Rapid, solid-phase based automated analysis of chromatin structure and transcription factor occupancy in living eukaryotic cells

Transcription factors, chromatin components and chromatin modification activities are involved in many diseases including cancer. However, the means by which alterations in these factors influence the epigenotype of specific cell types is poorly understood. One problem that limits progress is that regulatory regions of eukaryotic genes sometimes extend over large regions of DNA. To improve chromatin structure–function analysis over such large regions, we have developed an automated, relatively simple procedure that uses magnetic beads and a capillary sequencer for ligation-mediated-PCR (LM-PCR). We show that the procedure can be used for the rapid examination of chromatin fine-structure, nucleosome positioning as well as changes in transcription factor binding-site occupancy during cellular differentiation

Weight changes following lower limb arthroplasty : a prospective observational study

The aim of this study was to assess patterns of weight loss/gain following total hip or knee joint replacement. Four hundred and fifty primary lower limb arthroplasty patients, where the current surgery was the last limiting factor to improved mobility, were selected. Over a one year period 212 gained weight (mean 5.03kg), 92 remained static, and 146 lost weight. The median change was a weight gain of 0.50Kg (p=0.002). All patients had a significant improvement in Oxford outcome scores. Hip arthroplasty patients were statistically more likely to gain weight than knee arthroplasty patients. A successful arthroplasty, restoring a patient's mobility, does not necessarily lead to subsequent weight loss. The majority of patients put on weight with an overall net weight gain. No adverse effect on functional outcome was noted

Ultradian, circadian and seasonal rhythms in cortisol secretion and adrenal responsiveness to ACTH and yarding in unrestrained red deer (Cervus elaphus) stags

Seasonal changes in the activity and responsiveness of the adrenal gland in red deer (Cervus elaphus) stags were quantified by measuring 24 h endogenous cortisol secretory profiles and plasma cortisol responses to either administration of exogenous ACTH or a standardised stressor during November (period of velvet growth), February (pre-rut), April (mid-rut) and July (post-rut) (southern hemisphere) using a remote blood sampling device (DracPac). Ultradian rhythms in the concentration of plasma cortisol were observed resulting from the episodic secretion of cortisol from the adrenal cortex at a mean rate of 0.8 pulses/h. Circadian rhythms in plasma cortisol concentrations were also found in 11 out of the 20 complete 24 h profiles (mean amplitude, 3.8+/-1.4 ng/ml). Seasonal rhythms in mean 24 h plasma cortisol concentrations and cortisol pulse parameters were also observed. Mean 24 h plasma cortisol concentrations were higher in November (12.5+/-1.0 ng/ml) than in February (6.3+/-1.0 ng/ml), April (4.0+/-1.0 ng/ml) or July (4.2+/-1. 0 ng/ml). Cortisol pulse height, nadir and amplitude were all significantly higher in November than at other times of the year (P<0.01). Peak cortisol concentrations following infusion of ACTH(1-24) (0.04 IU kg(-1)) were higher (P<0.05) in November (55.8+/-2.7 ng/ml) and lower (P<0.001) in April (33.7+/-1.8 ng/ml) than those in February and July (48.7+/-2.0 ng/ml and 45.4+/-2.0 ng/ml respectively). The area under the cortisol response curve was significantly smaller (P<0.05) in April (266.6+/-15.3 ng/ml/190 min) than at other times of the year (February, 366.1+/-15.3 ng/ml/190 min; July, 340.7+/-15.3 ng/ml/190 min and November, 387.8+/-21.2 ng/ml/190 min). These data demonstrate that the adrenal gland of the red deer stag exhibits ultradian, circadian and seasonal rhythms in activity, and that its responsiveness to ACTH varies with season. November, a period of reproductive quiescence in the southern hemisphere, with new antler growth and rapid weight gain, is associated with higher mean plasma cortisol concentrations and a greater responsiveness to exogenous ACTH. In contrast, the breeding season is associated with lower adrenal activity and responsiveness

Low-frequency QPO from the 11 Hz accreting pulsar in Terzan 5: not frame dragging

We report on 6 RXTE observations taken during the 2010 outburst of the 11 Hz accreting pulsar IGR J17480-2446 located in the globular cluster Terzan 5. During these observations we find power spectra which resemble those seen in Z-type high-luminosity neutron star low-mass X-ray binaries, with a quasi-periodic oscillation (QPO) in the 35-50 Hz range simultaneous with a kHz QPO and broad band noise. Using well known frequency-frequency correlations, we identify the 35-50 Hz QPOs as the horizontal branch oscillations (HBO), which were previously suggested to be due to Lense-Thirring precession. As IGR J17480-2446 spins more than an order of magnitude more slowly than any of the other neutron stars where these QPOs were found, this QPO can not be explained by frame dragging. By extension, this casts doubt on the Lense-Thirring precession model for other low-frequency QPOs in neutron-star and perhaps even black-hole systems.Comment: 6 pages, 5 figures, Accepted for publication in ApJ

CRITICAL ECONOMIC FACTORS FOR SUCCESS OF A BIOMASS CONVERSION PLANT FOR AGRICULTURAL RESIDUE, YARD RESIDUE AND WOOD WASTE IN FLORIDA

This model evaluates the potential success of a cellulosic ethanol plant in Florida. Critical Economic factors of the plant were simulated to assess the ability of this project. These critical factors include the feedstock to be used, the cost of the facility, transportation costs and the discount rate for the net present value (NPV). Results and observations are presented in this paper.Biofuels, renewable energy, cellulosic ethanol, biomass, Agribusiness, Community/Rural/Urban Development, Crop Production/Industries, Financial Economics, Production Economics, Productivity Analysis, Resource /Energy Economics and Policy, Risk and Uncertainty,

A Clash of Fundamental Rights: Conflicts Between the Fifth and Sixth Amendments in Criminal Trials

The United States Constitution\u27s Fifth and Sixth Amendments protect the rights of criminal defendants and witnesses. The Fifth Amendment\u27s privilege against self-incrimination protects witnesses from forced self-incrimination, and the Sixth Amendment provides criminal defendants with the right to cross-examine prosecution witnesses and to have compulsory process for obtaining witnesses. These fundamental rights conflict when a prosecution witness invokes the Fifth Amendment privilege on cross-examination or when a defense witness invokes the privilege on direct-examination. A grant of either use or transactional immunity would remove the potential for self-incrimination, but courts are split on whether they possess the authority to grant such immunity to defense witnesses. This Note examines the judicial approaches to resolving the conflicts between the Fifth and Sixth Amendment, and it analyzes the factors that favor and those that oppose a grant of immunity to defense witnesses. This Note concludes that defense witnesses should be granted use immunity whenever their testimony might be exculpatory

Development of core outcome sets in hidradenitis suppurativa:a systematic review of outcome measure instruments to inform the process

Background The recent hidradenitis suppurativa (HS) Cochrane review identified outcome measure heterogeneity as an important issue to address when designing future HS trials. Objectives To follow the Harmonising Outcome Measures for Eczema (HOME) roadmap, by performing a systematic review of HS outcome measure instruments to inform the development of a HS core outcome set. Methods We performed a systematic review to identify validation evidence for outcome measure instruments used in HS randomised controlled trials (RCTs), and assessed the methodological quality of all HS outcome measure validity studies using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. Results The 12 RCTs included in the HS Cochrane review utilised a total of 30 outcome measure instruments, including 16 physician reported instruments, 11 patient reported instruments and three composite measures containing elements of both. Twenty-seven (90%) of the instruments lacked any validation data. Two further instruments have been developed and partially validated recently. Of the seven studies meeting our systematic review inclusion criteria, six were of ‘fair’ or ‘poor’ methodological quality, in part because most of the studies were not primarily designed for instrument validation. The HiSCR instrument is supported by good quality validation data but there are gaps including assessment of internal consistency, inter-rater reliability and minimal clinically important difference, and convergent validity fell below the acceptable range for some comparisons. Conclusions Multiple, usually unvalidated outcome measure instruments have been used in HS RCTs. Where validation evidence is available there are issues of low methodological quality or incomplete validity assessment and so no instruments can be fully recommended currently

An application of the requirement vs capability analysis to estimating design reliability of solid rocket motors

Design reliability parameters for solid propellant rocket engine