Annealing characteristics of neutron irradiated silicon transistors

When a transistor is subjected to neutron irradiation, a component of base current proportional to neutron fluence is induced. From the effects of annealing on the base and collector currents, the conclusion was drawn that there is an apparent difference in the annealing characteristics between the neutral and the space-charge regions of the semiconductor device. This study of the anomalous annealing indicates that the neutron-induced component of base current is a result of one, or a combination, of the following mechanisms: a quasi-tunneling recombination phenomena in the emitter-base space-charge region, or an influence of the p-n junction electric field on the formation, annealing, and electronic behavior of the neutron-induced defect centers. A field dependence of the formation and annealing of the neutron-induced defects appears to be present both during the introduction and annealing of the neutron-induced defect centers. It could not be finally determined whether or not the quasi-tunneling phenomena occurred although it can be shown on theoretical grounds that it is possible for such phenomena to occur. The annealing characteristics of the defects, as represented by changes in the collector and base currents, have been obtained. Three sets of devices were irradiated and then annealed, with one set having a forward bias during annealing, one set having no bias, and one set having a reverse bias. The dependence of the field on annealing is present but appears quite complex. The presence of the externally applied electric field during annealing appears to influence the annealing of neutron-induced defects similarly, regardless of whether the junction is forward or reverse biased --Abstract, page i-ii

In vivo kinetic approach reveals slow SOD1 turnover in the CNS

Therapeutic strategies that target disease-associated transcripts are being developed for a variety of neurodegenerative syndromes. Protein levels change as a function of their half-life, a property that critically influences the timing and application of therapeutics. In addition, both protein kinetics and concentration may play important roles in neurodegeneration; therefore, it is essential to understand in vivo protein kinetics, including half-life. Here, we applied a stable isotope-labeling technique in combination with mass spectrometric detection and determined the in vivo kinetics of superoxide dismutase 1 (SOD1), mutation of which causes amyotrophic lateral sclerosis. Application of this method to human SOD1-expressing rats demonstrated that SOD1 is a long-lived protein, with a similar half-life in both the cerebral spinal fluid (CSF) and the CNS. Additionally, in these animals, the half-life of SOD1 was longest in the CNS when compared with other tissues. Evaluation of this method in human subjects demonstrated successful incorporation of the isotope label in the CSF and confirmed that SOD1 is a long-lived protein in the CSF of healthy individuals. Together, the results of this study provide important insight into SOD1 kinetics and support application of this technique to the design and implementation of clinical trials that target long-lived CNS proteins

Will an increase in body temperature during status epilepticus in rat pups affect the extent and nature of damage to the hippocampus?

Febrile seizures are epileptic seizures, arising in connection with febrile conditions in children of prechool age. In adults with epilepsy is often present a history of febrile status epilepticus, seizure whose duration is longer than 20 minutes. To study the role of febrile status epilepticus (FSE) in the development of epilepsy and neuronal damage, it is necessary to have a relevant animal models. This work is focused on the morphological analysis of the new created model of febrile status epilepticus, using a combination of short-term hyperthermia and chemical induced status epilepticus at 10 days old rats. In adulthood, the animals were examined by video/EEG monitoring, and then morphometric analysis. The aim of this study was to determine the importance of short-term hyperthermia during SE for neuropathological changes using stereological measurements of hippocampal volume

High activation of STAT5A drives peripheral T-cell lymphoma and leukemia

Recurrent gain-of-function mutations in the transcription factors S7AT5A and much more in STAT5B were found in hematopoietic malignancies with the highest proportion in mature T- and natural killer-cell neoplasms (peripheral T-cell lymphoma, PTCL). No targeted therapy exists for these heterogeneous and often aggressive diseases. Given the shortage of models for PTCL, we mimicked graded STAT5A or STAT5B activity by expressing hyperactive Stat5a or STAT5B variants at low or high levels in the hematopoietic system of transgenic mice. Only mice with high activity levels developed a lethal disease resembling human PTCL. Neoplasia displayed massive expansion of CD8(+) T cells and destructive organ infiltration. T cells were cytokine-hypersensitive with activated memory CD8(+). T-lymphocyte characteristics. Histopathology and mRNA expression profiles revealed close correlation with distinct subtypes of PTCL. Pronounced STAT5 expression and activity in samples from patients with different subsets underline the relevance of JAK/STAT as a therapeutic target. JAK inhibitors or a selective STAT5 SH2 domain inhibitor induced cell death and ruxolitinib blocked T-cell neoplasia in vivo. We conclude that enhanced STAT5A or STAT5B action both drive PTCL development, defining both STAT5 molecules as targets for therapeutic intervention