Silicon resistor to measure temperature during rapid thermal annealing

A resistor composed of a piece of Si wafer and two thin silver wires attached to it, can reliably sense the temperature during rapid thermal annealing (RTA). As constant electric current passes through the Si piece, the resistivity change of Si with temperature produces a voltage signal that can be readily calibrated and converted to an actual temperature of the samples. An accuracy better than ±10 °C is achieved between 300° and 600 °C

Networks of intergenic long-range enhancers and snpRNAs drive castration-resistant phenotype of prostate cancer and contribute to pathogenesis of multiple common human disorders

Biological and mechanistic relevance of intergenic disease-associated genetic loci (IDAGL) containing highly statistically significant disease-linked SNPs remains unknown. Here we present the experimental and clinical evidence revealing important role of IDAGL in human diseases. Targeted RT-PCR screen coupled with sequencing of purified PCR products detects widespread transcription at multiple intergenic disease-associated genomic loci (IDAGL) and identifies 96 small non-coding trans-regulatory RNAs of ~ 100-300 nt in length containing SNPs associated with 21 common human disorders (snpRNAs). Functionality of snpRNAs is supported by multiple independent lines of experimental evidence demonstrating their cell-type-specific expression and evolutionary conservation of sequences, genomic coordinates, and biological effects. Analysis of chromatin state signatures, expression profiling experiments using microarray and Q-PCR technologies, and luciferase reporter assays indicate that many IDAGL are Polycomb-regulated long-range enhancers. Expression of snpRNAs in human and mouse cells markedly affects cellular behavior and induces allele-specific clinically-relevant phenotypic changes: NLRP1-locus snpRNAs exert regulatory effects on monocyte/macrophage trans-differentiation, induce prostate cancer (PC) susceptibility snpRNAs, and transform low-malignancy hormone-dependent human PC cells into highly malignant androgen-independent PC. Q-PCR analysis and luciferase reporter assays demonstrate that snpRNA sequences represent allele-specific “decoy” targets of microRNAs which function as SNP-allele-specific modifiers of microRNA expression and activity. We demonstrate that trans-acting RNA molecules facilitating androgen depletion-independent growth (ADIG) in vitro and castration-resistant (CR) phenotype in vivo of PC contain intergenic 8q24-locus SNP variants which were recently linked with increased risk of developing PC. Expression level of 8q24-locus PC susceptibility snpRNAs is regulated by NLRP1-locus snpRNAs, which are transcribed from the intergenic long-range enhancer sequence located in 17p13 region at ~ 30 kb distance from the NLRP1 gene. Q-PCR analysis of clinical PC samples reveals markedly increased snpRNA expression levels in tumor tissues compared to the adjacent normal prostate [122-fold and 45-fold in Gleason 7 tumors (p = 0.03); 370-fold and 127-fold in Gleason 8 tumors (p = 0.0001); for NLRP1-locus and 8q24-locus SnpRNAs, respectively]. Highly concordant expression profiles of the NLRP1-locus snpRNAs and 8q24 CR-locus snpRNAs (r = 0.896; p < 0.0001) in clinical PC samples and experimental evidence of trans-regulatory effects of NLRP1-locus snpRNAs on expression of 8q24-locus SnpRNAs indicate that ADIG and CR phenotype of human PC cells can be triggered by RNA molecules transcribed from the NLRP1-locus intergenic enhancer and down-stream activation of the 8q24-locus snpRNAs. Our results define the intergenic NLRP1 and 8q24 regions as regulatory loci of ADIG and CR phenotype of human PC, reveal previously unknown molecular links between the innate immunity/inflammasome system and development of hormone-independent PC, and identify novel diagnostic and therapeutic targets exploration of which should be highly beneficial for clinical management of PC

Following the rivers: historical reconstruction of California voles Microtus californicus (Rodentia: Cricetidae) in the deserts of eastern California

The California vole, Microtus californicus, restricted to habitat patches where water is available nearly year-round, is a remnant of the mesic history of the southern Great Basin and Mojave deserts of eastern California. The history of voles in this region is a model for species-edge population dynamics through periods of climatic change. We sampled voles from the eastern deserts of California and examined variation in the mitochondrial cytb gene, three nuclear intron regions, and across 12 nuclear microsatellite markers. Samples are allocated to two mitochondrial clades: one associated with southern California and the other with central and northern California. The limited mtDNA structure largely recovers the geographical distribution, replicated by both nuclear introns and microsatellites. The most remote population, Microtus californicus scirpensis at Tecopa near Death Valley, was the most distinct. This population shares microsatellite alleles with both mtDNA clades, and both its northern clade nuclear introns and southern clade mtDNA sequences support a hybrid origin for this endangered population. The overall patterns support two major invasions into the desert through an ancient system of riparian corridors along streams and lake margins during the latter part of the Pleistocene followed by local in situ divergence subsequent to late Pleistocene and Holocene drying events. Changes in current water resource use could easily remove California voles from parts of the desert landscape

Kinetics and moving species during Co2Si formation by rapid thermal annealing

We have investigated the growth kinetics and identified the moving species during Co2Si formation by rapid thermal annealing (RTA). For the kinetics study, samples which consisted of a thin Co film on an evaporated Si substrate were used. To study which species moves, samples imbedded with two very thin Ta markers were employed. Upon RTA, only one silicide phase, Co2Si, was observed to grow before all Co was consumed. The square root of time dependence and the activation energy of about 2.1±0.2 eV were observed during the Co2Si formation up to 680 °C. The marker study indicated that Co is the dominant mobile species during Co2Si formation by RTA. We conclude that Co2Si grows by the same mechanisms during RTA and conventional thermal annealing

Oral Transmucosal Delivery of Fentanyl Citrate for Breakthrough Cancer Pain Relief

Episodes of breakthrough cancer pain are relatively common occurrences for patients undergoing cancer treatments. Characterized by pain unrestrained by traditional medications, these physical burdens impose a significant degree of suffering. In order to control and eliminate this pain, Actiq, a pharmaceutical lollipop, has been developed to provide rapid oral transmucosal delivery of fentanyl citrate, a potent medicinal narcotic. To elucidate the pharmacokinetics of the drug under various dosages, a computer model of fentanyl diffusion in the oral cavity was designed in COMSOL. Upon solving the model process, concentration profiles of fentanyl in the mucosa over time were developed for various dosages. Sensitivity analyses were also performed to determine the effects of several parameters on fentanyl diffusion. The resulting concentration profiles showed that peak concentrations of 0.00079 g/m3, 0.0016 g/m3, and 0.0032 g/m3 for 200 ?g, 400 ?g, and 800 ?g dosages, respectively, were achieved at approximately 800 seconds. Additionally, based upon the sensitivity analyses, the fentanyl solubility and the lollipop radial dissolution rate have the greatest impact on fentanyl concentration and diffusion. Future research can be performed to optimize the drug diffusion by altering these two parameters, ultimately yielding a more effective Actiq product

Defining the chromatin signature of inducible genes in T cells

BACKGROUND Specific chromatin characteristics, especially the modification status of the core histone proteins, are associated with active and inactive genes. There is growing evidence that genes that respond to environmental or developmental signals may possess distinct chromatin marks. Using a T cell model and both genome-wide and gene-focused approaches, we examined the chromatin characteristics of genes that respond to T cell activation. RESULTS To facilitate comparison of genes with similar basal expression levels, we used expression-profiling data to bin genes according to their basal expression levels. We found that inducible genes in the lower basal expression bins, especially rapidly induced primary response genes, were more likely than their non-responsive counterparts to display the histone modifications of active genes, have RNA polymerase II (Pol II) at their promoters and show evidence of ongoing basal elongation. There was little or no evidence for the presence of active chromatin marks in the absence of promoter Pol II on these inducible genes. In addition, we identified a subgroup of genes with active promoter chromatin marks and promoter Pol II but no evidence of elongation. Following T cell activation, we find little evidence for a major shift in the active chromatin signature around inducible gene promoters but many genes recruit more Pol II and show increased evidence of elongation. CONCLUSIONS These results suggest that the majority of inducible genes are primed for activation by having an active chromatin signature and promoter Pol II with or without ongoing elongation

A robust optimisation model for hybrid remanufacturing and manufacturing systems under uncertain return quality and market demand

In remanufacturing research, most researchers predominantly emphasised on the recovery of whole product (core) rather than at the component level due to its complexity. In contrast, this paper addresses the challenges to focus on remanufacturing through component recovery, so as to solve production planning problems of hybrid remanufacturing and manufacturing systems. To deal with the uncertainties of quality and quantity of product returns, the processing time of remanufacturing, remanufacturing costs, as well as market demands, a robust optimisation model was developed in this research and a case study was used to evaluate its effectiveness and efficiency. To strengthen this research, a sensitivity analysis of the uncertain parameters and the original equipment manufacturer’s (OEM’s) pricing strategy was also conducted. The research finding shows that the market demand volatility leads to a significant increase in the under fulfilment and a reduction in OEM’s profit. On the other hand, recovery cost reduction, as endogenous cost saving, encourages the OEM to produce more remanufactured products with the increase in market demand. Furthermore, the OEM may risk profit loss if they raise the price of new products, and inversely, they could gain more if the price of remanufactured products is raised