176 research outputs found
Second-harmonic generation in silicon waveguides strained by silicon nitride
Silicon photonics meets the electronics requirement of increased speed and bandwidth with on-chip optical networks.
All-optical data management requires nonlinear silicon photonics. In silicon only third-order optical nonlinearities are present
owing to its crystalline inversion symmetry. Introducing a second-order nonlinearity into silicon photonics by proper material
engineering would be highly desirable. It would enable devices for wideband wavelength conversion operating at relatively low
optical powers. Here we show that a sizeable second-order nonlinearity at optical wavelengths is induced in a silicon waveguide
by using a stressing silicon nitride overlayer. We carried out second-harmonic-generation experiments and first-principle
calculations, which both yield large values of strain-induced bulk second-order nonlinear susceptibility, up to 40pm/V at
2.300 nm. We envisage that nonlinear strained silicon could provide a competing platform for a new class of integrated light
sources spanning the near- to mid-infrared spectrum from 1.2 to 10 micron
Transport by molecular motors in the presence of static defects
The transport by molecular motors along cytoskeletal filaments is studied
theoretically in the presence of static defects. The movements of single motors
are described as biased random walks along the filament as well as binding to
and unbinding from the filament. Three basic types of defects are
distinguished, which differ from normal filament sites only in one of the
motors' transition probabilities. Both stepping defects with a reduced
probability for forward steps and unbinding defects with an increased
probability for motor unbinding strongly reduce the velocities and the run
lengths of the motors with increasing defect density. For transport by single
motors, binding defects with a reduced probability for motor binding have a
relatively small effect on the transport properties. For cargo transport by
motors teams, binding defects also change the effective unbinding rate of the
cargo particles and are expected to have a stronger effect.Comment: 20 pages, latex, 7 figures, 1 tabl
Testing the theory of immune selection in cancers that break the rules of transplantation
Modification of cancer cells likely to reduce their immunogenicity, including loss or down-regulation of MHC molecules, is now well documented and has become the main support for the concept of immune surveillance. The evidence that these modifications, in fact, result from selection by the immune system is less clear, since the possibility that they may result from reorganized metabolism associated with proliferation or from cell de-differentiation remains. Here, we (a) survey old and new transplantation experiments that test the possibility of selection and (b) survey how transmissible tumours of dogs and Tasmanian devils provide naturally evolved tests of immune surveillance
Hormonal signaling in cnidarians : do we understand the pathways well enough to know whether they are being disrupted?
Author Posting. © The Author, 2006. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Ecotoxicology 16 (2007): 5-13, doi:10.1007/s10646-006-0121-1.Cnidarians occupy a key evolutionary position as basal metazoans and are ecologically
important as predators, prey and structure-builders. Bioregulatory molecules (e.g.,
amines, peptides and steroids) have been identified in cnidarians, but cnidarian signaling
pathways remain poorly characterized. Cnidarians, especially hydras, are regularly used
in toxicity testing, but few studies have used cnidarians in explicit testing for signal
disruption. Sublethal endpoints developed in cnidarians include budding, regeneration,
gametogenesis, mucus production and larval metamorphosis. Cnidarian genomic
databases, microarrays and other molecular tools are increasingly facilitating mechanistic
investigation of signaling pathways and signal disruption. Elucidation of cnidarian
signaling processes in a comparative context can provide insight into the evolution and
diversification of metazoan bioregulation. Characterizing signaling and signal disruption
in cnidarians may also provide unique opportunities for evaluating risk to valuable
marine resources, such as coral reefs
The consolidation of implicit sequence memory in obstructive sleep apnea
Obstructive Sleep Apnea (OSA) Syndrome is a relatively frequent sleep disorder characterized by disrupted sleep patterns. It is a well-established fact that sleep has beneficial effect on memory consolidation by enhancing neural plasticity. Implicit sequence learning is a prominent component of skill learning. However, the formation and consolidation of this fundamental learning mechanism remains poorly understood in OSA. In the present study we examined the consolidation of different aspects of implicit sequence learning in patients with OSA. We used the Alternating Serial Reaction Time task to measure general skill learning and sequence-specific learning. There were two sessions: a learning phase and a testing phase, separated by a 10-hour offline period with sleep. Our data showed differences in offline changes of general skill learning between the OSA and control group. The control group demonstrated offline improvement from evening to morning, while the OSA group did not. In contrast, we did not observe differences between the groups in offline changes in sequence-specific learning. Our findings suggest that disrupted sleep in OSA differently affects neural circuits involved in the consolidation of sequence learning
Low-Dose Vertical Inhibition of the RAF-MEK-ERK Cascade Causes Apoptotic Death of KRAS Mutant Cancers
We address whether combinations with a pan-RAF inhibitor (RAFi) would be effective in KRAS mutant pancreatic ductal adenocarcinoma (PDAC). Chemical library and CRISPR genetic screens identify combinations causing apoptotic anti-tumor activity. The most potent combination, concurrent inhibition of RAF (RAFi) and ERK (ERKi), is highly synergistic at low doses in cell line, organoid, and rat models of PDAC, whereas each inhibitor alone is only cytostatic. Comprehensive mechanistic signaling studies using reverse phase protein array (RPPA) pathway mapping and RNA sequencing (RNA-seq) show that RAFi/ERKi induced insensitivity to loss of negative feedback and system failures including loss of ERK signaling, FOSL1, and MYC; shutdown of the MYC transcriptome; and induction of mesenchymal-to-epithelial transition. We conclude that low-dose vertical inhibition of the RAF-MEK-ERK cascade is an effective therapeutic strategy for KRAS mutant PDAC.Peer reviewe
Neuroactive substances specifically modulate rhythmic body contractions in the nerveless metazoon Tethya wilhelma (Demospongiae, Porifera)
BACKGROUND: Sponges (Porifera) are nerve- and muscleless metazoa, but display coordinated motor reactions. Therefore, they represent a valuable phylum to investigate coordination systems, which evolved in a hypothetical Urmetazoon prior to the central nervous system (CNS) of later metazoa. We have chosen the contractile and locomotive species Tethya wilhelma (Demospongiae, Hadromerida) as a model system for our research, using quantitative analysis based on digital time lapse imaging. In order to evaluate candidate coordination pathways, we extracorporeally tested a number of chemical messengers, agonists and antagonists known from chemical signalling pathways in animals with CNS. RESULTS: Sponge body contraction of T. wilhelma was induced by caffeine, glycine, serotonine, nitric oxide (NO) and extracellular cyclic adenosine monophosphate (cAMP). The induction by glycine and cAMP followed patterns varying from other substances. Induction by cAMP was delayed, while glycine lead to a bi-phasic contraction response. The frequency of the endogenous contraction rhythm of T. wilhelma was significantly decreased by adrenaline and NO, with the same tendency for cAMP and acetylcholine. In contrast, caffeine and glycine increased the contraction frequency. The endogenous rhythm appeared irregular during application of caffeine, adrenaline, NO and cAMP. Caffeine, glycine and NO attenuated the contraction amplitude. All effects on the endogenous rhythm were neutralised by the washout of the substances from the experimental reactor system. CONCLUSION: Our study demonstrates that a number of chemical messengers, agonists and antagonists induce contraction and/or modulate the endogenous contraction rhythm and amplitude of our nerveless model metazoon T. wilhelma. We conclude that a relatively complex system of chemical messengers regulates the contraction behaviour through auto- and paracrine signalling, which is presented in a hypothetical model. We assume that adrenergic, adenosynergic and glycinergic pathways, as well as pathways based on NO and extracellular cAMP are candidates for the regulation and timing of the endogenous contraction rhythm within pacemaker cells, while GABA, glutamate and serotonine are candidates for the direct coordination of the contractile cells
Pro-inflammatory profile of preeclamptic placental mesenchymal stromal cells: new insights into the etiopathogenesis of preeclampsia.
The objective of the present study was to evaluate whether placental mesenchymal stromal cells (PDMSCs) derived from normal and preeclamptic (PE) chorionic villous tissue presented differences in their cytokines expression profiles. Moreover, we investigated the effects of conditioned media from normal and PE-PDMSCs on the expression of pro-inflammatory Macrophage migration Inhibitory Factor (MIF), Vascular Endothelial Growth Factor (VEGF), soluble FMS-like tyrosine kinase-1 (sFlt-1) and free β-human Chorionic Gonadotropin (βhCG) by normal term villous explants. This information will help to understand whether anomalies in PE-PDMSCs could cause or contribute to the anomalies typical of preeclampsia. METHODS: Chorionic villous PDMSCs were isolated from severe preeclamptic (n = 12) and physiological control term (n = 12) placentae. Control and PE-PDMSCs’s cytokines expression profiles were determined by Cytokine Array. Control and PE-PDMSCs were plated for 72 h and conditioned media (CM) was collected. Physiological villous explants (n = 48) were treated with control or PE-PDMSCs CM for 72 h and processed for mRNA and protein isolation. MIF, VEGF and sFlt-1 mRNA and protein expression were analyzed by Real Time PCR and Western Blot respectively. Free βhCG was assessed by immunofluorescent. RESULTS: Cytokine array showed increased release of pro-inflammatory cytokines by PE relative to control PDMSCs. Physiological explants treated with PE-PDMSCs CM showed significantly increased MIF and sFlt-1 expression relative to untreated and control PDMSCs CM explants. Interestingly, both control and PE-PDMSCs media induced VEGF mRNA increase while only normal PDMSCs media promoted VEGF protein accumulation. PE-PDMSCs CM explants released significantly increased amounts of free βhCG relative to normal PDMSCs CM ones. CONCLUSIONS: Herein, we reported elevated production of pro-inflammatory cytokines by PE-PDMSCs. Importantly, PE PDMSCs induced a PE-like phenotype in physiological villous explants. Our data clearly depict chorionic mesenchymal stromal cells as central players in placental physiopathology, thus opening to new intriguing perspectives for the treatment of human placental-related disorders as preeclampsia
The triggering receptor expressed on myeloid cells (TREM) in inflammatory bowel disease pathogenesis
The Triggering Receptors Expressed on Myeloid cells (TREM) are a family of cell-surface molecules that control inflammation, bone homeostasis, neurological development and blood coagulation. TREM-1 and TREM-2, the best-characterized receptors so far, play divergent roles in several infectious diseases. In the intestine, TREM-1 is highly expressed by macrophages, contributing to inflammatory bowel disease (IBD) pathogenesis. Contrary to current understanding, TREM-2 also promotes inflammation in IBD by fueling dendritic cell functions. This review will focus specifically on recent insights into the role of TREM proteins in IBD development, and discuss opportunities for novel treatment approaches
Non-equilibrium statistical mechanics: From a paradigmatic model to biological transport
Unlike equilibrium statistical mechanics, with its well-established
foundations, a similar widely-accepted framework for non-equilibrium
statistical mechanics (NESM) remains elusive. Here, we review some of the many
recent activities on NESM, focusing on some of the fundamental issues and
general aspects. Using the language of stochastic Markov processes, we
emphasize general properties of the evolution of configurational probabilities,
as described by master equations. Of particular interest are systems in which
the dynamics violate detailed balance, since such systems serve to model a wide
variety of phenomena in nature. We next review two distinct approaches for
investigating such problems. One approach focuses on models sufficiently simple
to allow us to find exact, analytic, non-trivial results. We provide detailed
mathematical analyses of a one-dimensional continuous-time lattice gas, the
totally asymmetric exclusion process (TASEP). It is regarded as a paradigmatic
model for NESM, much like the role the Ising model played for equilibrium
statistical mechanics. It is also the starting point for the second approach,
which attempts to include more realistic ingredients in order to be more
applicable to systems in nature. Restricting ourselves to the area of
biophysics and cellular biology, we review a number of models that are relevant
for transport phenomena. Successes and limitations of these simple models are
also highlighted.Comment: 72 pages, 18 figures, Accepted to: Reports on Progress in Physic
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