bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral DNA vaccines target the tumor vasculature and microenvironment and suppress tumor growth and metastasis
Authors: Xiang Rong , Luo Yunping , Niethammer Andreas G. , Reisfeld Ralph A.
Published: March 2008

Summary: Four novel oral DNA vaccines provide protection against melanoma, colon, breast, and lung carcinoma in mouse models. Vaccines are delivered by attenuated Salmonella typhimurium to secondary lymphoid organs and respectively target vascular endothelial growth factor receptor‐2, transcription factor Fos‐related antigen‐1, anti‐apoptosis protein survivin and Legumain, an asparaginyl endopeptidase specifically overexpressed on tumor‐associated macrophages (TAMs) in the tumor microenvironment (TME). These vaccines are all capable of inducing potent cell‐mediated protective immunity against self‐antigens, resulting in marked suppression of tumor growth and dissemination. Key mechanisms induced by these DNA vaccines include efficient suppression of angiogenesis in the tumor vasculature and marked activation of cytotoxic T cells, natural killer cells, and antigen‐presenting dendritic cells. The vaccine targeting Legumain establishes the new paradigm whereby a reduction in the density of TAMs in the TME decreases the release of factors potentiating tumor growth and angiogenesis. This, in turn, remodels the TME and decreases its immunosuppressive milieu and thereby potentiates the DNA vaccine's ability to effectively suppress tumor cell proliferation, vascularization, and metastasis. It is anticipated that such research efforts will lead to novel DNA‐based vaccines that will be effective for the treatment of cancer.
Multiple roles for CD4+ T cells in anti‐tumor immune responses
Authors: Kennedy Richard , Celis Esteban
Published: March 2008

Summary: Our understanding of the importance of CD4+ T cells in orchestrating immune responses has grown dramatically over the past decade. This lymphocyte family consists of diverse subsets ranging from interferon‐γ (IFN‐γ)‐producing T‐helper 1 (Th1) cells to transforming growth factor‐β (TGF‐β)‐secreting T‐regulatory cells, which have opposite roles in modulating immune responses to pathogens, tumor cells, and self‐antigens. This review briefly addresses the various T‐cell subsets within the CD4+ T‐cell family and discusses recent research efforts aimed at elucidating the nature of the ‘T‐cell help’ that has been shown to be essential for optimal immune function. Particular attention is paid to the role of Th cells in tumor immunotherapy. We review some of our own work in the field describing how CD4+ Th cells can enhance anti‐tumor cytotoxic T‐lymphocyte (CTL) responses by enhancing clonal expansion at the tumor site, preventing activation‐induced cell death and functioning as antigen‐presenting cells for CTLs to preferentially generate immune memory cells. These unconventional roles for Th lymphocytes, which require direct cell‐to‐cell communication with CTLs, are clear examples of how versatile these immunoregulatory cells are.
Reengineering dendritic cell‐based anti‐cancer vaccines
Authors: Koski Gary K. , Cohen Peter A. , Roses Robert E. , Xu Shuwen , Czerniecki Brian J.
Published: March 2008

Summary: Despite initial enthusiasm, dendritic cell (DC)‐based anti‐cancer vaccines have yet to live up to their promise as one of the best hopes for generating effective anti‐tumor immunity. One of the principal reasons for the generally disappointing results achieved thus far could be that the full potential of DCs has not been effectively exploited. Here, we argue that dramatic improvements in vaccine efficacy will probably require a careful re‐evaluation of current vaccine design. The formulation of new strategies must take into account the natural history of DCs, particularly their role in helping the immune system deal with infection. Equally critical is the emerging importance of soluble factors, notably interleukin‐12, in modulating the quality of immune responses. Vaccines should also be designed to recruit helper T cells and antibody‐producing B cells rather than simply cytotoxic T lymphocytes. Finally, the judicious selection of tumor, target antigen, and disease stage best suited for treatment should serve as the foundation of trial designs. Our discussion addresses a recent clinical vaccine trial to treat early breast cancer, where many elements of this new strategy were put into practice.
Strategies and challenges in eliciting immunity to melanoma
Authors: Ferguson Andrew R. , Nichols Lisa A. , Zarling Angela L. , Thompson Elizabeth D. , Brinkman C. Colin , Hargadon Kristian M. , Bullock Timothy N. , Engelhard Victor H.
Published: March 2008

Summary: The ability of CD8+ T cells to recognize melanoma tumors has led to the development of immunotherapeutic approaches that use the antigens CD8+ T cells recognize. However, clinical response rates have been disappointing. Here we summarize our work to understand the mechanisms of self‐tolerance that limit responses to currently utilized antigens and our approach to identify new antigens directly tied to malignancy. We also explore several aspects of the anti‐tumor immune response induced by peptide‐pulsed dendritic cells (DCs). DCs differentially augment the avidity of recall T cells specific for self‐antigens and overcome a process of aberrant CD8+ T‐cell differentiation that occurs in tumor‐draining lymph nodes. DC migration is constrained by injection route, resulting in immune responses in localized lymphoid tissue, and differential control of tumors depending on their location in the body. We demonstrate that CD8+ T‐cell differentiation in different lymphoid compartments alters the expression of homing receptor molecules and leads to the presence of systemic central memory cells. Our studies highlight several issues that must be addressed to improve the efficacy of tumor immunotherapy.
Antigen‐specific immunotherapy of cervical and ovarian cancer
Authors: Hung Chien‐Fu , Wu T. C. , Monie Archana , Roden Richard
Published: March 2008

Summary: We contrast the efforts to treat ovarian cancer and cervical cancer through vaccination because of their different pathobiology. A plethora of approaches have been developed for therapeutic vaccination against cancer, many of which target defined tumor‐associated antigens (TAAs). Persistent infection with oncogenic human papillomavirus (HPV) types causes cervical cancer. Furthermore, cervical cancer patients frequently mount both humoral and T‐cell immune responses to the HPV E6 and E7 oncoproteins, whose expression is required for the transformed phenotype. Numerous vaccine studies target these viral TAAs, including recent trials that may enhance clearance of pre‐malignant disease. By contrast, little is known about the etiology of epithelial ovarian cancer. Although it is clear that p53 mutation or loss is a critical early event in the development of epithelial ovarian cancer, no precursor lesion has been described for the most common serous histotype, and even the location of its origin is debated. These issues have complicated the selection of appropriate ovarian TAAs and the design of vaccines. Here we focus on mesothelin as a promising ovarian TAA, because it is overexpressed and immunogenic at high frequency in patients, is displayed on the cell surface, and potentially contributes to ovarian cancer biology.
A new technique to in vivo study the corneocyte features at the surface of the skin
Authors: Lévêque Jean Luc , François Ghislain , Sojic Neso , Giron Franck
Published: March 2008

Purpose of the study: To design, develop and validate a new device allowing the features of corneocytes at the surface of the skin to be visualized in vivo and objectively characterized.

Materials and methods: Monochromatic light is focused at the proximal end of a coherent bundle of optical fibres. Fluorescence of skin, stained with fluorescein, is then captured by the same fibre bundle and displayed, through a dichroic mirror, by a CCD camera. Fluorescence images are analysed using dedicated software to measure the projected area of cells.

Results: The new device allows the mean projected area of corneocytes to be routinely studied and quantified on most of the skin areas of the human body. Measurements carried out on two age groups of women confirm that corneocyte size on the forearm is smaller in young women than in older women.

Conclusion: The new non‐invasive device is easy to use and appear quite appropriate for cutaneous investigations carried out in clinical research.
Interaction between Lim15/Dmc1 and the homologue of the large subunit of CAF‐1 – a molecular link between recombination and chromatin assembly during meiosis
Authors: Ishii Satomi , Koshiyama Akiyo , Hamada Fumika N. , Nara Takayuki Y. , Iwabata Kazuki , Sakaguchi Kengo , Namekawa Satoshi H.
Published: March 2008

In eukaryotes, meiosis leads to genetically variable gametes through recombination between homologous chromosomes of maternal and paternal origin. Chromatin organization following meiotic recombination is critical to ensure the correct segregation of homologous chromosomes into gametes. However, the mechanism of chromatin organization after meiotic recombination is unknown. In this study we report that the meiosis‐specific recombinase Lim15/Dmc1 interacts with the homologue of the largest subunit of chromatin assembly factor 1 (CAF‐1) in the basidiomycete Coprinopsis cinerea (Coprinus cinereus). Using C. cinerea LIM15/DMC1 (CcLIM15) as the bait in a yeast two‐hybrid screen, we have isolated the C. cinerea homologue of Cac1, the largest subunit of CAF‐1 in Saccharomyces cerevisiae, and named it C. cinerea Cac1‐like (CcCac1L). Two‐hybrid assays confirmed that CcCac1L binds CcLim15 in vivo. β‐Galactosidase assays revealed that the N‐terminus of CcCac1L preferentially interacts with CcLim15. Co‐immunoprecipitation experiments showed that these proteins also interact in the crude extract of meiotic cells. Furthermore, we demonstrate that, during meiosis, CcCac1L interacts with proliferating cell nuclear antigen (PCNA), a component of the DNA synthesis machinery recently reported as an interacting partner of Lim15/Dmc1. Taken together, these results suggest a novel role of the CAF‐1–PCNA complex in meiotic events. We propose that the CAF‐1–PCNA complex modulates chromatin assembly following meiotic recombination.
Endogenous tetrahydroisoquinolines associated with Parkinson’s disease mimic the feedback inhibition of tyrosine hydroxylase by catecholamines
Authors: Scholz Joachim , Toska Karen , Luborzewski Alexander , Maass Astrid , Schünemann Volker , Haavik Jan , Moser Andreas
Published: March 2008

N‐methyl‐norsalsolinol and related tetrahydroisoquinolines accumulate in the nigrostriatal system of the human brain and are increased in the cerebrospinal fluid of patients with Parkinson’s disease. We show here that 6,7‐dihydroxylated tetrahydroisoquinolines such as N‐methyl‐norsalsolinol inhibit tyrosine hydroxylase, the key enzyme in dopamine synthesis, by imitating the mechanisms of catecholamine feedback regulation. Docked into a model of the enzyme’s active site, 6,7‐dihydroxylated tetrahydroisoquinolines were ligated directly to the iron in the catalytic center, occupying the same position as the catecholamine inhibitor dopamine. In this position, the ligands competed with the essential tetrahydropterin cofactor for access to the active site. Electron paramagnetic resonance spectroscopy revealed that, like dopamine, 6,7‐dihydroxylated tetrahydroisoquinolines rapidly convert the catalytic iron to a ferric (inactive) state. Catecholamine binding increases the thermal stability of tyrosine hydroxylase and improves its resistance to proteolysis. We observed a similar effect after incubation with N‐methyl‐norsalsolinol or norsalsolinol. Following an initial rapid decline in tyrosine hydroxylation, the residual activity remained stable for 5 h at 37 °C. Phosphorylation by protein kinase A facilitates the release of bound catecholamines and is the most prominent mechanism of tyrosine hydroxylase reactivation. Protein kinase A also fully restored enzyme activity after incubation with N‐methyl‐norsalsolinol, demonstrating that tyrosine hydroxylase inhibition by 6,7‐dihydroxylated tetrahydroisoquinolines mimics all essential aspects of catecholamine end‐product regulation. Increased levels of N‐methyl‐norsalsolinol and related tetrahydroisoquinolines are therefore likely to accelerate dopamine depletion in Parkinson’s disease.
Body Mass Index and its Association with Genitourinary Disorders in Men Undergoing Prostate Cancer Screening
Authors: Bhojani Naeem , Perrotte Paul , Hutterer Georg , Suardi Nazareno , Jeldres Claudio , Shariat Shahrokh F. , Capitanio Umberto , Arjane Philippe , Widmer Hugues , Benard Francois , Peloquin Francois , Montorsi Francesco , Karakiewicz Pierre
Published: March 2008

Introduction

Elevated body mass index (BMI) may predispose to several pelvic pathologies.

Aims

We tested the association between BMI and five end points, namely, (i) erectile dysfunction (ED); (ii) lower urinary tract symptoms (LUTS); (iii) chronic prostatitis-associated pain (CPP); and ejaculatory dysfunction that is subdivided between (iv) pain/discomfort on ejaculation; and (v) subjectively decreased ejaculate volume.

Methods

Age, height, and weight were prospectively recorded in a cohort of 590 consecutive healthy men undergoing prostate cancer screening. Continuously coded and categorized BMI (World Health Organization classification) were studied.

Main Outcome Measures

Age-adjusted analyses relied on logistic and linear regression models, according to data type.

Results

The average age was 54.1 years (range 30–83). Of all, 296 were overweight (50.2%, BMI 25–29.9 kg/m2) and 85 were obese (14.4%, BMI ≥ 30 kg/m2). After age adjustment, elevated continuously coded BMI (P < 0.001) and elevated categorized BMI (P = 0.01) were associated with worse erectile function. Conversely, after age adjustment, elevated continuously coded BMI (P = 0.02) and elevated categorized BMI (P = 0.05) were associated with a lower rate of subjectively decreased ejaculate volume. Finally, after age adjustment, elevated categorically coded BMI was related to lower rates of CPP (P < 0.001) and to a lower rate of pain/discomfort on ejaculation (P = 0.03).

Conclusions

In men undergoing prostate cancer screening, the effect of BMI on the five end points is not invariably detrimental. Elevated BMI may predispose to ED, but may also decrease the rate of pain/discomfort on ejaculation and may lower the reported rate of subjectively decreased ejaculate volume. Finally, it appeared to have no effect on LUTS.
Sexual Attitude and Perception on Sexual Relationship Among Long-Term Users of Sildenafil
Authors: Kim Sae-Chul
Published: March 2008

Introduction

High discontinuation rates of sildenafil were reported in its respdonders.

Aim

To investigate perception on and attitude toward sex among long-term users of sildenafil

Methods

A survey was conducted using random face-to-face interviews and a structured questionnaire on a population of 105 long-term sildenafil users (mean age; 57.8 years), who first took sildenafil 5 years or more previously and continued its use in the previous 6 months.

Main Outcome Measures

Six point-scale of perception on and attitude toward sex and valuation of sildenafil.

Results

Among the long-term users, 98% perceived that it is desirable to have sex even though they get old if they are healthy, 93% had a positive attitude toward sex, and 97% had an intercourse-focused perception of sexual relationship; these rates were higher for those with a lower income and less education. And 59% had intercourses and 40% took sildenafil one to two times a week. They ranked prominence in rigidity of erection as the major reason for the long-term sildenafil use. The rigidity was maintained after more than 5-year use.

Conclusion

An overall majority of the long-term users of sildenafil had a positive attitude toward sex, an active sexual behavior, and an intercourse-focused perception on sexual relationship. Sildenafil provided an optimal fit for the patients' needs. Prominence in rigidity of erection was ranked as the major reason for the long-term use.
The Impact of Lower Urinary Tract Symptoms and Urinary Incontinence on Female Sexual Dysfunction Using a Validated Instrument
Authors: Cohen Brian L. , Barboglio Paholo , Gousse Angelo
Published: March 2008

Introduction

Lower urinary tract symptoms (LUTS) is a common problem in women and frequently coexists with female sexual dysfunction (FSD). However, the relationship of LUTS and FSD is poorly characterized.

Aim

To evaluate the relationship of LUTS and urinary incontinence (UI) to FSD using a validated instrument, the female sexual function index (FSFI).

Methods

We performed an institutional review board-approved retrospective evaluation of 236 female patients over a 3-year time-period who completed an FSFI-validated questionnaire and underwent urodynamics (UDS) evaluation for LUTS or UI. Patients were categorized based upon history and physical exam into different LUTS groups. Additionally, the presence or absence of UI, detrusor overactivity (DO), stress urinary incontinence, and maximal cystometric capacity (MCC) > or <200 mL on UDS were used to further evaluate these patients. FSFI domain and total scores were compared between the different LUTS groups.

Main Outcome Measure

FSFI scores were evaluated for women with similar clinical LUTS diagnosis and UDS findings. The Kruskal–Wallis nonparametric test and the Dwass–Steel test determined statistical significance and performed multiple pairwise comparisons between the different voiding dysfunction groups and those with normal UDS (Leak-/DO-/urodynamic stress incontinence-).

Results

The mean age of the cohort was 49.5 (range 18–69), and there was no statistically significant difference in mean age within each LUTS subgroup. MCC<200 mL did not significantly impair female sexual function. Patients with clinical diagnosis of overactive bladder (OAB)-Dry had the highest sexual function while those with mixed urinary incontinence had the worst. Additionally, women with UI and DO had the greatest degree of FSD, which was significantly worse than those with normal UDS. Additionally, for women with or without UI, the presence of DO on UDS resulted in a trend toward worse sexual function.

Conclusions

The sexual function of women is negatively impacted by the presence of LUTS, with UI and DO causing the greatest degree of FSD. The sexual domains most affected are desire, lubrication, orgasm, and sexual satisfaction.
Something old, something new…
Authors: Stanley Kate , Cooke Graeme
Published: March 2008

Kate Stanley and Graeme Cooke argue that while the Conservatives’take on marriage and families is fundamentally flawed, we are yet to see a convincing narrative on the institution emerge from the centre‐left.
The lost generation
Authors: Paintin Katie
Published: March 2008

Katie Paintin argues that Sierra Leone's forgotten youth offer the key to stability in the country
FORCE, RATE AND WORK USED DURING INCISOR PENETRATION ON DIFFERENT TEXTURAL FOODS
Authors: XU XIANZHONG , WRIGHT PAUL S. , HECTOR MARK P. , HEATH M. ROBIN , FERMAN ANTONY M.
Published: March 2008

Experiments have been performed to study the biting force, rate of penetration and hence, energy expenditure during first‐bite incision of a variety of foodstuffs (cheese, apple, carrot and Hula Hoops). Biting forces were measured using a gauged cantilever beam mounted in an acrylic denture, and jaw movement was measured using a Sirognathograph system. The biting work, biting force rate and tooth velocity were calculated and analyzed in terms of those original measurements of biting force and tooth displacement. The results show that the maximum biting force, the maximum penetration rate and the total work used during incisor penetration were strongly dependent on the food texture (both size and mechanical properties). The effects of the food properties and sample size on those biting variables mentioned above are related to the stress–strain behaviors (including the viscoelasticity) of foods tested and the chewing pattern “matching” mechanism.

PRACTICAL APPLICATIONS

The study of the relationships between mastication variables, texture perception and the mechanical properties of foodstuffs is very important in food science and dentistry. Such knowledge could lead to improved strategies for new product design and good quality control in the food industry, and to extend from the restricted food choice and eating behavior imposed by limited chewing effectiveness of children with deciduous teeth to the dietary restrictions of the people with dentures. The presented work shows that the energy expenditure as well as the forces and teeth velocities during mastication may be a connector between food texture properties and the capabilities of the chewing muscles. This provides a new way to link masticatory behaviors and sensory assessment results, which gives a clear clue to clarify the nature of sensory perception of food texture and to understand the food reduction mechanisms during oral process.
PREDICTING SENSORY COHESIVENESS, HARDNESS AND SPRINGINESS OF SOLID FOODS FROM INSTRUMENTAL MEASUREMENTS
Authors: DI MONACO R. , CAVELLA S. , MASI P.
Published: March 2008

The sensory evaluation of cohesiveness, hardness and springiness of 15 solid food samples was performed by eight trained assessors. The rheologic response of the 15 samples was estimated by performing cyclic compression tests and stress–relaxation tests.

From the force–deformation curves of the first two cycles of the compression test, texture profile analysis parameters related to cohesiveness, hardness and springiness were calculated. Young's modulus (E), strain (di) and stress (si) at peak as well as irrecoverable strain (ri) and irrecoverable work (Li) were monitored during the first five cycles. From the stress–relaxation response, Peleg's linearization model parameters, K1 and K2, were estimated by best‐fit regression. These parameters were used for predicting sensory attributes.

Hardness and springiness were both accurately predicted by rheologic properties, while cohesiveness prediction was less representative.

PRACTICAL APPLICATIONS

This study contributes to enhance the knowledge in the research area of sensory instrumental correlation. Also, the research allows to better understanding that no single instrument is able to measure all texture attributes adequately. In fact, the results demonstrate that both stress–relaxation and cyclic compression tests need to be performed for the correct prediction of sensory responses.
THE USE OF TOMATO PULP POWDER AS A THICKENING AGENT IN THE FORMULATION OF TOMATO KETCHUP
Authors: FARAHNAKY A. , ABBASI A. , JAMALIAN J. , MESBAHI G.
Published: March 2008

In this current study, tomato pulp powder, the main waste of the tomato processing industry, was used as a thickening agent in the formulation of a commercial tomato ketchup at different levels (1, 2, 5, 7 and 10% w/w). Color parameters (L and a/b) and rheologic properties of the formulated ketchups with and without added tomato pulp powder were determined and compared. The addition of the pulp powder caused a significant increase in the L value of the samples, while a/b ratio decreased notably. The rheologic data obtained were fitted using a power law equation. The analysis of the data obtained revealed that low levels of tomato pulp powder can compete with other hydrocolloids in improving the consistency of tomato ketchup. All ketchup samples in this study were non‐Newtonian fluids and the apparent viscosity of the ketchups increased significantly with increasing concentration of tomato pulp powder and decreased with temperature increase.

Chemical composition (protein, total fat, reducing and total sugars, fiber, ascorbic acid and ash contents) and some physicochemical properties of the tomato pulp powder, including water absorption and solubility, were determined and the data were used for the interpretation of the rheologic and color changes as a result of the inclusion of the pulp powder in the formulation.

PRACTICAL APPLICATIONS

The direct use of food industry wastes in food formulations can help in reducing the production costs by decreasing raw material and disposal costs. The classic design of the tomato processing plants results in generating a large amount of tomato pulp. The results of this research confirmed that tomato pulp powder can be used instead of other hydrocolloids in tomato‐based products. The reuse of tomato pulp powder in foods can be beneficial to producers and the environment.
The Theory of Constraints and the Make‐or‐Buy Decision: An Update and Review
Authors: Balakrishnan Jaydeep , Cheng Chun Hung
Published: March 2008

The make‐or‐buy decision has traditionally been made using standard cost accounting methods. In this Journal, Gardiner and Blackstone (1991) made a strong case for incorporating the bottleneck capacity into the decision. However, their method did not guarantee the best solution for the more complicated make‐or‐buy problem. Additionally, their approach in some cases allowed organizations to forego opportunities for profit improvement. Since the publication of the Gardiner and Blackstone research, spreadsheets with in‐built Linear Programming (LP) based optimizers allow for quick “what‐if” analyses that encourage efforts toward optimal solutions for complicated problems. This article is a review and update of the Gardiner and Blackstone methodology based on spreadsheet LP that provides enhanced solutions in complex environments with multiple products and bottleneck situations. Specific managerial implications are offered.
Susceptibility of canine and feline Escherichia coli and canine Staphylococcus intermedius isolates to fluoroquinolones
Authors: Gottlieb S , Wigney DI , Martin PA , Norris JM , Malik R , Govendir M
Published: March 2008

Objectives and design  1) A prospective study to determine in vitro concentrations for a range of fluoroquinolones, gentamicin and amoxycillin‐clavulanate required to inhibit growth of recently collected, feline and canine Escherichia coli and canine Staphylococcus intermedius isolates. 2) A comparative retrospective study to compare the minimum inhibitory concentrations (MICs) of ciprofloxacin, enrofloxacin and amoxycillin‐clavulanate for archived canine E coli and S intermedius isolates collected ten to twenty years earlier, with those for recently collected isolates.

Procedure  Susceptibility was assessed using disk diffusion, agar dilution susceptibility testing and Epsilometer tests (E‐tests) for both recently collected and archived isolates.

Results  All feline E coli isolates and recently collected canine S intermedius isolates were susceptible to all fluoroquinolones. There was a statistically significant increase in the MIC range of ciprofloxacin and enrofloxacin for recently collected E coli, and in the MIC range of amoxycillin‐clavulanate for recently collected S intermedius isolates compared to archived isolates. Twelve of 59 recently collected canine E coli isolates were resistant to both ciprofloxacin and enrofloxacin. Resistant canine E coli isolates were associated with complicating host or infection site factors.

Conclusion  This is the first report comparing the MICs for all veterinary fluoroquinolones currently available in Australia for a representative sample of canine and feline E coli and canine S intermedius isolates. Importantly, this study identified 12 of 59 canine E coli isolates resistant to fluoroquinolones and identified the development of low level resistance in canine E coli to ciprofloxacin and enrofloxacin and canine S intermedius to amoxycillin‐clavulanate.
Serologic cross‐reactivity of AustralianMoraxella bovisto vaccinal bacterin strains as determined by competitive ELISA
Authors: McConnel CS , Shum L , Gleeson BL , House JK
Published: March 2008

Objective To conduct a serologic survey and define pili antigenic variability via the serologic cross‐reactivity ofMoraxella bovisisolates from naturally occurring infectious bovine keratoconjunctivitis (IBK) outbreaks in Australia. This project applies to the development of anM bovispili‐based vaccine targeting Australian strains originating from intensive cattle producing regions.

Procedure Ocular swabs were collected from cattle affected with clinical signs of IBK from 25 veterinary practices. Standard criteria were used to identify 70M bovis. Pure, piliated isolates were evaluated with a modified competitive enzyme‐linked immunosorbent assay (ELISA) for cell‐boundM bovispili to determine their serologic cross‐reactivity with pili of vaccinal bacterin strains EPP63, FLA64, and SAH 38.

Results Sixty‐four percent (45/70) ofM bovisisolates demonstrated homologous pili antigens to a vaccinal strain.M bovisisolates homologous to one of the three vaccinal strains were obtained in 77% (34/44) of IBK outbreaks sampled. No IBK outbreak had isolates homologous to more than one vaccinal strain; however, 29% (10/34) of outbreaks with a cross‐reacting strain had non‐cross‐reacting strains as well.

Conclusion The similar prevalence of pilus antigen homology to strain FLA64 was observed with isolates derived from NSW, Tasmania, and Victoria, compared with results of prior smaller serologic studies, suggests that the common pilus antigens inM boviswithin Australia have been relatively stable over the last 20 years. The prevalence of a limited number of pilus antigens inM bovissuggest that the application of a vaccine containing the bacterial strains EPP63, FLA64, and SAH38 may provide a useful management tool for reducing production losses associated with IBK in Australia.
Isolation of caprine herpesvirus 1 from a major outbreak of infectious pustular vulvovaginitis in goats
Authors: Piper KL , Fitzgerald CJ , Ficorilli N , Studdert MJ
Published: March 2008

We describe an outbreak of infectious pustular vulvovaginitis caused by Caprine herpesvirus 1 (CpHV1) in a group of approximately 200, 8 month old virgin does that were imported to Victoria from New Zealand. CpHV1 was isolated in cell cultures from vaginal swabs from three of three affected does but not from two bucks that had been with the does. The identity of the virus as a herpesvirus was confirmed by negative stain electron microscopy. Restriction endonuclease DNA fingerprint analysis showed that the DNA fingerprints were similar, but not identical, to previously described CpHV1 isolates made in New Zealand, New South Wales, and in other parts of the world. Acute and convalescent phase sera from selected does supported the diagnosis of CpHV1 infection. It is most likely that the disease was initiated by reactivation of latent virus in at least one of four bucks that served the does, since each was positive for CpHV neutralising antibody when first tested. This is the first report of CpHV infectious pustular vulvovaginitis in goats in Victoria and to our knowledge appears to be one of the largest outbreaks recorded anywhere.
Correlates of Fatigue in Patients With Heart Failure
Authors: Evangelista Lorraine S. , Moser Debra K. , Westlake Cheryl , Pike Nancy , Ter‐Galstanyan Alvina , Dracup Kathleen
Published: March 2008

This study was conducted to determine the prevalence of fatigue and identify its demographic, clinical, and psychological correlates in 150 heart failure (HF) patients (73% men, 66% Caucasian, mean age 55.0 years, mean ejection fraction 26.7%±11%), from a single HF center, using the Profile of Mood States‐Fatigue Subscale, the Minnesota Living With Heart Failure Questionnaire, and the Beck Depression Inventory. Sociodemographic and clinical data were obtained through self‐report and chart abstraction. High levels of fatigue were reported in 50.4% of men and 51.2% of women. In a multivariate model, maximal workload, physical health, emotional health, and depression explained 51% of the variance in fatigue (P<.001). Fatigue in patients with HF is associated with both clinical and psychosocial variables, offering a number of targets for intervention. These findings suggest the need for multiple risk factor intervention strategies that improve physical and emotional health to decrease fatigue. Patients with depression warrant particular scrutiny.
Sleep‐Disordered Breathing, Cognitive Functioning, and Adherence in Heart Failure: Linked Through Pathology?
Authors: Trupp Robin J. , Corwin Elizabeth J.
Published: March 2008

Heart failure (HF) is well recognized as a condition resulting from chronic neurohormonal activation. Sleep‐disordered breathing (SDB) as a neurohormonal disorder is less recognized. In SDB, whether obstructive or central in nature, nightly repetitive cycles of hypoxia‐reoxygenation produce intense sympathetic activation and deprive the body of much needed sleep. Both HF and SDB are associated with fatigue, cognitive impairment, and challenges for adherence to prescribed therapies. Together, the combination of HF and SDB can have particularly ominous consequences for cognitive functioning, decision making, adherence and, ultimately, outcomes. The suboptimal adherence seen in patients with both HF and SDB may result from a neurohormonal synergism that exists between the 2 conditions.
Synthesis and Design of a Novel 3T1R Fully-Parallel Manipulator
Authors: Salgado Oscar , Altuzarra Oscar , Petuya Víctor , Hernández Alfonso
Published: March 2008

In this paper a new topology of four degrees-of-freedom 3T1R fully-parallel manipulator is presented, which is defined only using lower kinematic pairs. The paper starts with a complete type synthesis of different topologies of fully-parallel manipulators that can perform the so-called Schönflies motion, based on the Theory of Groups of Displacements. After imposing some practical requirements, the different possibilities of manipulators are reduced to only one topology of fully-parallel and fully-symmetrical parallel manipulator. Then, the kinematic analysis of the manipulator is shown, including the closed-form resolution of both forward and inverse position problems, the velocity and the singularity analysis. Finally, a prototype of the manipulator is presented, which is intended to be used in pick and place applications.
Optimal Choice of the Shaft Angle for Involute Gear Hobbing
Authors: Innocenti Carlo
Published: March 2008

With reference to the machining of an involute spur or helical gear by the hobbing process, the paper suggests a new criterion for selecting the position of the hob axis relative to the gear axis. By adhering to the proposed criterion, the hob axis is set at the minimum distance from the gear axis, thus maximizing the depth of the tooth spaces of the gear. The new criterion is operatively implemented by solving a univariate equation, which stems from a new, synthetic analysis of the meshing of crossed-axis involute gears. A numerical example shows application of the suggested procedure to a case study and compares the optimal hob setting to the customary one.
Spherical Bistable Micromechanism
Authors: Lusk Craig P. , Howell Larry L.
Published: March 2008

A new micromechanism, the spherical bistable micromechanism (SBM), is described. The SBM has several advantageous features, which include two stable positions that require power only in transitioning from one position to the other; robustness against small disturbances; and a compact footprint and an output link with a stable out-of-plane orientation. The SBM may be useful in applications such as 2D optical mirror arrays or in erecting out-of-plane structures.
An Experimental Study of the Influence of Manufacturing Errors on the Planetary Gear Stresses and Planet Load Sharing
Authors: Ligata H. , Kahraman A. , Singh A.
Published: March 2008

In this paper, results of an experimental study are presented to describe the impact of certain types of manufacturing errors on gear stresses and the individual planet loads of an n-planet planetary gear set (n=3–6). The experimental setup includes a specialized test apparatus to operate a planetary gear set under typical speed and load conditions and gear sets having tightly controlled intentional manufacturing errors. The instrumentation system consists of multiple strain gauges mounted on the ring gear and a multichannel data collection and analysis system. A method for computing the planet load-sharing factors from root strain-time histories is proposed. Influence of carrier pinhole position errors on gear root stresses is quantified for various error and torque values applied to gear sets having three to six planets. The results clearly indicate that manufacturing errors influence gear stresses and planet load sharing significantly. Gear sets having larger number of planets are more sensitive to manufacturing errors in terms of planet load-sharing behavior.
Nanominerals, Mineral Nanoparticles, and Earth Systems
Authors: Hochella Michael F. , Lower Steven K. , Maurice Patricia A. , Penn R. Lee , Sahai Nita , Sparks Donald L. , Twining Benjamin S.
Published: March 2008

Minerals are more complex than previously thought because of the discovery that their chemical properties vary as a function of particle size when smaller, in at least one dimension, than a few nanometers, to perhaps as much as several tens of nanometers. These variations are most likely due, at least in part, to differences in surface and near-surface atomic structure, as well as crystal shape and surface topography as a function of size in this smallest of size regimes. It has now been established that these variations may make a difference in important geochemical and biogeochemical reactions and kinetics. This recognition is broadening and enriching our view of how minerals influence the hydrosphere, pedosphere, biosphere, and atmosphere.
Comment on "Physical Model for the Decay and Preservation of Marine Organic Carbon"
Authors: Boudreau Bernard P. , Arnosti Carol , Jørgensen Bo Barker , Canfield Donald E.
Published: March 2008

Rothman and Forney (Reports, 1 June 2007, p. 1325) described a model for the decay of marine organic carbon. However, the enzyme deactivation rates required by their model are too fast compared with available data, and the model fails to explain the similarity in observed decay rate constants from different experiments. Alternative models provide equally good fit to the observed temporal trend in decay rate constants.
Chloride-Bearing Materials in the Southern Highlands of Mars
Authors: Osterloo M. M. , Hamilton V. E. , Bandfield J. L. , Glotch T. D. , Baldridge A. M. , Christensen P. R. , Tornabene L. L. , Anderson F. S.
Published: March 2008

Chlorides commonly precipitate during the evaporation of surface water or groundwater and during volcanic outgassing. Spectrally distinct surface deposits consistent with chloride-bearing materials have been identified and mapped using data from the 2001 Mars Odyssey Thermal Emission Imaging System. These deposits are found throughout regions of low albedo in the southern highlands of Mars. Geomorphologic evidence from orbiting imagery reveals these deposits to be light-toned relative to their surroundings and to be polygonally fractured. The deposits are small (< ∼25 km
2
) but globally widespread, occurring in middle to late Noachian terrains with a few occurrences in early Hesperian terrains. The identification of chlorides in the ancient southern highlands suggests that near-surface water was available and widespread in early Martian history.
Atmospheric Hydroxyl Radical Production from Electronically Excited NO
2
and H
2
O
Authors: Li Shuping , Matthews Jamie , Sinha Amitabha
Published: March 2008

Hydroxyl radicals are often called the “detergent” of the atmosphere because they control the atmosphere's capacity to cleanse itself of pollutants. Here, we show that the reaction of electronically excited nitrogen dioxide with water can be an important source of tropospheric hydroxyl radicals. Using measured rate data, along with available solar flux and atmospheric mixing ratios, we demonstrate that the tropospheric hydroxyl contribution from this source can be a substantial fraction (50%) of that from the traditional O(
1
D) + H
2
O reaction in the boundary-layer region for high solar zenith angles. Inclusion of this chemistry is expected to affect modeling of urban air quality, where the interactions of sunlight with emitted NO
x
species, volatile organic compounds, and hydroxyl radicals are central in determining the rate of ozone formation.
Drosophila
Egg-Laying Site Selection as a System to Study Simple Decision-Making Processes
Authors: Yang Chung-hui , Belawat Priyanka , Hafen Ernst , Jan Lily Y. , Jan Yuh-Nung
Published: March 2008

The ability to select a better option from multiple acceptable ones is important for animals to optimize their resources. The mechanisms that underlie such decision-making processes are not well understood. We found that selection of egg-laying site in
Drosophila melanogaster
is a suitable system to probe the neural circuit that governs simple decision-making processes. First,
Drosophila
females pursue active probing of the environment before depositing each egg, apparently to evaluate site quality for every egg. Second,
Drosophila
females can either accept or reject a sucrose-containing medium, depending on the context. Last, communication of the “acceptability” of the sucrose-containing medium as an egg-laying option to the reproductive system depends on the function of a group of insulin-like peptide 7 (ILP7)–producing neurons. These findings suggest that selection of egg-laying site involves a simple decision-making process and provide an entry point toward a systematic dissection of this process.
Activation of FOXO1 by Cdk1 in Cycling Cells and Postmitotic Neurons
Authors: Yuan Zengqiang , Becker Esther B. E. , Merlo Paola , Yamada Tomoko , DiBacco Sara , Konishi Yoshiyuki , Schaefer Erik M. , Bonni Azad
Published: March 2008

Activation of cyclin-dependent kinase 1 (Cdk1) has been linked to cell death of postmitotic neurons in brain development and disease. We found that Cdk1 phosphorylated the transcription factor FOXO1 at Ser
249
in vitro and in vivo. The phosphorylation of FOXO1 at Ser
249
disrupted FOXO1 binding with 14-3-3 proteins and thereby promoted the nuclear accumulation of FOXO1 and stimulated FOXO1-dependent transcription, leading to cell death in neurons. In proliferating cells, Cdk1 induced FOXO1 Ser
249
phosphorylation at the G
2
/M phase of the cell cycle, resulting in FOXO1-dependent expression of the mitotic regulator Polo-like kinase (Plk). These findings define a conserved signaling link between Cdk1 and FOXO1 that may have a key role in diverse biological processes, including the degeneration of postmitotic neurons.
A Nitric Oxide–Inducible Lactate Dehydrogenase Enables
Staphylococcus aureus
to Resist Innate Immunity
Authors: Richardson Anthony R. , Libby Stephen J. , Fang Ferric C.
Published: March 2008

Staphylococcus aureus
is one of the most successful human pathogens, colonizing 2 billion individuals worldwide and causing invasive infections even in immunocompetent hosts.
S. aureus
can evade multiple components of host innate immunity, including the antimicrobial radical nitric oxide (NO
⚫
) produced by activated phagocytes. We show that
S. aureus
is capable of metabolically adapting to nitrosative stress by expressing an NO
⚫
-inducible
l
-lactate dehydrogenase (
ldh
1, SACOL0222) divergently transcribed from the NO
⚫
-detoxifying flavohemoglobin (
hmp
).
l
-Lactate production allows
S. aureus
to maintain redox homeostasis during nitrosative stress and is essential for virulence. NO
⚫
-inducible lactate dehydrogenase activity and NO
⚫
resistance distinguish
S. aureus
from the closely related commensal species
S. epidermidis
and
S. saprophyticus
.
Diagnosis of Tuberculous Meningitis Due to Detection of ESAT-6-Specific Gamma Interferon Production in Cerebrospinal Fluid Enzyme-Linked Immunospot Assay
Authors: Murakami Shuji , Takeno Mitsuhiro , Oka Hideaki , Ueda Atsuhisa , Kurokawa Takashi , Kuroiwa Yoshiyuki , Ishigatsubo Yoshiaki
Published: March 2008

A coma patient was diagnosed with tuberculous meningitis by the detection of ESAT-6-specific gamma interferon-secreting cells in the patient's cerebrospinal fluid by enzyme-linked immunospot assay prior to the identification of the pathogen in a culture of the cerebrospinal fluid.
Infection of Macrophages and Dendritic Cells with Primary R5-Tropic Human Immunodeficiency Virus Type 1 Inhibited by Natural Polyreactive Anti-CCR5 Antibodies Purified from Cervicovaginal Secretions
Authors: Eslahpazir Jobin , Jenabian Mohammad-Ali , Bouhlal Hicham , Hocini Hakim , Carbonneil Cédric , Grésenguet Gérard , Kéou François-Xavier Mbopi , LeGoff Jérôme , Saïdi Héla , Requena Mary , Nasreddine Nadine , de Dieu Longo Jean , Kaveri Srinivas V. , Bélec Laurent
Published: March 2008

Heterosexual contact is the primary mode of human immunodeficiency virus (HIV) type 1 (HIV-1) transmission worldwide. The chemokine receptor CCR5 is the major coreceptor that is associated with the mucosal transmission of R5-tropic HIV-1 during sexual intercourse. The CCR5 molecule is thus a target for antibody-based therapeutic strategies aimed at blocking HIV-1 entry into cells. We have previously demonstrated that polyreactive natural antibodies (NAbs) from therapeutic preparations of immunoglobulin G and from human breast milk contain NAbs directed against CCR5. Such antibodies inhibit the infection of human macrophages and T lymphocytes by R5-tropic isolates of HIV in vitro. In the present study, we demonstrate that human immunoglobulins from the cervicovaginal secretions of HIV-seronegative or HIV-seropositive women contain NAbs directed against the HIV-1 coreceptor CCR5. Natural affinity-purified anti-CCR5 antibodies bound to CCR5 expressed on macrophages and dendritic cells and further inhibited the infection of macrophages and dendritic cells with primary and laboratory-adapted R5-tropic HIV but not with X4-tropic HIV. Natural anti-CCR5 antibodies moderately inhibited R5-tropic HIV transfer from monocyte-derived dendritic cells to autologous T cells. Our results suggest that mucosal anti-CCR5 antibodies from healthy immunocompetent donors may hamper the penetration of HIV and may be suitable for use in the development of novel passive immunotherapy regimens in specific clinical settings of HIV infection.
Simultaneous Genotyping of All Hemagglutinin and Neuraminidase Subtypes of Avian Influenza Viruses by Use of Padlock Probes
Authors: Gyarmati Péter , Conze Tim , Zohari Siamak , LeBlanc Neil , Nilsson Mats , Landegren Ulf , Banér Johan , Belák Sándor
Published: March 2008

A subtyping assay for both the hemagglutinin (HA) and neuraminidase (NA) surface antigens of the avian influenza virus (AIV) has been developed. The method uses padlock probe chemistry combined with a microarray output for detection. The outstanding feature of this assay is its capability to designate both the HA and the NA of an AIV sample from a single reaction mixture. A panel of 77 influenza virus strains was tested representing the entire assortment of the two antigens. One hundred percent (77/77) of the samples tested were identified as AIV, and 97% (75/77) were subtyped correctly in accordance with previous examinations performed by classical diagnostic methods. Testing of heterologous pathogens verified the specificity of the assay. This assay is a convenient and practical tool for the study of AIVs, providing important HA and NA data more rapidly than conventional methods.