In Vitro Suppression of T Cell Proliferation Is a Conserved Function of Primary and Immortalized Human Cancer-Associated Fibroblasts

T cell immunotherapy is now a mainstay therapy for several blood-borne cancers as well as metastatic melanoma. Unfortunately, many epithelial tumors respond poorly to immunotherapy, and the reasons for this are not well understood. Cancer-associated fibroblasts (CAFs) are the most frequent non-neoplastic cell type in most solid tumors, and they are emerging as a key player in immunotherapy resistance. A range of immortalized CAF lines will be essential tools that will allow us to understand immune responses against cancer and develop novel strategies for cancer immunotherapy. To study the effect of CAFs on T cell proliferation, we created and characterized a number of novel immortalized human CAFs lines (Im-CAFs) from human breast, colon, and pancreatic carcinomas. Im-CAFs shared similar phenotypes, matrix remodeling and contraction capabilities, and growth and migration rates compared to the primary CAFs. Using primary isolates from breast carcinoma, colorectal carcinoma, and pancreatic ductal adenocarcinoma, we report that CAFs across major tumor types are able to potently suppress T cell proliferation in vitro. Im-CAFs retained this property. Im-CAFs are a key tool that will provide important insights into the mechanisms of CAF-mediated T cell suppression through techniques such as CRISPR-Cas9 modification, molecular screens, and pipeline drug testing.     

Wafer-scale MOCVD growth of monolayer MoS2 on sapphire and SiO2

Nano Research - High-quality and large-scale growth of monolayer molybdenum disulfide (MoS2) has caught intensive attention because of its potential in many applications due to unique electronic...     

Once is too much: Conditioned changes in accumbens dopamine following a single saccharin-morphine pairing.

The present study tested whether presentation of a taste cue would support conditioned suppression of dopamine in the nucleus accumbens (NAcc) following a single taste-drug pairing. Nondeprived male Sprague-Dawley rats were given 20-min access to a 0.15% saccharin conditioned stimulus (CS). Immediately thereafter, experimental rats were injected with morphine (15 mg/kg ip); standard controls were injected with saline; and explicitly unpaired controls were injected with morphine, but approximately 24 hr later. All rats were then given one 20-min CS-only test. Microdialysis samples from the NAcc were measured over 20-min intervals before, during, and after CS access on the conditioning and test trial. The results showed that a single saccharin-morphine pairing led to a marked reduction in CS intake, and the reduction in intake was accompanied by a conditioned blunting of the accumbens dopamine response to the saccharin reward cue. In turn, a single exposure to the saccharin cue also blunted the unconditioned dopamine response to morphine. Reward comparison effects, then, are cross-modal, bidirectional, and immediate, resulting in both unconditioned and conditioned changes in brain and behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The coupled oscillator model of between-hand coordination in alternate-hand tapping: A reappraisal.

Single and alternating hand tapping were compared to test the hypothesis that coordination during rhythmic movements is mediated by the control of specific time intervals. In Experiment 1, an auditory metronome was used to indicate a set of timing patterns in which a 1-s interval was divided into 2 subintervals. Performance, measured in terms of the deviation from the target patterns and variability, was similar under conditions in which the finger taps were made with 1 hand or alternated between the 2 hands. In Experiment 2, the modality of the metronome (auditory or visual) was found to influence the manner in which the produced intervals deviated from the target patterns. These results challenge the notion that bimanual coordination emerges from coupling constraints intrinsic to the 2-hand system. They are in accord with a framework that emphasizes the control of specific time intervals to form a series of well-defined motor events. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Backstepping in Infinite Dimension for a Class of Parabolic Distributed Parameter Systems

 In this paper a family of stabilizing boundary feedback control laws for a class of linear parabolic PDEs motivated by engineering applications is presented. The design procedure presented here can handle systems with an arbitrary finite number of open-loop unstable eigenvalues and is not restricted to a particular type of boundary actuation. Stabilization is achieved through the design of coordinate transformations that have the form of recursive relationships. The fundamental difficulty of such transformations is that the recursion has an infinite number of iterations. The problem of feedback gains growing unbounded as the grid becomes infinitely fine is resolved by a proper choice of the target system to which the original system is transformed. We show how to design coordinate transformations such that they are sufficiently regular (not continuous but L _∞). We then establish closed-loop stability, regularity of control, and regularity of solutions of the PDE. The result is accompanied by a simulation study for a linearization of a tubular chemical reactor around an unstable steady state. Date received: June 22, 2001. Date revised: January 17, 2002. RID="*" ID="*"This work was supported by grants from AFOSR, ONR, and NSF.     

Asymptotic Distribution of Eigenvalues for Damped String Equation: Numerical Approach

In the present paper, we consider a one-parameter family of the nonself-adjoint operators, which are the dynamics generators for systems governed by the wave equations containing dissipative terms. The equations contain viscous damping terms and are equipped with the boundary conditions involving an arbitrary complex parameter. In the current engineering literature, this type of boundary condition is used to model the action of smart materials (self-sensing/self-straining actuators). In the previous research of the first writer, the aforementioned dynamics generators have been studied analytically and precise asymptotic formulas for the eigenvalues have been derived (the asymptotic when the number of the eigenvalues tends to infinity). The goal of the present paper is to demonstrate that the analytic formulas are not only important theoretically, but also extremely efficient practically. Namely, we show that the leading terms in the asymptotic formulas approximate the actual eigenvalues with excellent accuracy. To justify the results, we use two methods, i.e., the Newton method and the Tchebychev method. First, Newton’s method is applied to the characteristic equation using asymptotic formulas as initial guesses to find the eigenvalues. The convergence of Newton’s method is improved by modifying the asymptotic formula. Second, we use Tchebychev discretization to circumvent the nonlinear characteristic equation and to obtain a finite-dimensional generalized eigenvalue problem that approximates the infinite-dimensional one. Finally, to solve the generalized eigenvalue problem, we use the QT algorithm.     

Ammonia traces detection based on photoacoustic spectroscopy for evaluating ammonia volatization from natural zeolites at typical crop field temperature

A Brazilian sedimentary zeolite-containing microporous material was characterized by determining its physical and chemical properties (surface area, pore volume, dinitrogen and ammonia desorption rates, oxide composition, and acid site characterization), and compared with two commercial natural zeolites. The characterization of these materials was performed using N₂ adsorption, X-ray fluorescence spectroscopy and temperature programmed desorption (TPD) techniques. Using photoacoustic spectroscopy, the performance of these microporous materials in the adsorption and delayed desorption of nitrogen-containing fertilizers was studied by monitoring the ammonia emission rate after their treatment with ammonium sulfate. Ammonia desorption curves were recorded under 30 °C and 60 °C, aiming to reproduce typical Brazilian cropfield temperature conditions.     

Combining algorithms for automatic detection of optic disc and macula in fundus images

This paper proposes an efficient combination of algorithms for the automated localization of the optic disc and macula in retinal fundus images. There is in fact no reason to assume that a single algorithm would be optimal. An ensemble of algorithms based on different principles can be more accurate than any of its individual members if the individual algorithms are doing better than random guessing. We aim to obtain an improved optic disc and macula detector by combining the prediction of multiple algorithms, benefiting from their strength and compensating their weaknesses. The location with maximum number of detectors’ outputs is formally the hotspot and is used to find the optic disc or macula center. An assessment of the performance of integrated system and detectors working separately is also presented. Our proposed combination of detectors achieved overall highest performance in detecting optic disc and fovea closest to the manually center chosen by the retinal specialist.