Levels of Circulating PD-L1 Are Decreased in Patients with Resectable Cholangiocarcinoma

Tumor resection represents the only curative treatment option for patients with biliary tract cancers (BTCs), including intrahepatic cholangiocarcinoma (CCA), perihilar and extrahepatic CCA and gallbladder cancer. However, many patients develop early tumor recurrence and are unlikely to benefit from surgery. Therefore, markers to identify ideal surgical candidates are urgently needed. Circulating programmed cell death 1 ligand 1 (PD-L1) has recently been associated with different malignancies, including pancreatic cancer which closely resembles BTC in terms of patients’ prognosis and tumor biology. Here, we aim at evaluating a potential role of circulating PD-L1 as a novel biomarker for resectable BTC. Methods: Serum levels of PD-L1 were analyzed by ELISA in 73 BTC patients and 42 healthy controls. Results: Circulating levels of preoperative PD-L1 were significantly lower in patients with BTC compared to controls. Patients with low PD-L1 levels displayed a strong trend towards an impaired prognosis, and circulating PD-L1 was negatively correlated with experimental markers of promalignant tumor characteristics such as CCL1, CCL21, CCL25 and CCL26. For 37 out of 73 patients, postoperative PD-L1 levels were available. Interestingly, after tumor resection, circulating PD-L1 raised to almost normal levels. Notably, patients with further decreasing PD-L1 concentrations after surgery showed a trend towards an impaired postoperative outcome. Conclusion: Circulating PD-L1 levels were decreased in patients with resectable BTC. Lack of normalization of PD-L1 levels after surgery might identify patients at high risk for tumor recurrence or adverse outcome.     

Isotopic composition of dissolved inorganic carbon in bottled waters on the Slovene market

This study investigates the stable isotopic composition of dissolved inorganic carbon (DIC), expressed as δ¹³C_DIC, in domestic and foreign bottled waters randomly collected on the Slovene market. All together 58 brands and 16 replicates were analysed. The δ¹³C_DIC values varied between −63.1‰ and +1.0‰ with an average of −12.3‰. Average δ¹³C_DIC values for naturally sparkling, artificially sparkling, still and flavoured waters were −3.3‰, −36.5‰, −10.0‰ and −11.0‰, respectively. The lowest values are characteristic of artificial sparkling waters (minimum −63.1‰) and can be attributed to injection of industrial CO₂ during bottled water production. Therefore, determination of the isotopic composition of DIC can represent a useful analytical tool to distinguish between natural and artificially sparkling waters. Furthermore, the method used enabled determination of the various origins of still waters. From the bottled waters sampled it was possible to discern waters that originate from deeper aquifers, from aquifers in equilibrium with soil CO₂, or from aquifers with their recharge in a mountainous area. Finally, δ¹³C_DIC values of flavoured waters illustrate that isotopic fractionation occurs during the production process and that δ¹³C_DIC values in products of some producers have a large variation.     

Analysis and Provision of QoS for Distributed Grid Applications

Grid computing provides the infrastructure necessary to access and use distributed resources as part of virtual organizations. When used in this way, Grid computing makes it possible for users to participate in collaborative and distributed applications such as tele-immersion, visualization, and computational simulation. Some of these applications operate in a collaborative mode, requiring data to be stored and delivered in a timely manner. This class of applications must adhere to stringent real-time constraints and Quality-of-Service (QoS) requirements. A QoS management approach is therefore required to orchestrate and guarantee the timely interaction between such applications and services. We discuss the design and a prototype implementation of a QoS system, and demonstrate how we enable Grid applications to become QoS compliant. We validate this approach through a case study of an image processing task derived from a nanoscale structures application.