Feedback passivity of nonlinear discrete-time systems with direct input-output link

This paper is devoted to the study of the feedback passivity property in nonlinear discrete-time systems. The relative degree and zero dynamics of the non-passive system are related to the feedback passivity of the system. Two main results are presented. First, some relative degree-related properties of passive systems in general form are stated. Second, sufficient conditions in order to render a multiple-input multiple-output (MIMO) system passive by means of a static state feedback control law are obtained.     

Daily recovery experiences: The role of volunteer work during leisure time.

This study focused on the role of volunteer work for daily recovery from work. In a 1-week diary study with 166 employees, we assessed the amount of time spent on volunteer work during leisure time, and the recovery facets of psychological detachment from work (i.e., mentally switching off from work), mastery experiences (i.e., pursuing challenging activities), and community experiences (i.e., cultivating relationships) every day before participants went to bed. Results from hierarchical linear modeling (n = 529 days) showed volunteer work during leisure time to be positively related to mastery experiences and community experiences suggesting volunteer work to contribute to successful recovery by creating new resources. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Synthesis and Biological Evaluation of Small Molecules as Potential Anticancer Multitarget Agents

Twenty-six triazole-based derivatives were designed for targeting both PD-L1 (programmed death receptor ligand 1) and VEGFR-2 (vascular endothelial growth factor receptor 2). These compounds were synthetized and biologically evaluated as multitarget inhibitors of VEGFR-2, PD-L1 and c-Myc proteins. The antiproliferative activity of these molecules on several tumor cell lines (HT-29, A-549, and MCF-7) and on the non-tumor cell line HEK-293 was determined. The effects on the abovementioned biological targets were evaluated for some selected compounds. Compound 23, bearing a p-chlorophenyl group, showed better results than sorafenib in regard to the downregulation of VEGFR-2 and a similar effect to BMS-8 on both PD-L1 and c-Myc proteins. The antiangiogenic and antivascular activities of chloro derivatives were also established by endothelial microtube formation assay on Matrigel^®.     

Improving the Management of Endometrial Cancer Patients through the Use of Liquid Biopsy Analyses: A Case Report

Endometrial cancer (EC) is the 4th most common neoplasm of the female genital tract, with 15–20% of patients being of high risk of recurrence which leads to a significant decrease in patient survival. Current therapeutic options for patients with EC are poor, being the combined therapy of carboplatin and paclitaxel the standard of care, with limited efficacy. Therefore, new therapeutic options and better monitoring tools are needed to improve the management of the disease. In the current case report, we showcase the value of liquid biopsy analyses in a microsatellite instability EC patient with initially good prognosis that however underwent rapid progression disease within 6 months post-surgery; through the study of plasma cfDNA/ctDNA dynamics to assess the tumour evolution during treatment, as well as the study of the uterine aspirate as a valuable sample that captures the intra-tumour heterogeneity that allows a comprehensive genomic profiling of the disease to identify potential therapeutic options. Furthermore, preclinical models were generated at the time of tumour progression to assess the efficacy of the identified targeted therapies.     

Facile Microwave Assisted Synthesis of Silver Nanostars for Ultrasensitive Detection of Biological Analytes by SERS

We report a very simple, rapid and reproducible method for the fabrication of anisotropic silver nanostars (AgNS) that can be successfully used as highly efficient SERS substrates for different bioanalytes, even in the case of a near-infra-red (NIR) excitation laser. The nanostars have been synthesized using the chemical reduction of Ag⁺ ions by trisodium citrate. This is the first research reporting the synthesis of AgNS using only trisodium citrate as a reducing and stabilizing agent. The key elements of this original synthesis procedure are rapid hydrothermal synthesis of silver nanostars followed by a cooling down procedure by immersion in a water bath. The synthesis was performed in a sealed bottom flask homogenously heated and brought to a boil in a microwave oven. After 60 s, the colloidal solution was cooled down to room temperature by immersion in a water bath at 35 °C. The as-synthesized AgNS were washed by centrifugation and used for SERS analysis of test molecules (methylene blue) as well as biological analytes: pharmaceutical compounds with various Raman cross sections (doxorubicin, atenolol & metoprolol), cell lysates and amino acids (methionine & cysteine). UV-Vis absorption spectroscopy, (Scanning) Transmission Electron Microscopy ((S)TEM) and Atomic Force Microscopy (AFM) have been employed for investigating nanostars’ physical properties.     

Lightweight Bytecode Verification

In this paper, we provide a theoretical foundation for and improvements to the existing bytecode verification technology, a critical component of the Java security model, for mobile code used with the Java “micro edition” (J2ME), which is intended for embedded computing devices. In Java, remotely loaded “bytecode” class files are required to be bytecode verified before execution, that is, to undergo a static type analysis that protects the platform's Java run-time system from so-called type confusion attacks such as pointer manipulation. The data flow analysis that performs the verification, however, is beyond the capacity of most embedded devices because of the memory requirements that the typical algorithm will need. We propose to take a proof-carrying code approach to data flow analysis in defining an alternative technique called “lightweight analysis” that uses the notion of a “certificate” to reanalyze a previously analyzed data flow problem, even on poorly resourced platforms. We formally prove that the technique provides the same guarantees as standard bytecode safety verification analysis, in particular that it is “tamper proof” in the sense that the guarantees provided by the analysis cannot be broken by crafting a “false” certificate or by altering the analyzed code. We show how the Java bytecode verifier fits into this framework for an important subset of the Java Virtual Machine; we also show how the resulting “lightweight bytecode verification” technique generalizes and simulates the J2ME verifier (to be expected as Sun's J2ME “K-Virtual machine” verifier was directly based on an early version of this work), as well as Leroy's “on-card bytecode verifier,” which is specifically targeted for Java Cards.     

Genetics and Epigenetics of Spontaneous Intracerebral Hemorrhage

Intracerebral hemorrhage (ICH) is a complex and heterogeneous disease, and there is no effective treatment. Spontaneous ICH represents the final manifestation of different types of cerebral small vessel disease, usually categorized as: lobar (mostly related to cerebral amyloid angiopathy) and nonlobar (hypertension-related vasculopathy) ICH. Accurate phenotyping aims to reflect these biological differences in the underlying mechanisms and has been demonstrated to be crucial to the success of genetic studies in this field. This review summarizes how current knowledge on genetics and epigenetics of this devastating stroke subtype are contributing to improve the understanding of ICH pathophysiology and their potential role in developing therapeutic strategies.     

Antitumor Effects of Ral-GTPases Downregulation in Glioblastoma

Glioblastoma (GBM) is the most common tumor in the central nervous system in adults. This neoplasia shows a high capacity of growth and spreading to the surrounding brain tissue, hindering its complete surgical resection. Therefore, the finding of new antitumor therapies for GBM treatment is a priority. We have previously described that cyclin D1-CDK4 promotes GBM dissemination through the activation of the small GTPases RalA and RalB. In this paper, we show that RalB GTPase is upregulated in primary GBM cells. We found that the downregulation of Ral GTPases, mainly RalB, prevents the proliferation of primary GBM cells and triggers a senescence-like response. Moreover, downregulation of RalA and RalB reduces the viability of GBM cells growing as tumorspheres, suggesting a possible role of these GTPases in the survival of GBM stem cells. By using mouse subcutaneous xenografts, we have corroborated the role of RalB in GBM growth in vivo. Finally, we have observed that the knockdown of RalB also inhibits cell growth in temozolomide-resistant GBM cells. Overall, our work shows that GBM cells are especially sensitive to Ral-GTPase availability. Therefore, we propose that the inactivation of Ral-GTPases may be a reliable therapeutic approach to prevent GBM progression and recurrence.