Im Datendschungel - Veterinärpharmkologisches Verzeichnis im Internet

Für den Tierarzt, insbesondere den viel beschäftigen Praktiker, ist die unaufhaltsam wachsende Flut von veterinärmedizinischen Publikationen ein nahezu unlösbares Problem: Wie soll er seinen Wissensstand in allen für seine Tätigkeit relevanten Gebieten fortlaufend aktualisieren

The Case Against Credit Card Interest Rate Regulation

This article analyzes recent proposals to regulate credit card interest rates on a national scale. The proposals are a modern chapter in a very old story. Usury laws-laws forbidding or limiting payment for money loans-are among the most ancient forms of price control. Like previous economic studies of usury controls, this one concludes that they are unjustified because the supply of credit is highly competitive, and would be harmful because they would cause an artificial contraction in the supply of credit and other economic inefficiencies

Dynamics and pattern formation in invasive tumor growth

In this work, we study the in-vitro dynamics of the most malignant form of the primary brain tumor: Glioblastoma Multiforme. Typically, the growing tumor consists of the inner dense proliferating zone and the outer less dense invasive region. Experiments with different types of cells show qualitatively different behavior. Wild-type cells invade a spherically symmetric manner, but mutant cells are organized in tenuous branches. We formulate a model for this sort of growth using two coupled reaction-diffusion equations for the cell and nutrient concentrations. When the ratio of the nutrient and cell diffusion coefficients exceeds some critical value, the plane propagating front becomes unstable with respect to transversal perturbations. The instability threshold and the full phase-plane diagram in the parameter space are determined. The results are in a good agreement with experimental findings for the two types of cells.Comment: 4 pages, 4 figure

Engineered microneedles for transcutaneous vaccine delivery

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biological Engineering, 2013.Cataloged from PDF version of thesis.Includes bibliographical references (p. 151-165).Immunization is a powerful approach for the prevention and control of infectious disease, however despite the successes of modem vaccine development, there remain several notable obstacles for the advancement of vaccine-mediated improvements in global healthcare. Many of the current limitations in vaccine availability and administration are the result of obligate needle-based delivery, which in addition to contributing to reduced speed, ease, and compliance in administration, has been shown to contribute to reduced overall safety due to needle re-use and needle-based injuries. Needle-based vaccine delivery to immunologically passive tissues such as muscle may limit efficacy, thus motivating the targeting of more inherently potent immune-competent sites. These inherent limitations of needle-based vaccination on global health have led to a strong impetus to develop needle-free vaccination strategies which have the potential to improve vaccine efficacy and availability, enhance the ease, speed, and safety of vaccine administration, and reduce vaccination associated costs world-wide. Here we present the design and preclinical testing of several parallel materials strategies for the noninvasive delivery of subunit vaccines to the skin. We have utilized laser ablative micro-molding of poly(dimethylsiloxane) to generate bio resorbable poly(lactide-co-glycolide) micro-structured skin patches bearing -100 micron-scale needles arrayed across their surface. Upon topical application, these 'microneedle arrays' are able to safely, and painlessly insert into the immune-competent epidermal skin layers to generate microscopic conduits through which otherwise impermeant vaccines and therapeutics are able to passage into the body. We have leveraged this approach in combination with layer-by-layer (LbL) directed assembly to generate vaccine-loaded conformal coatings on the surface of these microneedle arrays, which are then delivered into the skin through topical patch application. The construction of coatings containing antigen-expressing plasmid DNA (pDNA), together with immune-stimulatory RNA, and degradable cationic polymers provided tunable control over vaccine dosage, rapid and effective vaccine delivery in murine and primate skin models, and potent immunogenicity against a model HIV antigen in mice. In this case, DNA vaccine delivery was able to elicit strong functional CD8' T cell and humoral responses matching or exceeding the potency of in vivo electroporation, currently the most promising approach for clinical DNA delivery in humans. Further efforts have explored the use of LbL for encapsulation and delivery of soluble and particulate protein subunit vaccines, giving enhanced generation of diverse and potent humoral responses in mice. In other work, we have developed an approach enabling rapid delivery of micron-scale degradable polymer matrices or hydrogel depots using dissolvable composite microneedle structures for the delivery of vaccines with programmable kinetics. These efforts have demonstrated the potential of persistent vaccine release on tuning immune potency following non-invasive microneedle delivery, including induction of potent effector and memory CD8* T cell responses and more powerful and diverse antigen-specific humoral responses. Finally, we have developed an approach for simple loading and delivery of clinically advanced recombinant adenoviral vaccine vectors from sugar-glass coatings on bioresorbable microneedles. Formulation in microneedle coatings improved vaccine stability at room temperature and preclinical testing of these vaccine patches in mice and nonhuman primates demonstrated equivalent immunogenicity compared to parenteral injection, eliciting strong systemic and disseminated mucosal CD8' and CD4* T cell responses to a model HIV antigen. These cellular responses were correlated with a similarly potent systemic and mucosal humoral response, together suggesting the utility of this approach for non-invasive adenoviral immunization in a model close to humans. Together these results strongly demonstrate the potential of materials engineering strategies for the effective formulation, delivery, and release of recombinant vaccines by microneedle patches targeting the skin. In addition to the significant practical advantages enabled by microneedle delivery including improved safety, convenience, and storage, we have shown that advanced formulation strategies paired with controlled release are able to initiate humoral and cellular adaptive immunity more potently than possible through parenteral injection. Comprehensive tests in both mice and primates have suggested that these principles may be broadly applied to enhance various recombinant vaccination strategies potentially targeting numerous disease targets. Finally, initial tests performed in nonhuman primates have indicated the promise of engineered microneedle approaches for successful translation to humans. Overall, these findings provide a strong basis for the continued development of similar vaccination strategies for the comprehensive transformation of conventional vaccination enabling significant vaccine-mediated improvements in global health.by Peter C. DeMuth.Ph.D

The structure ofAl(111)-K−(√3 × √3)R30° determined by LEED: stable and metastable adsorption sites

It is found that the adsorption of potassium on Al(111) at 90 K and at 300 K both result in a (√3 × √3)R0° structure. Through a detailed LEED analysis it is revealed that at 300 K the adatoms occupy substitutional sites and at 90 K the adatoms occupy on-top sites; both geometries have hitherto been considered as very unusual. The relationship between bond length and coordination is discussed with respect to the present results, and with respect to other quantitative studies of alkali-metal/metal adsorption systems

Design of (ω-N-(O-acyl)hydroxy amid) aminodicarboxylic acid pyrrolidides as potent inhibitors of proline-specific peptidases

AbstractA novel class of competitive, acylating inhibitors for the proline-specific peptidases: dipeptidyl peptidase IV, dipeptidyl peptidase II and prolyl endopeptidase, has been developed. The inhibitor molecules combine the efficacy of aminoacyl pyrrolidides and the potential transacylating capability of diacyl hydroxyl amines. The N-terminal deblocked inhibitors are potent reversible inhibitors of porcine kidney dipeptidyl peptidase IV, human placenta dipeptidyl peptidase II exhibiting K1 values in the μM range. Boc-protected (ω-N-hydroxy acyl amid) aminodiacarboxylic acid pyrrolidides inhibit substrate hydrolysis by prolyl endopeptidases from different sources competitively reaching K, values of 30 nM to 60 μM. Additionally, α-N-BOC-(ω-N-hydroxy acetyl) glutaminyl pyrrolidide modifies human placenta prolyl endopeptidase in a time-dependent reaction

Multilingual assessment of early child development: Analyses from repeated observations of children in Kenya.

In many low- and middle-income countries, young children learn a mother tongue or indigenous language at home before entering the formal education system where they will need to understand and speak a countrys official language(s). Thus, assessments of children before school age, conducted in a nations official language, may not fully reflect a childs development, underscoring the importance of test translation and adaptation. To examine differences in vocabulary development by language of assessment, we adapted and validated instruments to measure developmental outcomes, including expressive and receptive vocabulary. We assessed 505 2-to-6-year-old children in rural communities in Western Kenya with comparable vocabulary tests in three languages: Luo (the local language or mother tongue), Swahili, and English (official languages) at two time points, 5-6 weeks apart, between September 2015 and October 2016. Younger children responded to the expressive vocabulary measure exclusively in Luo (44%-59% of 2-to-4-year-olds) much more frequently than did older children (20%-21% of 5-to-6-year-olds). Baseline receptive vocabulary scores in Luo (β = 0.26, SE = 0.05, p < 0.001) and Swahili (β = 0.10, SE = 0.05, p = 0.032) were strongly associated with receptive vocabulary in English at follow-up, even after controlling for English vocabulary at baseline. Parental Luo literacy at baseline (β = 0.11, SE = 0.05, p = 0.045) was associated with child English vocabulary at follow-up, while parental English literacy at baseline was not. Our findings suggest that multilingual testing is essential to understanding the developmental environment and cognitive growth of multilingual children

Associations between neighborhood characteristics: well-being and health vary over the life course

Background: Neighborhood characteristics are important determinants of individual health and well-being. For example, characteristics such as noise and pollution affect health directly, while other characteristics affect health and well-being by either providing resources (e.g. social capital in the neighborhood), which individuals can use to cope with health problems, or limiting the use thereof (e.g. crime). This also suggests that there might be age differentials in the impact of these characteristics, since individuals at different stages of life might need different resources. However, there is a lack of empirical evidence on age differentials in associations between well-being, health, and neighborhood characteristics. Objective: This paper studies associations between a wide range of neighborhood characteristics with the health and well-being of residents of the greater Berlin area. In particular, we focus on differences in the effects between younger (aged 20-35) and older (aged 60+) residents. Methods: We used data from the Berlin Aging Study II (312 younger and 993 older residents of the Berlin metropolitan area in Germany). We used survey data on health and well-being, combined these with subjective perceptions of the neighborhood, and geo-referenced indicators on the neighborhood, e.g. amenities (public transport, physicians, and hospitals). Results: The results show that access to public transportation is associated with better outcomes on all measures of health and well-being, and social support is associated with higher life satisfaction and better mental health. There are considerable differences between both age groups: while the associations between access to public transport and health and well-being are similar for both age groups, neighborhood social capital shows stronger associations for older residents. However, the difference is not always statistically significant. Conclusion: Having access to services is associated with better health and well-being regardless of age. Local policy makers should focus on lowering barriers to mobility in order to improve the health and well-being of the population. Since the social capital of a neighborhood is associated with better health and well-being among older residents, investments that increase social capital (e.g. community centers) might be warranted in neighborhoods with higher shares of older residents