Immunotherapy as a Therapeutic Strategy for Gastrointestinal Cancer—Current Treatment Options and Future Perspectives

Gastrointestinal (GI) cancer constitutes a highly lethal entity among malignancies in the last decades and is still a major challenge for cancer therapeutic options. Despite the current combinational treatment strategies, including chemotherapy, surgery, radiotherapy, and targeted therapies, the survival rates remain notably low for patients with advanced disease. A better knowledge of the molecular mechanisms that influence tumor progression and the development of optimal therapeutic strategies for GI malignancies are urgently needed. Currently, the development and the assessment of the efficacy of immunotherapeutic agents in GI cancer are in the spotlight of several clinical trials. Thus, several new modalities and combinational treatments with other anti-neoplastic agents have been identified and evaluated for their efficiency in cancer management, including immune checkpoint inhibitors, adoptive cell transfer, chimeric antigen receptor (CAR)-T cell therapy, cancer vaccines, and/or combinations thereof. Understanding the interrelation among the tumor microenvironment, cancer progression, and immune resistance is pivotal for the optimal therapeutic management of all gastrointestinal solid tumors. This review will shed light on the recent advances and future directions of immunotherapy for malignant tumors of the GI system.     

Securing Recommender Systems Against Shilling Attacks Using Social-Based Clustering

Recommender systems (RS) have been found supportive and practical in e-commerce and been established as useful aiding services. Despite their great adoption in the user communities, RS are still vulnerable to unscrupulous producers who try to promote their products by shilling the systems. With the advent of social networks new sources of information have been made available which can potentially render RS more resistant to attacks. In this paper we explore the information provided in the form of social links with clustering for diminishing the impact of attacks. We propose two algorithms, CluTr and WCluTr, to combine clustering with "trust" among users. We demonstrate that CluTr and WCluTr enhance the robustness of RS by experimentally evaluating them on data from a public consumer recommender system Epinions.com.     

A nexus of Cyber-Geography and Cyber-Psychology: Topos/“Notopia” and identity in hacking

This paper explores the Cyber-Psychological and Cyber-Geographic aspects of hacking and hacktivism. An examination of the literature related to hackers and hacking reveals a complex nexus of spatial (including cyber-spatial such as “Notopia”) and psychological aspects of hacking, from which emerges a central question of how humans perceive and manipulate their cyber-identities. Concealing (real and cyber) identities is typical in hacking. With our progressive acculturation with identity-less and place-less modes of existence, our cyber-identities through time may be studied from within John Locke’s criterion of “memory” and the spatial-geographical criterion of identity.     

The impact of Ti and temperature on the stability of Nb5Si3 phases: a first-principles study

Abstract

Nb-silicide based alloys could be used at T > 1423 K in future aero-engines. Titanium is an important additive to these new alloys where it improves oxidation, fracture toughness and reduces density. The microstructures of the new alloys consist of an Nb solid solution, and silicides and other intermetallics can be present. Three Nb₅Si₃ polymorphs are known, namely αNb₅Si₃ (tI32 Cr₅B₃-type, D8_l), βNb₅Si₃ (tI32 W₅Si₃-type, D8_m) and γNb₅Si₃ (hP16 Mn₅Si₃-type, D8₈). In these 5–3 silicides Nb atoms can be substituted by Ti atoms. The type of stable Nb₅Si₃ depends on temperature and concentration of Ti addition and is important for the stability and properties of the alloys. The effect of increasing concentration of Ti on the transition temperature between the polymorphs has not been studied. In this work first-principles calculations were used to predict the stability and physical properties of the various Nb₅Si₃ silicides alloyed with Ti. Temperature-dependent enthalpies of formation were computed, and the transition temperature between the low (α) and high (β) temperature polymorphs of Nb₅Si₃ was found to decrease significantly with increasing Ti content. The γNb₅Si₃ was found to be stable only at high Ti concentrations, above approximately 50 at. % Ti. Calculation of physical properties and the Cauchy pressures, Pugh’s index of ductility and Poisson ratio showed that as the Ti content increased, the bulk moduli of all silicides decreased, while the shear and elastic moduli and the Debye temperature increased for the αNb₅Si₃ and γNb₅Si₃ and decreased for βNb₅Si₃. With the addition of Ti the αNb₅Si₃ and γNb₅Si₃ became less ductile, whereas the βNb₅Si₃ became more ductile. When Ti was added in the αNb₅Si₃ and βNb₅Si₃ the linear thermal expansion coefficients of the silicides decreased, but the anisotropy of coefficient of thermal expansion did not change significantly.     

Quantitative analysis of a certified e-mail protocol in mobile environments: A probabilistic model checking approach

Formal analysis techniques, such as probabilistic model checking, offer an effective mechanism for model-based performance and verification studies of communication systems’ behavior that can be abstractly described by a set of rules i.e., a protocol. This article presents an integrated approach for the quantitative analysis of the Certified E-mail Message Delivery (CEMD) protocol that provides security properties to electronic mail services. The proposed scheme employs a probabilistic model checking analysis and provides for the first time insights on the impact of CEMD’s error tolerance on computational and transmission cost. It exploits an efficient combination of quantitative analysis and specific computational and communication parameters, i.e., the widely used Texas Instruments TMS320C55x Family operating in an High Speed Downlink Packet Access (HSDPA) mobile environment, where multiple CEMD participants execute parallel sessions with high bit error rates (BERs). Furthermore, it offers a tool-assistant approach for the protocol designers and analysts towards the verification of their products under varying parameters. Finally, this analysis can be also utilized towards reliably addressing cost-related issues of certain communication protocols and deciding on their cost-dependent viability, taking into account limitations that are introduced by hardware specifications of mobile devices and noisy mobile environments.     

Tuning the Stability of Graphene Layers by Phthalocyanine‐Based oPPV Oligomers Towards Photo‐ and Redoxactive Materials

In contrast to pristine zinc phthalocyanine (1), zinc phthalocyanine based oPPV‐oligomers (2–4) of different chain lengths interact tightly and reversibly with graphite, affording stable and finely dispersed suspensions of mono‐ to few‐layer graphene—nanographene (NG)—that are photoactive. The p‐type character of the oPPV backbones and the increasing length of the oPPV backbones facilitate the overall π–π interactions with the graphene layers. In NG/2, NG/3, and NG/4 hybrids, strong electronic coupling between the individual components gives rise to charge transfer from the photoexcited zinc phthalocyanines to NG to form hundreds of picoseconds lived charge transfer states. The resulting features, namely photo‐ and redoxactivity, serve as incentives to construct and to test novel solar cells. Solar cells made out of NG/4 feature stable and repeatable photocurrent generation during several ‘on‐off’ cycles of illumination with monochromatic IPCE values of around 1%.     

Physical characterization of thermally induced networks of lupin protein isolates prepared by isoelectric precipitation and dialysis

Summary Protein isolates of Lupinus albus were obtained from full fat and defatted lupin flour using isoelectric precipitation or dialysis. Calorimetric tests demonstrated that the main protein fractions of the isolates denature well below 100 °C. Mechanical spectra of isolate dispersions obtained at 80 °C indicated the formation of a 'pseudogel' whose cohesion increased during cooling to 10 °C. Subsequent heating to 90 °C encouraged extensive formation of disulphide bonds as it produced gels that were insoluble in sodium dodecyl sulphate and urea solutions. Dialysis produced isolates of lower gelling concentrations, which also formed networks of a stronger relative elastic character. The presence of NaCl at concentrations up to 0.5 m had a reinforcing effect on networks. Protein over-aggregation caused the opposite effect at higher salt levels. Finally, a comparison with results in the literature on soybean protein gelation suggested similar denaturation temperatures and a common pattern of structure formation for the two legume proteins.