methods for Solving Singularly Perturbed Boundary Value Problems
Authors: Kumar Manoj , Parul
Published: November 2011

This paper contains a surprisingly large amount of material and indeed can serve as an introduction to some of ideas and methods of singular perturbation theory. The work done in this area during the periods 1984–2000 and 2000–2005 has already been surveyed in 2002 and 2007 but our main objective is to produce a collection of important research articles of physical significance. In this paper, the crux of research articles published by numerous researchers during 2006–2010 in referred journals has been presented, and this leads to conclusions and recommendations about what methods to use on singular perturbation problems.
Adolescent Offending and the Segregation of Poverty in Urban Neighbourhoods and Schools: An Assessment of Contextual Effects from the Standpoint of Situational Action Theory
Authors: Pauwels Lieven
Published: November 2011

Contextual research on adolescent offending is primarily based on the idea that residential areas provide a major ecological setting that (indirectly) shapes observed differences in adolescent offending. The social disorganisation/collective efficacy perspective has tried to explain why structural disadvantage of residential areas affects residents′ involvement in offending. On the other hand, contextual research has also been conducted within the school setting. This separate contextual approach is problematic as it does not reflect the reality of adolescents′ lives. Adolescents are exposed to different ecological settings. They are also exposed to many other settings that may provide opportunities to offend, as outlined in the situational action theory (SAT) of crime causation. This study contributes to the literature on the urban context of offending in three ways. First, the effects of adolescents′ residential neighbourhood and school context on adolescent offending are assessed simultaneously. Second, this study elaborates on SAT from a cross‐level point of view. Third, this contribution makes use of non‐hierarchical multilevel modelling, which is a statistically correct method of testing hypotheses that involve multiple contexts. Our study revealed the existence of small contextual effects of school‐level disadvantage, whereas the effect of neighbourhood‐level disadvantage is entirely due to neighbourhood composition.
An Efficient Data-Gathering Scheme for Heterogeneous Sensor Networks via Mobile Sinks
Authors: Lin Po-Liang , Ko Ren-Song
Published: November 2011

Typical Wireless Sensor Networks (WSNs) use static sinks to collect data from all sensor nodes via multihop forwarding. This results in the hot spot problem since the nodes close to the sink have a tendency to consume more energy in relaying data from other nodes. Many approaches using mobile sinks have been proposed to prevent this problem, but these approaches still suffer from the buffer overflow problem due to the limited memory capacity of the sensor nodes. This paper proposes an approach in which the mobile sink traverses a subset of nodes. Given the characteristics of wireless communication, such an approach can effectively alleviate the buffer overflow problem without incurring additional energy consumption. To further alleviate the buffer overflow problem, we propose the Allotment Mechanism which allows nodes with different data sampling rates to share their memory and, thus, extend the overflow deadline. Finally, the effectiveness of the proposed approach is verified via the GloMoSim network simulator. The results show that our approach incurs fewer buffer overflows than other data-gathering schemes.
Potentiometric Multisensory Systems with Novel Ion-Exchange Polymer-Based Sensors for Analysis of Drugs
Authors: Bobreshova Olga V. , Parshina Anna V. , Polumestnaya Ksenia A.
Published: November 2011

This paper examines potentiometric multisensory systems that consist of novel cross-sensitive PD-sensors (Potential Donnan-sensors). The analytical signal of PD-sensors is the Donnan potential at the ion-exchange polymer/electrolyte test solution interface. The use of novel sensors for the quantitative analysis of multicomponent aqueous solutions of amino acids, vitamins and medical substances is based on protolytic and ion-exchange reactions at the interfaces of ion-exchangers and test solutions. The potentiometric sensor arrays consist of PD-sensors and ion-selective electrodes. Such systems were developed for the multicomponent quantitative analysis of lysine monohydrochloride, thiamine chloride and novocaine hydrochloride solutions that contained salts of alkaline and alkaline-earth metals, as well as for mixed solutions of nicotinic acid and pyridoxine hydrochloride. Multivariate methods of analysis were used for sensor calibration and the analysis of the total response of sensor arrays. The errors of measurement of the electrolytes in aqueous solutions did not exceed 10%. The developed multisensory systems were used to determine the composition of a therapeutic “Mineral salt with low content of sodium chloride” and to determine concentrations of novocaine in sewage samples from a dental clinic.
The Role of Complement in the Development and Manifestation of Murine Atherogenic Inflammation: Novel Avenues
Authors: Francescut Lorenza , Steiner Tanja , Byrne Simon , Cianflone Katherine , Francis Sheila , Stover Cordula
Published: November 2011

Atherosclerosis is a chronic progressive inflammatory disease which manifests in the arterial vascular tree. It is a major cause of cardiovascular morbidity and contributes significantly to mortality in the developed world. Triggers for this inflammatory process are elevated levels of cholesterol, bacterial infection and obesity. The immune response in atherosclerosis is essentially pro-atherogenic, leading to lipid accumulation and cellular changes within the arterial wall. Small-animal models of atherosclerosis are used to study the relevance of candidate factors (cells, genes, diets) in the development and progression of lesions. From a multidisciplinary viewpoint, there are challenges and limitations to this approach. Activation of complement determines or modifies the outcome of acute and chronic inflammation. This review dissects the role of complement in the early development as well as the progressive manifestation of murine atherosclerosis and the advances in knowledge provided by the use of specific mouse models. It gives a critical overview of existing models, analyses seemingly conflicting results obtained with complement-deficient mouse models, highlights the importance of interrelationships between pro-coagulpant activity, adipose tissue, macrophages and complement, and uncovers exciting avenues of topical research.
Comorbidities Related to BMI Category in Children and Adolescents: German/Austrian/Swiss Obesity Register APV Compared to the German KiGGS Study
Authors: Flechtner-Mors Marion , Thamm Michael , Wiegand Susanna , Reinehr Thomas , Schwab Karl O. , Kiess Wieland , Widhalm Kurt , Holl Reinhard W. ,   for the APV initiative and the BMBF Competence Network Obesity
Published: November 2011

Purpose: To assess cardiovascular risk factors in overweight or obese children and adolescents in Germany, Austria and Switzerland and to investigate the relationship to BMI category. Methods: Data of 63,025 overweight or obese patients (APV population) were compared to normal-weight subjects from a representative study on health status of 14,298 children and adolescents in Germany (KiGGS survey). The weight status was assessed by BMI, and BMI-SDS values were cal-culated using national reference data. Results: In normal-weight KiGGS subjects, mean BMI was 17.3 ± 2.5 (BMI-SDS -0.1 ± 0.8). In the overweight or obese APV population, mean BMI was 30.2 ± 5.6 (BMI-SDS 2.5 ± 0.6). In normal-weight subjects blood pressure, total cholesterol, LDL-cholesterol, and triglycerides were elevated in 6.1, 8.6, 7.0 and 3.0%, respectively, and HDL-cholesterol was reduced in 3.0%, whereas in overweight/obese subjects the percentages of abnormal values were 35.3, 13.8, 14.5, 13.6, and 10.1%, respectively. Conclusions: Cardiovascular risk is increased in obese children and adolescents. There is a strong need to monitor blood pressure and serum lipids in this group of patients. Our results emphasize the importance of prevention of obesity in order to reduce cardiovascular risk.
Palliative Care Concepts in Respiratory Disease
Authors: Heigener D.F. , Rabe K.F.
Published: November 2011

Many respiratory diseases besides lung cancer are still not curable. There is an unmet need for palliative care, especially in non-malignant conditions. In this article we focus on symptomatic treatment of typical symptoms in respiratory disease beyond causal treatment.
Expression of Endoglin in Primary Endometrial Cancer
Authors: Zakrzewski Piotr K. , Cygankiewicz Adam I. , Mokrosiński Jacek , Nowacka-Zawisza Maria , Semczuk Andrzej , Rechberger Tomasz , Krajewska Wanda M.
Published: November 2011

Objective: Alterations in the transforming growth factor-β (TGF-β) signaling cascade are engaged in the development of human neoplasms through the deregulation of proliferation, differentiation and migration. However, in endometrial cancer, the role of endoglin, which acts as an accessory receptor in the TGF-β pathway, is still unknown. The aim of our study was the evaluation of endoglin mRNA and protein expression levels in endometrial cancer as compared to normal endometrium. TGF-β1 and TGF-β type II receptor were involved in the investigation since they directly cooperate with endoglin during signal propagation. Obtained results were correlated with clinicopathological parameters of studied material to determine endoglin contribution to tumor development and progression. Methods: mRNA level assessment was performed using real-time technique, whereas protein expression was determined by ELISA assay. Results: The endoglin mRNA level was not significantly altered in cancerous samples as compared to normal tissue, whereas its protein level demonstrated significant upregulation (p < 0.001) associated with increased tumor malignancy, assessed by histological grade and myometrium infiltration. Conclusions: An increase in endoglin protein expression level may interfere with the oncogenic potential of TGF-β1 and TGF-β type II receptor in endometrial cancer. Correlation of the endoglin level with pronounced cancer malignancy suggests that it may be regarded as a potential prognostic marker of primary endometrial cancer.
Searching for Copy Number Changes in Nonsyndromic X-Linked Intellectual Disability
Authors: Utine G.E. , Kiper P.Ö. , Alanay Y. , Haliloğlu G. , Aktaş D. , Boduroğlu K. , Tunçbilek E. , Alikaşifoğlu M.
Published: November 2011

Intellectual disability (ID) has a prevalence of 2–3% with 0.3% of the population being severely retarded. Etiology is heterogeneous, owing to numerous genetic and environmental factors. Underlying etiology remains undetermined in 75–80% of mildly disabled patients and 20–50% of those severely disabled. Twelve percent of all ID is thought to be X-linked (XLID). This study covers copy number analysis of some of the known XLID genes, using multiplex ligation-dependent probe amplification (MLPA) in 100 nonsyndromic patients. One of the patients was found to have duplication in all exons of MECP2 gene, and another had duplication in the fifth exon of TM4SF2/TSPAN7 gene. Affymetrix® 6.0 whole-genome SNP microarray confirmed the duplication in MECP2 and showed duplication of exons 2–7 in TM4SF2/TSPAN7, respectively. MECP2 duplication has recently been recognized as a syndromic cause of XLID in males, whereas duplications in TM4SF2/TSPAN7 are yet to be determined as a cause of XLID. Being an efficient, rapid, easy-to-perform, easy-to-interpret, and cost-effective method of copy number analysis of specific DNA sequences, MLPA presents wide clinical utility and may be included in diagnostic workup of ID, particularly when microarrays are unavailable as a first-line approach.
Matrix Metalloproteinase-10 Effectively Reduces Infarct Size in Experimental Stroke by Enhancing Fibrinolysis via a Thrombin-Activatable Fibrinolysis Inhibitor–Mediated Mechanism
Authors: Orbe J. , Barrenetxe J. , Rodriguez J.A. , Vivien D. , Orset C. , Parks W.C. , Birkland T.P. , Serrano R. , Purroy A. , Martinez de Lizarrondo S. , Angles-Cano E. , Páramo J.A.
Published: November 2011

Background—

The fibrinolytic and matrix metalloproteinase (MMP) systems cooperate in thrombus dissolution and extracellular matrix proteolysis. The plasminogen/plasmin system activates MMPs, and some MMPs have been involved in the dissolution of fibrin by targeting fibrin(ogen) directly or by collaborating with plasmin. MMP-10 has been implicated in inflammatory/thrombotic processes and vascular integrity, but whether MMP-10 could have a profibrinolytic effect and represent a promising thrombolytic agent is unknown.

Methods and Results—

The effect of MMP-10 on fibrinolysis was studied in vitro and in vivo, in MMP-10–null mice (
Mmp10
−/−
), with the use of 2 different murine models of arterial thrombosis: laser-induced carotid injury and ischemic stroke. In vitro, we showed that MMP-10 was capable of enhancing tissue plasminogen activator–induced fibrinolysis via a thrombin-activatable fibrinolysis inhibitor inactivation–mediated mechanism. In vivo, delayed fibrinolysis observed after photochemical carotid injury in
Mmp10
−/−
mice was reversed by active recombinant human MMP-10. In a thrombin-induced stroke model, the reperfusion and the infarct size in sham or tissue plasminogen activator–treated animals were severely impaired in
Mmp10
−/−
mice. In this model, administration of active MMP-10 to wild-type animals significantly reduced blood reperfusion time and infarct size to the same extent as tissue plasminogen activator and was associated with shorter bleeding time and no intracranial hemorrhage. This effect was not observed in thrombin-activatable fibrinolysis inhibitor–deficient mice, suggesting thrombin-activatable fibrinolysis inhibitor inactivation as one of the mechanisms involved in the MMP-10 profibrinolytic effect.

Conclusions—

A novel profibrinolytic role for MMP-10 in experimental ischemic stroke is described, opening new pathways for innovative fibrinolytic strategies in arterial thrombosis.
Angiotensin II–Induced Hypertension Is Modulated by Nuclear Factor-κB in the Paraventricular Nucleus
Authors: Cardinale Jeffrey P. , Sriramula Srinivas , Mariappan Nithya , Agarwal Deepmala , Francis Joseph
Published: November 2011

Hypertension is considered a low-grade inflammatory condition, and understanding the role of transcription factors in guiding this response is pertinent. A prominent transcription factor that governs inflammatory responses and has become a focal point in hypertensive research is nuclear factor-κB (NFκB). Within the hypothalamic paraventricular nucleus (PVN), a known brain cardioregulatory center, NFκB becomes potentially even more important in ultimately coordinating the systemic hypertensive response. To definitively demonstrate the role of NFκB in the neurogenic hypertensive response, we hypothesized that PVN NFκB blockade would attenuate angiotensin II–induced hypertension. Twelve-week–old male Sprague-Dawley rats were implanted with radiotelemetry probes for blood pressure measurement and allowed a 7-day recovery. After baseline blood pressure recordings, rats were administered either continuous NFκB decoy oligodeoxynucleotide infusion or microinjection of a serine mutated adenoviral inhibitory-κB vector, or their respective controls, bilaterally into the PVN to inhibit NFκB at two levels of its activation pathway. Simultaneously, rats were implanted subcutaneously with an angiotensin II or saline-filled 14-day osmotic minipump. After the 2-week treatments, rats were euthanized and brain tissues collected for PVN analysis. Bilaterally inhibited NFκB rats had a decrease in blood pressure, NFκB p65 subunit activity, proinflammatory cytokines, and reactive oxygen species, including the angiotensin II type 1 receptor, angiotensin-converting enzyme, tumor necrosis factor, and superoxide in angiotensin II–treated rats. Moreover, after NFκB blockade, key protective antihypertensive renin-angiotensin system components were upregulated. This demonstrates the important role that transcription factor NFκB plays within the PVN in modulating and perpetuating the hypertensive response via renin-angiotensin system modulation.
Myth and Misrepresentation in Australian Foreign Policy: Menzies and Engagement with Asia
Authors: Benvenuti Andrea , Jones David Martin
Published: November 2011

The prevailing orthodoxy in the academic literature devoted to the history of Australia's post-1945 international relations posits that a mixture of suspicion and condescension permeated the attitude of the governments headed by Robert Menzies (1949–1966) toward the Asia-Pacific region. Menzies's regional policies, according to this view, not only prevented Australia from engaging meaningfully with its Asian neighbors but also ended up antagonizing them. This article rejects the conventional view and instead shows that the prevailing left-Labor assessments of Menzies's regional policy are fundamentally marred by an anachronistic disregard of the diplomatic dynamics, political challenges, and economic realities of Cold War Asia.
Efficacy and Evidence: Evaluating U.S. Goals at the American National Exhibition in Moscow, 1959
Authors: Mickiewicz Ellen
Published: November 2011

The American National Exhibition in Moscow (ANEM) in 1959 during the administration of Dwight Eisenhower was intended to show the adversary “a corner of America” and the abundance and technological advances produced by the United States. Neither before nor since has a cultural-diplomatic initiative of similar scale, cost, and bureaucratic and international complexity been attempted. Some former U.S. officials maintain to this day that the success of the venture cannot be determined and that “the jury is still out.” This article not only contributes the assessment of a working participant at the ANEM throughout its duration but also draws on a wealth of archival materials. This analysis “from below” and simultaneously “from above” reveals new perspectives that challenge many of the conclusions drawn by diplomatic and cultural historians concerning the events in Moscow and their aftermath. The article offers a more nuanced and informed understanding of the most ambitious U.S. cultural-diplomatic self-portrayal.
Regression-Guided Clustering: A Semisupervised Method for Circulation-to-Environment Synoptic Classification
Authors: Cannon Alex J.
Published: November 2011

Regression-guided clustering is introduced as a means of constructing circulation-to-environment synoptic climatological classifications. Rather than applying an unsupervised clustering algorithm to synoptic-scale atmospheric circulation data, one instead augments the atmospheric circulation dataset with predictions from a supervised regression model linking circulation to environment. The combined dataset is then entered into the clustering algorithm. The level of influence of the environmental dataset can be controlled by a simple weighting factor. The method is generic in that the choice of regression model and clustering algorithm is left to the user. Examples are given using standard multivariate linear regression models and the k-means clustering algorithm, both established methods in synoptic climatology. Results for southern British Columbia, Canada, indicate that model performance can be made to range between that of a fully unsupervised algorithm and a fully supervised algorithm.
Sensitivities of Orographic Precipitation to Terrain Geometry and Upstream Conditions in Idealized Simulations
Authors: Watson Campbell D. , Lane Todd P.
Published: November 2011

This study examines how variations in relatively simple terrain geometries influence orographic precipitation and its spatial patterns of sensitivity to small changes in upstream conditions. An idealized three-dimensional model is used to simulate a moist flow impinging upon three alpine-scale terrain shapes: a straight ridge, a concave ridge, and a convex ridge. A variety of simulations are conducted to investigate the sensitivity of precipitation patterns to ridge length and upstream thermodynamic and wind conditions for an impinging flow with a nondimensional mountain height of approximately unity. It is found that for the straight and convex ridges, the flow response is mostly linear for the conditions examined here and passes over the obstacles with little lateral deflection. The concave ridge, however, exhibits strengthened flow deceleration, wave breaking in the lee, and flow confluence between the ridge arms. The concave ridge also generates substantially more precipitation than the other two ridge geometries via an established precipitation-enhancing funneling mechanism near the ridge vertex. However, for some concave ridge configurations the results feature dual-precipitation maxima, which is an important difference from previous findings. Finally, results from a simple ensemble of simulations elucidate the sensitivity of precipitation patterns to small variations in upstream conditions and how these vary for the different terrain geometries.
Late-Twentieth-Century Simulation of Arctic Sea Ice and Ocean Properties in the CCSM4
Authors: Jahn Alexandra , Sterling Kara , Holland Marika M. , Kay Jennifer E. , Maslanik James A. , Bitz Cecilia M. , Bailey David A. , Stroeve Julienne , Hunke Elizabeth C. , Lipscomb William H. , Pollak Daniel A.
Published: November 2011

To establish how well the new Community Climate System Model, version 4 (CCSM4) simulates the properties of the Arctic sea ice and ocean, results from six CCSM4 twentieth-century ensemble simulations are compared here with the available data. It is found that the CCSM4 simulations capture most of the important climatological features of the Arctic sea ice and ocean state well, among them the sea ice thickness distribution, fraction of multiyear sea ice, and sea ice edge. The strongest bias exists in the simulated spring-to-fall sea ice motion field, the location of the Beaufort Gyre, and the temperature of the deep Arctic Ocean (below 250 m), which are caused by deficiencies in the simulation of the Arctic sea level pressure field and the lack of deep-water formation on the Arctic shelves. The observed decrease in the sea ice extent and the multiyear ice cover is well captured by the CCSM4. It is important to note, however, that the temporal evolution of the simulated Arctic sea ice cover over the satellite era is strongly influenced by internal variability. For example, while one ensemble member shows an even larger decrease in the sea ice extent over 1981–2005 than that observed, two ensemble members show no statistically significant trend over the same period. It is therefore important to compare the observed sea ice extent trend not just with the ensemble mean or a multimodel ensemble mean, but also with individual ensemble members, because of the strong imprint of internal variability on these relatively short trends.
Stochastic Simulation of Intermittent DSD Fields in Time
Authors: Schleiss Marc , Jaffrain Joel , Berne Alexis
Published: November 2011

A method for the stochastic simulation of (rain)drop size distributions (DSDs) in space and time using geostatistics is presented. At each pixel, the raindrop size distribution is described by a Gamma distribution with two or three stochastic parameters. The presence or absence of rainfall is modeled using an indicator field. Separable space–time variograms are used to estimate and reproduce the spatial and temporal structures of all these parameters. A simple and user-oriented procedure for the parameterization of the simulator is proposed. The only data required are DSD time series and radar rain-rate (or reflectivity) measurements. The proposed simulation method is illustrated for both frontal and convective precipitation using real data collected in the vicinity of Lausanne, Switzerland. The spatial and temporal structures of the simulated fields are evaluated and validated using DSD measurements from eight independent disdrometers.
Improving Medication Management Through the Redesign of the Hospital Code Cart Medication Drawer
Authors: Rousek Justin B. , Hallbeck M. Susan
Published: November 2011

Objective: This study utilized usability testing and human factors engineering (HFE) principles to create efficient code cart medication drawer modifications to improve code blue medical emergency (code) medication management.

Background: Effective access to medications during a code is a key component in delivering optimal care and has been found to be a major problem among health care organizations; however, little research has been conducted to improve the efficiency of medication management during a code.

Method: A total of 26 health care professionals (13 pharmacists and 13 nurses) were asked to locate items within a code cart medication drawer during two independent simulated code scenarios alternately using either a baseline medication drawer (control; Drawer 1) or a prototype medication drawer (prototype; Drawer 2), which was developed using HFE principles and usability testing. Overall medication retrieval time, wasteful actions, and survey responses were recorded.

Results: Drawer 2 had significantly faster trial completion times ( p = .005) and fewer wasteful actions ( p < .001) compared to Drawer 1. Participant survey results rated Drawer 2 (prototype) significantly higher (more favorable) for medication drawer visibility ( p < .001), usability ( p = .011), and organization ( p < .001) compared to Drawer 1 (baseline).

Conclusion: The HFE redesign concepts incorporated into Drawer 2 (consisting of visibility, grouping, and organization) produced successful, low-cost, and generalizable modifications that can improve patient care.

Application: The findings demonstrate that HFE and usability applied to code cart design are effective, are customizable, and can affect patient safety by saving valuable time and reducing wasted motions (including errors) during code situations.
Social Trust in Urban Neighbourhoods: The Effect of Relative Ethnic Group Position
Authors: Bakker Linda , Dekker Karien
Published: November 2011

Social trust is essential to a cohesive society. Previous studies have demonstrated the importance of individual and contextual determinants in explaining social trust. In this paper it is argued, by means of Blumer’s group position theory, that an individual’s position in the ethnic hierarchy relative to that of the neighbourhood residents influences his or her social trust in the neighbourhood. The multilevel regression analysis of data from the Amsterdam Safety Monitor 2009 provides tentative support for this theory. Building upon previous studies, the relevant individual and contextual determinants of social trust in the neighbourhood are also studied. Contrary to earlier findings, no neighbourhood effects are detected. Thus, it is neither the actual position in the ethnic hierarchy nor the effect of the neighbourhood, but the ethnic position relative to the neighbourhood residents that diminishes minority group members’ social trust through a threat that appears to be both socioeconomic and cultural.
Participatory media fandom: A case study of anime fansubbing
Authors: Lee Hye-Kyung
Published: November 2011

Recent years have seen the rise of consumers’ voluntary translation and distribution of foreign cultural products on a global scale. Such a practice not only facilitates the grassroots globalization of culture but also questions the cultural industries’ current model of global distribution. This article explores the nature and implications of fan-translation and distribution of cultural commodities through a case study of English fansubbing of anime (subtitling of Japanese animation in English). Anime fansubbing is situated at the disjuncture of the global mediascape, which intensifies with the increasing public access to means to copy and share, the expansion of collective knowledge and the rise of fans’ voluntary labour coordinated on a global scale. It exemplifies participatory media fandom whose globalization exceeds that of cultural industries in terms of extent and velocity. The article argues that fansubbing, pursued as a hobby, can unsettle the global mediascape by allowing multiple mediations of cultural text and presenting a new model of content distribution and its organization based on consumers’ voluntary work.
Images of liberation? Visual framing, humanitarianism and British press photography during the 2003 Iraq invasion
Authors: Parry Katy
Published: November 2011

Although the 2003 Iraq invasion was not wholly framed as a ‘humanitarian intervention’, the rhetoric of bringing liberation, democratization and human rights to the Iraqi people was widely advanced by the coalition and supporters as a legitimating reason for war. This article assesses the role played by press photography in legitimizing or challenging this crucial framing during the invasion across a range of UK national newspapers. Privileging visual content in research design, the study presents selected results from a comprehensive content and framing analysis of press photography during the invasion period (March–April 2003), specifically examining the prominence and treatment of photographs in the humanitarian-related visual coverage, along with the accompanying words used to define, support or detract from the events depicted. While finding that the rationale of humanitarianism generally played well for the coalition during this study period, this article explores the problematic nature of the narrative of liberation.
Ocropodium: open source OCR for small-scale historical archives
Authors: Blanke Tobias , Bryant Michael , Hedges Mark
Published: November 2011

Large-scale digitization projects dealing with text-based historical material face challenges that are not well catered for by commercial software. This article discusses the results of a project to build a scalable OCR workflow for historical collections based on open source tools that is particularly tailored towards use in small-scale historical archives. It argues that open source tools allow for better customization to match these requirements, particularly with regard to character model training and per-project language modelling. We offer insights into our accuracy evaluation results of various open source OCR tools, as well as a case study about the challenges and opportunities of open source OCR in historical archives.
F#!%ing Rudeness
Authors: Ickes William , Park Anna , Robinson Rebecca L.
Published: November 2011

In an online survey study ( n = 275), several demographic and personality variables were used to predict scores on the Rudeness Scale, a new measure of the propensity to verbally abuse strangers. The results of multiple regression analyses revealed a number of significant main effects. These effects revealed that the people in the authors’ sample who reported the greatest propensity to verbally abuse strangers were Hispanic/Latino or Black individuals who scored low in adherence to the standards of conventional morality but high in ego defensiveness (unwillingness to accept criticism or correction from others) and affect intensity for anger and frustration. The authors’ interpretation of the findings combines insights derived from Swann’s self-verification theory, contrasting views of ego defensiveness, and Larsen et al.’s work on affect intensity with a dispositional view of verbal rudeness that emphasizes its use as a weapon in interpersonal struggles for power, status, and “face.”