CD34+-enriched donor lymphocyte infusions in a case of pure red cell aplasia and late graft failure after major ABO-incompatible bone marrow transplantation

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. Increased life expectancy will result in a higher prevalence of AF. Treatment of AF constitutes a persistent medical dilemma. Different multicenter trials have confirmed that oral anticoagulant therapy is the best choice for the prevention of systemic embolism. It must be recognized, however, that the incidence of systemic embolism in patients with AF varies according to the presence and type of underlying heart disease. Advanced age increases the risk of emboli in patients with AF. At the same time, older patients have a higher risk of hemorrhage when treated with oral anticoagulants. Thus, careful titrated individual oral anticoagulant therapy targeted to a safe and effective INR must be considered in patients with AF. Another dilemma in AF patients is the convenience of restoring sinus rhythm and indicating permanent antiarrhythmic therapy versus the alternative of heart rate control plus oral anticoagulants. Several multicenter trials now in progress have addressed this issue and most likely will answer these questions. Identification of patients with paroxysmal AF and risk of systemic embolism constitutes another dilemma, since only a small proportion of these patients evolve to chronic arrhythmia. Advanced age, history of hypertension and left atrial enlargement in 2D Echo are well recognized risk factors for embolism in patients with non valvular paroxysmal AF. A history of previous embolism constitutes another risk factor and supports the hypothesis that AF may activate systemic coagulation factors and left atrial thrombus formation in some patients.     

Virtual Fragment Screening Identification of a Quinoline‐5,8‐dicarboxylic Acid Derivative as a Selective JMJD3 Inhibitor

The quinoline‐5,8 dicarboxylic acid scaffold has been identified by a fragment‐based approach as new potential lead compound for the development of JMJD3 inhibitors. Among them, 3‐(2,4‐dimethoxypyrimidin‐5‐yl)quinoline‐5,8‐dicarboxylic acid (compound 3 ) shows low micromolar inhibitory activity against Jumonji domain‐containing protein 3 (JMJD3). The experimental evaluation of inhibitory activity against seven related isoforms of JMJD3 highlighted an unprecedented selectivity toward the biological target of interest.     

GC-EI-MS Analysis of Fatty Acid Composition in Brain and Serum of Twitcher Mouse

Globoid cell leukodystrophy or Krabbe disease is an inherited autosomal recessive disorder caused by mutations in the galactosylceramidase gene. The objective of the study was to present information about the fatty acid (FA) composition of the brain and serum of twitcher mice, a mouse model of Krabbe disease, compared to wild type, in order to identify biomarker of disease progression. We defined the FA profiles by identifying the main components present in serum and brain using GC‐EI‐MS analysis. The FA percentage composition was measured and data were analyzed considering the disease and the mouse age as experimental factors. Significant correlations were established, both in brain and in serum, in the fatty acid percentage composition of twitcher compared to wild type mice. The most abundant saturated fatty acid in brain was the palmitic acid (C16:0) with mean values significantly increased in twitcher mouse (p = 0.0142); moreover, three monounsaturated, three polyunsaturated (PUFA) and a plasmalogen were significantly correlated to disease. In the serum highly significant differences were observed between the two groups for three polyunsaturated fatty acids. In fact, the docosahexaenoic acid (C22:6n3c) content was significantly increased (p = 0.0116), while the C20 PUFA (C20:3n6c and C20:5n3c) were significantly decreased in twitcher serum samples. Our study shows a specific FA profile that may help to define a possible pattern that could distinguish between twitcher and wild type; these data are likely to provide insight in the identification of new biomarkers to monitor the disease progression and thereby permit the critical analysis of therapeutic approaches.     

Scalaradial, a dialdehyde-containing marine metabolite that causes an unexpected noncovalent PLA2 Inactivation

Several marine terpenoids that contain at least one reactive aldehyde group, such as manoalide and its congeners, possess interesting anti-inflammatory activities that are mediated by the covalent inactivation of secretory phospholipase A(2) (sPLA(2)). Scalaradial, a 1,4-dialdehyde marine terpenoid that was isolated from the sponge Cacospongia mollior, is endowed with a relevant anti-inflammatory profile, both in vitro and in vivo, through selective sPLA(2) inhibition. Due to its peculiar dialdehyde structural feature, it has been proposed that scalaradial exerts its enzymatic inactivation by means of an irreversible covalent modification of its target. In the context of our on-going research on anti-PLA(2) natural products and their interaction at a molecular level, we studied scalaradial in an attempt to shed more light on the molecular mechanism of its PLA(2) inhibition. A detailed analysis of the reaction profile between scalaradial and bee venom PLA(2), a model sPLA(2) that shares a high structural homology with the human synovial enzyme, was performed by a combination of spectroscopic techniques, chemical reactions (selective modifications, biomimetic reactions), and classical protein chemistry (such as proteolytic digestion, HPLC and mass spectrometry), along with molecular modeling studies. Unexpectedly, our data clearly indicated the noncovalent forces to be the leading event in the PLA(2) inactivation process; thus, the covalent modification of the enzyme emerges as only a minor side event in the ligand-enzyme interaction. The overall picture might be useful in the design of SLD analogues as new potential anti-inflammatory compounds that target sPLA(2) enzymes.     

Influence of molecular architecture and processing on properties of semiconducting arylacetylene: Insulating poly(vinylidene fluoride) blends

Blends of chemically readily accessible, small-molecular arylacetylene derivatives with poly(vinylidene fluoride) (PVDF) are presented that allow reliable solution processing of field-effect transistor (FET) architectures with electronic characteristics comparable to those of the neat semiconductors. We demonstrate that having the chemical means and corresponding processing protocols to control solid-state microstructures by either adjusting the chemical nature of the organic semiconductor, blend composition or deposition temperature, permit straight-forward comparison between materials and allow probing if electronic characteristics are affected by the chemical structure of the organic semiconductor and/or selected processing protocols.     

The Rocky Road from Preclinical Findings to Successful Targeted Therapy in Pleural Mesothelioma

Pleural mesothelioma (PM) is a rare and aggressive disease that arises from the mesothelial cells lining the pleural cavity. Approximately 80% of PM patients have a history of asbestos exposure. The long latency period of 20–40 years from the time of asbestos exposure to diagnosis, suggests that multiple somatic genetic alterations are required for the tumorigenesis of PM. The genomic landscape of PM has been characterized by inter- and intratumor heterogeneity associated with the impairment of tumor suppressor genes such as CDKN2A, NF2, and BAP1. Current systemic therapies have shown only limited efficacy, and none is approved for patients with relapsed PM. Advances in understanding of the molecular landscape of PM has facilitated several biomarker-driven clinical trials but so far, no predictive biomarkers for targeted therapies are in clinical use. Recent advances in the PM genetics have provided optimism for successful molecular strategies in the future. Here, we summarize the molecular mechanism underlying PM pathogenesis and review potential therapeutic targets.     

众多产品亮相Wescon2004大会

今年的Wescon2004国际技术会议Wescon于2004．年9月21日至23日在美国加利福尼亚州阿纳海姆的阿纳海姆会议中心举行,与EnterpriseIntegrationExpo(研讨国防工业中以网络为中心的运作模式所产生的影响)和NANOWord(一项以纳米技术的教育、培训和商业应用展示为主线的活动)同地举行。来自众多学术领域的参展机构展示了其最新产品和技术。     

Co-manipulation with a library of virtual guiding fixtures

Virtual guiding fixtures constrain the movements of a robot to task-relevant trajectories, and have been successfully applied to, for instance, surgical and manufacturing tasks. Whereas previous work has considered guiding fixtures for single tasks, in this paper we propose a library of guiding fixtures for multiple tasks, and propose methods for (1) creating and adding guides based on machine learning; (2) selecting guides on-line based on probabilistic implementation of guiding fixtures; (3) refining existing guides based on an incremental learning method. We demonstrate in an industrial task that a library of guiding fixtures provides an intuitive haptic interface for joint human–robot completion of tasks, and improves performance in terms of task execution time, mental workload and errors.