bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of erythropoietin on healing of obstructive vs nonobstructive left colonic anastomosis: an experimental study
Authors: Moran Munevver , Ozmen M Mahir , Duzgun A Polat , Gok Riza , Renda Nurten , Seckin Selda , Coskun Faruk
Published: May 2007

Background

Anastomotic leakage is an important problem following primary resection in the left colon and is even more prominent when obstruction is present. We aimed to evaluate the possible effects of erythropoietin on the healing of anastomosis under both obstructive and non-obstructive states.

Methods

Forty male Wistar albino rats were divided into four groups. In group I, two cm left colonic resection and primary anastomosis were done. In group II, left colon were completely ligated and 24 hours later animals were re-operated for segmental resection. The same procedures were performed for rats in group III and IV in respect to group I and II and, 500 IU/kg a day erythropoietin were given in the latter two groups for seven days. For the quantative description of anastomotic healing mechanical, biochemical and histopathological parameters were employed on the seventh day and the animals were sacrificied.

Results

Although erythropoietin had positive effects on bursting pressure in group IV when compared to group II, it has no effect in group III. Despite the increased tissue hydroxyproline levels in group IV, erythropoietin failed to show any effects in group III.

Erythropoietin had positive effects on neovascularization, fibroblast proliferiation and storage of collagen in group IV.

Conclusion

We failed to find any direct and evident effects of erythropoietin on healing of left colonic anastomosis. On the other hand, erythropoietin might prevent negative effects of obstruction on healing.
Pharmacogenomics and the Yin/Yang actions of ginseng: anti-tumor, angiomodulating and steroid-like activities of ginsenosides
Authors: Yue Patrick Ying Kit , Mak Nai Ki , Cheng Yuen Kit , Leung Kar Wah , Ng Tzi Bun , Fan David Tai Ping , Yeung Hin Wing , Wong Ricky Ngok Shun
Published: May 2007

In Chinese medicine, ginseng (Panax ginseng C.A. Meyer) has long been used as a general tonic or an adaptogen to promote longevity and enhance bodily functions. It has also been claimed to be effective in combating stress, fatigue, oxidants, cancer and diabetes mellitus. Most of the pharmacological actions of ginseng are attributed to one type of its constituents, namely the ginsenosides. In this review, we focus on the recent advances in the study of ginsenosides on angiogenesis which is related to many pathological conditions including tumor progression and cardiovascular dysfunctions.

Angiogenesis in the human body is regulated by two sets of counteracting factors, angiogenic stimulators and inhibitors. The 'Yin and Yang' action of ginseng on angiomodulation was paralleled by the experimental data showing angiogenesis was indeed related to the compositional ratio between ginsenosides Rg1and Rb1. Rg1was later found to stimulate angiogenesis through augmenting the production of nitric oxide (NO) and vascular endothelial growth factor (VEGF). Mechanistic studies revealed that such responses were mediated through the PI3K→Akt pathway. By means of DNA microarray, a group of genes related to cell adhesion, migration and cytoskeleton were found to be up-regulated in endothelial cells. These gene products may interact in a hierarchical cascade pattern to modulate cell architectural dynamics which is concomitant to the observed phenomena in angiogenesis. By contrast, the anti-tumor and anti-angiogenic effects of ginsenosides (e.g. Rg3and Rh2) have been demonstrated in various models of tumor and endothelial cells, indicating that ginsenosides with opposing activities are present in ginseng. Ginsenosides and Panax ginseng extracts have been shown to exert protective effects on vascular dysfunctions, such as hypertension, atherosclerotic disorders and ischemic injury. Recent work has demonstrates the target molecules of ginsenosides to be a group of nuclear steroid hormone receptors. These lines of evidence support that the interaction between ginsenosides and various nuclear steroid hormone receptors may explain the diverse pharmacological activities of ginseng. These findings may also lead to development of more efficacious ginseng-derived therapeutics for angiogenesis-related diseases.
Novel action of apolipoprotein E (ApoE): ApoE isoform specifically inhibits lipid-particle-mediated cholesterol release from neurons
Authors: Gong Jian-Sheng , Morita Shin-ya , Kobayashi Mariko , Handa Tetsurou , Fujita Shinobu C , Yanagisawa Katsuhiko , Michikawa Makoto
Published: May 2007

Background

Since the majority of apolipoprotein E (apoE) existing in the cerebrospinal fluid is associated with high-density lipoprotein (HDL), one should focus on the role of the apoE-HDL complex rather than on that of free apoE in cholesterol metabolism in the central nervous system. However, the apoE-isoform-specific effect of apoE-HDL on cholesterol transport remains unclarified.

Results

Here we show that apoE3-HDL induced a marked cholesterol release from neurons, while apoE4-HDL induced little. To elucidate the mechanism underlying this phenomenon, we used a complex of lipid emulsion (EM) with recombinant apoE3 or apoE4 (apoE-EM) at various apoE concentrations. When a small number of apoE molecules were associated with EM, apoE3- and apoE4-EM, induced a marked cholesterol release to a level similar to that induced by EM alone. However, when apoE at given concentrations was incubated with EM, apoE3-EM induced a marked cholesterol release, while apoE4-EM induced little. Under these conditions, a greater number of apoE4 molecules were associated with EM than apoE3 molecules. When an increasing number of apoE molecules were associated with EM, both apoE3-EM and apoE4-EM induced little cholesterol release. Preincubation with β-mercaptoethanol increased the number of apoE3 molecules associated with EM similar to that of apoE4 molecules, indicating that the presence (apoE3) or absence (apoE4) of intermolecular disulfide bond formation is responsible for the association of a greater number of apoE4 molecules to EM than apoE3 molecules.

Conclusion

These results suggest that although apoE and a lipid particle are lipid acceptors, when apoE and a lipid particle form a complex, apoE on the particle surface inhibits the lipid particle-mediated cholesterol release from cells in an apoE-concentration-dependent manner.
Correlation of umbilical cord blood hormones and growth factors with stem cell potential: implications for the prenatal origin of breast cancer hypothesis
Authors: Savarese Todd M , Strohsnitter William C , Low Hoi Pang , Liu Qin , Baik Inkyung , Okulicz William , Chelmow David P , Lagiou Pagona , Quesenberry Peter J , Noller Kenneth L , Hsieh Chung-Cheng
Published: May 2007

Introduction

Prenatal levels of mitogens may influence the lifetime breast cancer risk by driving stem cell proliferation and increasing the number of target cells, and thereby increasing the chance of mutation events that initiate oncogenesis. We examined in umbilical cord blood the correlation of potential breast epithelial mitogens, including hormones and growth factors, with hematopoietic stem cell concentrations serving as surrogates of overall stem cell potential.

Methods

We analyzed cord blood samples from 289 deliveries. Levels of hormones and growth factors were correlated with concentrations of stem cell and progenitor populations (CD34+ cells, CD34+CD38- cells, CD34+c-kit+ cells, and granulocyte–macrophage colony-forming units). Changes in stem cell concentration associated with each standard deviation change in mitogens and the associated 95% confidence intervals were calculated from multiple regression analysis.

Results

Cord blood plasma levels of insulin-like growth factor-1 (IGF-1) were strongly correlated with all the hematopoietic stem and progenitor concentrations examined (one standard-deviation increase in IGF-1 being associated with a 15–19% increase in stem/progenitor concentrations, all P < 0.02). Estriol and insulin-like growth factor binding protein-3 levels were positively and significantly correlated with some of these cell populations. Sex hormone-binding globulin levels were negatively correlated with these stem/progenitor pools. These relationships were stronger in Caucasians and Hispanics and were weaker or not present in Asian-Americans and African-Americans.

Conclusion

Our data support the concept that in utero mitogens may drive the expansion of stem cell populations. The correlations with IGF-1 and estrogen are noteworthy, as both are crucial for mammary gland development.
TP53mutation status and gene expression profiles are powerful prognostic markers of breast cancer
Authors: Langerød Anita , Zhao Hongjuan , Borgan Ørnulf , Nesland Jahn M , Bukholm Ida RK , Ikdahl Tone , Kåresen Rolf , Børresen-Dale Anne-Lise , Jeffrey Stefanie S
Published: May 2007

Introduction

Gene expression profiling of breast carcinomas has increased our understanding of the heterogeneous biology of this disease and promises to impact clinical care. The aim of this study was to evaluate the prognostic value of gene expression-based classification along with established prognostic markers and mutation status of the TP53 gene (tumour protein p53) in a group of breast cancer patients with long-term (12 to 16 years) follow-up.

Methods

The clinical and histopathological parameters of 200 breast cancer patients were studied for their effects on clinical outcome using univariate/multivariate Cox regression. The prognostic impact of mutations in the TP53 gene, identified using temporal temperature gradient gel electrophoresis and sequencing, was also evaluated. Eighty of the samples were analyzed for gene expression using 42 K cDNA microarrays and the patients were assigned to five previously defined molecular expression groups. The strength of the gene expression based classification versus standard markers was evaluated by adding this variable to the Cox regression model used to analyze all samples.

Results

Both univariate and multivariate analysis showed that TP53 mutation status, tumor size and lymph node status were the strongest predictors of breast cancer survival for the whole group of patients. Analyses of the patients with gene expression data showed that TP53 mutation status, gene expression based classification, tumor size and lymph node status were significant predictors of survival. Breast cancer cases in the 'basal-like' and 'ERBB2+' gene expression subgroups had a very high mortality the first two years, while the 'highly proliferating luminal' cases developed the disease more slowly, showing highest mortality after 5 to 8 years. The TP53 mutation status showed strong association with the 'basal-like' and 'ERBB2+' subgroups, and tumors with mutation had a characteristic gene expression pattern.

Conclusion

TP53 mutation status and gene-expression based groups are important survival markers of breast cancer, and these molecular markers may provide prognostic information that complements clinical variables. The study adds experience and knowledge to an ongoing characterization and classification of the disease.
Species-wide distribution of highly polymorphic minisatellite markers suggests past and present genetic exchanges among house mouse subspecies
Authors: Bonhomme François , Rivals Eric , Orth Annie , Grant Gemma R , Jeffreys Alec J , Bois Philippe RJ
Published: May 2007

Background

Four hypervariable minisatellite loci were scored on a panel of 116 individuals of various geographical origins representing a large part of the diversity present in house mouse subspecies. Internal structures of alleles were determined by minisatellite variant repeat mapping PCR to produce maps of intermingled patterns of variant repeats along the repeat array. To reconstruct the genealogy of these arrays of variable length, the specifically designed software MS_Align was used to estimate molecular divergences, graphically represented as neighbor-joining trees.

Results

Given the high haplotypic diversity detected (mean He= 0.962), these minisatellite trees proved to be highly informative for tracing past and present genetic exchanges. Examples of identical or nearly identical alleles were found across subspecies and in geographically very distant locations, together with poor lineage sorting among subspecies except for the X-chromosome locus MMS30 in Mus mus musculus. Given the high mutation rate of mouse minisatellite loci, this picture cannot be interpreted only with simple splitting events followed by retention of polymorphism, but implies recurrent gene flow between already differentiated entities.

Conclusion

This strongly suggests that, at least for the chromosomal regions under scrutiny, wild house mouse subspecies constitute a set of interrelated gene pools still connected through long range gene flow or genetic exchanges occurring in the various contact zones existing nowadays or that have existed in the past. Identifying genomic regions that do not follow this pattern will be a challenging task for pinpointing genes important for speciation.
Exon arrays provide accurate assessments of gene expression
Authors: Kapur Karen , Xing Yi , Ouyang Zhengqing , Wong Wing Hung
Published: May 2007

We have developed a strategy for estimating gene expression on Affymetrix Exon arrays. The method includes a probe-specific background correction and a probe selection strategy in which a subset of probes with highly correlated intensities across multiple samples are chosen to summarize gene expression. Our results demonstrate that the proposed background model offers improvements over the default Affymetrix background correction and that Exon arrays may provide more accurate measurements of gene expression than traditional 3' arrays.
Modulation of NFAT-dependent gene expression by the RhoA signaling pathway in T cells
Authors: Helms Whitney S , Jeffrey Jerry L , Holmes Derek A , Townsend Michael B , Clipstone Neil A , Su Lishan
Published: May 2007

We have reported previously that p115Rho guanine nucleotide exchange factor, its upstream activator Gα13, and its effector RhoA are able to inhibit HIV-1 replication. Here, we show that RhoA is able to inhibit HIV-1 gene expression through the NFAT-binding site in the HIV long-terminal repeat. Constitutively active NFAT counteracts the inhibitory activity of RhoA, and inhibition of NFAT activation also inhibits HIV-1 gene expression. We have shown further that RhoA inhibits NFAT-dependent transcription and IL-2 production in human T cells. RhoA does not inhibit nuclear localization of NFAT but rather, inhibits its transcriptional activity. In addition, RhoA decreases the level of acetylated histone H3, but not NFAT occupancy, at the IL-2 promoter. These data suggest that activation of RhoA can modulate IL-2 gene expression by inhibiting the transcriptional activity of NFAT and chromatin structure at the IL-2 promoter during T cell activation.
Microtubules regulate PI-3K activity and recruitment to the phagocytic cup during Fcγ receptor-mediated phagocytosis in nonelicited macrophages
Authors: Khandani Arian , Eng Edward , Jongstra-Bilen Jenny , Schreiber Alan D , Douda David , Samavarchi-Tehrani Payman , Harrison Rene E
Published: May 2007

Phagocytosis is a complex sequence of events involving coordinated remodeling of the plasma membrane with the underlying cytoskeleton. Although the role of the actin cytoskeleton is becoming increasingly elucidated, the role of microtubules (MTs) remains poorly understood. Here, we examine the role of MTs during FcγR-mediated phagocytosis in RAW264.7 mouse macrophages. We observe that MTs extend into the phagosomal cups. The MT-depolymerizing agents, colchicine and nocodazole, cause a sizeable reduction in phagocytosis of large particles in RAW264.7 cells. Phagocytosis in primed macrophages is unaffected by MT-depolymerizing agents. However, activation of macrophages coincides with an increased population of drug-stable MTs, which persist in functional phagocytic cups. Scanning electron microscopy analysis of unprimed macrophages reveals that pseudopod formation is reduced markedly following colchicine treatment, which is not a consequence of cell rounding. MT depolymerization in these cells does not affect particle binding, Syk, or Grb2-associated binder 2 recruitment or phosphotyrosine accumulation at the site of phagocytosis. Ras activation also proceeds normally in macrophages treated with colchicine. However, MT disruption causes a decrease in accumulation of AKT-pleckstrin homology-green fluorescent protein, a probe that binds to PI-3K products at the sites of particle binding. A corresponding decline in activated AKT is observed in colchicine-treated cells using immunoblotting with a phospho-specific-AKT (ser473) antibody. Furthermore, the translocation of the p85α regulatory subunit of PI-3K is reduced at the phagocytic cup in colchicine-treated cells. These findings suggest that MTs regulate the recruitment and localized activity of PI-3K during pseudopod formation.
Humanized NOD/LtSz‐scid IL2 Receptor Common Gamma Chain Knockout Mice in Diabetes Research
Authors: SHULTZ LEONARD D. , PEARSON TODD , KING MARIE , GIASSI LISA , CARNEY LISA , GOTT BRUCE , LYONS BONNIE , ROSSINI ALDO A. , GREINER DALE L.
Published: May 2007

Abstract:  There are many rodent models of autoimmune diabetes that have been used to study the pathogenesis of human type 1 diabetes (T1D), including the non‐obese diabetic (NOD) mouse, the biobreeding (BB) rat, and the transgenic mouse models. However, mice and rats are not humans, and these rodent models do not completely recapitulate the autoimmune pathogenesis of the human disease. In addition, many of the reagents, tools, and therapeutics proposed for use in humans may be species specific and cannot be investigated in rodents. Researchers have used nonhuman primates to more closely mimic the human immune system and, to study species‐specific therapeutics, but these studies are associated with additional ethical and economic constraints and, to date, no model of autoimmune diabetes in this species has been described. New animal models are needed that will permit the in vivo investigation of human immune systems and analyses of the pathogenesis of human T1D without putting individuals at risk. To fill this need, we are developing humanized mouse models for the in vivo study of T1D. These models are based on our newly generated stock of NOD‐scid IL2rγnull mice, which engraft at higher levels with human hematolymphoid cells and exhibit enhanced function of the engrafted human immune systems compared with previous humanized mouse models. Overall, development of these new generations of humanized mice should facilitate in vivo studies of the human immune system as well as permit the investigation of the pathogenesis and effector phases of human T1D.
Mouse Models for Studies of Cardiovascular Complications of Type 1 Diabetes
Authors: SHEN XIA , BORNFELDT KARIN E.
Published: May 2007

Abstract:  Mouse models represent a powerful tool for investigating the underlying mechanisms of disease. Type 1 diabetes results in a markedly increased risk of cardiovascular disease. The cardiovascular complications are manifested primarily as ischemic heart disease caused by accelerated atherosclerosis, but also as cardiomyopathy, defined as ventricular dysfunction in the absence of clear ischemic heart disease. Several mouse models are now available to study atherosclerosis and cardiomyopathy associated with type 1 diabetes. For studies of diabetes‐accelerated atherosclerosis, these models include low‐density lipoprotein (LDL) receptor–deficient and apolipoprotein E–deficient mice in which diabetes is induced by streptozotocin or viral infection. In these mouse models, type 1 diabetes can be induced without marked changes in plasma lipid levels, thereby mimicking the accelerated atherosclerosis seen in patients with type 1 diabetes. However, mouse models that exhibit thrombotic events and myocardial infarctions as a result of diabetes still need to be developed. Conversely, cardiomyopathy associated with diabetes has now been extensively evaluated in streptozotocin‐treated C57BL/6 mice, and in transgenic mice expressing calmodulin under a β‐cell‐specific promoter. These mouse models have given significant insight into the molecular mechanisms causing cardiomyopathy, and indicate that increased oxidative stress contributes to diabetes‐associated cardiomyopathy. In this review, we will discuss the available mouse models for studies of cardiovascular complications of type 1 diabetes, the potential mechanisms underlying these complications, and the need for new and improved mouse models.
A New Humanized HLA Transgenic Mouse Model of Multiple Sclerosis Expressing Class II on Mouse CD4 T Cells
Authors: MANGALAM ASHUTOSH , RODRIGUEZ MOSES , DAVID CHELLA
Published: May 2007

Abstract:  Among all the genetic factors associated with susceptibility to multiple sclerosis (MS), the strongest association has been seen with expression of certain major histocompatibility complex (MHC) class II molecules, although analysis of their exact function remains complicated. In general, the expression of class II is restricted to professional antigen‐presenting cells; however, human but not mouse CD4+ T cells express class II on their surface. Functional studies of class II+ CD4+ T cells have been hampered due to lack of a proper animal model. Here, we describe development and characterization of a new humanized class II transgenic (tg) mouse expressing HLA‐DR3 on mouse endogenous class II–negative background.
Coxsackievirus Infections and NOD Mice
Authors: TRACY STEVEN , DRESCHER KRISTEN M.
Published: May 2007

Abstract:  Human enteroviruses (HEVs) like the group B coxsackieviruses (CVBs) are prime candidates for infectious, environmental causes of human type 1 diabetes (T1D). Non‐obese diabetic (NOD) female mice are well protected from T1D onset if inoculated with CVB when young. Older, prediabetic NOD mice can rapidly develop T1D following inoculation with CVB, mimicking clinical reports of disease‐associated T1D onset. The ability to induce rapid T1D in NOD mice is linked to the rate of replication of the CVB strain in β cell cultures and pancreatic tissue, indicating that any CVB strain is potentially diabetogenic under the correct conditions. Rapid T1D onset is preceded by CVB replication in islet cells including β cells. Although CVB strains do not productively infect healthy islets of young mice, CVBs can replicate in healthy islets in the presence of murine IL‐4. These models expand much of what is known or suspected regarding the etiologic role of HEVs in human T1D.
The Virtual NOD Mouse
Authors: ZHENG YANAN , KREUWEL HUUB T. C. , YOUNG DANIEL L. , SHODA LISL K. M. , RAMANUJAN SAROJA , GADKAR KAPIL G. , ATKINSON MARK A. , WHITING CHAN C.
Published: May 2007

Abstract:  Type 1 diabetes is a complex, multifactorial disease characterized by T cell–mediated autoimmune destruction of insulin‐secreting pancreatic β cells. To facilitate research in type 1 diabetes, a large‐scale dynamic mathematical model of the female non‐obese diabetic (NOD) mouse was developed. In this model, termed the Entelos® Type 1 Diabetes PhysioLab® platform, virtual NOD mice are constructed by mathematically representing components of the immune system and islet β cell physiology important for the pathogenesis of type 1 diabetes. This report describes the scope of the platform and illustrates some of its capabilities. Specifically, using two virtual NOD mice with either average or early diabetes‐onset times, we demonstrate the reproducibility of experimentally observed dynamics involved in diabetes progression, therapeutic responses to exogenous IL‐10, and heterogeneity in disease onset. Additionally, we use the Type 1 Diabetes PhysioLab platform to investigate the impact of disease heterogeneity on the effectiveness of exogenous IL‐10 therapy to prevent diabetes onset. Results indicate that the inability of a previously published IL‐10 therapy protocol to protect NOD mice who exhibit early diabetes onset is due to high levels of pancreatic lymph node (PLN) inflammation, islet infiltration, and β cell destruction at the time of treatment initiation. Further, simulation indicates that earlier administration of the treatment protocol can prevent NOD mice from developing diabetes by initiating treatment during the period when the disease is still sensitive to IL‐10's protective function.
Resistance to the Induction of Mixed Chimerism in Spontaneously Diabetic NOD Mice Depends on the CD40/CD154 Pathway and Donor MHC Disparity
Authors: LUO BIN , WU TAO , PAN YISHENG , SOZEN HAKAN , HAO JIANQIANG , ZHANG YU , SUTHERLAND DAVID E. R. , HERING BERNHARD J. , GUO ZHIGUANG
Published: May 2007

Abstract:  Blockade of CD40/CD154 pathway has proven effective in promoting the induction of allogeneic mixed chimerism. Using NOD mouse model of human type 1 diabetes, we investigated whether allogeneic mixed chimerism can be induced in prediabetic NOD mice and in spontaneously diabetic NOD mice under nonmyeloablative and irradiation‐free conditioning therapy and anti‐CD154 mAb as a short‐term posttransplant treatment. We found that spontaneously diabetic NOD mice are more resistant to the induction of allogeneic mixed chimerism than prediabetic NOD mice under our nonmyeloablative and irradiation‐free conditioning therapy. This alloresistance in spontaneously diabetic NOD mice is dependent on the CD40/CD154 pathway and donor MHC disparity.
Diabetes Research in Jeopardy
Authors: ROSSINI ALDO A. , GREINER DALE L.
Published: May 2007

Abstract:  Finding a cure for an autoimmune disease, such as diabetes, must be viewed as a marathon. Although there are occasional quick sprints forward on the road to discovery, the bulk of research is carried out steadily over time. Over the years, researchers have made progressive strides toward a cure, but our field is now facing a crisis. We need youthful researchers with fresh new perspectives to carry on the work started by forerunners in the field. In fact, many young people never get the opportunity to work in a scientific field. Of those who do choose to study science, after receiving a bachelor's degree in that field, only 4% eventually receive their doctorate. There are many reasons for the abrupt end of the academic path for these students. Perhaps they are stymied in their education, frustrated by the lack of grant support and mentorship provided to young scientists. On average, a scientist receives his or her first NIH R01 award at the age of 43 years. Moreover, many young researchers lack the mentorship they seek from more established scientists. This hurdle can be overcome by providing young scientists the ability to work unreservedly with other mature scientists. Ideally, a Diabetes Research Center needs to be geared toward facilitating collaboration and free exchange of ideas to promote the maturation of young scientists. Additionally, this environment, can offer young scientists the resources that would otherwise be unavailable to them. This concept is fundamental to creating more experienced and prolific scientists in the field of diabetes.
Experimental Autoimmune Encephalomyelitis Mediated by CD8+ T Cells
Authors: JI QINGYONG , GOVERMAN JOAN
Published: May 2007

Abstract:  Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system that is believed to have an autoimmune origin. CD4+ T cells have been well studied for their involvement in the pathogenesis of MS and its animal model, experimental autoimmune encephalomyelitis (EAE). CD8+ T cells, however, have been overlooked until recently, when more attention has focused on their potential role in pathogenic mechanisms in MS. Here we summarize our work in generating a CD8+ T cell–mediated EAE model. We discuss immune tolerance mechanisms that regulate CD8+ T cells specific for myelin basic protein (MBP), and describe initial results regarding triggers of CD8+ T cell–mediated disease. The availability of CD8+ T cell–mediated EAE models will help to elucidate the pathogenic roles of CD8+ T cells in MS, and provide tools for development of novel therapies for MS.
“Humanized” HLA Transgenic NOD Mice to Identify Pancreatic β Cell Autoantigens of Potential Clinical Relevance to Type 1 Diabetes
Authors: SERREZE DAVID V. , MARRON MICHELE P. , DiLORENZO TERESA P.
Published: May 2007

Abstract:  The mechanistic basis by which the H2g7 major histocompatibility complex (MHC) provides the primary risk factor for the development of T cell–mediated autoimmune type 1 diabetes (T1D) in non‐obese diabetic (NOD) mice involves contributions not only from the unusual Ag7 class II molecule, but also from the more common Kd and/or Db class I variants it encodes. Similarly, transgenic studies in NOD mice have confirmed the possibility first suggested in association studies that in the proper genetic context the common human HLA‐A2.1 class I variant can mediate diabetogenic CD8 T cell responses. T1D continues to develop in a further refined NOD stock that expresses human HLA‐A2.1, but no murine class I molecules (designated NOD.β2m‐.HHD). Islet‐specific glucose‐6‐phosphatase catalytic subunit–related protein (IGRP) is an important antigenic target of diabetogenic CD8 cells in standard NOD mice. Three IGRP‐derived peptides have also been identified that are presented by human HLA‐A2.1 molecules to diabetogenic CD8 T cells in NOD.β2m‐.HHD mice. At least one of these IGRP peptides (265‐273) can also be the target of autoreactive CD8 T cells in HLA‐A2.1‐expressing human T1D patients. Studies are currently under way to determine whether HLA‐A2.1‐restricted IGRP peptides can be used in a tolerance‐inducing protocol that inhibits T1D development in NOD. β2m‐.HHD mice. If so, this knowledge could ultimately lead to the development of a similar T1D prevention protocol in humans.
Building Different Mouse Models for Human MS
Authors: BETTELLI ESTELLE
Published: May 2007

Abstract:  Multiple sclerosis (MS) is a clinically and pathologically heterogeneous inflammatory/demyelinating disease of the central nervous system (CNS). Many patients first present with isolated optic neuritis. In some variants of MS, like Devic's disease or neuromyelitis optica (NMO), lesions are predominantly found in the optic nerves and spinal cord but not in the brain. The immunological bases of the different forms of MS are unknown. Here, we summarize our published findings on two mouse models: 2D2 myelin oligodendrocyte glycoprotein (MOG)–specific T cell receptor (TCR) transgenic mice, which develop spontaneous isolated optic neuritis, and 2D2 mice crossed with MOG‐specific IgH knockin (TH) mice, which spontaneously develop a severe form of experimental autoimmune encephalomyelitis (EAE) with a selective distribution of meningeal and parenchymal inflammatory lesions in the spinal cord and optic nerves similar to that found in human Devic's disease.
Impaired T Cell Receptor Signaling in Foxp3+ CD4 T Cells
Authors: CARSON BRYAN D. , ZIEGLER STEVEN F.
Published: May 2007

Abstract:  Dominant tolerance to autoantigens is primarily achieved through the action of the CD4+CD25+Foxp3+ subset of T cells, which have the capability of suppressing autoreactive T cells that have escaped deletion during thymic selection. The essential role of the forkhead/winged‐helix transcription factor Foxp3 in the development and function of these cells has been well documented. What is less clear is the role of Foxp3 in the altered TCR signaling that is seen in Tregs. We have used a Foxp3 transgenic mouse line to demonstrate that Foxp3 expression correlates with attenuated TCR signaling, and that the deficit in Foxp3‐transgenic CD4 T cells, as well as in CD4+CD25+ Tregs, affects multiple biochemical pathways.
Best Intentions or False Promises: Multilateral Interventions in Darfur, Afghanistan, and Southern Lebanon
Authors: Rupp Richard
Published: May 2007

Richard Rupp is associate professor and acting head of the Department of History and Political Science at Purdue University Calumet. He is the author of NATO after 9/11: An Alliance in Continuing Decline.
Design and machining of cylindrical cam with meshing indexing disc
Authors: Hsieh J
Published: May 2007

Cams are fundamentally important machine elements, which provide a simple means of generating virtually any follower motion. This paper presents a simple yet comprehensive method for the design and machining of a cylindrical cam with a meshing indexing disc. In the proposed methodology, homogenous coordinate transformation and conjugate surface theory are employed to develop a kinematic model for the cam profile design. The pressure angle and the principal curvature of the designed cam are analysed using the analytical expression derived for the profile. The required NC data equations are obtained by solving the CNC link variables by equating the machine tool ability function with the tool location matrix. The proposed methodology is verified by machining the designed cylindrical cam using a 4-axis CNC machine. The inspection results obtained from a 4-axis CMM show that the profile measurements of the machining cam are in excellent agreement with those of the designed profile. The results confirm that the methodology presented in this study enables the cam design and manufacturing tasks to be successfully integrated. As a result, the production process is flexible, automatic, cost efficient, and controllable.
Simulation of muscle characteristics using an electromagnetic actuator
Authors: Park I H , Lee I H , Yeon J H , Chang I B , Han D C
Published: May 2007

To accurately predict human body motion during a vehicle crash, active and passive characteristics of a muscle must be expressed. The crash test dummy presently used only expresses the passive characteristics of a muscle by using springs, so it has limited accuracy in predicting human body motion of current crash test dummies. In this paper, a muscle activation system composed of an electromagnetic actuator and a tensile spring is proposed to resolve such limitation of the current crash test dummy. The proposed actuator reproduces the active characteristics of a muscle. Because the flux path of the actuator is designed by reluctance path modulation using an electromagnet and two permanent magnets, the actuator improves upon non-linearity and power consumption of a conventional electromagnetic actuator. The tensile spring is adopted to resolve the short moving range of the actuator, to increase the bandwidth limit of the muscle activation system, and to reproduce the passive characteristics of a muscle. Tests reproducing the force-length and force-velocity characteristics of a muscle were carried out to verify the performance of the developed muscle activation system. The experimental results showed that the muscle activation system successfully reproduced the force-length and force-velocity characteristics of a muscle.
Laser pulse heating: Modelling of cavity formation
Authors: Saad M , Yilbas B S , Shuja S Z
Published: May 2007

Laser pulse heating of steel surfaces is considered and a non-conduction limited heating situation is modelled using an energy method. A numerical scheme employing a control volume approach is introduced to discretize the governing equations of energy. A laser pulse used in the experiment is employed in the simulations to compare the cavity depth with the experimental findings. It is found that the size of the mushy zone across the solid-liquid interface in the early heating period is larger than that corresponding to later heating periods. Similar behaviour is observed for the mushy zone across the liquid-vapour interface, provided that the mushy zone size differs for both cases. A cavity depth of the order of 1 μm is developed along the axial direction, which agrees well with experiment. The cavity profile in the radial direction follows its counterpart obtained from the experiment.
A test rig for the investigation of airflow through collapsible tubes
Authors: Oruç V , Çarpinlioğlu M Ö
Published: May 2007

In this paper, an experimental set-up for investigating airflow through collapsible tubes has been described in detail. The test rig is basically composed of an airtight chamber socalled ‘Starling resistor’, which includes a length of collapsible tube attached to rigid tubes at its ends, a compressor supplying steady airflow, and measuring devices. The self-excited oscillations that develop due to strong fluid-pipe interaction cause the flow to be time dependent. A data acquisition system is utilized to obtain the measurements. Therefore, it is possible to measure simultaneously the time-dependent parameters, which are upstream and downstream pressures, velocity downstream of the collapsible tube. It has been verified by referring to the experimental results that the calibration of the whole system is satisfied and the measuring instruments give sensible output in combination with the data acquisition system. The presented test rig should be useful in point of view for testing possibility of airflow in soft elastic tubes.
Experimental study on the effect of turning angle on drag and lift forces for various cut angles on spheres
Authors: Pudjanarsa A
Published: May 2007

An experimental study on the effect of turning angle on drag and lift forces for various cut angles on spheres is performed. Five different cut angles on different spheres were applied including: 30°, 45°, 53°, 55°, and 75°.

Drag and lift forces were measured using a wind tunnel force balance and the wind speed was set so that a corresponding Reynolds number of 5.3 × 104 was achieved. Wind turning angle was varied from 0° to 60°.

Experimental results show that, in general, drag and lift forces increase as the turning angle increases. At 0° turning angle, Cd minimum is attained at a cut angle of 53° and is ∼32 per cent less than Cd without cut angle. The maximum C1 is attained at a cut angle of 75° for a turning angle of 50° for approximately 0.68. This value of C1,max is about 855 per cent higher than that of the same turning angle for a cut angle of 30°. At a particular turning angle, lift attains a maximum and beyond that turning angle-drag and lift forces decrease. Minimum value of drag and lift forces reached at the cut angle of 30° for all turning angles.
Operating temperature in high-speed ball bearing
Authors: Wang L Q , Chen G C , Gu L , Zheng D Z
Published: May 2007

Frictional heating in high-speed bearings has been one of the primary factors for the failure of the main shaft bearing in aero engines. In order to exactly evaluate the heat generation and temperature in the bearing, a process has been developed, based on power consumption, which allows evaluation of heat generation in the high-speed ball bearing. A model for computing the temperature of the high-speed ball bearing with axisymmetric load is set up. In this model, heat sources in the raceways are treated as moving and the heat generation in the ball and cage is averaged on the circumferential zone through which the heat source passes. Using the process and model presented here, heat generation and the transient temperature of a ball bearing are obtained.
Origin and future of hydration lubrication
Authors: Ikeuchi K
Published: May 2007

Some of the biological surfaces, gels, boundary films, and graft polymerized surfaces are coated with gel layer or polymer brush. It seems that low friction results from a common lubrication mechanism while they have been studied dependently. This paper defines hydration lubrication reviews the study in each field and gives future prospects.

Polymers adsorbed densely in good solvent expand in normal direction to the surface and form a brush-like structure. The brush is compressed and a repulsive force arises with an approach of another body and the applied force is supported by fluid. Polymer brush is produced by means of graft polymerization. It is possible to reduce friction and wear of catheters and artificial joints by graft polymerization. Hydration lubrication is inevitable in preventing wear of articular cartilage. Hydrated surface layer on the internal wall of human small intestine assists digestion and prevents the wall from injury. Thus, hydration lubrication is an important subject of biomechanics and may be useful for medical treatments and machine elements.
Tribological scaling
Authors: Taylor R. I.
Published: May 2007

The issues associated with tribological scaling are discussed, focusing on specific examples from (a) journal bearing lubrication, (b) piston ring lubrication, (c) elastohydrodynamic line contact lubrication, and (d) fluid scaling.

It is demonstrated that in general it is possible, for two dissimilar lubricated contacts, to define dimensionless parameters (such as, for example, a Sommerfeld parameter and an eccentricity ratio) such that if they have the same value for one of these parameters, then the other dimensionless parameter will also be the same. However, other parameters of interest, such as friction, wear, and lubricant temperature rise, will in general be different. Therefore for a complete tribological understanding of a contact, the best approach is to attempt to reproduce the geometries, kinematics, and operating conditions as closely as possible.
Investigation on load-dependent roughness variations
Authors: Ciulli E , Pugliese G , Bassani R
Published: May 2007

In order to investigate the level of influence of roughness in the evaluation of the dimensionless film thickness Λ a study has been started to find a simplified but sufficiently general method to take into account the roughness variations of bodies, even with different characteristics, because of varying load. The investigation is based on a linear measured roughness profile.

In this work, a model developed for the approximation of measured profiles through parabolas and formulas used for solving the contact mechanics problem are reported. The first results obtained with some specimens, used in previous works for experimental investigations on non-conformal line contacts, are presented. The specimens' surfaces are analysed both by a three-dimensional computer-controlled stylus profilometer and by an apparatus that allows investigations also under loaded conditions using optical interferometry. A way to compare the experimental and the theoretical results, in order to make some necessary verifications correlating line and surface aspects, is indicated. A first estimation of the variation of Λ under load is finally made.

The method developed for the evaluation of roughness variations under load seems to furnish reasonable results in quite good agreement with the experimental ones. The results obtained with the investigated non-conformal line contacts, presenting characteristics in not complete agreement with the model-based hypotheses, give a certain confidence about the applicability of this simplified methodology to different kinds of contacts.
Effect of load variation on the friction properties of articular cartilage
Authors: Katta J , Pawaskar S. S. , Jin Z. M. , Ingham E , Fisher J
Published: May 2007

Synovial joints are known for their remarkable load bearing capacity while maintaining very low friction and wear over their lifetime. Although other joint components play a role in the lubrication mechanisms, articular cartilage with its unique biphasic characteristics is believed to be largely responsible for the observed low friction properties in these joints. In the current study, a pin-on-plate machine was used in a cartilage loaded against cartilage configuration to study the effect of load variation on cartilage friction properties. Both static and dynamic loading conditions were tested under three different contact stress levels - 0.2, 0.3, and 0. 4 MPa with phosphate buffered saline as the lubricant. Indentation experiments were performed and modelled through finite-element (FE) method to determine the biphasic material properties of cartilage. A second FE model adopting the derived biphasic properties of cartilage was then used to simulate the static friction tests and determine the interstitial fluid load support in the cartilage tissue under different loads. An increase in contact stress was found to reduce the friction levels significantly ( p < 0.05) between the articulating cartilage surfaces in both dynamic and static models, while the percentage of fluid load support within the cartilage was almost identical. It was shown that while interstitial fluid pressurization of cartilage plays the major role, another extraneous factor or mechanism that influences the friction between cartilage surfaces is needed to completely explain the results observed.
Modelling of fluid support inside articular cartilage during sliding
Authors: Pawaskar S. S. , Jin Z. M. , Fisher J
Published: May 2007

Considerable attention has been drawn to the lubricatingmechanism of synovial joints. Biphasic lubrication was proposed by Mowand Lai [1] based on the load partitioning mechanism between fluid and solid phases of articular cartilage. Forster et al. [12] carried out experimental studies to investigate the same, whereas Ateshian et al. [13, 17] further investigated it theoretically using interstitial fluid pressurization. Forster and Fisher [15] showed that start-up frictional coefficient was higher than that under a wide range of sliding conditions and that biphasic nature of the cartilage does play a significant role in joint lubrication. The experimental and theoretical studies of frictional behaviour of the cartilage have been carried out by several researchers; however, finite-element modelling is far less in comparison, and mainly focused on deformation rather than sliding conditions. In the present study, two finite-element modelswere developed to study the effect of sliding on fluid load support in the cartilage and its implications to frictional and lubricating characteristics. The results predicted by the static modelwere same as those given by a metallic plate sliding over the cartilage surface, whereas the model of a metallic cylindrical indenter sliding over the cartilage surface with the migrating contact area showed remarkably higher fluid load support for relatively long-time durations. The results agreed with the experimental results presented by Forster and Fisher [15] and Bell et al. [24] and, in general, with those of other researchers with respect to weeping, boosted, and self-generating lubrication mechanism. Further extensive studies need to be carried out to compare the finite-element prediction with the experimental studies under other conditions.
Friction characteristics between metal contacting surfaces from antiwear additives with application to metal V-belt type continuously variable transmission lubricants
Authors: Narita K , Priest M
Published: May 2007

This study has focused on the application of lubricating oil additives in metal V-belt pushing type continuously variable transmission fluids (B-CVTFs) achieve higher friction coefficient and more stable lubricant film formation between the metal-metal contacting surfaces. The metal-metal tribological characteristics of various kinds of antiwear additives and a detergent were experimentally investigated using a ball on plate reciprocating tribometer (Plint TE77), which enables lubricant film formation to be monitored during a rubbing test. Zinc-dithio phosphates (ZnDTPs), a significant difference in instantaneous film formation was observed between primary and secondary type ZnDTP at the moment of increasing step load, due to the variation of the antiwear activity of different ZnDTPs. ZnDTPs in the presence of over-based calcium sulphonate detergent demonstrated slightly less tribofilm formationcompared with ZnDTP alone due to the competition for the rubbing surface. Very interestingly, in the case of phosphonic ester with calcium sulphonate, synergism was observed with more stable film formation and 8 per cent higher friction coefficient than without calcium sulphonate, a positive outcome for a B-CVTF. From surface analysis, it is hypothesized that the tribofilms species composed of iron phosphate, calcium phosphate, and calcium carbonate were generated by the reaction between phosphonic ester and calcium sulphonate, and that the resulting tribofilm plays a dual role in preventingwear and inhibiting the entrainment of lubricant into the interface, resulting in higher friction.