Neuroproteomics and systems biology-based discovery of protein biomarkers for traumatic brain injury and clinical validation

The rapidly growing field of neuroproteomics has expanded to track global proteomic changes underlying various neurological conditions such as traumatic brain injury (TBI), stroke, and Alzheimer's disease. TBI remains a major health problem with approximately 2?million incidents occurring annually in the United States, yet no affective treatment is available despite several clinical trials. The absence of brain injury diagnostic biomarkers was identified as a significant road-block to therapeutic development for brain injury. Recently, the field of neuroproteomics has undertaken major advances in the area of neurotrauma research, where several candidate markers have been identified and are being evaluated for their efficacy as biological biomarkers in the field of TBI. One scope of this review is to evaluate the current status of TBI biomarker discovery using neuroproteomics techniques, and at what stage we are at in their clinical validation. In addition, we will discuss the need for strengthening the role of systems biology and its application to the field of neuroproteomics due to its integral role in establishing a comprehensive understanding of specific brain disorder and brain function in general. Finally, to achieve true clinical input of these neuroproteomic findings, these putative biomarkers should be validated using preclinical and clinical samples and linked to clinical diagnostic assays including ELISA or other high-throughput assays.     

Electrical reflection coefficient and velocity shift for groove gratings

The electrical reflection coefficient r(e) and velocity shift (Deltanu/nu)(e) for grooves has never been formulated. All previous calculations for r(e) and (Deltanu/nu)(e) have used formulas valid for the reflection of a surface acoustic wave (SAW) from an array of conducting strips. However, the discontinuity in electrical boundary conditions leading to these formulas does not exist in groove gratings. A new expression for the electrical reflection coefficient and velocity shift for some material overlays is derived from both the variational principle and perturbation theory. The results for various substrates are compared to show the agreement between the two approaches. The implications of this new formulation for the design of grooved arrays on various materials are discussed, effectively resolving the discrepancy between theory and experiment.     

Inhibition of feline collateral vessel development following experimental thrombolic occlusion

We compared development of feline hindlimb collateral circulation after acute occlusion of the terminal aorta by ligation, thrombus formation, and formation of a "closed" aortic loop containing thromboplastin. Collateral circulation development was assessed by aortograms, scintillation scans, neurological signs following occlusion, measurement of hindlimb muscle blood flow, and forelimb and hindlimb temperature. In cats in which aortic occlusion was the result of ligation or thromboplastin in the aortic loop, paralysis was not evident. Aortograms and scintillation scans indicated hindlimb blood flow. Both muscle temperature and blood flow data indicated that the return of blood flow was rapid. The 5th lumbar artery appears to be the origin of the collateral vessels. The mid-zone component is a dorsal and ventral vertebral route and an epaxial muscle route. The reentry components are the 6th or 7th lumbar arteries. The collateral vessels arise from preexisting collateral vessels. Of those cats in which aortic occlusion was the result of a thrombus, all exhibited paralysis. Aortograms, scintillation scans, muscle temperature, and hindlimb blood flow data indicated reduced hindlimb blood flow. The results suggest that the thrombus has an inhibitory effect on the development of collateral circulation.     

Identifying Outliers in Correlated Water Quality Data

Evaluating water quality data for outliers is a good quality control/quality assessment procedure whether the data are used for monitoring or for modeling. Often water quality data are correlated, e.g., carbonaceous biochemical oxygen demand (CBOD) has some correlation with NH3. Univariate methods for identifying outliers do not consider the correlation between variables and may identify too many data points as outliers or miss observations which have extreme ratios between variables, e.g., a raw wastewater sample with relatively low CBOD but high NH3. Testing for outliers using multivariate methods such as the Mahalanobis distance, Jackknife distance, p-values, or Hadi’s automatically incorporates the correlation or covariance between variables and is fundamentally more correct. Such multivariate methods can better identify potential outliers and avoid eliminating valid data.     

The Serotonergic Agonists Quipazine, CGS-12066A, and α-Methylserotonin Alter Motor Activity and Induce Hindlimb Stepping in the Intact and Spinal Rat Fetus.

The effects of serotonergic agonists were examined in intact and spinal fetuses, using an in vivo fetal rat preparation. On Gestational Day 20, fetuses were prepared with a midthoracic or sham spinal transection. Dose-response curves were obtained for quipazine (nonselective 5-hydroxytryptamine [5-HT] agonist; 1.0-10.0 mg/kg), CGS-12066A (5-HT1B agonist; 1.0-30.0 mg/kg), and α-methylserotonin (α-Me-5-HT; 5-HT? agonist; 0.2-15.0 mg/kg). During a 10-min test, each of the agonists (delivered via intraperitoneal injection) influenced fetal behavior: They increased the occurrence of head movements, mouthing, and hindlimb stepping. Quipazine and α-Me-5-HT also promoted hindlimb activity in spinal fetuses. Thus, stimulation of the fetal 5-HT system modulates motor activity at multiple levels of the developing central nervous system. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Computer user verification using login string keystroke dynamics

The keystroke dynamics of a computer user's login string provide a characteristic pattern that can be used for identity verification. Timing vectors for several hundred login attempts were collected for ten “valid” users and ten “forgers”, and classification analysis was applied to discriminate between them. Three different classifiers were applied, and in each case the key hold times were more effective features for discrimination than the interkey times. Best performance was achieved by an inductive learning classifier using both interkey and hold times. A high rate of typographical errors during login entry is reported. In practice, these are usually corrected errors-that is, they are strings which include backspaces to correct earlier errors-but their presence confounds the use of typing-style analysis as a practical means of securing access to computer systems     

以公共结构及语言进行应用系统一体化

介绍了美国佛罗里达电力照明公司对主要业务系统基于公共结构及语言,进行信息集成的工作过程和经验,对企业信息一体化的技术内容和框架结构做了总体介绍,并根据应用实际阐述了公共信息模型的扩展,对其他企业开展信息系统一体化工作具有一定的借鉴作用.     

The effect of hydrogen, tritium and decay helium on the fracture toughness of a stainless steel superalloy

The effect of tritium and helium-3 on tensile properties, fracture toughness properties and fracture mechanisms was studied in a modified A-286 alloy, and compared to the effects of hydrogen. The yield strength and work hardening rate showed no sensitivity to helium-3 in the concentration range studied, but the tensile ductility decreased with increased helium concentration. Fracture toughness with tritium plus helium decreased below that obtained with hydrogen alone. Helium-3 caused a decrease in tensile ductility and fracture toughness because it precipitates on and induces failure at grain boundaries.     

Redox properties of human medium-chain acyl-CoA dehydrogenase, modulation by charged active-site amino acid residues

The modulation of the electron-transfer properties of human medium-chain acyl-CoA dehydrogenase (hwtMCADH) has been studied using wild-type and site-directed mutants by determining their midpoint potentials at various pH values and estimating the involved pKs. The mutants used were E376D, in which the negative charge is retained; E376Q, in which one negative charge (pKa approximately 6. 0) is removed from the active center; E99G, in which a different negative charge (pKa approximately 7.3) also is affected; and E376H (pKa approximately 9.3) in which a positive charge is present. Em for hwtMCADH at pH 7.6 is -0.114 V. Results for the site-directed mutants indicate that loss of a negative charge in the active site causes a +0.033 V potential shift. This is consistent with the assumption that electrostatic interactions (as in the case of flavodoxins) and specific charges are important in the modulation of the electron-transfer properties of this class of dehydrogenases. Specifically, these charge interactions appear to correlate with the positive Em shift observed upon binding of substrate/product couple to MCADH [Lenn, N. D., Stankovich, M. T., and Liu, H. (1990) Biochemistry 29, 3709-3715], which coincides with a pK increase of Glu376-COOH from approximately 6 to 8-9 [Rudik, I., Ghisla, S., and Thorpe, C. (1998) Biochemistry 37, 8437-8445]. From the pH dependence of the midpoint potentials of hwtMCADH two mechanistically important ionizations are estimated. The pKa value of approximately 6.0 is assigned to the catalytic base, Glu376-COOH, in the oxidized enzyme based on comparison with the pH behavior of the E376H mutant, it thus coincides with the pK value recently estimated [Vock, P., Engst, S., Eder, M., and Ghisla, S. (1998) Biochemistry 37, 1848-1860]. The pKa of approximately 7.1 is assigned to Glu376-COOH in reduced hwtMCADH. Comparable values for these pKas for Glu376-COOH in pig kidney MCADH are pKox = 6.5 and pKred = 7.9. The Em measured for K304E-MCADH (a major mutant resulting in a deficiency syndrome) is essentially identical to that of hwtMCADH, indicating that the disordered enzyme has an intact active site.