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Terms modified by Bench Selected AbstractsBench to Bedside: Pharmacogenomics, Adverse Drug Interactions, and the Cytochrome P450 SystemACADEMIC EMERGENCY MEDICINE, Issue 12 2005Rishi Sikka MD As physicians attempt to improve the quality of health care, one area of particular concern has been preventable medical errors from adverse drug interactions. The cytochrome P450 family of enzymes has been implicated in a large number of these preventable, adverse drug interactions. This report reviews the basic biochemistry and pharmacogenomics underlying the reactions catalyzed by the cytochrome P450 family of enzymes. An emphasis is placed on the phenotypic variations within a population and the resulting clinical effects. In addition, six members of the cytochrome P450 superfamily that are responsible for the metabolism of the majority of pharmaceutical agents are profiled in detail. These enzymes, CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP2E1, and CYP1A2, are reviewed with regard to their phenotypic variation in the population and the resulting clinical and therapeutic implications. [source] Bench,shelf system dynamic characteristics and their effects on equipment and contentsEARTHQUAKE ENGINEERING AND STRUCTURAL DYNAMICS, Issue 13 2006Tara C. Hutchinson Abstract Economic losses during past earthquakes are strongly associated with damage and failure to nonstructural equipment and contents. Among the vast types of nonstructural elements, one important category, is scientific equipment in biological or chemical laboratories. These equipment are often mounted on heavy ceramic bench-tops of bench,shelf systems, which in turn may amplify the dynamic motions imposed. To investigate the seismic response of these types of systems, a series of shake table and field experiments were conducted considering different representative bench and shelf-mounted equipment and contents. Results from shake table experiments indicate that these equipment are generally sliding-dominated. In addition, the bench,shelf system is observed to be very stiff and when lightly loaded, has a fundamental frequency between 10 and 16 Hz. An approximate 50% reduction in the first and second fundamental frequencies is observed considering practical loading conditions. Insight into a broader range of system response is provided by conducting eigenvalue and time history analyses. Non-linear regression through the numerical data indicate acceleration amplification ratios , range from 2.6 to 1.4 and from 4.3 to 1.6, for fixed,fixed and pinned,pinned conditions, respectively. Both the experimental and numerical results support the importance of determining the potential dynamic amplification of motion in the context of accurately determining the maximum sliding displacement of support equipment and contents. Copyright © 2006 John Wiley & Sons, Ltd. [source] Bench to Bedside: Electrophysiologic and Clinical Principles of Noninvasive Hemodynamic Monitoring Using Impedance CardiographyACADEMIC EMERGENCY MEDICINE, Issue 6 2003Richard L. Summers MD Abstract The evaluation of the hemodynamic state of the severely ill patient is a common problem in emergency medicine. While conventional vital signs offer some insight into delineating the circulatory pathophysiology, it is often impossible to determine the true clinical state from an analysis of blood pressure and heart rate alone. Cardiac output measurements by thermodilution have been the criterion standard for the evaluation of hemodynamics. However, this technology is invasive, expensive, time-consuming, and impractical for most emergency department environments. Impedance cardiography (ICG) is a noninvasive method of obtaining continuous measurements of hemodynamic data such as cardiac output that requires little technical expertise. ICG technology was first developed by NASA in the 1960s and is based on the idea that the human thorax is electrically a nonhomogeneous, bulk conductor. Variation in the impedance to flow of a high-frequency, low-magnitude alternating current across the thorax results in the generation of a measured waveform from which stroke volume can be calculated by a modification of the pulse contour method. To adequately judge the possible role of this technology in the practice of emergency medicine, it is important to have a sufficient understanding of the basic scientific principles involved as well as the clinical validity and limitations of the technique. [source] Botulinum Neurotoxin for the Treatment of Migraine and Other Primary Headache Disorders: From Bench to BedsideHEADACHE, Issue 2003David W. Dodick MD Botulinum toxin type A, a neurotoxin, is effective for treating a variety of disorders of involuntary muscle contraction including cervical dystonia, blepharospasm, and hemifacial spasm. It inhibits neuromuscular signaling by blocking the release of acetylcholine at the neuromuscular junction. The biological effects of the toxin are transient, with normal neuronal signaling returning within approximately 3 to 6 months postinjection. Recent clinical findings suggest that botulinum toxin type A may inhibit pain associated with migraine and other types of headache. However, the mechanism by which this toxin inhibits pain is not fully understood and is under investigation. Research findings suggest that botulinum toxin type A inhibits the release of neurotransmitters from nociceptive nerve terminals and, in this way, may possess an analgesic effect. A number of retrospective open-label chart reviews and 3 double-blind, placebo-controlled trials have demonstrated that localized injections of botulinum toxin type A significantly reduce the frequency, severity, and disability associated with migraine headaches. Although the majority of patients in these studies experienced no botulinum toxin type A-mediated side effects, a small percentage of patients did report transient minor side effects including blepharoptosis, diplopia, and injection-site weakness. Currently, 4 randomized, placebo-controlled, clinical trials are being conducted to evaluate the efficacy, optimal dosing, and side-effect profile of botulinum toxin type A as a novel treatment for migraine and other types of headache. These studies may provide further evidence that botulinum toxin type A is an effective option for the preventive treatment of migraine. [source] Update on Bioabsorbable Stents: From Bench to ClinicalJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 5 2006F.A.C.C., RON WAKSMAN M.D. Permanent metallic stents are associated with limitations such as continued mechanical stress, transfer to the tissue, and continued biological interaction with the surrounding tissue. They are also associated with late stent thrombosis and artifacts when non-invasive technologies such as MRI and MSCT are used. The potential advantages of bioabsorbable polymeric or metallic stents are to leave no stent behind, they are fully compatible with MRI and MSCT imaging, and are not associated with late stent thrombosis. This review covers the different stent programs as they move from bench to bed and clinical trials. Bioabsorbable stents are considered the next frontier of stenting and we will discuss their potential to fulfill this promise in interventional cardiology. [source] Tribute to Justice SouterJOURNAL OF SUPREME COURT HISTORY, Issue 1 2010SANDRA DAY O'CONNOR When the U.S. Supreme Court Justices took their seats at the beginning of the 2009 Term, the Bench looked different. Gone from the Bench, after nineteen years, was David H. Souter. He returned to his home in New Hampshire, a state he likes enormously. Justice Souter will be missed by his former colleagues and by advocates before the Court, by legal scholars nationwide and by all who follow the Court's work and activities. [source] In Defense of "Public Reason": Supreme Court Justice William JohnsonJOURNAL OF SUPREME COURT HISTORY, Issue 2 2007SANDRA F. VANBURKLEO For those of us who gravitate toward rebels and upstarts, Supreme Court Justice William Johnson has uncommon appeal, if only because he was the first member of the federal Bench to kick up his heels in a sustained, effective, and deliberate way. In 1954, Johnson's only biographer, Donald Morgan, proclaimed him "the first dissenter,"1 a force for democratization in the style of Thomas Jefferson and Andrew Jackson, the man who persuaded Chief Justice John Marshall to compromise on the question of unitary opinions and institutionalize (if not applaud) publication of concurring or dissenting departures from the majority's official reasoning. [source] Courtroom to Classroom: Justice Harlan's Lectures at George Washington University Law SchoolJOURNAL OF SUPREME COURT HISTORY, Issue 3 2005ANDREW NOVAK John Marshall Harlan had a singularly successful legal career as an Associate Justice of the Supreme Court that spanned thirty-three years, from 1877 to 1911, one of the longest terms in history. For twenty-one of those years on the Court he also distinguished himself as a professor of constitutional law at George Washington University. Along with his colleague on the Bench and on the faculty, Associate Justice David J. Brewer, Harlan carried a full course load, teaching just about every subject: evidence, torts, property law, corporation law, commercial law, international law, and his specialty, constitutional law. [source] The Story of the Attempted Assassination of Justice Field by a Former Associate on the Supreme Bench of CaliforniaJOURNAL OF SUPREME COURT HISTORY, Issue 2 2005HON. GEORGE C. GORHAM [source] Immunobiology of Chronic Lung Allograft Dysfunction: New Insights from the Bench and BeyondAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009R. A. Shilling The first successful human lung transplants were performed in the 1980s. Since that time lung transplantation has been a therapeutic modality for end-stage pulmonary diseases. However, chronic rejection, known as obliterative bronchiolitis (OB)/bronchiolitis obliterans syndrome (BOS), is the key reason why the 5-year survival is only 50%, which is significantly worse than most other solid organ transplants. Recent studies have provided exciting advances that are beginning to be translated into findings in humans. This review will highlight the current advances in understanding the mechanisms of OB/BOS in lung transplant recipients. [source] Cell-based Therapy to Regenerate Myocardium: from Bench to BedsideARTIFICIAL ORGANS, Issue 1 2004Shinji Tomita Abstract:, The field of cell-based therapy to regenerate myocardium has been expanding rapidly, with significant advances being made in both the laboratory and the clinical area. In this article we review this field, including our experiences and discuss remaining issues and possibilities for future clinical applications. [source] Quantitative determination of saquinavir from Caco-2 cell monolayers by HPLC-UVBIOMEDICAL CHROMATOGRAPHY, Issue 1 2003Sibel Demirbas Ucpinar Abstract The validation and quantitative determination of the protease inhibitor, saquinavir, from confluent Caco-2 monolayers and from aqueous solution is reported. The high performance liquid chromatographic method consisted of an UltramexÔ 5 C8 reverse-phase column (250,×,4.6,mm i.d.) and a mobile phase of acetonitrile:water:triethylamine (55:44:1, v/v/v, pH 6.5). Samples were analyzed using an ultraviolet detector at 238,nm, and diltiazem hydrochloride (66,µg/mL) was used as an internal standard. A linear response over a broad concentration range (0.4,8.0,µg/mL, r2,=,0.997) was obtained. The limit of detection and quantitation was set at 0.14 and 0.4,µg/mL, respectively. Over a 4 day period, the intra-day and inter-day precision ranged from 1 to 7% with a mean of 4%, and from 1 to 2% with a mean of 1.5%, respectively. Bench,top and storage stability of saquinavir was found to be satisfactory. The permeability of saquinavir through Caco-2 monolayers was estimated using this assay. Copyright © 2002 John Wiley & Sons, Ltd. [source] "Enzyme Test Bench," a high-throughput enzyme characterization technique including the long-term stabilityBIOTECHNOLOGY & BIOENGINEERING, Issue 2 2009Kirill Rachinskiy Abstract A new high throughput technique for enzyme characterization with specific attention to the long term stability, called "Enzyme Test Bench," is presented. The concept of the Enzyme Test Bench consists of short term enzyme tests in 96-well microtiter plates under partly extreme conditions to predict the enzyme long term stability under moderate conditions. The technique is based on the mathematical modeling of temperature dependent enzyme activation and deactivation. Adapting the temperature profiles in sequential experiments by optimal non-linear experimental design, the long term deactivation effects can be purposefully accelerated and detected within hours. During the experiment the enzyme activity is measured online to estimate the model parameters from the obtained data. Thus, the enzyme activity and long term stability can be calculated as a function of temperature. The engineered instrumentation provides for simultaneous automated assaying by fluorescent measurements, mixing and homogenous temperature control in the range of 10,85,±,0.5°C. A universal fluorescent assay for online acquisition of ester hydrolysis reactions by pH-shift is developed and established. The developed instrumentation and assay are applied to characterize two esterases. The results of the characterization, carried out in microtiter plates applying short term experiments of hours, are in good agreement with the results of long term experiments at different temperatures in 1 L stirred tank reactors of a week. Thus, the new technique allows for both: the enzyme screening with regard to the long term stability and the choice of the optimal process temperature regarding such process parameters as turn over number, space time yield or optimal process duration. The comparison of the temperature dependent behavior of both characterized enzymes clearly demonstrates that the frequently applied estimation of long term stability at moderate temperatures by simple activity measurements after exposing the enzymes to elevated temperatures may lead to suboptimal enzyme selection. Thus, temperature dependent enzyme characterization is essential in primary screening to predict its long term behavior. Biotechnol. Bioeng. 2009;103: 305,322. © 2008 Wiley Periodicals, Inc. [source] GOOD GIFTS FOR THE COMMON GOOD: Blood and Bioethics in the Market of Genetic ResearchCULTURAL ANTHROPOLOGY, Issue 3 2007DEEPA S. REDDY This article is based on ethnographic fieldwork conducted with the Indian community in Houston, as part of a NIH,NHGRI-sponsored ethics study and sample collection initiative entitled "Indian and Hindu Perspectives on Genetic Variation Research." At the heart of this research is one central exchange,blood samples donated for genetic research,that draws both the Indian community and a community of researchers into an encounter with bioethics. I consider the meanings that come to be associated with blood donation as it passes through various hands, agendas, and associated ethical filters on its way to the lab bench: how and why blood is solicited, how the giving and taking of blood is rationalized, how blood as material substance is alienated, processed, documented, and made available for the promised ends of basic science research. Examining corporeal substances and asking what sorts of gifts and problems these represent, I argue, sheds some light on two imbricated tensions expressed by a community of Indians, on the one hand, and of geneticists and basic science researchers, on the other hand: that gifts ought to be free (but are not), and that science ought to be pure (but is not). In this article, I explore how experiences of bioethics are variously shaped by the histories and habits of Indic giving, prior sample collection controversies, commitments to "good science" and the common "good of humanity," and negotiations of the sites where research findings circulate. [source] Diagnosis of Nonmelanoma Skin Cancer/Keratinocyte Carcinoma: A Review of Diagnostic Accuracy of Nonmelanoma Skin Cancer Diagnostic Tests and TechnologiesDERMATOLOGIC SURGERY, Issue 10 2007METTE MOGENSEN MD BACKGROUND Nonmelanoma skin cancer (NMSC) is the most prevalent cancer in the light-skinned population. Noninvasive treatment is increasingly used for NMSC patients with superficial lesions, making the development of noninvasive diagnostic technologies highly relevant. OBJECTIVE The scope of this review is to present data on the current state-of-the-art diagnostic methods for keratinocyte carcinoma: basal cell carcinoma, squamous cell carcinoma, and actinic keratosis. METHODS AND MATERIALS MEDLINE, BIOSIS, and EMBASE searches on NMSC and physical and clinical examination, biopsy, molecular marker, ultrasonography, Doppler, optical coherence tomography, dermoscopy, spectroscopy, fluorescence imaging, confocal microscopy, positron emission tomography, computed tomography, magnetic resonance imaging, terahertz imaging, electrical impedance and sensitivity, specificity, and diagnostic accuracy. RESULTS State-of-the-art diagnostic research has been limited in this field, but encouraging results from the reviewed diagnostic trials have suggested a high diagnostic accuracy for many of the technologies. Most of the studies, however, were pilot or small studies and the results would need to be validated in larger trials. CONCLUSIONS Some of these new imaging technologies have the capability of providing new, three-dimensional in vivo, in situ understanding of NMSC development over time. Some of the new technologies described here have the potential to make it from the bench to the clinic. [source] Leading science: staying informed without micromanaging (achieving and keeping the balance)DRUG DEVELOPMENT RESEARCH, Issue 2 2005Alice M. Sapienza Abstract Those who lead scientific efforts understand that they must contribute to judgments of both value and meaning of new data emerging from the bench. However, there is a fine line between staying informed, on the one hand, and quashing morale and creativity by overmanaging scientists at the bench. We discuss why we believe that micromanagement may be more likely to occur in science and how it can impact the caliber of scientific output. We also provide guidelines for how leaders can move with the data appropriately and keep the balance between staying abreast of work versus putting the brakes on work. Drug Dev. Res. 64:99,104, 2005. © 2005 Wiley-Liss, Inc. [source] Bench,shelf system dynamic characteristics and their effects on equipment and contentsEARTHQUAKE ENGINEERING AND STRUCTURAL DYNAMICS, Issue 13 2006Tara C. Hutchinson Abstract Economic losses during past earthquakes are strongly associated with damage and failure to nonstructural equipment and contents. Among the vast types of nonstructural elements, one important category, is scientific equipment in biological or chemical laboratories. These equipment are often mounted on heavy ceramic bench-tops of bench,shelf systems, which in turn may amplify the dynamic motions imposed. To investigate the seismic response of these types of systems, a series of shake table and field experiments were conducted considering different representative bench and shelf-mounted equipment and contents. Results from shake table experiments indicate that these equipment are generally sliding-dominated. In addition, the bench,shelf system is observed to be very stiff and when lightly loaded, has a fundamental frequency between 10 and 16 Hz. An approximate 50% reduction in the first and second fundamental frequencies is observed considering practical loading conditions. Insight into a broader range of system response is provided by conducting eigenvalue and time history analyses. Non-linear regression through the numerical data indicate acceleration amplification ratios , range from 2.6 to 1.4 and from 4.3 to 1.6, for fixed,fixed and pinned,pinned conditions, respectively. Both the experimental and numerical results support the importance of determining the potential dynamic amplification of motion in the context of accurately determining the maximum sliding displacement of support equipment and contents. Copyright © 2006 John Wiley & Sons, Ltd. [source] Bank and Business Performance MeasurementECONOMIC NOTES, Issue 2 2002Stuart M. Turnbull Given the objective of maximizing the wealth of existing shareholders, this paper discusses some of the issues that arise in attempting to measure the performance of individual businesses within a bank. The paper describes two return measures , return on assets within a business and the return on the ,equity' of an individual business , and discusses the appropriate bench,marks. The paper ends with a discussion of the cost of unused allocated capital and the appropriate performance metric. (J.E.L.: G30, G31). [source] Cardiac regeneration by progenitor cells , bedside before bench?EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 7 2005J. Bauersachs Abstract Recent experimental and clinical trials give rise to the hope that progenitor cells could replace scar tissue after myocardial infarction with healthy functional myocardium. However, while a significant increase in left ventricular ejection fraction has been described after progenitor cell transplantation in several clinical trials, long-term results are lacking, and the mechanisms underlying the improvement of ejection fraction are unclear. Therefore, the efficacy of progenitor cell transplantation after myocardial infarction has not been established, and potential problems may have been underestimated. In-depth laboratory and animal studies are needed to determine the best cell type, optimal amount of cells, and time point for transplantation. Treatment of patients with progenitor cells outside well controlled prospective trials should be avoided. [source] Maternal-fetal interface: from bench to bedsideEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2005Article first published online: 10 MAR 200 No abstract is available for this article. [source] Rivaroxaban , an oral, direct Factor Xa inhibitor , lessons from a broad clinical study programmeEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2009Sylvia Haas Abstract Anticoagulants are recommended for the prevention and treatment of venous thromboembolism (VTE), prevention of stroke in patients with atrial fibrillation (AF) and secondary prevention in patients with acute coronary syndrome (ACS). There is a clinical need for novel anticoagulants offering improvements over current standard of care, such as fixed oral dosing and no need for routine monitoring. Rivaroxaban, an oral, once-daily, direct Factor Xa inhibitor, has recently completed the RECORD phase III programme for the prevention of VTE in patients undergoing total hip or knee replacement (THR or TKR), an indication for which it is approved in Europe and Canada. It is being investigated in large-scale phase III studies for VTE treatment and prevention of stroke in patients with AF, and phase III studies will soon commence for secondary prevention in patients with ACS. Phase I studies demonstrated that no routine anticoagulation monitoring was required, while phase II studies suggested that fixed daily doses had a wide therapeutic window. The four RECORD studies consistently showed that rivaroxaban was significantly more effective than enoxaparin in the prevention of VTE after THR and TKR, with a similar safety profile. This review describes the development of this novel anticoagulant, from bench to bedside. [source] From bench to patients: We really can move mountainsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 9 2010Article first published online: 13 JUL 2010 No abstract is available for this article. [source] Security, Social Control, Democracy and Migration within the ,Constitution' of the EUEUROPEAN LAW JOURNAL, Issue 1 2005Dario Melossi Such conditions, and the theory thereof, first developed in North America, and then increasingly in Europe after World War II and especially since the 1970s. From such a comparative-historical perspective, the paper then tries to shed light on the debate that was ignited by Dieter Grimm on the very possibility of a ,democratic constitutionalisation' of Europe. The connections between language, social control, and a (democratic) European constitution are then discussed, and specific attention is given to the nexus that has been constructed in today's Europe between migration, criminalisation and security, as a sort of test bench of those connections. [source] THE SECOND ANNUAL MEYER ELKIN ADDRESSFAMILY COURT REVIEW, Issue 1 2000The Changing Family in the New Millennium A year ago, our journal had the opportunity to publish the inaugural Meyer Elkin Address by Jonah, Peter, and Marian Wright Edelman. This past summer, the Association of Family and Conciliation Courts was honored to have George Thomson speak at its conference in Vancouver, British Columbia. Thomson was presented with this honor for his hard work and dedication to family law in Canada and throughout the world. The Family and Conciliation Courts Review is honored to publish this speech by Thomson. Described by his colleagues as a "miracle worker" and "superman", Thomson has led a fascinating career that has followed several different paths. As an undergraduate student, Thomson attained a B.A. in philosophy and English from Queen's University in Kingston, Ontario. He remained at Queen's University and received an LL.B., then completed his formal education with an LL.M. from the University of California. Thomson has had a diverse background in the legal field, serving as an educator, a judge, and a government official. From 1968 until 1971, he worked as both an associate professor and assistant dean at the University of Western Ontario in London, Ontario. After his brief stint with the university, he was appointed judge of the Provincial Court for the Province of Ontario. Thomson held this position for five years before becoming an associate deputy minister of Community and Social Services, where he served as the head of the Children's Services Division. In the 1980s, Thomson returned to the bench in the provincial court. Additionally, he was the director of education for the Law Society of Upper Canada. Most notably, however, Thomson chaired a provincial committee on social welfare reform. By 1989, Thomson had moved from the bench into governmental work. He briefly served as the deputy minister of citizenship for Ontario. He was then appointed the deputy minister of labor until 1992. From 1992 until 1994, Thomson served as Ontario's deputy attorney general. He then became the deputy minister of justice and deputy attorney general of Canada. Most recently, Thomson has been a special advisor to the minister of justice and attorney general of Canada. The following Meyer Elkin address was presented at the annual Convention of the Association of Family and Conciliation Courts in Vancouver, Canada, in June 1999. [source] Haemostasis: from bench to bedsideHAEMOPHILIA, Issue 5 2002Article first published online: 28 AUG 200 First page of article [source] Evaluating the transport and removal of chromate using pyrite and biotite columnsHYDROLOGICAL PROCESSES, Issue 14 2007Chul-Min Chon Abstract To remove chromate from a wastewater, a porous permeable reactive barrier system (PRBS), using pyrite and biotite, was adapted. This study included bench-scale column experiments to evaluate the efficiency of the PRBS and investigate the reaction process. The total chromium concentration of the effluent from the biotite and pyrite columns reached the influent concentration of 0·10 mM after passing through more than 150 pore volumes (PVs) and 27 PVs respectively, and remained constant thereafter. The CrVI concentration in the effluent from the biotite column became constant at about 0·08 mM, accounting for approximately 80% of the influent concentration, after passing through 200 PVs. Moreover, in the pyrite column, the CrVI concentration remained at about 0·01 mM, 10% of the input level, after passing through 116 PVs. This shows that both columns maintained their levels of chromate reduction once the CrVI breakthrough curves (BTCs) had reached the steady state, though the steady-state output concentration of total chromium had reached the influent level. The variances of the iron concentration closely followed those of the chromium. The observed data for both columns were fitted to the predicted BTCs calculated by CXTFIT, a program for estimating the solute transport parameters from experimental data. The degradation coefficient µ of the total chromium BTCs for both columns was zero, suggesting the mechanisms for the removal of chromate limit the µ of the CrVI BTCs. The CrVI degradation of the pyrite column (6·60) was much greater than that of the biotite column (0·27). In addition, the CrVI retardation coefficient R of the pyrite column (253) was also larger than that of the biotite column (125). The R values for the total chromium BTCs from both columns were smaller than those of the CrVI BTC. Whereas the total chromium BTC for the pyrite column showed little retardation (1·5), the biotite column showed considerable retardation (80). The results for the 900 °C heat-treated biotite column were analogous to those of the control column (quartz sand). This suggests that the heat-treated biotite played no role in the retardation and removal of hexavalent chromium. The parameters of the heat-treated biotite were calculated to an R of 1·2 and µ of 0·01, and these values confirmed quantitatively that the heated biotite had little effect on the transport of CrVI. These solute transport parameters, calculated by CXTFIT from the data obtained from the column tests, can provide quantitative information for the evaluation of bench- or field-scale columns as a removal technology for CrVI in wastewater or contaminated groundwater. Copyright © 2006 John Wiley & Sons, Ltd. [source] Role of cytokines in rheumatoid arthritis: an education in pathophysiology and therapeuticsIMMUNOLOGICAL REVIEWS, Issue 1 2008Marc Feldmann Summary: Advances in cDNA and monoclonal antibody technology in the 1980s fuelled the discovery and characterization of the properties of cytokines. It became apparent that because cytokines were expressed in tissues derived from autoimmune diseases, they were likely to be of fundamental importance in disease pathogenesis and developing a new class of biological therapeutics. In this review, we describe the history of bench to bedside translation of work that led to the identification of tumor necrosis factor (TNF) as a key regulator of the loss of homeostatic immune-inflammatory responses in rheumatoid arthritis (RA) and a good therapeutic target. First in human clinical trials in collaboration with a biotechnology company, the safety and efficacy of TNF blockade with a chimeric monoclonal antibody was substantiated in patients refractory to standard anti-rheumatoid drugs. Abnormal immune-inflammatory responses after therapy showed improvement and remain a focus of ongoing research in many laboratories. Longer term multi-center studies that followed with several anti-TNF biologicals have demonstrated the augmented efficacy, including inducing clinical remission, of low dose methotrexate and anti-TNF therapy co-therapy, but serious infections and lymphomas in a low frequency have been observed. In the course of the past decades, three ,blockbuster' anti-TNF biologicals are in the clinic. Over a million patients with RA and other immune-mediated diseases have been successfully treated, and a better perspective on the risk of harm and its management has become part of good clinical practice. This success has encouraged a burgeoning industry of biologicals for chronic diseases. [source] Texture Analysis and Finite Element Modeling of Operational Stresses in Ceramic Injection Molding Components for High-Pressure PumpsINTERNATIONAL JOURNAL OF APPLIED CERAMIC TECHNOLOGY, Issue 4 2005Martin Wenzelburger Texturization of microstructures in ceramic components during injection of thermoplastic feedstocks into the mold is a well-known problem in ceramic injection molding (CIM) technology. The influences of textures on the mechanical properties of components with anisotropic properties, which depend on crystallite structure and orientation, usually involve weakening of the structure by the formation of separation planes and accumulation of stresses, which can lead to crack initiation and subcritical failure. A light optical texture analysis technique was developed for the analysis of thin section preparations from optically anisotropic ceramic materials. An internal Al2O3 gear rim for high-pressure gear pumps that is manufactured by CIM was chosen for the evaluation of this technique. Components were produced from thermoplastic ceramic feedstocks with different rheological behavior. Thin sections were prepared from the sintered parts. The texture was analyzed by polarized transmission light microscopy of the thin sections and colorimetric analysis of the crystal orientation. For the evaluation of the component properties, function, and lifetime, operating tests on a test bench were carried out as well as finite element (FE) simulation of the stress distribution in the components under operational load with regard to the texturization. The results were used for the localization of stress gradients and their comparison and correlation to the texturization. The functionality of this texture analysis method was proved by the tests, and it is expected to be a convenient novel method for the analysis and optimization of the parameters in CIM processes and the design of injection gate and mold. [source] Small-angle neutron scattering investigation of plastically deformed stainless steelJOURNAL OF APPLIED CRYSTALLOGRAPHY, Issue 3-1 2003Vassily Lebedev The microstuctural evolution of plastically deformed steels has been studied by small-angle neutron scattering at ambient temperature in the range of momentum transfer q = (4,/,)sin(,/2) = 0.01,5 nm,1 where , is neutron wavelength and , is the scattering angle. Samples of austenite stainless steels were pulled on a standard bench to cause a plastic deformation, S = 0,60%, up to the fracture of the material. As a result of the deformation an increase of an order of magnitude was observed in the scatterred intensity I(q)~1/[1+(qRC)2](6- Ds)/2. The analysis of the I(q) distribution has shown the surface fractal nature of the observed nano-scale structures. The evolution of internal surface via intensive growth of pores (size RC~20,40 nm) was found and a linear decrease of the surface fractal dimension 2.9,Ds(S),2.1 was observed. These findings can be used to design the fracture criteria for materials of industrial application. [source] Emerging targets and novel strategies in the treatment of AIDS-related Kaposi's sarcoma: Bidirectional translational scienceJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2006Bruce J. Dezube Through the mentorship process, Dr. Arthur Pardee emphasized the critical importance of bidirectional translational research,not only advancing drug development from bench to bedside, but also bringing back precious clinical material to the laboratory to assess the biologic effects of therapeutic agents on their targets. This mini-review focuses on the signal transduction pathways of Kaposi's sarcoma (KS) and on how the knowledge of such pathways has led to the rational development of molecularly targeted pathogenesis-driven therapies. Acquired immune deficiency syndrome (AIDS) related-KS results from co-infection with human immunodeficiency virus and KS herpesvirus/human herpesvirus-8 (KSHV/HHV8), which leads to the development of an angiogenic-inflammatory state that is critical in the pathogenesis of KS. KS is driven by KSHV/HHV8-specific pathways, which include viral G protein-coupled receptor (vGPCR), viral interleukin-6 (vIL-6), and viral chemokine homologues. In addition, cellular growth/angiogenic pathways, such as vascular endothelial growth factor (VEGF), insulin-like growth factor, platelet-derived growth factor (PDGF), angiopoietin and matrix metalloproteinases (MMPs) are "pirated" by KSHV/HHV8. As a very tangible example of how translational research has led to a marked improvement in patient outcome, the signal transduction inhibitor imatinib (a tyrosine kinase inhibitor of c-kit and PDGF) was administered to patients with KS whose tumors were serially biopsied. Not only did the patients' tumors regress, but also the regression was correlated with the inhibition of PDGF receptor (PDGFR) in the biopsy samples. Recent and future clinical trials of molecularly targeted therapy for the treatment of KS are a prelude to a shift in the paradigm of how KS is managed. J. Cell. Physiol. 209: 659,662, 2006. © 2006 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||||||||||||||||||||||||||