Cutaneous infections by nontuberculous mycobacteria (NTM) are not usual but their relative importance has changed during the last few years and still further changes are expected. This study comprised 13 patients from whom NTM were recovered from skin biopsy specimens, sinus exudates or cutaneous abscesses. All samples were processed according to standard methods, and the isolates were identified by biochemical testing. Skin biopsy specimens, when available, were processed for histopathological study. The clinical records of the patients were reviewed, and the relevant clinical, microbiological and epidemiological data collected. The clinical manifestations were noted to be relatively nonspecific and consisted of draining sinuses, abscesses, ulcers and nodules with multicentric or sporotrichoid patterns. Tissue culture isolated Mycobacterium fortuitum complex in nine patients, M. avium in three, and M. marinum in one. In the nine patients studied by histopathology, various patterns were observed. These included dermo-hypodermal abscesses, suppurative granulomas, tuberculoid granulomas and granulomas with a perifollicular distribution. Cutaneous lesions can thus be the first and the only sign of NTM disease, and culture still remains the definitive diagnostic procedure.
A direct torque control (DTC) strategy for dual three-phase induction motor drives is discussed in this paper. The induction machine has two sets of stator three-phase windings spatially shifted by 30 electrical degrees. The DTC strategy is based on a predictive algorithm and is implemented in a synchronous reference frame aligned with the machine stator flux vector. The advantages of the discussed control strategy are constant inverter switching frequency, good transient and steady-state performance, and low distortion of machine currents with respect to direct self-control (DSC) and other DTC schemes with variable switching frequency. Experimental results are presented for a 10-kW DTC dual three-phase induction motor drive prototype.
SUMMARYCytotoxic T cells (CTL) may play an important role in host defence against mycobacterial infections. CD4 CTL are preferentially induced by mycobacteria, but both CD4 and CD8 CTL may be necessary components of a protective immune response. The 65-kD mycobacterium heat shock protein (hsp65) is a poor inducer of CTL in multibacillary leprosy (MB) patients. In this study we evaluate the possible role of cytokines in modulating the cytotoxic activity of CTL from leprosy patients and normal individuals (N) against autologous macrophages presenting Mycobacterium leprae hsp65. Our results show that hsp65-specific CTL were generated from both CD4 and CD8 lymphocytes. In N, individual cytokines as well as the combination of them were able to modify the hsp65-induced cytotoxic activity. The effect of cytokines on leprosy patients' lymphocytes was different in MB and paucibacillary (PB) patients. Thus, IL-6, IL-2, IFN-g or TNF-a did not modify the generation of hsp65-CTL from either MB (with or without an erythema nodosum episode (ENL)) or PB. In all the patients the simultaneous addition of two cytokines was required in order to increase CTL generation. In MB, IL-6 plus IFN-g or IL-2 increased both CD4 and CD8 CTL, while TNF-a plus IFN-g up-regulated only CD4 CTL. In PB, CD8 CTL were prominent with IL-6 plus IFN-g, while the increase was significant in CD4 CTL with IL-6 plus IL-2. Down-regulation of CTL was observed by addition of IL-4, IL-10, anti-IFN-g or anti-TNFa in N controls. Our data demonstrate that IFN-g and TNF-a must be present for at least the first 60 h of the induction stage in order to generate full hsp65 CTL. Hence, IFN-g and TNF-a would be key factors in the generation of hsp65 CTL.
Despite the promising features of neural interfaces, their trade-off between information transfer and invasiveness has limited translation and viability outside research settings. Here, we present a non-invasive neural interface that provides access to spinal motoneuron activities from a sensor band at the wrist. The interface decodes electric signals present at the tendon endings of the forearm muscles by using a model of signal generation and deconvolution. First, we evaluated the reliability of the interface to detect motoneuron firings, and thereafter we used the decoded neural activity for the prediction of finger movements in offline and real-time conditions. The results showed that motoneuron activity decoded from the wrist accurately predicted individual and combined finger commands and therefore allowed for highly accurate real-time control. These findings demonstrate the feasibility of a wearable, non-invasive, neural interface at the wrist for precise real-time control based on the output of the spinal cord.
A number of novel paclitaxel (Taxol®) analogs that contain modifications at the C 2 , C 7 and C 10 position have been prepared during the course of a taxol SAR study. These analogs include deoxygenated, fluorinated and C 7 -C 19 cyclopropane paclitaxel derivatives. Several very interesting skeletal rearrangements within the taxol and baccatin core were also discovered while developing analog syntheses. The details of the chemistry and the biological evaluation of these analogs will be discussed.Paclitaxel (Taxol®) 1, a highly oxygenated diterpenoid isolated from the bark of Taxus brevifolia (7), has recently been approved for the treatment of advanced ovarian cancer (2). In the ongoing clinical trials involving breast and lung cancer, taxol has also demonstrated clinical potential (3). Paclitaxel functions by arresting cell replication in the mitotic phase of the cell cycle. These effects are attributed to paclitaxel's ability to polymerize tubulin into highly stable microtubules (4). The discovery of paclitaxel's unique antimitotic mechanism and its clinical impact have stimulated intensive research efforts that are aimed at designing novel analogs with improved biological profiles (5).The structure of paclitaxel 1 and its semisynthetic side chain analog, docetaxel (Taxotere®) 2, are shown in Figure 1. Figure 2 contains the structures of baccatin III 3 and 10-desacetylbaccatin III (10-DAB), 4, important precursors of the clinically active taxanes. 10-DAB, a natural product from Taxus baccata (6), is being used by BristolMyers Squibb as a starting material for the semisynthesis of paclitaxel 1. Likewise, Rhône-Poulenc Rorer utilizes the same compound as their starting material in the semisynthesis of docetaxel 2. It should be pointed out that Taxotere® 2 is more potent than Taxol® 1 in certain in vitro assays and in vivo models, and is currently in clinical trials in Europe and Japan (7).Our involvement in the study of paclitaxel's SAR began four years ago when relatively little was known about the subject (#). The initial goal of our research was to systematically modify each of the functional groups on the core, such as, the C2 benzoate (9), C10 acetate (10), C7 hydroxyl group (77), and oxetane ring (72), and then to subsequently evaluate the in vitro activity of these modified analogs. The initial results from our core SAR study thus form the topics of this article and they are: (i) deoxygenation at C 2 , C7 and C10; (ii) fluorination studies at C7; (iii) regioselective oxetane ring opening chemistry.
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