bluuebunny/crossref_metadata_2025 huggingface dataset:
Open the Door Whenever Opportunity Knocks
Authors: Downs Mallery H. , Kaminsky Alexis , Lewis Johnnye
Published: September 2006

ABSTRACT
The Community Environmental Health Program/Community Outreach and Education Program (CEHP/COEP) New Mexico Center for Environmental Health Sciences has learned that listening and responding to opportunities that arise in local communities can be a more effective means of reaching health care providers, lay health workers, and community members than structured plans of action. While specific opportunities that have occurred in New Mexico may be unique, they are presented here with the hope that they might suggest new strategies to the reader and help to identify parallel opportunities in other communities. The paper is organized around three major opportunities to which CEHP/COEP has responded: (1) the need for more informed health care in communities with unique and complex environmental and occupational exposures due to their proximity to National Laboratories; (2) the need for resources on environmental health within local provider networks and issue‐specific groups; and (3) the need for community environmental health projects within the College of Nursing. CEHP/COEP's responses, observations, and lessons learned through these experiences are discussed. In the end, the major lesson is that the ability to respond to opportunities requires flexibility and creativity; by sticking doggedly to plans, valuable—and sometimes more profitable and productive—opportunities may be missed.
Does Dixon's Integrative Environmental Health Model Inform an Understanding of Rural Parents' Perceptions of Local Environmental Health Risks?
Authors: Harnish Kelly E. , Butterfield Patricia , Hill Wade G.
Published: September 2006

ABSTRACT
A qualitative study of parents' perceptions of local environmental health risks was conducted to assess the fit between concepts from Dixon's Integrative Environmental Health Model (DIEH model) and field‐generated data. This research was part of a prospective study addressing environmental exposures of rural low‐income children. Home visit data from 11 parents were analyzed (1) thematically and (2) according to DIEH concepts. These complementary analyses allowed the researchers to examine perceptions that were congruent with or diverged from the DIEH model. Findings revealed that participants were concerned about children's exposure to pathogenic molds and cigarette smoke and felt uninformed about risks and prevention strategies. Barriers to preventive actions included families' lack of time and a disinterest in brochures. Participants reported being “stuck” in substandard housing by poverty and family demands. They expressed concern about risks, but were unsure “what to worry about.” Results provided the researchers with confidence that the DIEH model aligned with participants' cognitive constructions of risk. As a result, the DIEH model was incorporated into the conceptualization for the clinical trial phase of the study. This type of check between a theoretical approach and field data can be a helpful intermediate step for researchers involved in multiyear studies.
The Spanish Influenza of 1918 in St. Louis, Missouri
Authors: Kalnins Irene
Published: September 2006

ABSTRACT
In view of current concern about a possible pandemic of virulent avian influenza, it is timely to revisit the public health response to the “Spanish” influenza of 1918. St. Louis, Missouri, was the most successful of nine largest cities in limiting the death toll from influenza and pneumonia through the use of public health measures during the first 8 weeks of the epidemic. A second wave of cases increased the final death rate, but it remained below that of other major cities. Public health officials attributed the lower death rate to the early and rigorous ban on public gatherings.
CPU86017: a Novel Class III Antiarrhythmic Agent with Multiple Actions at Ion Channels
Authors: Dai De‐Zai
Published: September 2006

CPU86017 is a novel Class III antiarrhythmic agent derived from berberine and with an improved pharmacological profile, solubility and bioavailability. It is active in suppressing arrhythmias in several animal models. The ED50 of CPU86017 for suppressing ischemia/reperfusion arrhythmias in rats was 0.22 mg/kg against 2.23 mg/kg for lidocaine. CPU86017 is about 10‐fold more potent than lidocaine. It blocks IKR.tail, IKS, and ICaL currents with IC50 values of 25, 14.4, and 11.5 μM, respectively. The plasma t1/2 of CPU86017, i.v. bolus, in rabbits and dogs is approximately 90 min. The effective plasma levels of CPU86017 in rabbits required to delay the appearance of oubain‐induced ventricular arrhythmias is in the range of 0.13–0.31 μg/mL. Higher levels of the drug are required to eliminate ventricular arrhythmias produced by two‐stage ligation of the coronary artery in anesthetized dogs. Drug levels in myocardium are much higher than in plasma. CPU80617 has an antioxidant effect that is likely to contribute to its antiarrhythmic activity. The abnormal expression of the ryanodine receptor type 2 (RyR2) and of FKBP12.6 is reduced by CPU80617 during its ventricular tachyarrhythmia‐suppressing action. CPU86017 appears to be a promising antiarrhythmic agent with a cardioprotective action. It can be expected to protect from malignant arrhythmias and sudden cardiac death by suppressing molecular events caused by channelopathies.
Role of Adenosine as Adjunctive Therapy in Acute Myocardial Infarction
Authors: Forman Mervyn B. , Stone Gregg W. , Jackson Edwin K.
Published: September 2006

Although early reperfusion and maintained patency is the mainstay therapy for ST elevation myocardial infarction, experimental studies demonstrate that reperfusion per se induces deleterious effects on viable ischemic cells. Thus “myocardial reperfusion injury” may compromise the full potential of reperfusion therapy and may account for unfavorable outcomes in high‐risk patients. Although the mechanisms of reperfusion injury are complex and multifactorial, neutrophil‐mediated microvascular injury resulting in a progressive decrease in blood flow (“no‐reflow” phenomenon) likely plays an important role. Adenosine is an endogenous nucleoside found in large quantities in myocardial and endothelial cells. It activates four well‐characterized receptors producing various physiological effects that attenuate many of the proposed mechanisms of reperfusion injury. The cardio‐protective effects of adenosine are supported by its role as a mediator of pre‐ and post‐conditioning. In experimental models, administration of adenosine in the peri‐reperfusion period results in a marked reduction in infarct size and improvement in ventricular function. The cardioprotective effects in the canine model have a narrow time window with the drug losing its effect following three hours of ischemia. Several small clinical studies have demonstrated that administration of adenosine with reperfusion therapy reduces infarct size and improves ventricular function. In the larger AMISTAD and AMISTAD II trials a 3‐h infusion of adenosine as an adjunct to reperfusion resulted in a striking reduction in infarct size (55–65%).Post hocanalysis of AMISTAD II showed that this was associated with significantly improved early and late mortality in patients treated within 3.17 h of symptoms. An intravenous infusion of adenosine for 3 h should be considered as adjunctive therapy in high risk‐patients undergoing reperfusion therapy.
The Impact of Insurance Fraud Detection Systems
Authors: Schiller Jörg
Published: September 2006

Abstract

This article analyzes the impact of detection systems in an insurance fraud context. In a noncommitment Costly State Verification setting insurers can only detect fraudulent claims by performing costly audits, and policyholders are overcompensated by the optimal insurance contract. We show that auditing becomes more effective and overcompensation can be reduced, when insurers are able to condition their audits on the information provided by detection systems.
Subjective Economic Risk to Beneficiaries in Notional Defined Contribution Accounts
Authors: Vidal‐Meliá Carlos , Domínguez‐Fabián Inmaculada , Enrique Devesa‐Carpio José
Published: September 2006

Abstract

This article aims to quantify the aggregate subjective economic risk to which beneficiaries would be exposed if a retirement pension system based on notional account philosophy were introduced. We use scenario generation techniques to make projections of the factors that determine the real expected internal rate of return (IRR) and the expected replacement rate (RR) for the beneficiary according to six retirement formulae based on the most widely accepted rates or indices. We then apply the model to the case of Spain. Our projections are based on Herce and Alonso's macroeconomic scenario 2000–2050 (2000) and include information about the past performance of the indices and the time period the forecast is to cover. The results of the IRR calculation—average value, standard deviation, and value‐at‐risk (VaR)—are analyzed both in objective terms and for different degrees of participants' risk aversion.
From Cooperative to Opportunistic Federalism: Reflections on the Half‐Century Anniversary of the Commission on Intergovernmental Relations
Authors: Conlan Tim
Published: September 2006

In 1955, the Commission on Intergovernmental Relations—the Kestnbaum Commission—embellished the intellectual framework of cooperative federalism and laid out a policy agenda for promoting it. Since then, our intergovernmental system has evolved from a predominantly cooperative federal–state–local system to one characterized by corrosive opportunistic behavior, greater policy prescriptiveness, eroding institutional capacity for intergovernmental analysis, and shifting paradigms of public management. These trends threaten to undermine effective intergovernmental relations and management. Recent developments, however, offer some promise for building new institutions of intergovernmental analysis, more effective paradigms of intergovernmental public management, and greater horizontal cooperation.
Abu Ghraib, Administrative Evil, and Moral Inversion: The Value of “Putting Cruelty First”
Authors: Adams Guy B. , Balfour Danny L. , Reed George E.
Published: September 2006

The torture and abuse of detainees at Abu Ghraib prison and at other sites in Iraq, Afghanistan, and Cuba raise disturbing questions that have few, if any, easy answers. Were these intentionally evil acts committed by a few bad apples who took advantage of the power they wielded over the detainees? Or were they cases of administrative evil in which the obvious evil of torture and abuse was masked from the perpetrators, including those who performed subsidiary and supportive functions? The more fundamental question is, are torture and abuse always wrong? How close did the United States come to moral inversion in this case? Judith Shklar’s concept of “putting cruelty first” aids our understanding of this case and points toward a trajectory that could help prevent future moral inversions and administrative evil.
In Pursuit of the Public Interest
Authors: Lewis Carol W.
Published: September 2006

What does the injunction “serve the public interest” really mean for public managers, and why is it important? By way of an answer, this analysis systematizes different perspectives on the public interest and offers a multifaceted formulation of the public manager’s duty. It is a process involving the exploration of two concerns—democracy and mutuality—in the current time frame and two others—sustainability and legacy—in the future time frame.
Budgeting for Fiscal Stability over the Business Cycle: A Countercyclical Fiscal Policy and the Multiyear Perspective on Budgeting
Authors: Hou Yilin
Published: September 2006

This essay is a theoretical exploration of a new budgetary system to cope with fiscal uncertainty and instability.

1

It examines policies requiring positive year‐end balances and infers that annual budget cycles lead to a mismatch between the budget cycle and the continuity of public service provision. The author considers a multiyear perspective on budgeting as a potential solution, with countercyclical fiscal reserves to help ensure stability during fluctuating economic conditions. By adopting budget stabilization funds and keeping sufficient reserves, states can better maintain trend‐level public services during recessions. Panel data analysis provides empirical evidence that such funds helped stabilize state general expenditures during downturns. The adoption of countercyclical fiscal policy and budget stabilization funds is a step toward a longer‐term perspective on budgeting, thus promoting fiscal stability over the economic cycle.
Does Performance Budgeting Work? An Examination of the Office of Management and Budget’s PART Scores
Authors: Gilmour John B. , Lewis David E.
Published: September 2006

In this paper, the authors use the Bush administration’s management grades from the Program Assessment Rating Tool (PART) to evaluate performance budgeting in the federal government—in particular, the role of merit and political considerations in formulating recommendations for 234 programs in the president’s fiscal year 2004 budget. PART scores and political support were found to influence budget choices in expected ways, and the impact of management scores on budget decisions diminished as the political component was taken into account. The Bush administration’s management scores were positively correlated with proposed budgets for programs housed in traditionally Democratic departments but not in other departments. The federal government’s most ambitious effort to use performance budgeting to date shows both the promise and the problems of this endeavor.
Using Videotaped Feedback During Intervention With Married Couples: A Qualitative Assessment
Authors: Long Edgar C. J. , Angera Jeffrey J. , Hakoyama Mikiyasu
Published: September 2006

Abstract: Sixteen married couples volunteered to participate in a 6‐week empathy training program. Ten of the 16 couples observed and made comments about their taped interaction at the end of the program. Individuals watched the tape of their own interaction at the follow‐up and were asked several qualitative questions, including what they noticed about themselves. The five themes that emerged in the comments individuals made after watching themselves on videotape included surprised by self, discomfort watching the tape, increased self‐awareness of emotions, observed patterns of interaction, and nondefensive self‐disclosure. We discuss the potential utility of the videotape methodology for marriage educators and interventionists.
Families of Persons With Substance Use and Mental Disorders: A Literature Review and Conceptual Framework*
Authors: Townsend Aloen L. , Biegel David E. , Ishler Karen J. , Wieder Barbara , Rini Amy
Published: September 2006

Abstract: There are significant knowledge gaps concerning the experiences of families of persons with co‐occurring substance and mental disorders and the impact of families on treatment of individuals with these disorders. This paper presents a conceptual framework for examining family involvement of adults in treatment for co‐occurring substance and mental disorders. An overview of the characteristics, problems, and needs of these individuals and their family members is presented. The extant literature pertaining to our conceptual framework is reviewed with focus on predictors of family involvement with clients, predictors of family member involvement in clients’ treatment, and consequences of family involvement for client treatment outcomes. Gaps in the research literature and implications for future research and practice are discussed.
Alternatives to platelet transfusions in the management of platelet dysfunction or thrombocytopenia
Authors: KICKLER THOMAS S.
Published: September 2006

Alternatives to platelet transfusions are important in preventing the adverse events associated with platelet transfusions. The use of platelet alternatives has not been extensively compared with platelet transfusions, although studies suggest that bleeding can be controlled and transfusions prevented. A variety of pharmacologic agents are available, which generally work by augmenting different hemostatic mechanisms. In addition to pharmacologic agents, recombinant activated factor VII is available for controlling inherited qualitative platelet disorders such as Glanzmann’s thrombasthenia. For the treatment of chemotherapy‐induced thrombocytopenia, the use of growth factors may shorten the duration of thrombocytopenia and prove to be an approach for reducing or preventing platelet transfusions. Although interesting research has been carried out for several decades in the aim of developing a platelet substitute, it is unlikely that a platelet substitute will be available for clinical use in the near future.
Pathogen inactivation of platelets
Authors: McCULLOUGH JEFFREY
Published: September 2006

The AIDS epidemic greatly increased patients’ and the public’s fear of blood transfusion and resulted in major increased efforts to reduce the risk of transfusion‐transmitted diseases. Testing strategies have been very effective in reducing the risk of transfusion‐transmitted diseases. However, the current approaches have shortcomings: (i) they apply only to known pathogens and not to other presently unknown infectious agents; (ii) they are reactive to new transmissible diseases and thus accept that some patients may be harmed before preventive measures can be implemented; (iii) they do not prevent bacterial contamination; (iv) they do not prevent transmission of other known or unknown infectious agents; and (v) they result in an excessive loss of otherwise suitable donors. Several approaches have been developed to inactivate pathogen in cellular blood components and plasma. Two companies are developing methods that are highly effective for pathogen inactivation, and toxicities of the methods seem to be minimal and not of clinical importance. The in vitro function and in vivo effectiveness of pathogen‐inactivated platelets are clinically acceptable. These exciting developments raise the possibility of a paradigm shift in our approach to reducing the risk of transfusion‐transmitted diseases.
The assessment of platelet function
Authors: TANAKA KENICHI A.
Published: September 2006

Platelet activation is involved in physiological hemostasis and in a variety of thromboembolic events leading to stroke, myocardial ischemia, and other organ dysfunction. Apart from congenital platelet dysfunction, acquired platelet defects are increasingly common in patients due to the widespread use of antiplatelet agents. Newer antiplatelet agents targeting platelet glycoprotein IIb–IIIa and adenosine‐5′‐diphosphate receptors inhibit platelet activation, and therefore assessing platelet inhibition may be important to prevent major bleeding, especially before a surgical intervention. In the past decade, the knowledge from genotypic analyses and prospective outcome studies suggested inter‐patient variability in the therapeutic response to antiplatelet therapies, which further stresses the need for individual platelet testing. In managing bleeding patients, platelet transfusion may be better guided by the use of platelet function tests because transfusion therapy is costly and potentially harmful if administered inappropriately. Basic understanding of the hemostatic roles of platelets, etiologies of platelet defects, and characteristics of current platelet assessment methods should help physicians who manage complex coagulation issues in critically ill patients.
Current controversies about the indications for platelet transfusion with a focus on patients with hematological malignancies
Authors: COLLINS GRAHAM , MURPHY MICHAEL F. , STANWORTH SIMON J.
Published: September 2006

This article discusses current platelet transfusion practice and compliance with guidelines for platelet transfusions. It then focuses on the evidence for platelet transfusion practice in patients with hematological malignancies. In particular, the review addresses two main topics central to a policy of prophylactic platelet transfusion:

1 What is the evidence to indicate if platelet transfusions should be given to prevent bleeding as compared with a strategy aimed to use platelet transfusions when bleeding occurs?

2 If platelet transfusions are given to prevent bleeding, how good is the evidence to indicate what is the appropriate threshold level of platelet count?
Observation of Electroluminescence and Photovoltaic Response in Ionic Junctions
Authors: Bernards Daniel A. , Flores-Torres Samuel , Abruña Héctor D. , Malliaras George G.
Published: September 2006

Electronic devices primarily use electronic rather than ionic charge carriers. Using soft-contact lamination, we fabricated ionic junctions between two organic semiconductors with mobile anions and cations, respectively. Mobile ionic charge was successfully deployed to control the direction of electronic current flow in semiconductor devices. As a result, these devices showed electroluminescence under forward bias and a photovoltage upon illumination with visible light. Thus, ionic charge carriers can enhance the performance of existing electronic devices, as well as enable new functionalities.
Comment on "Transitions to Asexuality Result in Excess Amino Acid Substitutions"
Authors: Butlin Roger
Published: September 2006

Paland and Lynch (Reports, 17 February 2006, p. 990) showed that in
Daphnia pulex
, the ratio of amino acid replacement to silent substitution in mitochondrial genes is higher in asexual lineages than in sexual lineages. If this base-composition bias is maintained by selection, it too should alter following transitions in reproductive mode. Analysis reveals no such change in the genomes of
D. pulex
.
Gene Transposition as a Cause of Hybrid Sterility in
Drosophila
Authors: Masly John P. , Jones Corbin D. , Noor Mohamed A. F. , Locke John , Orr H. Allen
Published: September 2006

We describe reproductive isolation caused by a gene transposition. In certain
Drosophila melanogaster
–
D. simulans
hybrids, hybrid male sterility is caused by the lack of a single-copy gene essential for male fertility,
JYAlpha
. This gene is located on the fourth chromosome of
D. melanogaster
but on the third chromosome of
D. simulans
. Genomic and molecular analyses show that
JYAlpha
transposed to the third chromosome during the evolutionary history of the
D. simulans
lineage. Because of this transposition, a fraction of hybrids completely lack
JYAlpha
and are sterile, representing reproductive isolation without sequence evolution.
Tectonic Uplift and Eastern Africa Aridification
Authors: Sepulchre Pierre , Ramstein Gilles , Fluteau Frédéric , Schuster Mathieu , Tiercelin Jean-Jacques , Brunet Michel
Published: September 2006

The history of Eastern African hominids has been linked to a progressive increase of open grassland during the past 8 million years. This trend was explained by global climatic processes, which do not account for the massive uplift of eastern African topography that occurred during this period. Atmosphere and biosphere simulations quantify the role played by these tectonic events. The reduced topographic barrier before 8 million years ago permitted a zonal circulation with associated moisture transport and strong precipitation. Our results suggest that the uplift itself led to a drastic reorganization of atmospheric circulation, engendering the strong aridification and paleoenvironmental changes suggested by the data.
Isolated Chloroplast Division Machinery Can Actively Constrict After Stretching
Authors: Yoshida Yamato , Kuroiwa Haruko , Misumi Osami , Nishida Keiji , Yagisawa Fumi , Fujiwara Takayuki , Nanamiya Hideaki , Kawamura Fujio , Kuroiwa Tsuneyoshi
Published: September 2006

Chloroplast division involves plastid-dividing, dynamin, and FtsZ (PDF) rings. We isolated intact supertwisted (or spiral) and circular PDF machineries from chloroplasts of the red alga
Cyanidioschyzon merolae
. After individual intact PDF machineries were stretched to four times their original lengths with optical tweezers, they spontaneously returned to their original sizes. Dynamin-released PDF machineries did not retain the spiral structure and could not be stretched. Thus, dynamin may generate the motive force for contraction by filament sliding in dividing chloroplasts, in addition to pinching-off the membranes.
Detecting Awareness in the Vegetative State
Authors: Owen Adrian M. , Coleman Martin R. , Boly Melanie , Davis Matthew H. , Laureys Steven , Pickard John D.
Published: September 2006

We used functional magnetic resonance imaging to demonstrate preserved conscious awareness in a patient fulfilling the criteria for a diagnosis of vegetative state. When asked to imagine playing tennis or moving around her home, the patient activated predicted cortical areas in a manner indistinguishable from that of healthy volunteers.
Essential Roles of Monocytes in Stimulating Human Peripheral Blood Mononuclear Cells with
Lactobacillus casei
To Produce Cytokines and Augment Natural Killer Cell Activity
Authors: Shida Kan , Suzuki Tomomi , Kiyoshima-Shibata Junko , Shimada Shin-ichiro , Nanno Masanobu
Published: September 2006

We examined the effect of a probiotic strain,
Lactobacillus casei
strain Shirota, on cytokine production and natural killer (NK) cell activity in human peripheral blood mononuclear cells (PBMNC). The cellular mechanisms of immunoregulation by
L. casei
strain Shirota were also investigated.
L. casei
strain Shirota stimulated PBMNC to secrete interleukin-12 (IL-12), gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and IL-10. However, depletion of monocytes from PBMNC eliminated the induction of these cytokines.
L. casei
strain Shirota was phagocytosed by monocytes and directly stimulated them to secrete IL-12, TNF-α, and IL-10. IFN-γ production was diminished by the addition of anti-IL-12 antibody to the PBMNC cultures. Purified T cells, but not NK cells, produced IFN-γ effectively when stimulated with
L. casei
strain Shirota in the presence of monocytes, indicating that monocytes triggered by
L. casei
strain Shirota help T cells to produce IFN-γ through secreting IL-12. In addition, NK cell activity and CD69 expression on NK cells increased after cultivation of PBMNC with
L. casei
strain Shirota. When monocytes were depleted from PBMNC,
L. casei
strain Shirota did not enhance NK cell activity. These results demonstrate that monocytes play critical roles in the induction of cytokines and following the augmentation of NK cell activity during the stimulation of human PBMNC with
L. casei
strain Shirota.
Stimulation of Human Monocytes with the Gram-Positive Vaccine VectorStreptococcus gordonii
Authors: Ciabattini Annalisa , Cuppone Anna Maria , Pulimeno Rita , Iannelli Francesco , Pozzi Gianni , Medaglini Donata
Published: September 2006

Streptococcus gordoniiis a bacterial vaccine vector which has previously been shown to activate dendritic cells in vitro and to induce local and systemic immune responses in vivo. In the present study, human monocytes (THP-1 cell line and peripheral blood monocytes) were characterized following interaction withS. gordonii. Treatment of human monocytes withS. gordoniibut not latex beads induced a clear up-regulation of CD83, CD40, CD80, and CD54 and the down-regulation of CD14. Furthermore, bacterial treatment stimulated an increased expression of Toll-like receptor 5 (TLR5), TLR6, and TLR7, production of the proinflammatory cytokines tumor necrosis factor alpha and interleukin 1 beta, and reduction of the phagocytic activity. This work shows that the immunostimulatory activity ofS. gordoniiis not restricted to induction of dendritic-cell maturation but also affects the differentiation process of human monocytes.
Development and Validation of a Fourfold Multiplexed Opsonization Assay (MOPA4) for Pneumococcal Antibodies
Authors: Burton Robert L. , Nahm Moon H.
Published: September 2006

Opsonophagocytic killing assays (OPAs) are essential for developing and improving pneumococcal vaccines. There is a need for a high-throughput, reliable, standardized, and fully characterized OPA for pneumococcal antibodies. To meet the need, we have developed and characterized a fourfold multiplexed OPA (MOPA4) against 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) of pneumococci. Thirteen target bacteria were made resistant to only one of the following antibiotics: optochin, streptomycin, spectinomycin, and trimethoprim. Following optimization of assay conditions, accuracy of MOPA4 was determined by testing 30 sera from old adults in the MOPA4 and the single-serotype assays. The opsonization titers obtained with both assays agreed well (
r
2
> 0.95). Although 22 (out of 390; ∼6%) results differed more than twofold, the differences were not reproducible. The assay was specific: preabsorbing test sera with homologous polysaccharide (PS) completely abrogated opsonic activity, but a pool of unrelated PS (5 μg/ml of each) had no effect. Intra- and interassay coefficients of variation were 10 and 22%, respectively. MOPA4 results were unaffected by having different target pneumococcal serotypes in each assay group. Also, HL60 cell-to-bacteria ratios could be varied twofold without affecting the results. We conclude that MOPA4 is sensitive, accurate, specific, precise, and robust enough for large-scale clinical studies. Furthermore, MOPA4 should allow evaluation of multivalent pneumococcal vaccines with the limited volume of serum typically available from young children.
Unique Model of Dormant Infection for Tuberculosis Vaccine Development
Authors: Kashino Suely S. , Ovendale Pamela , Izzo Angelo , Campos-Neto Antonio
Published: September 2006

Most individuals exposed toMycobacterium tuberculosisbecome infected but hinder the infectious process in dormant foci, known as latent tuberculosis. This limited infection usually stimulates strong T-cell responses, which provide lifelong resistance to tuberculosis. However, latent tuberculosis is still poorly understood, particularly because of the lack of a reliable animal model of dormant infection. Here we show that inoculation of mice with a unique streptomycin-auxotrophic mutant ofMycobacterium tuberculosisrecapitulates dormant infection. The mutant grows unimpaired in the presence of streptomycin and no longer grows but remains viable for long periods of time after substrate removal, shifting from the log growth phase to the latent stage, as indicated by augmented production of α-crystallin. Mice challenged with the mutant and inoculated with streptomycin for ∼3 weeks developed a limited infection characterized by a low bacteriological burden and the presence of typical granulomas. After substrate withdrawal, the infection was hindered but few microorganisms remained viable (dormant) in the animals' tissues for at least 6 months. In addition, the animals developed both potent T-cell responses toM. tuberculosisantigens, such as early culture filtrate, Ag85B, and ESAT-6, and resistance to reinfection with virulentM. tuberculosis. Therefore, infection of mice or other animals (e.g., guinea pigs) withM. tuberculosisstrain 18b constitutes a simple and attractive animal model for evaluation of antituberculosis vaccines in the context of anM. tuberculosis-presensitized host, a prevailing condition among humans in need of a vaccine.
Phase I Clinical Evaluation of a Synthetic Oligosaccharide-Protein Conjugate Vaccine against
Haemophilus influenzae
Type b in Human Adult Volunteers
Authors: Toraño Gilda , Toledo Maria E. , Baly Alberto , Fernandez-Santana Violeta , Rodriguez Francisco , Alvarez Yunia , Serrano Teresita , Musachio Alexis , Hernandez Ibis , Hardy Eugenio , Rodríguez Arlene , Hernandez Hector , Aguilar Aristides , Sánchez Raydel , Diaz Manuel , Muzio Verena , Dfana Jorgelina , Rodríguez Maria C. , Heynngnezz Lazaro , Verez-Bencomo Vicente
Published: September 2006

Since 1989, we have been involved in the development of a vaccine against
Haemophilus influenzae
type b. The new vaccine is based on the conjugation of synthetic oligosaccharides to tetanus toxoid. Our main goals have been (i) to verify the feasibility of using the synthetic antigen and (ii) to search for new production alternatives for this important infant vaccine. Overall, eight trials have already been conducted with adults, children (4 to 5 years old), and infants. We have described herein the details from the first two phase I clinical trials conducted with human adult volunteers under double blind, randomized conditions. The participants each received a single intramuscular injection to evaluate safety and initial immunogenicity. We have found an excellent safety profile and an antibody response similar to the one observed for the control vaccine.
Isolation of High-Affinity Single-Chain Antibodies against
Mycobacterium avium
subsp.
paratuberculosis
Surface Proteins from Sheep with Johne's Disease
Authors: Berger Sven , Hinz Dominik , Bannantine John P. , Griffin J. Frank T.
Published: September 2006

Johne's disease, caused by infection with
Mycobacterium avium
subsp.
paratuberculosis
, causes significant economic losses to the livestock farming industry. Improved investigative and diagnostic tools—necessary to understand disease processes and to identify subclinical infection—are much sought after. Here, we describe the production of single-chain antibodies with defined specificity for
M. avium
subsp.
paratuberculosis
surface proteins. Single-chain antibodies (scFv) were generated from sheep with Johne's disease by cloning heavy-chain and lambda light-chain variable regions and expressing these in fusion with gene III of filamentous phages. Two scFv clones (designated SurfS1.2 and SurfS2.2) were shown to be immunoreactive against
M. avium
subsp.
paratuberculosis
surface targets by flow cytometry, and immunoblotting identified specificity for a 34-kDa proteinase-susceptible determinant. Both antibodies were cross-reactive against
Mycobacterium avium
subsp.
avium
but nonreactive against
Mycobacterium bovis
or
Mycobacterium phlei
cells and were shown to be capable of enriching
M. avium
subsp.
paratuberculosis
cells by a factor of approximately 10
6
-fold when employed in magnetic bead separation of mixed
Mycobacterium
sp. cultures. Further, magnetic bead separation using SurfS1.2 and SurfS2.2 was capable of isolating as few as 10
3
M. avium
subsp.
paratuberculosis
cells from ovine fecal samples, indicating the diagnostic potential of these reagents. Finally, inclusion of SurfS1.2 or SurfS2.2 in in vitro broth culture with
M. avium
subsp.
paratuberculosis
indicated that surface binding activity did not impede bacterial growth, although colony clumping was prevented. These results are discussed in terms of the potential use of single-chain phage display monoclonal antibodies as novel diagnostic reagents.
The Selective Value of Bacterial Shape
Authors: Young Kevin D.
Published: September 2006

Why do bacteria have shape? Is morphology valuable or just a trivial secondary characteristic? Why should bacteria have one shape instead of another? Three broad considerations suggest that bacterial shapes are not accidental but are biologically important: cells adopt uniform morphologies from among a wide variety of possibilities, some cells modify their shape as conditions demand, and morphology can be tracked through evolutionary lineages. All of these imply that shape is a selectable feature that aids survival. The aim of this review is to spell out the physical, environmental, and biological forces that favor different bacterial morphologies and which, therefore, contribute to natural selection. Specifically, cell shape is driven by eight general considerations: nutrient access, cell division and segregation, attachment to surfaces, passive dispersal, active motility, polar differentiation, the need to escape predators, and the advantages of cellular differentiation. Bacteria respond to these forces by performing a type of calculus, integrating over a number of environmental and behavioral factors to produce a size and shape that are optimal for the circumstances in which they live. Just as we are beginning to answer how bacteria create their shapes, it seems reasonable and essential that we expand our efforts to understand why they do so.
Genetics ofStreptomyces rimosus, the Oxytetracycline Producer
Authors: Petković Hrvoje , Cullum John , Hranueli Daslav , Hunter Iain S. , Perić-Concha Nataša , Pigac Jasenka , Thamchaipenet Arinthip , Vujaklija Dušica , Long Paul F.
Published: September 2006

From a genetic standpoint,Streptomyces rimosusis arguably the best-characterized industrial streptomycete as the producer of oxytetracycline and other tetracycline antibiotics. Although resistance to these antibiotics has reduced their clinical use in recent years, tetracyclines have an increasing role in the treatment of emerging infections and noninfective diseases. Procedures for in vivo and in vitro genetic manipulations inS. rimosushave been developed since the 1950s and applied to study the genetic instability ofS. rimosusstrains and for the molecular cloning and characterization of genes involved in oxytetracycline biosynthesis. Recent advances in the methodology of genome sequencing bring the realistic prospect of obtaining the genome sequence ofS. rimosusin the near term.
The Bacterial Cytoskeleton
Authors: Shih Yu-Ling , Rothfield Lawrence
Published: September 2006

In recent years it has been shown that bacteria contain a number of cytoskeletal structures. The bacterial cytoplasmic elements include homologs of the three major types of eukaryotic cytoskeletal proteins (actin, tubulin, and intermediate filament proteins) and a fourth group, the MinD-ParA group, that appears to be unique to bacteria. The cytoskeletal structures play important roles in cell division, cell polarity, cell shape regulation, plasmid partition, and other functions. The proteins self-assemble into filamentous structures in vitro and form intracellular ordered structures in vivo. In addition, there are a number of filamentous bacterial elements that may turn out to be cytoskeletal in nature. This review attempts to summarize and integrate the in vivo and in vitro aspects of these systems and to evaluate the probable future directions of this active research field.
SELF-ASSEMBLY OF ORDERED SILVER NANOPARTICLE CHAINS ON TRIBLOCK COPOLYMER TEMPLATES
Authors: SHI ZHONGTAO , PAN DENGYU , ZHAO SHIFENG , WAN JIANGUO , WANG GUANGHOU , HAN MIN
Published: September 2006

Poly(styrene-b-butadiene-b-styrene) (SBS) triblock copolymer templates which present an in-plane cylinder pattern have been prepared by controlling the solvent evaporation rate. Then silver clusters have been deposited onto the SBS copolymer templates by low energy clusters beam deposition (LECBD) apparatus. The morphology of the sample has been characterized by AFM with tapping-mode. It is shown that silver clusters aggregate into nanoparticle chains onto the template at about 100% coverage. Optical absorption spectra reveal that the surface plasmon resonance (SPR) of silver nanoparticle chains occurs at 550 nm, being a red shift of -85 nm compared to silver nanoclusters deposited on the fused quartz substrate, and the width of SPR peak broadens.
BEHAVIOR OF ASYMMETRIC BISTABLE SYSTEM UNDER INFLUENCE OF CROSS-CORRELATED NOISES
Authors: GUDYMA YURIY , IVANS'KII BOHDAN
Published: September 2006

We study nonlinear dynamics of the asymmetric bistable system described by the general Landau potential in the presence of different noise sources. The corresponding phase diagram was obtained for the potential with the metastable state. The noise was found to change the stability of the metastable system: maximum of bimodal distribution passes into minimum and vice versa while changing one of the correlated noises. As a result, the initially asymmetric system can be reduced to symmetric one.
COMPUTATIONAL MODELING OF TISSUE SELF-ASSEMBLY
Authors: NEAGU ADRIAN , KOSZTIN IOAN , JAKAB KAROLY , BARZ BOGDAN , NEAGU MONICA , JAMISON RICHARD , FORGACS GABOR
Published: September 2006

As a theoretical framework for understanding the self-assembly of living cells into tissues, Steinberg proposed the differential adhesion hypothesis (DAH) according to which a specific cell type possesses a specific adhesion apparatus that combined with cell motility leads to cell assemblies of various cell types in the lowest adhesive energy state. Experimental and theoretical efforts of four decades turned the DAH into a fundamental principle of developmental biology that has been validated both in vitro and in vivo. Based on computational models of cell sorting, we have developed a DAH-based lattice model for tissues in interaction with their environment and simulated biological self-assembly using the Monte Carlo method. The present brief review highlights results on specific morphogenetic processes with relevance to tissue engineering applications. Our own work is presented on the background of several decades of theoretical efforts aimed to model morphogenesis in living tissues. Simulations of systems involving about 105 cells have been performed on high-end personal computers with CPU times of the order of days. Studied processes include cell sorting, cell sheet formation, and the development of endothelialized tubes from rings made of spheroids of two randomly intermixed cell types, when the medium in the interior of the tube was different from the external one. We conclude by noting that computer simulations based on mathematical models of living tissues yield useful guidelines for laboratory work and can catalyze the emergence of innovative technologies in tissue engineering.
FIRST-PRINCIPLES STUDY OF THE ELECTRONIC PROPERTIES OF GaAs(114)A (2×1) SURFACE
Authors: WANG SANJUN , SONG YOULIN , ZHAO XIANLIN , LI JINMING , LIU JINHAI , JIA YU
Published: September 2006

The electronic properties of the GaAs(114)A (2×1) surface are studied by using the first-principles method within density functional theory (DFT). The reconstructed geometric structure and surface band structure, together with the total density of states, are presented respectively. Our results show that the surface properties of GaAs(114)A turns to be semiconductive after α2(2×1) or β2(2×1) reconstruction. The gap between the highest occupied states and the lowest unoccupied states is 0.8 and 0.9 eV for α2(2×1) and β2(2×1) reconstruction respectively. Furthermore, the dispersion properties along the high symmetry lines of the two-dimensional surface Brillouin zone are also discussed.
COMPLEXITY PSEUDOVARIETIES ARE NOT LOCAL: TYPE II SUBSEMIGROUPS CAN FALL ARBITRARILY IN COMPLEXITY
Authors: RHODES JOHN , STEINBERG BENJAMIN
Published: September 2006

We prove the following two results announced by Rhodes: the Type II subsemigroup of a finite semigroup can fall arbitrarily in complexity; the complexity pseudovarieties Cn (n ≥ 1) are not local.
MULTI-HYPERSUBSTITUTIONS AND COLORED SOLID VARIETIES
Authors: DENECKE K. , KOPPITZ J. , SHTRAKOV SL.
Published: September 2006

Hypersubstitutions are mappings which map operation symbols to terms. Terms can be visualized by trees. Hypersubstitutions can be extended to mappings defined on sets of trees. The nodes of the trees, describing terms, are labelled by operation symbols and by colors, i.e. certain positive integers. We are interested in mappings which map differently-colored operation symbols to different terms. In this paper we extend the theory of hypersubstitutions and solid varieties to multi-hypersubstitutions and colored solid varieties. We develop the interconnections between such colored terms and multi-hypersubstitutions and the equational theory of Universal Algebra. The collection of all varieties of a given type forms a complete lattice which is very complex and difficult to study; multi-hypersubstitutions and colored solid varieties offer a new method to study complete sublattices of this lattice.
CONJUGACY INVARIANTS OF SUBSHIFTS: AN APPROACH FROM PROFINITE SEMIGROUP THEORY
Authors: COSTA ALFREDO
Published: September 2006

It is given a structural conjugacy invariant in the set of pseudowords whose finite factors are factors of a given subshift. Some profinite semigroup tools are developed for this purpose. With these tools a shift equivalence invariant of sofic subshifts is obtained, improving an invariant introduced by Béal, Fiorenzi and Perrin using different techniques. This new invariant is used to prove that some almost finite type subshifts with the same zeta function are not shift equivalent.
ON DUALIZING CLONES AS LAWVERE THEORIES
Authors: MAŠULOVIĆ DRAGAN
Published: September 2006

In this paper we treat clones as Lawvere theories and then dualize them as categories, rather than as single objects of a category of algebras. The approach applies only to some primitive-positive clones, but in return, a structure with somewhat surprising properties is obtained. To illustrate the method, we thoroughly investigate the lattice of clones of operations over a finite boolean algebra.
WAVE FIELD CORRELATIONS IN WEAKLY MISMATCHED RANDOM MEDIA
Authors: BAL GUILLAUME , RYZHIK LENYA
Published: September 2006

This paper concerns the derivation of a Fokker–Planck equation for the correlation of two high frequency wave fields propagating in two different random media. The mismatch between the random media needs be small, on the order of the wavelength, and their correlation length needs be large relative to the wavelength. The loss of correlation caused by the mismatch in the random media is quantified and the limit process for the phase difference is obtained. The derivation is based on a random Liouville equation to model high frequency correlations and on the method of characteristics to characterize mixing in the random Liouville equation. Applications of such correlation loss include the monitoring in time of random media and the analysis of time reversed waves in changing heterogeneous domains.
SPECTRAL PROPERTIES OF CHAOTIC PROCESSES
Authors: BERCU BERNARD , PRIEUR CLÉMENTINE
Published: September 2006

We investigate the spectral asymptotic properties of the stationary dynamical system ξt= φ(Tt(X0)). This process is given by the iterations of a piecewise expanding map T of the interval [0,1], invariant for an ergodic probability μ. The initial state X0is distributed over [0,1] according to μ and φ is a function taking values in ℝ. We establish a strong law of large numbers and a central limit theorem for the integrated periodogram as well as for Fourier transforms associated with (ξt: t ∈ ℕ). Several examples of expanding maps T are also provided.
IMPROVING THE SENSITIVITY AND SPECIFICITY OF PROTEIN HOMOLOGY SEARCH BY INCORPORATING PREDICTED SECONDARY STRUCTURES
Authors: MA BIN , WU LIEYU , ZHANG KAIZHONG
Published: September 2006

In this paper, we improve the homology search performance by the combination of the predicted protein secondary structures and protein sequences. Previous research suggested that the straightforward combination of predicted secondary structures did not improve the homology search performance, mostly because of the errors in the structure prediction. We solved this problem by taking into account the confidence scores output by the prediction programs.
AN AMINO ACID SUBSTITUTION MATRIX FOR PROTEIN CONFORMATION IDENTIFICATION
Authors: LIU XIN , ZHENG WEI-MOU
Published: September 2006

Amino acid substitution matrices play an essential role in protein sequence alignment, a fundamental task in bioinformatics. Most widely used matrices, such as PAM matrices derived from homologous sequences and BLOSUM matrices derived from aligned segments of PROSITE, did not integrate conformation information in their construction. There are a few structure-based matrices, which are derived from limited data of structure alignment. Using databases PDB_SELECT and DSSP, we create a database of sequence-conformation blocks which explicitly represent sequence-structure relationship. Members in a block are identical in conformation and are highly similar in sequence. From this block database, we derive a conformation-specific amino acid substitution matrix CBSM60. The matrix shows an improved performance in conformational segment search and homolog detection.