Advances in Human B Cell Phenotypic Profiling

To advance our understanding and treatment of disease, research immunologists have been called-upon to place more centralized emphasis on impactful human studies. Such endeavors will inevitably require large-scale study execution and data management regulation (“Big Biology”), necessitating standardized and reliable metrics of immune status and function. A well-known example setting this large-scale effort in-motion is identifying correlations between eventual disease outcome and T lymphocyte phenotype in large HIV-patient cohorts using multiparameter flow cytometry. However, infection, immunodeficiency, and autoimmunity are also characterized by correlative and functional contributions of B lymphocytes, which to-date have received much less attention in the human Big Biology enterprise. Here, we review progress in human B cell phenotyping, analysis, and bioinformatics tools that constitute valuable resources for the B cell research community to effectively join in this effort

Impact of patient characteristics on the risk of influenza/ILI-related complications

BACKGROUND: We sought to quantify the impact of patient characteristics on complications and health care costs associated with influenza and influenza-like illness (ILI) in a nonelderly population. METHODS: Patients with medical reimbursement claims for influenza in the 1996–1997 season were identified from the automated database of a large private New England Insurer (NEI). Influenza care during the 21- day follow-up period was characterized according to age, gender, vaccine status, co-morbidities, prior influenza/ILI episodes, treatments, and recent health care costs and related diagnoses. RESULTS: There were 6,241 patients. Approximately 20% had preexisting chronic lung disease. Overall, 23% had health care services for possible complications, among which respiratory diagnoses were the most common (13%). Two percent of the influenza/ILI episodes involved hospitalization, with a median stay of five days. Factors most strongly predictive of hospitalizations and complications were preexisting malignancy (hospitalizations OR = 3.7 and complications OR = 2.4), chronic heart disease (OR = 3.2 and OR = 1.8), diabetes (OR = 2.2 and OR = 1.7) and recent illnesses that would have counted as complications had they occurred during an influenza/ILI episode (hospitalizations OR = 3.2 and complications OR = 1.5). The same factors affected influenza-related costs and total costs of care as dramatically as they affected complication rates. CONCLUSIONS: Influenza/ILI-related costs are driven by the characteristics that predict complications of influenza. Patients with chronic illness and those with recent acute respiratory events are the most likely to experience complications and hospitalizations

A Homogenous Set of Globular Cluster Relative Distances and Reddenings

We present distance modulus and reddening determinations for 72 Galactic globular clusters from the homogeneous photometric database of Piotto et al. (2002), calibrated to the HST flight F439W and F555W bands. The distances have been determined by comparison with theoretical absolute magnitudes of the ZAHB. For low and intermediate metallicity clusters, we have estimated the apparent Zero Age Horizontal Branch (ZAHB) magnitude from the RR Lyrae level. For metal rich clusters, the ZAHB magnitude was obtained from the fainter envelope of the red HB. Reddenings have been estimated by comparison of the HST colour-magnitude diagrams (CMD) with ground CMDs of low reddening template clusters. The homogeneity of both the photometric data and the adopted methodological approach allowed us to obtain highly accurate relative cluster distances and reddenings. Our results are also compared with recent compilations in the literature.Comment: 12 pages, 6 figures, accepted for publication in Astronomy & Astrophysic

Global metallicity of globular cluster stars from colour-magnitude diagrams

We have developed an homogeneous evolutionary scenario for H- and He-burning low-mass stars by computing updated stellar models for a wide metallicity and age range (0.0002$\le Z \le$0.004 and 9$\le t(Gyr) \le$15, respectively) suitable to study globular clusters. This theoretical scenario allows us to provide self-consistent predictions about the dependence of selected observational features of the colour-magnitude diagram, such as the brightness of the Turn Off (TO), Zero Age Horizontal Branch (ZAHB) and Red Giant Branch bump (BUMP), on the cluster metallicity and age. Taking into account these predictions, we introduce a new observable based on the visual magnitude difference between the TO and the ZAHB, and the TO and the RGB-bump, given by $A=\Delta M_V$(TO-BUMP)$-0.566\Delta M_V$(TO-ZAHB). We show that the parameter $A$ does not depend at all on the cluster age, whereas it does strongly depend on the cluster global metallicity. The calibration of the parameter $A$ as a function of $Z$ is then provided, as based on our evolutionary models. We tested the reliability of this result by also considering stellar models computed by other authors,employing different input physics. Eventually, we present clear evidence that the variation of $\Delta M_V$(TO-BUMP) with $\Delta M_V$(TO-ZAHB) does supply a powerful probe of the global metal abundance, at least when homogeneous theoretical frameworks are adopted. We provide an estimate of the global metallicity of 36 globular clusters in the Milky Way, based on our {\it A-Z} calibration, and a large observational database of Galactic GCs. By considering the empirical [Fe/H] scales by both Zinn & West (1984) and Carretta & Gratton (1997), we are also able to provide an estimate of the GC $\alpha-$element enhancement.Comment: 10 pages, 10 figures, in press on MNRA

Superconducting nanowire photon number resolving detector at telecom wavelength

The optical-to-electrical conversion, which is the basis of optical detectors, can be linear or nonlinear. When high sensitivities are needed single-photon detectors (SPDs) are used, which operate in a strongly nonlinear mode, their response being independent of the photon number. Nevertheless, photon-number resolving (PNR) detectors are needed, particularly in quantum optics, where n-photon states are routinely produced. In quantum communication, the PNR functionality is key to many protocols for establishing, swapping and measuring entanglement, and can be used to detect photon-number-splitting attacks. A linear detector with single-photon sensitivity can also be used for measuring a temporal waveform at extremely low light levels, e.g. in long-distance optical communications, fluorescence spectroscopy, optical time-domain reflectometry. We demonstrate here a PNR detector based on parallel superconducting nanowires and capable of counting up to 4 photons at telecommunication wavelengths, with ultralow dark count rate and high counting frequency

9G4 Autoreactivity Is Increased in HIV-Infected Patients and Correlates with HIV Broadly Neutralizing Serum Activity

The induction of a broadly neutralizing antibody (BNAb) response against HIV-1 would be a desirable feature of a protective vaccine. Vaccine strategies thus far have failed to elicit broadly neutralizing antibody responses; however a minority of HIV-infected patients do develop circulating BNAbs, from which several potent broadly neutralizing monoclonal antibodies (mAbs) have been isolated. The findings that several BNmAbs exhibit autoreactivity and that autoreactive serum antibodies are observed in some HIV patients have advanced the possibility that enforcement of self-tolerance may contribute to the rarity of BNAbs. To examine the possible breakdown of tolerance in HIV patients, we utilized the 9G4 anti-idiotype antibody system, enabling resolution of both autoreactive VH4-34 gene-expressing B cells and serum antibodies. Compared with healthy controls, HIV patients had significantly elevated 9G4+ serum IgG antibody concentrations and frequencies of 9G4+ B cells, a finding characteristic of systemic lupus erythematosus (SLE) patients, both of which positively correlated with HIV viral load. Compared to the global 9G4−IgD− memory B cell population, the 9G4+IgD− memory fraction in HIV patients was dominated by isotype switched IgG+ B cells, but had a more prominent bias toward “IgM only" memory. HIV envelope reactivity was observed both in the 9G4+ serum antibody and 9G4+ B cell population. 9G4+ IgG serum antibody levels positively correlated (r = 0.403, p = 0.0019) with the serum HIV BNAbs. Interestingly, other serum autoantibodies commonly found in SLE (anti-dsDNA, ANA, anti-CL) did not correlate with serum HIV BNAbs. 9G4-associated autoreactivity is preferentially expanded in chronic HIV infection as compared to other SLE autoreactivities. Therefore, the 9G4 system provides an effective tool to examine autoreactivity in HIV patients. Our results suggest that the development of HIV BNAbs is not merely a consequence of a general breakdown in tolerance, but rather a more intricate expansion of selective autoreactive B cells and antibodies

Inflammation-induced effector CD4+ T cell interstitial migration is alpha-v integrin dependent

Leukocytes must traverse inflamed tissues to effectively control local infection. Although motility in dense tissues appears to be integrin-independent actin-myosin based, during inflammation changes to the extracellular matrix (ECM) may necessitate distinct motility requirements. Indeed, we found that T cell interstitial motility was critically dependent on RGD-binding integrins in the inflamed dermis. Inflammation-induced deposition of fibronectin was functionally linked to increased αv integrin expression on effector CD4+ T cells. Using intravital multi-photon imaging, we found that CD4+ T cell motility was dependent on αv expression. Selective αv blockade or knockdown arrested TH1 motility in the inflamed tissue and attenuated local effector function. These data show a context-dependent specificity of lymphocyte movement in inflamed tissues that is essential for protective immunity

Characterization of superconducting through-silicon vias as capacitive elements in quantum circuits

The large physical size of superconducting qubits and their associated on-chip control structures presents a practical challenge towards building a large-scale quantum computer. In particular, transmons require a high-quality-factor shunting capacitance that is typically achieved by using a large coplanar capacitor. Other components, such as superconducting microwave resonators used for qubit state readout, are typically constructed from coplanar waveguides which are millimeters in length. Here we use compact superconducting through-silicon vias to realize lumped element capacitors in both qubits and readout resonators to significantly reduce the on-chip footprint of both of these circuit elements. We measure two types of devices to show that TSVs are of sufficient quality to be used as capacitive circuit elements and provide a significant reductions in size over existing approaches

Demonstration of tunable three-body interactions between superconducting qubits

Nonpairwise multi-qubit interactions present a useful resource for quantum information processors. Their implementation would facilitate more efficient quantum simulations of molecules and combinatorial optimization problems, and they could simplify error suppression and error correction schemes. Here we present a superconducting circuit architecture in which a coupling module mediates 2-local and 3-local interactions between three flux qubits by design. The system Hamiltonian is estimated via multi-qubit pulse sequences that implement Ramsey-type interferometry between all neighboring excitation manifolds in the system. The 3-local interaction is coherently tunable over several MHz via the coupler flux biases and can be turned off, which is important for applications in quantum annealing, analog quantum simulation, and gate-model quantum computation.Comment: 14 pages, 11 figure