Characterization of the Mouse Epidermal Growth Factor Promoter and 5′-Flanking Region: ROLE FOR AN ATYPICAL TATA SEQUENCE

As a step toward delineating mechanisms that regulate its activity, we have characterized the mouse epidermal growth factor (EGF) promoter. Primer extension and S1 nuclease analyses identified prominent (+1/+2) and minor (+28) transcription start sites, with the dominant +1/+2 site located 33 bases downstream from a TTTAAA sequence. A restriction fragment that spanned these start sites and contained 390 base pairs of 5'-flanking sequence directed transcription from the +1/+2 site in vitro in the presence of HeLa cell nuclear extracts. Additionally, it promoted expression of a coupled luciferase reporter gene in transfected cell lines. The inclusion of additional 5'-flanking sequence either stimulated or inhibited luciferase expression depending on the cell line. Approximately 2 kilobases of EGF 5'-flanking sequence was determined and found to contain several motifs with partial homology to steroid hormone response elements. Despite this fact and evidence that EGF expression might be regulated by androgens in vivo, EGF promoter-luciferase constructs were not steroid-responsive in cells cotransfected with steroid receptor expression vectors. An oligonucleotide containing the aforementioned TTTAAA sequence specifically bound TATA-binding protein and TFIIA in gel shift assays, and an EGF promoter-luciferase construct in which the core TA dinucleotide was mutated to CG was not active in transfected cells. These data suggest that the TTTAAA sequence functions as an atypical TATA box

Readability and Suitability of COPD Consumer Information

Background. Information leaflets have been shown to positively or negatively impact adherence, depending on their content. The objective of this study was to perform an appraisal of the consumer information provided in COPD inhaler monographs. Methods. COPD inhalers were identified from the Health Canada Drug Product Database. Medication information and instructions for inhaler use were analyzed for readability by seven formulas, with an acceptability threshold of grades 6–8. Three researchers rated suitability using a modified Suitability Assessment of Materials (SAM) tool and assessed leaflets for explicit warnings. Results. Twenty-six inhalers with a COPD indication were evaluated. Medication information sections were rated as “difficult to read” or “hard,” and 85% (22/26) had a reading level above grade 8. The instructions for inhaler use were rated as “easy” or “fairly easy” to read and 63% (16/26) met the threshold by all formulas. While all leaflets achieved superior suitability ratings, extreme warnings included risk of premature death (n=12), risks of serious injury (n=26), serious interactions (n=26), and statements that convey a serious consequence to therapy (n=26). Conclusion. While COPD information leaflets in Canada performed well in terms of readability and suitability, overemphasis on side effects, warnings, and precautions may contribute to patient fear and nonadherence

CME/CNE Article: A Framework of Care in Multiple Sclerosis, Part 1: Updated Disease Classification and Disease-Modifying Therapy Use in Specific Circumstances

UNLABELLED: Activity Available Online: To access the article, post-test, and evaluation online, go to http://www.cmscscholar.org. TARGET AUDIENCE: The target audience for this activity is physicians, physician assistants, nursing professionals, and other health-care providers involved in the management of patients with multiple sclerosis (MS). LEARNING OBJECTIVES: Apply new information about MS to a comprehensive individualized treatment plan for patients with MSIntegrate the team approach into long-term planning in order to optimize rehabilitation care of patients with MSAccreditation Statement: This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of the Consortium of Multiple Sclerosis Centers (CMSC), Nurse Practitioner Alternatives (NPA), and Delaware Media Group. The CMSC is accredited by the ACCME to provide continuing medical education for physicians. The CMSC designates this journal-based CME activity for a maximum of 1.

Debris-Collecting Vacuum Machine with Grounded Safety System and Associated Methods

A debris collection machine includes a vacuum system (including a suction source operable to provide suction for pulling debris into a receptacle), a ground reference portion, a ground test portion, and a ground-checking module. The ground reference portion is electrically coupled with an electrically grounded reference point, and the ground test portion is electrically coupled with a portion of the vacuum system. The ground-checking module determines a resistance between from the ground reference portion and the ground test portion and prevents or terminates operation of the suction source of the vacuum system when the resistance exceeds a predetermined threshold value, e.g., which may correspond to a risk condition of spark generation that could ignite material in the receptacle

Superhumps in Cataclysmic Binaries. XXIII. V442 Ophiuchi and RX J1643.7+3402

We report the results of long observing campaigns on two novalike variables: V442 Ophiuchi and RX J1643.7+3402. These stars have high-excitation spectra, complex line profiles signifying mass loss at particular orbital phases, and similar orbital periods (respectively 0.12433 and 0.12056 d). They are well-credentialed members of the SW Sex class of cataclysmic variables. Their light curves are also quite complex. V442 Oph shows periodic signals with periods of 0.12090(8) and 4.37(15) days, and RX J1643.7+3402 shows similar signals at 0.11696(8) d and 4.05(12) d. We interpret these short and long periods respectively as a "negative superhump" and the wobble period of the accretion disk. The superhump could then possibly arise from the heating of the secondary (and structures fixed in the orbital frame) by inner-disk radiation, which reaches the secondary relatively unimpeded since the disk is not coplanar. At higher frequencies, both stars show another type of variability: quasi-periodic oscillations (QPOs) with a period near 1000 seconds. Underlying these strong signals of low stability may be weak signals of higher stability. Similar QPOs, and negative superhumps, are quite common features in SW Sex stars. Both can in principle be explained by ascribing strong magnetism to the white dwarf member of the binary; and we suggest that SW Sex stars are borderline AM Herculis binaries, usually drowned by a high accretion rate. This would provide an ancestor channel for AM Hers, whose origin is still mysterious.Comment: PDF, 41 pages, 4 tables, 16 figures; accepted, in press, to appear December 2002, PASP; more info at http://cba.phys.columbia.edu

Software defect prediction: do different classifiers find the same defects?

Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License CC BY 4.0 (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.During the last 10 years, hundreds of different defect prediction models have been published. The performance of the classifiers used in these models is reported to be similar with models rarely performing above the predictive performance ceiling of about 80% recall. We investigate the individual defects that four classifiers predict and analyse the level of prediction uncertainty produced by these classifiers. We perform a sensitivity analysis to compare the performance of Random Forest, Naïve Bayes, RPart and SVM classifiers when predicting defects in NASA, open source and commercial datasets. The defect predictions that each classifier makes is captured in a confusion matrix and the prediction uncertainty of each classifier is compared. Despite similar predictive performance values for these four classifiers, each detects different sets of defects. Some classifiers are more consistent in predicting defects than others. Our results confirm that a unique subset of defects can be detected by specific classifiers. However, while some classifiers are consistent in the predictions they make, other classifiers vary in their predictions. Given our results, we conclude that classifier ensembles with decision-making strategies not based on majority voting are likely to perform best in defect prediction.Peer reviewedFinal Published versio

Genome analysis of a simultaneously predatory and prey-independent, novel Bdellovibrio bacteriovorus from the River Tiber, supports in silico predictions of both ancient and recent lateral gene transfer from diverse bacteria

Background: Evolution equipped Bdellovibrio bacteriovorus predatory bacteria to invade other bacteria, digesting and replicating, sealed within them thus preventing nutrient-sharing with organisms in the surrounding environment. Bdellovibrio were previously described as “obligate predators” because only by mutations, often in gene bd0108, are 1 in ~1x107 of predatory lab strains of Bdellovibrio converted to prey-independent growth. A previous genomic analysis of B. bacteriovorus strain HD100 suggested that predatory consumption of prey DNA by lytic enzymes made Bdellovibrio less likely than other bacteria to acquire DNA by lateral gene transfer (LGT). However the Doolittle and Pan groups predicted, in silico, both ancient and recent lateral gene transfer into the B. bacteriovorus HD100 genome. Results: To test these predictions, we isolated a predatory bacterium from the River Tiber- a good potential source of LGT as it is rich in diverse bacteria and organic pollutants- by enrichment culturing with E. coli prey cells. The isolate was identified as B. bacteriovorus and named as strain Tiberius. Unusually, this Tiberius strain showed simultaneous prey-independent growth on organic nutrients and predatory growth on live prey. Despite the prey-independent growth, the homolog of bd0108 did not have typical prey-independent-type mutations. The dual growth mode may reflect the high carbon content of the river, and gives B. bacteriovorus Tiberius extended non-predatory contact with the other bacteria present. The HD100 and Tiberius genomes were extensively syntenic despite their different cultured-terrestrial/freshly-isolated aquatic histories; but there were significant differences in gene content indicative of genomic flux and LGT. Gene content comparisons support previously published in silico predictions for LGT in strain HD100 with substantial conservation of genes predicted to have ancient LGT origins but little conservation of AT-rich genes predicted to be recently acquired. Conclusions: The natural niche and dual predatory, and prey-independent growth of the B. bacteriovorus Tiberius strain afforded it extensive non-predatory contact with other marine and freshwater bacteria from which LGT is evident in its genome. Thus despite their arsenal of DNA-lytic enzymes; Bdellovibrio are not always predatory in natural niches and their genomes are shaped by acquiring whole genes from other bacteria

The Note synthesis and crystal structure of a cerium(III) complex of 2,6-bis [2-formylphenoxymethyl]pyridine

Abstract The synthesis and X-ray crystal structure of a ten-coordinate cerium(III) nitrate complex of 2,6-bis[2-formylphenoxymethyl]-pyridine is reported

Effects of prenatal exposure to a low dose atrazine metabolite mixture on pubertal timing and prostate development of male Long-Evans rats

The present study examines the postnatal reproductive development of male rats following prenatal exposure to an atrazine metabolite mixture (AMM) consisting of the herbicide atrazine and its environmental metabolites diaminochlorotriazine, hydroxyatrazine, deethylatrazine, and deisopropylatrazine. Pregnant Long Evans rats were treated by gavage with 0.09, 0.87, or 8.73 mg AMM/kg body weight (BW), vehicle, or 100 mg ATR/kg BW positive control, on gestation days 15-19. Preputial separation was significantly delayed in 0.87 mg and 8.73 mg AMM-exposed males. AMM-exposed males demonstrated a significant treatment-related increase in incidence and severity of inflammation in the prostate on postnatal day (PND) 120. A dose-dependent increase in epididymal fat masses and prostate foci were grossly visible in AMM-exposed offspring. These results indicate that a short, late prenatal exposure to mixture of chlorotriazine metabolites can cause chronic prostatitis in male LE rats. The mode of action for these effects is presently unclear