Involvement of zinc in intracellular oxidant/antioxidant balance

Methods to directly and indirectly identify the central sulcus are presented. In the axial plan, direct method is remarkable but obviously requires good visualization of the sulci in the central region. Sulci are readily visible in 90% of the cases on CT scans and in 50% of the cases on MRI. The method can also be applied when tumoral development erases the cerebral sulci by direct lecture of the controlateral rolandic region and right-left transfer. Within the precision limits of the method, it can be considered that the central sulci are symmetrical. The main signs are: the relative morphologies of the superior frontal sulcus and the precentral sulcus, the hook-shaped aspect of the middle part of the central sulcus, the internal end of the central sulcus projection anteriorly to the pars marginalis, the bifid nature of the internal end of the posterior central sulcus contouring the pars marginalis, and the lesser thickness of the posterior central gyrus compared with the precentral gyrus. The indirect method is less precise and is used when the direct method is unsuccessful. The central sulcus is identified on the sagittal images and, using the lateral view of the skull as a reference image, the topographic information is transferred to the axial images.     

Trends in registered psychiatric morbidity and forecasting psychotropic drug needs in Bulgarian hospitals

Registered psychiatric morbidity in Bulgaria as a whole and particularly in Plovdiv, the second largest region of the country, was assessed. Three aspects of psychotropic drug usage were analysed, namely, changes in registered psychotropic drugs, the prescribed daily dose (PDD) values for 2 years, and the preferred therapeutic schemes, and drug usage and needs in a psychiatric hospital with 365 beds. This was done by time series analysis for evaluation of psychiatric morbidity and drug consumption data, calculation of PDD for psychotropic medicines, and, based on a modification of the World Health Organization's morbidity method, assessment and prediction of drug use and needs in Plovdiv hospital. The results indicated that the registered morbidity had increased by 4% over the period 1989-93 to 2,427 psychiatric patients per 100,000 people. The increased consumption of especially benzodiazepines and sedative medicines was analyzed. Diazepam was prescribed the most often (91.1%), followed by levomepromazine (86.4%), haloperidol (82.7%), etc. Future drug consumption in Plovdiv hospital is expected to decrease because therapeutic practice in hospitals has been revised and improved on the basis of the World Health Organization's recommendations.     

Modulation of cAMP-dependent protein kinase by derivatives of chondroitin sulfate

Here, we report investigations about the direct effect of glycosaminoglycans, such as dermatan sulfate, chondroitin 4- and 6-sulfate upon cAMP-dependent protein kinase activity. The results indicate that glycosaminoglycans strongly influence the phosphorylation activity of this enzyme against histone type IIa and [Val6, Ala7]-kemptide. While chondroitin 4-sulfate and dermatan sulfate exhibit inhibitory effects, chondroitin 6-sulfate shows a stimulating effect. In addition, the chondroitin 6-sulfate is also able to reduce the chondroitin 4-sulfate and dermatan sulfate specific inhibition.     

Mutational analysis of the three cysteines and active-site aspartic acid 103 of ketosteroid isomerase from Pseudomonas putida biotype B

In order to clarify the roles of three cysteines in ketosteroid isomerase (KSI) from Pseudomonas putida biotype B, each of the cysteine residues has been changed to a serine residue (C69S, C81S, and C97S) by site-directed mutagenesis. All cysteine mutations caused only a slight decrease in the k(cat) value, with no significant change of Km for the substrate. Even modification of the sulfhydryl group with 5,5'-dithiobis(2-nitrobenzoic acid) has almost no effect on enzyme activity. These results demonstrate that none of the cysteines in the KSI from P. putida is critical for catalytic activity, contrary to the previous identification of a cysteine in an active-site-directed photoinactivation study of KSI. Based on the three-dimensional structures of KSIs with and without dienolate intermediate analog equilenin, as determined by X-ray crystallography at high resolution, Asp-103 was found to be located within the range of the hydrogen bond to the equilenin. To assess the role of Asp-103 in catalysis, Asp-103 has been replaced with either asparagine (D103N) or alanine (D103A) by site-directed mutagenesis. For D103A mutant KSI there was a significant decrease in the k(cat) value: the k(cat) of the mutant was 85-fold lower than that of the wild-type enzyme; however, for the D103N mutant, which retained some hydrogen bonding capability, there was a minor decrease in the k(cat) value. These findings support the idea that aspartic acid 103 in the active site is an essential catalytic residue involved in catalysis by hydrogen bonding to the dienolate intermediate.     

Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy

The immune-mediated graft-versus-leukemia effect is important to prevent relapse after allogeneic progenitor cell transplantation. This process requires engraftment of donor immuno-competent cells. The objective of this study was to assess the feasibility of achieving engraftment of allogeneic peripheral blood or bone marrow progenitor cell after purine analog containing nonmyeloablative chemotherapy. Patients with advanced leukemia or myelodysplastic syndromes (MDS) who were not candidates for a conventional myeloablative therapy because of older age or organ dysfunction were eligible. All patients had an HLA-identical or one-antigen-mismatched related donor. Fifteen patients were treated (13 with acute myeloid leukemia and 2 with MDS). The median age was 59 years (range, 27 to 71 years). Twelve patients were either refractory to therapy or beyond first relapse. Eight patients received fludarabine at 30 mg/m2/d for 4 days with idarubicin at 12 mg/m2/d for 3 days and ara-c at 2 g/m2/d for 4 days (n = 7) or melphalan at 140 mg/m2/d (n = 1). Seven patients received 2-chloro-deoxyadenosine at 12 mg/m2/d for 5 days and ara-C 1 at g/m2/d for 5 days. Thirteen patients received allogeneic peripheral blood stem cells and 1 received bone marrow after chemotherapy. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methyl-prednisolone. Treatment was generally well tolerated, with only 1 death from multiorgan failure before receiving stem cells. Thirteen patients achieved a neutrophil count of greater than 0.5 x 10(9)/L a median of 10 days postinfusion (range, 8 to 17 days). Ten patients achieved platelet counts of 20 x 10(9)/L a median of 13 days after progenitor cell infusion (range, 7 to 78 days). Eight patients achieved complete remissions (bone marrow blasts were < 5% with neutrophil recovery and platelet transfusion independence) that lasted a median of 60 days posttransplantation (range, 34 to 170+ days). Acute GVHD grade > or = 2 occurred in 3 patients. Chimerism analysis of bone marrow cells in 6 of 8 patients achieving remission showed > or = 90% donor cells between 14 and 30 days postinfusion, and 3 of 4 patients remaining in remission between 60 and 90 days continued to have > or = 80% donor cells. We conclude that purine analog-containing nonmyeloablative regimens allow engraftment of HLA-compatible hematopoietic progenitor cells. This approach permits us to explore the graft-versus-leukemia effect without the toxicity of myeloablative therapy and warrants further study in patients with leukemia who are ineligible for conventional transplantation with myeloablative regimens either because of age or concurrent medical conditions.     

Structuring communication software for quality-of-serviceguarantees

We propose architectural mechanisms for structuring host communication software to provide QoS guarantees. We present and evaluate a QoS sensitive communication subsystem architecture for end hosts that provides real time communication support for generic network hardware. This architecture provides services for managing communication resources for guaranteed QoS (real time) connections, such as admission control, traffic enforcement, buffer management, and CPU and link scheduling. The architecture design is based on three key goals: maintenance of QoS guarantees on a per connection basis, overload protection between established connections, and fairness in delivered performance to best effort traffic. Using this architecture we implement real time channels, a paradigm for real time communication services in packet switched networks. The proposed architecture features a process per channel model that associates a channel handler with each established channel. The model employed for handler execution is one of “cooperative” preemption, where an executing handler yields the CPU to a waiting higher priority handler at well defined preemption points. The architecture provides several configurable policies for protocol processing and overload protection. We present extensions to the admission control procedure for real time channels to account for cooperative preemption and overlap between protocol processing and link transmission at a sending host. We evaluate the implementation to demonstrate the efficacy with which the architecture maintains QoS guarantees on outgoing traffic while adhering to the stated design goals     

A comparative analysis of methods for pruning decision trees

In this paper, we address the problem of retrospectively pruning decision trees induced from data, according to a top-down approach. This problem has received considerable attention in the areas of pattern recognition and machine learning, and many distinct methods have been proposed in literature. We make a comparative study of six well-known pruning methods with the aim of understanding their theoretical foundations, their computational complexity, and the strengths and weaknesses of their formulation. Comments on the characteristics of each method are empirically supported. In particular, a wide experimentation performed on several data sets leads us to opposite conclusions on the predictive accuracy of simplified trees from some drawn in the literature. We attribute this divergence to differences in experimental designs. Finally, we prove and make use of a property of the reduced error pruning method to obtain an objective evaluation of the tendency to overprune/underprune observed in each method     

The held out wings (how) Drosophila gene encodes a putative RNA-binding protein involved in the control of muscular and cardiac activity

In an attempt to identify genes that are involved in Drosophila embryonic cardiac development, we have cloned and characterized a gene whose function is required late in embryogenesis to control heart rate and muscular activity. This gene has been named held out wings (how) because hypomorphic mutant alleles produce adult animals that have lost their ability to fly and that keep their wings horizontal at a 90 degree angle from the body axis. In contrast to the late phenotype observed in null mutants, the How protein is expressed early in the invaginating mesoderm and this expression is apparently under the control of twist. When the different mesodermal lineages segregate, the expression of How becomes restricted to the myogenic lineage, including the cardioblasts and probably all the myoblasts. Antibodies directed against the protein demonstrate that How is localized to the nucleus. how encodes a protein containing one KH-domain which has been implicated in binding RNA. how is highly related to the mouse quaking gene which plays a role at least in myelination and that could serve to link a signal transduction pathway to the control of mRNA metabolism. The properties of the how gene described herein suggest that this gene participates in the control of expression of as yet unidentified target mRNAs coding for proteins essential to cardiac and muscular activity.     

Mathematical foundations for error estimation in numericalsolutions of integral equations in electromagnetics

The problem of error estimation in the numerical solution of integral equations that arise in electromagnetics is addressed. The direct method (Green's theorem or field approach) and the indirect method (layer ansatz or source approach) lead to well-known integral equations both of the first kind [electric field integral equations (EFIE)] and the second kind [magnetic field integral equations (MFIE)]. These equations are analyzed systematically in terms of the mapping properties of the integral operators. It is shown how the assumption that field quantities have finite energy leads naturally to describing the mapping properties in appropriate Sobolev spaces. These function spaces are demystified through simple examples which also are used to demonstrate the importance of knowing in which space the given data lives and in which space the solution should be sought. It is further shown how the method of moments (or Galerkin method) is formulated in these function spaces and how residual error can be used to estimate actual error in these spaces. The condition number of all of the impedance matrices that result from discretizing the integral equations, including first kind equations, is shown to be bounded when the elements are computed appropriately. Finally, the consequences of carrying out all computations in the space of square integrable functions, a particularly friendly Sobolev space, are explained