Experience replay is widely used in AI to bootstrap reinforcement learning (RL) by enabling an agent to remember and reuse past experiences. Classical techniques include shuffled-, reversed-ordered- and prioritized-memory buffers, which have different properties and advantages depending on the nature of the data and problem. Interestingly, recent computational neuroscience work has shown that these techniques are relevant to model hippocampal reactivations recorded during rodent navigation.
View Article and Find Full Text PDFAlthough therapeutically efficacious, ipilimumab can exhibit dose-limiting toxicity that prevents maximal efficacious clinical outcomes and can lead to discontinuation of treatment. We hypothesized that an acidic pH-selective ipilimumab (pH Ipi), which preferentially and reversibly targets the acidic tumor microenvironment over the neutral periphery, may have a more favorable therapeutic index. While ipilimumab has pH-independent CTLA-4 affinity, pH Ipi variants have been engineered to have up to 50-fold enhanced affinity to CTLA-4 at pH 6.
View Article and Find Full Text PDFPurpose: Biomarkers of response and resistance to FLT3 tyrosine kinase inhibitors (TKI) are still emerging, and optimal clinical combinations remain unclear. The purpose of this study is to identify co-occurring mutations that influence clinical response to the novel FLT3 inhibitor pexidartinib (PLX3397).
Experimental Design: We performed targeted sequencing of pretreatment blasts from 29 patients with internal tandem duplication (ITD) mutations treated on the phase I/II trial of pexidartinib in relapsed/refractory -ITD+ acute myeloid leukemia (AML).
In traditional robotics, model-based controllers are usually needed in order to bring a robotic plant to the next desired state, but they present critical issues when the dimensionality of the control problem increases and disturbances from the external environment affect the system behavior, in particular during locomotion tasks. It is generally accepted that the motion control of quadruped animals is performed by neural circuits located in the spinal cord that act as a Central Pattern Generator and can generate appropriate locomotion patterns. This is thought to be the result of evolutionary processes that have optimized this network.
View Article and Find Full Text PDFEphB2 and EphA2 control stemness and differentiation in the intestinal mucosa, but the way they cooperate with the complex mechanisms underlying tumor heterogeneity and how they affect the therapeutic outcome in colorectal cancer (CRC) patients, remain unclear. MicroRNA (miRNA) expression profiling along with pathway analysis provide comprehensive information on the dysregulation of multiple crucial pathways in CRC.Through a network-based approach founded on the characterization of progressive miRNAomes centered on EphA2/EphB2 signaling during tumor development in the AOM/DSS murine model, we found a miRNA-dependent orchestration of EphB2-specific stem-like properties in earlier phases of colorectal tumorigenesis and the EphA2-specific control of tumor progression in the latest CRC phases.
View Article and Find Full Text PDFGenomic studies have revealed significant branching heterogeneity in cancer. Studies of resistance to tyrosine kinase inhibitor therapy have not fully reflected this heterogeneity because resistance in individual patients has been ascribed to largely mutually exclusive on-target or off-target mechanisms in which tumors either retain dependency on the target oncogene or subvert it through a parallel pathway. Using targeted sequencing from single cells and colonies from patient samples, we demonstrate tremendous clonal diversity in the majority of acute myeloid leukemia (AML) patients with activating internal tandem duplication mutations at the time of acquired resistance to the FLT3 inhibitor quizartinib.
View Article and Find Full Text PDFUnlabelled: Tyrosine kinase domain mutations are a common cause of acquired clinical resistance to tyrosine kinase inhibitors (TKI) used to treat cancer, including the FLT3 inhibitor quizartinib. Mutation of kinase "gatekeeper" residues, which control access to an allosteric pocket adjacent to the ATP-binding site, has been frequently implicated in TKI resistance. The molecular underpinnings of gatekeeper mutation-mediated resistance are incompletely understood.
View Article and Find Full Text PDFBatch dark fermentation experiments were performed on food waste and mixtures of food waste and wastewater activated sludge to evaluate the influence of pH on biological H2 production and compare the process performance with and without inoculum addition. The effect of a preliminary thermal shock treatment of the inoculum was also investigated as a means to harvest the hydrogenogenic biomass. The best performance in terms of both H2 generation potential and process kinetics was observed at pH=6.
View Article and Find Full Text PDFA stochastic model of intracellular calcium oscillations is analytically studied. The governing master equation is expanded under the linear noise approximation and a closed prediction for the power spectrum of fluctuations analytically derived. A peak in the obtained power spectrum profile signals the presence of stochastic, noise induced oscillations which extend also outside the region where a deterministic limit cycle is predicted to occur.
View Article and Find Full Text PDFThe problem of pattern formation in a generic two species reaction-diffusion model is studied, under the hypothesis that only one species can diffuse. For such a system, the classical Turing instability cannot take place. At variance, by working in the generalized setting of a stochastic formulation to the inspected problem, spatially organized patterns can develop, seeded by finite size corrections.
View Article and Find Full Text PDFEpigenetic alterations, such as CpG islands methylation and histone modifications, are recognized key characteristics of cancer. Glycogenes are a group of genes which epigenetic status was found to be changed in several tumors. In this study, we determined promoter methylation status of the glycogene beta-1,4-galactosyltransferase 1 (B4GALT1) in colorectal cancer patients.
View Article and Find Full Text PDFThe trimeric envelope glycoprotein complex (Env) is the focus of vaccine development programs aimed at generating protective humoral responses to human immunodeficiency virus type 1 (HIV-1). N-Linked glycans, which constitute almost half of the molecular mass of the external Env domains, produce considerable structural heterogeneity and are a major impediment to crystallization studies. Moreover, by shielding the peptide backbone, glycans can block attempts to generate neutralizing antibodies against a substantial subset of potential epitopes when Env proteins are used as immunogens.
View Article and Find Full Text PDFColorectal cancer (CRC) is a major health problem in industrialized countries. Although inflammation-linked carcinogenesis is a well accepted concept and is often observed within the gastrointestinal tract, the underlying mechanisms remain to be elucidated. Inflammation can indeed provide initiating and promoting stimuli and mediators, generating a tumour-prone microenvironment.
View Article and Find Full Text PDFCancer Immunol Immunother
October 2010
After more than 15 years of experimentation, DNA vaccines have become a promising perspective for tumour diseases, and animal models are widely used to study the biological features of human cancer progression and to test the efficacy of vaccination protocols. In recent years, immunisation with naked plasmid DNA encoding tumour-associated antigens or tumour-specific antigens has revealed a number of advantages: antigen-specific DNA vaccination stimulates both cellular and humoral immune responses; multiple or multi-gene vectors encoding several antigens/determinants and immune-modulatory molecules can be delivered as single administration; DNA vaccination does not induce autoimmune disease in normal animals; DNA vaccines based on plasmid vectors can be produced and tested rapidly and economically. However, DNA vaccines have shown low immunogenicity when tested in human clinical trials, and compared with traditional vaccines, they induce weak immune responses.
View Article and Find Full Text PDFThe use of biomass and waste to produce alternative fuels, due to environmental and energy security reasons, is a high-quality solution especially when integrated with high efficiency fuel cell applications. In this article we look into the coupling of an anaerobic digestion process of organic residues to electrochemical conversion to electricity and heat through a molten carbonate fuel cell (MCFC). In particular the pathway of the exceedingly harmful compound hydrogen sulphide (H(2)S) in these phases is analysed.
View Article and Find Full Text PDFRecent Pat Anticancer Drug Discov
November 2009
Eradication of cancer cells is imperative for a successful treatment of tumours. In addition to the existent chemotherapy or radiation therapy, other novel immunotherapeutic strategies to fight tumours are currently under investigation. One of these is cancer vaccination, an approach aimed at inducing effective immune responses in the host against defined tumour antigens.
View Article and Find Full Text PDFBackground: Plasmid DNA vaccination combined with electroporation (EP) provides a promising approach for the prevention of infectious diseases and for cancer immunotherapy. This technology has been described as being effective in activating humoral and cellular immune response in the host as well as in enhancing expression of the encoded antigen. Several reports showed EP has adjuvant-like properties when combined with plasmid DNA injection although the effect in the absence of DNA has not been investigated.
View Article and Find Full Text PDFRecent Pat Antiinfect Drug Discov
June 2008
To date, vaccination is an active area of investigation for its application to a great variety of human diseases including infections and cancer. In particular, naked-DNA vaccination has arisen as effective strategy in the preventive medicine field with promising future prospects. The ability of plasmid DNA to activate the humoural and the cellular arms of the immune system against the encoded antigen have resulted in intensive study of new strategies aimed at increasing the DNA vaccine immunogenicity.
View Article and Find Full Text PDFVaccines represent one of the most successful strategies in medical science. From the mechanistic perspective, vaccination works by manipulating the immune response through selecting, activating and expanding the memory of B and T cells. To determine the magnitude and quality of immune response, suitable vaccine adjuvants are required; therefore, much effort is going into finding new, effective and non-toxic adjuvant formulations focussed on the activation of key immune targets for inducing a long-term, potent and safe immune response.
View Article and Find Full Text PDFThe goal of this study was to evaluate tuberculosis control in Senegal especially with regard to organization, quality, and availability of care services. Study was carried out from January to October 2002 within the framework of the National Turberculosis Control Program (NTCP) in 10 public hospitals and 8 private facilities including 4 doctors' offices, 2 company medical dispensaries, and 2 medical laboratories. Case observations were collected at the same time as surveying of diagnostic and therapeutic departments.
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