Euler buckling instability and enhanced current blockade in suspended single-electron transistors

Single-electron transistors embedded in a suspended nanobeam or carbon nanotube may exhibit effects originating from the coupling of the electronic degrees of freedom to the mechanical oscillations of the suspended structure. Here, we investigate theoretically the consequences of a capacitive electromechanical interaction when the supporting beam is brought close to the Euler buckling instability by a lateral compressive strain. Our central result is that the low-bias current blockade, originating from the electromechanical coupling for the classical resonator, is strongly enhanced near the Euler instability. We predict that the bias voltage below which transport is blocked increases by orders of magnitude for typical parameters. This mechanism may make the otherwise elusive classical current blockade experimentally observable.Comment: 15 pages, 10 figures, 1 table; published versio

Discontinuous Euler instability in nanoelectromechanical systems

We investigate nanoelectromechanical systems near mechanical instabilities. We show that quite generally, the interaction between the electronic and the vibronic degrees of freedom can be accounted for essentially exactly when the instability is continuous. We apply our general framework to the Euler buckling instability and find that the interaction between electronic and vibronic degrees of freedom qualitatively affects the mechanical instability, turning it into a discontinuous one in close analogy with tricritical points in the Landau theory of phase transitions.Comment: 4+ pages, 3 figures, published versio

Mechanism of Deep-focus Earthquakes Anomalous Statistics

Analyzing the NEIC-data we have shown that the spatial deep-focus earthquake distribution in the Earth interior over the 1993-2006 is characterized by the clearly defined periodical fine discrete structure with period L=50 km, which is solely generated by earthquakes with magnitude M 3.9 to 5.3 and only on the convergent boundary of plates. To describe the formation of this structure we used the model of complex systems by A. Volynskii and S. Bazhenov. The key property of this model consists in the presence of a rigid coating on a soft substratum. It is shown that in subduction processes the role of a rigid coating plays the slab substance (lithosphere) and the upper mantle acts as a soft substratum. Within the framework of this model we have obtained the estimation of average values of stress in the upper mantle and Young's modulus for the oceanic slab (lithosphere) and upper mantle.Comment: 9 pages, 7 figure

Towards the integration of functions, relations and types in an AI programming language

This paper describes the design and implementation of the programming language PC-Life. This language integrates the functional and the Logic-oriented programming style and feature types supporting inheritance. This combination yields a language particularly suited to knowledge representation, especially for application in computational linguistics

Glycogen Synthase Kinase (GSK) 3β phosphorylates and protects nuclear myosin 1c from proteasome-mediated degradation to activate rDNA transcription in early G1 cells

Nuclear myosin 1c (NM1) mediates RNA polymerase I (pol I) transcription activation and cell cycle progression by facilitating PCAF-mediated H3K9 acetylation, but the molecular mechanism by which NM1 is regulated remains unclear. Here, we report that at early G1 the glycogen synthase kinase (GSK) 3β phosphorylates and stabilizes NM1, allowing for NM1 association with the chromatin. Genomic analysis by ChIP-Seq showed that this mechanism occurs on the rDNA as active GSK3β selectively occupies the gene. ChIP assays and transmission electron microscopy in GSK3β-/- mouse embryonic fibroblasts indicated that at G1 rRNA synthesis is suppressed due to decreased H3K9 acetylation leading to a chromatin state incompatible with transcription. We found that GSK3β directly phosphorylates the endogenous NM1 on a single serine residue (Ser-1020) located within the NM1 C-terminus. In G1 this phosphorylation event stabilizes NM1 and prevents NM1 polyubiquitination by the E3 ligase UBR5 and proteasome-mediated degradation. We conclude that GSK3β-mediated phosphorylation of NM1 is required for pol I transcription activation

Modelling pulmonary microthrombosis coupled to metastasis: distinct effects of thrombogenesis on tumorigenesis

Thrombosis can cause localized ischemia and tissue hypoxia, and both of these are linked to cancer metastasis. Vascular micro-occlusion can occur as a result of arrest of circulating tumour cells in small capillaries, giving rise to microthrombotic events that affect flow, creating localized hypoxic regions. To better understand the association between metastasis and thrombotic events, we generated an experimental strategy whereby we modelled the effect of microvascular occlusion in metastatic efficiency by using inert microbeads to obstruct lung microvasculature before, during and after intravenous tumour cell injection. We found that controlled induction of a specific number of these microthrombotic insults in the lungs caused an increase in expression of the hypoxia-inducible transcription factors (HIFs), a pro-angiogenic and pro-tumorigenic environment, as well as an increase in myeloid cell infiltration. Induction of pulmonary microthrombosis prior to introduction of tumour cells to the lungs had no effect on tumorigenic success, but thrombosis at the time of tumour cell seeding increased number and size of tumours in the lung, and this effect was strikingly more pronounced when the micro-occlusion occurred on the day following introduction of tumour cells. The tumorigenic effect of microbead treatment was seen even when thrombosis was induced five days after tumour cell injection. We also found positive correlations between thrombotic factors and expression of HIF2$\alpha$ in human tumours. The model system described here demonstrates the importance of thrombotic insult in metastatic success and can be used to improve understanding of thrombosis-associated tumorigenesis and its treatment.Research was supported through a Wellcome Trust Principal Research Fellowship to R.S.J. (RG59596). C.B. is supported through a Scientific Fellowship from Breast Cancer Now (2014MaySF275). C.E.E. received a Pump-Priming Grant from the University of Cambridge British Heart Foundation Centre of Research Excellence (RG68639)

Genome-wide analyses implicate 33 loci in heritable dog osteosarcoma, including regulatory variants near CDKN2A/B

Background: Canine osteosarcoma is clinically nearly identical to the human disease, but is common and highly heritable, making genetic dissection feasible. Results: Through genome-wide association analyses in three breeds (greyhounds, Rottweilers, and Irish wolfhounds), we identify 33 inherited risk loci explaining 55% to 85% of phenotype variance in each breed. The greyhound locus exhibiting the strongest association, located 150 kilobases upstream of the genes CDKN2A/B, is also the most rearranged locus in canine osteosarcoma tumors. The top germline candidate variant is found at a >90% frequency in Rottweilers and Irish wolfhounds, and alters an evolutionarily constrained element that we show has strong enhancer activity in human osteosarcoma cells. In all three breeds, osteosarcoma-associated loci and regions of reduced heterozygosity are enriched for genes in pathways connected to bone differentiation and growth. Several pathways, including one of genes regulated by miR124, are also enriched for somatic copy-number changes in tumors. Conclusions: Mapping a complex cancer in multiple dog breeds reveals a polygenic spectrum of germline risk factors pointing to specific pathways as drivers of disease

Resolved Photon Processes

We review the present level of knowledge of the hadronic structure of the photon, as revealed in interactions involving quarks and gluons ``in" the photon. The concept of photon structure functions is introduced in the description of deep--inelastic $e \gamma$ scattering, and existing parametrizations of the parton densities in the photon are reviewed. We then turn to hard \gamp\ and \gaga\ collisions, where we treat the production of jets, heavy quarks, hard (direct) photons, \jpsi\ mesons, and lepton pairs. We also comment on issues that go beyond perturbation theory, including recent attempts at a comprehensive description of both hard and soft \gamp\ and \gaga\ interactions. We conclude with a list of open problems.Comment: LaTeX with equation.sty, 85 pages, 29 figures (not included). A complete PS file of the paper, including figures, can be obtained via anonymous ftp from ftp://phenom.physics.wisc.edu/pub/preprints/1995/madph-95-898.ps.

A Synaptic Mechanism for Temporal Filtering of Visual Signals

The visual system transmits information about fast and slow changes in light intensity through separate neural pathways. We used in vivo imaging to investigate how bipolar cells transmit these signals to the inner retina. We found that the volume of the synaptic terminal is an intrinsic property that contributes to different temporal filters. Individual cells transmit through multiple terminals varying in size, but smaller terminals generate faster and larger calcium transients to trigger vesicle release with higher initial gain, followed by more profound adaptation. Smaller terminals transmitted higher stimulus frequencies more effectively. Modeling global calcium dynamics triggering vesicle release indicated that variations in the volume of presynaptic compartments contribute directly to all these differences in response dynamics. These results indicate how one neuron can transmit different temporal components in the visual signal through synaptic terminals of varying geometries with different adaptational properties