A proportional counter spectrometer study of the beta-decay of radioactive S-35, Pm-147, Ni-63, and C-14

A proportional counter spectrometer, hereinafter denoted as a p.c.s., of unique design has been constructed for the purpose of measuring beta-spectra whose energies lie below a few hundred Kev. The p.c.s. is well suited for the problem in that thin and uniform radioactive sources which are essential for accurate low energy spectral measurements can be employed. The utilization of radioactive sources of low surface densities is made possible by an allowable source area of a few square centimeters and an ~100 per cent geometrical efficiency for particle detection by the p.c.s. In addition, the p.c.s. obviates a Geiger-Huller counter window of finite thickness which is often associated with the magnetic spectrometers. The penetration of beta-particles through the Geiger-Muller counter window can lead to distortion of the beta-spectrum at low energies

Friedewald-Estimated Versus Directly Measured Low-Density Lipoprotein Cholesterol and Treatment Implications

ObjectivesThe aim of this study was to compare Friedewald-estimated and directly measured low-density lipoprotein cholesterol (LDL-C) values.BackgroundLDL-C is routinely estimated by the Friedewald equation to guide treatment; however, compatibility with direct measurement has received relatively little scrutiny, especially at levels <70 mg/dl now targeted in high-risk patients.MethodsWe examined 1,340,614 U.S. adults who underwent lipid profiling by vertical spin density gradient ultracentrifugation (Atherotech, Birmingham, Alabama) from 2009 to 2011. Following standard practice, Friedewald LDL-C was not estimated if triglyceride levels were ≥400 mg/dl (n = 30,174), yielding 1,310,440 total patients and 191,333 patients with Friedewald LDL-C <70 mg/dl.ResultsPatients were 59 ± 15 years of age and 52% were women. Lipid distributions closely matched those in the National Health and Nutrition Examination Survey. A greater difference in the Friedewald-estimated versus directly measured LDL-C occurred at lower LDL-C and higher triglyceride levels. If the Friedewald-estimated LDL-C was <70 mg/dl, the median directly measured LDL-C was 9.0 mg/dl higher (5th to 95th percentiles, 1.8 to 15.4 mg/dl) when triglyceride levels were 150 to 199 mg/dl and 18.4 mg/dl higher (5th to 95th percentiles, 6.6 to 36.0 mg/dl) when triglyceride levels were 200 to 399 mg/dl. Of patients with a Friedewald-estimated LDL-C <70 mg/dl, 23% had a directly measured LDL-C ≥70 mg/dl (39% if triglyceride levels were concurrently 150 to 199 mg/dl; 59% if triglyceride levels were concurrently 200 to 399 mg/dl).ConclusionsThe Friedewald equation tends to underestimate LDL-C most when accuracy is most crucial. Especially if triglyceride levels are ≥150 mg/dl, Friedewald estimation commonly classifies LDL-C as <70 mg/dl despite directly measured levels ≥70 mg/dl, and therefore additional evaluation is warranted in high-risk patients

Building Partnerships to Address Social and Technological Challenges to Enhance Farm Profitability and Improve Water Quality Through Better Grassland Management

With 2.1 million acres of pastureland and 1.25 million acres of hay land in Virginia, the rural Virginia landscape is predominately grassland. These lands form the base of the $3.96 billion-dollar livestock and dairy industry in Virginia. Managing these livestock in a profitable manner for farmers and beneficial to the environment is important. A cultural tradition with roots in colonial times has been to run animals in large fields year-round throughout Virginia. Livestock often graze from spring until fall (about 220 days), and farmers feed hay the remainder of the year. Spikes in the cost of fuel, fertilizer, and equipment are making traditional grazing/haying systems less profitable. The Virginia Cooperative Extension Farm Enterprise budgets show that that the cost of hay accounts for over 50$75 per cow by extending their grazing season. The same phenomenon applies to other types of grazing livestock. If ten percent of the livestock producers in the state adopted better grazing management to extend their grazing season by 60 days, profitability is expected for Virginia grazing livestock producers by over $5 million per year. Practices such as rotational grazing and stream exclusion are directly tied to National and State goals to improve water quality in the Chesapeake Bay. Virginia’s Phase III WIP (Chesapeake Bay Watershed Improvement Plan) seeks the exclusion of livestock from all perennial streams and achieving good rotational grazing practices on 347,000 acres of pasture. A number of agencies and private sector groups have been providing cost share and technical guidance to incentivize livestock stream exclusion and the installation of pasture management infrastructure. Installation is only part of the challenge. Farmers also need to be taught how to how to manage the system in a profitable manner and have been slow to adopt good pasture management practices. Preliminary data show that 87% of Virginia’s cow-calf producers manage their grasslands using traditional methods. Only six percent have extended their grazing season beyond 265 days

In vitro and in vivo mRNA delivery using lipid-enveloped pHresponsive polymer nanoparticles

Biodegradable core−shell structured nanoparticles with a poly(β-amino ester) (PBAE) core enveloped by a phospholipid bilayer shell were developed for in vivo mRNA delivery with a view toward delivery of mRNA-based vaccines. The pH-responsive PBAE component was chosen to promote endosome disruption, while the lipid surface layer was selected to minimize toxicity of the polycation core. Messenger RNA was efficiently adsorbed via electrostatic interactions onto the surface of these net positively charged nanoparticles. In vitro, mRNA-loaded particle uptake by dendritic cells led to mRNA delivery into the cytosol with low cytotoxicity, followed by translation of the encoded protein in these difficult-to-transfect cells at a frequency of 30%. Particles loaded with mRNA administered intranasally (i.n.) in mice led to the expression of the reporter protein luciferase in vivo as soon as 6 h after administration, a time point when naked mRNA given i.n. showed no expression. At later time points, luciferase expression was detected in naked mRNA-treated mice, but this group showed a wide variation in levels of transfection, compared to particle-treated mice. This system may thus be promising for noninvasive delivery of mRNA-based vaccines.United States. Dept. of Defense (Institute for Soldier Nanotechnology, contract W911NF-07-D-0004)Ragon Institute of MGH, MIT and HarvardSingapore. Agency for Science, Technology and ResearchHoward Hughes Medical Institute (Investigator

Different Drivers: Exploring employee involvement in corporate philanthropy

Corporate Philanthropy (CP) is multi-dimensional, differs between sectors and involves both individual and organizational decision-making to achieve business and social goals. However, the CP literature characteristically focuses on strategic decisions made by business leaders and ignores the role of employees, especially those in lower status and lower paid positions. To redress this imbalance, we conducted a qualitative study of employees’ involvement in CP processes in ten workplaces in the South East of England to identify whether and how they are involved in CP decision-making and to capture their perspective on the nature of CP and the benefits generated by such activities. We specifically chose to study workplaces where employees are involved in the actual execution of the CP strategy, prioritising companies with a visible presence on the high street. The results illustrate the benefits of involving employees in CP decision-making, which we argue derives in part from the ‘liminal-like states’ that typify CP activities organised by shop floor staff, involving the temporary overturning of hierarchies, humanising of workplaces and opportunities for lower-level staff to prioritise their personal philanthropic preferences and signal their charitable identity to colleagues and customers. Whilst the data also suggests that CP decision-making remains predominantly top-down and driven by profit-oriented goals, we conclude that employees should be involved in choosing charitable causes as well as in designing and implementing workplace fundraising, in order to maximise the advantages of CP for the company and for wider society

Compartment-Restricted Biotinylation Reveals Novel Features of Prion Protein Metabolism in Vivo

A selective tagging method for detecting minor alternatively-localized populations of a protein is used to study a disease-associated transmembrane form of prion protein. The analysis reveals key features of transmembrane prion protein metabolism and one way this is altered by human disease-causing mutants

Deep Sequencing the Transcriptome Reveals Seasonal Adaptive Mechanisms in a Hibernating Mammal

Mammalian hibernation is a complex phenotype involving metabolic rate reduction, bradycardia, profound hypothermia, and a reliance on stored fat that allows the animal to survive for months without food in a state of suspended animation. To determine the genes responsible for this phenotype in the thirteen-lined ground squirrel (Ictidomys tridecemlineatus) we used the Roche 454 platform to sequence mRNA isolated at six points throughout the year from three key tissues: heart, skeletal muscle, and white adipose tissue (WAT). Deep sequencing generated approximately 3.7 million cDNA reads from 18 samples (6 time points ×3 tissues) with a mean read length of 335 bases. Of these, 3,125,337 reads were assembled into 140,703 contigs. Approximately 90% of all sequences were matched to proteins in the human UniProt database. The total number of distinct human proteins matched by ground squirrel transcripts was 13,637 for heart, 12,496 for skeletal muscle, and 14,351 for WAT. Extensive mitochondrial RNA sequences enabled a novel approach of using the transcriptome to construct the complete mitochondrial genome for I. tridecemlineatus. Seasonal and activity-specific changes in mRNA levels that met our stringent false discovery rate cutoff (1.0×10−11) were used to identify patterns of gene expression involving various aspects of the hibernation phenotype. Among these patterns are differentially expressed genes encoding heart proteins AT1A1, NAC1 and RYR2 controlling ion transport required for contraction and relaxation at low body temperatures. Abundant RNAs in skeletal muscle coding ubiquitin pathway proteins ASB2, UBC and DDB1 peak in October, suggesting an increase in muscle proteolysis. Finally, genes in WAT that encode proteins involved in lipogenesis (ACOD, FABP4) are highly expressed in August, but gradually decline in expression during the seasonal transition to lipolysis

An overlooked connection: serotonergic mediation of estrogen-related physiology and pathology

BACKGROUND: In humans, serotonin has typically been investigated as a neurotransmitter. However, serotonin also functions as a hormone across animal phyla, including those lacking an organized central nervous system. This hormonal action allows serotonin to have physiological consequences in systems outside the central nervous system. Fluctuations in estrogen levels over the lifespan and during ovarian cycles cause predictable changes in serotonin systems in female mammals. DISCUSSION: We hypothesize that some of the physiological effects attributed to estrogen may be a consequence of estrogen-related changes in serotonin efficacy and receptor distribution. Here, we integrate data from endocrinology, molecular biology, neuroscience, and epidemiology to propose that serotonin may mediate the effects of estrogen. In the central nervous system, estrogen influences pain transmission, headache, dizziness, nausea, and depression, all of which are known to be a consequence of serotonergic signaling. Outside of the central nervous system, estrogen produces changes in bone density, vascular function, and immune cell self-recognition and activation that are consistent with serotonin's effects. For breast cancer risk, our hypothesis predicts heretofore unexplained observations of the opposing effects of obesity pre- and post-menopause and the increase following treatment with hormone replacement therapy using medroxyprogesterone. SUMMARY: Serotonergic mediation of estrogen has important clinical implications and warrants further evaluation