Polymer Fiber Probes Enable Optical Control of Spinal Cord and Muscle Function In Vivo

Restoration of motor and sensory functions in paralyzed patients requires the development of tools for simultaneous recording and stimulation of neural activity in the spinal cord. In addition to its complex neurophysiology, the spinal cord presents technical challenges stemming from its flexible fibrous structure and repeated elastic deformation during normal motion. To address these engineering constraints, we developed highly flexible fiber probes, consisting entirely of polymers, for combined optical stimulation and recording of neural activity. The fabricated fiber probes exhibit low‐loss light transmission even under repeated extreme bending deformations. Using our fiber probes, we demonstrate simultaneous recording and optogenetic stimulation of neural activity in the spinal cord of transgenic mice expressing the light sensitive protein channelrhodopsin 2 (ChR2). Furthermore, optical stimulation of the spinal cord with the polymer fiber probes induces on‐demand limb movements that correlate with electromyographical (EMG) activity.     

Ifosfamide and vinorelbine: an active regimen for patients with relapsed or refractory Hodgkin's disease

Twenty-six patients with relapsed or refractory Hodgkin's disease (HD) were treated with an intensive salvage regimen combining ifosfamide (3000 mg/m2/d, days 1-4 through continuous intravenous infusion) and vinorelbine (25 mg/m2, i.v. days 1 and 5) with mesna uroprotection and G-CSF support. Courses were given at 3-week intervals. Ten patients achieved a complete and 10 patients a partial response, yielding an overall response rate of 77%. The main toxic effect was neutropenia and the combination was well tolerated.     

Tunable chirped fibre Bragg grating device controlled by variablemagnetic fields

A novel dynamic chirping fibre Bragg grating device based on a magnetic field applied to a magnetostrictive transducer capable of tuning its dispersion is presented. Chirping ranges up to 300 ps/nm have been demonstrated, which are suitable for several applications such as tunable transversal filtering and dynamic dispersion compensation     

Tumor necrosis factor-alpha enhances antitumor effects of radiation against glioma xenografts

Benzodiazepine discontinuation is characterized by a syndrome of increased activity and reduced seizure threshold that is similar to effects mediated by the glutamatergic system. To elucidate the involvement of the glutamatergic system in benzodiazepine tolerance and discontinuation, we administered lorazepam, the NMDA antagonist CPP, and the combination of these compounds either concomitantly or consecutively to mice via osmotic pumps and evaluated pentylenetetrazole-induced seizure threshold, open-field activity, and benzodiazepine receptor binding during and after chronic administration. Animals receiving lorazepam alone developed partial tolerance at 7 days and complete tolerance at 14 days to the anticonvulsant effects of lorazepam. This effect was partly attenuated by CPP coadministration with lorazepam. This combination produced only partial tolerance. A reduction in seizure threshold was observed 4 days after discontinuation of lorazepam alone. This effect was abolished by coadministration of CPP with lorazepam and by CPP administration during the withdrawal period. Benzodiazepine binding in most structures examined was significantly reduced at 14 days during chronic lorazepam administration (versus 1 day), and coadministration of CPP did not alter this decrement. After lorazepam discontinuation, binding was increased at 4 and 7 days versus chronically treated animals and versus vehicle within the cerebral cortex. This effect was abolished by coadministration of CPP as well as by CPP administration during the lorazepam withdrawal period. These data support the involvement of the glutamatergic system in benzodiazepine tolerance and discontinuation.     

The Large Electrochemical Capacitance of Microporous Doped Carbon Obtained by Using a Zeolite Template

A novel microporous templated carbon material doped with nitrogen is synthesized by using a two‐step nanocasting process using acrylonitrile (AN) and propylene as precursors, and Na–Y zeolite as a scaffold. Liquid‐phase impregnation and in situ polymerization of the nitrogenated precursor inside the nanochannels of the inorganic scaffold, followed by gas‐phase impregnation with propylene, enables pore‐size control and functionality tuning of the resulting carbon material. The material thereby obtained has a narrow pore‐size distribution (PSD), within the micropore range, and a large amount of heteroatoms (i.e., oxygen and nitrogen). In addition, the carbon material inherits the ordered structure of the inorganic host. Such features simultaneously present in the carbon result in it being ideal for use as an electrode in a supercapacitor. Although presenting a moderately developed specific surface area (S_BET = 1680 m² g^–1), the templated carbon material displays a large gravimetric capacitance (340 F g^–1) in aqueous media because of the combined electrochemical activity of the heteroatoms and the accessible porosity. This material can operate at 1.2 V in an aqueous medium with good cycleability—‐beyond 10 000 cycles—and is extremely promising for use in the development of high‐energy‐density supercapacitors.     

Determining suitability of a fly ash for silica extraction and zeolite synthesis

Zeolitic material is obtained from fly ash both by direct conversion of the ash or from SiO₂ extracts obtained from fly ash. This study focuses on determining the suitability of a fly ash for SiO₂ extraction and for zeolite synthesis by direct conversion. The SiO₂ extraction experiments from different fly ashes show that the main parameters governing the SiO₂ extraction are: (a) a high bulk SiO₂ content (>52%, for obtaining an extraction yield of 100 g SiO₂ kg^?1) in the starting fly ash, (b) a high proportion (>55%) of the bulk SiO₂ present in the degradable glass matrix and the highly soluble opaline fraction, and (c) a high bulk SiO₂/Al₂O₃ ratio (>2.0) of the fly ash. The results from experiments of zeolite synthesis by direct conversion demonstrate that the most important criteria for the selection of a fly ash for this process are: (a) a high content of Al₂O₃ and SiO₂(>65%) (b) a high glass content (>63%) and (c) relatively low SiO₂/Al₂O₃ ratio (<2.0). Multivariate analysis confirms the importance of the above‐mentioned variables and shows some additional variables that have influence on ash behaviour under alkaline conditions. It quantifies the use of those variables for determining the suitability of ashes for SiO₂ extraction and zeolite synthesis and is able to distinguish between the two. Copyright © 2004 Society of Chemical Industry     

Regulation of BRCA1 and BRCA2 expression in human breast cancer cells by DNA-damaging agents

Germline mutations in the breast cancer susceptibility genes BRCA1 and BRCA2 have been linked to the development of breast cancer, ovarian cancer, and other malignancies. Recent studies suggest that the BRCA1 and BRCA2 gene products may function in the sensing and/or repair of DNA damage. To investigate this possibility, we determined the effects of various DNA-damaging agents and other cytotoxic agents on the mRNA levels of BRCA1 and BRCA2 in the MCF-7 and other human breast cancer cell lines. We found that several agents, including adriamycin (a DNA intercalator and inhibitor of topoisomerase II), camptothecin (a topoisomerase I inhibitor), and ultraviolet radiation induced significant decreases in BRCA1 and BRCA2 mRNA levels. Decreased levels of BRCA1 and BRCA2 mRNAs were observed within 6-12 h after treatment with adriamycin and persisted for at least 72 h. Adriamycin also induced decreases in BRCA1 protein levels; but these decreases required several days. U.V. radiation induced dose-dependent down-regulation of BRCA1 and BRCA2 mRNAs, with significant decreases in both mRNAs at doses as low as 2.5 J/m2, a dose that yielded very little cytotoxicity. Adriamycin-induced down-regulation of BRCA1 and BRCA2 mRNAs was first observed at doses that yielded relatively little cytotoxicity and little or no apoptotic DNA fragmentation. Adriamycin and U.V. radiation induced distinct dose- and time-dependent alterations in the cell cycle distribution; but these alterations did not correlate well with corresponding changes in BRCA1 and BRCA2 mRNA levels. However, the adriamycin-induced reduction in BRCA1 and BRCA2 mRNA levels was correlated with p53 functional status. MCF-7 cells transfected with a dominant negative mutant p53 (143 val-->ala) required at least tenfold higher doses of adriamycin to down-regulate BRCA1 and BRCA2 mRNAs than did parental MCF-7 cells or control-transfected MCF-7 clones. These results suggest that BRCA1 and BRCA2 may play roles in the cellular response to DNA-damaging agents and that there may be a p53-sensitive component to the regulation of BRCA1 and BRCA2 mRNA expression.     

Application of the Repeated Measures (Split-Plot) Design to the Development of Processes for Drug Substances

A case study from the chemical and pharmaceutical industries is used to show the value of the repeated measures design in developing processes for drug substances. This article advocates the use of the repeated measures design in situations that commonly arise in the chemical and pharmaceutical industries when repeated measurements are taken on the same experimental unit, instead of the common practice of comparing only individual conditions, a procedure that is inappropriate in many cases. One of the most important advantages of applying the repeated measures design is the abundance of data that can be obtained by taking into account the entire response curve instead of only isolated individual points on it.