Home About us Contact
|
Home About us Contact | ||
|
|
||
Main Target (main + target)
Selected AbstractsPrehistory of the Japanese Teratology Society: The pioneers of teratology in Japan and the founders of the SocietyCONGENITAL ANOMALIES, Issue 1 2001Yoshiro Kameyama ABSTRACT The significant achievements of teratological research in Japan were traced from the beginning of the 20th century to the foundation of Japanese Teratology Society (JTS) in 1961 as a bird's-eye view of the prehistory of JTS. The activities of the leaders of foresight who contributed to establish the JTS and to consolidate its basis for future growth were introduced in chronological order; Japanese pioneers before 1945, early developing stage of research (1948,1954), study groups furnishing the basis of JTS (1955,1961), and the final step for JTS establishment (1960,1961). Teratological research in Japan was initiated independent of foreign studies and had obtained original findings before World War II. The studies in Japan progressed with their main target the prevention of exogeneous malformations as a feasible approach from the standpoint of practical medicine. Accordingly, a close collaboration between experimental and clinical teratologists, one of the grand traditions of JTS, was in place even before the early stages of JTS foundation. [source] Temporal Variation in Cleanerfish and Client Behaviour: Does It Reflect Ectoparasite Availability?ETHOLOGY, Issue 6 2003Isabelle M. Côté We tested the importance of ectoparasites as the proximate cause of cleaning interactions by comparing the activity of Caribbean cleaning gobies (Elacatinus evelynae) and of their clients during three daily periods (early morning, midday, and late afternoon) in which ectoparasite availability varied naturally. Emergence from the benthos of gnathiid isopod larvae, the main target of cleaning goby predation, was higher at night, when cleaners were inactive, than during the day. As a result, overall ectoparasite loads on client fish tended to be higher in the morning. Inspection bouts by cleaning gobies were longest in the morning, but also at midday when ectoparasite availability on clients was lower. Client fish were observed at cleaning stations most often in the afternoon, when they harboured few ectoparasites, but they were more likely to adopt incitation poses, which increase the likelihood of being cleaned, in the morning than later in the day. Most cleaner and client behaviours therefore did not change predictably in response to natural diurnal variation in ectoparasite availability. Our study suggests that the ultimate and proximate causes of cleaning behaviour need not necessarily coincide. [source] Ace2, rather than ace1, is the major acetylcholinesterase in the silkworm, Bombyx moriINSECT SCIENCE, Issue 4 2009Hui-Juan Chen Abstract, Two acetylcholinesterase (ace) genes have been reported in many insect species. In pests such as Helicoverpa assulta and Plutella xylostellas, ace1 gene encodes the predominant synaptic enzyme that is the main target of organophosphorus (OP) and carbamate pesticides. It has been reported that pesticide selection has an impact on the ace gene evolution. The domesticated silkworm, Bombyx mori, also has two ace genes. We studied ace gene expression and enzyme activities in silkworm as this has not faced pesticide selection over the past decades. The expression levels of two ace genes, Bm- ace1 and Bm- ace2, were estimated by quantitative real-time polymerase chain reaction. Bm- ace2 was expressed more highly than Bm- ace1 in all tested samples of different developmental stages or tissues, suggesting ace2, rather than ace1, is the major type of acetylcholinesterase (AChE) in Bombyx mori. This is inconsistent with the aforementioned lepidopterons agricultural pests, partly be due to the widespread use of pesticides that may induce high expression of the ace1 gene in these pests. Besides high expression in the head, Bm- ace1 also expresses highly in the silk glands and Bm- ace2 is abundant in the germline, implying both ace genes may have potential non-hydrolytic roles in development. Furthermore, we found that the mRNA levels of two ace genes and their ratios (ace2/ace1) change day to day in the first and third instars. This challenges the conventional method of estimating enzymatic activity using crude extract as an enzyme solution, as it is a mixture of AChE1 and AChE2. An efficient and simple method for separating different AChEs is necessary for reliable toxicological analyses. [source] A short history of sweat gland biologyINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 3 2007K. Wilke Synopsis The axilla, especially its microflora and axillary sweat glands as well as their secretions, is the main target of cosmetic compositions such as deodorants or antiperspirants. There are three types of sweat glands present in the axillary skin, namely apocrine, eccrine and apoeccrine sweat glands. Here, we provide an overview of the morphological, structural and functional characteristics of the different gland types and present techniques that allow their clear distinction. Moreover, we describe different forms of perspiration as physical reactions to external and internal stimuli. Résumé Les glandes sudoripares axillaires et leurs sécrétions sont les points d'application principaux des produits antitranspirants et déodorants. Dans la peau axillaire, il y a trois formes différentes de glandes sudoripares appelées apocrines, eccrines et apoeccrines. Nous donnons une vue d'ensemble des propriétés fonctionnelles, morphologiques et structurelles des différentes glandes et présentons des techniques qui permettent leur distinction. Nous décrivons également les différents modes de transpiration corporelle entant que réactions physiques aux stimuli externes et internes. [source] Ectoparasites: are they the proximate cause of cleaning interactions?JOURNAL OF FISH BIOLOGY, Issue 2003I. M. Côté We tested the importance of ectoparasites in cleaning symbioses by comparing the activity of Caribbean cleaning gobies (Elacatinus evelynae) and of their clients during three daily periods (early morning, midday and late afternoon) in which ectoparasite availability varied naturally. Emergence from the benthos of gnathiid isopod larvae, the main target of cleaning goby predation, was higher at night, when cleaners are inactive, than during the day. Overall ectoparasite loads also tended to be higher on clients in the morning. This coincided with higher rates of visits to cleaning stations by client fish in the morning than at midday, but high rates of client visits were also recorded in the late afternoon. Clients were more likely to adopt stereotypical incitation poses, which increase the likelihood of being cleaned, in the morning than later in the day. Inspection bouts by cleaning gobies were longest in the morning. Cleaner and client behaviours therefore change predictably in response to natural diurnal variation in ectoparasite availability. These results add to a growing number of studies supporting the idea that cleaning symbioses are mutualisms dependent on ectoparasite removal. [source] Oxidative modification of mitochondrial proteins and cell death in Parkinson's diseaseJOURNAL OF NEUROCHEMISTRY, Issue 2002W. Maruyama Oxidative stress is one of the cell death mechanisms in neurodegenerative disorders, such as Parkinson's disease (PD) and Alzheimer's disease. Most of reactive oxygen species (ROS) generate in mitochondria through oxidative phosphorylation, and a part of them are not scavenged by antioxidative system and react with bioactive molecules. Recently, alpha-synuclein containing nitrotyrosine, a marker for oxidative modification by peroxynitrite, was identified in Lewy body. In addition, inhibitors of mitochondrial respiratory chain were reported to induce formation of Lewy body-like inclusion in vivo and in vitro. In this paper it was examined whether ROS and reactive nitrogen species (RNS) generated in mitochondria oxidize mitochondrial respiratory enzymes and induce the formation of inclusion body and cell death in PD. Human neuroblastoma SH-SY5Y cells were treated with a peroxynitrite donor, SIN-1, or an inhibitor of complex I, rotenone. After the treatment, proteins modified with toxic aldehydes, 4-hydroxynonenal and acrolein, and containing nitrotyrosine were analyzed by immunoblotting. Particularly in mitochondrial fraction, the oxidized protein was characterized by two-dimensional immunoblotting. Most of the oxidized proteins were detected in subunits proteins of complex I. These results indicate that mitochondrial complex I is a main target of oxidative stress in dopamine neurons and its dysfunction may be involved in the death mechanism in neurodegenerative disorders. [source] A Narrative-Based View of Coexistence EducationJOURNAL OF SOCIAL ISSUES, Issue 2 2004Gavriel Salomon Collective narratives of groups in conflict,their perceived histories, beliefs, self-image, and those of their adversaries,play a central role in interpreting and fueling the conflict,and, thus, can play an equally central role in facilitating coexistence. One of their main correlates is their implied delegitimization of the "other's" collective narrative, its pains, its sufferings, its history, and its aspirations. It is this deligitimization that ought to be the main target for change if coexistence is to be promoted, including the acknowledgement of one's own contribution to the conflict. Four dilemmas are discussed: coexistence programs for the dominant versus the subordinate groups; possible counterproductive outcomes; resistance against antagonistic, dominant narratives; and the problem of short-term intervention programs. [source] Absent reduction by HIV protease inhibitors of Candida albicans adhesion to endothelial cellsMYCOSES, Issue 3 2007Barbara Falkensammer Summary Highly active antiretroviral therapy including HIV protease inhibitors has led to a marked reduction of clinically relevant mucosal candidiasis. We have previously shown that HIV protease inhibitors directly inhibit adhesion of Candida albicans to epithelial cells at concentrations that are reached in vivo during antiretroviral therapy. The aim of this study was to establish whether HIV protease inhibitors also inhibit adhesion of Candida to endothelial cells, which play a major role in systemic fungal disease. Three C. albicans strains were incubated with human umbilical vein endothelial cells or an endothelial cell line in the presence of either Ritonavir, Saquinavir or Indinavir. Subsequently, adherence was determined by counting colony-forming units. The results were comparable and revealed that Ritonavir and Saquinavir significantly inhibited adherence to endothelial cells at only very high concentrations which are likely not reached in vivo, and Indinavir did not even inhibit then. Inhibition of adhesion of C. albicans to human cells by HIV protease inhibitors is not a general feature, but strongly cell type-dependent, and clearly not observed for endothelial cells in vitro, which are a main target of systemic candidiasis in vivo. [source] A Novel Device for Single Particle Light Scattering Size Analysis and Concentration Measurement at High Pressures and TemperaturesPARTICLE & PARTICLE SYSTEMS CHARACTERIZATION, Issue 2 2008Heinz Umhauer Abstract Based on the findings of previous work, a novel instrument was developed for the size analysis and concentration measurement of particles dispersed in gases at high temperatures (600,°C) and pressures (16 bar). The main motivation for the construction of this device was a measurement requirement at the conditions of a pressurized pulverized coal combustion (PPCC) test installation in Dorsten, Germany. The development of a high efficiency (>,50,%), coal based, combined cycle process, and specifically, the development of efficient gas cleaning technology for gas combustion under demanding conditions (1400,°C and 16 bar) was the main target. A suitable measurement technique was required for the determination of particle size and concentration downstream of the gas cleaning equipment, which is able to operate close to the given conditions. The performance of the novel device was tested in several measurement series with various monodisperse aerosols at ambient conditions as well as in high pressure, high temperature situations with very satisfactory results, i.e., the lower detection limit (50,% counting efficiency at ca. 0.3 ,m) and resolution of the novel device are comparable to state of the art instruments (of the same principle) intended for room temperature operation. [source] Structure of the ligand-binding domain of the EphB2 receptor at 2,Å resolutionACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 2 2009Yehuda Goldgur Eph tyrosine kinase receptors, the largest group of receptor tyrosine kinases, and their ephrin ligands are important mediators of cell,cell communication regulating cell attachment, shape and mobility. Recently, several Eph receptors and ephrins have also been found to play important roles in the progression of cancer. Structural and biophysical studies have established detailed information on the binding and recognition of Eph receptors and ephrins. The initial high-affinity binding of Eph receptors to ephrin occurs through the penetration of an extended G,H loop of the ligand into a hydrophobic channel on the surface of the receptor. Consequently, the G,H loop-binding channel of Eph receptors is the main target in the search for Eph antagonists that could be used in the development of anticancer drugs and several peptides have been shown to specifically bind Eph receptors and compete with the cognate ephrin ligands. However, the molecular details of the conformational changes upon Eph/ephrin binding have remained speculative, since two of the loops were unstructured in the original model of the free EphB2 structure and their conformational changes upon ligand binding could consequently not be analyzed in detail. In this study, the X-ray structure of unbound EphB2 is reported at a considerably higher 2,Å resolution, the conformational changes that the important receptor loops undergo upon ligand binding are described and the consequences that these findings have for the development of Eph antagonists are discussed. [source] Prevention of medication errors: detection and auditBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 6 2009Germana Montesi 1. Medication errors have important implications for patient safety, and their identification is a main target in improving clinical practice errors, in order to prevent adverse events. 2. Error detection is the first crucial step. Approaches to this are likely to be different in research and routine care, and the most suitable must be chosen according to the setting. 3. The major methods for detecting medication errors and associated adverse drug-related events are chart review, computerized monitoring, administrative databases, and claims data, using direct observation, incident reporting, and patient monitoring. All of these methods have both advantages and limitations. 4. Reporting discloses medication errors, can trigger warnings, and encourages the diffusion of a culture of safe practice. Combining and comparing data from various and encourages the diffusion of a culture of safe practice sources increases the reliability of the system. 5. Error prevention can be planned by means of retroactive and proactive tools, such as audit and Failure Mode, Effect, and Criticality Analysis (FMECA). Audit is also an educational activity, which promotes high-quality care; it should be carried out regularly. In an audit cycle we can compare what is actually done against reference standards and put in place corrective actions to improve the performances of individuals and systems. 6. Patient safety must be the first aim in every setting, in order to build safer systems, learning from errors and reducing the human and fiscal costs. [source] Basic Types and Structural Characteristics of Uplifts: An Overview of Sedimentary Basins in ChinaACTA GEOLOGICA SINICA (ENGLISH EDITION), Issue 2 2009Dengfa HE Abstract: The uplift is a positive structural unit of the crust It is an important window for continental dynamics owing to its abundant structural phenomena, such as fault, fold, unconformity and denudation of strata. Meanwhile, it is the very place to store important minerals like oil, natural gas, coal and uranium. Giant and large-scale oil and gas fields in China, such as the Daqing Oilfield, Lunnan-Tahe Oilfield, Penglai 19,3 Oilfield, Puguang Gas Field and Jingbian Gas Field, are developed mainly on uplifts. Therefore, it is the main target both for oil and gas exploration and for geological study. The uplift can be either a basement uplift, or one developed only in the sedimentary cover. Extension, compression and wrench or their combined forces may give rise to uplifts. The development process of uplifting, such as formation, development, dwindling and destruction, can be taken as the uplifting cycle. The uplifts on the giant Precambrian cratons are large in scale with less extensive structural deformation. The uplifts on the medium- and small-sized cratons or neo-cratons are formed in various shapes with strong structural deformation and complicated geological structure. Owing to changes in the geodynamic environment, uplift experiences a multi-stage or multi-cycle development process. Its geological structure is characterized in superposition of multi-structural layers. Based on the basement properties, mechanical stratigraphy and development sequence, uplifts can be divided into three basic types , the succession, superposition and destruction ones. The succession type is subdivided into the maintaining type and the lasting type. The superposition type can be subdivided into the composite anticlinal type, the buried-hill draped type, the faulted uplift type and the migration type according to the different scales and superimposed styles of uplifts in different cycles. The destruction type is subdivided into the tilting type and the negative inverted type. The development history of uplifts and their controlling effects on sedimentation and fluids are quite different from one another, although the uplifts with different structural types store important minerals. Uplifts and their slopes are the main areas for oil and gas accumulation. They usually become the composite oil and gas accumulation zones (belts) with multiple productive formations and various types of oil and gas reservoirs. [source] Intravenous infection of virulent shigellae causes fulminant hepatitis in miceCELLULAR MICROBIOLOGY, Issue 1 2005Maria Celeste Martino Summary Shigella spp. are pathogenic bacteria responsible for bacillary dysentery in humans. The major lesions in colonic mucosa are intense inflammation with apoptosis of macrophages and release of pro-inflammatory cytokines. The study of shigellosis is hindered by the natural resistance of rodents to oral infection with Shigella. Therefore, animal models exploit other routes of infection. Here, we describe a novel murine model in which animals receive shigellae via the caudal vein. Mice infected with 5 × 106 (LD50) virulent shigellae died at 48 h post infection, whereas animals receiving non-invasive mutants survived. The liver is the main target of infection, where shigellae induce microgranuloma formation. In mice infected with invasive bacteria, high frequency of apoptotic cells is observed within hepatic microgranulomas along with significant levels of mRNA for pro-inflammatory cytokines such as IL-1,, IL-18, IL-12 and IFN-,. Moreover, in the blood of these animals high levels of IL-6 and transaminases are detected. Our results demonstrate the intravenous model is suitable for pathogenicity studies and useful to explore the immune response after Shigella infection. [source] Reactions of Hydrogen Atoms with Met-Enkephalin and Related PeptidesCHEMISTRY - A EUROPEAN JOURNAL, Issue 7 2007Olivier Mozziconacci Abstract The reactions of hydrogen atoms with enkephalins and related peptides have been investigated by radiolytic methods in aqueous solutions and lipid vesicle suspensions. Pulse radiolysis experiments indicate that methionine residue (Met) is the main target. In Met-enkephalin (Tyr-Gly-Gly-Phe-Met) the attack of the hydrogen atom occurs to about 50,% on Met with formation of methanethiyl radical. The remaining percentage is divided roughly evenly between Tyr and Phe. With Leu-enkephalin (Tyr-Gly-Gly-Phe-Leu) the site of attack is limited to Tyr and Phe. Using a peptide,liposome (that is, 1-palmitoyl-2-oleoyl phosphatidylcholine vesicles) model, the cis,trans isomerization of phospholipids could be detected due to the catalytic action of thiyl radicals. The radiation chemical yields of the H. and, consequently of CH3S. radical, was modulated by the experimental conditions and the nature of peptide. Large amounts of trans lipids observed in phosphate buffer vesicle suspensions indicated the efficient role of double-bond isomerization as marker of Met-containing peptide damage. [source] Differential c-fos expression in the rhinencephalon and striatum after enhanced sleep,wake states in the catEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2000J. P. Sastre Abstract In order to delimit the supra-brainstem structures that are activated during the sleep,waking cycle, we have examined c-fos immunoreactivity in four groups of polygraphically recorded cats killed after 3 h of prolonged waking (W), slow-wave sleep (SWS), or paradoxical sleep (PS), following microinjection of muscimol (a ,-aminobutyric acid, GABA agonist) into the periaqueductal grey matter and adjacent areas [Sastre et al. (1996) , Neuroscience, 74, 415,426]. Our results demonstrate that there was a direct relationship between a significant increase in c-fos labelling and the amount of PS in the laterodorsalis tegmenti in the pons, supramamillary nucleus, septum, hippocampus, gyrus cingulate, amygdala, stria terminalis and the accumbens nuclei. Moreover, in all these structures, the number of Fos-like immunoreactive neurons in the PS group was significantly higher (three to 30-fold) than in the SWS and W groups. We suggest that the dense expression of the immediate-early gene c-fos in the rhinencephalon and striatum may be considered as a tonic component of PS at the molecular level and that, during PS, the rhinencephalon and striatum are the main targets of an excitatory system originating in the pons. [source] Co-administration of immunomodulator tuftsin and liposomised nystatin can combat less susceptible Candida albicans infection in temporarily neutropenic miceFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 3 2004Masood A Khan Abstract In order to develop a prospective chemotherapeutic agent against opportunistic infections, it is important to know that host factors such as degree of immunological debility as well as recovery of immune functions to normality may contribute significantly to a successful elimination of the pathogens. We demonstrated previously that concomitant delivery of antimicrobial agents and immunomodulators to the pathogen harbouring-host contributes to the complete elimination of the deep-seated fungal infections (aspergillosis and candidiasis) in animals with normal immune status. Considering that neutropenic hosts are the main targets of such infections, it can be argued about the potential of the immunomodulator-based therapy in subjects with non-functional immune system. To resolve the hypothesis, we studied the role of immunomodulator tuftsin against experimental murine candidiasis in temporarily neutropenic Balb/c mice. The neutropenic mice were challenged with an isolate of Candida albicans that was showing less susceptibility to both free and liposomised-amphotericin B. The co-administration of tuftsin increased the efficiency of liposomised-polyene antibiotics (nystatin and amphotericin B) against experimental murine candidiasis in immunocompromised Balb/c mice. Pretreatment with liposomised tuftsin prior to C. albicans infection clearly enhanced protection against candidiasis, suggesting a prophylactic role of tuftsin in normal and temporarily neutropenic animals. [source] Changes in Korean Corporate Governance: A Response to CrisisJOURNAL OF APPLIED CORPORATE FINANCE, Issue 1 2008E. Han Kim In the last months of 1997, the value of the Korean currency lost over half its value against the dollar, and the ruling party was swept from power in presidential elections. One of the fundamental causes of this national economic crisis was the widespread failure of Korean companies to earn their cost of capital, which contributed to massive shareholder losses and calls for corporate governance reform. Among the worst performers, and hence the main targets of governance reform, were family-controlled Korean business groups known as chaebol. Besides pursuing growth and size at the expense of value, such groups were notorious for expropriating minority shareholders through "tunneling" activities and other means. The reform measures introduced by the new administration were a mix of market-based solutions and government intervention. The government-engineered, large-scale swaps of business units among the largest chaebol,the so-called "big deals" that were designed to force each of the groups to identify and specialize in a core business,turned out to be failures, with serious unwanted side effects. At the same time, however, new laws and regulations designed to increase corporate transparency, oversight, and accountability have had clearly positive effects on Korean governance. Thanks to reductions in barriers to foreign ownership of Korean companies, such ownership had risen to about 37% at the end of 2006, up from just 13% ten years earlier. And in addition to the growing pressure for better governance from foreign investors, several newly formed Korean NGOs have pushed for increased transparency and accountability, particularly among the largest chaebol. The best governance practices in Korea today can be seen mainly in three kinds of corporations: (1) newly privatized companies; (2) large corporations run by professional management; and (3) banks with substantial equity ownership in the hands of foreign investors. The improvements in governance achieved by such companies,notably, fuller disclosure, better alignment of managerial incentives with shareholder value, and more effective oversight by boards,have enabled many of them to meet the global standard. And the governance policies and procedures of POSCO, the first Korean company to list on the New York Stock Exchange,as well as the recent recipient of a large equity investment by Warren Buffett,are held up as a model of best practice. At the other end of the Korean governance spectrum, however, there continue to be many large chaebol-affiliated or family-run companies that have resisted such reforms. And aided by the popular resistance to globalization, the lobbying efforts of such firms have succeeded not only in reducing the momentum of the Korean governance reform movement, but in reversing some of the previous gains. Most disturbing is the current push to allow American style anti-takeover devices, which, if successful, would weaken the disciplinary effect of the market for corporate control. [source] Solid-state glycation of ,-lactoglobulin by lactose and galactose: localization of the modified amino acids using mass spectrometric techniquesJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 1 2004François Fenaille Abstract The Maillard reaction is commonly encountered during food processing or storage, and also in human nutrition, hence there is a need for analytical methodologies to identify and characterize the modified proteins. This paper reports specific methods using mass spectrometric techniques to localize protein modifications induced by lactose and galactose on ,-lactoglobulin (,-Lg) under solid-state glycation conditions. The extent of glycation was first determined by liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS). The specific identification of lactose-modified amino acid residues was realized using both NanoESI-MS, NanoESI-MS/MS (neutral loss scanning modes) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) (with and without guanidination of lysine residues) on unfractionated digests. The results indicated that, after 8.25 h of incubation, the lysine residues were the main targets of lactose-induced modification. In addition to the 15 lysine residues, Leu1 (NH2 terminal) and the Arg124 were also found to be modified, thus leading to a total of 17 different modified amino acid residues (versus 15 found by LC/ESI-MS measurement). In a second set of experiments, different strategies consisting of constant neutral loss and precursor ion scanning were compared to characterize galactose-induced modifications. Owing to the high level of ,-Lg glycation, the combined use of these different strategies appeared to be necessary for determining the galactose-modified sites after 8.25 h of incubation. Thus, among the 22 galactose adducts deduced from the LC/ESI-MS measurement, apart from the N-terminal and classical lysine residues, we also observed a few arginine residues (Arg40, Arg124 and Arg148) that were modified, and also dialkylations on specific lysine residues (Lys47, Lys75). Copyright © 2003 John Wiley & Sons, Ltd. [source] Antiangiogenic drugs: Current knowledge and new approaches to cancer therapyJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2008Jose L. Mauriz Abstract Angiogenesis,process of new blood-vessel growth from existing vasculature,is an integral part of both normal developmental processes and numerous pathologies such as cancer, ischemic diseases and chronic inflammation. Angiogenesis plays a crucial role facilitating tumour growth and the metastatic process, and it is the result of a dynamic balance between proangiogenic and antiangiogenic factors. The potential to block tumour growth and metastases by angiogenesis inhibition represents an intriguing approach to the cancer treatment. Angiogenesis continues to be a topic of major scientific interest; and there are currently more antiangiogenic drugs in cancer clinical trials than those that fit into any other mechanistic category. Based on preclinical studies, researchers believe that targeting the blood vessels which support tumour growth could help treatment of a broad range of cancers. Angiogenic factors or their receptors, endothelial cell proliferation, matrix metalloproteinases or endothelial cell adhesion, are the main targets of an increasing number of clinical trials approved to test the tolerance and therapeutic efficacy of antiangiogenic agents. Unfortunately, contrary to initial expectations, it has been described that antiangiogenic treatment can cause different toxicities in cancer patients. The purpose of this article is to provide an overview of current attempts to inhibit tumour angiogenesis for cancer therapy. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:4129,4154, 2008 [source] Real-time MR temperature mapping of rabbit liver in vivo during thermal ablationMAGNETIC RESONANCE IN MEDICINE, Issue 2 2003Claudia Weidensteiner Abstract It has been shown that quantitative MRI thermometry using the proton resonance frequency (PRF) method can be used to noninvasively monitor the evolution of tissue temperature, and to guide minimally-invasive tumor ablation based on local hyperthermia. Although hepatic tumors are among the main targets for thermal ablation, PRF-based temperature MRI of the liver is difficult to perform because of motion artifacts, fat content, and low T. In this study the stability of real-time thermometry was tested on a clinical 1.5 T scanner for rabbit liver in vivo. The fast segmented EPI principle was used together with respiratory gating to limit respiratory motion artifacts. Lipid signal suppression was achieved with a binomial excitation pulse. Saturation slabs were applied to suppress artifacts due to flowing blood. The respiratory-gated MR thermometry in the rabbit liver in vivo showed a standard deviation (SD) of 1,3°C with a temporal resolution of 3 s per slice and 1.4 mm × 1.9 mm spatial resolution in plane (slice thickness = 5 mm). The method was used to guide thermal ablation experiments with a clinical infrared laser. The estimated size of the necrotic area, based on the thermal dose calculated from MR temperature maps, corresponded well with the actual lesion size determined by histology and conventional MR images obtained 5 days posttreatment. These results show that quantitative MR temperature mapping can be obtained in the liver in vivo, and can be used for real-time control of thermal ablation and for lesion size prediction. Magn Reson Med 50:322,330, 2003. © 2003 Wiley-Liss, Inc. [source] Rotation speed and stellar axis inclination from p modes: how CoRoT would see other sunsMONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 3 2006J. Ballot ABSTRACT In the context of future space-based asteroseismic missions, we have studied the problem of extracting the rotation speed and the rotation-axis inclination of solar-like stars from the expected data. We have focused on slow rotators (at most twice solar rotation speed), first, because they constitute the most difficult case and, secondly, because some of the Convection Rotation and planetary Transits (CoRoT) main targets are expected to have slow rotation rates. Our study of the likelihood function has shown a correlation between the estimates of inclination of the rotation axis i and the rotational splitting ,, of the star. By using the parameters, i and ,,,=,, sin i, we propose and discuss new fitting strategies. Monte Carlo simulations have shown that we can extract a mean splitting and the rotation-axis inclination down to solar rotation rates. However, at the solar rotation rate we are not able to correctly recover the angle i, although we are still able to measure a correct ,,, with a dispersion less than 40 nHz. [source] Government Shekels without Government Shackles?PUBLIC ADMINISTRATION REVIEW, Issue 1 2002The Administrative Challenges of Charitable Choice As President Bush plans to expand "Charitable Choice," civil libertarians worry that the legislation is part of a new assault on separation of church and state. Religious Right activists demand assurances that funds will not flow to groups like the Nation of Islam or Scientologists. African American pastors in urban areas,arguably the main targets of the initiative,are concerned that "government shekels" will be accompanied by "government shackles," that the costs and regulatory burdens accompanying collaborations with government will divert resources from client services and mute their prophetic voice. Caught in the middle are public managers, who must make the legislation work in the face of significant administrative challenges. Those challenges occur in three areas: contracting procedures, contract administration, and evaluation. In each of these categories, political realities and constitutional constraints will significantly complicate the manager's job. [source] A large-scale, high-efficiency and low-cost platform for structural genomics studiesACTA CRYSTALLOGRAPHICA SECTION D, Issue 8 2006Xiao-Dong Su A large-scale, high-efficiency and low-cost platform based on a Beckman Coulter Biomek FX and custom-made automation systems for structural genomics has been set up at Peking University, Beijing, People's Republic of China. This platform has the capacity to process up to 2000 genes per year for structural and functional analyses. Bacillus subtilis, a model organism for Gram-positive bacteria, and Streptococcus mutans, a major pathogen of dental caries, were selected as the main targets. To date, more than 470 B. subtilis and 1200 S.,mutans proteins and hundreds of proteins from other sources, including human liver proteins, have been selected as targets for this platform. The selected genes are mainly related to important metabolism pathways and/or have potential relevance for drug design. To date, 40 independent structures have been determined; of these 11 are in the category of novel structures by the criterion of having less than 30% sequence identity to known structures. More than 13 structures were determined by SAD/MAD phasing. The macromolecular crystallography beamline at the Beijing Synchrotron Radiation Facility and modern phasing programs have been crucial components of the operation of the platform. The idea and practice of the genomic approach have been successfully adopted in a moderately funded structural biology program and it is believed this adaptation will greatly improve the production of protein structures. The goal is to be able to solve a protein structure of moderate difficulty at a cost about US $10,000. [source] | |||||||||||||||||||||||||