Combined OX40 Agonist and PD-1 Inhibitor Immunotherapy Improves the Efficacy of Vascular Targeted Photodynamic Therapy in a Urothelial Tumor Model

Purpose: Vascular targeted photodynamic therapy (VTP) is a nonsurgical tumor ablation approach used to treat early-stage prostate cancer and may also be effective for upper tract urothelial cancer (UTUC) based on preclinical data. Toward increasing response rates to VTP, we evaluated its efficacy in combination with concurrent PD-1 inhibitor/OX40 agonist immunotherapy in a urothelial tumor-bearing model. Experimental design: In mice allografted with MB-49 UTUC cells, we compared the effects of combined VTP with PD-1 inhibitor/OX40 agonist with those of the component treatments on tumor growth, survival, lung metastasis, and antitumor immune responses. Results: The combination of VTP with both PD-1 inhibitor and OX40 agonist inhibited tumor growth and prolonged survival to a greater degree than VTP with either immunotherapeutic individually. These effects result from increased tumor infiltration and intratumoral proliferation of cytotoxic and helper T cells, depletion of Treg cells, and suppression of myeloid-derived suppressor cells. Conclusions: Our findings suggest that VTP synergizes with PD-1 blockade and OX40 agonist to promote strong antitumor immune responses, yielding therapeutic efficacy in an animal model of urothelial cancer.     

Caging dynamics in a granular fluid

We report an experimental investigation of the caging motion in a uniformly heated granular fluid for a wide range of filling fractions, varphi. At low varphi the classic diffusive behavior of a fluid is observed. However, as varphi is increased, temporary cages develop and particles become increasingly trapped by their neighbors. We statistically analyze particle trajectories and observe a number of robust features typically associated with dense molecular liquids and colloids. Even though our monodisperse and quasi-2D system is known to not exhibit a glass transition, we still observe many of the precursors usually associated with glassy dynamics. We speculate that this is due to a process of structural arrest provided, in our case, by the presence of crystallization.     

Granular segregation as a critical phenomenon

We present the results of an experimental study of patterned segregation in a horizontally shaken shallow layer of a binary mixture of dry particles. An order parameter for the segregated domains is defined and the effect of the variation of the combined filling fraction, C, of the mixture on the observed pattern formation is systematically studied. We find that there is a critical event associated with the onset of segregation, at C(c)=0.647+/-0.049, which has the characteristics of a continuous phase transition, including critical slowing down.     

A high statistics measurement of the Lambda(+)(c) lifetime

A high statistics measurement of the Lambda(+)(c) lifetime from the Fermilab fixed-target FOCUS photoproduction experiment is presented. We describe the analysis technique with particular attention to the determination of the systematic uncertainty. The measured value of 204.6 +/- 3.4 (stat) +/- 2.5 (syst) fs from 8034 +/- 122 Lambda(+)(c)-->pK(-)pi(+) decays represents a significant improvement over the present world average.     

Generation and propagation of a picosecond acoustic pulse at a buried interface: time-resolved x-ray diffraction measurements

We report on the propagation of coherent acoustic wave packets in (001) surface oriented Al0.3Ga0.7As/GaAs heterostructure, generated through localized femtosecond photoexcitation of the GaAs. Transient structural changes in both the substrate and film are measured with picosecond time-resolved x-ray diffraction. The data indicate an elastic response consisting of unipolar compression pulses of a few hundred picosecond duration traveling along [001] and [001] directions that are produced by predominately impulsive stress. The transmission and reflection of the strain pulses are in agreement with an acoustic mismatch model of the heterostructure and free-space interfaces.     

Adaptive dispersion compensation for remote fiber delivery of near-infrared femtosecond pulses

We report on remote delivery of 25-pJ broadband near-infrared femtosecond light pulses from a Ti:sapphire laser through 150 m of single-mode optical fiber. Pulse distortion caused by dispersion is overcome with precompensation by adaptive pulse shaping techniques, while nonlinearities are mitigated by use of an SF10 glass rod for the final stage of pulse compression. A near-transform-limited pulse duration of 130 fs was measured after the final compression.     

Role of copper species in the oxidative dimerization of arylboronic acids: synthesis of symmetrical biaryls

Certain Cu(I) and Cu(II) salts are able to mediate the dimerization of arylboronic acids in DMF. They provide the corresponding symmetrical biaryls in moderate to very good yields. It is possible to run the reaction catalytically under an oxygen atmosphere without a significant loss of yields.     

Experimental evidence for a light and broad scalar resonance in D(+) --> pi(-)pi(+)pi(+) decay

From a sample of 1172 +/- 61 D(+)-->pi(-)pi(+)pi(+) decays, we find gamma(D(+)-->pi(-)pi(+)pi(+))/gamma(D(+)-->K-pi(+)pi(+)) = 0.0311 +/- 0.0018(+0.0016)(-0.0026). Using a coherent amplitude analysis to fit the Dalitz plot of these decays, we find strong evidence that a scalar resonance of mass 478(+24)(-23) +/- 17 MeV/c(2) and width 324(+42)(-40) +/- 21 MeV/c(2) accounts for approximately half of all decays.     

On the definition of the excess permittivity of a fluid mixture. II

In a previous work, an ideal fluid mixture is assumed to be a homogeneous linear and isotropic system that verifies the following conditions: (I) no interaction between molecules, (II) point-like molecules and (III) under fixed temperature and pressure conditions the number of molecules per unit volume is the same for both the individual components and the mixture. It was shown that for such ideal mixture the permittivity is the sum of the individual permittivities weighted with the mole fractions of the components.In this work it is shown that independently of the latter assumption the permittivity of the system can be expressed as the sum of the individual permittivities weighted with the volume fractions of the components.