Demethylation of the progesterone receptor CpG island is not required for progesterone receptor gene expression

In a previous study we have shown that an intravenous infusion of pramlintide (an analogue of human amylin) delayed gastric emptying, but the dose of pramlintide was supraphysiological in relation to the amylin response to food in non-diabetic subjects. The purpose of this study was to examine the dose response relationship of subcutaneous injections of pramlintide on gastric emptying and to determine whether administration of the drug before one meal has an impact on the subsequent meal. Eleven men with insulin-dependent diabetes mellitus were studied in a double-blind, randomised, four-way crossover design. None had autonomic neuropathy. Euglycaemia was maintained overnight before the study day. At -30 min the patients self-injected their usual morning insulin and at -15 min they injected the study drug (either placebo or 30, 60 or 90 microg pramlintide) subcutaneously. At 0 min they ate a standard meal consisting of a pancake, labelled with 99mTc, and a milkshake containing 3-ortho-methylglucose (3-OMG). Gastric emptying images were obtained for the next 8 h. At 240 min the subjects ate a similar meal, but on this occasion the pancake was labelled with (111)In. All three doses of pramlintide delayed emptying of the solid component of the first meal (p < 0.004) with no significant difference between the drug doses. There were no differences between placebo and pramlintide after the second meal. All three doses of pramlintide resulted in a prolongation in the time to peak plasma 3-OMG level (p < 0.0001) after the first meal but there was no difference after the second meal.     

The Effects of Limited Spares and Scheduled Downtime Upon The Dependability of a Simple System

Preventive maintenance and repair during a mission have an important effect on the dependability of ships' systems. Space and weight limitations mean that not all repairs can be carried out during the mission and this limits the dependability which can be achieved. Using a simple diesel generator arrangement as an example, this paper discusses the relationships between dependability, downtime for preventive maintenance, proportion of failures repairable at sea, and equipment failure rate.     

Studies of aversive conditioning for alcoholics: A critical review of theory and research methodology.

Reviews studies of the applications of aversive conditioning procedures to alcoholics. The review is divided into sections on electrical and chemical aversive stimulation and is organized according to the level of research design used. While many positive outcomes are reported, inconsistent theoretical underpinnings of the research are also reported. The lack of systematic investigation of relationships between therapist, patient, and technique characteristics indicate the need for further investigation. The ethics of using the techniques reviewed with human Ss are discussed. (62 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fly's eye: a counting camera for thermal neutrons-some applications, problems, and prospects

An area detector for thermal neutrons based on image intensification techniques has been described. Some capabilities and limitations of the detection system have been discussed. Among the former are high spatial resolution, high instantaneous counting rate, electronic zoom, time-gating, and integration. The detector is limited in that the maximum counting rate for a resolution element is 60 regularly spaced counts per second. Also, the nonuniformity of response over the detector puts a limit on the useful size and necessitates point-by-point calibration. In addition, a higher efficiency for neutron detection would be desirable. Some typical applications of the system are crystal inspection, neutron magnetic diffraction topography, and searches for temperature-induced changes in diffraction patterns. The future application of solid-state television sensors and microchannel-plate intensifiers to improve the system were briefly mentioned.     

The influence of a back support harness on spinal forces during sheep shearing

Previous research has classified the occupation of sheep shearing as heavy work where shearers flex their spine and hips for long periods of time, handle awkward loads and expend high amounts of energy. The aim of this research was to investigate the magnitude of spinal forces produced during the shearing phase of the work and to determine whether the use of a commercially available back support harness would reduce these forces. Following discussion on task complexity and risk of back injury with senior shearing instructors, three component tasks of the shearing phase were identified as posing high risk of injury and were prioritized for primary analysis. Although the dragging out of a sheep in preparation for shearing and an unexpected loss of animal control were also identified as being of high risk, technological and instrumentation difficulties precluded their analysis. Twelve experienced shearers were videotaped while shearing with and without the use of a back harness. Surface mounted retro-reflective markers placed on the trunk defined three linked segments: Pelvis, Lumbar and Head, Arms, and Upper Trunk (HAUT). A 3D, link segment, top down, inverse dynamics approach was used to describe the motion and to estimate forces involved during the identified tasks of shearing. The spinal force/time profiles of this sample of shearers demonstrated large compressive and shear forces for all three tasks that are close to the NIOSH and University of Waterloo action limits for compressive and shear forces respectively (McGill 1997, Yingling and McGill 1999, Marras 2000). The use of the back support harness reduced these forces by substantial and statistically significant amounts. This effect was consistent across all three tasks. The results of this study demonstrate the production of high levels of compressive and shear forces within the spine of shearers during the three shearing tasks studied and that the use of a back support harness can substantially reduce these forces. Therefore the use of a back harness may reduce the cumulative load on the spine during shearing thereby moderating damage to the articular structures. However it is not known whether the harness would protect the spine from a sudden or unexpected force.     

Characterization of the binding site for inhibitors of the HPV11 E1-E2 protein interaction on the E2 transactivation domain by photoaffinity labeling and mass spectrometry

An indandione-containing class of inhibitors abrogates DNA replication of human papillomavirus (HPV) types 6 and 11 by binding reversibly to the transactivation domain (TAD) of the viral E2 protein and inhibiting its interaction with the viral E1 helicase. To locate the binding site of this class of protein-protein interaction inhibitors, a benzophenone derivative was used to generate an irreversibly labeled E2-TAD polypeptide. The single site of covalent modification of the E2-TAD was identified by proteolytic digestions using trypsin, LysC, and V8 proteases and characterization of the resulting peptides by LC-MS procedures. Through this methodology, the benzophenone attachment point was located at the terminal methyl of residue Met101. Evidence further pinpointed the site of photoaffinity attachment to the terminal carbon atom, which is significant in providing a definitive example of the ability to locate photoinduced cross-linking to a polypeptide with atomic resolution using solely mass spectrometric detection. The location of the inhibitor binding site vis-à-vis the Glu39 and Glu100 residues sensitive to mutation for HPV 11 E2-TAD is discussed in relation to the crystal structure of the E2-TAD from the related HPV type 16.     

Darcy's law for oscillatory flow

By stimulating the Helmholtz resonance of an empty narrow necked vessel, a small sinusoidal component can be superimposed on atmospheric pressure within the vessel. From the damping of this sinusoidal component on the introduction of a sand layer into the vessel, the permeability of the layer can be determined. For 250–300 μm sand it was found that Darcy's law for steady flow remained valid up to frequencies of 100 Hz.