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.     

Chemokine gene expression in rat pancreatic acinar cells is an early event associated with acute pancreatitis

BACKGROUND & AIMS: The molecular mechanisms underlying pancreatitis are largely unknown. The goal of this study was to identify an early genetic event that correlated with pancreatitis. METHODS: Differential display of messenger RNAs (mRNAs) was conducted on normal pancreas vs. those of animals with secretagogue-induced pancreatitis. Northern blots from normal animals and animals with experimental acute pancreatitis were probed with cloned complementary DNAs for chemokines. Pancreatitis was induced with cerulein and by retrograde injection of bile salts. Immunocytochemistry was used to identify the source of chemokine expression. Pyrrolidine dithiocarbamate was tested for effects on chemokine expression and pancreatitis. RESULTS: A differentially amplified band was consistently observed early after cerulein hyperstimulation. This band was identified as a portion of the mob-1 gene, an alpha-chemokine. Northern analysis indicated that mRNAs for mob-1 and another chemokine, mcp-1, were induced after cerulein hyperstimulation in vivo. mob-1 mRNA was also induced by retrograde injection of bile salts and by cerulein in acinar cells in vitro. mob-1 protein was localized to exocrine cells in pancreata of diseased animals. Pyrrolidine dithiocarbamate inhibited both chemokine gene expression and early inflammatory characteristics of pancreatitis. CONCLUSIONS: Chemokines are induced in acinar cells by treatments that induce pancreatitis and may play an important role in the early stages of the disease.     

Overnight closed suction drainage after axillary lymphadenectomy for breast cancer

Axillary lymphadenectomy in breast conservation surgery is associated with substantial morbidity in either seroma formation or infection. Seroma formation in the axilla requiring aspiration occurs in up to 42 per cent of patients treated without drainage. Prolonged outpatient suction drainage reduces but does not eliminate the incidence of seroma formation, while increasing cost, discomfort, and possibly infection rates. We studied the efficacy of overnight closed suction drainage in patients undergoing breast conservation surgery. Fifty consecutive patients undergoing a standard axillary dissection for breast cancer were studied. The axilla was drained with a 7-French closed suction drain. All drains were removed within 23 hours of surgery and prior to discharge from the outpatient surgical center. Patients were examined by the operating surgeon 7 to 10 days after surgery. One patient (2%) experienced a seroma postoperatively. No infections were observed in all 50 patients, and the remaining 49 patients did not experience visible or symptomatic seromas. The number of lymph nodes removed ranged between 5 and 33 with a mean of 15.5 +/- 0.6. Nine out of 50 (18%) patients had metastatic breast cancer to the axillary lymph nodes. Patients undergoing breast conservation surgery benefit from overnight closed suction drainage of the axilla. This short-term method reduces the incidence and the inherent morbidity of axillary seroma formation.     

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.