A phase I/II study of herpes simplex virus type 1 thymidine kinase "suicide" gene therapy for recurrent glioblastoma. Study Group on Gene Therapy for Glioblastoma

Despite extensive surgery for glioblastoma, residual tumor cells always lead to relapse. Gene therapy based on retrovirus-mediated gene transfer of herpes simplex virus type 1 thymidine kinase (HSV-1 TK), which specifically sensitizes dividing cells to ganciclovir (GCV) toxicity, may help eradicate such cells. During glioblastoma surgery, HSV-1 TK retroviral vector-producing cells (M11) were injected into the surgical cavity margins after tumor debulking. After a 7-day transduction period, GCV was administered for 14 days. Safety was assessed by clinical and laboratory evaluations, and efficacy was assessed by MRI-based relapse-free survival at month 4 and by overall survival. Twelve patients with recurrent glioblastoma were treated without serious adverse events related to M11 cell administration or GCV. Quality of life was not negatively influenced by this treatment. Overall median survival was 206 days, with 25% of the patients surviving longer than 12 months. At 4 months after treatment, 4 of 12 patients had no recurrence; their median overall survival was 528 days, compared with 194 days for patients with recurrence (p=0.03 by the log rank test). One patient is still free of detectable recurrence, steroid free and independent, 2.8 years after treatment. Thus, brain injections of M11 retroviral vector-producing cells for glioblastoma HSV-1 TK gene therapy were well tolerated and associated with significant therapeutic responses. These results warrant further development of this therapeutic strategy in brain tumor, including recurrent glioblastoma.     

Karyological, biochemical, and physiological aspects of Callophysus macropterus (Siluriformes, Pimelodidae) from the Solim?es and Negro Rivers (central Amazon)

Karyological characteristics, i.e., diploid number, chromosome morphology and nucleolus organizer regions (NORs), biochemical characteristics, i.e., electrophoretic analysis of blood hemoglobin and the tissue enzymes lactate dehydrogenase (LDH), malate dehydrogenase (MDH), alcohol dehydrogenase (ADH), and phosphoglucose isomerase (PGI), and physiological characteristics, i.e., relative concentration of hemoglobin and intraerythrocytic concentrations of organic phosphates were analyzed for the species Callophysus macropterus collected from Marchantaria Island (white water system--Solim?es River) and Anavilhanas Archipelago (black water system--Negro River). Karyological and biochemical data did not reveal significant differences between specimens collected at the two sites. However, the relative distribution of hemoglobin bands I and III (I = 16.33 +/- 1.05 and III = 37.20 +/- 1.32 for Marchantaria specimens and I = 6.33 +/- 1.32 and III = 48.05 +/- 1.55 for Anavilhanas specimens) and levels of intraerythrocytic GTP (1.32 +/- 0.16 and 2.76 +/- 0.18 for Marchantaria and Anavilhanas specimens, respectively), but not ATP or total phosphate, were significantly different, indicating a physiological adaptation to the environmental conditions of these habitats. It is suggested that C. macropterus specimens from the two collecting sites belong to a single population, and that they adjusted some physiological characteristics to adapt to local environmental conditions.     

Statistical smoothing of neuronal data

The purpose of smoothing (filtering) neuronal data is to improve the estimation of the instantaneous firing rate. In some applications, scientific interest centres on functions of the instantaneous firing rate, such as the time at which the maximal firing rate occurs or the rate of increase of firing rate over some experimentally relevant period. In others, the instantaneous firing rate is needed for probability-based calculations. In this paper we point to the very substantial gains in statistical efficiency from smoothing methods compared to using the peristimulus-time histogram (PSTH), and we also demonstrate a new method of adaptive smoothing known as Bayesian adaptive regression splines (DiMatteo 1, Genovese C R and Kass R E 2001 Biometrika 88 1055-71). We briefly review additional applications of smoothing with non-Poisson processes and in the joint PSTH for a pair of neurons.     

CRM in the European large-scale retail trade: Evidence and perspectives

This article sets forth the main findings of an empirical study carried out among the main actors in the sector of large-scale retailing in Europe, as regards their respective practical experience incrm (Customer Relationship Management) as well as the opportunities offered by the Internet technologies in this field. The evidence collected is checked against the problems expounded in the literature hinging on the following four main questions:

—the existence of national orientations that are taking shape in terms of the uses ofcrm

—the reality of the training processes of companies leading to e-crm as well as the acquisition of the technical and organisational maturity necessary to master these tools

—the variety of those uses and the issue of multichannelling

—the relative benefits of market relationship linked to the development ofcrm procedures

Thus this study offers an overview of emerging trends incrm peculiar to this sector.     

电炉JetBOxTM技术的发展

美国PTI公司发明的专利技术JetBOxTM超音速氧枪喷射系统被证明是一种能有效提高电弧炉产量同时又能减少电炉改造成本的技术.通过在各个炼钢电炉上使用这种独特而有效的化学能输入方式从而获得了良好的效果.由于每个电炉的JetBOxTM系统都是专门设计,能满足每个炼钢车间的不同要求,因此已经被成功地应用在用料篮加料的普通电炉、Consteel电炉、使用DRI/HBI的电炉以及热装铁水的电炉上,同样都获得了良好的运行效果.自2001年以来JetBOxTM系统已经在全世界超过60台不同的电炉上安全而有效地运行着,满足了不同钢厂的要求.     

Characterization of ferroresonant modes in HV substation with CB grading capacitors

This paper reports a ferroresonant experience involving inductive voltage transformers (VT's) in a 400 kV substation equipped with circuit breaker grading capacitors. Field measurements are presented and compared with ATP/EMTP simulation results, showing very good agreement. A parametric analysis has been performed to investigate the effect of the substation capacitance on the occurrence of ferroresonance. Fundamental frequency and sub-harmonic ferroresonant modes have been identified and compiled in a bifurcation diagram. The methodology presented can be used to create risk maps of avoidable switching operations or substation configurations.     

New Stainless Steel Solutions as Economic Alternatives to Classical 1.4301 Austenitic Grades

In the recent situation of a historically high nickel price, austenitic stainless steels, such as 1.4301, became too expensive compared to their actual technical value in many applications. This paper presents two new stainless steel grades developed by ArcelorMittal to replace 1.4301. The first one is a 20%Cr ferritic grade. The second one is a low‐Ni Cu‐bearing austenitic grade. The choices in the compositions are described as a function of the technical requirements, economical target and the production process limitations. The final properties are discussed as a function of the composition and compared with 1.4301 and other existing stainless steels. Finally, the complementarities of these two new grades are highlighted in regard to the different application markets considered.     

Ceramics based on partly stabilized zirconium dioxide: technology,structure, properties,and behavior under dynamic action

Technology is described for manufacturing dense ceramic from very fine powder based on zirconium dioxide partly stabilized with yttrium oxide. Some engineering properties of the manufactured ceramic are defined. Its microstructure and phase composition are studied. Ceramic properties with impact-wave loading are studied, and values of dynamic elastic limit and spalling strength are obtained.     

Light aversion in mice depends on nonimage-forming irradiance detection.

Detection of light in the eye underlies image-forming vision, but also regulates adaptive responses in physiology and behavior. Typically these adaptive responses do not involve image-forming vision, but depend on a relatively absolute measure of brightness (nonimage-forming irradiance detection). The goal of this study was to further understand how image-forming vision and nonimage-forming irradiance detection contribute to the effects of light on behavior. Three light dependent behaviors were assessed in wild-type, Rpe65-/- and rd1 mice. In Rpe65-/- mice, nonimage-forming irradiance detection is severely attenuated, but rod based visual acuity is relatively preserved. In rd1 mice visual acuity is nonrecordable, but nonimage-forming responses are less severely attenuated than Rpe65-/-. Positive masking, an image-forming vision dependent increase in wheel running, was absent in rd1 and restricted to higher irradiances in Rpe65-/-. Negative masking, a suppression of wheel running sensitivity with nonimage-forming irradiance detection input, was increased in rd1, but reduced in Rpe65-/- mice. By contrast, light aversion, an avoidance of brightly lit areas, was abolished in both Rpe65-/- and rd1. This shows that image-forming vision is not sufficient for light aversion, suggesting nonimage-forming irradiance detection motivates this behavior. Further, the differing effects of disease suggest that negative masking and light aversion are distinct responses with specialized nonimage-forming irradiance detection pathways. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Development of Microsatellite Markers in the Branched Broomrape Phelipanche ramosa L. (Pomel) and Evidence for Host-Associated Genetic Divergence

Phelipanche ramosa is a parasitic plant that infects numerous crops worldwide. In Western Europe it recently expanded to a new host crop, oilseed rape, in which it can cause severe yield losses. We developed 13 microsatellite markers for P. ramosa using next-generation 454 sequencing data. The polymorphism at each locus was assessed in a sample of 96 individuals collected in France within 6 fields cultivated with tobacco, hemp or oilseed rape. Two loci were monomorphic. At the other 11 loci, the number of alleles and the expected heterozygosity ranged from 3 to 6 and from 0.31 to 0.60, respectively. Genetic diversity within each cultivated field was very low. The host crop from which individuals were collected was the key factor structuring genetic variation. Individuals collected on oilseed rape were strongly differentiated from individuals collected on hemp or tobacco, which suggests that P. ramosa infecting oilseed rape forms a genetically diverged race. The microsatellites we developed will be useful for population genetics studies and for elucidating host-associated genetic divergence in P. ramosa.