A Highly Potent and Cellularly Active β‐Peptidic Inhibitor of the p53/hDM2 Interaction

New and improved : The incorporation of a 6‐chlorotryptophan (6‐Cl‐Trp) into a β‐peptide (M)‐3₁₄ helix leads to a high‐affinity hDM2 inhibitor, as demonstrated by fluorescence fluctuation analysis at single molecule resolution. When conjugated to penetratin, the newly derived hDM2 binder specifically inhibits tumour cell growth in vitro.

     

Liquid fuels fromMesua ferrea L. seed oil

Mesua ferrea L. seed oil consists of triglycerides of linoleic, oleic, palmitic and stearic acids. These acids were pyrolyzed separately in the presence of different amounts of solid sodium carbonate. Pyrolysis experiments revealed that linoleic and oleic acids can be converted to hydrocarbons of a wide range of molecular weights by pyrolyzing them with even 1% by wt of sodium carbonate up to a temperature of 500°C, whereas palmitic and stearic acids can be converted to hydrocarbons only by pyrolyzing them with equivalent amounts or more of sodium carbonate up to a temperature of about 650°C. The fractions of boiling range 60–320°C of all of the pyrolytic oils were analyzed for their hydrocarbon types by the method of fluorescent indicator adsorption (FIA). The aromatic contents of the pyrolytic oils of linoleic and oleic acids were found to be much higher than those of palmitic and stearic acids. GS and GC-MS analyses of all the saturate fractions indicated mainly normal alkanes with a carbon number range of 6 to 17.     

Fabrication and Testing of Oxide/Oxide Microcomposites with Monazite and Hibonite as Interlayers

Oxide/oxide microcomposites were fabricated and tested to evaluate the effectiveness of monazite (LaPO₄) and hibonite (CaAl₁₂O₁₉) as interlayers in sapphire-reinforced Al₂O₃-matrix composites. For interlayer thicknesses of 0.3-0.5 µm, both interlayers showed evidence of crack deflection; however, debond lengths in hibonite-coated specimens were limited to just a small fraction of the fiber diameter. Monazite-coated specimens showed multiple matrix cracks and extensive debonding at the coating/matrix interface. Composite strengths were relatively high for both coatings, considering the fiber strength degradation during processing. The strengths were greater than the calculated matrix cracking stresses. However, the mean strengths were not significantly different from those of the control specimens, although coated composites had higher Weibull moduli. The lack of difference in strength is attributed to porosity in the matrix. The results imply that matrix density needs to be >85% to evaluate novel interface strategies reliably.     

Evidence for quantum confinement effects in CdSe/ZnSe multilayer thin films prepared by the physical vapor deposition method

CdSe/ZnSe heterostructure multilayer thin films were prepared with different sublayer thicknesses of CdSe using the physical vapor deposition method. X-ray diffraction studies were used to calculate the average size of the particles and confirmed the (1 1 1) plane of ZnSe. Due to the stacking of alternate CdSe and ZnSe layers, stress was created in the multilayer systems. This results in quantum size effects. Experimentally measured energy values from (hν) vs. (αhν)² dependence confirm the presence of spin–orbit split in the valence band of CdSe. The calculated band gap energies are greater than that of bulk CdSe. Crystallite sizes (12–4 nm) were calculated based on the predictions of the effective mass approximation model (i.e. Brus model). Results show that the diameters of crystallites are smaller than the Bohr exciton diameter (11.2 nm) of CdSe. Upon particle size decrease, the photoluminescence peak is shifted from the green region to the blue region. Analysis shows that the sublayer thickness of CdSe material changes the properties of CdSe/ZnSe multilayer systems.     

Kinetic analysis of cellular internalization and expulsion of unstructured D-chirality cell penetrating peptides

Most cell penetrating peptides (CPPs) are unstructured and susceptible to proteolytic degradation. One alternative is to incorporate D-chirality amino acids into unstructured CPPs to allow for enhanced uptake and intracellular stability. This work investigates CPP internalization using a series of time, concentration, temperature, and energy dependent studies, resulting in a three-fold increase in uptake and 50-fold increase in stability of D-chirality peptides over L-chirality counterparts. CPP internalization occurred via a combination of direct penetration and endocytosis, with a percentage of internalized CPP expelling from cells in a time-dependent manner. Mechanistic studies identified that cells exported the intact internalized D-chirality CPPs via an exocytosis independent pathway, analogous to a direct penetration method out of the cells. These findings highlight the potential of a D-chirality CPP as bio-vector in therapeutic and biosensing applications, but also identify a new expulsion method suggesting a relationship between uptake kinetics, intracellular stability, and export kinetics.     

Growth points in research on memory and hippocampus.

We present an overview of two of our ongoing projects relating processes in the hippocampus to memory. We are trying to understand why retrograde amnesia occurs after damage to the hippocampus. Our experiments establish the generality of several new retrograde amnesia phenomena that are at odds with the consensus view of the role of the hippocampus in memory. We show in many memory tasks that complete damage to the hippocampus produces retrograde amnesia that is equivalent for recent and remote memories. Retrograde amnesia affects a much wider range of memory tasks than anterograde amnesia. Normal hippocampal processes can interfere with retention of a long-term memory stored outside the hippocampus. We conclude that the hippocampus competes with nonhippocampal systems during memory encoding and retrieval. Finally, we outline a project to understand and manipulate adult hippocampal neurogenesis in order to repair damaged hippocampal circuitry to recover lost cognitive functions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Attenuation of cocaine-induced locomotor activity by butyrylcholinesterase.

A primary enzyme for the metabolism of cocaine is butyrylcholinesterase (BChE). To determine whether the systemic administration of BChE can increase the metabolism of cocaine sufficiently to alter a behavioral effect, rats were tested in a locomotor activity chamber after receiving 17 mg of cocaine per kg intraperitoneally. In rats pretreated intravenously with 5,000 IU of horse serum-derived BChE, the locomotor activity effect was significantly attenuated. BChE pretreatment increased plasma BChE levels approximately 400-fold. When added to rat plasma, this amount of BChE reduced the cocaine half-life from over 5 hr to less than 5 min. BChE altered the cocaine metabolic pattern such that the relatively nontoxic metabolite ecgonine methyl ester was produced, rather than benzoylecgonine. These results suggest that systemic administration of BChE can increase the metabolism of cocaine sufficiently to alter a behavioral effect of cocaine and thus should be investigated as a potential treatment for cocaine abuse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A DIAGNOSTIC TEST FOR NONLINEAR SERIAL DEPENDENCE IN TIME SERIES FITTING ERRORS

Abstract. Time series analysts have begun to consider the applicability of nonlinear models. In order for nonlinear models to be accepted by practitioners, practicai tests must be avilable to test for the presence of nonlinearity in both raw time series and in the residuals from fitted models. A diagnostic test, based on the bispectrum, for the presence of nonlinear serial dependence in these time series is investigated here using artificial data. Detection of such nonlinear dependence is taken to indicate that nonlinear modelling methods are necessary. The theory behind the test is reviewed and simulations driven by pseudorandom numbers are presented for a variety of models and sample sizes. The simulations indicate that the test has substantial power for many models. In addition, theoretical and empirical results are presented which show that the bispectral diagnostic test is equally powerful for both the source series and for the fitting errors from a line& model. Thus, while the test is suitable for use as a diagnostic test on the fitting errors of linear time series models, prior linear modeling of the time series is not required.