Microcomputer-Based Approaches for Preventing Drug and Alcohol Abuse Among Adolescents from Ethnic-Racial Minority Backgrounds

This study was designed to empirically assess the potential of microcomputer-based intervention with black adolescents from economically disadvantaged backgrounds. Subjects were 26, 11 through 14-year-old black females and males recruited from three boroughs in New York City. A sample task was administered via microcomputer system followed by a postintervention measurement battery. Observational measures were also employed to assess interactional variables. Subjects' attitudes toward educational content in general, and toward drug and alcohol information delivery in particular, appeared to be a significant intervening variable that could alter the overall efficacy of computer-delivered interventions. Both observational and postintervention measures indicated an overall positive subject response to computer-administered instruction. In contrast, however, respondents indicated a negative response to microcomputer delivery of drug and alcohol related materials. Results of the experiment are discussed along with rationales and future research directions.     

Photocatalytic activities of N-doped nano-titanias and titanium nitride

TiO₂ doped with various loadings of nitrogen was prepared by nitridation of a nano-TiO₂ powder in an ammonia/argon atmosphere at a range of temperatures from 400 to 1100 °C. The nano-TiO₂ starting powder was produced in a continuous hydrothermal flow synthesis (CHFS) process involving reaction between a flow of supercritical water and an aqueous solution of a titanium salt. The structures of the resulting nanocatalysts were investigated using powder X-ray diffraction (XRD) and Raman spectroscopy. Products ranging from N-doped anatase TiO₂ to phase-pure titanium nitride (TiN) were obtained depending on post-synthesis heat-treatment temperature. The results suggest that TiN started forming when the TiO₂ was heat-treated at 800 °C, and that pure phase TiN was obtained at 1000 °C after 5 h nitridation. The amounts and nature of the Ti, O and N at the surface were determined by X-ray photoelectron spectroscopy (XPS). A shift of the band-gap to lower energy and increasing absorption in the visible light region, were observed by increasing the heat-treatment temperature from 400 to 700 °C.     

The C-Terminal Domain of LRRK2 with the G2019S Substitution Increases Mutant A53T α-Synuclein Toxicity in Dopaminergic Neurons In Vivo

Alpha-synuclein (α-syn) and leucine-rich repeat kinase 2 (LRRK2) play crucial roles in Parkinson’s disease (PD). They may functionally interact to induce the degeneration of dopaminergic (DA) neurons via mechanisms that are not yet fully understood. We previously showed that the C-terminal portion of LRRK2 (ΔLRRK2) with the G2019S mutation (ΔLRRK2^G2019S) was sufficient to induce neurodegeneration of DA neurons in vivo, suggesting that mutated LRRK2 induces neurotoxicity through mechanisms that are (i) independent of the N-terminal domains and (ii) “cell-autonomous”. Here, we explored whether ΔLRRK2^G2019S could modify α-syn toxicity through these two mechanisms. We used a co-transduction approach in rats with AAV vectors encoding ΔLRRK2^G2019S or its “dead” kinase form, ΔLRRK2^DK, and human α-syn with the A53T mutation (AAV-α-syn^A53T). Behavioral and histological evaluations were performed at 6- and 15-weeks post-injection. Results showed that neither form of ΔLRRK2 alone induced the degeneration of neurons at these post-injection time points. By contrast, injection of AAV-α-syn^A53T alone resulted in motor signs and degeneration of DA neurons. Co-injection of AAV-α-syn^A53T with AAV-ΔLRRK2^G2019S induced DA neuron degeneration that was significantly higher than that induced by AAV-α-syn^A53T alone or with AAV-ΔLRRK2^DK. Thus, mutated α-syn neurotoxicity can be enhanced by the C-terminal domain of LRRK2^G2019 alone^, through cell-autonomous mechanisms.     

Nationwide energy supply chain analysis for hybrid feedstock processes with significant CO2 emissions reduction

Integrating diverse energy sources to produce cost‐competitive fuels requires efficient resource management. An optimization framework is proposed for a nationwide energy supply chain network using hybrid coal, biomass, and natural gas to liquids (CBGTL) facilities, which are individually optimized with simultaneous heat, power, and water integration using 162 distinct combinations of feedstock types, capacities, and carbon conversion levels. The model integrates the upstream and downstream operations of the facilities, incorporating the delivery of feedstocks, fuel products, electricity supply, water, and CO₂ sequestration, with their geographical distributions. Quantitative economic trade‐offs are established between supply chain configurations that (a) replace petroleum‐based fuels by 100%, 75%, and 50% and (b) utilize the current energy infrastructures. Results suggest that cost‐competitive fuels for the US transportation sector can be produced using domestically available coal, natural gas, and sustainably harvested biomass via an optimal network of CBGTL plants with significant GHG emissions reduction from petroleum‐based processes. © 2012 American Institute of Chemical Engineers AIChE J, 2012     

Nucleotide and nucleotide sugar analysis by liquid chromatography-electrospray ionization-mass spectrometry on surface-conditioned porous graphitic carbon

We examined the analysis of nucleotides and nucleotide sugars by chromatography on porous graphitic carbon with mass spectrometric detection, a method that evades contamination of the MS instrument with ion pairing reagent. At first, adenosine triphosphate (ATP) and other triphosphate nucleotides exhibited very poor chromatographic behavior on new columns and could hardly be eluted from columns previously cleaned with trifluoroacetic acid. Satisfactory performance of both new and older columns could, however, be achieved by treatment with reducing agent and, unexpectedly, hydrochloric acid. Over 40 nucleotides could be detected in cell extracts including many isobaric compounds such as ATP, deoxyguanosine diphosphate (dGTP), and phospho-adenosine-5'-phosphosulfate or 3',5'-cyclic adenosine 5'-monophosphate (AMP) and its much more abundant isomer 2',3'-cyclic AMP. A fast sample preparation procedure based on solid-phase extraction on carbon allowed detection of very short-lived analytes such as cytidine 5'-monophosphate (CMP)-2-keto-deoxy-octulosonic acid. In animal cells and plant tissues, about 35 nucleotide sugars were detected, among them rarely considered metabolites such as uridine 5'-diphosphate (UDP)-l-arabinopyranose, UDP-L-arabinofuranose, guanosine 5'-diphosphate (GDP)-L-galactofuranose, UDP-L-rhamnose, and adenosine diphosphate (ADP)-sugars. Surprisingly, UDP-arabinopyranose was also found in Chinese hamster ovary (CHO) cells. Due to the unique structural selectivity of graphitic carbon, the method described herein distinguishes more nucleotides and nucleotide sugars than previously reported approaches.     

Treatment Strategies that Enhance the Efficacy and Selectivity of Mitochondria-Targeted Anticancer Agents

Nearly a century has passed since Otto Warburg first observed high rates of aerobic glycolysis in a variety of tumor cell types and suggested that this phenomenon might be due to an impaired mitochondrial respiratory capacity in these cells. Subsequently, much has been written about the role of mitochondria in the initiation and/or progression of various forms of cancer, and the possibility of exploiting differences in mitochondrial structure and function between normal and malignant cells as targets for cancer chemotherapy. A number of mitochondria-targeted compounds have shown efficacy in selective cancer cell killing in pre-clinical and early clinical testing, including those that induce mitochondria permeability transition and apoptosis, metabolic inhibitors, and ROS regulators. To date, however, none has exhibited the standards for high selectivity and efficacy and low toxicity necessary to progress beyond phase III clinical trials and be used as a viable, single modality treatment option for human cancers. This review explores alternative treatment strategies that have been shown to enhance the efficacy and selectivity of mitochondria-targeted anticancer agents in vitro and in vivo, and may yet fulfill the clinical promise of exploiting the mitochondrion as a target for cancer chemotherapy.     

Human Endometrial Carcinogenesis Is Associated with Significant Reduction in Long Non-Coding RNA,TERRA

Telomeres are transcribed as long non-coding RNAs called TERRAs (Telomeric repeat containing RNA) that participate in a variety of cellular regulatory functions. High telomerase activity (TA) is associated with endometrial cancer (EC). This study aimed to examine the levels of three TERRAs, transcribed at chromosomes 1q-2q-4q-10q-13q-22q, 16p and 20q in healthy (n = 23) and pathological (n = 24) human endometrium and to examine their association with cellular proliferation, TA and telomere lengths. EC samples demonstrated significantly reduced levels of TERRAs for Chromosome 16p (Ch-16p) (p < 0.002) and Chromosome 20q (Ch-20q) (p = 0.0006), when compared with the postmenopausal samples. No significant correlation was found between TERRA levels and TA but both Ch-16p and Ch-20q TERRA levels negatively correlated with the proliferative marker Ki67 (r = −0.35, p = 0.03 and r = −0.42, p = 0.01 respectively). Evaluation of single telomere length analysis (STELA) at XpYp telomeres demonstrated a significant shortening in EC samples when compared with healthy tissues (p = 0.002). We detected TERRAs in healthy human endometrium and observed altered individual TERRA-specific levels in malignant endometrium. The negative correlation of TERRAs with cellular proliferation along with their significant reduction in EC may suggest a role for TERRAs in carcinogenesis and thus future research should explore TERRAs as potential therapeutic targets in EC.     

Projection-based two-phase minimum and maximum length scale control in topology optimization

The objective of this paper is a tradeoff between changing design and controlling sampling uncertainty in reliability-based design optimization (RBDO). The former is referred to as ‘living with uncertainty’, while the latter is called ‘shaping uncertainty’. In RBDO, a conservative estimate of the failure probability is defined using the mean and the upper confidence limit, which are obtained from samples and from the normality assumption. Then, the sensitivity of the conservative probability of failure is derived with respect to design variables as well as the number of samples. It is shown that the proposed sensitivity is much more accurate than that of the finite difference method and close to the analytical sensitivity. A simple RBDO example showed that once the design variables reach near the optimum point, the number of samples is adjusted to satisfy the conservative reliability constraints. This example showed that not only shifting design but also shaping uncertainty plays a critical role in the optimization process.