Construction of a homodimeric dihydrofolate reductase-thymidylate synthase bifunctional enzyme

A gene encoding a bifunctional homodimeric dihydrofolate reductase- thymidylate synthase (DHFR-TS) was constructed by destroying the stop codon of Escherichia coli dihydrofolate reductase (DHFR) and joining the coding sequences of the monofunctional enzymes by a five amino acid linker. The protein was designed to mimic features of active site proximity and electrostatics in the protozoan DHFR-TSs which are believed to be important in channeling of the DHFR substrate, H2folate, to TS. The genetically engineered catalytically active homodimeric bifunctional DHFR-TS was expressed, purified and characterized. The component activities of the purified bifunctional enzyme had kinetic properties similar to those of the monofunctional TS and DHFR, but unlike the authentic bifunctional enzymes from protozoa this enzyme did not kinetically channel dihydrofolate from DHFR to TS.      

The politics of conservative elites and the 'liberal media' argument

Recent evidence suggests that conservative elites' claims of a liberal media are having an impact upon public perceptions of news coverage. With this in mind, we examined two related questions in the context of the 1988, 1992, and 1996 presidential elections. First, what factors may be prompting conservative elites to make allegations of liberal media bias? Second, what factors may influence when news media report these criticisms during presidential campaigns? Findings suggest that these criticisms of news media are at least partly strategic and reflect a dynamic relationship between political elites and journalists during a presidential campaign.     

1，4-环己二酮单乙二醇缩酮的合成研究

对1,4-环已二酮的单保护反应进行了研究,在自制催化荆催化下,用n(乙二醇)∶n(1,4-环己二酮)=1∶1进行脱水缩合反应,在环己烷溶液中除去部分未保护的原料,在乙酸乙酯中用亚硫酸氢钠提取单保护产物,用10%的碳酸钠脱去亚硫酸氢钠,结晶精制而得产品1,4-环己二酮单乙二醇缩酮[1,4-二氧杂螺(4,5)癸烷-8-酮],收率为68.2%,气相色谱测定其纯度为99.8%.     

Serial Mitsuda tests for identification of reactional tuberculoid and reactional borderline leprosy forms

The authors studied the Mitsuda reaction in 37 leprosy patients (18 reactional tuberculoid, 19 reactional borderline cases) and compared the results with clinical findings, histopathology and bacilloscopy. Evaluation of the Mitsuda reaction was carried out on days 30, 60, 90 and 120. Most of the reactional tuberculoid patients showed a Mitsuda reaction of +3 in opposition to the reactional borderline patients who showed only +. Bacilloscopic analysis revealed that in 75% of the reactional tuberculoid cases there were rare or no bacilli; bacilli were present in 95% of the reactional borderline cases. The authors conclude that reactional tuberculoid cases have a greater ability to clear bacilli than reactional borderline cases, and that the Mitsuda reaction is a useful tool for the differentiation between these two types of leprosy.     

Role of null hypothesis significance testing (NHST) in the design of neuropsychologic research

Diphenhydramine is generally considered an innocuous drug with a minimal risk for abuse and untoward side effects. We describe children and adolescents with chronic hematologic and oncologic diseases who exhibited drug-seeking behavior or anticholinergic symptoms with the use of diphenhydramine. These cases illustrate that the assumption that this drugs is without significant adverse effects may be unwarranted, especially for children and adolescents with chronic diseases.     

Correlation of genetic instability and apoptosis in the presence of oncogenic Ki-Ras

The product of the ras proto-oncogene has been implicated as an essential signal transducer, involved in a variety of biological or pathological activities, including apoptosis. The aim of this investigation was to further explore the mechanisms of apoptosis triggered by Ras. Stable expression of constitutively-activated (v)-Ki-Ras in Balb/c-3T3 mouse fibroblasts resulted in a loss of G1 arrest in response to treatments which induced cell cycle arrest in the parental Balb/c-3T3 cells, accompanied by decreased expression of the p53 tumor suppressor protein and the GADD45 gene, the product of which is involved in DNA repair, and deregulated expression of the MDM-2 gene, the product of which can regulate p53 expression. Ki-Ras expression also increased the frequency of PALA-selectable CAD gene amplification, and paradoxically the susceptibility to PALA-induced apoptosis. After persistent serum-starvation, cells expressing the activated ras gene lost clonogenic potential, indicating impaired capability for genetic repair in the cells. Taken together, these data suggest that activated Ki-ras may confer genetic instabilty upon cells, possibly through interference with tumor suppressors, such as p53. While this instability may facilitate adaptation to environmental stresses, this instability in the genome also renders cells containing activated ras genes intrinsically more susceptible to programmed cell death, possibly by accumulation of undesirable or lethal genetic events during the process of tumor development.     

A comparison of standardized and narrative letters of recommendation

OBJECTIVE: To compare the Council of Emergency Medicine Residency Directors' (CORD's) standardized letters of recommendation (SLORs) with traditional narrative letters of recommendation (NLORs) with regard to interrater reliability, consistency, and time of interpretation. METHODS: In part I of the study, four members of the residency selection committee each evaluated the same 20 SLORs and 20 NLORs from which all identifying characteristics had been deleted. Using Likert-type scales of the global assessment, each letter was assigned a numeric value from 1 to 7. The interrater reliability was calculated for both types of letters using the Kendall coefficient of concordance. Average time to interpretation of the letters was also determined. In part II, using the same numeric values as in part I, 207 single-author SLOR/NLOR pairs were evaluated to determine whether the global assessment of the SLOR was consistent with that of its partner NLOR. Interpretation of the NLOR was performed blinded to the SLOR. Statistical analysis was calculated using Spearman correlation coefficients. RESULTS: In part I of the study, the interrater reliability of the SLOR was 0.97, as compared with 0.78 for the NLOR. The average time to interpret the global assessment of the SLOR was 16 seconds, vs 90 seconds for the NLOR. In part II of the study, of the 207 SLOR/NLOR pairs, 112 (54%) were assigned the same numeric value, 80 (39%) differed by one, 13 (6%) differed by two, and two (1%) differed by three, for an overall correlation of 0.58. CONCLUSIONS: Compared with NLORs, the CORD SLOR offers better interrater reliability with less interpretation time. Single-author SLOR/NLOR pairs submitted for a single applicant do not correlate well. Residency selection committees must decide whether the added work of interpreting NLORs is beneficial.