Ablative Radiotherapy Reprograms the Tumor Microenvironment of a Pancreatic Tumor in Favoring the Immune Checkpoint Blockade Therapy

The low overall survival rate of patients with pancreatic cancer has driven research to seek a new therapeutic protocol. Radiotherapy (RT) is frequently an option in the neoadjuvant or palliative settings for pancreatic cancer treatment. This study explored the effect of RT protocols on the tumor microenvironment (TME) and their consequent impact on anti-programmed cell death ligand-1 (PD-L1) therapy. Using a murine orthotopic pancreatic tumor model, UN-KC-6141, RT-disturbed TME was examined by immunohistochemical staining. The results showed that ablative RT is more effective than fractionated RT at recruiting T cells. On the other hand, fractionated RT induces more myeloid-derived suppressor cell infiltration than ablative RT. The RT-disturbed TME presents a higher perfusion rate per vessel. The increase in vessel perfusion is associated with a higher amount of anti-PD-L1 antibody being delivered to the tumor. Animal survival is increased by anti-PD-L1 therapy after ablative RT, with 67% of treated animals surviving more than 30 days after tumor inoculation compared to a median survival time of 16.5 days for the control group. Splenocytes isolated from surviving animals were specifically cytotoxic for UN-KC-6141 cells. We conclude that the ablative RT-induced TME is more suited than conventional RT-induced TME to combination therapy with immune checkpoint blockade.     

Speed superiority of scaled double-gate CMOS

Unloaded ring-oscillator simulations, performed with a generic process/physics-based compact model for double-gate (DG) MOSFETs and supplemented with model-predicted on-state currents and gate capacitances for varying supply voltages (V_DD), are used to show and explain the speed superiority of extremely scaled DG CMOS over the single-gate (e.g., bulk-Si) counterpart. The DG superiority for unloaded circuits is most substantive for low V_DD < ~1 V     

Efficient random subcloning of DNA sheared in a recirculating point-sink flow system

Based on a high-performance liquid chromatographic pump, we have built a device that allows recirculation of DNA through a 63-microm orifice with ensuing fractionation to a minimum fragment size of approximately 300 base pairs. Residence time of the DNA fragments in the converging flow created by a sudden contraction was found to be sufficiently long to allow extension of the DNA molecules into a highly extended conformation and, hence, breakage to occur at midpoint. In most instances, 30 passages sufficed to obtain a narrow size distribution, with >90% of the fragments lying within a 2-fold size distribution. The shear rate required to achieve breakage was found to be inversely proportional to the 1.0 power of the molecular weight. Compared with a restriction digest, up to 40% of all fragments could be cloned directly, with only marginal improvements in cloning efficiency having been observed upon prior end repair with Klenow, T4 polymerase or T4 polynucleotide kinase. Sequencing revealed a fairly random distribution of the fragments.     

Using a cost-construction model to assess the cost of educating undergraduate medical students at the University of Texas--Houston Medical School

Spontaneous resolution of deformities after excision of facial skin lesions has been known and used for a long time by plastic surgeons. The resorption mechanism of deformity is based on natural skin expansion, and seems to be directly related to the action of the muscles of facial expression and their skin relations. Natural expansion has been shown to be effective in children. Between 1990 and 1994 excision of skin lesions, including congenital nevi, leading to postoperative deformity of the cheek, labial commissure, nose, eyelid and forehead, was performed on 35 patients, aged from 3 month to 12 years. The average follow-up is 24 months. For 26 patients (74%), natural resorption was observed 4 or 6 weeks later with good aesthetic results. For 6 patients (17%), the deformity persisted 3 or 6 months later, but did not require any further surgery. For 3 patients (9%), a second operation was necessary. Using the skins natural capacity for expansion in the treatment of facial skin defects in children is a method of reconstruction which has already been used for excision in enforced position. The platysma and muscles of facial expression by their action on skin mobilisation, allow natural expansion. A better knowledge of cutaneous biomechanical properties enables plastic surgeons to find an alternative to other classical methods.     

Evaluating generalized predictive control for a brushless DC drive

This paper proposes a new control approach for a brushless DC motor drive using the generalized predictive control (GPC) algorithm. Based on the same least-squares framework as in the controller design, we further develop the method to design an observer. The GPC algorithm uses the receding horizon approach whereby the control signals are determined by minimizing a quadratic cost function. Our study shows that the rise time and settling time of the servo system have an approximate linear relationship with the prediction horizon. Thus, it is used to tune the controller of the drive. Moreover, the control weighting factor can be used to smooth the controller output. The proposed algorithm has been implemented using a digital signal processor (DSP) and tested in real time with a prototype system. The performance and robustness of the algorithms have been evaluated both in simulation and experiment. The results show that the drive performs reasonably well despite load changes and step changes in the position setpoint. Furthermore, it is fairly robust against motor parameters change     

Design criterion for low-loss optical coupler tapers

A criterion for the local taper angle of a low-loss single-mode fibre coupler is established by considering the dominant mode coupling in the coupler taper. Effects due to structure parameters, such as cladding/core thickness ratio, corecladding index difference and core separation, are investigated. It is found that the criterion for the coupler taper can be well approximated by that for the single-mode fibre taper with the same structure parameters.     

Channel capacity and state estimation for state-dependent Gaussian channels

We formulate a problem of state information transmission over a state-dependent channel with states known at the transmitter. In particular, we solve a problem of minimizing the mean-squared channel state estimation error E/spl par/S/sup n/ - S/spl circ//sup n//spl par/ for a state-dependent additive Gaussian channel Y/sup n/ = X/sup n/ + S/sup n/ + Z/sup n/ with an independent and identically distributed (i.i.d.) Gaussian state sequence S/sup n/ = (S/sub 1/, ..., S/sub n/) known at the transmitter and an unknown i.i.d. additive Gaussian noise Z/sup n/. We show that a simple technique of direct state amplification (i.e., X/sup n/ = /spl alpha/S/sup n/), where the transmitter uses its entire power budget to amplify the channel state, yields the minimum mean-squared state estimation error. This same channel can also be used to send additional independent information at the expense of a higher channel state estimation error. We characterize the optimal tradeoff between the rate R of the independent information that can be reliably transmitted and the mean-squared state estimation error D. We show that any optimal (R, D) tradeoff pair can be achieved via a simple power-sharing technique, whereby the transmitter power is appropriately allocated between pure information transmission and state amplification.