bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recapitulation of cell signaling events associated with astrogliosis using the brain slice preparation
Authors: Damiani Candice L. , O’Callaghan James P. 
Published: December 2006

AbstractAstroglial activation constitutes a dominant response to all types of injuries of the CNS. Despite the ubiquitous nature of this cellular reaction to neural injury, a little is known concerning the signaling mechanisms that initiate it. Recently, we demonstrated that astrocytic hypertrophy and enhanced expression of glial fibrillary acidic protein resulting from toxicant‐induced neurodegeneration are linked to activation of the janus kinase (JAK)‐signal transducer and activator of transcription‐3 (STAT3) pathway. These observations implicate ligands at the gp130 receptor as potential upstream effectors of astrogliosis. Here we used the brain slice preparation to examine potential activators of the JAK‐STAT3 pathway. Following incubation of freshly cut striatal slices in phosphate‐free oxygenated buffer for up to 75 min, we found that slicing the striatum itself was a sufficient stimulus to initiate a rapid activation of the JAK‐STAT3 pathway as assessed with immunoblots of pSTAT3(tyr705) using phospho‐state specific antibodies. The mRNA for the gp130 cytokines, leukemia inhibitory factor, interleukin‐6 and oncostatin M or the β‐chemokine, monocyte chemoattractive protein (CCl2) also were up‐regulated in the slice. Moreover, we could enhance the activation of STAT3(tyr705) by adding exogenous cytokines to the slice and we could inhibit phosphorylation of STAT3(tyr705) by addition of tyrosine kinase inhibitors (Lav A and AG490) or neutralizing antibodies directed against leukemia inhibitory factor or oncostatin M. These data suggest that STAT3 activation is an early event in slice‐induced glial activation and establishes the brain slice preparation method as a reliable model to examine the signaling mechanisms that underlie glial activation.
Reduced Frontal Lobe Activity in Subjects With High Impulsivity and Alcoholism
Authors: Chen Andrew C. H. , Porjesz Bernice , Rangaswamy Madhavi , Kamarajan Chella , Tang Yongqiang , Jones Kevin A. , Chorlian David B. , Stimus Arthur T. , Begleiter Henri 
Published: December 2006

Objective: Impulsivity is an important characteristic of many psychiatric disorders, including substance‐related disorders. These disinhibitory disorders have a similar underlying genetic diathesis, with each disorder representing a different expression of the same underlying genetic liability. This study assessed whether there is a relationship between impulsivity and alcohol dependence, and their correlations with P3 (P300) amplitude, a proposed endophenotype of alcoholism.Methods: Healthy control subjects (n=58) and subjects with DSM‐IV diagnosis of alcohol dependence (n=57) were assessed with a visual oddball task. Event‐Related Potentials (ERPs) were recorded from 61 scalp electrodes and P3 amplitudes measured. Barratt Impulsiveness Scale (BIS), version 11, was used to evaluate impulsivity. Source localization of P3 was computed using low‐resolution brain electromagnetic tomography (LORETA).Results: Alcoholic subjects manifested reductions in target P3 amplitudes (p<0.0001). Using LORETA, significantly reduced activation was mapped in the cingulate, medial, and superior frontal regions in alcoholic subjects and highly impulsive subjects. Alcoholic subjects had significantly higher scores on the BIS (p<0.0001) than nonalcoholic individuals. There were significant negative correlations between total scores on BIS and P3 amplitude (r=−0.274, p=0.003, on Pz; r=−0.250, p=0.007, on Cz).Conclusions: Our results demonstrate a strong frontal focus of reduced activation during processing of visual targets in alcoholic subjects and individuals with higher impulsivity. The findings suggest that impulsivity may be an important factor that underlies the pathogenesis of alcohol dependence. Studies are underway to examine the relationship between impulsivity and ERPs in offspring of alcoholic subjects, and to identify genes associated with the underlying predisposition involved in disinhibitory disorders.
Differentiating spitzoid melanomas from Spitz nevi through CD99 expression
Authors: King Mark S. , Porchia Sylvia J. , Hiatt Kim M. 
Published: December 2006

Background:  A true diagnostic marker differentiating Spitz nevi (SN) from spitzoid melanoma (sMM) has been elusive. CD99, a transmembrane glycoprotein, believed to play a role in many neoplastic processes, has yet to be investigated in this regard. Recently, the expression of CD99 has been shown in 60% of primary melanomas. Other studies exploring the expression of CD99 in melanocytic lesions have not been performed. Here, we evaluate the presence of CD99 in these two histologically difficult to differentiate entities.Methods:  Cases of sMM were selected based on the presence of key microscopic words: spitz, spindled and/or epitheliod. In addition, all the cases of SN over the past 7 years were retrieved. Each case was stained with anti‐human CD99 and analyzed for the presence of CD99 staining.Results:  Fifteen of 27 cases (56%) of sMM expressed CD99 compared with only 3 of 58 cases (5%) of SN.Conclusions:  This study shows 56% of sMM and only 5% of SN express CD99. Eight of the sMM showed strong diffuse staining, a pattern not seen in any of the SN. This study does not elucidate the role that CD99 plays in these melanocytic processes; however, it does show that CD99 can be a useful tool in distinguishing sMM from SN.
Melanophages reside in hypermelanotic, aberrantly glycosylated tumor areas and predict improved outcome in primary cutaneous malignant melanoma
Authors: Handerson Tamara , Berger Aaron , Harigopol Malini , Rimm David , Nishigori Chikako , Ueda Masato , Miyoshi Eiji , Taniguchi Naoyuki , Pawelek John 
Published: December 2006

Background:  Previously, hypermelanotic regions of cutaneous malignant melanoma (CMM) were found to contain a mixture of highly melanized melanoma cells and melanophages. Both cell types produced β1,6‐branched oligosaccharides. These sugars are used for motility by myeloid cells and cancer cells alike and are associated with poor survival in carcinomas of the breast, colon and lung. This study further investigated associations between melanophages and β1,6‐branched oligosaccharides and their potential contributions to patient outcome.Methods:  Individual archival melanomas and high‐throughput melanoma tissue microarrays were stained for melanophages with azure blue/S100 and for β1,6‐branched oligosaccharides with the lectin leukocytic phytohemagglutinin (LPHA, a selective marker for β1,6‐branched oligosaccharides).Results:  In primary CMM, melanophages were highly enriched in hypermelanotic, LPHA‐positive tumor regions and correlated with improved outcome at 10‐ and 20‐year follow ups. While the combination of melanophages, LPHA positivity and high pigmentation indicated better outcome, a subset of LPHA‐positive cells not associated with melanophages indicated worse outcome.Conclusion:  This is the first report of an anti‐tumor role for the melanophage in melanoma biology. There appeared to be two classes of β1,6‐branched oligosaccharide‐producing melanoma cells with opposing effects on outcome: one that attracted melanophages (better) and another that did not (worse). The findings disclose new aspects of the immune system and aberrant glycosylation in CMM.
Delayed Access to Alcohol Accelerates Self‐Administration of Alcohol on a Progressive Ratio Schedule
Authors: Pickering Chris , Moreira Tiago , Liljequist Sture 
Published: December 2006

Abstract:  In a previous report, we found that a 5‐min. delay in alcohol access increases ethanol intake in rats trained to self‐administer 5% ethanol. To assess the effects of this delay on the motivation to self‐administer ethanol, Wistar rats were trained on a progressive ratio schedule of reinforcement and presented with the 5‐min. delay. There was no change in break point (6 presses/delivery), active (125 presses/30 min.) or inactive (10 presses/30 min.) lever presses after the 5‐min. delay compared to baseline. However, response cessation occurred 10 min. earlier in this delay session compared to baseline indicating that consumption was accelerated by delayed access to alcohol.
DISENTANGLING THE RISKS: PARENT CRIMINAL JUSTICE INVOLVEMENT AND CHILDREN'S EXPOSURE TO FAMILY RISKS
Authors: PHILLIPS SUSAN D. , ERKANLI ALAATTIN , KEELER GORDON P. , COSTELLO E. JANE , ANGOLD ADRIAN 
Published: December 2006

Research Summary:The analyses reported in this article are based on data from a longitudinal epidmiologic study of youth from 11 rural counties in North Carolina—the Great Smoky Mountains Study. Nearly half (47.4%) of the children in the population represented in this study had a parent or other parent figure who had been arrested as an adult. Analyses showed that parent risk factors (i.e., substance abuse, mental illness, and lack of education) had a significant direct effect on children's exposure to family risks. These parent risk factors were also associated with greater odds of parental involvement in the criminal justice system (CJS), which in turn, had a significant association with children's likelihood of experiencing two types of family risks (i.e., economic strain and instability), net the effect of parent risk factors. Parent CJS involvement, however, was not significantly associated with family risks related to family structure or quality of care. Exposure to risks in these latter domains was better explained by the direct effect of parental substance abuse, mental health problems, and lack of education.Policy Implications:These findings provide empirical evidence that parent CJS involvement is significantly related to children's exposure to certain types of family risks independent of the possible confounding effect of parent risks. The fact that the two domains of family risks that were associated with CJS involvement were economic adversity and family stability is noteworthy as these mirror two of the ecological correlates of crime that are thought to be perpetuated by high levels of incarceration—poverty and population mobility. Second, these findings suggest that it is unrealistic to expect correctional programs that focus on inmates' relationships with their children to single‐handedly impact intergenerational incarceration. Programs of this nature may play an important role in offsetting some of the more immediate adverse effects parental incarceration might have on children, but these analyses suggest that they need to be coupled with rehabilitation efforts that target parental substance abuse, mental health problems, and inadequate education. This conclusion is made because although parent CJS involvement carries its own risks for children experiencing certain family risks (i.e., economic strain and instability), these parent problems are still significant predictors of the same as well as other family risks, which in turn, past research has linked to adverse youth outcomes such as substance abuse and delinquency.
VIOLENCE RISK SCREENING IN COMMUNITY CORRECTIONS*
Authors: DAVIES GARTH , DEDEL KELLY 
Published: December 2006

Research Summary:Issues of safety and screening for potential violence are particularly salient in community correctional settings. These contexts require a risk assessment mechanism that can both classify offenders according to their risk of violent recidivism and be administered quickly and effectively by nonclinicians. Existing assessment instruments such as the LSI‐R, PCL‐R‐2, VRAG, and HCR‐20 are of limited utility in relation to predicting violence in community corrections. This research describes the creation and validation of the Violence Risk Screening Instrument that better meets the requirements of community corrections. Violent recidivism among men was best predicted by a three‐item instrument consisting of Severe Violence, Domestic Violence, and Unstable Lifestyle.Policy Implications:Balancing the treatment and supervision needs of offenders with the task of ensuring public safety within a context of limited resources makes risk assessment and triage essential. Resource constraints mean that not all offenders can receive high levels of supervision; similarly, best practice research on responsivity suggests that only those offenders at higher risk will benefit from high levels of supervision (Andrews and Bonta, 1994). In the past two decades, the use of risk assessment instruments has brought greater objectivity to the process of classifying offenders into risk groups. However, a single risk assessment instrument cannot classify offenders according to all forms of risk. As supervision strategies become more precise and more focused on specific forms of risk, so too must the instruments that are used to derive the classification. The Violence Risk Screening Instrument proposed here is valuable insofar as it meets the requisite criteria for community corrections: It has demonstrable predictive utility, and it can be administered by line‐level personnel. Furthermore, it allows community corrections agencies to conserve limited resources for offenders determined to be at greatest risk of jeopardizing public safety.
Knowledge Diffusion and Networking in the Organic Production Sector: A Case Study
Authors: Morone Piergiuseppe , Sisto Roberta , Taylor Richard 
Published: December 2006

Knowledge Diffusion and Networking in the Organic Production Sector: A Case StudyRecent uncertainty throughout the food system has put pressure on European farmers, now facing economic globalisation, changing consumer preferences, and a new legal and regulatory framework. Under these new circumstances, policy‐makers must identify new strategies for developing food production systems in ways that benefit the whole of society, whilst minimising negative effects upon the environment. In this regard, the organic food sector, characterised by an ever more complex legislative framework and policy environment, presents an opportunity and a challenge for policy‐makers as well as for farms and firms. This article reports findings from a case study of knowledge diffusion in the organic sector in the province of Foggia, a developmentally backward area in Southern Italy. Our study shows that despite a cohesive‘network of interactions’ among organic producers, exchanges of knowledge are fairly marginal. This communication void is partially filled by local institutions that are shown to be effective in diffusing juridical and technical knowledge but less effective in providing commercial/market information. Further institutional efforts are required to cover these knowledge gaps. The study draws attention to some policy issues that can be shared by groups of organic producers elsewhere with characteristics similar to the Foggian case study, similarities that call for institutions to facilitate the creation, interpretation, and sharing of knowledge.
Modeling of Spur and Helical Gear Planetary Drives With Flexible Ring Gears and Planet Carriers
Authors: Abousleiman V. , Velex P. , Becquerelle S. 
Published: December 2006

Abstract
A model is presented which enables the simulation of the three-dimensional static and dynamic behavior of planetary/epicyclic spur and helical gears with deformable parts. The contributions of the deflections of the ring gear and the carrier are introduced via substructures derived from 3D finite element models. Based on a modal condensation technique, internal gear elements are defined by connecting the ring-gear substructure and a planet lumped parameter model via elastic foundations which account for tooth contacts. Discrete mesh stiffness and equivalent normal deviations are introduced along the contact lines, and their values are recalculated as the mating flank positions vary with time. A constraint mode substructuring technique is used to simulate the planet carrier as a superelement which is connected to the planet center. Planetary/epicyclic gear models are completed by assembling lumped parameter sun gear/planet elements along with shaft elements, lumped stiffness, masses and inertias. The corresponding equations of motion are solved by combining a time-step integration scheme and a contact algorithm for all simultaneous meshes. Several quasistatic and dynamic results are given which illustrate the potential of the proposed hybrid model and the interest of taking into account ring gear and carrier deflections.
Influence of Planetary Needle Bearings on the Performance of Single and Double Pinion Planetary Systems
Authors: Singh Avinash 
Published: December 2006

Abstract
Planetary gears are widely used in automotive and aerospace applications. Due to demands for greater power density, these gearsets often operate at extremely high stress levels. This has caused system level influences once considered secondary to become critical to the success of planetary gears. One such system level effect that has been largely overlooked is the influence of support structures like planetary needle bearings. There are interactions between the gear distributed loads and the resulting bearing loads and deflections that have implications for both gear and bearing designs. Also, double pinion planetary arrangements are increasingly becoming common. There are still greater interactions between the gear and bearing components in double pinion planetary arrangements. In this paper, we will examine the influence of the bearing deflections (tilt) on the gear load distribution and contact pattern. We will also show the influence of distributed gear loads on the bearing loads (moments) and deflections (tilts). Both, single and double pinion planetary arrangements will be considered. It will be shown that the tilting stiffnesses of the needle bearings have a major influence on gear contact pattern and consequently on contact and bending stresses. It will also be shown that the double pinion planetary arrangement is more likely to result in off-centered loading. Parametric studies will be performed to show the influence of a few design parameters. Theoretical derivations will be validated by numerical simulations. A system level gear analysis model will be used to illustrate the issues involved and quantify the results.
Prediction of Mechanical Efficiency of Parallel-Axis Gear Pairs
Authors: Xu H. , Kahraman A. , Anderson N. E. , Maddock D. G. 
Published: December 2006

AbstractA computational model is proposed for the prediction of friction-related mechanical efficiency losses of parallel-axis gear pairs. The model incorporates a gear load distribution model, a friction model, and a mechanical efficiency formulation to predict the instantaneous mechanical efficiency of a gear pair under typical operating, surface, and lubrication conditions. The friction model uses a new friction coefficient formula obtained by using a validated non-Newtonian thermal elastohydrodynamic lubrication (EHL) model in conjunction with a multiple linear regression analysis. The load and friction coefficient distribution predictions are used to compute instantaneous torque/power losses and the mechanical efficiency of a gear pair at any given rotational position. Efficiency measurements from gear pairs having various gear designs and surface treatments are compared to model predictions. Mechanical efficiency predictions are shown to be within 0.1% of the measured values, indicating that the proposed efficiency model is accurate. Results of a parametric study are presented at the end to highlight the influence of key basic gear geometric parameters, tooth modifications, operating conditions, surface finish, and lubricant properties on mechanical efficiency losses.
Inhibition of CXCR4 with the novel RCP168 peptide overcomes stroma-mediated chemoresistance in chronic and acute leukemias
Authors: Zeng Zhihong , Samudio Ismael J. , Munsell Mark , An Jing , Huang Ziwei , Estey Elihu , Andreeff Michael , Konopleva Marina 
Published: December 2006

Abstract
The chemokine receptor CXCR4 mediates the migration of hematopoietic cells to the stroma-derived factor 1α (SDF-1α)–producing bone marrow microenvironment. Using peptide-based CXCR4 inhibitors derived from the chemokine viral macrophage inflammatory protein II, we tested the hypothesis that the inhibition of CXCR4 increases sensitivity to chemotherapy by interfering with stromal/leukemia cell interactions. First, leukemic cells expressing varying amounts of surface CXCR4 were examined for their chemotactic response to SDF-1α or stromal cells, alone or in the presence of different CXCR4 inhibitors. Results showed that the polypeptide RCP168 had the strongest antagonistic effect on the SDF-1α– or stromal cell–induced chemotaxis of leukemic cells. Furthermore, RCP168 blocked the binding of anti-CXCR4 monoclonal antibody 12G5 to surface CXCR4 in a concentration-dependent manner and inhibited SDF-1α–induced AKT and extracellular signal-regulated kinase phosphorylation. Finally, RCP168 significantly enhanced chemotherapy-induced apoptosis in stroma-cocultured Jurkat, primary chronic lymphocytic leukemia, and in a subset of acute myelogenous leukemia cells harboring Flt3 mutation. Equivalent results were obtained with the small-molecule CXCR4 inhibitor AMD3465. Our data therefore suggest that the SDF-1α/CXCR4 interaction contributes to the resistance of leukemia cells to chemotherapy-induced apoptosis. Disruption of these interactions by the peptide CXCR4 inhibitor RCP168 represents a novel strategy for targeting leukemic cells within the bone marrow microenvironment. [Mol Cancer Ther 2006;5(12):3113–21]
Direct targeting of αvβ3 integrin on tumor cells with a monoclonal antibody, Abegrin™
Authors: Mulgrew Kathy , Kinneer Krista , Yao Xiao-Tao , Ward Beth K. , Damschroder Melissa M. , Walsh Bill , Mao Su-Yau , Gao Changshou , Kiener Peter A. , Coats Steve , Kinch Michael S. , Tice David A. 
Published: December 2006

AbstractThe humanized monoclonal antibody Abegrin™, currently in phase II trials for treatment of solid tumors, specifically recognizes the integrin αvβ3. Due to its high expression on mature osteoclasts, angiogenic endothelial cells, and tumor cells, integrin αvβ3 functions in several pathologic processes important to tumor growth and metastasis. Targeting of this integrin with Abegrin™ results in antitumor, antiangiogenic, and antiosteolytic activities. Here, we exploit the species specificity of Abegrin™ to evaluate the effects of direct targeting of tumor cells (independent of targeting of endothelia or osteoclasts). Flow cytometry analysis of human tumor cell lines shows high levels of αvβ3 on many solid tumors, including cancers of the prostate, skin, ovary, kidney, lung, and breast. We also show that tumor growth of αvβ3-expressing tumor cells is inhibited by Abegrin™ in a dose-dependent manner. We present a novel finding that high-dose administration can actively impair the antitumor activity of Abegrin™. We also provide evidence that antibody-dependent cellular cytotoxicity contributes to in vitro and in vivo antitumor activity. Finally, it was observed that peak biological activity of Abegrin™ arises at serum levels that are consistent with those achieved in clinical trials. These results support a concept that Abegrin™ can be used to achieve selective targeting of the many tumor cells that express αvβ3 integrin. In combination with the well-established concept that αvβ3 plays a key role in cancer-associated angiogenesis and osteolytic activities, this triad of activity could provide new opportunities for therapeutic targeting of cancer. [Mol Cancer Ther 2006;5(12):3122–9]