Automated tester permits precise calibration of pressure transducers from 0 to 1050 psi

Automated portable checker allows last-minute calibration of pressure transducers before testing. It uses a pressure console and equipment that can produce test pressures of 0-1050 psi. The console can be connected to other apparatus for measurement and visual display of the electrical output

Effects of Diet Composition and Insulin Resistance Status on Plasma Lipid Levels in a Weight Loss Intervention in Women.

BackgroundOptimal macronutrient distribution of weight loss diets has not been established. The distribution of energy from carbohydrate and fat has been observed to promote differential plasma lipid responses in previous weight loss studies, and insulin resistance status may interact with diet composition and affect weight loss and lipid responses.Methods and resultsOverweight and obese women (n=245) were enrolled in a 1-year behavioral weight loss intervention and randomly assigned to 1 of 3 study groups: a lower fat (20% energy), higher carbohydrate (65% energy) diet; a lower carbohydrate (45% energy), higher fat (35% energy) diet; or a walnut-rich, higher fat (35% energy), lower carbohydrate (45% energy) diet. Blood samples and data available from 213 women at baseline and at 6 months were the focus of this analysis. Triglycerides, total cholesterol, and high- and low-density lipoprotein cholesterol were quantified and compared between and within groups. Triglycerides decreased in all study arms at 6 months (P<0.05). The walnut-rich diet increased high-density lipoprotein cholesterol more than either the lower fat or lower carbohydrate diet (P<0.05). The walnut-rich diet also reduced low-density lipoprotein cholesterol in insulin-sensitive women, whereas the lower fat diet reduced both total cholesterol and high-density lipoprotein cholesterol in insulin-sensitive women (P<0.05). Insulin sensitivity and C-reactive protein levels also improved.ConclusionsWeight loss was similar across the diet groups, although insulin-sensitive women lost more weight with a lower fat, higher carbohydrate diet versus a higher fat, lower carbohydrate diet. The walnut-rich, higher fat diet resulted in the most favorable changes in lipid levels.Clinical trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT01424007

The IL-6 Gene Promoter SNP and Plasma IL-6 in Response to Diet Intervention.

We recently reported that interleukin-6 (IL-6), an inflammatory marker associated with breast pathology and the development of breast cancer, decreases with diet intervention and weight loss in both insulin-sensitive and insulin-resistant obese women. Here, we tested whether an individual's genotype at an IL6 SNP, rs1800795, which has previously been associated with circulating IL-6 levels, contributes to changes in IL-6 levels or modifies the effect of diet composition on IL-6 in these women. We genotyped rs1800795 in overweight/obese women (N = 242) who were randomly assigned to a lower fat (20% energy), higher carbohydrate (65% energy) diet; a lower carbohydrate (45% energy), higher fat (35% energy) diet; or a walnut-rich (18% energy), higher fat (35% energy), lower carbohydrate (45% energy) diet in a 1-year weight loss intervention study of obesity-related biomarkers for breast cancer incidence and mortality. Plasma IL-6 levels were measured at baseline, 6 and 12 months. At baseline, individuals with a CC genotype had significantly lower IL-6 levels than individuals with either a GC or GG genotype (p < 0.03; 2.72 pg/mL vs. 2.04 pg/mL), but this result was not significant when body mass index (BMI) was accounted for; the CC genotype group had lower BMI (p = 0.03; 32.5 kg/m² vs. 33.6 kg/m²). We did not observe a 2-way interaction of time*rs1800795 genotype or diet*rs1800795 genotype. Our findings provide evidence that rs1800795 is associated with IL-6 levels, but do not support a differential interaction effect of rs1800795 and diet composition or time on changes in circulating IL-6 levels. Diet intervention and weight loss are an important strategy for reducing plasma IL-6, a risk factor of breast cancer in women, regardless of their rs1800795 genotype

Valence and magnetism in EuPd3S4\rm EuPd_3S_4 and (Y,La)xEu1−xPd3S4\rm (Y,La)_xEu_{1-x}Pd_3S_4

$^{151}$Eu M\"ossbauer spectroscopy shows that yttrium substitution in mixed-valent $\rm EuPd_3S_4$ drives the initial 50:50 mix of Eu$^{3+}$ and Eu$^{2+}$ towards pure Eu$^{2+}$, whereas lanthanum substitution has the opposite effect, but only for substitution levels above 50\%. We find that total valence electron count and chemical pressure effects cannot account for the observed behaviour, however conserving the cell volume provides a consistent description of the changes in the Eu$^{2+}$:Eu$^{3+}$ ratio. Remarkably, lanthanum substitution also leads to a clear transition from static mixed-valent behavior at lower temperatures to dynamic mixed valent behavior at higher temperatures, with the onset temperature monotonically increasing with Eu content and extrapolating to a value of $\sim$340~K for the pure $\rm EuPd_3S_4$ compound. Magnetic order persists at least as far as x=0.875 in both series, despite the drastic reduction in the amount of moment-carrying Eu$^{2+}$ ions.Comment: 16 pages, 26 figure

Requirements for market entry of gene drive-modified mosquitoes for control of vector-borne diseases: analogies to other biologic and biotechnology products

Gene drive-modified mosquitoes (GDMMs) are proposed as new tools for control and elimination of malaria and other mosquito-borne diseases, and promising results have been observed from testing conducted in containment. Although still at an early stage of development, it is important to begin now to consider approval procedures and market entry strategies for the eventual implementation of GDMMs in the context of disease control programs, as these could impact future research plans. It is expected that, as for other types of new products, those seeking to bring GDMMs to market will be required to provide sufficient information to allow the regulator(s) to determine whether the product is safe and effective for its proposed use. There already has been much emphasis on developing requirements for the biosafety components of the “safe and effective” benchmark, largely concerned with their regulation as genetically modified organisms. Other potential approval requirements have received little attention, however. Although GDMMs are expected to be implemented primarily in the context of public health programs, any regulatory analogies to other public health products, such as pharmaceuticals, vaccines, or chemical pesticides, must take into account the characteristics of live mosquito products. Typical manufacturing standards related to product identity, potency or quality will need to be adapted to GDMMs. Valuable lessons can be drawn from the regulatory approval processes for other whole organism and genetically modified (GM) organism products. Supply chain requirements, such as scale of production, location and design of production facilities, and methods of distribution and delivery, will be dependent upon the characteristics of the particular GDMM product, the conditions of use, and the region to be served. Plans for fulfilling supply chain needs can build upon experience in the development of other live insect products for use in public health and agriculture. Implementation of GDMMs would benefit from additional research on enabling technologies for long-term storage of mosquito life stages, efficient mass production, and area-wide delivery of GDMMs. Early consideration of these practical requirements for market entry will help to mitigate downstream delays in the development of these promising new technologies

Awareness regarding eye donation among stakeholders in Srikakulam district in South India

Background There is a huge need for the availability of transplantable donor corneas worldwide to reduce the burden of corneal blindness due to corneal opacity. Voluntary eye donation depends on the awareness levels of various stakeholders in the community. This study aimed to assess the awareness level regarding eye donation among various stakeholders in Srikakulam district in the state of Andhra Pradesh, India. Methods 355 subjects were selected from the district using multi stage random sampling. A pre tested semi structured questionnaire was used to collect information regarding each individual’s awareness, knowledge, and perception regarding eye donation. Each response was scored individually and a total score was calculated. Univariate and multivariate regression analysis was used to determine the factors associated with willingness towards eye donation and increased awareness levels. Results Of the 355 subjects interviewed, 192 (54%) were male and 163 (46%) were female. The mean age of the stakeholders was 35.9 years (SD ±16.1) and all the study subjects were literate. Ninety-three percent of subjects were aware of the concept of eye donation. Knowledge levels were similar among the teaching community and persons engaged in social service, but lower among students (p < 0.05). Among the stakeholders, there was considerable ambiguity regarding whether persons currently wearing spectacles or suffering from a chronic illnesses could donate their eyes. Older age group (p < 0.001), female gender (p < 0.001) and education (p < 0.001) were associated with increased knowledge levels. 82% of the subjects were willing to donate their eyes and this was unaffected by gender or geographical location (rural vs urban). Conclusions Awareness levels and willingness to donate eyes are high among the stakeholders in Srikakulam district in India. The services of stakeholders could be utilized, in conjunction with other community based eye donation counselors, to promote awareness regarding eye donation among the general population

Development of Novel In Vivo Chemical Probes to Address CNS Protein Kinase Involvement in Synaptic Dysfunction

Serine-threonine protein kinases are critical to CNS function, yet there is a dearth of highly selective, CNS-active kinase inhibitors for in vivo investigations. Further, prevailing assumptions raise concerns about whether single kinase inhibitors can show in vivo efficacy for CNS pathologies, and debates over viable approaches to the development of safe and efficacious kinase inhibitors are unsettled. It is critical, therefore, that these scientific challenges be addressed in order to test hypotheses about protein kinases in neuropathology progression and the potential for in vivo modulation of their catalytic activity. Identification of molecular targets whose in vivo modulation can attenuate synaptic dysfunction would provide a foundation for future disease-modifying therapeutic development as well as insight into cellular mechanisms. Clinical and preclinical studies suggest a critical link between synaptic dysfunction in neurodegenerative disorders and the activation of p38αMAPK mediated signaling cascades. Activation in both neurons and glia also offers the unusual potential to generate enhanced responses through targeting a single kinase in two distinct cell types involved in pathology progression. However, target validation has been limited by lack of highly selective inhibitors amenable to in vivo use in the CNS. Therefore, we employed high-resolution co-crystallography and pharmacoinformatics to design and develop a novel synthetic, active site targeted, CNS-active, p38αMAPK inhibitor (MW108). Selectivity was demonstrated by large-scale kinome screens, functional GPCR agonist and antagonist analyses of off-target potential, and evaluation of cellular target engagement. In vitro and in vivo assays demonstrated that MW108 ameliorates beta-amyloid induced synaptic and cognitive dysfunction. A serendipitous discovery during co-crystallographic analyses revised prevailing models about active site targeting of inhibitors, providing insights that will facilitate future kinase inhibitor design. Overall, our studies deliver highly selective in vivo probes appropriate for CNS investigations and demonstrate that modulation of p38αMAPK activity can attenuate synaptic dysfunction

Human Tyrosine Hydroxylase Natural Allelic Variation: Influence on Autonomic Function and Hypertension

The catecholamine biosynthetic pathway consists of several enzymatic steps in series, beginning with the amino acids phenylalanine and tyrosine, and eventuating in the catecholamines norepinephrine (noradrenaline) and epinephrine (adrenaline). Since the enzyme tyrosine hydroxylase (TH; tyrosine 3-mono-oxygenase; EC 1.14.16.2; chromosome 11p15.5) is generally considered to be rate-limiting in this pathway, probed as to whether common genetic variation at the TH gene occurred, and whether such variants contributed to inter-individual alterations in autonomic function, either biochemical or physiological. We began with sequencing a tetranucleotide (TCAT) repeat in the first intron, and found that the two most common versions, (TCAT)6 and (TCAT)10i, predicted heritable autonomic traits in twin pairs. We then conducted systematic polymorphism discovery across the ~8 kbp locus, and discovered numerous variants, principally non-coding. The proximal promoter block contained four common variants, and its haplotypes and SNPs (especially C-824T, rs10770141) predicted catecholamine secretion, environmental stress-induced BP increments, and hypertension. Finally, we found that two of the common promoter variants, C-824T (rs10770141) and A-581G (rs10770140), were functional in that they differentially affected transcriptional activity of the isolated promoter, disrupted recognition motifs for specific transcription factor binding, altered the promoter responses to the co-transfected (exogenous) factors, and bound the endogenous factors in the chromatin fraction of the nucleus. We concluded that common variation in the proximal TH promoter is functional, giving rise to changes in autonomic function and consequently cardiovascular risk