RF pulse concatenation for spatially selective inversion

It is shown that spatially selective inversion and saturation can be achieved by concatenation of RF pulses with lower flip angles. A concatenation rule which enables global doubling of the flip angle of any given excitation pulse applied to initial z magnetization is proposed. In this fashion, the selectivity of the single pulse is preserved, making the high selectivity achievable in the low flip-angle regime available for inversion and large flip-angle saturation purposes. The profile quality achievable with exemplary concatenated pulses is investigated in comparison with adiabatic inversion. It is verified that by using concatenated inversion in the transfer insensitive labeling technique (TILT), the MT artifact is suppressed. Copyright 2000 Academic Press.

Targeted nasal vaccination provides antibody-independent protection against Staphylococcus aureus.

Despite showing promise in preclinical models, anti-Staphylococcus aureus vaccines have failed in clinical trials. To date, approaches have focused on neutralizing/opsonizing antibodies; however, vaccines exclusively inducing cellular immunity have not been studied to formally test whether a cellular-only response can protect against infection. We demonstrate that nasal vaccination with targeted nanoparticles loaded with Staphylococcus aureus antigen protects against acute systemic S. aureus infection in the absence of any antigen-specific antibodies. These findings can help inform future developments in staphylococcal vaccine development and studies into the requirements for protective immunity against S. aureus.

What is the influence of vaccination's routes on the regression of tumors located at mucosal sites?

Tumor-regressions following tumor-associated-antigen vaccination in animal models contrast with the limited clinical outcomes in cancer patients. Most animal studies however used subcutaneous-tumor-models and questions arise as whether these are relevant for tumors growing in mucosae; whether specific mucosal-homing instructions are required; and how this may be influenced by the tumor.

Monitoring tumor antigen specific T-cell responses in cancer patients and phase I clinical trials of peptide-based vaccination.

Numerous phase I and II clinical trials testing the safety and immunogenicity of various peptide vaccine formulations based on CTL-defined tumor antigens in cancer patients have been reported during the last 7 years. While specific T-cell responses can be detected in a variable fraction of immunized patients, an even smaller but significant fraction of these patients have objective tumor responses. Efficient therapeutic vaccination should aim at boosting naturally occurring antitumor T- and B-cell responses and at sustaining a large number of tumor antigen specific and fully functional effector T cells at tumor sites. Recent progress in our ability to quantitatively and qualitatively monitor tumor antigen specific CD8 T-cell responses will greatly help in making rapid progress in this field.

Amine-reactive OVA multimers for auto-vaccination against cytokines and other mediators: perspectives illustrated for GCP-2 in L. major infection.

Anticytokine auto-vaccination is a powerful tool for the study of cytokine functions in vivo but has remained rather esoteric as a result of numerous technical difficulties. We here describe a two-step procedure based on the use of OVA multimers purified by size exclusion chromatography after incubation with glutaraldehyde at pH 6. When such polymers are incubated with a target protein at pH 8.5 to deprotonate reactive amines, complexes are formed that confer immunogenicity to self-antigens. The chemokine GCP-2/CXCL6, the cytokines GM-CSF, IL-17F, IL-17E/IL-25, IL-27, and TGF-β1, and the MMP-9/gelatinase B are discussed as examples. mAb, derived from such immunized mice, have obvious advantages for in vivo studies of the target proteins. Using a mAb against GCP-2, obtained by the method described here, we provide the first demonstration of the major role played by this chemokine in rapid neutrophil mobilization after Leishmania major infection. Pre-activated OVA multimers reactive with amine residues thus provide an efficient carrier for auto-vaccination against 9-90 kDa autologous proteins.

Gravitational wave pulse and soliton wave collision

We study the collision of a gravitational wave pulse and a soliton wave on a spatially homogeneous background. This collision is described by an exact solution of Einsteins equations in a vacuum which is generated from a nondiagonal seed by means of a soliton transformation. The effect produced by the soliton on the amplitude and polarization of the wave is considered.

Vaccination with a recombinant protein encoding the tumor-specific antigen NY-ESO-1 elicits an A2/157-165-specific CTL repertoire structurally distinct and of reduced tumor reactivity than that elicited by spontaneous immune responses to NY-ESO-1-expressing Tumors.

In a recent vaccination trial assessing the immunogenicity of an NY-ESO-1 (ESO) recombinant protein administered with Montanide and CpG, we have obtained evidence that this vaccine induces specific cytolytic T lymphocytes (CTL) in half of the patients. Most vaccine-induced CTLs were directed against epitopes located in the central part of the protein, between amino acids 81 and 110. This immunodominant region, however, is distinct from another ESO CTL region, 157-165, that is a frequent target of spontaneous CTL responses in A2+ patients bearing ESO tumors. In this study, we have investigated the CTL responses to ESO 157-165 in A2+ patients vaccinated with the recombinant protein. Our data indicate that after vaccination with the protein, CTL responses to ESO 157-165 are induced in some, but not all, A2+ patients. ESO 157-165-specific CTLs induced by vaccination with the ESO protein were functionally heterogeneous in terms of tumor recognition and often displayed decreased tumor reactivity as compared with ESO 157-165-specific CTLs isolated from patients with spontaneous immune responses to ESO. Remarkably, protein-induced CTLs used T-cell receptors similar to those previously isolated from patients vaccinated with synthetic ESO peptides (Vbeta4.1) and distinct from those used by highly tumor-reactive CTLs isolated from patients with spontaneous immune responses (Vbeta1.1, Vbeta8.1, and Vbeta13.1). Together, these results demonstrate that vaccination with the ESO protein elicits a repertoire of ESO 157-165-specific CTLs bearing T-cell receptors that are structurally distinct from those of CTLs found in spontaneous immune responses to the antigen and that are heterogeneous in terms of tumor reactivity, being often poorly tumor reactive.

Pulse propagation sustained by noise in arrays of bistable electronic circuits

One-dimensional arrays of nonlinear electronic circuits are shown to support propagation of pulses when operating in a locally bistable regime, provided the circuits are under the influence of a global noise. These external random fluctuations are applied to the parameter that controls the transition between bistable and monostable dynamics in the individual circuits. As a result, propagating fronts become destabilized in the presence of noise, and the system self-organizes to allow the transmission of pulses. The phenomenon is also observed in weakly coupled arrays, when propagation failure arises in the absence of noise.

Heat pulse line-source method to determine thermal conductivity of consolidated rocks

An instrument designed to measure thermal conductivity of consolidated rocks, dry or saturated, using a transient method is presented. The instrument measures relative values of the thermal conductivity, and it needs calibration to obtain absolute values. The device can be used as heat pulse line source and as continuous heat line source. Two parameters to determine thermal conductivity are proposed: TMAX, in heat pulse line source, and SLOPE, in continuous heat line source. Its performance is better, and the operation simpler, in heat pulse line-source mode with a measuring time of 170 s and a reproducibility better than 2.5%. The sample preparation is very simple on both modes. The performance has been tested with a set of ten rocks with thermal conductivity values between 1.4 and 5.2 W m¿1 K¿1 which covers the usual range for consolidated rocks.

DNA topology: feeling the pulse of a topoisomerase.

The action of individual type II DNA topoisomerases has been followed in real time by observing the elastic response of single DNA molecules to sequential strand passage events. Micromanipulation methods provide a complementary approach to biochemical studies for investigating the mechanism of DNA topoisomerases.

Can routine offering of influenza vaccination in office-based settings reduce racial and ethnic disparities in adult influenza vaccination?

BACKGROUND: Influenza vaccination remains below the federally targeted levels outlined in Healthy People 2020. Compared to non-Hispanic whites, racial and ethnic minorities are less likely to be vaccinated for influenza, despite being at increased risk for influenza-related complications and death. Also, vaccinated minorities are more likely to receive influenza vaccinations in office-based settings and less likely to use non-medical vaccination locations compared to non-Hispanic white vaccine users. OBJECTIVE: To assess the number of "missed opportunities" for influenza vaccination in office-based settings by race and ethnicity and the magnitude of potential vaccine uptake and reductions in racial and ethnic disparities in influenza vaccination if these "missed opportunities" were eliminated. DESIGN: National cross-sectional Internet survey administered between March 4 and March 14, 2010 in the United States. PARTICIPANTS: Non-Hispanic black, Hispanic and non-Hispanic white adults living in the United States (N = 3,418). MAIN MEASURES: We collected data on influenza vaccination, frequency and timing of healthcare visits, and self-reported compliance with a potential provider recommendation for vaccination during the 2009-2010 influenza season. "Missed opportunities" for seasonal influenza vaccination in office-based settings were defined as the number of unvaccinated respondents who reported at least one healthcare visit in the Fall and Winter of 2009-2010 and indicated their willingness to get vaccinated if a healthcare provider strongly recommended it. "Potential vaccine uptake" was defined as the sum of actual vaccine uptake and "missed opportunities." KEY RESULTS: The frequency of "missed opportunities" for influenza vaccination in office-based settings was significantly higher among racial and ethnic minorities than non-Hispanic whites. Eliminating these "missed opportunities" could have cut racial and ethnic disparities in influenza vaccination by roughly one half. CONCLUSIONS: Improved office-based practices regarding influenza vaccination could significantly impact Healthy People 2020 goals by increasing influenza vaccine uptake and reducing corresponding racial and ethnic disparities.

Gravitational wave pulse and soliton wave collision

We study the collision of a gravitational wave pulse and a soliton wave on a spatially homogeneous background. This collision is described by an exact solution of Einsteins equations in a vacuum which is generated from a nondiagonal seed by means of a soliton transformation. The effect produced by the soliton on the amplitude and polarization of the wave is considered.