Exercise--it''s never too late: the strong-for-life program

Design and associated good practices are described for a modular glovebox connector to improve control of radioactive and chemically toxic materials. The connector consists of an anodized aluminum circular port with a mating spacer, gaskets, and retaining rings for joining two parallel ends of commercially available or custom-manufactured glovebox enclosures. Use of the connector allows multiple gloveboxes to be quickly assembled or reconfigured in functional units. Connector dimensions can be scaled to meet operational requirements for access between gloveboxes. Options for construction materials are discussed, along with recommendations for installation of the connector in new or retrofitted systems. Associated good practices include application of surface coatings and caulking, use of disposable glovebags, and proper selection and protection of gasket and glove materials. Use of the connector at an inhalation toxicology research facility has reduced the time and expense required to reconfigure equipment for changing operational requirements, the dispersion of contamination during reconfigurations, and the need for decommissioning and disposal of contaminated enclosures.     

I'm Pc01002/SpringPeeper/ED288l.6; Who are You?

In considering identity management, the first issue is—What is identity? This is, of course, an issue that has plagued poets, philosophers, and playwrights for centuries. We're concerned with a more prosaic version of the question: How does an entity recognize another entity? This important question occurs when access to resources, such as health or financial records, services, or benefits, is limited to specific entities. The entity in question could be a person, a computer, or even a device with quite limited memory and computational power. In this issue of IEEE Security & Privacy—the first of what we suspect will be several special issues on identity management—we have chosen to focus on identity management in which the entity being identified is a person.     

Ergonomics diagnosis components in rehabilitation: statistical evaluation of an assessment instrument

The current paper examines an assessment instrument used for combined medical and occupational rehabilitation (MOR) in a group of German hospitals. Patients with a history of musculo-skeletal disease make up a significant proportion of those undergoing rehabilitation. Scale and factor structures, discriminant factors and clustering procedures used in the Bavaria rehabilitation patient assessment method (BRPAM) are investigated in a cross-sectional study involving a sample of 800 patients. Although the results reveal good correlation between differences in the job demand/patient capability profiles and the typical stresses to which the relevant occupation is exposed, analyses also indicate that several factors and items are unstable. According to subjective assessment by the patients, the therapeutic objectives are fully attained in some 80% of cases. Discrepancies between job demands and patient capability revealed by the BRPAM yield pointers to choice of therapy and its chances of success, but these need to be examined in greater detail in long-term studies.     

Inactivation of S-adenosyl-L-homocysteine hydrolase and antiviral activity with 5',5',6',6'-tetradehydro-6'-deoxy-6'-halohomoadenosine analogues (4'-haloacetylene analogues derived from adenosine)

Treatment of a protected 9-(5, 6-dideoxy-beta-D-ribo-hex-5-ynofuranosyl)adenine derivative with silver nitrate and N-iodosuccinimide (NIS) and deprotection gave the 6'-iodo acetylenic nucleoside analogue 3c. Halogenation of 3-O-benzoyl-5,6-dideoxy-1, 2-O-isopropylidene-alpha-D-ribo-hex-5-enofuranose gave 6-halo acetylenic sugars that were converted to anomeric 1,2-di-O-acetyl derivatives and coupled with 6-N-benzoyladenine. These intermediates were deprotected to give the 6'-chloro 3a, 6'-bromo 3b, and 6'-iodo 3c acetylenic nucleoside analogues. Iodo compound 3c appears to inactivate S-adenosyl-L-homocysteine hydrolase by a type I ("cofactor depletion") mechanism since complete reduction of enzyme-bound NAD+ to NADH was observed and no release of adenine or iodide ion was detected. In contrast, incubation of the enzyme with the chloro 3a or bromo 3b analogues resulted in release of Cl- or Br- and Ade, as well as partial reduction of E-NAD+ to E-NADH. Compounds 3a, 3b, and 3c were inhibitory to replication of vaccinia virus, vesicular stomatitis virus, parainfluenza-3 virus, and reovirus-1 (3a < 3b < 3c, in order of increasing activity). The antiviral effects appear to correlate with type I mechanism-based inhibition of S-adenosyl-L-homocysteine hydrolase. Mechanistic considerations are discussed.     

A novel mechanism-based inhibitor (6'-bromo-5', 6'-didehydro-6'-deoxy-6'-fluorohomoadenosine) that covalently modifies human placental S-adenosylhomocysteine hydrolase

Most inhibitors of S-adenosylhomocysteine (AdoHcy) hydrolase function as substrates for the "3'-oxidative activity" of the enzyme and convert the enzyme from its active form (NAD+) to its inactive form (NADH) (Liu, S., Wolfe, M. S., and Borchardt, R. T. (1992) Antivir. Res. 19, 247-265). In this study, we describe the effects of a mechanism-based inhibitor, 6'-bromo-5', 6'-didehydro-6'-deoxy-6'-fluorohomoadenosine (BDDFHA), which functions as a substrate for the "6'-hydrolytic activity" of the enzyme with subsequent formation of a covalent linkage with the enzyme. Incubation of human placental AdoHcy hydrolase with BDDFHA results in a maximum inactivation of 83% with the remaining enzyme activity exhibiting one-third of the kcat value of the native enzyme. This partial inactivation is concomitant with the release of both Br- and F- ions and the formation of adenine (Ade). The enzyme can be covalently labeled with [8-3H]BDDFHA, resulting in a stoichiometry of 2 mol of BDDFHA/mol of the tetrameric enzyme. The 3H-labeled enzyme retains its original NAD+/NADH content. Tryptic digestion and subsequent protein sequencing of the [8-3H]BDDFHA-labeled enzyme revealed that Arg196 is the residue that is associated with the radiolabeled inhibitor. The partition ratio of the Ade formation (nonlethal event) to covalent acylation (lethal event) is approximately 1:1. From these experimental results, a possible mechanism by which BDDFHA inactivates AdoHcy hdyrolase is proposed: enzyme-mediated water addition at the C-6' position of BDDFHA followed by elimination of Br- ion results in the formation of homoAdo 6'-carboxyl fluoride (HACF). HACF then partitions in two ways: (a) attack by a proximal nucleophile (Arg196) to form an amide bond after expulsion of F- ion (lethal event) or (b) depurination to form Ade and hexose-derived 6-carboxyl fluoride (HDCF), which is further hydrolyzed to hexose-derived 6-carboxylic acid (HDCA) and F- ion (nonlethal event).     

Methodologic aspects of body water kinetic dynamic studies

Tissue status at the site of experimental bone defects filled by two compositions based on polyacrylamide gel and hydroxyapatite with (experimental group) and without (controls) lysozyme was studied in rats by the histomorphological method. "Negative" symptoms, such as inflammation, formation of osteocyte-free bone at the interface of the defect, and reduction of red bone marrow were more manifest in the controls than in animals treated with lysozyme. In the test group substitution of composite material for connective tissue structures and bone reparation were much more active and rapid than in the controls. Inflammation and dystrophic changes at the interface of defects were less pronounced and gradually resolved.     

Klinefelter's syndrome as a model of anomalous cerebral laterality: testing gene dosage in the X chromosome pseudoautosomal region using a DNA microarray

Consistent handedness and language laterality are two of the most striking behavioral and cognitive asymmetries observed in humans. Alterations in the typical pattern of cerebral laterality, termed "anomalous dominance," is observed in left-handers and some patients with verbal learning disabilities. We undertook the study of a genetically distinct group of subjects, XXY males (Klinefelter's syndrome; KS), who demonstrate anomalous dominance in a variety of testing paradigms in order to begin to elucidate the molecular basis of anomalous dominance in this population. KS subjects manifest specific verbal learning disability, evidence of altered functional laterality for phonologic processing, and an increase in left-handedness when measured by skill. It is proposed that an alteration in gene dosage in the pseudoautosomal region (PAR) of the sex chromosomes is the most likely explanation for anomalous dominance in these patients. This is especially intriguing in light of previously described genetic models of cerebral laterality that suggest a contributing locus in the PAR, or adjacent high homology regions of the X chromosome. We have developed an ordered DNA microarray covering the X chromosome PAR at high resolution for hybridization with two-color fluorescently labeled probes. We demonstrate the ability to detect changes in hybridization signal that will facilitate efficient large-scale screening of this region for alterations in gene dosage associated with features of anomalous dominance and other cognitive or behavioral phenotypes.     

Adaptation and verification of the relocatable Gill-Thomas-Cosman frame in stereotactic radiotherapy

PURPOSE: Stereotactic radiotherapy (SRT) combines techniques of stereotactic radiosurgery (SRS) with radiation therapy fractionation schemes. Fractionation in SRT necessitates a relocatable immobilization system to precisely reproduce the patient's position at each treatment. The Gill-Thomas-Cosman (GTC) head frame is such an immobilization device compatible with the Brown-Roberts-Wells (BRW) stereotactic system. We describe this device, our modifications to the original design, the repeat position accuracy, and the daily verification procedure. METHODS AND MATERIALS: The original GTC frame was tested on volunteers. This testing led to an improved strapping system, the decision to construct the oral fixation appliance at our dental clinic, and the construction of a depth confirmation helmet to rapidly confirm the position of the frame on a daily basis. The GTC frame, at our institution, is not acceptable for children requiring anesthesia, and a new frame, the "Boston Childrens' Hospital" frame, was designed. This device uses the base ring of the GTC frame. Airway access is maintained through fixation on the nasal-glabellar region and the ear canal rather than the hard palate and upper gingiva. RESULTS: The modifications of the GTC frame and the verification protocol result in repeat positioning of the frame with respect to the patient anatomy, with a standard deviation of 0.4 mm for both the modified GTC frame and the Boston Childrens' Hospital frame. The relocatibility of the frames has been established in over 2,000 patient setups in over 60 patients to date. DISCUSSION: The GTC frame is a noninvasive and versatile fixation system that provides patient comfort, as well as accurate relocatibility for SRT. The frame is not appropriate for single fraction radiosurgery, as a large setup error (> 2 mm) for a single treatment cannot be excluded. The GTC frame is compatible with the BRW system, and treatment planning for SRT and SRS patients is identical. We currently treat 10-13 SRT patients per day with intracranial neoplasms on a dedicated stereotactic therapy unit. In addition, the Boston Childrens' Hospital frame allows the use of stereotactic therapy in the treatment of children under 6 years of age. This population will benefit especially from precise and highly focal cranial irradiation.     

Diazo Compounds in the Photocopying Industry

The relationship between the structures of diazos used in the industry and their chemical and physical properties are discussed. Photocopying processes using diazos are surveyed and the properties required by the diazos employed are considered.