Vibrating Wire Thermometry in Superfluid 3He

We report systematic measurements of the response of a Vibrating Wire Resonator (VWR) in normal and superfluid liquid ³He. Special attention has been paid to the hydrodynamic regime of the superfluid B-phase, where the response parameters of the VWR do not follow a simple law. We show that a simple interpolation between the region where first order slip-corrections can be applied and the ballistic regime is insufficient. Measuring an empirical effective viscosity, we propose a temperature calibration method which allows the use of VWRs as a secondary thermometer at intermediate and high pressures in the temperature range 0.2 T _c < T < 50 mK.     

Centurion syndrome. Idiopathic anterior displacement of the medial canthus

Bone marrow transplantation (BMT) using HLA-partially matched family donors has produced disappointing results (25-30% of long-term survivors) in patients with severe aplastic anemia. We describe two children affected by severe aplastic anemia, not responsive to immunosuppressive therapy, who underwent allogeneic bone marrow transplantation using a HLA-partially matched family donor. Both cases presented 2 first class HLA-antigens (A and B) disparity between donor and recipient. The pretransplant conditioning regimen consisted of cyclophosphamide, thoracoabdominal irradiation, cytosine-arabinoside, and antilymphocyte globulin. As graft versus host disease (GVHD) prophylaxis, Cyclosporine-A was administered at usual dosages for 6 months. A full marrow engraftment was observed in both cases. Only grade I acute GVHD, promptly responsive to corticosteroid therapy, developed with no chronic GVHD. Five months after transplant, both children progressively developed hypertension, renal function impairment, thrombocytopenia, and severe normochromic anemia, with erythropoietin serum levels lower than expected for the haematocrit. After antihypertension treatment and supportive therapy, the clinical picture progressively improved, while treatment with recombinant human erythropoietin completely corrected the long-lasting anemia. The two children are alive and well 28 months after the transplant, with a Karnofsky score of 100% and a normal peripheral blood count. The authors suggest that, once immunosuppressive therapy has failed, BMT from donors other than HLA-identical sibling is a feasible approach in children affected by severe aplastic anemia, not having an HLA-identical donor.     

Green Tax Reforms and Computational Economics A Do-it-yourself Approach

The double or even triple dividend hypothesis of green tax reforms has beena major issue of dispute in both the scientific community and the politicalarena during the last decade. Theoretical analysis has provided a number ofimportant qualitative insights to the debate but lacks of actual policyrelevance due to very restrictive assumptions. Applied research that takes thestep from stylized analytical to complex numerical models usually comes as ablackbox to non-expert modelers. This paper aims at bridging the gap betweenstylized theoretical work and numerical analysis. We develop a flexible,interactive simulation model which is accessible underhttp://brw.zew.de. Users can specify their own green tax reforms andevaluate the induced economic and environmental effects. Based on illustrativesimulations, we demonstrate the usefulness of our do-it-yourself approach fora better understanding of the double (triple) dividend hypothesis.     

Structure-Activity Relationships of Benzamides and Isoindolines Designed as SARS-CoV Protease Inhibitors Effective against SARS-CoV-2

Inhibition of coronavirus (CoV)-encoded papain-like cysteine proteases (PL^pro) represents an attractive strategy to treat infections by these important human pathogens. Herein we report on structure-activity relationships (SAR) of the noncovalent active-site directed inhibitor (R)-5-amino-2-methyl-N-(1-(naphthalen-1-yl)ethyl) benzamide ( 2 b ), which is known to bind into the S3 and S4 pockets of the SARS-CoV PL^pro. Moreover, we report the discovery of isoindolines as a new class of potent PL^pro inhibitors. The studies also provide a deeper understanding of the binding modes of this inhibitor class. Importantly, the inhibitors were also confirmed to inhibit SARS-CoV-2 replication in cell culture suggesting that, due to the high structural similarities of the target proteases, inhibitors identified against SARS-CoV PL^pro are valuable starting points for the development of new pan-coronaviral inhibitors.     

Antisense Oligonucleotide-Based Rescue of Aberrant Splicing Defects Caused by 15 Pathogenic Variants in ABCA4

The discovery of novel intronic variants in the ABCA4 locus has contributed significantly to solving the missing heritability in Stargardt disease (STGD1). The increasing number of variants affecting pre-mRNA splicing makes ABCA4 a suitable candidate for antisense oligonucleotide (AON)-based splicing modulation therapies. In this study, AON-based splicing modulation was assessed for 15 recently described intronic variants (three near-exon and 12 deep-intronic variants). In total, 26 AONs were designed and tested in vitro using a midigene-based splice system. Overall, partial or complete splicing correction was observed for two variants causing exon elongation and all variants causing pseudoexon inclusion. Together, our results confirm the high potential of AONs for the development of future RNA therapies to correct splicing defects causing STGD1.     

Mechanical properties of certain oriented crystalline polymers

The yield stress is a simple function of the deformation ratio in the direction of testing for specimens oriented by uniaxial or biaxial stretching or rolling. Unless the yield stress increases more rapidly than in proportion to the deformation ratio, there will be instability during tensile creep under high loads. The relative merit of various polymers differs for creep and stress relaxation. Fatigue and bend recovery are also related to the molecular structure.     

A finite element method for poro mechanical modelling of geotechnical problems using local second gradient models

In this paper, a new finite element method is described and applied. It is based on a theory developed to model poromechanical problems where the mechanical part is obeying a second gradient theory. The aim of such a work is to properly model the post localized behaviour of soils and rocks saturated with a pore fluid. Beside the development of this new coupled theory, a corresponding finite element method has been developed. The elements used are based on a weak form of the relation between the deformation gradient and the second gradient, using a field of Lagrange multipliers. The global problem is solved by a system of equations where the kinematic variables are fully coupled with the pore pressure. Some numerical experiments showing the effectiveness of the method ends the paper. Copyright © 2005 John Wiley & Sons, Ltd.     

In-situ comprehensive calibration of a tri-port nano-electro-mechanical device

We report on experiments performed in vacuum and at cryogenic temperatures on a tri-port nano-electro-mechanical (NEMS) device. One port is a very nonlinear capacitive actuation, while the two others implement the magnetomotive scheme with a linear input force port and a (quasi-linear) output velocity port. We present an experimental method enabling a full characterization of the nanomechanical device harmonic response: the nonlinear capacitance function C(x) is derived, and the normal parameters k and m (spring constant and mass) of the mode under study are measured through a careful definition of the motion (in meters) and of the applied forces (in Newtons). These results are obtained with a series of purely electric measurements performed without disconnecting/reconnecting the device, and rely only on known dc properties of the circuit, making use of a thermometric property of the oscillator itself: we use the Young modulus of the coating metal as a thermometer, and the resistivity for Joule heating. The setup requires only three connecting lines without any particular matching, enabling the preservation of a high impedance NEMS environment even at MHz frequencies. The experimental data are fit to a detailed electrical and thermal model of the NEMS device, demonstrating a complete understanding of its dynamics. These methods are quite general and can be adapted (as a whole, or in parts) to a large variety of electromechanical devices.     

Development of Anti-LRRC15 Small Fragments for Imaging Purposes Using a Phage-Display ScFv Approach

The human leucine-rich repeat-containing protein 15 (LRRC15) is a membrane protein identified as a marker of CAF (cancer-associated fibroblast) cells whose overexpression is positively correlated with cancer grade and outcome. Nuclear molecular imaging (i.e., SPECT and PET) to track LRRC15 expression could be very useful in guiding further therapeutic strategies. In this study, we developed an ScFv mouse phage-display library to obtain small fragment antibodies against human LRRC15 for molecular imaging purposes. Mice were immunized with recombinant human LRRC15 (hLRRC15), and lymph node cells were harvested for ScFv (single-chain variable fragment) phage-display analysis. The built library was used for panning on cell lines with constitutive or induced expression after transfection. The choice of best candidates was performed by screening various other cell lines, using flow cytometry. The selected candidates were reformatted into Cys-ScFv or Cys-diabody by addition of cysteine, and cloned in mammalian expression vectors to obtain batches of small fragments that were further used in site-specific radiolabeling tests. The obtained library was 1.2 × 10⁷ cfu/µg with an insertion rate >95%. The two panning rounds performed on cells permittedenrichment of 2 × 10⁻³. Screening with flow cytometry allowed us to identify 28 specific hLRRC15 candidates. Among these, two also recognized murine LRCC15 and were reformatted into Cys-ScFv and Cys-diabody. They were expressed transiently in a mammalian system to obtain 1.0 to 4.5 mg of Cys fragments ready for bioconjugation and radiolabeling. Thus, in this paper, we demonstrate the relevance of the phage-display ScFv library approach for the fast-track development of small antibodies for imaging and/or immunotherapy purposes.