404 research outputs found
Coherent charge transport through molecular wires: influence of strong Coulomb repulsion
We derive a master equation for the electron transport through molecular
wires in the limit of strong Coulomb repulsion. This approach is applied to two
typical situations: First, we study transport through an open conduction
channel for which we find that the current exhibits an ohmic-like behaviour.
Second, we explore the transport properties of a bridged molecular wire, where
the current decays exponentially as a function of the wire length. For both
situations, we discuss the differences to the case of non-interacting
electrons.Comment: 15 pages, 4 figures, elsart style, accepted at Chem Phy
First-Principles Analysis of Molecular Conduction Using Quantum Chemistry Software
We present a rigorous and computationally efficient method to do a
parameter-free analysis of molecular wires connected to contacts. The
self-consistent field approach is coupled with Non-equilibrium Green's Function
(NEGF) formalism to describe electronic transport under an applied bias.
Standard quantum chemistry software is used to calculate the self-consistent
field using density functional theory (DFT). Such close coupling to standard
quantum chemistry software not only makes the procedure simple to implement but
also makes the relation between the I-V characteristics and the chemistry of
the molecule more obvious. We use our method to interpolate between two extreme
examples of transport through a molecular wire connected to gold (111)
contacts: band conduction in a metallic (gold) nanowire, and resonant
conduction through broadened, quasidiscrete levels of a phenyl dithiol
molecule. We obtain several quantities of interest like I-V characteristic,
electron density and voltage drop along the molecule.Comment: Accepted for publication in J. Chem. Phys. (Special issue on
molecular electronics, Ed. Mark Ratner
First-Principles Based Matrix-Green's Function Approach to Molecular Electronic Devices: General Formalism
Transport in molecular electronic devices is different from that in
semiconductor mesoscopic devices in two important aspects: (1) the effect of
the electronic structure and (2) the effect of the interface to the external
contact. A rigorous treatment of molecular electronic devices will require the
inclusion of these effects in the context of an open system exchanging particle
and energy with the external environment. This calls for combining the theory
of quantum transport with the theory of electronic structure starting from the
first-principles. We present a rigorous yet tractable matrix Green's function
approach for studying transport in molecular electronic devices, based on the
Non-Equilibrium Green's Function Formalism of quantum transport and the
density-functional theory of electronic structure using local orbital basis
sets. By separating the device rigorously into the molecular region and the
contact region, we can take full advantage of the natural spatial locality
associated with the metallic screening in the electrodes and focus on the
physical processes in the finite molecular region. This not only opens up the
possibility of using the existing well-established technique of molecular
electronic structure theory in transport calculations with little change, but
also allows us to use the language of qualitative molecular orbital theory to
interpret and rationalize the results of the computation. For the device at
equilibrium, our method provides an alternative approach for solving the
molecular chemisorption problem. For the device out of equilibrium, we show
that the calculation of elastic current transport through molecules, both
conceptually and computationally, is no more difficult than solving the
chemisorption problem.Comment: To appear in Chemical Physic
Charging effects in biased molecular devices
The influence of the charging effects on the transport characteristics of a
molecular wire bridging two metallic electrodes in the limit of weak contacts
is studied by generalized Breit-Wigner formula. Molecule is modeled as a
quantum dot with discrete energy levels, while the coupling to the electrodes
is treated within a broad band theory. Owing to this model we find
self-consistent occupation of particular energy levels and orbital energies of
the wire in the presence of transport. The nonlinear conductance and
current-voltage characteristics are investigated as a function of bias voltage
in the case of symmetric and asymmetric coupling to the electrodes. It is shown
that the shape of that curves are determined by the combined effect of the
electronic structure of the molecule and by electron-electron repulsion.Comment: 5 pages, 3 figures; accepted in Physica
Allergic rhinitis
Allergic rhinitis is a common disorder that is strongly linked to asthma and conjunctivitis. It is usually a long-standing condition that often goes undetected in the primary-care setting. The classic symptoms of the disorder are nasal congestion, nasal itch, rhinorrhea and sneezing. A thorough history, physical examination and allergen skin testing are important for establishing the diagnosis of allergic rhinitis. Second-generation oral antihistamines and intranasal corticosteroids are the mainstay of treatment. Allergen immunotherapy is an effective immune-modulating treatment that should be recommended if pharmacologic therapy for allergic rhinitis is not effective or is not tolerated. This article provides an overview of the pathophysiology, diagnosis, and appropriate management of this disorder
Endoglin, a novel biomarker and therapeutical target to prevent malignant peripheral nerve sheath tumor growth and metastasis.
PURPOSE
Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive soft-tissue sarcomas that lack effective treatments, underscoring the urgent need to uncover novel mediators of MPNST pathogenesis that may serve as potential therapeutic targets. Tumor angiogenesis is considered a critical event in MPNST transformation and progression. Here, we have investigated whether endoglin (ENG), a TGF-β coreceptor with a crucial role in angiogenesis, could be a novel therapeutic target in MPNSTs.
EXPERIMENTAL DESIGN
ENG expression was evaluated in human peripheral nerve sheath tumor tissues and plasma samples. Effects of tumor cell-specific ENG expression on gene expression, signaling pathway activation and in vivo MPNST growth and metastasis were investigated. The efficacy of ENG targeting in monotherapy or in combination with MEK inhibition was analyzed in xenograft models.
RESULTS
ENG expression was found to be upregulated in both human MPNST tumor tissues and plasma circulating small extracellular vesicles. We demonstrated that ENG modulates Smad1/5 and MAPK/ERK pathway activation and pro-angiogenic and pro-metastatic gene expression in MPNST cells and plays an active role in tumor growth and metastasis in vivo. Targeting with ENG-neutralizing antibodies (TRC105/M1043) decreased MPNST growth and metastasis in xenograft models by reducing tumor cell proliferation and angiogenesis. Moreover, combination of anti-ENG therapy with MEK inhibition effectively reduced tumor cell growth and angiogenesis.
CONCLUSIONS
Our data unveil a tumor-promoting function of ENG in MPNSTs and support the use of this protein as a novel biomarker and a promising therapeutic target for this disease.We apologize to those authors whose work could not be cited due to size limitations. We thank Dr. Eduard Serra, Dr. Conxi Lázaro and Dr. David Lyden for their support in the project. We also thank Héctor Tejero for his help in analyzing RNA-seq data. Dr. Peinado laboratory is funded by US Department of Defense (W81XWH-16-1-0131), Agencia Estatal de Investigación/Ministerio de Ciencia e Innovación (AEI/MCIN) (PID2020-118558RB-I00/AEI/10.13039/501100011033),
Fundación Proyecto Neurofibromatosis, European Union’s Horizon 2020 research and innovation programme “proEVLifeCycle” under the Marie Skłodowska-Curie grant agreement No 860303, and Fundación Científica AECC. We are also grateful for the support of the Ministerio de Universidades (Programa de Formación de Profesorado Universitario (FPU)) for the fellowship FPU016/05356 awarded to T. González-Muñoz and to the Translational NeTwork for the CLinical application of Extracellular VesicleS (TeNTaCLES) RED2018-102411-T(AEI/10.13039/501100011033). A. Di Giannatale was supported during this work by a research gran Nuovo-Soldati Foundation. The CNIO, certified as Severo Ochoa Excellence Centre, is supported by the Spanish Government through the Instituto de Salud Carlos III.N
Green function techniques in the treatment of quantum transport at the molecular scale
The theoretical investigation of charge (and spin) transport at nanometer
length scales requires the use of advanced and powerful techniques able to deal
with the dynamical properties of the relevant physical systems, to explicitly
include out-of-equilibrium situations typical for electrical/heat transport as
well as to take into account interaction effects in a systematic way.
Equilibrium Green function techniques and their extension to non-equilibrium
situations via the Keldysh formalism build one of the pillars of current
state-of-the-art approaches to quantum transport which have been implemented in
both model Hamiltonian formulations and first-principle methodologies. We offer
a tutorial overview of the applications of Green functions to deal with some
fundamental aspects of charge transport at the nanoscale, mainly focusing on
applications to model Hamiltonian formulations.Comment: Tutorial review, LaTeX, 129 pages, 41 figures, 300 references,
submitted to Springer series "Lecture Notes in Physics
The Allometry of Host-Pathogen Interactions
Understanding the mechanisms that control rates of disease progression in humans and other species is an important area of research relevant to epidemiology and to translating studies in small laboratory animals to humans. Body size and metabolic rate influence a great number of biological rates and times. We hypothesize that body size and metabolic rate affect rates of pathogenesis, specifically the times between infection and first symptoms or death.We conducted a literature search to find estimates of the time from infection to first symptoms (t(S)) and to death (t(D)) for five pathogens infecting a variety of bird and mammal hosts. A broad sampling of diseases (1 bacterial, 1 prion, 3 viruses) indicates that pathogenesis is controlled by the scaling of host metabolism. We find that the time for symptoms to appear is a constant fraction of time to death in all but one disease. Our findings also predict that many population-level attributes of disease dynamics are likely to be expressed as dimensionless quantities that are independent of host body size.Our results show that much variability in host pathogenesis can be described by simple power functions consistent with the scaling of host metabolic rate. Assessing how disease progression is controlled by geometric relationships will be important for future research. To our knowledge this is the first study to report the allometric scaling of host/pathogen interactions
Haemophilus haemolyticus Interaction with Host Cells Is Different to Nontypeable Haemophilus influenzae and Prevents NTHi Association with Epithelial Cells
Nontypeable Haemophilus influenzae (NTHi) is an opportunistic pathogen that resides in the upper respiratory tract and contributes to a significant burden of respiratory related diseases in children and adults. Haemophilus haemolyticus is a respiratory tract commensal that can be misidentified as NTHi due to high levels of genetic relatedness. There are reports of invasive disease from H. haemolyticus, which further blurs the species boundary with NTHi. To investigate differences in pathogenicity between these species, we optimized an in vitro epithelial cell model to compare the interaction of 10 H. haemolyticus strains with 4 NTHi and 4 H. influenzae-like haemophili. There was inter- and intra-species variability but overall, H. haemolyticus had reduced capacity to attach to and invade nasopharyngeal and bronchoalveolar epithelial cell lines (D562 and A549) within 3 h when compared with NTHi. H. haemolyticus was cytotoxic to both cell lines at 24 h, whereas NTHi was not. Nasopharyngeal epithelium challenged with some H. haemolyticus strains released high levels of inflammatory mediators IL-6 and IL-8, whereas NTHi did not elicit an inflammatory response despite higher levels of cell association and invasion. Furthermore, peripheral blood mononuclear cells stimulated with H. haemolyticus or NTHi released similar and high levels of IL-6, IL-8, IL-10, IL-1β, and TNFα when compared with unstimulated cells but only NTHi elicited an IFNγ response. Due to the relatedness of H. haemolyticus and NTHi, we hypothesized that H. haemolyticus may compete with NTHi for colonization of the respiratory tract. We observed that in vitro pre-treatment of epithelial cells with H. haemolyticus significantly reduced NTHi attachment, suggesting interference or competition between the two species is possible and warrants further investigation. In conclusion, H. haemolyticus interacts differently with host cells compared to NTHi, with different immunostimulatory and cytotoxic properties. This study provides an in vitro model for further investigation into the pathogenesis of Haemophilus species and the foundation for exploring whether H. haemolyticus can be used to prevent NTHi disease
- …