Moduli space actions on the Hochschild Co-Chains of a Frobenius algebra I: Cell Operads

This is the first of two papers in which we prove that a cell model of the moduli space of curves with marked points and tangent vectors at the marked points acts on the Hochschild co--chains of a Frobenius algebra. We also prove that a there is dg--PROP action of a version of Sullivan Chord diagrams which acts on the normalized Hochschild co-chains of a Frobenius algebra. These actions lift to operadic correlation functions on the co--cycles. In particular, the PROP action gives an action on the homology of a loop space of a compact simply--connected manifold. In this first part, we set up the topological operads/PROPs and their cell models. The main theorems of this part are that there is a cell model operad for the moduli space of genus $g$ curves with $n$ punctures and a tangent vector at each of these punctures and that there exists a CW complex whose chains are isomorphic to a certain type of Sullivan Chord diagrams and that they form a PROP. Furthermore there exist weak versions of these structures on the topological level which all lie inside an all encompassing cyclic (rational) operad.Comment: 50 pages, 7 figures. Newer version has minor changes. Some material shifted. Typos and small things correcte

Can Light Signals Travel Faster than c in Nontrivial Vacuua in Flat space-time? Relativistic Causality II

In this paper we show that the Scharnhorst effect (Vacuum with boundaries or a Casimir type vacuum) cannot be used to generate signals showing measurable faster-than-c speeds. Furthermore, we aim to show that the Scharnhorst effect would violate special relativity, by allowing for a variable speed of light in vacuum, unless one can specify a small invariant length scale. This invariant length scale would be agreed upon by all inertial observers. We hypothesize the approximate scale of the invariant length.Comment: 12 pages no figure

EasyCloneMulti: A Set of Vectors for Simultaneous and Multiple Genomic Integrations in <i>Saccharomyces cerevisiae</i>

Saccharomyces cerevisiae is widely used in the biotechnology industry for production of ethanol, recombinant proteins, food ingredients and other chemicals. In order to generate highly producing and stable strains, genome integration of genes encoding metabolic pathway enzymes is the preferred option. However, integration of pathway genes in single or few copies, especially those encoding rate-controlling steps, is often not sufficient to sustain high metabolic fluxes. By exploiting the sequence diversity in the long terminal repeats (LTR) of Ty retrotransposons, we developed a new set of integrative vectors, EasyCloneMulti, that enables multiple and simultaneous integration of genes in S. cerevisiae. By creating vector backbones that combine consensus sequences that aim at targeting subsets of Ty sequences and a quickly degrading selective marker, integrations at multiple genomic loci and a range of expression levels were obtained, as assessed with the green fluorescent protein (GFP) reporter system. The EasyCloneMulti vector set was applied to balance the expression of the rate-controlling step in the β-alanine pathway for biosynthesis of 3-hydroxypropionic acid (3HP). The best 3HP producing clone, with 5.45 g.L(-1) of 3HP, produced 11 times more 3HP than the lowest producing clone, which demonstrates the capability of EasyCloneMulti vectors to impact metabolic pathway enzyme activity

Antibodies to TRIM46 are associated with paraneoplastic neurological syndromes.

Paraneoplastic neurological syndromes (PNS) are often characterized by the presence of antineuronal antibodies in patient serum or cerebrospinal fluid. The detection of antineuronal antibodies has proven to be a useful tool in PNS diagnosis and the search for an underlying tumor. Here, we describe three patients with autoantibodies to several epitopes of the axon initial segment protein tripartite motif 46 (TRIM46). We show that anti-TRIM46 antibodies are easy to detect in routine immunohistochemistry screening and can be confirmed by western blotting and cell-based assay. Anti-TRIM46 antibodies can occur in patients with diverse neurological syndromes and are associated with small-cell lung carcinoma

Haematopoietic cell transplantation in Switzerland, changes and results over 20 years: a report from the Swiss Blood Stem Cell Transplantation Working Group for Blood and Marrow Transplantation registry 1997-2016.

In 1997, the Swiss Blood Stem Cell Transplantation Group (SBST) initiated a mandatory national registry for all haematopoietic stem cell transplants (HCTs) in Switzerland. As of 2016, after 20 years, information was available for 7899 patients who had received an HCT (2781 allogeneic [35%] and 5118 autologous [65%]). As some patients had more than one transplant the total number of transplants was 3067 allogeneic and 6448 autologous. We compared patient characteristics and outcome of the first decade (1997-2006) and second decade (2007-2016) of the registry. There were numerous changes over time. For allogeneic HCT, transplant rates, and therefore use of HCT technology, increased from 14 to 21.8 HCTs per 1 million inhabitants per year from the first to the second decade. Likewise autologous HCTs increased from 24.8 to 37.2 annually corrected for population growth. Allogeneic transplant recipients were older (38.4 vs 48.3 years) and more frequently had unrelated donors in the second decade. Similarly, age increased for recipients of autologous HCT (50.8 vs 56.4 years). Analysis of outcome showed that the probabilities of overall and progression-free survival were stable over time, in spite of the treatment of older and higher risk patients. In multivariate analysis, nonrelapse mortality decreased in recipients of allogeneic HCT (relative risk 0.68, 95% confidence interval 0.52-0.87) over the two decades. Improvement in adjusted nonrelapse mortality compensated for the fact that higher risk patients were treated in more recent years, resulting in similar overall survival. Five-year survival probabilities were 56% (53-59%) in the first and 54% (51-57%) in the second decade for allogeneic HCT, and 59% (57-61%) in the first and 61% (59-63%) in the second decade for autologous HCT. Detailed analyses of changes over time are presented. This study included all HCTs performed in Switzerland during the period of observation and the data are useful for quality assurance programmes, healthcare cost estimation and healthcare planning. Between 50 and 60% of patients were long-term survivors after both types of HCT, indicating growing populations of surviving patients requiring long-term care and observation

A novel patient-derived tumorgraft model with TRAF1-ALK anaplastic large-cell lymphoma translocation.

Although anaplastic large-cell lymphomas (ALCL) carrying anaplastic lymphoma kinase (ALK) have a relatively good prognosis, aggressive forms exist. We have identified a novel translocation, causing the fusion of the TRAF1 and ALK genes, in one patient who presented with a leukemic ALK+ ALCL (ALCL-11). To uncover the mechanisms leading to high-grade ALCL, we developed a human patient-derived tumorgraft (hPDT) line. Molecular characterization of primary and PDT cells demonstrated the activation of ALK and nuclear factor kB (NFkB) pathways. Genomic studies of ALCL-11 showed the TP53 loss and the in vivo subclonal expansion of lymphoma cells, lacking PRDM1/Blimp1 and carrying c-MYC gene amplification. The treatment with proteasome inhibitors of TRAF1-ALK cells led to the downregulation of p50/p52 and lymphoma growth inhibition. Moreover, a NFkB gene set classifier stratified ALCL in distinct subsets with different clinical outcome. Although a selective ALK inhibitor (CEP28122) resulted in a significant clinical response of hPDT mice, nevertheless the disease could not be eradicated. These data indicate that the activation of NFkB signaling contributes to the neoplastic phenotype of TRAF1-ALK ALCL. ALCL hPDTs are invaluable tools to validate the role of druggable molecules, predict therapeutic responses and implement patient specific therapies

Dynamic model of supercritical Organic Rankine Cycle waste heat recovery system for internal combustion engine

The supercritical Organic Rankine Cycle (ORC) for the Waste Heat Recovery (WHR) from Internal Combustion (IC) engines has been a growing research area in recent years, driven by the aim to enhance the thermal efficiency of the ORC and engine. Simulation of a supercritical ORC-WHR system before a real-time application is important as high pressure in the system may lead to concerns about safety and availability of components. In the ORC-WHR system, the evaporator is the main contributor to thermal inertia of the system and is considered to be the critical component since the heat transfer of this device influences the efficiency of the system. Since the thermo-physical properties of the fluid at supercritical pressures are dependent on temperature, it is necessary to consider the variations in properties of the working fluid. The wellknown Finite Volume (FV) discretization method is generally used to take those property changes into account. However, a FV model of the evaporator in steady state condition cannot be used to predict the thermal inertia of the cycle when it is subjected to transient heat sources. In this paper, a dynamic FV model of the evaporator has been developed and integrated with other components in the ORC-WHR system. The stability and transient responses along with the performance of the ORC-WHR system for the transient heat source are investigated and are also included in this paper