241 research outputs found
Counting solutions from finite samplings
We formulate the solution counting problem within the framework of inverse
Ising problem and use fast belief propagation equations to estimate the entropy
whose value provides an estimate on the true one. We test this idea on both
diluted models (random 2-SAT and 3-SAT problems) and fully-connected model
(binary perceptron), and show that when the constraint density is small, this
estimate can be very close to the true value. The information stored by the
salamander retina under the natural movie stimuli can also be estimated and our
result is consistent with that obtained by Monte Carlo method. Of particular
significance is sizes of other metastable states for this real neuronal network
are predicted.Comment: 9 pages, 4 figures and 1 table, further discussions adde
Alignment of Carbon Nanotubes Comprising Magnetically Sensitive Metal Oxides in Nanofluids
The present invention is a nanoparticle mixture or suspension or nanofluid comprising nonmagnetically sensitive nanoparticles, magnetically sensitive nanoparticles, and surfactant(s). The present invention also relates to methods of preparing and using the same
Suppression of Grain Boundaries in Graphene Growth on Superstructured Mn-Cu(111) Surface
As undesirable defects, grain boundaries (GBs) are widespread in epitaxial
graphene using existing growth methods on metal substrates. Employing density
functional theory calculations, we first identify that the misorientations of
carbon islands nucleated on a Cu(111) surface lead to the formation of GBs as
the islands coalesce. We then propose a two-step kinetic pathway to effectively
suppress the formation of GBs. In the first step, large aromatic hydrocarbon
molecules are deposited onto a superstructured Cu-Mn
alloyed surface to seed the initial carbon clusters of a single orientation; in
the second step, the seeded islands are enlarged through normal chemical vapor
deposition of methane to form a complete graphene sheet. The present approach
promises to overcome a standing obstacle in large scale single-crystal graphene
fabrication
Determining the electronic performance limitations in top-down fabricated Si nanowires with mean widths down to 4 nm
Silicon nanowires have been patterned with mean widths down to 4 nm using top-down lithography and dry etching. Performance-limiting scattering processes have been measured directly which provide new insight into the electronic conduction mechanisms within the nanowires. Results demonstrate a transition from 3-dimensional (3D) to 2D and then 1D as the nanowire mean widths are reduced from 12 to 4 nm. The importance of high quality surface passivation is demonstrated by a lack of significant donor deactivation, resulting in neutral impurity scattering ultimately limiting the electronic performance. The results indicate the important parameters requiring optimization when fabricating nanowires with atomic dimensions
Low escape-rate genome safeguards with minimal molecular perturbation of Saccharomyces cerevisiae
As the use of synthetic biology both in industry and in academia grows, there is an increasing need to ensure biocontainment. There is growing interest in engineering bacterial- and yeast-based safeguard (SG) strains. First-generation SGs were based on metabolic auxotrophy; however, the risk of cross-feeding and the cost of growth-controlling nutrients led researchers to look for other avenues. Recent strategies include bacteria engineered to be dependent on nonnatural amino acids and yeast SG strains that have both transcriptional- and recombinational-based biocontainment. We describe improving yeast Saccharomyces cerevisiae-based transcriptional SG strains, which have near-WT fitness, the lowest possible escape rate, and nanomolar ligands controlling growth. We screened a library of essential genes, as well as the best-performing promoter and terminators, yielding the best SG strains in yeast. The best constructs were fine-tuned, resulting in two tightly controlled inducible systems. In addition, for potential use in the prevention of industrial espionage, we screened an array of possible "decoy molecules" that can be used to mask any proprietary supplement to the SG strain, with minimal effect on strain fitness
Notch regulates Th17 differentiation and controls trafficking of IL-17 and metabolic regulators within Th17 cells in a context-dependent manner
Th17 cells play critical roles in host defense and autoimmunity. Emerging data support a role for Notch signaling in Th17 cell differentiation but whether it is a positive or negative regulator remains unclear. We report here that T cell-specific deletion of Notch receptors enhances Th17 cell differentiation in the gut, with a corresponding increase in IL-17 secretion. An increase in Th17 cell frequency was similarly observed following immunization of T cell specific Notch mutant mice with OVA/CFA. However, in this setting, Th17 cytokine secretion was impaired, and increased intracellular retention of IL-17 was observed. Intracellular IL-17 co-localized with the CD71 iron transporter in the draining lymph node of both control and Notch-deficient Th17 cells. Immunization induced CD71 surface expression in control, but not in Notch-deficient Th17 cells, revealing defective CD71 intracellular transport in absence of Notch signaling. Moreover, Notch receptor deficient Th17 cells had impaired mTORC2 activity. These data reveal a context-dependent impact of Notch on vesicular transport during high metabolic demand suggesting a role for Notch signaling in the bridging of T cell metabolic demands and effector functions. Collectively, our findings indicate a prominent regulatory role for Notch signaling in the fine-tuning of Th17 cell differentiation and effector function
Elevated expression of c-kit in small venous malformations of blue rubber bleb nevus syndrome
The blue rubber bleb nevus syndrome (BRBNS, syn. bean syndrome) is a rare disease
characterized by multiple cutaneous and gastrointestinal venous malformations
associated with severe bleeding. However, the underlying molecular mechanisms
are unknown and no targeted therapeutic approach exists to date. Here we report
the case of a 19-year-old male patient with severe BRBNS in whom we analyzed the
expression of tyrosine kinases frequently involved in tumor development by
immunohistochemistry (vascular endothelial growth factor receptor-2, stem cell
growth factor receptor (c-kit), platelet-derived growth factor
receptor-β, and stem cell tyrosine kinase-1). A prominent expression of
c-kit was detectable in smaller blood vessels, which also showed a moderate
expression of the proliferation marker MIB1. Surprisingly, other growth factor
receptors stained negatively. We therefore conclude that pharmacological
inhibition of the c-kit signaling pathway in cavernous hemangiomas by selective
kinase inhibitors may offer options in the treatment of BRBNS patients
Phospho-regulation, nucleotide binding and ion access control in potassium-chloride cotransporters
Potassium-coupled chloride transporters (KCCs) play crucial roles
in regulating cell volume and intracellular chloride concentration.
They are characteristically inhibited under isotonic conditions via
phospho-regulatory sites located within the cytoplasmic termini.
Decreased inhibitory phosphorylation in response to hypotonic cell
swelling stimulates transport activity, and dysfunction of this
regulatory process has been associated with various human
diseases. Here, we present cryo-EM structures of human KCC3b
and KCC1, revealing structural determinants for phosphoregulation in both N- and C-termini. We show that phosphomimetic KCC3b is arrested in an inward-facing state in which
intracellular ion access is blocked by extensive contacts with the
N-terminus. In another mutant with increased isotonic transport
activity, KCC1D19, this interdomain interaction is absent, likely
due to a unique phospho-regulatory site in the KCC1 N-terminus.
Furthermore, we map additional phosphorylation sites as well as a
previously unknown ATP/ADP-binding pocket in the large Cterminal domain and show enhanced thermal stabilization of
other CCCs by adenine nucleotides. These findings provide fundamentally new insights into the complex regulation of KCCs and
may unlock innovative strategies for drug development
Shp-2 is critical for ERK and metabolic engagement downstream of IL-15 receptor in NK cells
The phosphatase Shp-2 was implicated in NK cell development and functions due to its interaction with NK inhibitory receptors, but its exact role in NK cells is still unclear. Here we show, using mice conditionally deficient for Shp-2 in the NK lineage, that NK cell development and responsiveness are largely unaffected. Instead, we find that Shp-2 serves mainly to enforce NK cell responses to activation by IL-15 and IL-2. Shp-2-deficient NK cells have reduced proliferation and survival when treated with high dose IL-15 or IL-2. Mechanistically, Shp-2 deficiency hampers acute IL-15 stimulation-induced raise in glycolytic and respiration rates, and causes a dramatic defect in ERK activation. Moreover, inhibition of the ERK and mTOR cascades largely phenocopies the defect observed in the absence of Shp-2. Together, our data reveal a critical function of Shp-2 as a molecular nexus bridging acute IL-15 signaling with downstream metabolic burst and NK cell expansion
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