VISTA checkpoint inhibition by pH-selective antibody SNS-101 with optimized safety and pharmacokinetic profiles enhances PD-1 response

VISTA, an inhibitory myeloid-T-cell checkpoint, holds promise as a target for cancer immunotherapy. However, its effective targeting has been impeded by issues such as rapid clearance and cytokine release syndrome observed with previous VISTA antibodies. Here we demonstrate that SNS-101, a newly developed pH-selective VISTA antibody, addresses these challenges. Structural and biochemical analyses confirmed the pH-selectivity and unique epitope targeted by SNS-101. These properties confer favorable pharmacokinetic and safety profiles on SNS-101. In syngeneic tumor models utilizing human VISTA knock-in mice, SNS-101 shows in vivo efficacy when combined with a PD-1 inhibitor, modulates cytokine and chemokine signaling, and alters the tumor microenvironment. In summary, SNS-101, currently in Phase I clinical trials, emerges as a promising therapeutic biologic for a wide range of patients whose cancer is refractory to current immunotherapy regimens

Design of multihundredwatt DIPS for robotic space missions

Design of a dynamic isotope power system (DIPS) general purpose heat source (GPHS) and small free piston Stirling engine (FPSE) is being pursued as a potential lower cost alternative to radioisotope thermoelectric generators (RTG's). The design is targeted at the power needs of future unmanned deep space and planetary surface exploration missions ranging from scientific probes to SEI precursor missions. These are multihundredwatt missions. The incentive for any dynamic system is that it can save fuel which reduces cost and radiological hazard. However, unlike a conventional DIPS based on turbomachinery converions, the small Stirling DIPS can be advantageously scaled to multihundred watt unit size while preserving size and weight competitiveness with RTG's. Stirling conversion extends the range where dynamic systems are competitive to hundreds of watts (a power range not previously considered for dynamic systems). The challenge of course is to demonstrate reliability similar to RTG experience. Since the competative potential of FPSE as an isotope converter was first identified, work has focused on the feasibility of directly integrating GPHS with the Stirling heater head. Extensive thermal modeling of various radiatively coupled heat source/heater head geometries were performed using data furnished by the developers of FPSE and GPHS. The analysis indicates that, for the 1050 K heater head configurations considered, GPHS fuel clad temperatures remain within safe operating limits under all conditions including shutdown of one engine. Based on these results, preliminary characterizations of multihundred watt units were established

Monte-Carlo Simulations of the Dynamical Behavior of the Coulomb Glass

We study the dynamical behavior of disordered many-particle systems with long-range Coulomb interactions by means of damage-spreading simulations. In this type of Monte-Carlo simulations one investigates the time evolution of the damage, i.e. the difference of the occupation numbers of two systems, subjected to the same thermal noise. We analyze the dependence of the damage on temperature and disorder strength. For zero disorder the spreading transition coincides with the equilibrium phase transition, whereas for finite disorder, we find evidence for a dynamical phase transition well below the transition temperature of the pure system.Comment: 10 pages RevTeX, 8 Postscript figure

Measuring Information Transfer

An information theoretic measure is derived that quantifies the statistical coherence between systems evolving in time. The standard time delayed mutual information fails to distinguish information that is actually exchanged from shared information due to common history and input signals. In our new approach, these influences are excluded by appropriate conditioning of transition probabilities. The resulting transfer entropy is able to distinguish driving and responding elements and to detect asymmetry in the coupling of subsystems.Comment: 4 pages, 4 Figures, Revte

The nucleon's octet axial-charge g_A^8 with chiral corrections

The value of the nucleon's flavour-singlet axial-charge extracted from polarised deep inelastic scattering is sensitive to the value of the octet axial-charge g_A^8 which is usually taken from an analysis of hyperon beta-decays within the framework of SU(3) symmetry, namely 0.58 \pm 0.03. Using the Cloudy Bag model we find that the value of g_A^8 is reduced by as much as 20% below the usual phenomenological value. This increases the value of the flavour singlet axial charge (g_A^0|_inv) derived from deep inelastic data and significantly reduces the difference between it and g_A^8.Comment: 12 page

Parton Distributions for the Octet and Decuplet Baryons

We calculate the parton distributions for both polarized and unpolarized octet and decuplet baryons, using the MIT bag, dressed by mesons. We show that the hyperfine interaction responsible for the $\Delta - N$ and $\Sigma^0 - \Lambda$ splittings leads to large deviations from SU(3) and SU(6) predictions. For the $\Lambda$ we find significant polarized, non-strange parton distributions which lead to a sizable $\Lambda$ polarization in polarized, semi-inclusive $ep$ scattering. We also discuss the flavour symmetry violation arising from the meson-cloud associated with the chiral structure of baryons.Comment: 29 pages, 15 figure

Bacterial contamination of air and surfaces during dental procedures—An experimental pilot study using Staphylococcus aureus

Objective: The oral cavity contains numerous microorganisms, including antimicrobial-resistant bacteria. These microorganisms can be transmitted via respiratory particles from patients to healthcare providers and vice versa during dental care. We evaluated the spread of Staphylococcus aureus during standardized dental procedures using different scaling devices and rinsing solutions. Methods: During systematic therapy for dental biofilm removal (guided biofilm therapy), using an airflow or ultrasound device to a model simulation head. Staphylococcus aureus suspension was injected into the mouth of the model to mimic saliva. Different suction devices (conventional saliva ejector or a prototype) and rising solutions (water or chlorhexidine) were used. To assess contamination with S. aureus, an air-sampling device was placed near the oral cavity and samples of surface areas were collected. Results: S. aureus was only detected by air sampling when the conventional saliva ejector with airflow was used. No growth was observed during treatments with the ultrasonic piezo instrument or the prototype suction device. Notably, a rinsing solution of chlorhexidine digluconate decreased the bacterial load compared to water. Surface contamination was rarely detected (1 of 120 samples). Conclusions: Although our findings indicate potential airborne bacterial transmission during routine prophylactic procedures, specific treatment options during biofilm removal appear to reduce air contamination. These options include ultrasonic piezo devices or the prototype suction device. The use of chlorhexidine reduced the CFU counts of S. aureus detected by air sampling. Surface contamination during dental procedures was a rare occurrence

X-ray phase contrast imaging of biological specimens with tabletop synchrotron radiation

Since their discovery in 1896, x-rays have had a profound impact on science, medicine and technology. Here we show that the x-rays from a novel tabletop source of bright coherent synchrotron radiation can be applied to phase contrast imaging of biological specimens, yielding superior image quality and avoiding the need for scarce or expensive conventional sources

Longitudinal Ion Acceleration from High-Intensity Laser Interactions with Underdense Plasma

Longitudinal ion acceleration from high-intensity (I ~ 10^20 Wcm^-2) laser interactions with helium gas jet targets (n_e ~ 0.04 n_c) have been observed. The ion beam has a maximum energy for He^2+ of approximately 40 MeV and was directional along the laser propagation path, with the highest energy ions being collimated to a cone of less than 10 degrees. 2D particle-in-cell simulations have been used to investigate the acceleration mechanism. The time varying magnetic field associated with the fast electron current provides a contribution to the accelerating electric field as well as providing a collimating field for the ions. A strong correlation between the plasma density and the ion acceleration was found. A short plasma scale-length at the vacuum interface was observed to be beneficial for the maximum ion energies, but the collimation appears to be improved with longer scale-lengths due to enhanced magnetic fields in the ramp acceleration region.Comment: 18 pages, 6 figure

Do interactions increase or reduce the conductance of disordered electrons? It depends!

We investigate the influence of electron-electron interactions on the conductance of two-dimensional disordered spinless electrons. By using an efficient numerical method which is based on exact diagonalization in a truncated basis of Hartree-Fock states we are able to determine the exact low-energy properties of comparatively large systems in the diffusive as well as in the localized regimes. We find that weak interactions increase the d.c. conductance in the localized regime while they decrease the d.c. conductance in the diffusive regime. Strong interactions always decrease the conductance. We also study the localization of single-particle excitations close to the Fermi energy which turns out to be only weakly influenced by the interactions.Comment: final version as publsihed, 4 pages REVTEX, 6 EPS figures include