bluuebunny/crossref_metadata_2025 huggingface dataset:
Incontinentia Pigmenti in Boys: A Series and Review of the Literature
Authors: Ardelean Daniela , Pope Elena
Published: December 2006

Abstract:  Incontinentia pigmenti is a rare X‐linked genodermatosis, often associated with male lethality in utero. Occurrences of this disease in boys have been reported, however, its clinical phenotype has not been well characterized. The purpose of this study was to report on additional instances of incontinentia pigmenti in boys and to review the clinical, laboratory, and molecular characteristics of all published such patients. A retrospective chart review and Medline search using the keywords incontinentia pigmenti, males, and NEMO gene was undertaken. Six new boys with incontinentia pigmenti were found in our database and 36 more were previously reported in the literature. The vesiculo‐bullous stage was the most frequent clinical presentation at diagnosis (80%). Fifteen percent of patients had an initial unilateral presentation. Recurrences of this stage were noted in 16%. Stages 2 and 3 of the disease were present in only 72.5% and 75% of patients, respectively. Only 15% of the boys had a documented stage 4. Extracutaneous manifestations were also documented (30%– central nervous system manifestations, 35%– eye involvement, 30%– alopecia, 40%– teeth anomalies). Thirty two percent of boys had peripheral eosinophilia. Only five had evidence of NEMO gene mutation. The male phenotype has clinical features similar to those of the female phenotype. Unilateral presentation is a distinct occurrence in boys, especially in early stages. Anomalies are the most common extracutaneous findings, followed by eye, hair, and central nervous system abnormalities.
Subcutaneous Panniculitis‐like T‐Cell Lymphoma in a 26‐Month‐Old Child with a Review of the Literature
Authors: Yim Jun Hee , Kim Mi‐Yeon , Kim Hyung Ok , Cho Bin , Chung Nak‐Gyun , Park Young Min
Published: December 2006

Abstract:  Subcutaneous panniculitis‐like T‐cell lymphoma is a rare cytotoxic T‐cell lymphoma of the skin that preferentially infiltrates the subcutaneous tissue. We report here this lymphoma occurring in a 26‐month‐old Korean girl. She presented with multiple erythematous subcutaneous nodules on both extremities and her back along with systemic symptoms. She had a protracted course of multiple erythematous subcutaneous nodules for 1 month and a spiking fever was often noted. The histopathologic findings for the subcutaneous nodules were lobular panniculitis‐like material that was composed of atypical lymphocytes and histiocytes. The atypical lymphocytes characteristically rimmed individual fat cells in a lace‐like pattern and some of the histiocytes showed phagocytosed white blood cells occasionally. Immunophenotypic studies showed CD3+, CD45RO+, CD20−, CD4−, CD8+, and CD56−. She is currently being treated with combination chemotherapy of cyclophosphamide, doxorubicin, vincristine, and prednisolone.
Erythema Multiforme due to Mycoplasma pneumoniae Infection in Two Children
Authors: Schalock Peter C. , Dinulos James G. H. , Pace Nicole , Schwarzenberger Kathryn , Wenger Jodi K.
Published: December 2006

Abstract:  Mycoplasma pneumoniae is an important and highly relevant cause of bullous erythema multiforme, isolated mucositis, and Stevens–Johnson syndrome in children. In this article, we present two children with respiratory Mycoplasma pneumoniae infection and associated cutaneous findings within the spectrum of erythema multiforme. We review the literature associating these three entities with Mycoplasma pneumoniae infection and discuss controversies regarding the classification of erythema multiforme, as well as update reported infectious causes of the bullous form. Many understand the erythema multiforme spectrum to include bullous erythema multiforme, mucositis, and Stevens–Johnson syndrome in the order of increasing severity. We feel that this relationship should be reconsidered to help better understand the prognosis and outcomes. It is our opinion that bullous erythema multiforme is a separate, yet related condition that can occur in the context of Mycoplasma pneumoniae infection. With many similarities to mucositis and Stevens–Johnson syndrome, bullous erythema multiforme can be considered part of a spectrum of disease that includes Stevens–Johnson syndrome. Unlike mucositis and Stevens–Johnson syndrome, bullous erythema multiforme caused by Mycoplasma pneumoniae infection has low morbidity for the child. Mycoplasma pneumoniae‐associated mucositis and Stevens–Johnson syndrome seem to occur along a spectrum with separate prognosis and potential pathogenesis compared with bullous erythema multiforme. Making the distinction between these conditions is valuable for predicting the child's prognosis. Patients who develop symptoms consistent with these conditions should be appropriately evaluated for Mycoplasma pneumoniae infection and closely monitored.
Congenital, Ill‐Defined, Yellowish Plaque: The Nasal Dermoid
Authors: Julapalli Meena R. , Cohen Bernard A. , Hollier Larry H. , Metry Denise W.
Published: December 2006

Abstract:  Congenital midline nasal masses are rare anomalies, of which dermoid cysts are the most common type. Nasal dermoids have been classically described in the literature as pale, flesh‐colored, pearly, or erythematous nodules or masses. The presentation of a nasal dermoid as an ill‐defined, yellowish plaques has not been emphasized previously. We describe three infants who presented with congenital, ill‐defined, yellowish plaques of the midline nasal dorsum. We attribute the yellowish color to the relative prominence of sebaceous glands within the cyst, given the nasal location. Recognition of this unusual presentation of a nasal dermoid is important in order that appropriate imaging and intervention be undertaken.
Carotenemia in Infancy and its Association with Prevalent Feeding Practices
Authors: Venkatesh Karthik Sivaramakrishnan , Campbell‐Davidson David , Isherwood David
Published: December 2006

Abstract:  Carotenemia in infancy is a relatively rare but benign condition, invariably of dietary origin, that can be confused with jaundice. It is characterized by an abnormal yellowish orange pigmentation of the skin, most prominently seen in the palms, soles, and naso‐labial folds. Infant feeding patterns have shown an increasing trend toward the usage of homogenized and pureed vegetables as well as meat‐based commercial preparations. Whether this is reflected in an increased incidence of carotenemia in this age group still remains unclear. We report a series of infants identified by a retrospective review of records, observed over a 3‐year period (1999–2002) in a tertiary children's hospital, who developed the condition that resolved spontaneously without intervention, as they grew older, on a changing diet.
Longevity Bonds: Financial Engineering, Valuation, and Hedging
Authors: Blake David , Cairns Andrew , Dowd Kevin , MacMinn Richard
Published: December 2006

Abstract

This article examines the main characteristics of longevity bonds (LBs) and shows that they can take a large variety of forms which can vary enormously in their sensitivities to longevity shocks. We examine different ways of financially engineering LBs and consider problems arising from the dearth of ultra‐long government bonds and the choice of the reference population index. The article also looks at valuation issues in an incomplete markets context and finishes with an examination of how LBs can be used as a risk management tool for hedging longevity risks.
A Two‐Factor Model for Stochastic Mortality with Parameter Uncertainty: Theory and Calibration
Authors: Cairns Andrew J. G. , Blake David , Dowd Kevin
Published: December 2006

Abstract

In this article, we consider the evolution of the post‐age‐60 mortality curve in the United Kingdom and its impact on the pricing of the risk associated with aggregate mortality improvements over time: so‐called longevity risk. We introduce a two‐factor stochastic model for the development of this curve through time. The first factor affects mortality‐rate dynamics at all ages in the same way, whereas the second factor affects mortality‐rate dynamics at higher ages much more than at lower ages. The article then examines the pricing of longevity bonds with different terms to maturity referenced to different cohorts. We find that longevity risk over relatively short time horizons is very low, but at horizons in excess of ten years it begins to pick up very rapidly.

A key component of the article is the proposal and development of a method for calculating the market risk‐adjusted price of a longevity bond. The proposed adjustment includes not just an allowance for the underlying stochastic mortality, but also makes an allowance for parameter risk. We utilize the pricing information contained in the November 2004 European Investment Bank longevity bond to make inferences about the likely market prices of the risks in the model. Based on these, we investigate how future issues might be priced to ensure an absence of arbitrage between bonds with different characteristics.
Multivariate Exponential Tilting and Pricing Implications for Mortality Securitization
Authors: Cox Samuel H. , Lin Yijia , Wang Shaun
Published: December 2006

Abstract

Normalized exponential tilting is an extension of classical theories, including the Capital Asset Pricing Model (CAPM) and the Black–Merton–Scholes model, to price risks with general‐shaped distributions. The need for changing multivariate probability measures arises in pricing contingent claims on multiple underlying assets or liabilities. In this article, we apply it to valuation of mortality‐based securities written on mortality indices of several countries. We show how to use multivariate exponential tilting to price the first pure mortality security, the Swiss Re bond. The same technique can be applied in other mortality securitization pricing.
State Debt Limits: How Many Are Enough?
Authors: DENISON DWIGHT V. , HACKBART MERL , MOODY MICHAEL
Published: December 2006

There is a growing concern among state policy makers that unrestrained debt may exceed politically acceptable or financially sustainable levels of debt. Many states have established limits to restrict debt, but many of these limits are circumvented through issuing more complex and specialized bonds. In this article, we focus on the use of debt limits as an instrument to manage a state's debt in context of two key questions: (1) under what circumstances should a state consider multiple debt limits and (2) if multiple limits are established, what factors should be considered in setting such multiple limits. In addressing these issues, we consider the theoretical and conceptual issues associated with setting debt limits, we highlight current state debt limit policies, and discuss factors that appear to be influencing decisions to establish and set multiple limits.
Transparency of Risk and Reward in U.K. Public–Private Partnerships
Authors: HOOD JOHN , FRASER IAN , McGARVEY NEIL
Published: December 2006

Public–Private Partnerships (PPPs) are an increasingly common mechanism for the renewal of public sector infrastructure, although in the United Kingdom, these have been criticized as representing poor value for money. An inherent assumption of much of this criticism is that a corollary of detriment for the public sector is benefit for the private sector. This paper highlights the difficulty of objectively verifying the many criticisms and assumptions regarding risk and reward associated with PPPs. Public and private sector disclosure policies and systems are analyzed and we conclude that neither sector practices openness and transparency. This results in a democratic accountability deficit in the public sector and a lack of meaningful data being made available to stakeholders in private companies.
Why Do Some Family Businesses Out–Compete? Governance, Long–Term Orientations, and Sustainable Capability
Authors: Le Breton–Miller Isabelle , Miller Danny
Published: December 2006

This article seeks to link the domains of corporate governance, investment policies, competitive asymmetries, and sustainable capabilities. Conditions such as concentrated ownership, lengthy tenures, and profound business expertise give some family–controlled business (FCB) owners the discretion, incentive, knowledge, and ultimately, the resources to invest deeply in the future of the firm. These long–term investments accrue from particular governance conditions and engender competitive asymmetries—organizational qualities that are hard for other firms to copy, and thus, if tied to the value chain, create capabilities that are sustainable. Investments in staff and training, e.g., create tacit knowledge and preserve it within the firm. Investments in enduring relationships with partners enhance access to resources and free firms to focus on core competencies. And devotion to a compelling mission dedicates most of these investments to a core competency. When such investments are farsighted, orchestrated, and ongoing, capabilities will tend to evolve in a cumulative trajectory, making them doubly hard to imitate and thereby extending competitive advantage. Arguments are supported by making reference to the literature on corporate governance and agency theory and to emerging research on FCBs.
Commentary: “Family Firms and Social Responsibility: Preliminary Evidence from the S&P 500”
Authors: Wiklund Johan
Published: December 2006

This commentary focuses on four themes: (1) empirical relevance of corporate social responsibility (CSR) in family firms; (2) complementary theoretical explanations to CSR behavior in family firms; (3) the need for stringent definitions in family business research; and (4) the potential for dual causality between family ownership and more generous CSR policies. Specifically, I argue that agency theory can lead to additional valuable insights about CSR in family firms.
Corporate Entrepreneurship in Family Firms: A Family Perspective
Authors: Kellermanns Franz W. , Eddleston Kimberly A.
Published: December 2006

Entrepreneurship has been recognized as an important factor contributing to firm success. Despite the potential benefit of corporate entrepreneurship to sustain the family firm across generations, corporate entrepreneurship has been underresearched in the family firm literature. We investigate how generational involvement, willingness to change, and the ability to recognize technological opportunities impact corporate entrepreneurship in family firms. We also examine strategic planning in family firms as a facilitating process. Our findings suggest that willingness to change and technological opportunity recognition are positively related to corporate entrepreneurship in family firms. We further found strategic planning to significantly moderate the relationships between (1) generational involvement and (2) technological opportunity recognition and corporate entrepreneurship. These findings and implications for management and research are discussed.
Altruism and Agency in the Family Firm: Exploring the Role of Family, Kinship, and Ethnicity
Authors: Karra Neri , Tracey Paul , Phillips Nelson
Published: December 2006

This article examines the relationship between altruism and agency costs in family business through an in–depth case study of a family firm. We found that altruism reduced agency costs in the early stages of the business, but that agency problems increased as the venture became larger and more established. Moreover, we suggest that altruistic behavior need not be confined to family and close kin, but may extend through networks of distant kin and ethnic ties. We thus present a more complex view of the agency relationship in family business than is often portrayed in the existing literature.
Commentary: A Framework for Managing the Familiness and Agency Advantages in Family Firms
Authors: Habbershon Timothy G.
Published: December 2006

This article uses a family–influenced, international, new venture creation case as a platform for addressing the importance of context when exploring entrepreneurship in start–up and growth companies. I raise crucial issues about how agency relationships and costs are evaluated in family firms, arguing that the competitiveness implications of agency can only be fully assessed in light of the larger context considerations. I suggest that agency is best evaluated as inputs and outputs in a contextual ecosystem. I utilize a family business ecosystems model to show that family is a distinct context for entrepreneurship and that it generates an idiosyncratic bundle of resources and capabilities that provide a potential agency advantage in new venture creation. Since the case findings indicate that the agency inputs and outputs change over time, I conclude by placing the potential agency advantages and constraints into an organizational life cycle framework. The goal of the article is to further the discussion on how families find their advantage in the entrepreneurial process.
In Vitro Mineralization of Silicon Containing Calcium Phosphate Bioceramics
Authors: Dorozhkin Sergey V.
Published: December 2006

In vitro mineralization of silicon containing calcium phosphate (Si‐CaP) bioceramics was investigated in the constant‐composition double‐diffusion (CCDD) device under physiological conditions. The experiments were performed with porous pellets made of Si‐CaP, which was synthesized from Ca(NO3)2·4H2O, NH4H2PO4, ammonia and fumed silica according to a newly developed single‐stage preparation route. Twice as condensed aqueous solutions of the Kokubo's revised simulated body fluid (rSBF) were used as mineralizing medium. All samples of Si‐CaP bioceramics possessed excellent in vitro mineralizing properties and, therefore, this material is ready for further trials with cells. Simultaneously, the workability of the CCDD device in a less condensed (twofold instead of the previously used fourfold) aqueous solutions of rSBF was confirmed.
Delayed multidisciplinary management of an extrusively luxated maxillary central incisor
Authors: Sübay Rüstem Kemal , Kayataş Müzeyyen , Caniklioğlu Cem
Published: December 2006

Abstract –  This paper reports a case of delayed (1 month after the injury) multidisciplinary management of an extrusively luxated permanent central incisor. The extruded tooth was diagnosed as necrotic without coronal discoloration. Upon completion of root canal treatment, the tooth was repositioned orthodontically and finally restored for esthetic purposes with a composite resin. The tooth was diagnosed as normal in the 1 year check‐up.
Orofacial injuries associated with prehospital management of febrile convulsion in Nigerian children
Authors: Ndukwe Kizito C. , Folayan Morenike O. , Ugboko Vincent I. , Elusiyan Jerome B.E. , Laja Olajumoke O.
Published: December 2006

Abstract –  The aim of this prospective study was to determine in a population of pediatric patients with febrile convulsions the prevalence and pattern of orofacial and dental injuries caused by traditional remedies used in a suburban Nigerian community. Over the study period of 28 months, 75 cases of febrile convulsion presented to the Children's Emergency unit of our hospital. Of these, 27 children (36%) sustained orofacial injuries caused by forceful insertion of a spoon into the mouth (96.3%) or a bite (3.7%) during convulsive episodes. The ages of the patients ranged from 12 to 84 months with a mean 39.8 ± 18.3 months. There were 15 males and 11 females with a male to female ratio of 1.4:1. The orofacial and dental injuries sustained from prehospital treatment at home were lacerations and bruising of soft tissues including lips, tongue, mucosa and commissures and tooth subluxation, displacement or avulsion. Other injuries sustained outside the mouth include second‐degree burns to the feet, a chin laceration and facial bruises resulting from a fall. Many oral injuries were overlooked by pediatricians. Prompt recognition and appropriate management of febrile convulsion would be of great benefit to the pediatric patients.
Roles of reactive oxygen species in the corpus luteum
Authors: SUGINO Norihiro
Published: December 2006

Cells living under aerobic conditions always face the oxygen paradox. Oxygen is necessary for cells to maintain their lives. However, reactive oxygen species such as superoxide radicals, hydroxyl radicals and hydrogen peroxide are generated from oxygen and damage cells. Oxidative stress occurs as a consequence of the excessive production of reactive oxygen species and impaired antioxidant defense systems. Antioxidant enzymes include superoxide dismutase (SOD), which is a specific enzyme to scavenge superoxide radicals; copper‐zinc SOD, located in the cytosol and Mn‐SOD, located in the mitochondria. Both types of SOD belong to the first enzymatic step to scavenge superoxide radicals. It has been reported that a number of local factors such as cytokines, growth factors and eicosanoids are involved in the regulation of the corpus luteum (CL) function in addition to gonadotropins. Since reactive oxygen species are generated and SOD is expressed in the CL, there is a possibility that reactive oxygen species and SOD work as local regulators of the CL function. The present review reports that reactive oxygen species and their scavenging systems play important roles in the regulation of the CL function.
Molecular cloning and expression analysis of cDNA encoding bovine adipogenin
Authors: HONG Yeon‐Hee , OGIHARA Yumi , HISHIKAWA Daisuke , GOTOH Chizu , IGA Tomoyo , SUZUKI Yasuki , SONG Sang‐Houn , NAKAJIMA Keiichi , KOZAKAI Takaharu , SASAKI Shin‐ichi , ROH Sang‐Gun
Published: December 2006

Adipose tissue plays a central role in energy homeostasis. In a previous report, we reported adipogenin, an adipocyte‐specific membrane protein whose expression is higher in fat and increases during the adipocyte differentiation of 3T3‐L1 cells, as a candidate gene for involvement in adipogenesis. Here, we isolated the bovine adipogenin gene using in silico cloning and the target region for polymerase chain reaction amplification in the database. cDNA, including a 246 base pair (bp) open reading frame, was identified in the adipose tissues of cattle. In silico gene analysis showed that the bovine adipogenin‐encoded protein has a predicted MW of 9882.45, encoding 81 amino acids and located on bovine chromosome 13. The deduced amino acid sequence of bovine adipogenin conserved 86%, 66% and 78% identity with that in pigs, mice and humans, respectively. A semi‐quantitative reverse transcriptase polymerase chain reaction showed that bovine adipogenin mRNA was more highly expressed in subcutaneous, perirenal and mescentric adipose tissue than in non‐adipose tissue. The level of bovine adipogenin mRNA is dramatically elevated during the adipocyte differentiation of four different kinds of preadipocytes prepared from subcutaneous, perirenal, mesenteric and parametrial adipose tissues. Our results suggest that adipogenin plays an important role in the regulation of adipocyte development in cattle and may be a strong candidate gene for obesity in mammals.
A Cytotoxic Neolignan from Schisandra propinqua (Wall.) Baill.
Authors: Xu Li‐Jia , Huang Feng , Chen Si‐Bao , Li Lian‐Niang , Chen Shi‐Lin , Xiao Pei‐Gen
Published: December 2006

In the course of our study of bioactive natural products from Schisandra plants, we isolated a neolignan from an EtOAc extract of the stems of Schisandra propinqua (Wall.) Baill. The structure of the new compound was determined to be 4, 4‐di (4‐hydroxy‐3‐methoxyphenly)‐2, 3‐dimethylbutanol (compound 1) on the basis of 1H‐ and 13C‐NMR spectra and 2D NMR methods. Eight known compounds, compounds 2‐9, were also isolated and identified, of which compounds 3, 4, 6 and 9 were isolated for the first time from this plant. In addition, compounds 1‐4 were evaluated for cytotoxicity by an 3‐(4,5‐dimethyl‐2 thiazoyl)‐2,5‐diphenyl‐2H‐tetrazolium bromide (MTT) assay. Compound 1 showed significant potential cytotoxic ability in the bioassay.

(Managing editor: Wei Wang)
Influence of Roasting Conditions on the Acrylamide Content and the Color of Roasted Almonds
Authors: Lukac Helen , Amrein Thomas M. , Perren Rainer , Conde‐Petit Béatrice , Amadò Renato , Escher Felix
Published: December 2006

ABSTRACT:  The influence of roasting conditions on the acrylamide content and on the color of roasted almonds of 3 cultivars was investigated. The temperature inside the almond kernel, the water content, the color, and the acrylamide content were determined at different roasting temperatures and times. The formation of acrylamide started only when the kernel temperature had exceeded approximately 130 °C. The activation energy for the acrylamide formation during the roasting of almonds was 123 kJ·mol−1. The color as measured by the degree of brightness correlated well with the acrylamide content as acrylamide content increased with increasing darkness. Therefore, control of roasting temperature presents the critical factor for limiting the acrylamide concentration in the final product. At constant roasting conditions, almonds with higher initial moisture content contained less acrylamide after roasting, which is probably due to the influence of moisture on the development product temperature during roasting.
Joint Gap Kinematics in Posterior-Stabilized Total Knee Arthroplasty Measured by a New Tensor With the Navigation System
Authors: Matsumoto Tomoyuki , Muratsu Hirotsugu , Tsumura Nobuhiro , Mizuno Kiyonori , Kuroda Ryosuke , Yoshiya Shinichi , Kurosaka Masahiro
Published: December 2006

Background: The management of soft tissue balance during surgery is essential for the success of total knee arthroplasty (TKA) but remains difficult, leaving it much to the surgeon’s feel. Previous assessments for soft tissue balance have been performed under unphysiological joint conditions, with patellar eversion and without the prosthesis only at extension and 90 deg of flexion. We therefore developed a new tensor for TKA procedures, enabling soft tissue balance assessment throughout the range of motion while reproducing postoperative joint alignment with the patellofemoral (PF) joint reduced and the tibiofemoral joint aligned. Our purpose in the present study was to clarify joint gap kinematics using the tensor with the CT-free computer assisted navigation system. Method of Approach: Joint gap kinematics, defined as joint gap change during knee motion, was evaluated during 30 consecutive, primary posterior-stabilized (PS) TKA with the navigation system in 30 osteoarthritic patients. Measurements were performed using a newly developed tensor, which enabled the measurement of the joint gap throughout the range of motion, including the joint conditions relevant after TKA with PF joint reduced and trial femoral component in place. Joint gap was assessed by the tensor at full extension, 5 deg, 10 deg, 15 deg, 30 deg, 45 deg, 60 deg, 90 deg, and 135 deg of flexion with the patella both everted and reduced. The navigation system was used to obtain the accuracy of implantations and to measure an accurate flexion angle of the knee during the intraoperative joint gap measurement. Results: Results showed that the joint gap varied depending on the knee flexion angle. Joint gap showed an accelerated decrease during full knee extension. With the PF joint everted, the joint gap increased throughout knee flexion. In contrast, the joint gap with the PF joint reduced increased with knee flexion but decreased after 60 deg of flexion. Conclusions: We clarified the characteristics of joint gap kinematics in PS TKA under physiological and reproducible joint conditions. Our findings can provide useful information for prosthetic design and selection and allow evaluation of surgical technique throughout the range of knee motion that may lead to consistent clinical outcomes after TKA.
A Transversely Isotropic Viscoelastic Constitutive Equation for Brainstem Undergoing Finite Deformation
Authors: Ning Xinguo , Zhu Qiliang , Lanir Yoram , Margulies Susan S.
Published: December 2006

The objective of this study was to define the constitutive response of brainstem undergoing finite shear deformation. Brainstem was characterized as a transversely isotropic viscoelastic material and the material model was formulated for numerical implementation. Model parameters were fit to shear data obtained in porcine brainstem specimens undergoing finite shear deformation in three directions: parallel, perpendicular, and cross sectional to axonal fiber orientation and determined using a combined approach of finite element analysis (FEA) and a genetic algorithm (GA) optimizing method. The average initial shear modulus of brainstem matrix of 4-week old pigs was 12.7Pa, and therefore the brainstem offers little resistance to large shear deformations in the parallel or perpendicular directions, due to the dominant contribution of the matrix in these directions. The fiber reinforcement stiffness was 121.2Pa, indicating that brainstem is anisotropic and that axonal fibers have an important role in the cross-sectional direction. The first two leading relative shear relaxation moduli were 0.8973 and 0.0741, respectively, with corresponding characteristic times of 0.0047 and 1.4538s, respectively, implying rapid relaxation of shear stresses. The developed material model and parameter estimation technique are likely to find broad applications in neural and orthopaedic tissues.
Disc Mechanics With Trans-Endplate Partial Nucleotomy are not Fully Restored Following Cyclic Compressive Loading and Unloaded Recovery
Authors: Vresilovic Edward J. , Johannessen Wade , Elliott Dawn M.
Published: December 2006

Mechanical function of the intervertebral disc is maintained through the interaction between the hydrated nucleus pulposus, the surrounding annulus fibrosus, and the superior and inferior endplates. In disc degeneration the normal transfer of load between disc substructures is compromised. The objective of this study was to explore the mechanical role of the nucleus pulposus in support of axial compressive loads over time. This was achieved by measuring the elastic slow ramp and viscoelastic stress-relaxation mechanical behaviors of cadaveric sheep motion segments before and after partial nucleotomy through the endplate (keeping the annulus fibrosus intact). Mechanics were evaluated at five conditions: Intact, intact after 10,000cycles of compression, acutely after nucleotomy, following nucleotomy and 10,000cycles of compression, and following unloaded recovery. Radiographs and magnetic resonance images were obtained to examine structure. Only the short time constant of the stress relaxation was altered due to nucleotomy. In contrast, cyclic loading resulted in significant and large changes to both the stiffness and stress relaxation behaviors. Moreover, the nucleotomy had little to no effect on the disc mechanics after cyclic loading, as there were no significant differences comparing mechanics after cyclic loading with or without the nucleotomy. Following unloaded recovery the mechanical changes that had occurred as a consequence of cyclic loading were restored, leaving only a sustained change in the short time constant due to the trans-endplate nucleotomy. Thus the swelling and redistribution of the remaining nucleus pulposus was not able to fully restore mechanical behaviors. This study reveals insights into the role of the nucleus pulposus in disc function, and provides new information toward the potential role of altered nucleus pulpous function in the degenerative cascade.
Tilt Determination in MEMS Inertial Vestibular Prosthesis
Authors: Weinberg Marc. S. , Wall Conrad , Robertsson Jimmy , O’Neil Edward , Sienko Kathleen , Fields Robert
Published: December 2006

Background: There is a clear need for a prosthesis that improves postural stability in the balance impaired. Such a device would be used as a temporary aid during recovery from ablative inner-ear surgery, a postural monitor during rehabilitation (for example, hip surgery), and as a permanent prosthesis for those elderly prone to falls. Method of approach: Recently developed, small instruments have enabled wearable prostheses to augment or replace vestibular functions. The current prosthesis communicates by vibrators mounted on the subject’s trunk. In this paper we emphasize the unique algorithms that enable tilt indication with modestly performing micromachined gyroscopes and accelerometers. Results: For large angles and multiple axes, gyro drift and unwanted lateral accelerations are successfully rejected. In single-axis tests, the most dramatic results were obtained in standard operating tests where balance-impaired subjects were deprived of vision and proprioceptive inputs. Balance-impaired subjects who fell (into safety restraints) when not aided were able to stand with the prosthesis. Initial multiaxis tests with healthy subjects have shown that sway is reduced in both forward-back and sideward directions. Conclusions: Positive results in initial testing and a sound theoretical basis for the hardware warrant continued development and testing, which is being conducted at three sites.
In Vitro and In Vivo Activities of a New Cephalosporin, FR264205, against
Pseudomonas aeruginosa
Authors: Takeda Shinobu , Nakai Toru , Wakai Yoshimi , Ikeda Fumiaki , Hatano Kazuo
Published: December 2006

FR264205 is a novel parenteral 3′-aminopyrazolium cephalosporin. This study evaluated the in vitro and in vivo activities of FR264205 against
Pseudomonas aeruginosa
. The MIC of FR264205 at which 90% of 193 clinical isolates of
P. aeruginosa
were inhibited was 1 μg/ml, 8- to 16-fold lower than those of ceftazidime (CAZ), imipenem (IPM), and ciprofloxacin (CIP). FR264205 also exhibited this level of activity against CAZ-, IPM-, and CIP-resistant
P. aeruginosa
. The reduction in the susceptibility of FR264205 by AmpC β-lactamase was lower than that of CAZ, indicating a relatively high stability of FR264205 against AmpC β-lactamase, the main resistance mechanism for cephalosporins. Neither expression of efflux pumps nor deficiency of OprD decreased the activity of FR264205. No spontaneous resistance mutants were selected in the presence of FR264205, and the reduction in susceptibility to FR264205 was lower than that to CAZ, IPM, and CIP after serial passage, suggesting that FR264205 has a low propensity for selecting resistance. In murine pulmonary, urinary tract, and burn wound models of infection caused by
P. aeruginosa
, the efficacy of FR264205 was superior or comparable to those of CAZ and IPM. These results indicate that FR264205 should have good potential as an antibacterial agent for
P. aeruginosa
.
Synergistic Interaction between Phenothiazines and Antimicrobial Agents against
Burkholderia pseudomallei
Authors: Chan Ying Ying , Ong Yong Mei , Chua Kim Lee
Published: December 2006

The gram-negative soil bacillus
Burkholderia pseudomallei
is the causative agent of melioidosis, a severe and potentially fatal septicemic disease that is endemic to Southeast Asia and northern Australia. Its intrinsic resistance to many antibiotics is attributed mainly to the presence of several drug efflux pumps, and therefore, inhibitors of such pumps are expected to restore the activities of many clinically important antimicrobial agents that are the substrates of these pumps. The phenothiazine antipsychotic and antihistaminic drugs prochlorperazine, chlorpromazine, and promazine have a synergistic interaction with a wide spectrum of antimicrobial agents, thereby enhancing their antimicrobial potency against
B. pseudomallei
. Antimicrobial agents that interacted synergistically with the phenothiazines include streptomycin, erythromycin, oleandomycin, spectinomycin, levofloxacin, azithromycin, and amoxicillin-clavulanic acid. The MICs of these antibiotics were reduced as much as 8,000-fold in the presence of the phenothiazines. Antimicrobial agents which did not interact synergistically with the phenothiazines include gentamicin, amoxicillin, and ampicillin. Omeprazole, a proton pump inhibitor, provided an augmentation of antimicrobial activities similar to that of the phenothiazines, suggesting that the phenothiazines might have interfered with the proton gradient at the inner membrane.
B. pseudomallei
cells accumulated more erythromycin in the presence of the phenothiazines, an effect similar to that of carbonyl cyanide
m
-chlorophenylhydrazone, a proton gradient uncoupler. In the presence of the phenothiazines, a much reduced concentration of erythromycin (0.06× MIC) also protected human lung epithelial cells and macrophage cells from
B. pseudomallei
infection and attenuated its cytotoxicity.
Cysteine Protease Inhibitors Block
Toxoplasma gondii
Microneme Secretion and Cell Invasion
Authors: Teo Chin Fen , Zhou Xing Wang , Bogyo Matthew , Carruthers Vern B.
Published: December 2006

Toxoplasma gondii
enters host cells via an active, self-driven process to fulfill its need for intracellular replication and survival. Successful host cell invasion is governed by sequential release of secretory proteins from three specialized organelles, including the micronemes, which contribute adhesive proteins necessary for parasite attachment and penetration. Cumulative evidence from studies of
Trypanosoma
species and malaria parasites has shown that cysteine protease inhibitors represent potent anti-parasitic agents capable of curing infections in vivo. In this study, we screened a series of selective cysteine protease inhibitors for their effects on
T. gondii
cell invasion. Two of these compounds, morpholinourea-leucyl-homophenolalaninyl-phenyl-vinyl-sulfone and
N
-benzoxycarbonyl-(leucyl)
3
-phenyl-vinyl-sulfone, impaired
T. gondii
invasion and gliding motility at low-micromolar concentrations. Unexpectedly, these inhibitors did not affect surface proteolysis of microneme products but instead impaired an earlier step by precluding the secretion of microneme-derived adhesins to the parasite surface. Our findings suggest that cysteine protease activity is required for microneme secretion and cell invasion by
T. gondii
.
Cytotoxic Effect of Curcumin on Malaria Parasite
Plasmodium falciparum
: Inhibition of Histone Acetylation and Generation of Reactive Oxygen Species
Authors: Cui Long , Miao Jun , Cui Liwang
Published: December 2006

The emergence of multidrug-resistant parasites is a major concern for malaria control, and development of novel drugs is a high priority. Curcumin, a natural polyphenolic compound, possesses diverse pharmacological properties. Among its antiprotozoan activities, curcumin was potent against both chloroquine-sensitive and -resistant
Plasmodium falciparum
strains. Consistent with findings in mammalian cell lines, curcumin's prooxidant activity promoted the production in
P. falciparum
of reactive oxygen species (ROS), whose cytotoxic effect could be antagonized by coincubation with antioxidants and ROS scavengers. Curcumin treatment also resulted in damage of both mitochondrial and nuclear DNA, probably due to the elevation of intracellular ROS. Furthermore, we have demonstrated that curcumin inhibited the histone acetyltransferase (HAT) activity of the recombinant
P. falciparum
general control nonderepressed 5 (PfGCN5) in vitro and reduced nuclear HAT activity of the parasite in culture. Curcumin-induced hypoacetylation of histone H3 at K9 and K14, but not H4 at K5, K8, K12, and K16, suggested that curcumin caused specific inhibition of the PfGCN5 HAT. Taken together, these results indicated that at least the generation of ROS and down-regulation of PfGCN5 HAT activity accounted for curcumin's cytotoxicity for malaria parasites.
IS
21-558
Insertion Sequences Are Involved in the Mobility of the Multiresistance Gene
cfr
Authors: Kehrenberg Corinna , Aarestrup Frank M. , Schwarz Stefan
Published: December 2006

During a study of florfenicol-resistant porcine staphylococci from Denmark, the genes
cfr
and
fexA
were detected in the chromosomal DNA or on plasmids of
Staphylococcus hyicus
,
Staphylococcus warneri
, and
Staphylococcus simulans
. A novel variant of the phenicol resistance transposon Tn
558
was detected on the ca. 43-kb plasmid pSCFS6 in
S. warneri
and
S. simulans
isolates. Sequence analysis of a 22,010-bp segment revealed that the new Tn
558
variant harbored an additional resistance gene region integrated into the
tnpC
reading frame. This resistance gene region consisted of the clindamycin exporter gene
lsa
(B) and the gene
cfr
for combined resistance to phenicols, lincosamides, oxazolidinones, pleuromutilins, and streptogramin A antibiotics bracketed by IS
21-558
insertion sequences orientated in the same direction. A 6-bp target site duplication was detected at the integration site within
tnpC
. Transpositionally active forms of the IS
21-558
element, known as minicircles, were detected by PCR and suggest that this insertion sequence is involved in the mobility of the multiresistance gene
cfr
. Based on the knowledge of the transposition pathways of IS
21
-like insertion sequences and the sequence features detected, the resistance gene region of plasmid pSCFS6 is believed to have developed via IS
21-558
-mediated cointegrate formation. The data obtained in this study identified the multiresistance gene
cfr
not only in three novel host species but also in a novel genetic context whose further analysis suggested that insertion sequences of the type IS
21-558
are likely to be involved in the dissemination of
cfr
.
Immunochemical Characterization of Temperature-Regulated Production of Enterocin L50 (EntL50A and EntL50B), Enterocin P, and Enterocin Q byEnterococcus faeciumL50
Authors: Criado Raquel , Gutiérrez Jorge , Martín María , Herranz Carmen , Hernández Pablo E. , Cintas Luis M.
Published: December 2006

Polyclonal antibodies with specificity for enterocin L50A (EntL50A), enterocin L50B (EntL50B), and enterocin Q (EntQ) produced byEnterococcus faeciumL50 have been generated by immunization of rabbits with chemically synthesized peptides derived from the C terminus of EntL50A (LR1) and EntL50B (LR2) and from the complete enterocin Q (EntQ) conjugated to the carrier protein keyhole limpet hemocyanin (KLH). The sensitivity and specificity of these antibodies were evaluated by a noncompetitive indirect enzyme-linked immunosorbent assay (NCI-ELISA) and a competitive indirect ELISA (CI-ELISA). The NCI-ELISA was valuable for detecting anti-EntL50A-, anti-EntL50B-, and anti-EntQ-specific antibodies in the sera of the LR1-KLH-, LR2-KLH-, and EntQ-KLH-immunized animals, respectively. Moreover, these antibodies and those specific for enterocin P (EntP) obtained in a previous work (J. Gutiérrez, R. Criado, R. Citti, M. Martín, C. Herranz, M. F. Fernández, L. M. Cintas, and P. E. Hernández, J. Agric. Food Chem.52:2247-2255, 2004) were used in an NCI-ELISA to detect and quantify the production of EntL50A, EntL50B, EntP, and EntQ by the multiple-bacteriocin producerE. faeciumL50 grown at different temperatures (16 to 47°C). Our results show that temperature has a strong influence on bacteriocin production by this strain. EntL50A and EntL50B are synthesized at 16 to 32°C, but production becomes negligible when the growth temperature is above 37°C, whereas EntP and EntQ are synthesized at temperatures ranging from 16 to 47°C. Maximum EntL50A and EntL50B production was detected at 25°C, while EntP and EntQ are maximally produced at 37 and 47°C, respectively. The loss of plasmid pCIZ1 (50 kb) and/or pCIZ2 (7.4 kb), encoding EntL50A and EntL50B as well as EntQ, respectively, resulted in a significant increase in production and stability of the chromosomally encoded EntP.
Quantitative Detection of Hepatitis A Virus and Enteroviruses Near the United States-Mexico Border and Correlation with Levels of Fecal Indicator Bacteria
Authors: Gersberg Richard M. , Rose Michael A. , Robles-Sikisaka Refugio , Dhar Arun K.
Published: December 2006

For decades, untreated sewage flowing northward from Tijuana, Mexico, via the Tijuana River has adversely affected the water quality of the recreational beaches of San Diego, California. We used quantitative reverse transcription-PCR to measure the levels of hepatitis A virus (HAV) and enteroviruses in coastal waters near the United States-Mexico border and compared these levels to those of the conventional fecal indicators,
Escherichia coli
and enterococci. Over a 2-year period from 2003 to 2005, a total of 20 samples were assayed at two sites during both wet and dry weather: the surfzone at the mouth of the Tijuana River and the surfzone near the pier at Imperial Beach (IB), California (about 2 km north of the mouth of the Tijuana River). HAV and enterovirus were detected in 79 and 93% of the wet-weather samples, respectively. HAV concentrations in these samples ranged from 105 to 30,771 viral particles/liter, and enterovirus levels ranged from 7 to 4,417 viral particles/liter. The concentrations of HAV and enterovirus were below the limit of detection for all dry weather samples collected at IB. Regression analyses showed a significant correlation between the densities of both fecal bacterial indicators and the levels of HAV (
R
2
> 0.61,
P
< 0.0001) and enterovirus (
R
2
> 0.70,
P
< 0.0001), a finding that supports the use of conventional bacterial indicators to predict the levels of these viruses in recreational marine waters.
Constitutive Delivery of Bovine β-Lactoglobulin to the Digestive Tracts of Gnotobiotic Mice by EngineeredLactobacillus casei
Authors: Hazebrouck S. , Oozeer R. , Adel-Patient K. , Langella P. , Rabot S. , Wal J.-M. , Corthier G.
Published: December 2006

The gut microbiota is critical for maturation of the immune system. Recent evidence suggests that early establishment of lactobacilli in the intestinal microbiota, during neonatal colonization or by probiotic supplementation, could prevent the development of allergic disorders. Postnatal maturation of the gut immune system with allergen-producing lactobacilli colonizing the digestive tract could then affect the development of further allergic sensitization. In this paper, we describe construction of a recombinantLactobacillus caseistrain that can constitutively deliver bovine β-lactoglobulin (BLG), a major cow's milk allergen, to the guts of gnotobiotic mice. Theblggene was inserted into theL. caseichromosome downstream of an endogenous promoter. BLG production was improved by fusing the propeptide LEISSTCDA (LEISS) to the BLG mature moiety. This led to a 10-fold increase in LEISS-BLG production compared to the production obtained without the propeptide and also led to enhanced secretion corresponding to 5% of the total production. After inoculation into germfree C3H/HeN mice, the genetic stability of the recombinant strain and in vivo BLG production were confirmed for at least 10 weeks. BLG stimulation of spleen cells from mice monoassociated with the BLG-producing lactobacilli induced secretion of the Th1 cytokine gamma interferon and, to a lesser extent, the Th2 cytokine interleukin-5. No BLG-specific immunoglobulin G1 (IgG1), IgG2a, or IgA was detected in sera or in fecal samples. These results suggest that gut colonization with allergen-producing lactobacilli could provide a useful model for studying the modulation of allergic disorders.