DNA Methylation of PI3K/AKT pathway-related genes predicts outcome in patients with pancreatic cancer: a comprehensive bioinformatics-based study

Pancreatic cancer (PCA) is one of the most lethal malignancies worldwide with a 5-year survival rate of 9%. Despite the advances in the field, the need for an earlier detection and effective therapies is paramount. PCA high heterogeneity suggests that epigenetic alterations play a key role in tumour development. However, only few epigenetic biomarkers or therapeutic targets have been identified so far. Here we explored the potential of distinct DNA methylation signatures as biomarkers for early detection and prognosis of PCA. PI3K/AKT-related genes differentially expressed in PCA were identified using the Pancreatic Expression Database (n = 153). Methylation data from PCA patients was obtained from The Cancer Genome Atlas (n = 183), crossed with clinical data to evaluate the biomarker potential of the epigenetic signatures identified and validated in independent cohorts. The majority of selected genes presented higher expression and hypomethylation in tumour tissue. The methylation signatures of specific genes in the PI3K/AKT pathway could distinguish normal from malignant tissue at initial disease stages with AUC > 0.8, revealing their potential as PCA diagnostic tools. ITGA4, SFN, ITGA2, and PIK3R1 methylation levels could be independent prognostic indicators of patients’ survival. Methylation status of SFN and PIK3R1 were also associated with disease recurrence. Our study reveals that the methylation levels of PIK3/AKT genes involved in PCA could be used to diagnose and predict patients’ clinical outcome with high sensitivity and specificity. These results provide new evidence of the potential of epigenetic alterations as biomarkers for disease screening and management and highlight possible therapeutic targets.This work was supported by the FCT Research Center Grant UID/BIM/04773/2013 CBMR 1334, Câmara Municipal de Loulé, by the Liga Portuguesa Contra o Cancro/Portuguese League against Cancer through the Grant LPCC-PT Foundation 2016 to V.P.R. and by the Spanish Ministry of Science, Innovation and Universities through Grant RTI2018-094629-B-I00 to W.L.info:eu-repo/semantics/publishedVersio

A linear programming-based method for job shop scheduling

We present a decomposition heuristic for a large class of job shop scheduling problems. This heuristic utilizes information from the linear programming formulation of the associated optimal timing problem to solve subproblems, can be used for any objective function whose associated optimal timing problem can be expressed as a linear program (LP), and is particularly effective for objectives that include a component that is a function of individual operation completion times. Using the proposed heuristic framework, we address job shop scheduling problems with a variety of objectives where intermediate holding costs need to be explicitly considered. In computational testing, we demonstrate the performance of our proposed solution approach

A review on hierarchical routing protocols for wireless sensor networks

The routing protocol for Wireless Sensor Networks (WSNs) is defined as the manner of data dissemination from the network field (source) to the base station (destination). Based on the network topology, there are two types of routing protocols in WSNs, they are namely flat routing protocols and hierarchical routing protocols. Hierarchical routing protocols (HRPs) are more energy efficient and scalable compared to flat routing protocols. This paper discusses how topology management and network application influence the performance of cluster-based and chain-based hierarchical networks. It reviews the basic features of sensor connectivity issues such as power control in topology set-up, sleep/idle pairing and data transmission control that are used in five common HRPs, and it also examines their impact on the protocol performance. A good picture of their respective performances give an indication how network applications, i.e whether reactive or proactive, and topology management i.e. whether centralized or distributed would determine the network performance. Finally, from the ensuring discussion, it is shown that the chain-based HRPs guarantee a longer network lifetime compared to cluster-based HRPs by three to five times

A Compact SPICE Model for Organic TFTs and Applications to Logic Circuit Design

This work introduces a compact DC model developed for organic thin film transistors (OTFTs) and its SPICE implementation. The model relies on a modified version of the gradual channel approximation that takes into account the contact effects, occurring at nonohmic metal/organic semiconductor junctions, modeling them as reverse biased Schottky diodes. The model also comprises channel length modulation and scalability of drain current with respect to channel length. To show the suitability of the model, we used it to design an inverter and a ring oscillator circuit. Furthermore, an experimental validation of the OTFTs has been done at the level of the single device as well as with a discrete-component setup based on two OTFTs connected into an inverter configuration. The experimental tests were based on OTFTs that use small molecules in binder matrix as an active layer. The experimental data on the fabricated devices have been found in good agreement with SPICE simulation results, paving the way to the use of the model and the device for the design of OTFT-based integrated circuits.This work was supported in part by the MIUR by means of the national Program PON R&C 2007-2013 and in part by project “Elettronica su Plastica per Sistemi Smart disposable” PON02 00355 3416798

A Compact SPICE Model for Organic TFTs and Applications to Logic Circuit Design

This work introduces a compact DC model developed for organic thin film transistors (OTFTs) and its SPICE implementation. The model relies on a modified version of the gradual channel approximation that takes into account the contact effects, occurring at nonohmic metal/organic semiconductor junctions, modeling them as reverse biased Schottky diodes. The model also comprises channel length modulation and scalability of drain current with respect to channel length. To show the suitability of the model, we used it to design an inverter and a ring oscillator circuit. Furthermore, an experimental validation of the OTFTs has been done at the level of the single device as well as with a discrete-component setup based on two OTFTs connected into an inverter configuration. The experimental tests were based on OTFTs that use small molecules in binder matrix as an active layer. The experimental data on the fabricated devices have been found in good agreement with SPICE simulation results, paving the way to the use of the model and the device for the design of OTFT-based integrated circuits.This work was supported in part by the MIUR by means of the national Program PON R&C 2007-2013 and in part by project “Elettronica su Plastica per Sistemi Smart disposable” PON02 00355 3416798

Breastfeeding Success among Infants with Phenylketonuria

Breast milk is the nutrition of choice for human infants (American Academy of Pediatrics, 2005; American Association of Family Physicians, 2008; Association of Women’s Health Obstetric and Neonatal Nurses, 2005; Canadian Paediatric Society, 2005; U.S. Preventive Services Task Force, 2008; World Health Organization, 2009). The literature on the benefits of breast milk and breastfeeding for infants and mothers has established multiple positive outcomes for infants (Hoddinott, Tappin, & Wright, 2008; Horta, Bahl, Martines, & Victora, 2007; Ip et al., 2007). Breast milk has advantages for infants that distinguish it from standard commercial infant formulas. These advantages include growth factors, hormones, immunological factors, and long-chain polyunsaturated fatty acids. For infants with phenylketonuria (PKU), breast milk has additional advantages over any standard commercial infant formula, such as a lower concentration of protein and a lower content of the amino acid, phenylalanine. Despite these benefits, some clinics encourage mothers of infants with PKU to breastfeed whereas others present breastfeeding as an unacceptable option. Although the possible risks and benefits of breastfeeding infants with PKU have been discussed, there is limited research and practice describing breastfeeding infants with PKU. As a result, breastfeeding infants with PKU is based more upon limited clinical experiences rather than upon evidence based practice that aims to apply the best scientific evidence gained from research to clinical decision making

A combined ULBP2 and SEMA5A expression signature as a prognostic and predictive biomarker for colon cancer

Background: Prognostic biomarkers for cancer have the power to change the course of disease if they add value beyond known prognostic factors, if they can help shape treatment protocols, and if they are reliable. The aim of this study was to identify such biomarkers for colon cancer and to understand the molecular mechanisms leading to prognostic stratifications based on these biomarkers. Methods and Findings: We used an in house R based script (SSAT) for the in silico discovery of stage-independent prognostic biomarkers using two cohorts, GSE17536 and GSE17537, that include 177 and 55 colon cancer patients, respectively. This identified 2 genes, ULBP2 and SEMA5A, which when used jointly, could distinguish patients with distinct prognosis. We validated our findings using a third cohort of 48 patients ex vivo. We find that in all cohorts, a combined ULBP2/SEMA5A classification (SU-GIB) can stratify distinct prognostic sub-groups with hazard ratios that range from 2.4 to 4.5 (p=0.01) when overall- or cancer-specific survival is used as an end-measure, independent of confounding prognostic parameters. In addition, our preliminary analyses suggest SU-GIB is comparable to Oncotype DX colon(®) in predicting recurrence in two different cohorts (HR: 1.5-2; p=0.02). SU-GIB has potential as a companion diagnostic for several drugs including the PI3K/mTOR inhibitor BEZ235, which are suitable for the treatment of patients within the bad prognosis group. We show that tumors from patients with worse prognosis have low EGFR autophosphorylation rates, but high caspase 7 activity, and show upregulation of pro-inflammatory cytokines that relate to a relatively mesenchymal phenotype. Conclusions: We describe two novel genes that can be used to prognosticate colon cancer and suggest approaches by which such tumors can be treated. We also describe molecular characteristics of tumors stratified by the SU-GIB signature. © Ivyspring International Publisher