The forward kinematics of doubly-planar Gough-Stewart platforms and the position analysis of strips of tetrahedra

The final publication is available at link.springer.comA strip of tetrahedra is a tetrahedron-tetrahedron truss where any tetrahedron has two neighbors except those in the extremes which have only one. The problem of finding all the possible lengths for an edge in the strip compatible with a given distance imposed between the strip end-points has been revealed of relevance due to the large number of possible applications. In this paper, this is applied to solve the forward kinematics of 6-6 Gough-Stewart platforms with planar base and moving platform, a problem which is known to have up to 40 solutions (20 if we do not consider mirror configurations with respect to the base as different solutions).Peer ReviewedPostprint (author's final draft

Digital MDA for enumeration of total nucleic acid contamination

Multiple displacement amplification (MDA) is an isothermal, sequence-independent method for the amplification of high molecular weight DNA that is driven by ϕ29 DNA polymerase (DNAP). Here we report digital MDA (dMDA), an ultrasensitive method for quantifying nucleic acid fragments of unknown sequence. We use the new assay to show that our custom ϕ29 DNAP preparation is free of contamination at the limit of detection of the dMDA assay (1 contaminating molecule per assay microliter). Contamination in commercially available preparations is also investigated. The results of the dMDA assay provide strong evidence that the so-called ‘template-independent’ MDA background can be attributed to high-molecular weight contaminants and is not primer-derived in the commercial kits tested. dMDA is orders of magnitude more sensitive than PCR-based techniques for detection of microbial genomic DNA fragments and opens up new possibilities for the ultrasensitive quantification of DNA fragments in a wide variety of application areas using MDA chemistry and off-the-shelf hardware developed for digital PCR

Light-Front Quantisation as an Initial-Boundary Value Problem

In the light front quantisation scheme initial conditions are usually provided on a single lightlike hyperplane. This, however, is insufficient to yield a unique solution of the field equations. We investigate under which additional conditions the problem of solving the field equations becomes well posed. The consequences for quantisation are studied within a Hamiltonian formulation by using the method of Faddeev and Jackiw for dealing with first-order Lagrangians. For the prototype field theory of massive scalar fields in 1+1 dimensions, we find that initial conditions for fixed light cone time {\sl and} boundary conditions in the spatial variable are sufficient to yield a consistent commutator algebra. Data on a second lightlike hyperplane are not necessary. Hamiltonian and Euler-Lagrange equations of motion become equivalent; the description of the dynamics remains canonical and simple. In this way we justify the approach of discretised light cone quantisation.Comment: 26 pages (including figure), tex, figure in latex, TPR 93-

Dynamical Chiral Symmetry Breaking on the Light Front I. DLCQ Approach

Dynamical chiral symmetry breaking in the DLCQ method is investigated in detail using a chiral Yukawa model closely related to the Nambu-Jona-Lasinio model. By classically solving three constraints characteristic of the light-front formalism, we show that the chiral transformation defined on the light front is equivalent to the usual one when bare mass is absent. A quantum analysis demonstrates that a nonperturbative mean-field solution to the ``zero-mode constraint'' for a scalar boson (sigma) can develop a nonzero condensate while a perturbative solution cannot. This description is due to our identification of the ``zero-mode constraint'' with the gap equation. The mean-field calculation clarifies unusual chiral transformation properties of fermionic field, which resolves a seemingly inconsistency between triviality of the null-plane chiral charge Q_5|0>=0 and nonzero condensate. We also calculate masses of scalar and pseudoscalar bosons for both symmetric and broken phases, and eventually derive the PCAC relation and nonconservation of Q_5 in the broken phase.Comment: Revised version to appear in Phys. Rev. D. 19 pages, 4 figures, REVTEX. Derivation of the PCAC relation is given. Its relation to the nonconservation of chiral charge is clarified. 1 figure and some references adde

Chiral Condensates in the Light-Cone Vacuum

In light-cone quantization, the standard procedure to characterize the phases of a system by appropriate ground state expectation values fails. The light-cone vacuum is determined kinematically. We show that meaningful quantities which can serve as order parameters are obtained as expectation values of Heisenberg operators in the equal (light-cone) time limit. These quantities differ from the purely kinematical expectation values of the corresponding Schroedinger operators. For the Nambu--Jona-Lasinio and the Gross-Neveu model, we describe the spontaneous breakdown of chiral symmetry; we derive within light-cone quantization the corresponding gap equations and the values of the chiral condensate.Comment: Latex, 9 pages, no figur

Systemic chemotherapy induces microsatellite instability in the peripheral blood mononuclear cells of breast cancer patients

INTRODUCTION: Systemic chemotherapy is an important part of treatment for breast cancer. We conducted the present study to evaluate whether systemic chemotherapy could produce microsatellite instability (MSI) in the peripheral blood mononuclear cell fraction of breast cancer patients. METHODS: We studied 119 sequential blood samples from 30 previously untreated breast cancer patients before, during and after chemotherapy. For comparison, we also evaluated 20 women who had no relevant medical history (control group). RESULTS: In 27 out of 30 patients we observed MSI in at least one sample, and six patients had loss of heterozygosity. We found a significant correlation between the number of MSI events per sample and chemotherapy with alkylating agents (P < 0.0001). We also observed an inverse correlation between the percentage of cells positive for hMSH2 and the number of MSI events per sample (P = 0.00019) and use of alkylating agents (P = 0.019). CONCLUSION: We conclude that systemic chemotherapy may induce MSI and loss of heterozygosity in peripheral blood mononuclear cells from breast cancer patients receiving alkylating agents, possibly mediated by a chemotherapy-induced decrease in the expression of hMSH2. These effects may be related to the generation of secondary leukaemia in some patients, and may also intensify the genetic instability of tumours and increase resistance to treatment

Pitfalls in mutational testing and reporting of common KIT and PDGFRA mutations in gastrointestinal stromal tumors

<p>Abstract</p> <p>Background</p> <p>Mutation analysis of <it>KIT </it>and <it>PDGFRA </it>genes in gastrointestinal stromal tumors is gaining increasing importance for prognosis of GISTs and for prediction of treatment response. Several groups have identified specific mutational subtypes in <it>KIT </it>exon 11 associated with an increased risk of metastatic disease whereas GISTs with <it>PDGFRA </it>mutations often behave less aggressive. Furthermore, in advanced GIST disease with proven <it>KIT </it>exon 9 mutation the doubled daily dose of 800 mg imatinib increases the progression free survival and is now recommended both in the European and the American Guidelines. In Germany, there are still no general rules how to perform mutational analysis.</p> <p>Methods</p> <p>When comparing results from six different molecular laboratories we recognized the need of standardisation. Six German university laboratories with experience in mutation analysis in GISTs joined together to develop recommendations for the mutation analysis of the most common and clinically relevant hot spots, i. e. <it>KIT </it>exons 9 and 11 and <it>PDGFRA </it>exon 18. We performed a three-phased interlaboratory trial to identify pitfalls in performing molecular analysis in GISTs.</p> <p>Results</p> <p>We developed a design for a continuous external laboratory trial. In 2009 this external trial was conducted by 19 laboratories via the initiative for quality assurance in pathology (QuiP) of the German Society of Pathology and the Professional Association of German Pathologists.</p> <p>Conclusions</p> <p>By performing a three-phased internal interlaboratory trial and conducting an external trial in Germany we were able to identify potential pitfalls when performing KIT and PDGFRA mutational analysis in gastrointestinal stromal tumors. We developed standard operation procedures which are provided with the manuscript to allow other laboratories to prevent these pitfalls.</p

Clinical and molecular practice of European thoracic pathology laboratories during the COVID-19 pandemic. The past and the near future

BACKGROUND: This study evaluated the consequences in Europe of the COVID-19 outbreak on pathology laboratories orientated toward the diagnosis of thoracic diseases. MATERIALS AND METHODS: A survey was sent to 71 pathology laboratories from 21 European countries. The questionnaire requested information concerning the organization of biosafety, the clinical and molecular pathology, the biobanking, the workload, the associated research into COVID-19, and the organization of education and training during the COVID-19 crisis, from 15 March to 31 May 2020, compared with the same period in 2019. RESULTS: Questionnaires were returned from 53/71 (75%) laboratories from 18 European countries. The biosafety procedures were heterogeneous. The workload in clinical and molecular pathology decreased dramatically by 31% (range, 3%-55%) and 26% (range, 7%-62%), respectively. According to the professional category, between 28% and 41% of the staff members were not present in the laboratories but did teleworking. A total of 70% of the laboratories developed virtual meetings for the training of residents and junior pathologists. During the period of study, none of the staff members with confirmed COVID-19 became infected as a result of handling samples. CONCLUSIONS: The COVID-19 pandemic has had a strong impact on most of the European pathology laboratories included in this study. Urgent implementation of several changes to the organization of most of these laboratories, notably to better harmonize biosafety procedures, was noted at the onset of the pandemic and maintained in the event of a new wave of infection occurring in Europe

Microsatellite instability and intratumoural heterogeneity in 100 right-sided sporadic colon carcinomas

Microsatellite instability has been proposed as an alternative pathway of colorectal carcinogenesis. The aim of this study was to evaluate the interest of immunohistochemistry as a new tool for highlighting mismatch repair deficiency and to compare the results with a PCR-based microsatellite assay. A total of 100 sporadic proximal colon adenocarcinomas were analysed. The expression of hMLH1, hMSH2 and hMSH6 proteins evaluated by immunohistochemistry was altered in 39% of the cancers, whereas microsatellite instability assessed by PCR was detected in 43%. There was discordance between the two methods in eight cases. After further analyses performed on other tumoural areas for these eight cases, total concordance between the two techniques was observed (Kappa=100%). Our results demonstrate that immunohistochemistry may be as efficient as microsatellite amplification in the detection of unstable phenotype provided that at least two samples of each carcinoma are screened, because of intratumoural heterogeneity