A Novel Trans Conformation of Ligand-Free Calmodulin

10.1371/journal.pone.0054834PLoS ONE81

Investigation of Cable Insulation and Mechanical Properties of Niobium-Tin Composite

As a part of the Fermilab high field Nb{sub 3}Sn dipole development program, various issues of magnet technology are being investigated. In cable insulation development, S-2 fiber glass sleeve and a new ceramic insulation developed by Composite Technology Development Inc. (CTD) were studied as a possible candidates. For each type of insulation, Nb{sub 3}Sn ten-stack samples were reacted and then vacuum impregnated with epoxy. Measurements of modulus of elasticity and Poisson�s ratio under compression were made at room temperature and at 4.2 K. For comparison, an epoxy impregnated NbTi composite was also tested

Tailoring CD19xCD3-DART exposure enhances T-cells to eradication of B-cell neoplasms.

Many patients with B-cell malignancies can be successfully treated, although tumor eradication is rarely achieved. T-cell-directed killing of tumor cells using engineered T-cells or bispecific antibodies is a promising approach for the treatment of hematologic malignancies. We investigated the efficacy of CD19xCD3 DART bispecific antibody in a broad panel of human primary B-cell malignancies. The CD19xCD3 DART identified 2 distinct subsets of patients, in which the neoplastic lymphocytes were eliminated with rapid or slow kinetics. Delayed responses were always overcome by a prolonged or repeated DART exposure. Both CD4 and CD8 effector cytotoxic cells were generated, and DART-mediated killing of CD4+ cells into cytotoxic effectors required the presence of CD8+ cells. Serial exposures to DART led to the exponential expansion of CD4 + and CD8 + cells and to the sequential ablation of neoplastic cells in absence of a PD-L1-mediated exhaustion. Lastly, patient-derived neoplastic B-cells (B-Acute Lymphoblast Leukemia and Diffuse Large B Cell Lymphoma) could be proficiently eradicated in a xenograft mouse model by DART-armed cytokine induced killer (CIK) cells. Collectively, patient tailored DART exposures can result in the effective elimination of CD19 positive leukemia and B-cell lymphoma and the association of bispecific antibodies with unmatched CIK cells represents an effective modality for the treatment of CD19 positive leukemia/lymphoma

Superconducting magnets in high-radiation environment at super colliders

The principal challenges arising from beam-induced energy deposition in superconducting (SC) magnets at high-energy high-luminosity hadron and lepton colliders are described. Radiation constraints are analyzed that include quench stability, dynamic heat loads on the cryogenic system, radiation damage limiting the component lifetime, and residual dose rates related to hands-on maintenance. These issues are especially challenging for the interaction regions (IR), particularly for the considered upgrade layouts of the Large Hadron Collider. Up to a few kW of beam power can dissipate in a single SC magnet, and a local peak power density can substantially exceed the quench levels. Just formally, the magnet lifetime is limited to a few months under these conditions. Possible solutions and the ways to mitigate these problems are described in this paper along with R&D needed

Anisotropic deformation behavior under various strain paths in commercially pure titanium Grade 1 and Grade 2 sheets

In this study, the anisotropic deformation behavior in commercially pure titanium Grade 1 and Grade 2 sheets under various strain paths was examined. A small but sharp stress peak arose during tension following compression in the Grade 1 sheet when loaded in the rolling direction, and the occurrence of a stress peak was retarded when the sheet was subjected to cyclic loading; however, such behavior did not occur in the Grade 2 sheet. Similarly, the work-hardening rate was different between the initial and latter stages of compression following tension. These behaviors did not arise when the sheets were loaded in other directions. The type of active twin mode was different depending on the loading path. When loaded in the rolling direction in both Grade 1 and Grade 2 sheets, twinning and detwinning were active, respectively, during compression and tension following compression, whereas twinning and detwinning were active during tension and compression following tension. The twinning activity was much more pronounced in the Grade 1 sheet than in the Grade 2 sheet. The abovementioned stress-strain responses were presumed to result from twinning and detwinning activities as for magnesium alloy sheets. However, we concluded that the effect of twinning activity on the stress-strain curves was much smaller in the titanium sheet than in magnesium alloy sheets

Field quality of quadrupole R&D models for the LHC IR

Superconducting quadrupole magnets operating in superfluid helium at 1.9 K, with 70 mm bore and nominal field gradient of 205 T/m at collision optics, are being developed by the US LHC Accelerator Project for the Interaction Regions of the Large Hadron Collider (LHC). A magnet model program to validate and optimize the design is underway. This paper reports results of field quality measurements of four model magnets. (3 refs)

Quench performance of Fermilab high gradient quadrupole short models for the LHC Interaction Regions

Fermilab and LBNL are in the midst of superconducting magnet R&D program to test and optimize the design of quadrupoles to be used in the LHC Interaction Region inner triplets. The magnets are required to deliver a 215 T/m gradient across a 70 mm aperture. Five quadrupole short models have been fabricated and four of them have been tested. This paper describes the last model design details and reports the results of the magnet quench performance study. (5 refs)

Flotillins Interact with PSGL-1 in Neutrophils and, upon Stimulation, Rapidly Organize into Membrane Domains Subsequently Accumulating in the Uropod

BACKGROUND: Neutrophils polarize and migrate in response to chemokines. Different types of membrane microdomains (rafts) have been postulated to be present in rear and front of polarized leukocytes and disruption of rafts by cholesterol sequestration prevents leukocyte polarization. Reggie/flotillin-1 and -2 are two highly homologous proteins that are ubiquitously enriched in detergent resistant membranes and are thought to shape membrane microdomains by forming homo- and hetero-oligomers. It was the goal of this study to investigate dynamic membrane microdomain reorganization during neutrophil activation. METHODOLOGY/PRINCIPAL FINDINGS: We show now, using immunofluorescence staining and co-immunoprecipitation, that endogenous flotillin-1 and -2 colocalize and associate in resting spherical and polarized primary neutrophils. Flotillins redistribute very early after chemoattractant stimulation, and form distinct caps in more than 90% of the neutrophils. At later time points flotillins accumulate in the uropod of polarized cells. Chemotactic peptide-induced redistribution and capping of flotillins requires integrity and dynamics of the actin cytoskeleton, but does not involve Rho-kinase dependent signaling related to formation of the uropod. Both flotillin isoforms are involved in the formation of this membrane domain, as uropod location of exogenously expressed flotillins is dramatically enhanced by co-overexpression of tagged flotillin-1 and -2 in differentiated HL-60 cells as compared to cells expressing only one tagged isoform. Flotillin-1 and -2 associate with P-selectin glycoprotein ligand 1 (PSGL-1) in resting and in stimulated neutrophils as shown by colocalization and co-immunoprecipitation. Neutrophils isolated from PSGL-1-deficient mice exhibit flotillin caps to the same extent as cells isolated from wild type animals, implying that PSGL-1 is not required for the formation of the flotillin caps. Finally we show that stimulus-dependent redistribution of other uropod-located proteins, CD43 and ezrin/radixin/moesin, occurs much slower than that of flotillins and PSGL-1. CONCLUSIONS/SIGNIFICANCE: These results suggest that flotillin-rich actin-dependent membrane microdomains are importantly involved in neutrophil uropod formation and/or stabilization and organize uropod localization of PSGL-1