Effects of protein kinase C activators on phorbol ester-sensitive and -resistant EL4 thymoma cells

Phorbol ester-sensitive EL4 murine thymoma cells respond to phorbol 12-myristate 13-acetate with activation of ERK mitogen-activated protein kinases, synthesis of interleukin-2, and death, whereas phorbol ester-resistant variants of this cell line do not exhibit these responses. Additional aspects of the resistant phenotype were examined, using a newly-established resistant cell line. Phorbol ester induced morphological changes, ERK activation, calcium-dependent activation of the c-Jun N-terminal kinase (JNK), interleukin-2 synthesis, and growth inhibition in sensitive but not resistant cells. A series of protein kinase C activators caused membrane translocation of protein kinase C's (PKCs) alpha, eta, and theta in both cell lines. While PKC eta was expressed at higher levels in sensitive than in resistant cells, overexpression of PKC eta did not restore phorbol ester-induced ERK activation to resistant cells. In sensitive cells, PKC activators had similar effects on cell viability and ERK activation, but differed in their abilities to induce JNK activation and interleukin-2 synthesis. PD 098059, an inhibitor of the mitogen activated protein (MAP)/ERK kinase kinase MEK, partially inhibited ERK activation and completely blocked phorbol ester-induced cell death in sensitive cells. Thus MEK and/or ERK activation, but not JNK activation or interleukin-2 synthesis, appears to be required for phorbol ester-induced toxicity. Alterations in phorbol ester response pathways, rather than altered expression of PKC isoforms, appear to confer phorbol ester resistance to EL4 cells.     

Cytoplasmic creatine kinases from giant pandas

The muscle and brain creatine kinases of giant panda have been isolated and purified. The purified muscle and brain enzymes (MM and BB) are homogeneous on both the polyacrylamide gel electrophoresis in the presence and absence of SDS. Both enzymes are dimers, consisting of two identical subunits each with a molecular weight of 42,000 daltons. The characteristics of muscle and brain enzymes have been studied, respectively. The hybridized enzyme, MB, was prepared by hybridization of MM and BB. The kinetic parameters of MM, BB and MB were determined, respectively. The results from modification of SH groups show that the SH groups of panda creatine kinases are essential for their activity and among the all SH groups in the enzyme only one per subunit is essential for enzymatic activity.     

Derivation of HLA-A11/Kb transgenic mice: functional CTL repertoire and recognition of human A11-restricted CTL epitopes

Transgenic mice expressing chimeric human (alpha1 and alpha2 HLA-A11 domains) and murine (alpha3, transmembrane, and cytoplasmic H-2Kb domains) class I molecules were derived. These mice were used as a model system to study the immunogenicity of human CTL epitopes and also to examine the aspects of Ag processing differences of mice vs man. Immunization of these mice with seven known HLA-A11-restricted CTL epitopes emulsified in IFA resulted in vigorous specific CTL responses. A larger panel of 45 A11-binding peptides was used to examine the relationship between immunogenicity in the HLA-A11/Kb transgenic mice and HLA-A11 binding capacity. Twenty-one of 28 (75%) peptides with high binding affinities (50% inhibitory concentration (IC50), 2-50 nM) and 7 of 13 (54%) intermediate binding peptides (IC50, 50-500 nM range) were immunogenic. In parallel, 19 of these peptides were used for in vitro primary immunizations of PBMC derived from HLA-A11 healthy human donors. It was found that 8 of 8 peptides that were able to elicit CTL in primary human in vitro cultures were also immunogenic in HLA-A11/Kb mice. Finally, HLA-A11/Kb transgenic mice were found to generate an A11/Kb restricted CTL response following immunization with influenza virus A/PR/8/34, suggesting that, at least to some extent, A11 epitopes are generated by transgenic mice as a result of natural in vivo processing and presentation.     

Course of functioning in adolescents 1 year after alcohol and other drug treatment.

Clinical course was studied in 131 male and female adolescents with current alcohol use disorder (AUD) at baseline (BL). Participants were classified into 4 groups according to their diagnosis and drinking pattern 1 year later. The 4 groups were compared with each other and with 37 community control participants. Results showed that over half of the clinical sample no longer had a current AUD at 1 year; about 64% were and 36% were not still drinking. BL discriminators of 1-year status were alcohol dependence, other drug use, and coping. All of the clinical groups tended to show improvement at 1 year in the main dependent variables, and the abstainers' level of drug use and coping were comparable with that of the community participants. These findings suggest that many adolescents improve in functioning during the 1 year after alcohol and drug treatment and that a stress and coping model is useful for studying clinical course of AUDs in adolescents. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Optical phaselock receiver with multigigahertz signal bandwidth

Describes a balanced pinFET receiver which employs two signal amplification paths for homodyne detection of multigigabit-per-second, pilot-carrier PSK optical signals. Using narrow-line 1.51 mu m semiconductor lasers, the authors have employed this receiver to phaselock a local oscillator to a 295 pW pilot carrier with 8 degrees RMS phase error.<>     

Effect of a high-temperature cycle on the mechanical properties of silicon carbide/titanium metal matrix composites

The effects of fibre/matrix interface strength and thermal residual stresses on the mechanical properties of a silicon carbide/titanium composite were investigated. A 3-ply [0/90/0] composite was subjected to a simulated superplastic forming/diffusion bonding (SPF/DB) temperature cycle which changed fibre/matrix interfacial strength and thermal residual stresses in the composite. The [0/90/0] composite subjected to the SPF/DB process showed a 25% decrease in ultimate tensile strength (UTS) and a 30% decrease in failure strain compared to the as-fabricated (ASF) material. The fatigue life for the SPF/DB specimens was approximately 50% lower than the ASF specimens. The fracture surface of the ASF specimens was very irregular accompanied by substantial fibre pull-out as compared to the planar fracture surface of the SPF/DB cycled specimens that showed negligible fibre pull-out. The large changes in the tensile strength and fatigue life due to the SPF/DB cycle are explained by a difference in the failure mechanisms occurring as a result of the SPF/DB-induced changes in the strength of the fibre/matrix interface and higher thermal residual stresses. Unreinforced titanium was also tested to study the effect of the SPF/DB cycle on the matrix static properties. Fibres were etched from the composite and then individually tested for modulus and strength. Finally, a microscopic examination of the fibre/matrix interface was performed to study the effects of the SPF/DB cycle on the interface.