Electronic structure of monolayer and bilayer black phosphorus with charged defects

We use an atomistic approach to study the electronic properties of monolayer and bilayer black phosphorus in the vicinity of a charged defect. In particular, we combine screened defect potentials obtained from first-principles linear response theory with large-scale tight-binding simulations to calculate the wave functions and energies of bound acceptor and donor states. As a consequence of the anisotropic band structure, the defect states in these systems form distorted hydrogenic orbitals with a different ordering from that in isotropic materials. For the monolayer, we study the dependence of the binding energies of charged adsorbates on the defect height and the dielectric constant of a substrate in an experimental setup. We also compare our results with an anisotropic effective mass model and find quantitative and qualitative differences when the charged defect is close to the black phosphorus or when the screening from the substrate is weak. For the bilayer, we compare results for charged adsorbates and charged intercalants and find that intercalants induce more prominent secondary peaks in the local density of states because they interact strongly with electronic states on both layers. These insights can be directly tested in scanning tunneling spectroscopy measurements and enable a detailed understanding of the role of Coulomb impurities in electronic devices

Optical properties of charged defects in monolayer MoS₂

We present theoretical calculations of the optical spectrum of monolayer MoS2 with a charged defect. In particular, we solve the Bethe–Salpeter equation based on an atomistic tight-binding model of the MoS2 electronic structure which allows calculations for large supercells. The defect is modelled as a point charge whose potential is screened by the MoS2 electrons. We find that the defect gives rise to new peaks in the optical spectrum approximately 100–200 meV below the first free exciton peak. These peaks arise from transitions involving in-gap bound states induced by the charged defect. Our findings are in good agreement with experimental measurements

Patch-based models for visual object classes

This thesis concerns models for visual object classes that exhibit a reasonable amount of regularity, such as faces, pedestrians, cells and human brains. Such models are useful for making “within-object” inferences such as determining their individual characteristics and establishing their identity. For example, the model could be used to predict the identity of a face, the pose of a pedestrian or the phenotype of a cell and segment parts of a human brain. Existing object modelling techniques have several limitations. First, most current methods have targeted the above tasks individually using object specific representations; therefore, they cannot be applied to other problems without major alterations. Second, most methods have been designed to work with small databases which do not contain the variations in pose, illumination, occlusion and background clutter seen in ‘real world’ images. Consequently, many existing algorithms fail when tested on unconstrained databases. Finally, the complexity of the training procedure in these methods makes it impractical to use large datasets. In this thesis, we investigate patch-based models for object classes. Our models are capable of exploiting very large databases of objects captured in uncontrolled environments. We represent the test image with a regular grid of patches from a library of images of the same object. All the domain specific information is held in this library: we use one set of images of the object to help draw inferences about others. In each experimental chapter we investigate a different within-object inference task. In particular we develop models for classification, regression, semantic segmentation and identity recognition. In each task, we achieve results that are comparable to or better than the state of the art. We conclude that patch-based representation can be successfully used for the above tasks and shows promise for other applications such as generation and localization

Serotonin and hallucinogens

This brief review traces the serotonin (5-HT) hypothesis of the action of hallucinogenic drugs from the early 1950s to the present day. There is now converging evidence from biochemical, electrophysiological, and behavioral studies that the two major classes of psychedelic hallucinogens, the indoleamines (e.g., LSD) and the phenethylamines (e.g., mescaline), have a common site of action as partial agonists at 5-HT 2A and other 5-HT 2 receptors in the central nervous system. The noradrenergic locus coeruleus and the cerebral cortex are among the regions where hallucinogens have prominent effects through their actions upon a 5-HT The accidental discovery in 1943 of the hallucinogenic properties of the synthetic ergoline compound LSD (dlysergic acid diethylamide) by the chemist Albert Hoffman is well known. Five years later, in 1948, serotonin (later determined to be 5-hydroxytryptamine or 5-HT) was found in bovine blood serum NEURONAL ACTIONS OF HALLUCINOGENIC DRUGS Effects of Hallucinogens on 5-HT Neurons of the Raphe Nuclei The identification of 5-HT as a neurotransmitter was not achieved until the mid-1960s, when monoaminergic neuronal pathways in the brain were discovered and mapped by histochemical fluorescence methods (Dähl-strom and Fuxe 1964). These maps, which revealed that 5-HT neuronal cell bodies were clustered in the raphe nuclei of the brainstem, provided the basis for singlecell electrophysiological recordings from identified 5-HT neurons. LSD was found to have a potent inhibitory effect upon the tonically firing 5-HT neurons of the dorsal raphe nucleus In subsequent years, the delineation of multiple 5-HT receptor subtypes by radiolabeled ligand binding and molecular methods (see Affinity for 5-HT 2 Receptors Correlates with Hallucinogenic Potency Glennon, Titeler, and their colleagues showed that there is an excellent correlation between the affinity of both indoleamine and phenethylamine hallucinogens for 5-HT 2 receptors and hallucinogenic potency in humans Actions at 5-HT 2C receptors, which have been associated with anxiogenic responses Hallucinogens Enhance Sensory Responses in the Locus Coeruleus via 5-HT 2A Receptors The locus coeruleus (LC) consists of two dense clusters of noradrenergic neurons located bilaterally in the upper pons at the lateral border of the 4th ventricle. The LC, which projects diffusely to virtually all regions of the neuraxis, receives an extraordinary convergence of somatic, visceral, and other sensory inputs from all regions of the body, has been likened to a novelty detector for salient external stimuli (Aston-Jones and Bloom 1981; Cedarbaum and Aghajanian 1978). In this context, it is of interest that the systemic administration of LSD, mescaline, or other psychedelic hallucinogens in anesthetized rats, although decreasing spontaneous activity, produces a paradoxical facilitation of the activation of LC neurons by sensory stimuli (Aghajanian 1980; Rasmussen and Aghajanian 1986); this effect is not through a direct action on LC cell bodies, because it cannot be mimicked by the local, microiontophoretic application of the drugs. The effects of hallucinogens on LC neurons can be reversed by low intravenous doses of selective 5-HT 2 antagonists, such as ritanserin (Rasmussen and Aghajanian 1986). Antipsychotic drugs are also able to reverse the actions of hallucinogens in the locus coeruleus at doses correlating with their affinity for 5-HT 2A but not dopamine and adrenergic receptors Because the effects of systemically administered hallucinogens are through an activation of afferent inputs rather than through a direct action upon LC cell bodies, the LC itself cannot be used as a model for studying the direct cellular actions of hallucinogens. Nevertheless, the effects of the hallucinogens upon the LC are of interest, because this nucleus receives such an extraordinarily widespread convergence of sensory information, both somatosensory and visceral, relaying this information to virtually all other parts of the neuraxis, including the cerebral cortex. 5-HT 2A Receptors Enhance Glutamate Release in Neocortex The ubiquitous effects of hallucinogens on such complex processes as cognition, perception, and mood suggest the involvement of the cerebral cortex. The direct, postsynaptic effect of 5-HT in the cortex are variable: depolarization, hyperpolarization, or no change, depending upon whether the effects of excitatory 5-HT 2 receptors or inhibitory 5-HT 1A receptors are predominant in any given layer V pyramidal cell Whole-cell patch clamp recordings have demonstrated that 5-HT induces a small, but significant, increase in the amplitude of spontaneous EPSCs, an effect that may involve a postsynaptic amplification mechanism (Aghajanian and Marek 1997). Such a postsynaptic effect is consistent with the finding of a high density of 5-HT 2A receptor immunoreactivity in the apical dendrites of cortical pyramidal cells (Jakab and GoldmanRakic 1998; A Focal Mechanism for 5-HT 2A -Induced Glutamate Release onto Apical Dendrites of Layer V Pyramidal Cells A novel mechanism, independent of impulse flow, seems to be involved in the increase in glutamate release induced by 5-HT 2A receptor activation. Blockade of 5-HT-induced EPSCs by bath application of the fast sodium channel blocker tetrodotoxin (TTX) or perfusion of the slice with a solution containing no added calcium ("0" calcium) would generally suggest that 5-HT had activated glutamatergic cells in the slice, leading to an impulse-flow-dependent release of glutamate. Several lines of evidence argue against this conventional interpretation. First, we rarely found any neurons induced to fire by bath application of 5-HT (unlike our experience in the piriform cortex, where we readily found GABAergic interneurons excited by 5-HT). Second, none of the pyramidal cells (a potential source of intracortical excitatory inputs) in our sample were depolarized by 5-HT sufficiently to reach threshold for firing. Third, EPSCs could be induced by the microiontophoresis of 5-HT onto the apical dendrites of layer V pyramidal cells, but no cell firing was detected while recording extracellularly through the microiontophoretic electrod

Resonant and bound states of charged defects in two-dimensional semiconductors

A detailed understanding of charged defects in two-dimensional semiconductors is needed for the development of ultrathin electronic devices. Here, we study negatively charged acceptor impurities in monolayer WS2 using a combination of scanning tunneling spectroscopy and large-scale atomistic electronic structure calculations. We observe several localized defect states of hydrogenic wave function character in the vicinity of the valence band edge. Some of these defect states are bound, while others are resonant. The resonant states result from the multivalley valence band structure of WS2, whereby localized states originating from the secondary valence band maximum at Γ hybridize with continuum states from the primary valence band maximum at K/K′. Resonant states have important consequences for electron transport as they can trap mobile carriers for several tens of picoseconds

Encyclopedia of psychopharmacology

Definition of microiontophoresis and related methods as found in the Encyclopedia of Psychopharmacology.peer-reviewe

Endothelial cell junctions and the regulation of vascular permeability and leukocyte transmigration

The endothelial lining of the vasculature forms the physical barrier between the blood and underlying tissues. Junctions between adjacent endothelial cells are dynamically modulated to sustain vascular homeostasis and to support the transendothelial migration of leukocytes during inflammation. A variety of factors initiate intracellular signaling pathways which regulate the opening and resealing of junctional complexes. This review focuses on three primary signaling pathways initiated within endothelial cells by the binding of vasoactive factors and leukocyte adhesion: Rho GTPases, reactive oxygen species, and tyrosine phosphorylation of junctional proteins. These pathways converge to regulate junctional permeability, either by affecting the stability of junctional proteins or by modulating their interactions. Although much progress has been made in understanding the relationships of these pathways, many questions remain to be answered. A full understanding of the signaling cascades that affect endothelial junctions should identify novel therapeutic targets for diseases that involve excessive permeability or inappropriate leukocyte infiltration into tissues

Severe reversible cardiac failure after bortezomib treatment combined with chemotherapy in a non-small cell lung cancer patient: a case report

BACKGROUND: Bortezomib (Velcade(®)), a dipeptide boronate proteasome inhibitor, is a novel anti-cancer agent registered for multiple myeloma (MM). It has also shown promising clinical activity in non-small cell lung cancer (NSCLC). Clinical experience with bortezomib so far indicates that overall incidence of cardiac failure associated with bortezomib therapy remains incidental. Nevertheless, acute development or exacerbation of congestive cardiac failure has been associated with bortezomib treatment. CASE PRESENTATION: We present here a case of severe, but reversible, congestive cardiac failure in a lung cancer patient who had no prior cardiac history, after receiving an experimental treatment of bortezomib combined with chemotherapy. Elevated levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), as retrospectively measured in archived serum samples, were suggestive of pre-existent (sub-clinical) left ventricular dysfunction. CONCLUSION: Based on literature, we hypothesize that baseline presence of sub clinical cardiomyopathy, characterized by a dysregulation of the ubiquitin-proteasome system, could have predisposed this patient for a cardiac side effect induced by systemic proteasome inhibition. Patients with heart disease or risk factors for it should be closely monitored when being submitted to treatment with proteasome inhibition therapy such as bortezomib. Caution is therefore warranted in lung cancer patients who often present with cardiac comorbidities

Development of a population-based microsimulation model of osteoarthritis in Canada

OBJECTIVES: The purpose of the study was to develop a population-based simulation model of osteoarthritis (OA) in Canada that can be used to quantify the future health and economic burden of OA under a range of scenarios for changes in the OA risk factors and treatments. In this article we describe the overall structure of the model, sources of data, derivation of key input parameters for the epidemiological component of the model, and preliminary validation studies. DESIGN: We used the Population Health Model (POHEM) platform to develop a stochastic continuous-time microsimulation model of physician-diagnosed OA. Incidence rates were calibrated to agree with administrative data for the province of British Columbia, Canada. The effect of obesity on OA incidence and the impact of OA on health-related quality of life (HRQL) were modeled using Canadian national surveys. RESULTS: Incidence rates of OA in the model increase approximately linearly with age in both sexes between the ages of 50 and 80 and plateau in the very old. In those aged 50+, the rates are substantially higher in women. At baseline, the prevalence of OA is 11.5%, 13.6% in women and 9.3% in men. The OA hazard ratios for obesity are 2.0 in women and 1.7 in men. The effect of OA diagnosis on HRQL, as measured by the Health Utilities Index Mark 3 (HUI3), is to reduce it by 0.10 in women and 0.14 in men. CONCLUSIONS: We describe the development of the first population-based microsimulation model of OA. Strengths of this model include the use of large population databases to derive the key parameters and the application of modern microsimulation technology. Limitations of the model reflect the limitations of administrative and survey data and gaps in the epidemiological and HRQL literature