bluuebunny/crossref_metadata_2025 huggingface dataset:
Defoliation of Brassica napus increases severity of blackleg caused by Leptosphaeria maculans: implications for dual‐purpose cropping
Authors: Sprague Susan J. , Kirkegaard John A. , Marcroft Stephen J. , Graham John M.
Published: June 2010

Canola (Brassica napus) crops for grazing and grain (dual‐purpose) production provide an economic break‐crop alternative for dual‐purpose cereals in Australian mixed farming systems. Infection by Leptosphaeria maculans is the most prevalent disease in Australian canola crops with airborne inoculum released throughout the autumn and winter when crops are grazed. Glasshouse and field experiments were conducted to investigate the effect of mechanical defoliation (simulated grazing) on disease severity at plant maturity. In glasshouse experiments, stem canker severity increased from 4% to 24% in severely defoliated plants, but light defoliation had no effect compared with undefoliated control plants. Disease severity was increased with defoliation in all field experiments. Defoliation increased crown canker severity from 22.6% to 39.3% at Wagga Wagga and from 3.0% to 7.1% at Canberra and lodging from 9.6% to 11.9% at Naracoorte in the same set of cultivars assessed at each site. The increase in disease severity with defoliation was less in canola lines with moderate to high levels of stem canker resistance. Plants defoliated before stem elongation tended to develop less disease than those defoliated during the reproductive phase of plant growth. These findings suggest that the impact of grazing on L. maculans infection of canola crops can be minimised by sowing cultivars with a high level of stem canker resistance and grazing during the vegetative stage of plant growth prior to stem elongation. Further research is required to determine whether these management strategies are applicable in canola crops defoliated by grazing animals.
Financial Literacy Explicated: The Case for a Clearer Definition in an Increasingly Complex Economy
Authors: REMUND DAVID L.
Published: June 2010

This study explicates the concept of financial literacy, which has blossomed in use this century. Scholars, policy officials, financial experts and consumer advocates have used the phrase loosely to describe the knowledge, skills, confidence and motivation necessary to effectively manage money. As a result, financial literacy has varying conceptual definitions in existing research, as well as diverse operational definitions and values. This study dissects the differing financial literacy definitions and measures, urging researchers toward common ground. A clearer definition should improve future research, in turn helping consumers better understand and adapt to changing life events and an increasingly complex economy.
The Effects of Financial Education on the Financial Knowledge of High School Students
Authors: WALSTAD WILLIAM B. , REBECK KEN , MacDONALD RICHARD A.
Published: June 2010

This study investigated the effects of a financial education program on high school students' knowledge of personal finance. A comparison of pretest and posttest scores achieved on a reliable and valid thirty‐item instrument suggested that the Financing Your Future curriculum increased financial knowledge across many concepts. The scores increased regardless of the course in which the curriculum was used and across student characteristics. The assessment contributes to the growing literature showing that a well‐specified and properly implemented program in financial education can positively and significantly influence the financial knowledge of high school students.
Takayasu's arteritis with associated aortic insufficiency and coronary ostial obliteration
Authors: Castlemain Theresa M.
Published: June 2010

Purpose: To describe the presentation, assessment, and management of Takayasu's arteritis (TA), a rare vascular condition exhibited predominantly in females in their second and third decades of life.

Data sources: Thorough review of current scientific literature was obtained from electronic databases and medical journals (CINAHL and PubMed). A case study is presented to illustrate TA, which was reviewed and approved by the Human Subjects Committee for the release of protected health information.

Conclusions: Clinical presentation of TA varies depending on the location of vessel involvement. Diagnosis is challenging because of the complex pathogenesis of TA. The chronic nature of TA requires ongoing evaluation and adjustment of medication regimens. The patient's quality of life is improved with maintenance of TA in a quiescent state.

Implications for Practice: Presentation of a young woman with symptoms suggestive of vascular inflammatory changes should prompt consideration of TA within the differential diagnosis.
Outcomes of an osteoporosis disease‐management program managed by nurse practitioners
Authors: Greene Denise , Dell Richard M.
Published: June 2010

Purpose: To detail the outcomes of an osteoporosis disease‐management program where nurse practitioners (NPs) have taken a leadership role in screening, diagnosing, and treating patients at risk for osteoporosis.

Data sources: An electronic medical record (EMR) was used to collect demographic, pharmacy, dual x‐ray absorptiometry (DXA) scan, and fracture data from a population of over 625,000 patients with one or more risk factors for osteoporosis. Monthly reports were generated and distributed to the NPs to assist them in identifying patients that required screening or treatment.

Conclusions: Over a 6‐year period there was a 263% increase in the number of screening DXA scans done each year, a 153% increase in the number of patients on anti‐osteoporosis medications each year, and a 38.1% decrease in the expected hip fracture rate.

Implications for practice: NPs play an important leadership role in managing osteoporosis within a large health maintenance organization. The screening and interventions used can be applied by any NP in any practice setting on an individual basis to reduce hip fracture rates in the United States.
Synthesis and Antifungal Activities of New Pyrazole Derivatives via 1,3‐dipolar Cycloaddition Reaction
Authors: Zhang Chuan‐Yu , Liu Xing‐Hai , Wang Bao‐Lei , Wang Su‐Hua , Li Zheng‐Ming
Published: June 2010

A series of cycloadducts‐‐pyrazoles via 1,3‐dipolar cycloaddition reactions of generated nitrilimines with N‐(4‐chloro‐2‐fluorophenyl)maleimide were described. The novel compounds synthesized were characterized by 1H NMR, MS, and elemental analysis. The fungicidal tests showed that most of the title compounds exhibit significant fungicidal activities against Corynespora cassiicola.
Tumor Necrosis Factor Alpha Converting Enzyme: An Encouraging Target for Various Inflammatory Disorders
Authors: Bahia Malkeet S. , Silakari Om
Published: June 2010

Tumor necrosis factor alpha is one of the most common pro‐inflammatory cytokines responsible for various inflammatory disorders. It plays an important role in the origin and progression of rheumatoid arthritis and also in other autoimmune disease conditions. Some anti‐tumor necrosis factor alpha antibodies like Enbrel®, Humira®and Remicade®have been successfully used in these disease conditions as antagonists of tumor necrosis factor alpha. Inhibition of generation of active form of tumor necrosis factor alpha is a promising therapy for various inflammatory disorders. Therefore, the inhibition of an enzyme (tumor necrosis factor alpha converting enzyme), which is responsible for processing inactive form of tumor necrosis factor alpha into its active soluble form, is an encouraging target. Many tumor necrosis factor alpha converting enzyme inhibitors have been the candidates of clinical trials but none of them have reached in to the market because of their broad spectrum inhibitory activity for other matrix metalloproteases. Selectivity of tumor necrosis factor alpha converting enzyme inhibition over matrix metalloproteases is of utmost importance. If selectivity is achieved successfully, side‐effects can be over‐ruled and this approach may become a novel therapy for treatment of rheumatoid arthritis and other inflammatory disorders. This cytokine not only plays a pivotal role in inflammatory conditions but also in some cancerous conditions. Thus, successful targeting of tumor necrosis factor alpha converting enzyme may result in multifunctional therapy.
Simultaneously Optimized Support Vector Regression Combined With Genetic Algorithm for QSAR Analysis of KDR/VEGFR‐2 Inhibitors
Authors: Sun Min , Chen Junqing , Cai Jin , Cao Meng , Yin Shuangqing , Ji Min
Published: June 2010

Considering the fact that majority of support vector regression models have not been fully optimized in the realm of quantitative structure‐activity relationship, an idea of simultaneous optimization has been proposed and evaluated on a set of novel kinase insert domain receptor/vascular endothelial growth factor receptor‐2 inhibitors including naphthalene and indazole‐based compounds in this study. After the powerful feature searching process using genetic algorithm, the final support vector regression model was constructed on an optimal set of six descriptors, based on which simultaneous optimization was carried out. Specifically, the global optimum is grid searched in the joint parametric space defined by cost (C), γ and ε, where performance of support vector regression using each combination of (C, γ, ε) is evaluated and recorded, resulting in bulky information. Based on the data decomposition strategies provided in the main paper, the best performance was achieved for C = 1.2, γ = 0.15 and ε = 0.065. As a comparison, a linear model based on genetic algorithm‐multiple linear regression has also been developed and compared. Performances of these models are rigorously validated using both leave‐one‐out cross‐validation and also external validation. The significant higher R2 (0.908, 0.837) and lower root‐mean‐square error (0.237, 0.311) for 45 training and 16 test samples compared to that of genetic algorithm‐multiple linear regression (0.764, 0.700 and 0.402, 0.421) confirm the superior performance of genetic algorithm‐support vector regression. Robustness and predictive ability of this model is further prudently evaluated. The resulting models introduced not only the idea of simultaneous optimization in support vector regression, but also an efficient strategy for estimating the vascular endothelial growth factor receptor‐2 inhibitory activity of novel naphthalene and indazole‐based compounds. Moreover, some insights into the structural features related to the biological activity of these compounds have also been provided, which might be of great help for further designing novel vascular endothelial growth factor receptor‐2/kinase insert domain receptor inhibitors with potent activity.
Carbonic Anhydrase Inhibitors: Inhibition of Human Erythrocyte Isozymes I and II with a Series of Phenolic Acids
Authors: Beyza Öztürk Sarıkaya S. , Gülçin İlhami , Supuran Claudiu T.
Published: June 2010

The inhibitory effects of some phenolic acids on the cytosolic human carbonic anhydrase (hCA, EC 4.2.1.1) isozymes hCA I and hCA II were investigated. Ellagic acid, gallic acid, ferulic acid, caffeic acid, quercetin, p‐coumaric acid, p‐hydroxybenzoic acid, and syringic acid showed KI values in the range of 99–1061 μm for hCA I and of 105–758 μm against hCA II, respectively. Quercetin (for hCA I), p‐coumaric acid (for hCA II), and gallic acid (for hCA II) exhibited competitive inhibitory effects with 4‐nitrophenyl acetate as substrate. All of the other phenolic acids were found as non‐competitive inhibitors with 4‐nitrophenylacetate as substrate for hCA I and hCA II. The phenolic acids investigated here showed thus interesting hCA I and hCA II inhibitory effects and might be used as leads for generating enzyme inhibitors possibly targeting other CA isoforms which have not been yet assayed for their interactions with such agents.
Long‐term survival of humpback whales radio‐tagged in Alaska from 1976 through 1978
Authors: Mizroch Sally A. , Tillman Michael F. , Jurasz Susan , Straley Janice M. , Von Ziegesar Olga , Herman Louis M. , Pack Adam A. , Baker Scott , Darling Jim , Glockner‐Ferrari Debbie , Ferrari Mark , Salden Dan R. , Clapham Phillip J.
Published: June 2010

Abstract

Invasive tags designed to provide information on animal movements through radio or satellite monitoring have tremendous potential for the study of whales and other cetaceans. However, to date there have been no published studies on the survival of tagged animals over periods of years or decades. Researchers from the National Marine Mammal Laboratory and the Woods Hole Oceanographic Institution tracked five humpback whales with implanted radio tags in southeastern Alaska in August 1976 and July 1977, and tracked two humpback whales in Prince William Sound, Alaska, in June 1978. All seven of these individually identified humpback whales were resighted at least 20 yr after first being tagged, and five of the seven have been observed for more than 30 yr; some of them are among the most resighted humpback whales in the North Pacific. Photos of tagging sites taken during and subsequent to tagging operations show persistent but superficial scarring and no indication of infection.

These pioneering field studies demonstrated both long‐term survival of the whales and the short‐term effects of deploying radio tags, which at the time were larger and more invasive than those typically used today.
Potential role of immunosenescence in cancer development
Authors: Fulop Tamas , Kotb Rami , Fortin Carl F. , Pawelec Graham , de Angelis Flavia , Larbi Anis
Published: June 2010

The incidence and prevalence of most cancers increase with age. The reasons for this may include tumor escape mechanisms and decreased immunosurveillance, but most are caused by the time required for carcinogenesis, according to most scientists. The immune system is a unique mechanism of defense against pathogens and possibly cancers; however, there is a body of evidence that the immune system of the aged is eroded, a phenomenon termed immunosenescence. There is a growing interest in immunosenescence and how it may contribute to the increased number of cancers with aging. Each arm of the immune system, innate and adaptive, is altered with aging, contributing to increased tumorigenesis. Understanding the contribution of immunosenescence to cancer development and progression may lead to better interventions for the elderly.
Ascorbate improves metabolic abnormalities in Wrn mutant mice but not the free radical scavenger catechin
Authors: Lebel Michel , Massip Laurent , Garand Chantal , Thorin Eric
Published: June 2010

Werner syndrome (WS) is a premature aging disorder caused by mutations in a RecQ‐like DNA helicase. Mice lacking the helicase domain of the WRN homologue exhibit many phenotypic features of WS. Importantly, mutant WrnΔhel/Δhel mice show abnormal increases in visceral fat deposition and fasting blood triglyceride levels followed by insulin resistance and high blood glucose levels. These mice also exhibit increased heart and liver tissue reactive oxygen species concomitantly with oxidative DNA damage, indicating a pro‐oxidant status. We treated mice with either ascorbate or catechin hydrate for 9 months. Vitamin C supplementation reduced oxidative stress in liver and heart tissues and reversed hypertriglyceridemia, hyperglycemia, and insulin resistance and reduced fat weight in mutant WrnΔhel/Δhel mice. Although the free scavenger catechin hydrate also reduced oxidative DNA damage in heart and liver tissues, it did not reverse any of the metabolic phenotype aspects in treated mutant mice. Finally, vitamin C and catechin hydrate did not affect the metabolic status of wild‐type mice. These results indicate that vitamin C supplementation could be beneficial for WS patients.
HSPB1, actin filament dynamics, and aging cells
Authors: Doshi Bindi M. , Hightower Lawrence E. , Lee Juliet
Published: June 2010

Investigations into the possible roles of human HSPB1 in aging have focused on its role as a molecular chaperone protecting partially folded or unfolded proteins, particularly during oxidative stress. A thorough analysis of potential roles of HSPB1 in aging cells has been hampered by a limited knowledge of its functions in living cells. Most studies have employed cell‐free extracts and purified proteins. For example, HSPB1 is known to bind actin in vitro, and this observation led to the hypothesis that HSPB1 regulates actin filament dynamics. In the study summarized herein, the role of HSPB1 in regulating actin filament dynamics was further investigated by using cultured human cells. These results show that HSPB1 and actin form a complex in vivo and that HSPB1 is important for cell motility. A model for HSPB1 as a regulator of actin filament dynamics is presented, and evidence from the literature on cytoskeletal alterations in aging cells is discussed.
Evaluating the role of p38 MAP kinase in growth of Werner syndrome fibroblasts
Authors: Davis Terence , Bachler Marcus A. , Wyllie Fiona S. , Bagley Mark C. , Kipling David
Published: June 2010

The accelerated aging of Werner syndrome (WS) fibroblasts can be prevented by treatment with the p38 kinase inhibitor SB203580. If accelerated cellular senescence underlies the premature ageing features seen in this human aging model, then p38 inhibitors may have therapeutic potential in WS. However, SB203580 can inhibit in vitro several kinases that are involved in control of cellular growth, in particular, c‐Raf1, CK1, and RIPK2. Thus, a better understanding of the role of this inhibitor in WS cells is required. Here we use a combination of kinase inhibitors and small intefering RNA‐induced gene knockdown to show that it is inhibition of the stress‐induced p38 MAP kinase that is the most plausible explanation for the effects of SB203580 on the growth of WS cells. As the development of highly selective p38 inhibitors with low toxicity is a major effort of the pharmaceuticals sector, these studies help pave the way for possible therapeutics for WS.
A screen for genes involved in respiration control and longevity in Schizosaccharomyces pombe
Authors: Roux Antoine E. , Arseneault Geneviève , Chartrand Pascal , Ferbeyre Gerardo , Rokeach Luis A.
Published: June 2010

We present results showing that glucose signaling has proaging effects in the yeast Schizosaccharomyces pombe. Deletion of the receptor that senses extracellular glucose (Git3) increases the life span of S. pombe, while constitutive activation of the Gα subunit acting downstream of this receptor (Gpa2) shortens its life span. The latter mutant is also impaired for growth under respiration conditions. We have used this phenotype in a selection strategy to identify genes that when overexpressed can rescue the respiratory defect of constitutively active Gα subunit mutants. Here, we report an extended version of the work we presented at the IABG meeting and the results of this screen. This strategy allowed us to isolate four genes: psp1+/moc1+, cka1+, adh1+, and rpb10+. Interestingly, the overexpression of these genes was also capable of increasing the chronological life span of wild‐type yeast cells.
Astaxanthin Extraction from Shrimp Wastes and its Stability in 2 Model Systems
Authors: Franco‐Zavaleta M.E. , Jiménez‐Pichardo R. , Tomasini‐Campocosio A. , Guerrero‐Legarreta I.
Published: June 2010

Abstract:  The objective of this work was to study the stability of astaxanthin, obtained from shrimp wastes, and incorporated to 2 model systems: egg albumin protein solution and sunflower oil. Shrimp wastes were ensiled by a treatment with formic/acetic acids (4%–4% v/w wastes) and stored at 4 °C for 24 h. The pigment was extracted with organic solvents (petroleum ether:acetone:water, 15 : 75 : 10) and concentrated. The storage parameters studied were: illumination (light/dark), temperature (4/20 °C), atmosphere (air/air‐free), and storage time (0, 1, 2, 3, 4, 5 wk). Results showed that total xantophylls and astaxanthin were more stable in sunflower oil than in the protein system. Total xantophylls showed more stability than astaxanthin, possibly due to the presence of other, more stable carotenoids quantified together with xantophylls. Astaxanthin concentration was significantly affected by storage time; its degradation followed a first‐order reaction rate under all the studied conditions. This pigment was stable only for 17 d, even when stored in air‐free flasks, under refrigeration, and in the dark.

Practical Application:  Shrimp catching and farming generate large amounts of polluting wastes; they can be an important source of added‐value red‐orange pigments. However, these pigments are highly unstable to various transformation processes and to storage conditions. This research studied the effect of storage on 2 model systems (protein and lipid) on pigment degradation.
Kinetics of Formation and Physicochemical Characterization of Thermally‐Induced β‐Lactoglobulin Aggregates
Authors: Zúñiga R.N. , Tolkach A. , Kulozik U. , Aguilera J.M.
Published: June 2010

Abstract:  The kinetics of heat denaturation and aggregation for β‐lactoglobulin dispersions (5% w/v) were studied at 3 pHs (6, 6.4, and 6.8) and at a heating temperature of 80 °C. Protein aggregates were characterized for hydrodynamic diameter, microstructure, and molecular weight by means of dynamic light scattering, transmission electron microscopy, and polyacrylamide gel electrophoresis, respectively. Concentration of native β‐lactoglobulin decreased with holding time and with a decrease in the pH. Apparent rate constants were calculated for β‐lactoglobulin denaturation applying the general kinetic equation solved for a reaction order of 1.5. Values of the apparent reaction rate constant k = 7.5, 6.3 and 5.6 × 10−3 s−1 were found for pH 6, 6.4, and 6.8, respectively. Decreasing the pH of the dispersions produced higher aggregate sizes. After a holding time of 900 s, average hydrodynamic diameters for β‐lactoglobulin aggregates at pH 6, 6.4, and 6.8 were 96, 49, and 42 nm, respectively. These results were confirmed by transmission electron microscopy images, where a shift in the size and morphology of aggregates was found, from large and spherical at pH 6 to smaller and linear aggregates at pH 6.8. β‐Lactoglobulin formed disulfide‐linked intermediates (dimers, trimers, tetramers) and so on) which then formed high molecular weight aggregates. From the results obtained by DLS, TEM, and SDS‐PAGE a mechanism for β‐lactoglobulin aggregation was proposed. This study shows that heat treatment can be used to produce protein aggregates with different sizes and morphologies to be utilized as ingredients in foods.
Heat Stability of Aggregated Particles of Casein Micelles and κ‐Carrageenan
Authors: Flett Kelly L. , Corredig Milena , Goff H. Douglas
Published: June 2010

Abstract:  Aggregated particles of casein micelles and κ‐carrageenan were produced as a dried milk ingredient, then reconstituted and subjected to a heat treatment of 70 °C for 10 min. The reconstituted aggregates were found to be unstable when heated. Light scattering results showed that the aggregates dissociated partially into casein micelles. It was hypothesized that the removal of ions during ultrafiltration before spray‐drying to produce the powdered ingredient significantly decreased stability upon reconstitution and heat treatment. When ions, either from whey permeate or calcium addition, were added to reconstituted aggregates, stability was greatly enhanced and the aggregates remained intact when subjected to heat. The effect of heat treatment on aggregates freshly produced with skim milk powder and κ‐carrageenan was also studied. These aggregates were found to be stable during heating due to the unchanged ionic environment. Therefore, incorporation of powdered aggregates of casein micelles and κ‐carrageenan into products would require the addition of whey permeate or calcium after reconstitution for stability during subsequent heating.

Practical Application:  Casein micelles and κ‐carrageenan readily form aggregates when cooled together in solution with shearing. These aggregates have the potential to add functionality to skim milk powder; however, they have to be stable to subsequent applications. This research demonstrates that careful control of ionic balance is required to dry the aggregates, reconstitute them, and heat the reconstituted solution to pasteurization temperatures, but when controlled the intact aggregates can be maintained.
Effect of the Addition of Common Bean (Phaseolus vulgaris L.) Flour on the In Vitro Digestibility of Starch and Undigestible Carbohydrates in Spaghetti
Authors: Gallegos‐Infante Jose‐Alberto , Bello‐Perez Luis Arturo , Rocha‐Guzman Nuria Elizabeth , Gonzalez‐Laredo Ruben Francisco , Avila‐Ontiveros Martha
Published: June 2010

Abstract:  Spaghetti is considered to be a slowly digestible starch food, a feature ruled by the particular physical properties of the product. Several studies have been reported to increase nutritional value of spaghetti, using legumes. We have studied the addition of common bean flour on the starch in vitro digestibility. Spaghetti was prepared with semolina and different concentrations of common bean flour (0%, 15%, 30%, and 45%, w/w). Proximate analysis, optimal cooking time, and cooking loss were estimated in crude spaghetti. Total, available, and resistant starches, indigestible fractions, and in vitro starch hydrolysis kinetics were accomplished in cooked spaghetti. Pasta with 30% and 45% of common bean flour showed higher values of protein. Particularly, the lowest cooking time was observed for composite spaghetti with 45% of common bean flour. There was a significant increase in cooking loss when common bean flour in the composite was added. Composite spaghetti samples with increasing common bean flour showed decreasing values of total starch but an important increase in the resistant starch (RS) level and indigestible insoluble fraction values. Plain pasta made with semolina showed the highest enzymatic hydrolysis rate, which decreased when common bean flour was added to the spaghetti. Spaghetti with a higher level of common bean flour was more slowly available, which may have positive implications for human health.
Detection and Prevention of Ocular Phototoxicity of Ciprofloxacin and Other Fluoroquinolone Antibiotics†
Authors: Zhao Baozhong , Chignell Colin F. , Rammal Mustapha , Smith Frank , Hamilton Mary G. , Andley Usha P. , Roberts Joan E.
Published: June 2010

Fluoroquinolone (FLQ) drugs are a potent family of antibiotics used to treat infections including ocular infections. To determine if these antibiotics may be phototoxic to the eye, we exposed human lens epithelial cells to 0.125–1 mm FLQs (ciprofloxacin [Cipro], lomefloxacin [Lome], norfloxacin [Nor] and ofloxacin [Ofl]), the precursor quinolone nalidixic acid (Nalid) and UVA radiation (2.5 J cm−2). Based on fluorescence confocal microscopy, FLQs are diffused throughout the cytoplasm and preferentially located in the lysosomes of lens epithelial cells. Neither FLQ exposure alone nor UVA exposure alone reduced cell viability. However, with exposure to UVA radiation the FLQs studied (Cipro, Nor, Lome and Ofl) induced a phototoxic reaction that included necrosis, apoptosis, loss of cell viability as measured by MTS, and membrane damage as determined by the lactate dehydrogenase assay. Both Nalid and all FLQs studied (Cipro, Nor, Lome and Ofl) photopolymerized the lens protein α‐crystallin. Phototoxic damage to lens epithelial cells and/or α‐crystallin will lead to a loss of transparency of the human lens. However, if precautions are taken to filter all UV radiation from the eye while taking these antibiotics, eye damage may be prevented.
Comparison of the diagnostic methods on the canine adenovirus type 2 infection
Authors: Yoon Soon‐Seek , Byun Jae‐Won , Park Young‐Il , Kim Min‐Jeong , Bae You‐Chan , Song Jae‐Young
Published: June 2010

Background and aims: Canine adenovirus type 2 (CAV‐2) infection is typically diagnosed histopathologically since intranuclear inclusion bodies (IN/IBs) are demonstrable in the infected lung. However, it is sometimes difficult to identify IN/IBs, particularly in autolyzed tissues or samples from both early and late stages of infection, and other methods were presently developed. Methods: Stray dog samples were evaluated by histopathology, polymerase chain reaction (PCR), and immunohistochemistry (IHC) to investigate the status of the CAV‐2 infection on the stray dogs in Korea. Histologic tests were performed, and dogs with pneumonic lungs were further evaluated by IHC and PCR. Results: Pathognomonic IN/IBs were identified in 3 of 213 lungs; CAV‐2 PCR was positive for 27 of 213 pneumonic lungs. A total of 7 of 27 CAV‐2 PCR‐positive lungs were IHC‐positive. No PCR‐negative lung was IHC‐positive. Positive results were primarily detected in the IN/IBs of the bronchial epithelial cells, macrophages, and very rarely in the cytoplasm of bronchial epithelial cells. Conclusions: IHC was a more reliable diagnostic method than conventional pathologic methods in the present study, and suggests that IHC should be routinely used in the diagnosis of CAV‐2 infection. Further, PCR alone may not be adequate for CAV‐2 diagnosis.
Development of a novel multi‐triplex qPCR method for the assessment of bacterial community structure in oral populations
Authors: Ciric Lena , Pratten Jonathan , Wilson Michael , Spratt David
Published: June 2010

Gingivitis and dental caries are two of the most predominant diseases in humans. Both conditions are easily treated with the removal of the plaque biofilm by brushing or the use of oral hygiene products. In both cases, pathogenic taxa found within the plaque biofilm are the causal agents of the disease. Actinomyces naeslundii, Fusobacterium nucleatum and Prevotalla intermedia have all been implicated in the development of gingivitis, while Streptococcus mutans is the main organism associated with dental caries. Many studies have so far focused on the use of culture methods to detect and enumerate the pathogenic taxa within plaque samples. However, these methods are both labour intensive and biased towards culturable taxa. In the present study, a novel high‐throughput multi‐triplex quantitative PCR method was developed with the aim to investigate the community dynamics associated with oral communities. Three triplex assays were designed targeting taxa associated with gingivitis and dental caries as well as oral health. Saliva samples collected from healthy individuals were used in order to validate the newly developed method.
Common variable immunodeficiency in a horse with chronic peritonitis
Authors: Tennent‐Brown B. S. , Navas de Solis C. , Foreman J. H. , Goetz T. E. , Fredrickson R. L. , Borst L. B. , Flaminio M. J. B. F.
Published: June 2010

This report describes the clinical progression of a Quarter Horse filly with common variable immunodeficiency (CVID). Equine CVID is a primary immunodeficiency in which affected animals are unable to mount an appropriate antibody response and suffer recurrent bacterial infections. The filly in this report had a history of chronic respiratory tract infections but presented for assessment of poor weight gain and was diagnosed withActinobacillus equuliperitonitis.
Visualizing the Landscape of Selection Biomarkers in Current Phase III Oncology Clinical Trials
Authors: Sikorski Robert , Yao Bin
Published: June 2010

A global analysis of selection biomarkers currently in use in
oncology phase III clinical trials reveals a terrain that is both rich
and sparse.
Translational Science: A View from a Biotechnology Investor
Authors: Klausner Richard
Published: June 2010

If biotechnology is to remain a prime venue for the translation of science into innovative medical products, then the venture capital firms that fund these companies must replace
deal flow
business plans with
idea flow
approaches.
Destination: Stent
Authors: Cheng Elaine
Published: June 2010

Magnetic nanoparticles carrying a therapeutic agent can be specifically targeted to stents to prevent re-occlusion of blood vessels.
Role of Fks1p and Matrix Glucan in
Candida albicans
Biofilm Resistance to an Echinocandin, Pyrimidine, and Polyene
Authors: Nett Jeniel E. , Crawford Kyler , Marchillo Karen , Andes David R.
Published: June 2010

Candida
infections frequently involve drug-resistant biofilm growth on device surfaces. Glucan synthase gene
FKS1
has been linked to triazole resistance in
Candida
biofilms. We tested the impact of
FKS1
modulation on susceptibility to additional antifungal classes. Reduction of
FKS1
expression rendered biofilms more susceptible to amphotericin B, anidulafungin, and flucytosine. Increased resistance to anidulafungin and amphotericin B was observed for biofilms overexpressing
FKS1
. These findings suggest that
Candida
biofilm glucan sequestration is a multidrug resistance mechanism.
In Vitro Antituberculosis Activities of ACH-702, a Novel Isothiazoloquinolone, against Quinolone-Susceptible and Quinolone-Resistant Isolates
Authors: Pucci Michael J. , Ackerman Maria , Thanassi Jane A. , Shoen Carolyn M. , Cynamon Michael H.
Published: June 2010

ACH-702 is a new isothiazoloquinolone with potent
in vitro
and
in vivo
activities against important bacterial pathogens, including
Staphylococcus aureus.
In this study, ACH-702 was found to have promising
in vitro
antibacterial activity against
Mycobacterium tuberculosis
, with MICs of ≤1 μg/ml, comparable to that of the fluoroquinolone moxifloxacin for quinolone-susceptible isolates but superior to that for quinolone-resistant isolates. Biochemical assays involving
M. tuberculosis
gyrase enzymes indicated that ACH-702 had significantly improved inhibitory activity compared with fluoroquinolones.
Novel Hepatitis C Virus Reporter Replicon Cell Lines Enable Efficient Antiviral Screening against Genotype 1a
Authors: Robinson Margaret , Yang Huiling , Sun Siu-Chi , Peng Betty , Tian Yang , Pagratis Nikos , Greenstein Andrew E. , Delaney William E.
Published: June 2010

The hepatitis C virus (HCV) subgenomic replicon is the primary tool for evaluating the activity of anti-HCV compounds in drug discovery research. Despite the prevalence of HCV genotype 1a (∼70% of U.S. HCV patients), few genotype 1a reporter replicon cell lines have been described; this is presumably due to the low replication capacity of such constructs in available Huh-7 cells. In this report, we describe the selection of highly permissive Huh-7 cell lines that support robust replication of genotype 1a subgenomic replicons harboring luciferase reporter genes. These novel cell lines support the replication of multiple genotype 1a replicons (including the H77 and SF9 strains), are significantly more permissive to genotype 1a HCV replication than parental Huh7-Lunet cells, and maintain stable genotype 1a replication levels suitable for antiviral screening. We found that the sensitivity of genotype 1a luciferase replicons to known antivirals was highly consistent between individual genotype 1a clonal cell lines but could vary significantly between genotypes 1a and 1b. Sequencing of the nonstructural region of 12 stable replicon cell clones suggested that the enhanced permissivity is likely due to cellular component(s) in these new cell lines rather than the evolution of novel adaptive mutations in the replicons. These new reagents will enhance drug discovery efforts targeting genotype 1a and facilitate the profiling of compound activity among different HCV genotypes and subtypes.
Mass Balance and Pharmacokinetics of [
14
C]Telavancin following Intravenous Administration to Healthy Male Volunteers
Authors: Shaw Jeng-Pyng , Cheong Jonathan , Goldberg Michael R. , Kitt Michael M.
Published: June 2010

The mass balance and pharmacokinetics of telavancin, a semisynthetic lipoglycopeptide antimicrobial agent, were characterized in an open-label, phase 1 study of six healthy male subjects. After a single 1-h intravenous infusion of 10 mg/kg [
14
C]telavancin (0.68 μCi/kg), blood, urine, and feces were collected at regular intervals up to 216 h postdose. Whole blood, plasma, urine, and fecal samples were assayed for total radioactivity using scintillation counting; plasma and urine were also assayed for parent drug and metabolites using liquid chromatography with tandem mass spectrometry. The concentration-time profiles for telavancin and total radioactivity in plasma were comparable from 0 to 24 h after the study drug administration. Telavancin accounted for >95% and 83% of total radioactivity in plasma at 12 h and 24 h, respectively. By 216 h, approximately 76% of the total administered dose was recovered in urine while only 1% was collected in feces. Unchanged telavancin accounted for most (83%) of the eliminated dose. Telavancin metabolite THRX-651540 along with two other hydroxylated metabolites (designated M1 and M2) accounted for the remaining radioactivity recovered from urine. The mean concentrations of total radioactivity in whole blood were lower than the concentration observed in plasma, and mean concentrations of THRX-651540 in plasma were minimal relative to mean plasma telavancin concentrations. These observations demonstrate that most of an administered telavancin dose is eliminated unchanged via the kidneys. Intravenous telavancin at 10 mg/kg was well tolerated by all subjects.
Prevention of
Escherichia coli
K1 Penetration of the Blood-Brain Barrier by Counteracting the Host Cell Receptor and Signaling Molecule Involved in
E. coli
Invasion of Human Brain Microvascular Endothelial Cells
Authors: Zhu Longkun , Pearce Donna , Kim Kwang Sik
Published: June 2010

Escherichia coli
meningitis is an important cause of mortality and morbidity, and a key contributing factor is our incomplete understanding of the pathogenesis of
E. coli
meningitis. We have shown that
E. coli
penetration into the brain requires
E. coli
invasion of human brain microvascular endothelial cells (HBMEC), which constitute the blood-brain barrier.
E. coli
invasion of HBMEC involves its interaction with HBMEC receptors, such as
E. coli
cytotoxic necrotizing factor 1 (CNF1) interaction with its receptor, the 67-kDa laminin receptor (67LR), and host signaling molecules including cytosolic phospholipase A
2
α (cPLA
2
α). In the present study, we showed that treatment with etoposide resulted in decreased expression of 67LR on HBMEC and inhibited
E. coli
invasion of HBMEC. Pharmacological inhibition of cysteinyl leukotrienes, lipoxygenated products of arachidonic acid released by cPLA
2
α, using montelukast (an antagonist of the type 1 cysteinyl leukotriene receptor) also inhibited
E. coli
invasion of HBMEC.
E. coli
penetration into the brain was significantly decreased by etoposide as well as by montelukast, and a combination of etoposide and montelukast was significantly more effective in inhibiting
E. coli
K1 invasion of HBMEC than single agents alone. These findings demonstrate for the first time that counteracting the HBMEC receptor and signaling molecule involved in
E. coli
invasion of HBMEC provides a novel approach for prevention of
E. coli
penetration into the brain, the essential step required for development of
E. coli
meningitis.
Yersinia enterocoliticaPromotes Robust Mucosal Inflammatory T-Cell Immunity in Murine Neonates
Authors: Echeverry Andrea , Saijo Shinobu , Schesser Kurt , Adkins Becky
Published: June 2010

Mucosal immunity to gastrointestinal pathogens in early life has been studied only slightly. Recently, we developed an infection model in murine neonates using the gastroenteric pathogenYersinia enterocolitica. Here, we report that oral infection of neonatal mice with low doses of virulentY. enterocoliticaleads to vigorous intestinal and systemic adaptive immunity.Y. enterocoliticainfection promoted the development of anti-LcrV memory serum IgG1 and IgG2a responses of comparable affinity and magnitude to adult responses. Strikingly, neonatal mesenteric lymph node CD4+T cells producedYersinia-specific gamma interferon (IFN-γ) and interleukin-17A (IL-17A), exceeding adult levels. The robust T- and B-cell responses elicited in neonates exposed toY. enterocoliticawere associated with long-term protection against mucosal challenge with this pathogen. Using genetically deficient mice, we found that IFN-γ and CD4+cells, but not B cells, are critical for protection of neonates during primaryY. enterocoliticainfection. In contrast, adults infected with low bacterial doses did not require either cell population for protection. CD4-deficient neonatal mice adoptively transferred with CD4+cells from wild-type, IFN-γ-deficient, or IL-17AF-deficient mice were equally protected from infection. These data demonstrate that inflammatory CD4+T cells are required for protection of neonatal mice and that this protection may not require CD4-derived IFN-γ, IL-17A, or IL-17F. Overall, these studies support the idea thatY. enterocoliticapromotes the development of highly inflammatory mucosal responses in neonates and that intestinal T-cell function may be a key immune component in protection from gastrointestinal pathogens in early life.
A CROSS-CULTURAL STUDY ON RISK, UNCERTAINTY, AND INFORMATION
Authors: NARA YUMIKO
Published: June 2010

In this paper, the author aims to examine the differences in perception concerning the anxiety toward the risk among three countries — Japan, the United States of America and China. The anxiety, in this case, is triggered by uncertainty. This paper also intends to clarify the effect of information to improve people's risk management targeted on the respondents of the Chinese population focusing on earthquake disasters. The social survey using questionnaire has been carried out in order to obtain the needed quantitative data for my research project. It is interesting to conclude that both respondents in China and in the United States tend to accept the impact of uncertainty better. They have shown somewhat lower level of anxiety toward nineteen items of the risks as compared with that of the Japanese respondents. The significant effects on information designed as a part of the risk management action plan as well as the living sufficiency safeguard are clearly observed.
A FUZZY MATHEMATICAL MODEL OF NUCLEAR STABILITY
Authors: MORDESON JOHN N. , WETHING HILARY C. , CLARK TERRY D.
Published: June 2010

We use techniques from fuzzy mathematics to develop metrics for measuring how well the US is achieving its overarching national security goal: to protect itself, its allies and its friends from both nuclear attack and coercive pressures by states possessing nuclear weapons. The metrics are linear equations assigning weights to each of the six components of the overarching goal. These weights are based on expert opinions. We determine the degree to which the experts consider certain goals as the most important. We conclude by examining the degree of agreement among experts.
SCENARIO VIOLATION AS GAPS BETWEEN ACTIVITY PATTERNS
Authors: ABE AKINORI , OHSAWA YUKIO , KUWAHARA NORIAKI , OZAKU HIROMI ITOH , SAGARA KAORU , KOGURE KIYOSHI
Published: June 2010

In this paper, we propose interactive and visual discovery method of hidden factors for accidents or incidents. Accidents or incidents tend to occur because of very small differences from an ideal situation. From the above viewpoint, we introduce scenario violation model and regard scenario violation as a gap from the proper scenario. Previously, we proposed abduction-based scenario violation determination strategy, but in this paper, we adopt the Kamishibai-KeyGraph to analyze multiple patterns at the same time. Then, we show a gap discovery procedure by using the Kamishibai-KeyGraph.
The biostratigraphic importance of conchostracans in the continental Triassic of the northern hemisphere
Authors: Kozur Heinz W. , Weems Robert E.
Published: June 2010

Conchostracans or clam shrimp (order Conchostraca Sars) are arthropods with a carapace consisting of two chitinous lateral valves. Triassic conchostracans range in size from 2 to 12.5 mm long and are common in deposits that formed in fresh water lakes, isolated ponds and brackish areas. Their dessication- and freeze-resistant eggs can be dispersed by wind over long distances. Therefore many conchostracan species are distributed throughout the entire northern hemisphere. In the Late Permian to Middle Triassic interval, several of these forms are also found in Gondwana. Many wide-ranging conchostracan species have short stratigraphic ranges, making them excellent guide forms for subdivision of Triassic time and for long-range correlations. The stratigraphic resolution that can be achieved with conchostracan zones is often as high as for ammonoid and conodont zones found in pelagic marine deposits. This makes conchostracans the most useful group available for biostratigraphic subdivision and correlation in continental lake deposits. Upper Triassic Gondwanan conchostracan faunas are different from conchostracan faunas of the northern hemisphere. In the Norian, some slight provincialism can be observed even within the northern hemisphere. For example, the Sevatian
Redondestheria
seems to be restricted to North America and
Acadiestheriella
n. gen. so far has been found only in the Sevatian deposits from the Fundy Basin of southeastern Canada. Here we establish a conchostracan zonation for the Changhsingian (Late Permian) to Hettangian (Early Jurassic) of the northern hemisphere that, for the most part, is very well correlated with the marine scale. This zonation is especially robust for the Changhsingian to early Anisian, late Ladinian to Cordevolian and Rhaetian to Hettangian intervals. For most of the Middle and Upper Triassic, this zonation is still preliminary. Five new genera, six new species and a new subspecies of conchostracans are described that are stratigraphically important.