Relationship Between 6- Mercaptopurine Toxicity And Uric Acid Synthesis In The Chick

Six-mercaptopurine is a chemotherapeutic drug which has been used extensively in clinical research as well as biological and biochemical experimental studies. Studies on the absorption, distribution, toxicity, and metabolism of 6-mercaptopurine (6-MP) in experimental animals and in the human have been reported in recent reviews. The extreme toxicity of 6-MP and its analogs have been observed in various species. Phillips (1954) reported that toxicity occurs in rabbits at a dosage level of 10 to 15 mg/ kg bdy wt/day, while 100 mg/kg bdy wt/day may be required to produce similar effects in guinea pigs. According to Hamilton and Elion (1954), toxicity often appears in man at a dosage of 2.5 mg/kg bdy wt/day. The toxicity of this purine and its derivatives has imposed obvious limitations in their use for treatment of leukemia. Studies in our laboratory during the past year have demonstrated that the chick can tolerate 1200-1800 mg/kg bdy wt/ day of 6-MP. The writer could find no report of any investigation which involved the chick in regard to the unusual relative high tolerance of this compound, nor any reference to the metabolic degradation of this purine or its derivatives in this species. The present status of research in this area has indicated that the therapeutic effectiveness of 6-MP and other purine derivatives, may be potentiated in man. It has been established that the end product of purine metabolism in man and in the chick is uric acid, although it is excreted in much larger amounts in the chick. In view of the chick\u27s normal high tolerance for 6-MP, it seems logical to assume that this species may possess a mechanism which enables it to normally detoxify the oxidative metabolic end-products associated with the degradation of 6-MP and other derivatives more efficiently than man or other previously studied species

Tension and Energy: Components of Arousal and their Effect on Intention to Give

In the current study we explore a multidimensional conceptualization of arousal to better understand the effect of donation appeals incorporating negative messages on intention to give. More specifically, an experiment is conducted to determine whether varying the level of message negativity has an impact on donor intentions to give where the mechanism by which intentions increase is examined. Using structural equation modeling, the relationship between message negativity, two dimensions of arousal (tension and energy) and intention to donate is estimated. We collected data using the background of an on-campus fund raising program for abused Afghani women held at a mid-size, southern university. The university’s freshman reading program using the book “Three Cups of Tea” generated a student fund raising initiative to support an educational initiative in Afghanistan. We developed a simulated donation message to induce activation/arousal and then measured arousal and intention to give. Two descriptions of the life of women in Afghanistan were developed as the stimuli messages for the experiment and presented to the subjects under the heading “EDUCATION FOR AFGHAN WOMEN.” The scenarios were developed from the descriptions in “Three Cups of Tea” to portray a negative and arousal-producing situation. Scenario Two was designed to produce a higher level of arousal with description of assaults with acid and self- immolation. The findings suggest message negativity positively influences donor intentions to give via the generation of tension. While increased energy levels were also observed among participants exposed to more negative messages, this did not translate into greater donation intentions. The implications of these findings and suggestions for future research are discusse

The Dimerization Domain in DapE Enzymes Is Required for Catalysis

The emergence of antibiotic-resistant bacterial strains underscores the importance of identifying new drug targets and developing new antimicrobial compounds. Lysine and meso-diaminopimelic acid are essential for protein production and bacterial peptidoglycan cell wall remodeling and are synthesized in bacteria by enzymes encoded within dap operon. Therefore dap enzymes may serve as excellent targets for developing a new class of antimicrobial agents. The dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase (DapE) converts N-succinyl-L,L-diaminopimelic acid to L,Ldiaminopimelic acid and succinate. The enzyme is composed of catalytic and dimerization domains, and belongs to the M20 peptidase family. To understand the specific role of each domain of the enzyme we engineered dimerization domain deletion mutants of DapEs from Haemophilus influenzae and Vibrio cholerae, and characterized these proteins structurally and biochemically. No activity was observed for all deletion mutants. Structural comparisons of wild-type, inactive monomeric DapE enzymes with other M20 peptidases suggest that the dimerization domain is essential for DapE enzymatic activity. Structural analysis and molecular dynamics simulations indicate that removal of the dimerization domain increased the flexibility of a conserved active site loop that may provide critical interactions with the substrate

Validation of a Predictive Model for Survival in Patients With Advanced Cancer: Secondary Analysis of RTOG 9714.

BackgroundThe objective of this study was to validate a simple predictive model for survival of patients with advanced cancer.MethodsPrevious studies with training and validation datasets developed a model predicting survival of patients referred for palliative radiotherapy using three readily available factors: primary cancer site, site of metastases and Karnofsky performance score (KPS). This predictive model was used in the current study, where each factor was assigned a value proportional to its prognostic weight and the sum of the weighted scores for each patient was survival prediction score (SPS). Patients were also classified according to their number of risk factors (NRF). Three risk groups were established. The Radiation Therapy and Oncology Group (RTOG) 9714 data was used to provide an additional external validation set comprised of patients treated among multiple institutions with appropriate statistical tests.ResultsThe RTOG external validation set comprised of 908 patients treated at 66 different radiation facilities from 1998 to 2002. The SPS method classified all patients into the low-risk group. Based on the NRF, two distinct risk groups with significantly different survival estimates were identified. The ability to predict survival was similar to that of the training and previous validation datasets for both the SPS and NRF methods.ConclusionsThe three variable NRF model is preferred because of its relative simplicity

ChloroplastDB: the Chloroplast Genome Database

The Chloroplast Genome Database (ChloroplastDB) is an interactive, web-based database for fully sequenced plastid genomes, containing genomic, protein, DNA and RNA sequences, gene locations, RNA-editing sites, putative protein families and alignments (). With recent technical advances, the rate of generating new organelle genomes has increased dramatically. However, the established ontology for chloroplast genes and gene features has not been uniformly applied to all chloroplast genomes available in the sequence databases. For example, annotations for some published genome sequences have not evolved with gene naming conventions. ChloroplastDB provides unified annotations, gene name search, BLAST and download functions for chloroplast encoded genes and genomic sequences. A user can retrieve all orthologous sequences with one search regardless of gene names in GenBank. This feature alone greatly facilitates comparative research on sequence evolution including changes in gene content, codon usage, gene structure and post-transcriptional modifications such as RNA editing. Orthologous protein sets are classified by TribeMCL and each set is assigned a standard gene name. Over the next few years, as the number of sequenced chloroplast genomes increases rapidly, the tools available in ChloroplastDB will allow researchers to easily identify and compile target data for comparative analysis of chloroplast genes and genomes

ICEF2004-960 MICROPHONES AND KNOCK SENSORS FOR FEEDBACK CONTROL OF HCCI ENGINES

ABSTRACT Homogeneous charge compression ignition (HCCI) engines lack direct in-cylinder CA50 engine crank position in CAD at 50% heat release CAD crank angle degrees HCCI homogeneous charge compression ignition µ sample mean ∇ differencing operator, ∇Y t = Y t −Y t−1 P t predicted (at engine position t) value of a series φ fuel-air equivalence ratio PID proportional-integral-derivative control law RPM revolutions per minute SI spark-ignited TDC top-dead-center of the compression stroke V voltage Y t time t values of data series WN(µ,σ 2 ) normally-distributed white noise process with mean µ and variance σ

Complete plastid genome sequences of Drimys, Liriodendron, and Piper: implications for the phylogenetic relationships of magnoliids

BACKGROUND: The magnoliids with four orders, 19 families, and 8,500 species represent one of the largest clades of early diverging angiosperms. Although several recent angiosperm phylogenetic analyses supported the monophyly of magnoliids and suggested relationships among the orders, the limited number of genes examined resulted in only weak support, and these issues remain controversial. Furthermore, considerable incongruence resulted in phylogenetic reconstructions supporting three different sets of relationships among magnoliids and the two large angiosperm clades, monocots and eudicots. We sequenced the plastid genomes of three magnoliids, Drimys (Canellales), Liriodendron (Magnoliales), and Piper (Piperales), and used these data in combination with 32 other angiosperm plastid genomes to assess phylogenetic relationships among magnoliids and to examine patterns of variation of GC content. RESULTS: The Drimys, Liriodendron, and Piper plastid genomes are very similar in size at 160,604, 159,886 bp, and 160,624 bp, respectively. Gene content and order are nearly identical to many other unrearranged angiosperm plastid genomes, including Calycanthus, the other published magnoliid genome. Overall GC content ranges from 34–39%, and coding regions have a substantially higher GC content than non-coding regions. Among protein-coding genes, GC content varies by codon position with 1st codon > 2nd codon > 3rd codon, and it varies by functional group with photosynthetic genes having the highest percentage and NADH genes the lowest. Phylogenetic analyses using parsimony and likelihood methods and sequences of 61 protein-coding genes provided strong support for the monophyly of magnoliids and two strongly supported groups were identified, the Canellales/Piperales and the Laurales/Magnoliales. Strong support is reported for monocots and eudicots as sister clades with magnoliids diverging before the monocot-eudicot split. The trees also provided moderate or strong support for the position of Amborella as sister to a clade including all other angiosperms. CONCLUSION: Evolutionary comparisons of three new magnoliid plastid genome sequences, combined with other published angiosperm genomes, confirm that GC content is unevenly distributed across the genome by location, codon position, and functional group. Furthermore, phylogenetic analyses provide the strongest support so far for the hypothesis that the magnoliids are sister to a large clade that includes both monocots and eudicots

The Effect of the Di-Tertiary Butyl Peroxide (DTBP) additive on HCCI Combustion of Fuel Blends of Ethanol and Diethyl Ether

The influence of the small amounts (1-3%) of the additive di-tertiary butyl peroxide (DTBP) on the combustion event of Homogeneous Charge Compression Ignition (HCCI) engines was investigated using engine experiments, numerical modeling, and carbon-14 isotope tracing. DTBP was added to neat ethanol and diethyl ether (DEE) in ethanol fuel blends for a range of combustion timings and engine loads. The addition of DTBP to the fuel advanced combustion timing in each instance, with the DEE-in-ethanol mixture advancing more than the ethanol alone. A numerical model reproduced the experimental results. Carbon-14 isotope tracing showed that more ethanol burns to completion in DEE-in-ethanol blends with a DTBP additive when compared to results for DEE-in-ethanol without the additive. However, the addition of DTBP did not elongate the heat release in either case. The additive advances combustion timing for both pure ethanol and for DEE-in-ethanol mixtures, but the additive results in more of an advance in timing for the DEE-in-ethanol mixture. This suggests that although there are both thermal and kinetic influences from the addition of DTBP, the thermal effects are more important

Rex Shunt Preoperative Imaging: Diagnostic Capability of Imaging Modalities

The purpose of this study was to evaluate the diagnostic capability of imaging modalities used for preoperative mesenteric-left portal bypass (“Rex shunt”) planning. Twenty patients with extrahepatic portal vein thrombosis underwent 57 preoperative planning abdominal imaging studies. Two readers retrospectively reviewed these studies for an ability to confidently determine left portal vein (PV) patency, superior mesenteric vein (SMV) patency, and intrahepatic left and right PV contiguity. In this study, computed tomographic arterial portography allowed for confident characterization of left PV patency, SMV patency and left and right PV continuity in 100% of the examinations. Single phase contrast-enhanced CT, multi-phase contrast-enhanced CT, multiphase contrast-enhanced MRI, and transarterial portography answered all key diagnostic questions in 33%, 30%, 0% and 8% of the examinations, respectively. In conclusion, of the variety of imaging modalities that have been employed for Rex shunt preoperative planning, computed tomographic arterial portography most reliably allows for assessment of left PV patency, SMV patency, and left and right PV contiguity in a single study