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.     

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.     

Epidemiology of Trauma and Posttraumatic Stress Disorder in Mexico.

Prevalence rates of trauma and posttraumatic stress disorder (PTSD) were estimated from a probability sample of 2,509 adults from 4 cities in Mexico. PTSD was assessed according to Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 1994) criteria using the Composite International Diagnostic Interview (CIDI; WHO, 1997). Lifetime prevalence of exposure and PTSD were 76% and 11.2%, respectively. Risk for PTSD was highest in Oaxaca (the poorest city), persons of lower socioeconomic status, and women. Conditional risk for PTSD was highest following sexual violence, but nonsexual violence and traumatic bereavement had greater overall impact because of their frequency. Of lifetime cases, 62% became chronic; only 42% received medical or professional care. The research demonstrates the importance of expanding the epidemiologic research base on trauma to include developing countries around the world. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neuropsychological functioning and personality characteristics of migrainous and nonmigrainous female college students.

Examined the theory that chronic migraine headaches can lead to permanent changes in brain function in 71 female college students. Ss were 20 classic migraineurs, 27 common migraineurs, and 24 controls. No significant group differences were found on the Halstead Reitan Neuropsychological Test Battery and additional memory tests. Classic migraineurs had significantly higher scores than common migraineurs on the Hysteria and Paranoia scales of the Minnesota Multiphasic Personality Inventory (MMPI) and significantly higher scores than the controls on Hypochondriasis and Hysteria scales. Explanations for the lack of cognitive deficits in this group are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)