The Impact of Universal Extra Dimensions on FCNC Processes

We review the results of two papers on FCNC processes in the Appelquist, Cheng and Dobrescu (ACD) model with one universal extra dimension.Comment: Invited talk at the Workshop on the CKM Unitarity Triangle, IPPP Durham, April 2003 (eConf C0304052). 7 pages LaTeX, 5 eps figure

Analysis and Design of Modular Overhead Protection System Utilizing Readily Available Materials

This research investigated passive overhead protective measures for existing facilities in an urban environment that are vulnerable to enemy munitions fire. A new modular structural system was designed utilizing commercially available construction material consisting of structural tubing, scaffolding clamps, base plates, and simple roofing components. Structural analysis software was used to model nine modular structures to understand the relationship between the load bearing capacity of the structural members and overall dimensions of the system. Environmental variables for the models were set to the Parwan Province in Afghanistan; this region presents worst-case scenarios both for environmental factors and threat of enemy fire. American Institute of Steel Construction, Unified Facilities Criteria, and American Society of Civil Engineer codes were used as design standards for the analysis. For the final design, the members were sized according to the maximum axial, shear, and flexural forces exposed to a single member. Preliminary findings show that commercially available materials can be used to quickly, efficiently, and cost-effectively install overhead protection in austere hostile environments. An economic analysis was conducted to determine if the size of members should be adjusted throughout the design to improve cost effectiveness. However, due to low marginal benefits, the structural tubing should be kept consistent throughout the design to simplify the construction process

NOD/scid IL-2Rgnull mice: a preclinical model system to evaluate human dendritic cell-based vaccine strategies in vivo

<p>Abstract</p> <p>Background</p> <p>To date very few systems have been described for preclinical investigations of human cellular therapeutics <it>in vivo</it>. However, the ability to carry out comparisons of new cellular vaccines <it>in vivo </it>would be of substantial interest for design of clinical studies. Here we describe a humanized mouse model to assess the efficacy of various human dendritic cell (DC) preparations. Two reconstitution regimes of NOD/scid IL2Rg^null(NSG) mice with adult human peripheral blood mononuclear cells (PBMC) were evaluated for engraftment using 4-week and 9-week schedules. This led to selection of a simple and rapid protocol for engraftment and vaccine evaluation that encompassed 4 weeks.</p> <p>Methods</p> <p>NSG recipients of human PBMC were engrafted over 14 days and then vaccinated twice with autologous DC via intravenous injection. Three DC vaccine formulations were compared that varied generation time <it>in vitro </it>(3 days versus 7 days) and signals for maturation (with or without Toll-like receptor (TLR)3 and TLR7/8 agonists) using MART-1 as a surrogate antigen, by electroporating mature DC with <it>in vitro </it>transcribed RNA encoding full length protein. After two weekly vaccinations, the splenocyte populations containing human lymphocytes were recovered 7 days later and assessed for MART-1-specific immune responses using MHC-multimer-binding assays and functional assessment of specific killing of melanoma tumor cell lines.</p> <p>Results</p> <p>Human monocyte-derived DC generated <it>in vitro </it>in 3 days induced better MART-1-specific immune responses in the autologous donor T cells present in the humanized NSG mice. Moreover, consistent with our <it>in vitro </it>observations, vaccination using mature DC activated with TLR3 and TLR7/8 agonists resulted in enhanced immune responses <it>in vivo</it>. These findings led to a ranking of the DC vaccine effects <it>in vivo </it>that reflected the hierarchy previously found for these mature DC variations <it>in vitro</it>.</p> <p>Conclusions</p> <p>This humanized mouse model system enables comparisons among different DC vaccine types to be rapidly assessed <it>in vivo</it>. In addition, <it>ex vivo </it>analyses of human CD3⁺T cells recovered from the spleens of these mice are also possible, including studies on lymphocyte subsets, Th1/Th2 polarization, presence of regulatory T cells and the impact of DC vaccination on their functions.</p

The Impact of Universal Extra Dimensions on the Unitarity Triangle and Rare K and B Decays

We calculate the contributions of the Kaluza-Klein (KK) modes to the K_L-K_S mass difference \Delta M_K, the parameter \epsilon_K, the B^0_{d,s}-\bar B^0_{d,s} mixing mass differences \Delta M_{d,s} and rare decays K^+\to \pi^+\nu\bar\nu, K_L\to \pi^0\nu\bar\nu, K_L\to\mu\bar\mu, B\to X_{s,d}\nu\bar\nu and B_{s,d}\to\mu\bar\mu in the Appelquist, Cheng and Dobrescu (ACD) model with one universal extra dimension. For the compactification scale 1/R= 200 GeV the KK effects in these processes are governed by a 17% enhancement of the \Delta F=2 box diagram function S(x_t,1/R) and by a 37% enhancement of the Z^0 penguin diagram function C(x_t/1/R) relative to their Standard Model (SM) values. This implies the suppressions of \vtd by 8%, of \bar\eta by 11% and of the angle \gamma in the unitarity triangle by 10^\circ. \Delta M_s is increased by 17%. \Delta M_K is essentially uneffected. All branching ratios considered in this paper are increased with a hierarchical structure of enhancements: K^+\to \pi^+\nu\bar\nu (16%), K_L\to \pi^0\nu\bar\nu (17%), B\to X_{d}\nu\bar\nu (22%), (K_L\to\mu\bar\mu)_{\rm SD} (38%), B\to X_{s}\nu\bar\nu (44%), B_{d}\to\mu\bar\mu (46%) and B_{s}\to\mu\bar\mu (72%). For 1/R= 250 (300) GeV all these effects are decreased roughly by a factor of 1.5 (2.0). We emphasize that the GIM mechanism assures the convergence of the sum over the KK modes in the case of Z^0 penguin diagrams and we give the relevant Feynman rules for the five dimensional ACD model. We also emphasize that a consistent calculation of branching ratios has to take into account the modifications in the values of the CKM parameters

Microalbuminuria is a major determinant of elevated plasma retinol-binding protein 4 in type 2 diabetic patients

Plasma retinol-binding protein 4 (RBP4) may be a new adipokine linked to obesity-induced insulin resistance and type 2 diabetes. The impact of diabetic nephropathy on plasma RBP4 levels, however, is not known. We tested the hypothesis that microalbuminuria is associated with elevated plasma concentrations of RBP4 in type 2 diabetic subjects. Retinol, its binding protein and transthyretin (TTR) were measured in the plasma and urine of 62 type 2 diabetic subjects, 26 of whom had microalbuminuria. The results were compared to 35 healthy control subjects. Despite no differences in plasma retinol, concentrations of the RBP4 were significantly elevated in plasma of diabetic patients and significantly higher in those with microalbuminuria. The higher plasma levels of the binding protein in subjects with microalbuminuria were accompanied by both significantly elevated plasma TTR and increased urinary levels of RBP4. There were no correlations of plasma-binding protein levels and parameters of insulin resistance. Our study suggests that plasma RBP4 levels in type 2 diabetic patients are affected by incipient nephropathy. Therefore, further studies evaluating RBP4 as a regulator of systemic insulin resistance and type 2 diabetes will need to take renal function into consideration

Etablierung der homöopathischen Mastitistherapie in einem biologisch-dynamisch wirtschaftenden Milcherzeugerbetrieb unter Berücksichtigung ökologischer, epidemiologischer und ökonomischer Gesichtspunkte.

6 Summary The dairy cow mastitis as a disease with an immense economic impact is widely spread in organic as well as in conventional farms. Due to the lack of alternatives to antibiotic treatment, most therapeutical measures are based on antibiotics even in organic farms and against common regulations. In contrary to these procedures the EU regulations (Council Regulation EC 1804/99)as well as the consumer’s anticipation demand the possibly lowest levels of residual charges of dairy products and environment. A two and a half year study in a bio-dyn dairy herd in Brandenburg (Germany) with 300 dairy cows suffering from udder health problems was conducted to evaluate if clinical mastitis in dairy cows is to control successfully with homeopathic remedies to minimize antibiotic treatment. To assess the efficacy of the homeopathic treatment the investigations are made using a double blind placebo controlled study design (RCCT). Using a predetermined treatment protocol and a certain diagnostic pattern to match right remedies in the sense of the homeopathic remedy pictures, the intention of the chosen treatment schedule was to provide a very transparent concept which can be used also by unexperienced veterinarians. For treatment of acute mastitis the following remedies were used: Phytolacca D6, Bryonia D6 , Echinacea D6 and Belladonna D6. Aconitum D6 was added in case of fever at the beginning of disease. Cases of chronical and subclinical mastitis were treated by Echinacea D6, Phytolacca D6 and Hepar sulfuris D8. In the first part of the study nearly all mastitis cases were treated only with homeopathics avoiding antibiotics strictly. The unsatisfying results in this part lead to a modification in the second part in which in case of certain infections (S.aureus, Sc.spp.) a limited use of antibiotics was admitted. Furthermore, selected udders with subclinical and chronical infections with these kind of bacteria were dried off antibiotically. Simultaneously the farmer was engaged to intensify the efforts to optimize preventive and environmental measures in the herd. In the second part of the study 126 cows (148 quarters) suffered from clinical mastitis (Verum: n=60; Placebo: n=66). The cure rates were nearly identical. In the whole population the clinical cure rate (CCR) immediately after treatment was 95%, 7 to 8 weeks after treatment 65%. The 107 clinically affected quarters which were infected by pathogenic bacteria showed a bacteriological cure rate (BCR) of 55% each and a complete bacterio-cytological cure rate (BCCR) of 35% and 40% after 4-5 weeks and 7-8 weeks after treatment, respectively. During the observation time of 8 weeks a total of 12 cows in each of the treatment groups produced a homologous recurrent infection. 6 cows in the verum group and 4 cows in the placebo group developed a new infection in one of the other quarters. The treatment results seems to be satisfying while the enhanced but still not optimized environmental conditions in the herd are possibly responsible for the high amount of new infections and recurrences. Looking at the results of the study at all, the use of antibiotics could be decreased by 75% due to the therapy management (in spite of the change of it because of unsatisfying results) in combination with preventive measures. Additionally the herd udder health could be increased. So the mean herd somatic cell count decreased by 75.000 somatic cells/ml to 165.000 somatic cells/ml. Furthermore, the milk yield increased by 250 kg to 6.500 kg/cow/year. The count of infections with S. aureus in the herd decreased dramatically. The decreasing input of antibiotics in mastitis therapy in the project farm lead to a decrease of 36.000 kg antibiotically loaded milk compared to a hypothetic conventional mastitis management. Furthermore, the omission of withdrawal times after homeopathic treatment resulted in a benefit of additional production milk of 25.000 kg. The antibiotics minimizing therapy concept of the second part of this investigation which could be evaluated under practice conditions can be recommended for other farms too if simultaneous herd prevention measures can be assured by the farm manager to ensure good preconditions for the convalescence of the cows. The cure rates after placebo are unexpected high. Due to these results it is profoundly debatable whether the strategies of conventional therapy of bovine mastitis are suitable to ensure herd udder health. It should be evaluated which part of the cure rate is amounted by self cure and which other factors have an effect on the healing. The nearly identical cure rates in both treatment groups do not allow the proof of homeopathic efficacy at all. Indeed, comparing the bacteriologically caused mastitis cases (107 quarters), there is a significantly higher cure rate in the verum group (p < 0.05)

Fast magnesium conducting electrospun solid polymer electrolyte

Magnesium Ion based Solid State Batteries (MIBs) are subject of intensive studies due to abundance of magnesium, its advantages in volumetric capacity, and the reduced dendrite growth. Here we report on a true solid polymer electrolyte system without liquid additives or plasticizers that reaches conductivities above 10−5 S cm−1 at room temperature and above 10−4 S cm−1 at 50 °C. An electrospun polymer electrolyte membrane fabricated from a polymer electrolyte featuring a composition of PEO : Mg(TFSI)2 36 : 1 [where PEO stands for poly(ethyleneoxide) and Mg(TFSI)2 for magnesium bis(trifluoromethanesulfonyl) imide] was identified as the best performing system. Magnesium transport was substantiated by different methods, and the electrochemical properties including solid electrolyte interface (SEI) formation were investigated. Electrospinning as a preparation method has been identified as a powerful tool to enhance the electrochemical properties beyond conventional polymer membrane fabrication techniques

Hyperostosis in siblings

Infantile cortical hyperostosis – Caffey-Silverman disease – is a familial disorder manifesting in the late fetal period or infancy with excessive periosteal bone formation. Signs and symptoms regress spontaneously within months and result in expanded, deformed bones. The paucity of clinical symptoms may lead to delayed investigation and confusion of the remaining bone changes with those in other conditions. This problem is exemplified by two siblings misdiagnosed as osteogenesis imperfecta. The diagnosis of Caffey-Silverman disease was confirmed by molecular analysis showing the specific COL1A1 mutation in the patients and their clinically unaffected mother. Reduced penetrance rather than autosomal recessive inheritance explains multiple affected siblings born to healthy parents.

Three-day dendritic cells for vaccine development: Antigen uptake, processing and presentation

<p>Abstract</p> <p>Background</p> <p>Antigen-loaded dendritic cells (DC) are capable of priming naïve T cells and therefore represent an attractive adjuvant for vaccine development in anti-tumor immunotherapy. Numerous protocols have been described to date using different maturation cocktails and time periods for the induction of mature DC (mDC) <it>in vitro</it>. For clinical application, the use of mDC that can be generated in only three days saves on the costs of cytokines needed for large scale vaccine cell production and provides a method to produce cells within a standard work-week schedule in a GMP facility.</p> <p>Methods</p> <p>In this study, we addressed the properties of antigen uptake, processing and presentation by monocyte-derived DC prepared in three days (3d mDC) compared with conventional DC prepared in seven days (7d mDC), which represent the most common form of DC used for vaccines to date.</p> <p>Results</p> <p>Although they showed a reduced capacity for spontaneous antigen uptake, 3d mDC displayed higher capacity for stimulation of T cells after loading with an extended synthetic peptide that requires processing for MHC binding, indicating they were more efficient at antigen processing than 7d DC. We found, however, that 3d DC were less efficient at expressing protein after introduction of <it>in vitro </it>transcribed (<it>ivt</it>)RNA by electroporation, based on published procedures. This deficit was overcome by altering electroporation parameters, which led to improved protein expression and capacity for T cell stimulation using low amounts of <it>ivt</it>RNA.</p> <p>Conclusions</p> <p>This new procedure allows 3d mDC to replace 7d mDC for use in DC-based vaccines that utilize long peptides, proteins or <it>ivt</it>RNA as sources of specific antigen.</p

Knockdown of Indy/CeNac2 extends Caenorhabditis elegans life span by inducing AMPK/aak-2

Reducing the expression of the Indy (Acronym for 'I'm Not Dead, Yet') gene in lower organisms promotes longevity and leads to a phenotype that resembles various aspects of caloric restriction. In C. elegans, the available data on life span extension is controversial. Therefore, the aim of this study was to determine the role of the C. elegans INDY homolog CeNAC2 in life span regulation and to delineate possible molecular mechanisms. siRNA against Indy/CeNAC2 was used to reduce expression of Indy/CeNAC2. Mean life span was assessed in four independent experiments, as well as whole body fat content and AMPK activation. Moreover, the effect of Indy/CeNAC2 knockdown in C. elegans with inactivating variants of AMPK (TG38) was studied. Knockdown of Indy/CeNAC2 increased life span by 22±3 % compared to control siRNA treated C. elegans, together with a decrease in whole body fat content by ~50%. Indy/CeNAC2 reduction also increased the activation of the intracellular energy sensor AMPK/aak2. In worms without functional AMPK/aak2, life span was not extended when Indy/CeNAC2 was reduced. Inhibition of glycolysis with deoxyglucose, an intervention known to increase AMPK/aak2 activity and life span, did not promote longevity when Indy/CeNAC2 was knocked down. Together, these data indicate that reducing the expression of Indy/CeNAC2 increases life span in C. elegans, an effect mediated at least in part by AMPK/aak2