15,703 results match your criteria broad activation


Aluminum Nitride to Silicon Direct Bonding for an Alternative Silicon-On-Insulator Platform.

ACS Appl Mater Interfaces 2021 Aug 4. Epub 2021 Aug 4.

Department of Electrical Engineering and Automation, Aalto University, P.O. Box 13500, FIN-00076 Aalto, Finland.

The next generation of microelectromechanical systems (MEMS) requires new materials and platforms that can exploit the intrinsic properties of advanced materials and structures, such as materials with high thermal conductivity, broad optical transmission spectra, piezoelectric properties, and miniaturization potential. Therefore, we need to look beyond standard SiO-based silicon-on-insulator (SOI) structures to realize ubiquitous MEMS. This work proposes using AlN as an alternative SOI structure due to several inherent material property advantages as well as functional advantages. Read More

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Mechanically Triggered Release of Functionally Diverse Molecular Payloads from Masked 2-Furylcarbinol Derivatives.

ACS Cent Sci 2021 Jul 14;7(7):1216-1224. Epub 2021 Jul 14.

Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States.

Polymers that release functional small molecules in response to mechanical force are appealing targets for drug delivery, sensing, catalysis, and many other applications. Mechanically sensitive molecules called mechanophores are uniquely suited to enable molecular release with excellent selectivity and control, but mechanophore designs capable of releasing cargo with diverse chemical functionality are limited. Here, we describe a general and highly modular mechanophore platform based on masked 2-furylcarbinol derivatives that spontaneously decompose under mild conditions upon liberation via a mechanically triggered reaction, resulting in the release of a covalently installed molecular payload. Read More

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Chimeric non-antigen receptors in T cell-based cancer therapy.

J Immunother Cancer 2021 Aug;9(8)

Division of Medical Oncology, Department of Medicine, University of Colorado - Anschutz Medical Campus, Aurora, Colorado, USA

Adoptively transferred T cell-based cancer therapies have shown incredible promise in treatment of various cancers. So far therapeutic strategies using T cells have focused on manipulation of the antigen-recognition machinery itself, such as through selective expression of tumor-antigen specific T cell receptors or engineered antigen-recognition chimeric antigen receptors (CARs). While several CARs have been approved for treatment of hematopoietic malignancies, this kind of therapy has been less successful in the treatment of solid tumors, in part due to lack of suitable tumor-specific targets, the immunosuppressive tumor microenvironment, and the inability of adoptively transferred cells to maintain their therapeutic potentials. Read More

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FAP imaging in rare cancer entities-first clinical experience in a broad spectrum of malignancies.

Eur J Nucl Med Mol Imaging 2021 Aug 3. Epub 2021 Aug 3.

National Center for Tumor Diseases (NCT), Heidelberg, Germany.

Purpose:  Ga-FAPI (fibroblast activation protein inhibitor) is a rapidly evolving and highly promising radiotracer for PET/CT imaging, presenting excellent results in a variety of tumor entities, particularly in epithelial carcinomas. This retrospective analysis sought to evaluate the potential and impact of FAPI-PET/CT in rare cancer diseases with respect to improvement in staging and therapy, based on tracer uptake in normal organs and tumors.

Material And Methods: Fifty-five patients with rare tumor entities, defined by a prevalence of 1 person out of 2000 or less, received a  Ga-FAPI-PET/CT scan. Read More

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KSO activation by glucose at room temperature for the synthesis and functionalization of heterocycles in water.

Chem Commun (Camb) 2021 Aug 3. Epub 2021 Aug 3.

Department of Pharmaceutical Technology (Process Chemistry), National Institute of Pharmaceutical Education and Research, S. A. S. Nagar, Punjab 160062, India.

While persulfate activation at room temperature using glucose has primarily been focused on kinetic studies of the sulfate radical anion, the utilization of this protocol in organic synthesis is rarely demonstrated. We reinvestigated selected K2S2O8-mediated known organic reactions that invariably require higher temperatures and an organic solvent. A diverse, mild functionalization and synthesis of heterocycles using the inexpensive oxidant K2S2O8 in water at room temperature is reported, demonstrating the sustainability and broad scope of the method. Read More

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Recapitulative haematopoietic development of human pluripotent stem cells in the absence of exogenous haematopoietic cytokines.

J Cell Mol Med 2021 Aug 2. Epub 2021 Aug 2.

CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.

To improve the recapitulative quality of human pluripotent stem cell (hPSC) differentiation, we removed exogenous haematopoietic cytokines from the defined differentiation system. Here, we show that endogenous stimuli and VEGF are sufficient to induce robust hPSC-derived haematopoiesis, intensive generation of haematopoietic progenitors, maturation of blood cells and the emergence of definitive precursor cells including those that phenotypically identical to early human embryonic haematopoietic stem cells (HSCs). Moreover, the cytokine-free system produces significantly higher numbers of haematopoietic progenitors compared to the published protocols. Read More

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Bispecific CAR T cells against EpCAM and inducible ICAM-1 overcome antigen heterogeneity and generate superior anti-tumor responses.

Cancer Immunol Res 2021 Aug 2. Epub 2021 Aug 2.

Radiology, Weill Cornell Medicine

Adoptive transfer of chimeric antigen receptor (CAR) T cells has demonstrated unparalleled responses in hematological cancers, yet antigen escape and tumor relapse occur frequently. CAR T-cell therapy for patients with solid tumors faces even greater challenges due to the immunosuppressive tumor environment and antigen heterogeneity. Here, we developed a bispecific CAR to simultaneously target epithelial cell adhesion molecule (EpCAM) and intercellular adhesion molecule 1 (ICAM-1) in order to overcome antigen escape and to improve the durability of tumor responses. Read More

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A space-fractional bidomain framework for cardiac electrophysiology: 1D alternans dynamics.

Chaos 2021 Jul;31(7):073123

Department of Engineering, Campus Bio-Medico University of Rome, 00128 Rome, Italy.

Cardiac electrophysiology modeling deals with a complex network of excitable cells forming an intricate syncytium: the heart. The electrical activity of the heart shows recurrent spatial patterns of activation, known as cardiac alternans, featuring multiscale emerging behavior. On these grounds, we propose a novel mathematical formulation for cardiac electrophysiology modeling and simulation incorporating spatially non-local couplings within a physiological reaction-diffusion scenario. Read More

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Mechanisms of regulatory T cell infiltration in tumors: implications for innovative immune precision therapies.

J Immunother Cancer 2021 Jul;9(7)

Division of Cancer Immunology, Research Institute/Exploratory Oncology Research and Clinical Trial Center (EPOC), National Cancer Center, Tokyo/Chiba, Japan.

With the broad application of cancer immunotherapies such as immune checkpoint inhibitors in multiple cancer types, the immunological landscape in the tumor microenvironment (TME) has become enormously important for determining the optimal cancer treatment. Tumors can be immunologically divided into two categories: inflamed and non-inflamed based on the extent of immune cell infiltration and their activation status. In general, immunotherapies are preferable for the inflamed tumors than for non-inflamed tumors. Read More

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Dichotomous thinking about social groups: Learning about one group can activate opposite beliefs about another group.

Cogn Psychol 2021 Jul 27;129:101408. Epub 2021 Jul 27.

University of California, Davis, United States.

Across three studies (N = 607), we examined people's use of a dichotomizing heuristic-the inference that characteristics belonging to one group do not apply to another group-when making judgments about novel social groups. Participants learned information about one group (e.g. Read More

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Recovery of CuO/C catalyst from spent anode material in battery to activate peroxymonosulfate for refractory organic contaminants degradation.

J Hazard Mater 2021 Jul 4;420:126552. Epub 2021 Jul 4.

College of Environmental Science and Engineering, Hunan University, Changsha 410082, PR China; Key Laboratory of Environment Biology and Pollution Control, Hunan University, Ministry of Education, Changsha 410082, PR China.

It is critical to developing low-cost and efficient catalysts to activate peroxymonosulfate for the degradation of organic contaminants, whereas it remains challenging. In the study, a recycle method to synthesize efficient heterogeneous catalysts was developed by exploiting the anode electrode of spent lithium-ion batteries as the raw material based on a one-step calcination process. The recycled anode material (AM) composed of copper oxide and graphite carbon was capable of efficiently activating peroxymonosulfate (PMS) to degrade a wide range of organic contaminants. Read More

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Integration of transcriptional and metabolic control in macrophage activation.

EMBO Rep 2021 Jul 30:e53251. Epub 2021 Jul 30.

Department of Experimental Oncology, European Institute of Oncology (IEO) IRCCS, Milan, Italy.

Macrophages react to microbial and endogenous danger signals by activating a broad panel of effector and homeostatic responses. Such responses entail rapid and stimulus-specific changes in gene expression programs accompanied by extensive rewiring of metabolism, with alterations in chromatin modifications providing one layer of integration of transcriptional and metabolic regulation. A systematic and mechanistic understanding of the mutual influences between signal-induced metabolic changes and gene expression is still lacking. Read More

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Reciprocal regulation of spontaneous synaptic vesicle fusion by Fragile X mental retardation protein and group I metabotropic glutamate receptors.

J Neurochem 2021 Jul 29. Epub 2021 Jul 29.

National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bengaluru, 560065, India.

Fragile X mental retardation protein (FMRP) is a neuronal protein mediating multiple functions, with its absence resulting in one of the most common monogenic causes of autism, Fragile X syndrome (FXS). Analyses of FXS pathophysiology have identified a range of aberrations in synaptic signaling pathways and plasticity associated with group I metabotropic glutamate (mGlu) receptors. These studies, however, have mostly focused on the postsynaptic functions of FMRP and mGlu receptor activation, and relatively little is known about their presynaptic effects. Read More

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Coordination of the Uptake and Metabolism of Amino Acids in -Infected Macrophages.

Front Immunol 2021 13;12:711462. Epub 2021 Jul 13.

Public Health Research Institute, New Jersey Medical School, Rutgers Biomedical and Health Sciences, Rutgers The State University of New Jersey, Newark, NJ, United States.

Macrophage polarization to the M1-like phenotype, which is critical for the pro-inflammatory and antimicrobial responses of macrophages against intracellular pathogens, is associated with metabolic reprogramming to the Warburg effect and a high output of NO from increased expression of NOS2. However, there is limited understanding about the uptake and metabolism of other amino acids during M1 polarization. Based on functional analysis of a group of upregulated transporters and enzymes involved in the uptake and/or metabolism of amino acids in -infected macrophages, plus studies of immune cell activation, we postulate a coherent scheme for amino acid uptake and metabolism during macrophage polarization to the M1-like phenotype. Read More

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Human Newborn Monocytes Demonstrate Distinct BCG-Induced Primary and Trained Innate Cytokine Production and Metabolic Activation .

Front Immunol 2021 13;12:674334. Epub 2021 Jul 13.

Precision Vaccines Program, Division of Infectious Diseases, Boston Children's Hospital, Boston, MA, United States.

Background: Newborns exhibit distinct immune responses and are at high risk of infection. Neonatal immunization with BCG, the live attenuated vaccine against tuberculosis (TB), is associated with broad protection against a range of unrelated pathogens, possibly reflecting vaccine-induced training of innate immune cells ("innate memory"). However, little is known regarding the impact of age on BCG-induced innate responses. Read More

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The p53 transcriptional response across tumor types reveals core and senescence-specific signatures modulated by long noncoding RNAs.

Proc Natl Acad Sci U S A 2021 Aug;118(31)

Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511;

The p53 pathway is a universal tumor suppressor mechanism that limits tumor progression by triggering apoptosis or permanent cell cycle arrest, called senescence. In recent years, efforts to reactivate p53 function in cancer have proven to be a successful therapeutic strategy in murine models and have gained traction with the development of a range of small molecules targeting mutant p53. However, knowledge of the downstream mediators of p53 reactivation in different oncogenic contexts has been limited. Read More

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Solid phase submonomer azapeptide synthesis.

Methods Enzymol 2021 20;656:169-190. Epub 2021 May 20.

Department of Chemistry, North Carolina State University, Raleigh, NC, United States. Electronic address:

Azapeptides contain at least one aza-amino acid, where the α-carbon has been replaced by a nitrogen atom, and have found broad applicability in fields ranging from medicinal chemistry to biomaterials. In this chapter, we provide a step-by-step protocol for the solid phase submonomer synthesis of azapeptides, which includes three steps: (1) hydrazone activation and coupling onto a resin-bound peptide, (2) chemoselective semicarbazone functionalization for installation of the aza-amino acid side chain, and (3) orthogonal deprotection of the semicarbazone to complete the monomer addition cycle. We focus on semicarbazone functionalization by N-alkylation with primary alkyl halides, and describe conditions for coupling onto aza-amino acids. Read More

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Rhodium(III)-catalyzed asymmetric [4+1] spiroannulations of -pivaloyl oximes with α-diazo compounds.

Chem Commun (Camb) 2021 Jul 29. Epub 2021 Jul 29.

Henan Key Laboratory of Organic Functional Molecule and Drug Innovation, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, China. and Institute of Molecular Science and Engineering, Institute of Frontier and Interdisciplinary Sciences, Shandong University, Qingdao, China and School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an 710062, China.

Chiral RhIII catalysts can catalyze the asymmetric [4+1] spiroannulation of O-pivaloyl oximes with α-diazo homophthalimides under redox-neutral and acid/base-neutral conditions, leading to formation of chiral spirocyclic imines as a result of C-H activation and N-O cleavage. The reaction proceeded with high efficiency and features broad substrate scope, mild reaction conditions, and high to excellent enantioselectivities. Read More

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Degradation of tetrabromobisphenol A through peroxymonaosulfate oxidation activated by LaSrCoMnO perovskite.

Environ Sci Pollut Res Int 2021 Jul 28. Epub 2021 Jul 28.

Research Group of Water Pollution Control and Water Reclamation, College of Chemical Engineering, Beijing University of Chemical Technology, No. 15 Beisanhuan East Road, Beijing, 100029, People's Republic of China.

LaSrCoMnO (LSCM) perovskite composite oxides prepared by co-doping of Co and Mn in B site-activated peroxymonosulfate (PMS) to degrade tetrabromobisphenol A. The characterization results indicated that the LSCM with x=0.3-0. Read More

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Early and Next-Generation KIT/PDGFRA Kinase Inhibitors and the Future of Treatment for Advanced Gastrointestinal Stromal Tumor.

Front Oncol 2021 12;11:672500. Epub 2021 Jul 12.

Department of Medicine, Portland VA Health Care System and OHSU Knight Cancer Institute, Oregon Health and Science University, Portland, OR, United States.

The majority of gastrointestinal stromal tumors (GIST) harbor an activating mutation in either the KIT or PDGFRA receptor tyrosine kinases. Approval of imatinib, a KIT/PDGFRA tyrosine kinase inhibitor (TKI), meaningfully improved the treatment of advanced GIST. Other TKIs subsequently gained approval: sunitinib as a second-line therapy and regorafenib as a third-line therapy. Read More

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Broad and Efficient Activation of Memory CD4 T Cells by Novel HAdV- and HCMV-Derived Peptide Pools.

Front Immunol 2021 7;12:700438. Epub 2021 Jul 7.

Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany.

Reactivation of Human Cytomegalovirus (HCMV) and Human Adenovirus (HAdV) in immunocompromised patients following stem cell transplantation (SCT) or solid organ transplantation (SOT) is associated with high morbidity and mortality. The adoptive transfer of virus-specific CD8 and CD4 T cells has been shown to re-establish the antiviral T-cell response and improve clinical outcome. The viral load in immunocompromised patients can efficiently be reduced solely by the infusion of virus-specific CD4 T cells. Read More

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Prefrontal GABAergic Interneurons Gate Long-Range Afferents to Regulate Prefrontal Cortex-Associated Complex Behaviors.

Front Neural Circuits 2021 12;15:716408. Epub 2021 Jul 12.

Department of Neurobiology and Anatomy, College of Medicine, Drexel University, Philadelphia, PA, United States.

Prefrontal cortical GABAergic interneurons (INs) and their innervations are essential for the execution of complex behaviors such as working memory, social behavior, and fear expression. These behavior regulations are highly dependent on primary long-range afferents originating from the subcortical structures such as mediodorsal thalamus (MD), ventral hippocampus (vHPC), and basolateral amygdala (BLA). In turn, the regulatory effects of these inputs are mediated by activation of parvalbumin-expressing (PV) and/or somatostatin expressing (SST) INs within the prefrontal cortex (PFC). Read More

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A high-content platform for physiological profiling and unbiased classification of individual neurons.

Cell Rep Methods 2021 May 2;1(1). Epub 2021 Apr 2.

Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

High-throughput physiological assays lose single-cell resolution, precluding subtype-specific analyses of activation mechanism and drug effects. We demonstrate APPOINT (automated physiological phenotyping of individual neuronal types), a physiological assay platform combining calcium imaging, robotic liquid handling, and automated analysis to generate physiological activation profiles of single neurons at large scale. Using unbiased techniques, we quantify responses to sequential stimuli, enabling subgroup identification by physiology and probing of distinct mechanisms of neuronal activation within subgroups. Read More

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AIE-Active Difluoroboron Complexes with N,O-Bidentate Ligands: Rapid Construction by Copper-Catalyzed C-H Activation.

Adv Sci (Weinh) 2021 Jul 26:e2101814. Epub 2021 Jul 26.

Organisch-Chemisches Institut, Westfälische Wilhelms-Universität Münster, Corrensstraße 40, Münster, 48149, Germany.

The development of organic materials with high solid-state luminescence efficiency is highly desirable because of their fundamental importance and applicability in optoelectronics. Herein, a rapid construction of novel BF complexes with N,O-bidentate ligands by using Cu(BF ) •6H O as a catalyst and BF source is disclosed, which avoids the need for pre-composing the N,O-bidentate ligands and features a broad substrate scope and a high tolerance level for sensitive functional groups. Moreover, molecular oxygen is employed as the terminal oxidant in this transformation. Read More

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Hydrodynamic model of blood flow in major arteries pulsing in various modes.

Med Biol Eng Comput 2021 Jul 24. Epub 2021 Jul 24.

Research Institute of Experimental Cardiology, 121552, Moscow, Russian Federation.

Traditionally, the arteries in mammals are viewed as the tubes with elastic wall, whose elasticity could be slowly (during a minute) tuned to change its diameter thereby regulating regional blood supply. Recent findings showed that an artery is a much more sophisticated organ, which can change elasticity of vascular wall within a fraction of a second during a cardiac cycle due to activation of its smooth muscles manifested by generation of arterial action potentials. The rapid variations in elasticity of vascular wall resulted in three basic modes of arterial pulsing: passive, active, and intermediate. Read More

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Inhibition of lung tumorigenesis by a small molecule CA170 targeting the immune checkpoint protein VISTA.

Commun Biol 2021 Jul 23;4(1):906. Epub 2021 Jul 23.

Center for Disease Prevention Research, Medical College of Wisconsin, Milwaukee, WI, USA.

Expressed on cells of the myeloid and lymphoid lineages, V-domain Ig Suppressor of T cell Activation (VISTA) is an emerging target for cancer immunotherapy. Blocking VISTA activates both innate and adaptive immunity to eradicate tumors in mice. Using a tripeptide small molecule antagonist of VISTA CA170, we found that it exhibited potent anticancer efficacy on carcinogen-induced mouse lung tumorigenesis. Read More

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Developmental brain dynamics of numerical and arithmetic abilities.

NPJ Sci Learn 2021 Jul 23;6(1):22. Epub 2021 Jul 23.

Faculty of Psychology and Educational Sciences, KU Leuven, University of Leuven, Leuven, Belgium.

The development of numerical and arithmetic abilities constitutes a crucial cornerstone in our modern and educated societies. Difficulties to acquire these central skills can lead to severe consequences for an individual's well-being and nation's economy. In the present review, we describe our current broad understanding of the functional and structural brain organization that supports the development of numbers and arithmetic. Read More

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X-ray videocystometry for high-speed monitoring of urinary tract function in mice.

Sci Adv 2021 Jul 23;7(30). Epub 2021 Jul 23.

Biomedical MRI, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium.

Lower urinary tract dysfunction (LUTd) represents a major health care problem with a high, unmet medical need. Design of additional therapies for LUTd requires precise tools to study bladder storage and voiding (dys)function in animal models. We developed videocystometry in mice, combining intravesical pressure measurements with high-speed fluoroscopy of the urinary tract. Read More

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Cytokine Release Syndrome Associated with T-Cell-Based Therapies for Hematological Malignancies: Pathophysiology, Clinical Presentation, and Treatment.

Int J Mol Sci 2021 Jul 17;22(14). Epub 2021 Jul 17.

Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, 41124 Modena, Italy.

Cytokines are a broad group of small regulatory proteins with many biological functions involved in regulating the hematopoietic and immune systems. However, in pathological conditions, hyperactivation of the cytokine network constitutes the fundamental event in cytokine release syndrome (CRS). During the last few decades, the development of therapeutic monoclonal antibodies and T-cell therapies has rapidly evolved, and CRS can be a serious adverse event related to these treatments. Read More

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Transition between Random and Periodic Electron Currents on a DNA Chain.

Int J Mol Sci 2021 Jul 8;22(14). Epub 2021 Jul 8.

Aix-Marseille Univ, Université de Toulon, CNRS, CPT, 13288 Marseille, France.

By resorting to a model inspired to the standard Davydov and Holstein-Fröhlich models, in the present paper we study the motion of an electron along a chain of heavy particles modeling a sequence of nucleotides proper to a DNA fragment. Starting with a model Hamiltonian written in second quantization, we use the Time Dependent Variational Principle to work out the dynamical equations of the system. It can be found that, under the action of an external source of energy transferred to the electron, and according to the excitation site, the electron current can display either a broad frequency spectrum or a sharply peaked frequency spectrum. Read More

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