Quantitative long-term imaging of the functional representation of a whisker in rat barrel cortex.

In this study, we implement chronic optical imaging of intrinsic signals in rat barrel cortex and repeatedly quantify the functional representation of a single whisker over time. The success of chronic imaging for more than 1 month enabled an evaluation of the normal dynamic range of this sensory representation. In individual animals for a period of several weeks, we found that: (i) the average spatial extent of the quantified functional representation of whisker C2 is surprisingly large--1.71 mm2 (area at half-height); (ii) the location of the functional representation is consistent; and (iii) there are ongoing but nonsystematic changes in spatiotemporal characteristics such as the size, shape, and response amplitude of the functional representation. These results support a modified description of the functional organization of barrel cortex, where although a precisely located module corresponds to a specific whisker, this module is dynamic, large, and overlaps considerably with the modules of many other whiskers.

Identification of a minimal sequence of the mouse pro-alpha 1(I) collagen promoter that confers high-level osteoblast expression in transgenic mice and that binds a protein selectively present in osteoblasts.

Based on our previous transgenic mice results, which strongly suggested that separate cell-specific cis-acting elements of the mouse pro-alpha 1(I) collagen promoter control the activity of the gene in different type I collagen-producing cells, we attempted to delineate a short segment in this promoter that could direct high-level expression selectively in osteoblasts. By generating transgenic mice harboring various fragments of the promoter, we identified a 117-bp segment (-1656 to -1540) that is a minimal sequence able to confer high-level expression of a lacZ reporter gene selectively in osteoblasts when cloned upstream of the proximal 220-bp pro-alpha 1(I) promoter. This 220-bp promoter by itself was inactive in transgenic mice and unable to direct osteoblast-specific expression. The 117-bp enhancer segment contained two sequences that appeared to have different functions. The A sequence (-1656 to -1628) was required to obtain expression of the lacZ gene in osteoblasts, whereas the C sequence (-1575 to -1540) was essential to obtain consistent and high-level expression of the lacZ gene in osteoblasts. Gel shift assays showed that the A sequence bound a nuclear protein present only in osteoblastic cells. A mutation in the A segment that abolished the binding of this osteoblast-specific protein also abolished lacZ expression in osteoblasts of transgenic mice.

The EU’s Human Rights Promotion in China and Myanmar: Trading Rights for Might? EU Diplomacy Paper No. 5, October 2014

This paper aims to answer two questions: generally, to what extent the human rights promotion of the European Union (EU) in third countries is consistent, and more specifically, why the EU’s approach towards human rights promotion in China and Myanmar differs despite similar breaches of human rights. It compares the EU’s approach to the two countries over two time periods in the late 1980s and 1990s in the context of the EU’s evolving human rights promotion. Based on the two case studies, this paper finds that the EU’s human rights promotion in third countries varies significantly. Whereas one would expect the EU’s approach to become increasingly assertive throughout the 1990s, this has only been the case with Myanmar. China’s economic and political importance to the EU appears to have counterweighed the general rise in European attention to third countries’ human rights records. In other words, this paper finds that commercial interests take precedence over human rights concerns in case of important trading partners.

Squaring the cycle: capital flows, financial cycles, and macro-prudential policy in the euro area. Bruegel Working Paper 2015/14, November 2015

• Before the financial and economic crisis, monetary policy unification and interest rate convergence resulted in the divergence of euroarea countries’ financial cycles. This divergence is deeply rooted in the financial integration spurred by currency union and strongly correlated with intra-euro area capital flows. Macro-prudential policy will need to deal with potentially divergent financial cycles, while catering for potential cross-border spillovers from domestic policies, which domestic authorities have little incentive to internalise. • The current framework is unfit to deal effectively with these challenges. The European Central Bank should be responsible for consistent and coherent application of macro-prudential policy, with appropriate divergences catering for national differences in financial conditions. The close link between domestic financial cycles and intra-euro area capital flows raises the question of whether macro-prudential policy in the euro area can be compatible with free flows of capital. Financial cycle divergence had its counterpart in the build-up of macroeconomic imbalances, so effective implementation of the Macroeconomic Imbalance Procedure would support and strengthen macro-prudential policy.

Rapid Communication: Cholesterol deficiency-associated APOB mutation impacts lipid metabolism in Holstein calves and breeding bulls.

During the last months, the number of reports on Holstein calves suffering from incurable idiopathic diarrhea dramatically increased. Affected calves showed severe hypocholesterolemia and mostly died within days up to a few months after birth. This new autosomal monogenic recessive inherited fat metabolism disorder, termed cholesterol deficiency (CD), is caused by a loss of function mutation of the bovine gene. The objective of the present study was to investigate specific components of lipid metabolism in 6 homozygous for the mutation (CDS) and 6 normal Holstein calves with different genotypes. Independent of sex, CDS had significantly lower plasma concentrations of total cholesterol (TC), free cholesterol (FC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C), triacylglycerides (TAG), and phospholipids (PL) compared with homozygous wild-type calves ( < 0.05). Furthermore, we studied the effect of the genotype on cholesterol metabolism in adult Holstein breeding bulls of Swissgenetics. Among a total of 254 adult males, the homozygous mutant genotype was absent, 36 bulls were heterozygous carriers (CDC), and 218 bulls were homozygous wild-type (CDF). In CDC bulls, plasma concentrations of TC, FC, HDL-C, LDL-C, VLDL-C, TAG, and PL were lower compared with CDF bulls ( < 0.05). The ratios of FC:cholesteryl esters (CE) and FC:TC were higher in CDC bulls compared with CDF bulls, whereas the ratio of CE:TC was lower in CDC bulls compared with CDF bulls ( < 0.01). In conclusion, the CD-associated mutation was shown to affect lipid metabolism in affected Holstein calves and adult breeding bulls. Besides cholesterol, the concentrations of PL, TAG, and lipoproteins also were distinctly reduced in homozygous and heterozygous carriers of the mutation. Beyond malabsorption of dietary lipids, deleterious effects of apolipoprotein B deficiency on hepatic lipid metabolism, steroid biosynthesis, and cell membrane function can be expected, which may result in unspecific symptoms of reduced fertility, growth, and health.

(Figure 2) Distribution of planktonic foraminifera in the upper Paleocene of DSDP Hole 93-605

Good faunal preservation in the upper part of the Planorotatites pseudomenardii Zone at Deep Sea Drilling Project Site 605, northwestern Atlantic, allows a biometric analysis of the upper Paleocene planktonic foraminiferal species Planorotatites pseudomenardii (Belli), a keeled species that probably developed from a middle Paleocene unkeeled Planorotalites form. Multivariate analysis shows a consistent separation of all Planorotatites specimens into two groups, which are differentiated by the presence or absence of a complete keel; other variables are only of minor importance. The keeled group coincides with P. pseudomenardii. We recognize only one unkeeled species, Planorotalites chapmani (Parr), with Planorotalites ehrenbergi (Bolli), Planorotalites imitata (Subbotina), Planorotalites planoconica (Subbotina), Planorotalites troelseni (Loeblich and Tappan), and Planorotalites hausbergensis (Gohrbrandt) as junior synonyms. P. chapmani ranges from the middle Paleocene to at least the top of the upper Paleocene. The morphology of P. pseudomenardii does not change significantly, and although the frequency of Planorotalites is variable, the proportion of P. pseudomenardii to all Planorotalites varies only slightly around 65% in the upper two-thirds of its range at Site 605. However, in the top 1.5 m of its range the proportion of P. pseudomenardii decreases; in the same section, all Planorotalites specimens show a reduction in the size of their tests, suggesting that a temporary change in environmental conditions led to the exit of P. pseudomenardii\ in Magnetozone C24R at Site 605-apparently higher than expected from current standard zonations. Unkeeled Planorotalites, in contrast to R. pseudomenardii, persisted and regained normal size. The entry of P. pseudomenardii at Site 605 cannot be described in the same detail because of low frequencies of Planorotalites specimens and an erratic distribution of P. pseudomenardii in the lower part of its range. Many of the washed residues of the samples from these sediments are dominated by radiolarians, and the poorly preserved foraminiferal faunas may have abundant benthics, indicating carbonate dissolution. The initially low frequencies of P pseudomenardii relative to the unkeeled Planorotalites show a strong negative correlation with the total amount of radiolarians per sample and could be the result of preferential preservation, as well as of the same environmental conditions that caused the abundance of radiolarians.

Variations of fin whale vocalizations in the Northeast Pacific and the effects of environmental parameters on acoustic sensitivity

Senior thesis written for Oceanography 445

A Knowledge-based System for Intelligent Support in Pharmacogenomics Evidence Assessment: Ontology-driven Evidence Representation, Retrieval, Classification and Interpretation

Thesis (Ph.D.)--University of Washington, 2016-06

The Effect of Fructose vs. Glucose Beverages on Low-Grade Systemic Inflammation

Thesis (Ph.D.)--University of Washington, 2016-04

The role of insulin-like growth factor II and its receptor in mouse preimplantation development

Insulin-like growth factor II (IGF-II) and its receptor, the IGF-II/mannose-6-phosphate (IGF-II/M6P) receptor, are first expressed from the zygotic genome at the two-cell stage of mouse development. However, their role is not clearly defined. Insulin-like growth factor II is believed to mediate growth through the heterologous type 1 IGF and insulin receptors, whereas the IGF-II/M6P receptor is believed to act as a negative regulator of somatic growth by limiting the availability of excess levels of IGF-II. These studies demonstrate that IGF-II does have a role in growth regulation in the early embryo through the IGF-II/M6P receptor. Insulin-like growth factor II stimulated cleavage rate in two-cell embryos in vitro. Moreover, this receptor is required for the glycaemic response of two-cell embryos to IGF-II and for normal progression of early embryos to the blastocyst stage. Improved development of embryos in crowded culture supports the concept of an endogenous embryonic paracrine activity that enhances cell proliferation. These responses indicate that the IGF-II/M6P receptor is functional and likely to participate in such a regulatory circuit. The functional role of IGF-II and its receptor is discussed with reference to regulation of early development.

Hypertension, dyslipidemia, body mass index, Diabetes and smoking status in aboriginal australians in a remote community

Objectives: Study objectives were: 1) to describe the differences in the prevalence of CHID risk factors between Aboriginal people in a remote community and the general Australian population; and 2) to compare the predicted risks of CHD events between Aboriginal and non-Aboriginal Australians. Design: A cross-sectional study. Participants: 681 Aboriginal adults aged 25 to 74 years. Results: Aboriginal young adults had substantially higher prevalence of diabetes compared to non-Aboriginal Australians. The prevalence ratios for diabetes were 12.5, 5.6, 3.2, 1.3, and 0.73 for 25-, 35-, 45-, 55-, and 65- to 74-year-old females, respectively, The corresponding values for males were 12.1, 2.7, 2.9, 0.69, and 0.42. Young females had a higher prevalence of obesity, overweight, and abnormal waist circumference, while males and females 45 years and older tended to have a lower prevalence of overweight and ab. normal waist circumference. Compared to the general population, Aboriginal adults had a lower prevalence of abnormal total cholesterol but a higher prevalence of abnormal HDL, triglycerides, hypertension, and smoking. The risk ratios of abnormal total cholesterol for females ages 2534, 35-44, 45-54, 55-64, and 65-75 years were 0.38, 0.53, 0.48, 0.48, and 0.41, respectively. Conclusions: Aboriginal people in the remote community experienced different levels of CHD risk predictors from the general Australian population. They had a lower prevalence of abnormal total cholesterol and a higher prevalence of abnormal HDL, smoking, diabetes, and hypertension.

Normal values of balance tests in women aged 20-80

OBJECTIVES: To determine normal values for four commonly used clinical functional balance tests from community-dwelling women aged 20 to 80 and to identify any significant decline due to aging. DESIGN: A cross-sectional study was undertaken to provide normative values for four clinical balance tests across 6 decade cohorts. SETTING: The Betty Byrne-Henderson Center for Women and Aging, Royal Womens' Hospital, Brisbane, Australia. PARTICIPANTS: Four hundred fifty-six community-dwelling, independently ambulant women with no obvious neurological or musculoskeletal-related disability, aged 20 to 80, were randomly recruited from a large metropolitan region. MEASUREMENTS: The clinical balance measures/tests were the Timed Up and Go test, step test, Functional Reach test, and lateral reach test. Multivariate analysis was used to test the effect for age, height, and activity level. RESULTS: Normal data were produced for each test across each decade cohort. Gradual decline in balance performance was confirmed, with significant effect for age demonstrated. CONCLUSION: New normative data across the adult age decades are available for these clinical tests. Use of clinical balance tests could complement other balance tests and be used to screen women aged 40 to 60 whose performance is outside the normal values for age and to decrease later falls risk.

Prolotherapy injections, saline injections, and exercises for chronic low-back pain: A randomized trial

Objectives. To assess the efficacy of a prolotherapy injection and exercise protocol in the treatment of chronic nonspecific low back pain. Design. Randomized controlled trial with two- by- two factorial design, triple- blinded for injection status, and single- blinded for exercise status. Setting. General practice. Participants. One hundred ten participants with nonspecific low- back pain of average 14 years duration were randomized to have repeated prolotherapy ( 20% glucose/ 0.2% lignocaine) or normal saline injections into tender lumbo- pelvic ligaments and randomized to perform either flexion/ extension exercises or normal activity over 6 months. Main outcome measures: Pain intensity ( VAS) and disability scores ( Roland- Morris) at 2.5, 4, 6, 12, and 24 months. Results. Follow- up was achieved in 96% at 12 months and 80% at 2 years. Ligament injections, with exercises and with normal activity, resulted in significant and sustained reductions in pain and disability throughout the trial, but no attributable effect was found for prolotherapy injections over saline injections or for exercises over normal activity. At 12 months, the proportions achieving more than 50% reduction in pain from baseline by injection group were glucose- lignocaine: 0.46 versus saline: 0.36. By activity group these proportions were exercise: 0.41 versus normal activity: 0.39. Corresponding proportions for > 50% reduction in disability were glucose- lignocaine: 0.42 versus saline 0.36 and exercise: 0.36 versus normal activity: 0.38. There were no between group differences in any of the above measures. Conclusions. In chronic nonspecific low- back pain, significant and sustained reductions in pain and disability occur with ligament injections, irrespective of the solution injected or the concurrent use of exercises.

What is the best size descriptor to use for pharmacokinetic studies in the obese?

The prevalence of obesity in the western world is dramatically rising, with many of these individuals requiring therapeutic intervention for a variety of disease states. Despite the growing prevalence of obesity there is a paucity of information describing how doses should be adjusted, or indeed whether they need to be adjusted, in the clinical setting. This review is aimed at identifying which descriptors of body size provide the most information about the relationship between dose and concentration in the obese. The size descriptors, weight, lean body weight, ideal body weight, body surface area, body mass index, fat-free mass, percent ideal body weight, adjusted body weight and predicted normal body weight were considered as potential size descriptors. We conducted an extensive review of the literature to identify studies that have assessed the quantitative relationship between the parameters clearance (CL) and volume of distribution (V) and these descriptors of body size. Surprisingly few studies have addressed the relationship between obesity and CL or V in a quantitative manner. Despite the lack of studies there were consistent findings: (i) most studies found total body weight to be the best descriptor of V. A further analysis of the studies that have addressed V found that total body weight or another descriptor that incorporated fat mass was the preferred descriptor for drugs that have high lipophilicity; (ii) in contrast, CL was best described by lean body mass and no apparent relationship between lipophilicity or clearance mechanism and preference for body size descriptor was found. In conclusion, no single descriptor described the influence of body size on both CL and V equally well. For drugs that are dosed chronically, and therefore CL is of primary concern, dosing for obese patients should not be based on their total weight. If a weight-based dose individualization is required then we would suggest that chronic drug dosing in the obese subject should be based on lean body weight, at least until a more robust size descriptor becomes available.

Strength analysis of steel-concrete composite beams in combined bending and shear

Despite experimental evidences, the contributions of the concrete slab and composite action to the vertical shear strength of simply supported steel-concrete composite beams are not considered in current design codes, which lead to conservative designs. In this paper, the finite element method is used to investigate the flexural and shear strengths of simply supported composite beams under combined bending and shear. A three-dimensional finite element model has been developed to account for geometric and material nonlinear behavior of composite beams, and verified by experimental results. The verified finite element model is than employed to quantify the contributions of the concrete slab and composite action to the moment and shear capacities of composite beams. The effect of the degree of shear connection on the vertical shear strength of deep composite beams loaded in shear is studied. Design models for vertical shear strength including contributions from the concrete slab and composite action and for the ultimate moment-shear interaction ate proposed for the design of simply supported composite beams in combined bending and shear. The proposed design models provide a consistent and economical design procedure for simply supported composite beams.