1,497 research outputs found
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 (âBig Biologyâ), 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 1996â1997 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
A Highly Potent and Broadly Neutralizing H1 Influenza-Specific Human Monoclonal Antibody
Influenza's propensity for antigenic drift and shift, and to elicit predominantly strain specific antibodies (Abs) leaves humanity susceptible to waves of new strains with pandemic potential for which limited or no immunity may exist. Subsequently new clinical interventions are needed. To identify hemagglutinin (HA) epitopes that if targeted may confer universally protective humoral immunity, we examined plasmablasts from a subject that was immunized with the seasonal influenza inactivated vaccine, and isolated a human monoclonal Ab (mAb), KPF1. KPF1 has broad and potent neutralizing activity against H1 influenza viruses, and recognized 83% of all H1 isolates tested, including the pandemic 1918 H1. Prophylactically, KPF1 treatment resulted in 100% survival of mice from lethal challenge with multiple H1 influenza strains and when given as late as 72âh after challenge with A/California/04/2009 H1N1, resulted in 80% survival. KPF1 recognizes a novel epitope in the HA globular head, which includes a highly conserved amino acid, between the Ca and Cb antigenic sites. Although recent HA stalk-specific mAbs have broader reactivity, their potency is substantially limited, suggesting that cocktails of broadly reactive and highly potent HA globular head-specific mAbs, like KPF1, may have greater clinical feasibility for the treatment of influenza infections.Peer reviewe
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 (0.00020.004 and 915, 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
(TO-BUMP)(TO-ZAHB). We show that the parameter
does not depend at all on the cluster age, whereas it does strongly depend
on the cluster global metallicity. The calibration of the parameter as a
function of 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 (TO-BUMP) with (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 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 9G4âIgDâ memory B cell population, the 9G4+IgDâ memory fraction in HIV patients was dominated by isotype switched IgG+ B cells, but had a more prominent bias toward âIgM 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 (râ=â0.403, pâ=â0.0019) 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
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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
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