Predicting carcinogenicity by using batteries of dependent short-term tests.

Among the various methods for predicting carcinogenicity from a battery of short-term tests (STTs), the carcinogenicity prediction and battery selection (CPBS) procedure is the most prominent. A major assumption of CPBS is that the STTs used in the prediction are conditionally independent. Results of recent National Toxicology Program studies of four commonly used in vitro STTs contradict this assumption, thereby necessitating modification of CPBS to accommodate dependencies. This is accomplished via log-linear modeling, which then also yields an important dividend: standard errors for the predicted probabilities of carcinogenicity

Improved plasmids for gene targeting at the his-3 locus of Neurospora crassa by electroporation: Correction

Two mistakes in our article on gene replacement by gene targeting at the his-3 locus (Margolin, B.S. et al., 1997, FGN 44:34-36) have come to our attention

Improved plasmids for gene targeting at the his-3 locus of Neurospora crassa by electroporation

We report two new plasmids, pBM60 and pBM61, and procedures to efficiently generate single- copy transformants targeted to the his-3 locus in Neurospora crassa

TGFBR1*6A and Int7G24A variants of transforming growth factor-β receptor 1 in Swedish familial and sporadic breast cancer

Two common variants in transforming growth factor-β receptor 1 (TGFBR1), TGFBR1*6A and Int7G24A, A allele, have been shown to act as low-penetrance tumour susceptibility alleles in several common cancers, including breast cancer. We evaluated the TGFBR1 9A/6A and Int7G24A variant frequencies in two breast cancer cohorts; a population-based cohort of breast cancer with defined family history (n=459) and in breast cancer patients from a familial cancer clinic (n=340) and in 856 controls from the Stockholm region. The familial patients from both cohorts were further divided into high- and low-risk familial breast cancer based on pedigree analysis. There was no overall association with either variant and breast cancer risk. The TGFBR1*6A allelic frequency was, however, higher in low-risk familial breast cancer (0.138), compared to controls (0.106; P=0.04). No significant difference was found in the high-risk familial (0.102) or sporadic cases (0.109; P=0.83 and 0.83, respectively). TGFBR1*6A carrier status was further associated with a high-grade sporadic breast cancer (odds ratio: 2.27; 95% confidence interval: 1.01–5.11; P=0.049). These results indicate that the TGFBR1*6A variant may be associated with an increased risk of low-risk familial breast cancer and might be a marker for poorly differentiated breast cancer. The Int7G24A variant was not associated with breast cancer risk or clinical presentation of the disease including prognosis in our material

Microwaves affect thermoregulatory behavior in rats

Rats, with their fur clipped, pressed a lever to turn on an infrared lamp while in a cold chamber. When 2450 Megahertz continuous wave microwaves were presented for 15 minutes, the rate of turning on the infrared lamp decreased as a function of the microwave power density, which ranged between 5 MW/cm/sup 2/ and 20 MW/cm/sup 2/. This result indicates that behaviorally significant levels of heating occur at exposure durations and intensities that do not produce reliable changes in either colonic temperature or other behavioral measures. Further study of how microwaves affect thermoregulatory behavior may help us understand phenomena such as reported non-thermal behavioral effects of microwaves

Detection of poliovirus by ICC/qPCR in concentrated water samples has greater sensitivity and is less costly using BGM cells in suspension as compared to monolayers

The integrated cell culture quantitative reverse transcriptase PCR (ICC/qRT-PCR) method is used in our lab to detect enteroviruses in environmental waters. Typically we utilize monolayers of 3 cell lines; buffalo green monkey kidney (BGM), human colonic carcinoma (CACO-2) and African rhesus monkey kidney (MA104) with the intent of providing one or more permissive hosts to a wide range of enteroviruses. In this study the BGM cell line was used to compare poliovirus infectivity in conventional monolayer cultures to BGM cells in suspensions. Propagated virus was subsequently amplified by qRT-PCR. Our PCR data showed lower cycle threshold (Ct) values in the suspensions which corresponded to a higher rate of infectivity than that observed in the monolayers. The difference in Ct values was determined statistically significant by One-way ANOVA (0.000). Infecting BGM cells in suspensions required less hands-on time, less chance of contamination and was more cost effective than utilizing the conventional monolayer technique

Efficacy of alemtuzumab over 6 years in relapsing–remitting multiple sclerosis patients who relapsed between courses 1 and 2: Post hoc analysis of the CARE-MS studies

Background: Alemtuzumab is administered as two annual courses for relapsing–remitting multiple sclerosis (MS). Patients may relapse before completing the two-course regimen. Objective: The objective was to evaluate 6-year outcomes in patients who relapsed between alemtuzumab Courses 1 and 2 (early relapsers). Methods: Post hoc analysis of patients from the Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis (CARE-MS) studies who enrolled in the extension. Results: Early relapsers (CARE-MS I: 15%; CARE-MS II: 24%) had more relapses in 1–2 years pre-alemtuzumab and higher mean baseline Expanded Disability Status Scale score than patients without relapse. Their annualized relapse rate declined from Year 1 (CARE-MS I: 1.3; CARE-MS II: 1.2) to Year 2 following Course 2 (0.3; 0.5) and remained low thereafter. Over 6 years, 60% remained free of 6-month confirmed disability worsening; 24% (CARE-MS I) and 34% (CARE-MS II) achieved 6-month confirmed disability improvement. During Year 6, 69% (CARE-MS I) and 68% (CARE-MS II) were free of magnetic resonance imaging (MRI) disease activity. Median percent yearly brain volume loss (Year 1: −0.67% (CARE-MS I); −0.47% (CARE-MS II)) declined after Course 2 (Year 6: −0.24%; −0.13%). Conclusion: Early relapsers’ outcomes improved after completing the second alemtuzumab course. These findings support administering the approved two-course regimen to maximize clinical benefit. ClinicalTrials.gov registration numbers: CARE-MS I, II, extension: NCT00530348, NCT00548405, NCT00930553

On distributions of functionals of anomalous diffusion paths

Functionals of Brownian motion have diverse applications in physics, mathematics, and other fields. The probability density function (PDF) of Brownian functionals satisfies the Feynman-Kac formula, which is a Schrodinger equation in imaginary time. In recent years there is a growing interest in particular functionals of non-Brownian motion, or anomalous diffusion, but no equation existed for their PDF. Here, we derive a fractional generalization of the Feynman-Kac equation for functionals of anomalous paths based on sub-diffusive continuous-time random walk. We also derive a backward equation and a generalization to Levy flights. Solutions are presented for a wide number of applications including the occupation time in half space and in an interval, the first passage time, the maximal displacement, and the hitting probability. We briefly discuss other fractional Schrodinger equations that recently appeared in the literature.Comment: 25 pages, 4 figure