Minors come of age: minor histocompatibility antigens and graft-versus-host disease

AbstractMinor histocompatibility antigens (miHA) are responsible for the occurrence of graft-versus-host disease in the setting of a major histocompatibility complex matched sibling allogeneic stem cell transplantation. These miHA are peptide fragments that are associated with major histocompatibility complex class I or class II antigens. Elegant experiments have led to the molecular characterization of these antigens. Efforts to prevent graft-versus-host disease could be targeted through this pathway by matching for these miHA or by preventing antigen recognition. Alternatively, these miHA could be exploited as targets for a more potent graft-versus-malignancy effect. This area of miHA promises to continue to be an exciting area of continued research

Grand Unified Yukawa Matrix Ansatz: The Standard Model Fermion Mass, Quark Mixing and CP Violation Parameters

We propose a new mass matrix ansatz: At the grand unified (GU) scale, the standard model (SM) Yukawa coupling matrix elements are integer powers of the square root of the GU gauge coupling constant \varepsilon \equiv \sqrt{\alpha_{\text{GU}}}, multiplied by order unity random complex numbers. It relates the hierarchy of the SM ermion masses and quark mixings to the gauge coupling constants, greatly reducing the SM parameters, and can give good fitting results of the SM fermion mass, quark mixing and CP violation parameters. This is a neat but very effective ansatz.Comment: 4 pages (two columns), by REVTeX 4, 2 tables, no figures, version for publication in CP

Adaptive locomotion of artificial microswimmers

Bacteria can exploit mechanics to display remarkable plasticity in response to locally changing physical and chemical conditions. Compliant structures play a striking role in their taxis behavior, specifically for navigation inside complex and structured environments. Bioinspired mechanisms with rationally designed architectures capable of large, nonlinear deformation present opportunities for introducing autonomy into engineered small-scale devices. This work analyzes the effect of hydrodynamic forces and rheology of local surroundings on swimming at low Reynolds number, identifies the challenges and benefits of utilizing elastohydrodynamic coupling in locomotion, and further develops a suite of machinery for building untethered microrobots with self-regulated mobility. We demonstrate that coupling the structural and magnetic properties of artificial microswimmers with the dynamic properties of the fluid leads to adaptive locomotion in the absence of on-board sensors

Longitudinal Analysis of T-Cell Receptor Variable β Chain Repertoire in Patients with Acute Graft-versus-Host Disease after Allogeneic Stem Cell Transplantation

AbstractT-cell receptor variable β chain (TCRBV) repertoire spectratyping involves the estimation of CDR3 length distributions for monitoring T-cell receptor diversity and has proven useful for analyses of immune reconstitution and T-cell clonal expansions in graft-versus-host disease (GVHD) and graft-versus-leukemia after allogeneic stem cell transplantation. We performed a longitudinal spectratype analysis of 23 TCRBV families in 28 patients who underwent allogeneic T cell–depleted peripheral blood stem cell transplantation. Sixteen patients subsequently developed acute GVHD. We recently developed statistical methods that bring increased power and flexibility to spectratype analysis and allow us to analyze TCRBV repertoire development under appropriately complex statistical models. Applying these methods, we found that patients with acute GVHD demonstrated TCRBV repertoire development statistically distinct from that repertoire development in patients without GVHD. Specifically, GVHD patients showed spectratypes indicative of lower diversity and greater deviation from the spectratypes expected in healthy individuals at intermediate times. Most individual TCRBV subfamilies had spectratypes statistically distinguishable between GVHD and non-GVHD patients at 6 months after transplantation. These results suggest that the T-cell receptor repertoire perturbations associated with acute GVHD are widely spread throughout the TCRBV families

Vascular Endothelial Cells Produce Soluble Factors That Mediate the Recovery of Human Hematopoietic Stem Cells after Radiation Injury

AbstractThe risk of terrorism with nuclear or radiologic weapons is considered to be high over the coming decade. Ionizing radiation can cause a spectrum of hematologic toxicities, from mild myelosuppression to myeloablation and death. However, the potential regenerative capacity of human hematopoietic stem cells (HSCs) after radiation injury has not been well characterized. In this study, we sought to characterize the effects of ionizing radiation on human HSCs and to determine whether signals from vascular endothelial cells could promote the repair of irradiated HSCs. Exposure of human bone marrow CD34+ cells to 400 cGy caused a precipitous decline in hematopoietic progenitor cell content and primitive cells capable of repopulating nonobese diabetic/severe combined immunodeficient mice (SCID-repopulating cells), which was not retrievable via treatment with cytokines. Conversely, culture of 400 cGy–irradiated bone marrow CD34+ cells with endothelial cells under noncontact conditions supported the differential recovery of both viable progenitor cells and primitive SCID-repopulating cells. These data illustrate that vascular endothelial cells produce soluble factors that promote the repair and functional recovery of HSCs after radiation injury and suggest that novel factors with radiotherapeutic potential can be identified within this milieu

Nonstandard order parameters and the origin of CP violation

The consideration of chirality-preserving 2-fermion order parameters may shed new light on the strong CP problem and the breakdown of flavor symmetries. We describe two situations, one having the standard KM picture for weak CP violation and another having new sources of weak CP violation.Comment: 12 pages, no figure

Pinning and Tribology of Tethered Monolayers on Disordered Substrates

We study the statistical mechanics and dynamics of crystalline films with a fixed internal connectivity on a random substrate. Defect free triangular lattices exhibit a sharp transition to a low temperature glassy phase with anomalous phonon fluctuations and a nonlinear force-displacement law with a continuously variable exponent, similar to the vortex glass phase of directed lines in 1+1 dimensions. The periodicity of the tethered monolayer acts like a filter which amplifies particular Fourier components of the disorder. However, the absence of annealed topological defects like dislocations is crucial: the transition is destroyed when the constraint of fixed connectivity is relaxed and dislocations are allowed to proliferate.Comment: revtex, preprint style, 27 pages. This submission is a revision of cond-mat/9607184. The revisions affect only Appendix B, Appendix C, and Eqs. 2.27, 2.28, 2.3

Donor Allospecific CD44high Central Memory T Cells Have Decreased Ability to Mediate Graft-vs.-Host Disease

Data from both animal models and humans have demonstrated that effector memory T cells (TEM) and central memory T cells (TCM) from unprimed donors have decreased ability to induce graft-vs-host disease (GVHD). Allospecific TEM from primed donors do not mediate GVHD. However, the potential of alloreactive TCM to induce GVHD is not clear. In this study, we sought to answer this question using a novel GVHD model induced by T cell receptor (TCR) transgenic OT-II T cells. Separated from OT-II mice immunized with OVA protein 8 weeks earlier, the allospecific CD44high TCM were able to mediate skin graft rejection after transfer to naive mice, yet had dramatically decreased ability to induce GVHD. We also found that these allospecific CD44high TCM persisted in GVHD target organs for more than 30 days post-transplantation, while the expansion of these cells was dramatically decreased during GVHD, suggesting an anergic or exhausted state. These observations provide insights into how allospecific CD4+ TCM respond to alloantigen during GVHD and underscore the fundamental difference of alloresponses mediated by allospecific TCM in graft rejection and GVHD settings

Absence of a Phase Transition in a Three--Dimensional Vortex Glass Model with Screening

We study the gauge glass model for the vortex glass transition in type--II superconductors, including screening of the interaction between vortices. {}From the size dependence of the domain wall energy we find that, in two--dimensions, the transition is at $T=0$ both with and without screening but the exponents are different in the two cases. In three-dimensions, we find that screening destroys the finite temperature transition found earlier when screening was neglected.Comment: 11 pages plus LaTeX with Revtex macros, 3 postscript figures, uuencoded and compressse