Generating a Schr\"odinger-cat-like state via a coherent superposition of photonic operations

We propose an optical scheme to generate a superposition of coherent states with enhanced size adopting an interferometric setting at the single-photon level currently available in the laboratory. Our scheme employs a nondegenerate optical parametric amplifier together with two beam splitters so that the detection of single photons at the output conditionally implements the desired superposition of second-order photonic operations. We analyze our proposed scheme by considering realistic on-off photodetectors with nonideal efficiency in heralding the success of conditional events. A high-quality performance of our scheme is demonstrated in view of various criteria such as quantum fidelity, mean output energy, and measure of quantum interference

Increasing the Potency and Breadth of an HIV Antibody by Using Structure-Based Rational Design

Antibodies against the CD4 binding site (CD4bs) on the HIV-1 spike protein gp120 can show exceptional potency and breadth. We determined structures of NIH45-46, a more potent clonal variant of VRC01, alone and bound to gp120. Comparisons with VRC01-gp120 revealed that a four-residue insertion in heavy chain complementarity–determining region 3 (CDRH3) contributed to increased interaction between NIH45-46 and the gp120 inner domain, which correlated with enhanced neutralization. We used structure-based design to create NIH45-46^(G54W), a single substitution in CDRH2 that increases contact with the gp120 bridging sheet and improves breadth and potency, critical properties for potential clinical use, by an order of magnitude. Together with the NIH45-46–gp120 structure, these results indicate that gp120 inner domain and bridging sheet residues should be included in immunogens to elicit CD4bs antibodies

Inverse relationship between oligoclonal expanded CD69- TTE and CD69+ TTE cells in bone marrow of multiple myeloma patients.

CD8+CD57+ terminal effector T (TTE) cells are a component of marrow-infiltrating lymphocytes and may contribute to the altered immune responses in multiple myeloma (MM) patients. We analyzed TTE cells in the bone marrow (BM) and peripheral blood (PB) of age-matched controls and patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering MM (SMM), and newly diagnosed (ND) MM using flow cytometry, mass cytometry, and FlowSOM clustering. TTE cells are heterogeneous in all subjects, with BM containing both CD69- and CD69+ subsets, while only CD69- cells are found in PB. Within the BM-TTE compartment, CD69- and CD69+ cells are found in comparable proportions in controls, while CD69- cells are dominant in MGUS and SMM and predominantly either CD69- or CD69+ cells in NDMM. A positive relationship between CD69+TTE and CD69-TTE cells is observed in the BM of controls, lost in MGUS, and converted to an inverse relationship in NDMM. CD69-TTE cells include multiple oligoclonal expansions of T-cell receptor/Vβ families shared between BM and PB of NDMM. Oligoclonal expanded CD69-TTE cells from the PB include myeloma-reactive cells capable of killing autologous CD38hi plasma cells in vitro, involving degranulation and high expression of perforin and granzyme. In contrast to CD69-TTE cells, oligoclonal expansions are not evident within CD69+TTE cells, which possess low perforin and granzyme expression and high inhibitory checkpoint expression and resemble T resident memory cells. Both CD69-TTE and CD69+TTE cells from the BM of NDMM produce large amounts of the inflammatory cytokines interferon-γ and tumor necrosis factor α. The balance between CD69- and CD69+ cells within the BM-TTE compartment may regulate immune responses in NDMM and contribute to the clinical heterogeneity of the disease

Sequence and Structural Convergence of Broad and Potent HIV Antibodies That Mimic CD4 Binding

Passive transfer of broadly neutralizing HIV antibodies can prevent infection, which suggests that vaccines that elicit such antibodies would be protective. Thus far, however, few broadly neutralizing HIV antibodies that occur naturally have been characterized. To determine whether these antibodies are part of a larger group of related molecules, we cloned 576 new HIV antibodies from four unrelated individuals. All four individuals produced expanded clones of potent broadly neutralizing CD4-binding-site antibodies that mimic binding to CD4. Despite extensive hypermutation, the new antibodies shared a consensus sequence of 68 immunoglobulin H (IgH) chain amino acids and arise independently from two related IgH genes. Comparison of the crystal structure of one of the antibodies to the broadly neutralizing antibody VRC01 revealed conservation of the contacts to the HIV spike

HIV therapy by a combination of broadly neutralizing antibodies in humanized mice

Human antibodies to human immunodeficiency virus-1 (HIV-1) can neutralize a broad range of viral isolates in vitro and protect non-human primates against infection. Previous work showed that antibodies exert selective pressure on the virus but escape variants emerge within a short period of time. However, these experiments were performed before the recent discovery of more potent anti-HIV-1 antibodies and their improvement by structure-based design. Here we re-examine passive antibody transfer as a therapeutic modality in HIV-1-infected humanized mice. Although HIV-1 can escape from antibody monotherapy, combinations of broadly neutralizing antibodies can effectively control HIV-1 infection and suppress viral load to levels below detection. Moreover, in contrast to antiretroviral therapy the longer half-life of antibodies led to control of viraemia for an average of 60 days after cessation of therapy. Thus, combinations of potent monoclonal antibodies can effectively control HIV-1 replication in humanized mice, and should be re-examined as a therapeutic modality in HIV-1-infected individuals

Technology and layout-related testing of static random-access memories

Static random-access memories (SRAMs) exhibit faults that are electrical in nature. Functional and electrical testing are performed to diagnose faulty operation. These tests are usually designed from simple fault models that describe the chip interface behavior without a thorough analysis of the chip layout and technology. However, there are certain technology and layout-related defects that are internal to the chip and are mostly time-dependent in nature. The resulting failures may or may not seriously degrade the input/output interface behavior. They may show up as electrical faults (such as a slow access fault) and/or functional faults (such as a pattern sensitive fault). However, these faults cannot be described properly with the functional fault models because these models do not take timing into account. Also, electrical fault models that describe merely the input/output interface behavior are inadequate to characterize every possible defect in the basic SRAM cell. Examples of faults produced by these defects are: (a) static data loss, (b) abnormally high currents drawn from the power supply, etc. Generating tests for such faults often requires a thorough understanding and analysis of the circuit technology and layout. In this article, we shall examine ways to characterize and test such faults. We shall divide such faults into two categories depending on the types of SRAMs they effect—silicon SRAMs and GaAs SRAMs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43015/1/10836_2004_Article_BF00972519.pd

Matrix models and sensitivity analysis of populations classified by age and stage : a vec-permutation matrix approach

© The Author(s), 2011. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Theoretical Ecology 5 (2012): 403-417, doi:10.1007/s12080-011-0132-2.Matrix population models in which individuals are classified by both age and stage can be constructed using the vec-permutation matrix. The resulting age-stage models can be used to derive the age-specific consequences of a stage-specific life history or to describe populations in which the vital rates respond to both age and stage. I derive a general formula for the sensitivity of any output (scalar, vector, or matrix-valued) of the model, to any vector of parameters, using matrix calculus. The matrices describing age-stage dynamics are almost always reducible; I present results giving conditions under which population growth is ergodic from any initial condition. As an example, I analyze a published stage-specific model of Scotch broom (Cytisus scoparius), an invasive perennial shrub. Sensitivity analysis of the population growth rate finds that the selection gradients on adult survival do not always decrease with age but may increase over a range of ages. This may have implications for the evolution of senescence in stage-classified populations. I also derive and analyze the joint distribution of age and stage at death and present a sensitivity analysis of this distribution and of the marginal distribution of age at death.This research was supported by National Science Foundation Grant DEB-0816514 and by a Research Award from the Alexander von Humboldt Foundation