Confinement interaction in nonlinear generalizations of the Wick-Cutkosky model

We consider nonlinear-mediating-field generalizations of the Wick-Cutkosky model. Using an iterative approach and eliminating the mediating field by means of the covariant Green function we arrive at a Lagrangian density containing many-point time-nonlocal interaction terms. In low-order approximations of $\phi^3{+}\phi^4$ theory we obtain the usual two-current interaction as well as a three-current interaction of a confining type. The same result is obtained without approximation for a version of the dipole model. The transition to the Hamiltonian formalism and subsequent canonical quantization is performed with time non-locality taken into account approximately. A relativistic three-particle wave equation is derived variationally by using a three-particle Fock space trial state. The non-relativistic limit of this equation is obtained and its properties are analyzed and discussed.Comment: 15 pages, 1 figure, LaTe

Study of Soil Compaction Using X-Ray Computed Tomography

The maximum dry density and optimum moisture content obtained from the laboratory compaction curve have been used customarily to characterize the field behavior of compacted soils. It is well known, however, that the microstructure of compacted soils is dependent on the method of compaction. The structure has an important influence on the engineering behavior of compacted soils. Therefore, in order to provide a better description of compacted soils, methods that can quantify the changes in microstructure are needed. In this study, compacted specimens at various densities and water content were scanned using X-ray Computed Tomography (CT). It has been found that there is direct correspondence between the CT numbers, soil dry density and moisture content. The scanning observations showed also the development of shear planes parallel to the surface of the compacted soil, and changes in structure of the soil towards a more uniform arrangement around the point of optimum moisture content. Compaction of the soil beyond the optimum moisture content appears to disperse soil particles with an overall uniform structure

The Rules of Human T Cell Fate in vivo.

The processes governing lymphocyte fate (division, differentiation, and death), are typically assumed to be independent of cell age. This assumption has been challenged by a series of elegant studies which clearly show that, for murine cells in vitro, lymphocyte fate is age-dependent and that younger cells (i.e., cells which have recently divided) are less likely to divide or die. Here we investigate whether the same rules determine human T cell fate in vivo. We combined data from in vivo stable isotope labeling in healthy humans with stochastic, agent-based mathematical modeling. We show firstly that the choice of model paradigm has a large impact on parameter estimates obtained using stable isotope labeling i.e., different models fitted to the same data can yield very different estimates of T cell lifespan. Secondly, we found no evidence in humans in vivo to support the model in which younger T cells are less likely to divide or die. This age-dependent model never provided the best description of isotope labeling; this was true for naïve and memory, CD4+ and CD8+ T cells. Furthermore, this age-dependent model also failed to predict an independent data set in which the link between division and death was explored using Annexin V and deuterated glucose. In contrast, the age-independent model provided the best description of both naïve and memory T cell dynamics and was also able to predict the independent dataset

Alternative schemes for measurement-device-independent quantum key distribution

Practical schemes for measurement-device-independent quantum key distribution using phase and path or time encoding are presented. In addition to immunity to existing loopholes in detection systems, our setup employs simple encoding and decoding modules without relying on polarization maintenance or optical switches. Moreover, by employing a modified sifting technique to handle the dead-time limitations in single-photon detectors, our scheme can be run with only two single-photon detectors. With a phase-postselection technique, a decoy-state variant of our scheme is also proposed, whose key generation rate scales linearly with the channel transmittance.Comment: 30 pages, 5 figure

Targeting Listeria monocytogenes consensus sequence of internalin genes using an antisense molecule

As an intracellular pathogen, Listeria monocytogenes can enter host cells where it can replicate and escape detection and eradication by the host immune response making the clearance of infection very challenging. Furthermore, with the advent of antimicrobial resistance, the need for alternative targets is inevitable. Internalin proteins are crucial to this bacterium as they contribute to bacterial entry to the systemic circulation. In this study, we targeted a highly conserved region of these proteins by an antisense sequence that was covalently conjugated to the cell penetrating peptides (CPP) to overcome the challenging delivery barriers. Then, we evaluated the efficiency of this construct in vitro. We also assessed the antigenicity, cytotoxicity, and probability of apoptosis induction by this construct. The studied CPP-PNA inhibited bacterial growth and suppressed the mRNA expression of internalins in a dose-dependent manner. In addition, at all studied concentrations, CPP-PNA significantly reduced the invasion rate of L. monocytogenes in the examined cell lines. Moreover, different concentrations of CPP-PNA did not have a significant antigenic, cytotoxic, and apoptotic properties compared to the control. These results suggest the effectiveness of CPP-antisense in targeting the mRNAs of internalins for various research, therapeutic and preventive purposes. However, additional research is required to evaluate the potency, safety, and pharmacokinetics of this compound for the prevention and treatment of listeriosis

Chromogenic in situ hybridisation test for breast cancer patients with equivocal IHC results - A study from Iran

Background: HER2/neu overexpression on cell membranes of breast cancer cells is due to HER2/neu gene amplification and it is important to identify potential candidates for anti HER2 therapy with trastuzumab. IHC, FISH and CISH are standard FDA approved assays currently used to determine HER2 status in routine practice. The aim of this study was to determine HER2 gene amplification, using the CISH method in breast carcinoma samples which had IHC +2 reactions. Materials and Methods: This study was conducted from 2008-2010 using 334 consecutive breast carcinoma samples referred from local laboratories to Mehr Hospital. CISH assays were performed for all cases, and IHC tests were also done for determining efficacy and accuracy of local labs. HER2 status in local IHC tests was compared with central IHC and CISH results. Results: Of 334 breast cancer patients, 16 were negative for HER2 IHC (0, +1), 201 cases were equivocal (+2), and 31 positive (+3). Of 334 referral cases, 88 were CISH positive (26.3) and 246 were CISH negative (73.7). Of 201 IHC +2 cases, HER2 gene amplification was observed in 42 cases (kappa: 0.42). A 29.9 concordance was found between local IHC and central IHC. Sensitivity and specificity of local IHC were 90 and 53.8, respectively. Conclusions: Low accuracy of IHC results in local labs was associated with the following factors: using former FDA-approved criteria for HER2 interpretation, utilizing non-validated kits, and lack of any quality assurance program. Therefore, following the new 2014 ASCO/CAP guideline and comprehensive quality assurance should be implemented to ensure accuracy of HER2 testing

The current and future burden of hepatitis B in Switzerland: a modelling study.

Chronic hepatitis B infection (defined as sustained detection of hepatitis B virus [HBV] surface antigen [HBsAg] protein in serum) is a leading cause of cirrhosis, hepatocellular carcinoma and liver-related deaths. A situation analysis carried out by the Swiss Federal Office of Public Health estimated the HBsAg prevalence in Switzerland to be 0.53% (95% CI: 0.32-0.89%) in 2015 (~44,000 cases). A lower prevalence of chronic HBV in the younger generation and the adoption of universal coverage in the first year of life are expected to decrease the burden of HBV; however, a number of people in key populations (including migrants) remain undiagnosed and untreated, and infected individuals remain at risk of progressing to cirrhosis, hepatocellular carcinoma and death. Our primary objective was to examine the current and estimate the future disease burden of HBV in Switzerland and the impact of migration. The secondary objective was to estimate the impact of changing future treatment numbers. A modelling study was performed using an existing, validated model (PRoGReSs Model) applied to the Swiss context. Model inputs were selected through a literature search and expert consensus. Population data from the Federal Statistical Office were used alongside prevalence data from the Polaris Observatory to estimate the number of HBV infections among people born abroad. The PRoGReSs Model was populated with and calibrated to the available data and what-if scenarios were developed to explore the impact of intervention on the future burden of disease. A Monte Carlo simulation was used to estimate 95% uncertainty intervals (95% UIs). In 2020, there were an estimated 50,100 (95% UI: 47,500-55,000) HBsAg+ cases among people born abroad. Among people born in Switzerland, there were approximately 62,700 (UI: 58,900-68,400) total HBV infections (0.72% [UI: 0.68-0.79%] prevalence). Prevalence among infants and children under the age of 5 were both <0.1%. By 2030, prevalence of HBV is expected to decrease, although morbidity and mortality will increase. Increasing diagnosis (90%) and treatment (80% of those eligible) to meet the global health sector strategy on viral hepatitis programme targets could prevent 120 cases of hepatocellular carcinoma and 120 liver-related deaths. Thanks to the historical vaccination programmes and the continued rollout of universal 3-dose coverage in the first year of life, Switzerland is expected to exceed the global health sector strategy targets for the reduction of incidence. While overall prevalence is decreasing, the current diagnosis and treatment levels remain below global health sector strategy targets

Spatial distribution and catalytic mechanisms of β-glucosidase activity at the root-soil interface

© 2016, Springer-Verlag Berlin Heidelberg.We compared modifications of soil zymography, a new in situ technique to visualize enzyme activities, based on contact of fluorgenic substrate-saturated membranes with soil either through the gel layer (gel zymography) or without gel application (direct zymography). We coupled zymography with quantitative measurements of enzyme kinetics to characterize catalytic mechanisms of β-glucosidase activity at the plant-soil interface including root surface (rhizoplane), rhizosphere, and bulk soil. Direct zymography refined and focused image resolution. The area of hotspots (i.e., spots with most intensive enzyme activity) as well as color intensity ratios estimated using direct zymography exceeded by a factor of 2 the corresponding values obtained with gel zymography. As determined by direct zymography, the percentage of hotspots associated to root surfaces was 58–68 % of total hotspot area. Hotspot area comprised only 6.8 ± 0.1 % of the total area of an image and 9.0 ± 3 % of the root surface area. The intensity of β-glucosidase activity, however, was up to 20 times higher in the hotspots versus bulk soil. The contribution of rhizosphere to β-glucosidase activity of the whole image (77–82 %) was four times higher than the contribution of the root surface. Enzyme kinetic parameters indicated different enzyme systems in bulk and rhizosphere soil. Higher substrate affinity and catalytic efficiency in bulk than in rhizosphere soil suggested relative domination of microorganisms with more efficient enzyme systems in the former. Coupling direct zymography and kinetic assays enabled mapping the two-dimensional (2D) distribution of enzyme activity at the root-soil interface and estimating the catalytic properties of root-associated and soil-associated enzymes

Spatial distribution and catalytic mechanisms of β-glucosidase activity at the root-soil interface

© 2016 Springer-Verlag Berlin Heidelberg We compared modifications of soil zymography, a new in situ technique to visualize enzyme activities, based on contact of fluorgenic substrate-saturated membranes with soil either through the gel layer (gel zymography) or without gel application (direct zymography). We coupled zymography with quantitative measurements of enzyme kinetics to characterize catalytic mechanisms of β-glucosidase activity at the plant-soil interface including root surface (rhizoplane), rhizosphere, and bulk soil. Direct zymography refined and focused image resolution. The area of hotspots (i.e., spots with most intensive enzyme activity) as well as color intensity ratios estimated using direct zymography exceeded by a factor of 2 the corresponding values obtained with gel zymography. As determined by direct zymography, the percentage of hotspots associated to root surfaces was 58–68 % of total hotspot area. Hotspot area comprised only 6.8 ± 0.1 % of the total area of an image and 9.0 ± 3 % of the root surface area. The intensity of β-glucosidase activity, however, was up to 20 times higher in the hotspots versus bulk soil. The contribution of rhizosphere to β-glucosidase activity of the whole image (77–82 %) was four times higher than the contribution of the root surface. Enzyme kinetic parameters indicated different enzyme systems in bulk and rhizosphere soil. Higher substrate affinity and catalytic efficiency in bulk than in rhizosphere soil suggested relative domination of microorganisms with more efficient enzyme systems in the former. Coupling direct zymography and kinetic assays enabled mapping the two-dimensional (2D) distribution of enzyme activity at the root-soil interface and estimating the catalytic properties of root-associated and soil-associated enzymes

High-Performance Motion Correction of Fetal MRI

Fetal Magnetic Resonance Imaging (MRI) shows promising results for pre-natal diagnostics. The detection of potentially lifethreatening abnormalities in the fetus can be difficult with ultrasound alone. MRI is one of the few safe alternative imaging modalities in pregnancy. However, to date it has been limited by unpredictable fetal and maternal motion during acquisition. Motion between the acquisitions of individual slices of a 3D volume results in spatial inconsistencies that can be resolved by slice-to-volume reconstruction (SVR) methods to provide high quality 3D image data. Existing algorithms to solve this problem have evolved from very slow implementations targeting a single organ to general high-performance solutions to reconstruct the whole uterus. In this paper we give a brief overview over the current state-of-the art in fetal motion compensation methods and show currently emerging clinical applications of these technique