Timing verification of dynamically reconfigurable logic for Xilinx Virtex FPGA series

This paper reports on a method for extending existing VHDL design and verification software available for the Xilinx Virtex series of FPGAs. It allows the designer to apply standard hardware design and verification tools to the design of dynamically reconfigurable logic (DRL). The technique involves the conversion of a dynamic design into multiple static designs, suitable for input to standard synthesis and APR tools. For timing and functional verification after APR, the sections of the design can then be recombined into a single dynamic system. The technique has been automated by extending an existing DRL design tool named DCSTech, which is part of the Dynamic Circuit Switching (DCS) CAD framework. The principles behind the tools are generic and should be readily extensible to other architectures and CAD toolsets. Implementation of the dynamic system involves the production of partial configuration bitstreams to load sections of circuitry. The process of creating such bitstreams, the final stage of our design flow, is summarized

Localization of the human dihydrolipoamide dehydrogenase gene (DLD) to 7q31→q32

The gene for human dihydrolipoamide dehydrogenase (DLD) has been localized to the long arm of chromosome 7, within bands q31→q32, by gel-blot hybridization analysis with DNA from a panel of somatic cell hybrids containing various portions of human chromosome 7.published_or_final_versio

Localization of the human gene encoding the 13.3-kDa subunit of mitochondrial complex III (UQCRB) to 8q22 by in situ hybridization

We have localized the human gene encoding the 13.3-kDa subunit of mitochondrial complex III (UQCRB) to chromosome 8 using both radioactive in situ hybridization and fluorescence in situ hybridization. The additional peak obtained with the former method is attributed to the higher sensitivity of this technique, which results in hybridization of the probe to the less conserved pseudogene. We therefore conclude that the functional gene is most likely located at 8q22.published_or_final_versio

The effect of contrasting biosolids application strategies on soil quality

Purpose: Incorporating biosolids into the soil improves plant yield compared with surface application, but it can result in the increased uptake of trace elements. However, there is a lack of knowledge about how different types of biosolids applications affect soil quality. We aimed to determine the effect of the type and rate of biosolids application on soil quality and the mobility of contaminants. Methods: Soil quality was determined by soil fertility (inorganic N, exchangeable P, Mg, Ca, K), exchangeable trace and non-essential elements (Al, Mn, Zn, Cu and Cd) and biological activity (dehydrogenase activity). We measured the properties of soil pore water, bulk soil and rhizosphere in a pot and a rhizobox experiment, with increasing concentration of biosolids (equiv. 16 t ha¯¹, 48 t ha¯¹ and 145 t ha¯¹ dry weight), applied on the surface, incorporated to 25 cm, or incorporated into a patch. Results and discussion: The incorporation of biosolids into the soil increased the exchangeable Zn, Cu, Cr, Ni and Cd, compared with surface application. The surface application of biosolids increased the inorganic N in the soil compared with biosolids incorporation (680 mg kg¯¹ vs. 380 mg kg¯¹), and decreased soil pH by 1.1 units. This aligned with solubilisation of Al (43 mg kg¯¹ vs. 6 mg kg¯¹) and Mn (43 mg kg¯¹ vs. 33 mg kg¯¹) and explains the decreased microbial activity in the soil compared with the unamended soil. Incorporating biosolids in the soil increased the biological activity, likely due to biosolids-borne microbes. The root systems significantly increased microbial activity, pH, and the concentration of NH₄⁺, NO₃⁻, and exchangeable P, S, Mg, Na, Zn, Cu and Ni, and significantly decreased exchangeable concentration of Mn and Fe

Mutation Rates of TGFBR2 and ACVR2 Coding Microsatellites in Human Cells with Defective DNA Mismatch Repair

Microsatellite instability promotes colonic tumorigenesis through generating frameshift mutations at coding microsatellites of tumor suppressor genes, such as TGFBR2 and ACVR2. As a consequence, signaling through these TGFβ family receptors is abrogated in DNA Mismatch repair (MMR)-deficient tumors. How these mutations occur in real time and mutational rates of these human coding sequences have not previously been studied. We utilized cell lines with different MMR deficiencies (hMLH1−/−, hMSH6−/−, hMSH3−/−, and MMR-proficient) to determine mutation rates. Plasmids were constructed in which exon 3 of TGFBR2 and exon 10 of ACVR2 were cloned +1 bp out of frame, immediately after the translation initiation codon of an enhanced GFP (EGFP) gene, allowing a −1 bp frameshift mutation to drive EGFP expression. Mutation-resistant plasmids were constructed by interrupting the coding microsatellite sequences, preventing frameshift mutation. Stable cell lines were established containing portions of TGFBR2 and ACVR2, and nonfluorescent cells were sorted, cultured for 7–35 days, and harvested for flow cytometric mutation detection and DNA sequencing at specific time points. DNA sequencing revealed a −1 bp frameshift mutation (A9 in TGFBR2 and A7 in ACVR2) in the fluorescent cells. Two distinct fluorescent populations, M1 (dim, representing heteroduplexes) and M2 (bright, representing full mutants) were identified, with the M2 fraction accumulating over time. hMLH1 deficiency revealed 11 (5.91×10−4) and 15 (2.18×10−4) times higher mutation rates for the TGFBR2 and ACVR2 microsatellites compared to hMSH6 deficiency, respectively. The mutation rate of the TGFBR2 microsatellite was ∼3 times higher in both hMLH1 and hMSH6 deficiencies than the ACVR2 microsatellite. The −1 bp frameshift mutation rates of TGFBR2 and ACVR2 microsatellite sequences are dependent upon the human MMR background

Lacticacidaemia due to pyruvate dehydrogenase deficiency, with evidence of protein polymorphism in the α-subunit of the enzyme

In three infants with neonatal lacticacidaemia, a deficiency in the E 1 (pyruvate dehydrogenase) component of the pyruvate dehydrogenase complex was demonstrated in skin fibroblast cultures. Residual activites of the pyruvate dehydrogenase complex in the activated state were 1.6%, 3.9% and 18.8% of control values, respectively. Immunoprecipitation of extracts of cultures skin fibroblasts grown on 35 S-methionine with anti-pyruvate dehydrogenase complex antibody revealed an abnormality in the E 1 α-component of these three patients when visualised after sodium dodecyl sulphate/polyacrylamide gel electrophoresis. This component appeared to have a slightly lower molecular weight than did this protein from control cell strains. Cell strains from other patients with a deficiency of the pyruvate dehydrogenase complex did not exhibit this defect. Three patients also showed dysmorphism and developmental abnormalities of the central nervous system.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47532/1/431_2004_Article_BF00441736.pd

Genome-Wide Association Analysis Identifies a Mutation in the Thiamine Transporter 2 (SLC19A3) Gene Associated with Alaskan Husky Encephalopathy

Alaskan Husky Encephalopathy (AHE) has been previously proposed as a mitochondrial encephalopathy based on neuropathological similarities with human Leigh Syndrome (LS). We studied 11 Alaskan Husky dogs with AHE, but found no abnormalities in respiratory chain enzyme activities in muscle and liver, or mutations in mitochondrial or nuclear genes that cause LS in people. A genome wide association study was performed using eight of the affected dogs and 20 related but unaffected control AHs using the Illumina canine HD array. SLC19A3 was identified as a positional candidate gene. This gene controls the uptake of thiamine in the CNS via expression of the thiamine transporter protein THTR2. Dogs have two copies of this gene located within the candidate interval (SLC19A3.2 – 43.36–43.38 Mb and SLC19A3.1 – 43.411–43.419 Mb) on chromosome 25. Expression analysis in a normal dog revealed that one of the paralogs, SLC19A3.1, was expressed in the brain and spinal cord while the other was not. Subsequent exon sequencing of SLC19A3.1 revealed a 4bp insertion and SNP in the second exon that is predicted to result in a functional protein truncation of 279 amino acids (c.624 insTTGC, c.625 C>A). All dogs with AHE were homozygous for this mutation, 15/41 healthy AH control dogs were heterozygous carriers while 26/41 normal healthy AH dogs were wild type. Furthermore, this mutation was not detected in another 187 dogs of different breeds. These results suggest that this mutation in SLC19A3.1, encoding a thiamine transporter protein, plays a critical role in the pathogenesis of AHE.University of California, Davis. School of Veterinary Medicine. Center for Companion Animal Healt

Myogenin Regulates Exercise Capacity and Skeletal Muscle Metabolism in the Adult Mouse

Although skeletal muscle metabolism is a well-studied physiological process, little is known about how it is regulated at the transcriptional level. The myogenic transcription factor myogenin is required for skeletal muscle development during embryonic and fetal life, but myogenin's role in adult skeletal muscle is unclear. We sought to determine myogenin's function in adult muscle metabolism. A Myog conditional allele and Cre-ER transgene were used to delete Myog in adult mice. Mice were analyzed for exercise capacity by involuntary treadmill running. To assess oxidative and glycolytic metabolism, we performed indirect calorimetry, monitored blood glucose and lactate levels, and performed histochemical analyses on muscle fibers. Surprisingly, we found that Myog-deleted mice performed significantly better than controls in high- and low-intensity treadmill running. This enhanced exercise capacity was due to more efficient oxidative metabolism during low- and high-intensity exercise and more efficient glycolytic metabolism during high-intensity exercise. Furthermore, Myog-deleted mice had an enhanced response to long-term voluntary exercise training on running wheels. We identified several candidate genes whose expression was altered in exercise-stressed muscle of mice lacking myogenin. The results suggest that myogenin plays a critical role as a high-level transcriptional regulator to control the energy balance between aerobic and anaerobic metabolism in adult skeletal muscle