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Find video protocols related to scientific articles indexed in Pubmed.
THE EFFECTS OF THYMOQUINONE AND DOXORUBICIN ON LEUKEMIA AND CARDIOMYOCYTE CELL LINES.
Biomed Sci Instrum
PUBLISHED: 11-19-2014
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Acute Lymphoblastic Leukemia remains the most common cancer for children, and if left untreated is rapidly fatal. The gold standard for treatment of ALL in children is with a class of drugs known as the antracyclines. Long term outcomes following treatment of leukemia with antracylines can result in cardiac abnormalities including arrhythmias, congestive heart failure, myocardial infarction, hypertension and left ventricular failure. Thymoquinone is a natural product that has demonstrated anti-proliferative, anti-inflammatory, anti-cancer, and chemo-protective effects in control trials as well as a reduction in cardiotoxicity in antracyline treated rats. The aims of the study were to determine if thymoqunione could be used to reduce leukemia cell viability without injuring primary cardiomyocyte, and to determine its effects if used in conjunction with a known chemotherapeutic agent. Cellular viability and morphological changes were observed in the, RAW leukemia cells and cardiac myocytes following treatment with thymoquinone, antracyline (doxorubicin), alone and in combination for 24, 48 and 72 hours. The results suggest that thymoquinone treatment in RAW leukemia cells reduced the cell number without altering the morphology, while doxorubicin reduced cell number and induced spindle cell formation and increased cellular damage. Findings also suggest RAW cell apoptosis increased in combination therapy with thymoquinone and doxorubicin. Thymoquinone administered to cardiomyocytes showed similar morphological changes as control over time in culture; whereas doxorubicin treated cells showed evidence of loss of connectivity and disruption of cell membranes. Combination treatment with doxorubicin and thymoquinone demonstrated significant cardiac myocyte survival at concentrations when used alone were able to reduce the leukemia cells. Overall, the data is promising and may provide a treatment regime to protect the heart tissue. Additional work is warrant to understand the mechanisms involved to reduce cardio toxicity by combining thymoquinone with doxorubicin.
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Importance of the DNA "bond" in programmable nanoparticle crystallization.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 10-08-2014
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If a solution of DNA-coated nanoparticles is allowed to crystallize, the thermodynamic structure can be predicted by a set of structural design rules analogous to Pauling's rules for ionic crystallization. The details of the crystallization process, however, have proved more difficult to characterize as they depend on a complex interplay of many factors. Here, we report that this crystallization process is dictated by the individual DNA bonds and that the effect of changing structural or environmental conditions can be understood by considering the effect of these parameters on free oligonucleotides. Specifically, we observed the reorganization of nanoparticle superlattices using time-resolved synchrotron small-angle X-ray scattering in systems with different DNA sequences, salt concentrations, and densities of DNA linkers on the surface of the nanoparticles. The agreement between bulk crystallization and the behavior of free oligonucleotides may bear important consequences for constructing novel classes of crystals and incorporating new interparticle bonds in a rational manner.
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Apertureless Cantilever-Free Pen Arrays for Scanning Photochemical Printing.
Small
PUBLISHED: 07-23-2014
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A novel, apertureless, cantilever-free pen array can be used for dual scanning photochemical and molecular printing. Serial writing with light is enabled by combining self-focusing pyramidal pens with an opaque backing between pens. The elastomeric pens also afford force-tuned illumination and simultaneous delivery of materials and optical energy. These attributes make the technique a promising candidate for maskless high-resolution photopatterning and combinatorial chemistry.
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Capillary bridge rupture in dip-pen nanolithography.
Soft Matter
PUBLISHED: 06-27-2014
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Here, we explore fluid transfer from a nanoscale tip to a surface and elucidate the role of fluid flows in dip-pen nanolithography (DPN) of liquid inks. We find that while fluid transfer in this context is affected by dwell time and tip retraction speed from the substrate, their specific roles are dictated by the contact angle of the ink on the surface. This is shown by two observations: (1) the power law scaling of transferred fluid with dwell time depends on contact angle, and (2) slower retraction speeds result in more transfer on hydrophilic surfaces, but less transfer on hydrophobic surfaces. These trends, coupled with the observation of a transition from quasi-static to dynamic capillary rupture at a capillary number of 6 × 10(-6), show that the transfer process is a competition between surface energy and viscosity. Based on this, we introduce retraction speed as an important parameter in DPN and show that it is possible to print polymer features as small as 14 nm. Further explorations of this kind may provide a useful platform for studying capillary phenomena at the nanoscale.
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Oligonucleotide Flexibility Dictates Crystal Quality in DNA-Programmable Nanoparticle Superlattices.
Adv. Mater. Weinheim
PUBLISHED: 06-09-2014
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The evolution of crystallite size and microstrain in DNA-mediated nanoparticle superlattices is dictated by annealing temperature and the flexibility of the interparticle bonds. This work addresses a major challenge in synthesizing optical metamaterials based upon noble metal nanoparticles by enabling the crystallization of large nanoparticles (100 nm diameter) at high volume fractions (34% metal).
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MYCN is recruited to the RASSF1A promoter but is not critical for DNA hypermethylation in neuroblastoma.
Mol. Carcinog.
PUBLISHED: 05-21-2014
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Tumor suppressor genes such as RASSF1A are often epigenetically repressed by DNA hypermethylation in neuroblastoma, where the MYCN proto-oncogene is frequently amplified. MYC has been shown to associate with DNA methyltransferases, thereby inducing transcriptional repression of target genes, which suggested that MYCN might play a similar mechanistic role in the hypermethylation of tumor suppressor genes in neuroblastoma. This study tested that hypothesis by using co-immunoprecipitation and ChIP to investigate MYCN-DNA methyltransferase interactions, together with MYCN knock-down and over-expression systems to examine the effect of MYCN expression changes on gene methylation, employing both candidate gene and genome-wide assays. We show that MYCN interacts with DNA methyltransferases and is recruited to the promoter region of RASSF1A. However, using four model systems, we showed that long-term silencing of MYCN induces only a small loss of DNA methylation at the RASSF1A promoter in MYCN amplified neuroblastoma cell lines and over-expression of MYCN does not induce any DNA methylation, suggesting that MYCN is not critical for DNA hypermethylation in neuroblastoma.
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Langmuir analysis of nanoparticle polyvalency in DNA-mediated adsorption.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 05-15-2014
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Many nanoparticle adsorption processes are dictated by the collective interactions of surface-bound ligands. These adsorption processes define how nanoparticles interact with biological systems and enable the assembly of nanoparticle-based materials and devices. Herein, we present an approach for quantifying nanoparticle adsorption thermodynamics in a manner that satisfies the assumptions of the Langmuir model. Using this approach, we study the DNA-mediated adsorption of polyvalent anisotropic nanoparticles on surfaces and explore how deviations from model assumptions influence adsorption thermodynamics. Importantly, when combined with a solution-based van't?Hoff analysis, we find that polyvalency plays a more important role as the individual interactions become weaker. Furthermore, we find that the free energy of anisotropic nanoparticle adsorption is consistent across multiple shapes and sizes of nanoparticles based on the surface area of the interacting facet.
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Universal noble metal nanoparticle seeds realized through iterative reductive growth and oxidative dissolution reactions.
J. Am. Chem. Soc.
PUBLISHED: 05-15-2014
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Control over nanoparticle shape and size is commonly achieved via a seed-mediated approach, where nanoparticle precursors, or seeds, are hypothesized to act as templates for the heterogeneous nucleation of anisotropic products. Despite the wide variety of shapes that have been produced via this approach, high yield and uniformity have been more difficult to achieve. These shortcomings are attributed to limited structural control and characterization of the initial distribution of seeds. Herein, we report how iterative reductive growth and oxidative dissolution reactions can be used to systematically control seed structural uniformity. Using these reactions, we verify that seed structure dictates anisotropic nanoparticle uniformity and show that iterative seed refinement leads to unprecedented noble metal nanoparticle uniformities and purities for eight different shapes produced from a single seed source. Because of this uniformity, the first nanoparticle optical extinction coefficients for these eight shapes were analytically determined.
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Evaluating the effects of scaling up on the performance of bioelectrochemical systems using a technical scale microbial electrolysis cell.
Bioresour. Technol.
PUBLISHED: 03-31-2014
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This study focuses on the challenges of the scaling up process of bioelectrochemical systems on the example of a technical scale microbial electrolysis cell referred to as the "prototype". Anodically treating real wastewater and operated in continuous mode at a hydraulic retention time of 1.23 d with an average chemical oxygen demand (COD)-loading rate of 0.5 g O2 d(-1) L Reactor(-1) the prototype on average showed COD removal efficiency of 67% with effluent concentrations of 210 mg O2 L(-1) and an ammonium elimination rate of 17.8 ± 3.9 mg Nd(-1) L Reactor(-1) resulting in effluent concentrations of 30.7 ± 3.7 mg NL(-1) with a removal efficiency of 40% at a current generation of 72 ?A cm(-2) and Coulomb efficiency of 11%. A model is described as a method for comparing conventional and BES based technology using the above mentioned criteria and balancing them against the respective loading rates.
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Shape-selective deposition and assembly of anisotropic nanoparticles.
Nano Lett.
PUBLISHED: 03-24-2014
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We report the large-area assembly of anisotropic gold nanoparticles into lithographically defined templates with control over their angular position using a capillary force-based approach. We elucidate the role of the geometry of the templates in the assembly of anisotropic nanoparticles consisting of different shapes and sizes. These insights allow us to design templates that immobilize individual triangular nanoprisms and concave nanocubes in a shape-selective manner and filter undesired impurity particles from a mixture of triangular prisms and other polyhedra. Furthermore, by studying the assembly of two particles in the same template, we elucidate the importance of interparticle forces in this method. These advances allow for the construction of face-to-face and edge-to-edge nanocube dimers as well as triangular nanoprism bowtie antennas. As an example of the fundamental studies enabled by this assembly method, we investigate the surface-enhanced Raman scattering (SERS) of face-to-face concave cube dimers both experimentally and computationally and reveal a strong polarization dependence of the local field enhancement.
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Distinct lineage-dependent structural and functional organization of the hippocampus.
Cell
PUBLISHED: 02-21-2014
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The hippocampus, as part of the cerebral cortex, is essential for memory formation and spatial navigation. Although it has been extensively studied, especially as a model system for neurophysiology, the cellular processes involved in constructing and organizing the hippocampus remain largely unclear. Here, we show that clonally related excitatory neurons in the developing hippocampus are progressively organized into discrete horizontal, but not vertical, clusters in the stratum pyramidale, as revealed by both cell-type-specific retroviral labeling and mosaic analysis with double markers (MADM). Moreover, distinct from those in the neocortex, sister excitatory neurons in the cornu ammonis 1 region of the hippocampus rarely develop electrical or chemical synapses with each other. Instead, they preferentially receive common synaptic input from nearby fast-spiking (FS), but not non-FS, interneurons and exhibit synchronous synaptic activity. These results suggest that shared inhibitory input may specify horizontally clustered sister excitatory neurons as functional units in the hippocampus.
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Combinatorial screening of mesenchymal stem cell adhesion and differentiation using polymer pen lithography.
Methods Cell Biol.
PUBLISHED: 01-21-2014
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The extracellular matrix (ECM) is a complex, spatially inhomogeneous environment that is host to myriad cell-receptor interactions that promote changes in cell behavior. These biological systems can be probed and simulated with engineered surfaces, but doing so demands careful control over the arrangement of ligands. Here, we describe how such surfaces can be fabricated by utilizing polymer pen lithography (PPL), which is a cantilever-free scanning probe lithographic method that utilizes polymeric pen arrays to generate patterns over large areas. With the advent of PPL, fundamental questions in cell biology can be answered by recapitulating cell-ECM interactions to explore how these interactions lead to changes in cell behavior. Here, we describe an approach for the combinatorial screening of cell adhesion behavior to gain understanding of how ECM protein feature size dictates osteogenic differentiation of mesenchymal stem cells. The technique outlined here is generalizable to other biological systems and can be paired with quantitative analytical methods to probe important processes such as cell polarization, proliferation, signaling, and differentiation.
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Role of absorbed solvent in polymer pen lithography.
J Phys Chem B
PUBLISHED: 12-10-2013
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We report on the dynamic role of solvents in molecular printing and show that material transport can be mediated by both environmental solvent (i.e., humidity) and solvent absorbed in the pen. To explore the transport of materials in the absence of environmental solvent, a hydrophobic polymer was patterned using a polydimethylsiloxane (PDMS) pen array that had been soaked in undecane, a nonpolar solvent that readily absorbs into PDMS. We also explored the patterning of the hydrophilic polymer polyethylene glycol (PEG) and found that, even though PDMS only absorbs trace amounts of water, soaking a PDMS pen array in water enables PEG deposition in completely dry environments for over 2 h. We find that the length of time one can pattern in a dry environment is determined by the availability of absorbed solvent, a relationship that we elucidate by comparing the performance of pens with varying ability to absorb water. Furthermore, a calculation accounting for the dynamics of retained water captures these effects completely, allowing for generalization of this result to other solvents and providing a way to tune the desired solvent retention profile. Taken together, this work explores the subtle and dynamic role of solvent on molecular printing and provides an alternative to strict environmental humidity control for reliable molecular printing.
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Large-area molecular patterning with polymer pen lithography.
Nat Protoc
PUBLISHED: 11-21-2013
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The challenge of constructing surfaces with nanostructured chemical functionality is central to many areas of biology and biotechnology. This protocol describes the steps required for performing molecular printing using polymer pen lithography (PPL), a cantilever-free scanning probe-based technique that can generate sub-100-nm molecular features in a massively parallel fashion. To illustrate how such molecular printing can be used for a variety of biologically relevant applications, we detail the fabrication of the lithographic apparatus and the deposition of two materials, an alkanethiol and a polymer onto a gold and silicon surface, respectively, and show how the present approach can be used to generate nanostructures composed of proteins and metals. Finally, we describe how PPL enables researchers to easily create combinatorial arrays of nanostructures, a powerful approach for high-throughput screening. A typical protocol for fabricating PPL arrays and printing with the arrays takes 48-72 h to complete, including two overnight waiting steps.
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Life satisfaction in people with post-traumatic stress disorder.
J Ment Health
PUBLISHED: 11-08-2013
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Background/Aims There is limited research on the association between post-traumatic stress disorder (PTSD) and life satisfaction in community samples. We set out to investigate levels of life satisfaction and its demographic, trauma related and clinical predictors in a sample of people with PTSD (n ?=? 46). Methods Participants completed a battery of standardised self-report measures including Satisfaction with Life Scale, the PTSD Checklist and The Hospital Anxiety and Depression Scale. Results Our results indicated that people with moderately severe PTSD in the community are likely to experience lower levels of life satisfaction compared with those with other psychiatric conditions or those without any diagnoses. Multivariate analysis revealed that marital status and trauma symptoms were the only significant predictors of life satisfaction. In specific, being married and presenting with less severe posttraumatic symptomatology were both significantly associated with higher levels of life satisfaction in people with PTSD. Conclusions The strong association between traumatic symptomatology and life satisfaction may indicate that routine assessment for life satisfaction or similar positive constructs in people with PTSD, referred for psychological therapies might be useful. Information on positive psychology constructs may facilitate capitalising on clients strengths and not just on pathology.
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Combined Chemical and Physical Encoding with Silk Fibroin-Embedded Nanostructures.
Small
PUBLISHED: 09-09-2013
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Nanostructures spun into regenerated silk fibroin fibers encode physical and chemical information. These materials are composed of Raman enhancing nanoscale structures whose location in a linear array and chemical functionality endow them with a tunable identity or code. These structures remain functional after being electrospun into fibroin fibers and report a unique spectroscopic signature to prove the authenticity of a material through their code and by uniquely linking it to the composition of the host material.
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Chromosome evolution in Neotropical butterflies.
Hereditas
PUBLISHED: 07-20-2013
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We list the chromosome numbers for 65 species of Neotropical Hesperiidae and 104 species or subspecies of Pieridae. In Hesperiidae the tribe Pyrrhopygini have a modal n = 28, Eudaminae and Pyrgini a modal n = 31, while Hesperiinae have n = around 29. Among Pieridae, Coliadinae have a strong modal n = 31 and among Pierinae Anthocharidini are almost fixed for n = 15 while Pierini vary with n = 26 as the most common chromosome number. Dismorphiinae show wide variation. We discuss these results in the context of chromosome numbers of over 1400 Neotropical butterfly species and subspecies derived from about 3000 populations published here and in earlier papers of a series. The overall results show that many Neotropical groups are characterized by karyotype instability with several derived modal numbers or none at all, while almost all taxa of Lepidoptera studied from the other parts of the world have one of n = 29-31 as modal numbers. Possibly chromosome number changes become fixed in the course of speciation driven by biotic interactions. Population subdivision and structuring facilitate karyotype change. Factors that stabilize chromosome numbers include hybridization among species sharing the same number, migration, sexual selection and possibly the distribution of chromosomes within the nucleus.
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A cantilever-free approach to dot-matrix nanoprinting.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 07-16-2013
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Scanning probe lithography (SPL) is a promising candidate approach for desktop nanofabrication, but trade-offs in throughput, cost, and resolution have limited its application. The recent development of cantilever-free scanning probe arrays has allowed researchers to define nanoscale patterns in a low-cost and high-resolution format, but with the limitation that these are duplication tools where each probe in the array creates a copy of a single pattern. Here, we report a cantilever-free SPL architecture that can generate 100 nanometer-scale molecular features using a 2D array of independently actuated probes. To physically actuate a probe, local heating is used to thermally expand the elastomeric film beneath a single probe, bringing it into contact with the patterning surface. Not only is this architecture simple and scalable, but it addresses fundamental limitations of 2D SPL by allowing one to compensate for unavoidable imperfections in the system. This cantilever-free dot-matrix nanoprinting will enable the construction of surfaces with chemical functionality that is tuned across the nano- and macroscales.
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Russell body gastroenteritis: an aberrant manifestation of chronic inflammation in gastrointestinal mucosa.
Case Rep Med
PUBLISHED: 07-08-2013
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First described in 1998, Russell body gastritis is a rare chronic inflammatory condition characterized by abundant intramucosal polyclonal plasma cells, which contain intracytoplasmic eosinophilic globules of immunoglobulins (Russell bodies) that displace the nucleus, with an accompanying chronic inflammatory infiltrate. Russell bodies represent a cellular response to overstimulation of plasma cells, leading to the accumulation of abundant, nondegradable, condensed immunoglobulin in dilated rough endoplasmic reticulum cisternae. Russell body gastritis usually occurs in the gastric antrum, but two cases of Russell body duodenitis have been recently described. Herein, we report an unusual case of Barrett esophagus with prominent lymphoplasmacytic infiltration and Russell bodies, which expands the current spectrum of Russell body gastritis/duodenitis. Given the various anatomic locations in which Russell body gastritis may arise, we suggest that "Russell body gastroenteritis" may be a more appropriate designation for this uncommon reactive condition.
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Insulin-like growth factor binding protein-3 (IGFBP-3) plays a role in the anti-tumorigenic effects of 5-Aza-2-deoxycytidine (AZA) in breast cancer cells.
Exp. Cell Res.
PUBLISHED: 05-28-2013
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Breast cancer progression is associated with loss of estrogen receptor (ER-?), often due to epigenetic silencing. IGFBP genes have consistently been identified among the most common to be aberrantly methylated in tumours. To understand the impact of losing IGFBP-3 tumour expression via DNA methylation, we treated four breast cancer cell lines (MCF-7, T47D, Hs578T and MDA-MB-231) with a DNA methyltransferase inhibitor, 5-Aza-2-deoxycytidine (AZA) to determine IGFBP-3s role in the effects of AZA on total cell number and survival relative to changes in the ER. AZA induced cell growth inhibition, death and a reduction in the formation of colonies, despite increasing ER-? expression in ER-negative cells but reducing ER-? in ER-positive cells. Regardless of the differential effects on the ER-?, AZA consistently increased the abundance of IGFBP-3 and negating this increase in IGFBP-3 with siRNA reduced the AZA-induced growth inhibition and induction of cell death and virtually negated the AZA-induced inhibition of colony formation. With ER-? positive cells AZA increased the abundance of the tumour suppressor gene, p53 and induced demethylation of the IGFBP-3 promoter, whereas with ER negative cells, AZA epigenetically increased the transcription factor AP2-?, which when silenced prevented the increase in IGFBP-3. IGFBP-3 plays an important role in the anti-tumorigenic effects of AZA on breast cancer cells.
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Desktop nanofabrication with massively multiplexed beam pen lithography.
Nat Commun
PUBLISHED: 05-21-2013
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The development of a lithographic method that can rapidly define nanoscale features across centimetre-scale surfaces has been a long-standing goal for the nanotechnology community. If such a desktop nanofab could be implemented in a low-cost format, it would bring the possibility of point-of-use nanofabrication for rapidly prototyping diverse functional structures. Here we report the development of a new tool that is capable of writing arbitrary patterns composed of diffraction-unlimited features over square centimetre areas that are in registry with existing patterns and nanostructures. Importantly, this instrument is based on components that are inexpensive compared with the combination of state-of-the-art nanofabrication tools that approach its capabilities. This tool can be used to prototype functional electronic devices in a mask-free fashion in addition to providing a unique platform for performing high-throughput nano- to macroscale photochemistry with relevance to biology and medicine.
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The role of viscosity on polymer ink transport in dip-pen nanolithography.
Chem Sci
PUBLISHED: 05-04-2013
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Understanding how ink transfers to a surface in dip-pen nanolithography (DPN) is crucial for designing new ink materials and developing the processes to pattern them. Herein, we investigate the transport of block copolymer inks with varying viscosities, from an atomic force microscope (AFM) tip to a substrate. The size of the patterned block copolymer features was determined to increase with dwell time and decrease with ink viscosity. A mass transfer model is proposed to describe this behaviour, which is fundamentally different from small molecule transport mechanisms due to entanglement of the polymeric chains. The fundamental understanding developed here provides mechanistic insight into the transport of large polymer molecules, and highlights the importance of ink viscosity in controlling the DPN process. Given the ubiquity of polymeric materials in semiconducting nanofabrication, organic electronics, and bioengineering applications, this study could provide an avenue for DPN to expand its role in these fields.
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Hybrid semiconductor core-shell nanowires with tunable plasmonic nanoantennas.
Adv. Mater. Weinheim
PUBLISHED: 03-26-2013
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Multi-segmented nanowires with optically active hybrid core-shell regions are fabricated between two metal nanoantennas. These nanowires generate significant photocurrent under illumination and are solution-dispersible.
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Locally altering the electronic properties of graphene by nanoscopically doping it with Rhodamine 6G.
Nano Lett.
PUBLISHED: 03-19-2013
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We show that Rhodamine 6G (R6G), patterned by dip-pen nanolithography on graphene, can be used to locally n-dope it in a controlled fashion. In addition, we study the transport and assembly properties of R6G on graphene and show that in general the ?-? stacking between the aromatic components of R6G and the underlying graphene drives the assembly of these molecules onto the underlying substrate. However, two distinct transport and assembly behaviors, dependent upon the presence or absence of R6G dimers, have been identified. In particular, at high concentrations of R6G on the tip, dimers are transferred to the substrate and form contiguous and stable lines, while at low concentrations, the R6G is transferred as monomers and forms patchy, unstable, and relatively ill-defined features. Finally, Kelvin probe force microscopy experiments show that the local electrostatic potential of the graphene changes as function of modification with R6G; this behavior is consistent with local molecular doping, highlighting a path for controlling the electronic properties of graphene with nanoscale resolution.
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Survey of patients view on functional split of consultant psychiatrists.
BMC Health Serv Res
PUBLISHED: 02-14-2013
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The functional split model of consultant psychiatrist care for inpatients has been one of the major service redesign that has occurred in the NHS in the last decade. It is unclear if this new split model offers any advantages over the previous sectorised model of working. More recent evidence has suggested that patients, carers and professionals have varied views regarding the benefits of this model. This survey of patients views on models of consultant working is the first in Scotland and we have attempted to include a large sample size. The results suggest that after providing sufficient information on both models, the majority of patients from various Scottish health boards have opted for the traditional sectorised model of working.
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Impact of flavour solvent (propylene glycol or triacetin) on vanillin, 5-(hydroxymethyl)furfural, 2,4-decadienal, 2,4-heptadienal, structural parameters and sensory perception of shortcake biscuits over accelerated shelf life testing.
Food Chem
PUBLISHED: 02-13-2013
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The influence of choice of flavour solvent, propylene glycol (PG) or triacetin (TA), was investigated during accelerated shelf life (ASL) testing of shortcake biscuits. Specifically, the differential effect on the stability of added vanillin, the natural baked marker compound 5-(hydroxymethyl)furfural (HMF), specific markers of oxidative rancidity (2,4-decadienal, 2,4-heptadienal), and the structural parameters of hardness and fracturability. Significantly more HMF was formed during baking of biscuits prepared with TA; these biscuits were also more stable to oxidative degradation and loss of vanillin during ageing than biscuits prepared with PG. Fresh TA biscuits were significantly more brittle than fresh PG biscuits. There was no impact of solvent choice on hardness. Sensory evaluation of hardness, vanilla flavour and oily off-note was tested during ASL testing. There was no significant impact of storage on sensory ratings for either the PG or TA biscuits.
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Plow and ridge nanofabrication.
Small
PUBLISHED: 01-21-2013
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Traditionally, scanning probe lithography tools are limited in resolution by the radius of curvature of the tip used. Herein, an approach is described for patterning the ridge of piled-up polymer that naturally occurs when a scanning probe is pressed against a soft surface. The use of this phenomenon to transfer patterns to hard materials with 20 nm resolution is demonstrated.
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Tuning the spring constant of cantilever-free tip arrays.
Nano Lett.
PUBLISHED: 01-03-2013
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A method to measure and tune the spring constant of tips in a cantilever-free array by adjusting the mechanical properties of the elastomeric layer on which it is based is reported. Using this technique, large-area silicon tip arrays are fabricated with spring constants tuned ranging from 7 to 150 N/m. To illustrate the benefit of utilizing a lower spring constant array, the ability to pattern on a delicate 50 nm silicon nitride substrate is explored.
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Delineating the pathways for the site-directed synthesis of individual nanoparticles on surfaces.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 01-02-2013
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Although nanoparticles with exquisite properties have been synthesized for a variety of applications, their incorporation into functional devices is challenging owing to the difficulty in positioning them at specified sites on surfaces. In contrast with the conventional synthesis-then-assembly paradigm, scanning probe block copolymer lithography can pattern precursor materials embedded in a polymer matrix and synthesize desired nanoparticles on site, offering great promise for incorporating nanoparticles into devices. This technique, however, is extremely limited from a materials standpoint. To develop a materials-general method for synthesizing nanoparticles on surfaces for broader applications, a mechanistic understanding of polymer-mediated nanoparticle formation is crucial. Here, we design a four-step synthetic process that enables independent study of the two most critical steps for synthesizing single nanoparticles on surfaces: phase separation of precursors and particle formation. Using this process, we elucidate the importance of the polymer matrix in the diffusion of metal precursors to form a single nanoparticle and the three pathways that the precursors undergo to form nanoparticles. Based on this mechanistic understanding, the synthetic process is generalized to create metal (Au, Ag, Pt, and Pd), metal oxide (Fe(2)O(3), Co(2)O(3), NiO, and CuO), and alloy (AuAg) nanoparticles. This mechanistic understanding and resulting process represent a major advance in scanning probe lithography as a tool to generate patterns of tailored nanoparticles for integration with solid-state devices.
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Production and organization of neocortical interneurons.
Front Cell Neurosci
PUBLISHED: 01-01-2013
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Inhibitory GABA (?-aminobutyric acid)-ergic interneurons are a vital component of the neocortex responsible for shaping its output through a variety of inhibitions. Consisting of many flavors, interneuron subtypes are predominantly defined by their morphological, physiological, and neurochemical properties that help to determine their functional role within the neocortex. During development, these cells are born in the subpallium where they then tangentially migrate over long distances before being radially positioned to their final location in the cortical laminae. As development progresses into adolescence, these cells mature and form chemical and electrical connections with both glutamatergic excitatory neurons and other interneurons ultimately establishing the cortical network. The production, migration, and organization of these cells are determined by vast array of extrinsic and intrinsic factors that work in concert in order to assemble a proper functioning cortical inhibitory network. Failure of these cells to undergo these processes results in abnormal positioning and cortical function. In humans, this can bring about several neurological disorders including schizophrenia, epilepsy, and autism spectrum disorders. In this article, we will review previous literature that has revealed the framework for interneuron neurogenesis and migratory behavior as well as discuss recent findings that aim to elucidate the spatial and functional organization of interneurons within the neocortex.
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Clonal production and organization of inhibitory interneurons in the neocortex.
Science
PUBLISHED: 10-29-2011
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The neocortex contains excitatory neurons and inhibitory interneurons. Clones of neocortical excitatory neurons originating from the same progenitor cell are spatially organized and contribute to the formation of functional microcircuits. In contrast, relatively little is known about the production and organization of neocortical inhibitory interneurons. We found that neocortical inhibitory interneurons were produced as spatially organized clonal units in the developing ventral telencephalon. Furthermore, clonally related interneurons did not randomly disperse but formed spatially isolated clusters in the neocortex. Individual clonal clusters consisting of interneurons expressing the same or distinct neurochemical markers exhibited clear vertical or horizontal organization. These results suggest that the lineage relationship plays a pivotal role in the organization of inhibitory interneurons in the neocortex.
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Triaxial AFM probes for noncontact trapping and manipulation.
Nano Lett.
PUBLISHED: 07-21-2011
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We show that a triaxial atomic force microscopy probe creates a noncontact trap for a single particle in a fluid via negative dielectrophoresis. A zero in the electric field profile traps the particle above the probe surface, avoiding adhesion, and the repulsive region surrounding the zero pushes other particles away, preventing clustering. Triaxial probes are promising for three-dimensional assembly and for selective imaging of a particular property of a sample using interchangeable functionalized particles.
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A controlled comparison of the effectiveness and efficiency of two psychological therapies for posttraumatic stress disorder: eye movement desensitization and reprocessing vs. emotional freedom techniques.
J. Nerv. Ment. Dis.
PUBLISHED: 06-02-2011
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The present study reports on the first ever controlled comparison between eye movement desensitization and reprocessing (EMDR) and emotional freedom techniques (EFT) for posttraumatic stress disorder. A total of 46 participants were randomized to either EMDR (n = 23) or EFT (n = 23). The participants were assessed at baseline and then reassessed after an 8-week waiting period. Two further blind assessments were conducted at posttreatment and 3-months follow-up. Overall, the results indicated that both interventions produced significant therapeutic gains at posttreatment and follow-up in an equal number of sessions. Similar treatment effect sizes were observed in both treatment groups. Regarding clinical significant changes, a slightly higher proportion of patients in the EMDR group produced substantial clinical changes compared with the EFT group. Given the speculative nature of the theoretical basis of EFT, a dismantling study on the active ingredients of EFT should be subject to future research.
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Coaxial atomic force microscope probes for imaging with dielectrophoresis.
Appl Phys Lett
PUBLISHED: 04-12-2011
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We demonstrate atomic force microscope (AFM) imaging using dielectrophoresis (DEP) with coaxial probes. DEP provides force contrast allowing coaxial probes to image with enhanced spatial resolution. We model a coaxial probe as an electric dipole to provide analytic formulas for DEP between a dipole, dielectric spheres, and a dielectric substrate. AFM images taken of dielectric spheres with and without an applied electric field show the disappearance of artifacts when imaging with DEP. Quantitative agreement between our model and experiment shows that we are imaging with DEP.
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A microfluidic microprocessor: controlling biomimetic containers and cells using hybrid integrated circuit/microfluidic chips.
Lab Chip
PUBLISHED: 09-08-2010
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We present an integrated platform for performing biological and chemical experiments on a chip based on standard CMOS technology. We have developed a hybrid integrated circuit (IC)/microfluidic chip that can simultaneously control thousands of living cells and pL volumes of fluid, enabling a wide variety of chemical and biological tasks. Taking inspiration from cellular biology, phospholipid bilayer vesicles are used as robust picolitre containers for reagents on the chip. The hybrid chip can be programmed to trap, move, and porate individual living cells and vesicles and fuse and deform vesicles using electric fields. The IC spatially patterns electric fields in a microfluidic chamber using 128 × 256 (32,768) 11 × 11 ?m(2) metal pixels, each of which can be individually driven with a radio frequency (RF) voltage. The chips basic functions can be combined in series to perform complex biological and chemical tasks and can be performed in parallel on the chips many pixels for high-throughput operations. The hybrid chip operates in two distinct modes, defined by the frequency of the RF voltage applied to the pixels: Voltages at MHz frequencies are used to trap, move, and deform objects using dielectrophoresis and voltages at frequencies below 1 kHz are used for electroporation and electrofusion. This work represents an important step towards miniaturizing the complex chemical and biological experiments used for diagnostics and research onto automated and inexpensive chips.
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Scaling of transverse nuclear magnetic relaxation due to magnetic nanoparticle aggregation.
J Magn Magn Mater
PUBLISHED: 08-07-2010
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The aggregation of superparamagnetic iron oxide (SPIO) nanoparticles decreases the transverse nuclear magnetic resonance (NMR) relaxation time T2CP of adjacent water molecules measured by a Carr-Purcell-Meiboom-Gill (CPMG) pulse-echo sequence. This effect is commonly used to measure the concentrations of a variety of small molecules. We perform extensive Monte Carlo simulations of water diffusing around SPIO nanoparticle aggregates to determine the relationship between T2CP and details of the aggregate. We find that in the motional averaging regime T2CP scales as a power law with the number N of nanoparticles in an aggregate. The specific scaling is dependent on the fractal dimension d of the aggregates. We find T2CP?N-0.44 for aggregates with d = 2.2, a value typical of diffusion limited aggregation. We also find that in two-nanoparticle systems, T2CP is strongly dependent on the orientation of the two nanoparticles relative to the external magnetic field, which implies that it may be possible to sense the orientation of a two-nanoparticle aggregate. To optimize the sensitivity of SPIO nanoparticle sensors, we propose that it is best to have aggregates with few nanoparticles, close together, measured with long pulse-echo times.
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Analysis and classification of broadband echoes using bio-inspired dolphin pulses.
J. Acoust. Soc. Am.
PUBLISHED: 06-17-2010
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To date most sonars use narrow band pulses and often only the echo envelope is used for object detection and classification. This paper considers the advantages afforded by bio-inspired sonar for object identification and classification through the analysis and the understanding of the broadband echo structure. Using the biomimetic dolphin based sonar system in conjunction with bio-inspired pulses developed from observations of bottlenose dolphins performing object identification tasks, results are presented from experiments carried out in a wave tank and harbor. In these experiments responses of various targets to two different bio-inspired signals are measured and analyzed. The differences in response demonstrate the strong dependency between signal design and echo interpretation. In the simulations and empirical data, the resonance phenomena of these targets cause strong notches and peaks in the echo spectra. With precision in the localization of these peaks and dips of around 1 kHz, the locations are very stable for broadside insonification of the targets and they can be used as features for classification. This leads to the proposal of a broadband classifier which operates by extracting the notch positions in the target echo spectra.
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Prospective isolation of cortical interneuron precursors from mouse embryonic stem cells.
J. Neurosci.
PUBLISHED: 04-02-2010
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Despite their therapeutic potential, progress in generating fully differentiated forebrain neurons from embryonic stem cells (ESCs) has lagged behind that from more caudal regions of the neuraxis. GABAergic interneuron precursors have the remarkable ability to migrate extensively and survive after transplantation into postnatal cortex, making them an attractive candidate for use in cell-based therapy for seizures or other neuropsychiatric disorders. We have modified a mouse ESC line with an Lhx6-GFP reporter construct that allows for the isolation of newly generated cortical interneuron precursors. When transplanted into postnatal cortex, these cells can migrate into the cortical parenchyma, survive for months, and display morphological, neurochemical, and electrophysiological properties characteristic of mature interneurons. This work demonstrates that forebrain neuronal subtypes with complex traits can be generated from embryonic stem cells, and provides a novel approach to the study of cortical interneuron development and to the establishment of cell-based therapies for neurological disease.
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Posttraumatic symptomatology and dissociation in outpatients with chronic posttraumatic stress disorder.
J Trauma Dissociation
PUBLISHED: 01-12-2010
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A number of studies have concluded that dissociative features are common in patients with posttraumatic stress disorder (PTSD). The present study aimed to investigate correlates of dissociation in outpatients with chronic PTSD in Scotland. For the purposes of this study, a total of 102 participants completed the Dissociative Experiences Scale, the Positive and Negative Affect Schedule, and the Clinician-Administered PTSD Scale. Information regarding trauma characteristics (i.e., type and presence of physical injury) was also collected. Regression analysis revealed that increased severity and frequency of posttraumatic symptoms, as measured by the Clinician-Administered PTSD Scale total, was the only significant predictor of dissociation. In line with previous research, our findings indicate that chronic PTSD symptoms could be contributing to the maintenance of clinical dissociation and vice versa in this sample of Scottish outpatients.
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Proposed triaxial atomic force microscope contact-free tweezers for nanoassembly.
Nanotechnology
PUBLISHED: 08-28-2009
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We propose a triaxial atomic force microscope contact-free tweezer (TACT) for the controlled assembly of nanoparticles suspended in a liquid. The TACT overcomes four major challenges faced in nanoassembly, as follows. (1) The TACT can hold and position a single nanoparticle with spatial accuracy smaller than the nanoparticle size (approximately 5 nm). (2) The nanoparticle is held away from the surface of the TACT by negative dielectrophoresis to prevent van der Waals forces from making it stick to the TACT. (3) The TACT holds nanoparticles in a trap that is size-matched to the particle and surrounded by a repulsive region so that it will only trap a single particle at a time. (4) The trap can hold a semiconductor nanoparticle in water with a trapping energy greater than the thermal energy. For example, a 5 nm radius silicon nanoparticle is held with 10 k(B)T at room temperature. We propose methods for using the TACT as a nanoscale pick-and-place tool to assemble semiconductor quantum dots, biological molecules, semiconductor nanowires, and carbon nanotubes.
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High Voltage Dielectrophoretic and Magnetophoretic Hybrid Integrated Circuit / Microfluidic Chip.
J Microelectromech Syst
PUBLISHED: 07-19-2009
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A hybrid integrated circuit (IC) / microfluidic chip is presented that independently and simultaneously traps and moves microscopic objects suspended in fluid using both electric and magnetic fields. This hybrid chip controls the location of dielectric objects, such as living cells and drops of fluid, on a 60 × 61 array of pixels that are 30 × 38 ?m(2) in size, each of which can be individually addressed with a 50 V peak-to-peak, DC to 10 MHz radio frequency voltage. These high voltage pixels produce electric fields above the chips surface with a magnitude , resulting in strong dielectrophoresis (DEP) forces . Underneath the array of DEP pixels there is a magnetic matrix that consists of two perpendicular sets of 60 metal wires running across the chip. Each wire can be sourced with 120 mA to trap and move magnetically susceptible objects using magnetophoresis (MP). The DEP pixel array and magnetic matrix can be used simultaneously to apply forces to microscopic objects, such as living cells or lipid vesicles, that are tagged with magnetic nanoparticles. The capabilities of the hybrid IC / microfluidic chip demonstrated in this paper provide important building blocks for a platform for biological and chemical applications.
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Frequent long-range epigenetic silencing of protocadherin gene clusters on chromosome 5q31 in Wilms tumor.
PLoS Genet.
PUBLISHED: 03-30-2009
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Wilms tumour (WT) is a pediatric tumor of the kidney that arises via failure of the fetal developmental program. The absence of identifiable mutations in the majority of WTs suggests the frequent involvement of epigenetic aberrations in WT. We therefore conducted a genome-wide analysis of promoter hypermethylation in WTs and identified hypermethylation at chromosome 5q31 spanning 800 kilobases (kb) and more than 50 genes. The methylated genes all belong to alpha-, beta-, and gamma-protocadherin (PCDH) gene clusters (Human Genome Organization nomenclature PCDHA@, PCDHB@, and PCDHG@, respectively). This demonstrates that long-range epigenetic silencing (LRES) occurs in developmental tumors as well as in adult tumors. Bisulfite polymerase chain reaction analysis showed that PCDH hypermethylation is a frequent event found in all Wilms tumor subtypes. Hypermethylation is concordant with reduced PCDH expression in tumors. WT precursor lesions showed no PCDH hypermethylation, suggesting that de novo PCDH hypermethylation occurs during malignant progression. Discrete boundaries of the PCDH domain are delimited by abrupt changes in histone modifications; unmethylated genes flanking the LRES are associated with permissive marks which are absent from methylated genes within the domain. Silenced genes are marked with non-permissive histone 3 lysine 9 dimethylation. Expression analysis of embryonic murine kidney and differentiating rat metanephric mesenchymal cells demonstrates that Pcdh expression is developmentally regulated and that Pcdhg@ genes are expressed in blastemal cells. Importantly, we show that PCDHs negatively regulate canonical Wnt signalling, as short-interfering RNA-induced reduction of PCDHG@ encoded proteins leads to elevated beta-catenin protein, increased beta-catenin/T-cell factor (TCF) reporter activity, and induction of Wnt target genes. Conversely, over-expression of PCDHs suppresses beta-catenin/TCF-reporter activity and also inhibits colony formation and growth of cancer cells in soft agar. Thus PCDHs are candidate tumor suppressors that modulate regulatory pathways critical in development and disease, such as canonical Wnt signaling.
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Microwave dielectric heating of drops in microfluidic devices.
Lab Chip
PUBLISHED: 03-19-2009
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We present a technique to locally and rapidly heat water drops in microfluidic devices with microwave dielectric heating. Water absorbs microwave power more efficiently than polymers, glass, and oils due to its permanent molecular dipole moment that has large dielectric loss at GHz frequencies. The relevant heat capacity of the system is a single thermally isolated picolitre-scale drop of water, enabling very fast thermal cycling. We demonstrate microwave dielectric heating in a microfluidic device that integrates a flow-focusing drop maker, drop splitters, and metal electrodes to locally deliver microwave power from an inexpensive, commercially available 3.0 GHz source and amplifier. The temperature change of the drops is measured by observing the temperature dependent fluorescence intensity of cadmium selenide nanocrystals suspended in the water drops. We demonstrate characteristic heating times as short as 15 ms to steady-state temperature changes as large as 30 degrees C above the base temperature of the microfluidic device. Many common biological and chemical applications require rapid and local control of temperature and can benefit from this new technique.
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Vividness of mental imagery in Posttraumatic Stress Disorder (PTSD): the role of depression.
J Behav Ther Exp Psychiatry
PUBLISHED: 01-06-2009
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The present study aimed to investigate demographics, trauma variables, PTSD symptomatology, co-morbid psychopathology, dissociation and personality variables as correlates of vividness of imagery (i.e. general ability to imagine objects) in people with PTSD. Participants were 98 outpatients with PTSD who completed a number of self- and assessor-rated measures. Vividness of imagery was assessed using the Betts Questionnaire Upon Imagery (QMI). Regression analysis showed that the only statistically significant predictor of mental imagery was depression, as measured by the Montgomery Asberg Depression Rating Scale (MADRS). The implications of these results for the management of depression in people with PTSD are discussed.
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The importance of cantilever dynamics in the interpretation of Kelvin probe force microscopy.
J Appl Phys
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A realistic interpretation of the measured contact potential difference (CPD) in Kelvin probe force microscopy (KPFM) is crucial in order to extract meaningful information about the sample. Central to this interpretation is a method to include contributions from the macroscopic cantilever arm, as well as the cone and sharp tip of a KPFM probe. Here, three models of the electrostatic interaction between a KPFM probe and a sample are tested through an electrostatic simulation and compared with experiment. In contrast with previous studies that treat the KPFM cantilever as a rigid object, we allow the cantilever to bend and rotate; accounting for cantilever bending provides the closest agreement between theory and experiment. We demonstrate that cantilever dynamics play a major role in CPD measurements and provide a simulation technique to explore this phenomenon.
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Multifunctional cantilever-free scanning probe arrays coated with multilayer graphene.
Proc. Natl. Acad. Sci. U.S.A.
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Scanning probe instruments have expanded beyond their traditional role as imaging or "reading" tools and are now routinely used for "writing." Although a variety of scanning probe lithography techniques are available, each one imposes different requirements on the types of probes that must be used. Additionally, throughput is a major concern for serial writing techniques, so for a scanning probe lithography technique to become widely applied, there needs to be a reasonable path toward a scalable architecture. Here, we use a multilayer graphene coating method to create multifunctional massively parallel probe arrays that have wear-resistant tips of uncompromised sharpness and high electrical and thermal conductivities. The optical transparency and mechanical flexibility of graphene allow this procedure to be used for coating exceptionally large, cantilever-free arrays that can pattern with electrochemical desorption and thermal, in addition to conventional, dip-pen nanolithography.
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The various faces of autoimmune endocrinopathies: non-tumoral hypergastrinemia in a patient with lymphocytic colitis and chronic autoimmune gastritis.
Exp. Mol. Pathol.
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Serum gastrin levels exceeding 1000pg/ml (normal, <100) usually raise the suspicion for a neuroendocrine tumor (NET) that secretes gastrin. Rarely, such elevated gastrin levels are seen in patients with pernicious anemia which most commonly is associated with autoimmune gastritis (AG). AG can occur concomitantly with other autoimmune disorders including lymphocytic colitis (LC). Gastrin stimulates enterochromaffin-like cells which increase histamine secretion. Histamine excess can cause diarrhea as can bacterial overgrowth or LC. We present a 57-year-old woman with diarrhea, sporadic epigastric pain, and bloating. She also had a history of interstitial cystitis and took pentosan polysulfate and cetirizine. She had no history of ulcers, renal impairment or carcinoid syndrome. Fasting serum gastrin was 1846pg/ml. Esophagoduodenal gastroscopy and biopsies revealed chronic gastritis and a pH of 7 with low stomach acid. Serum gastrin and plasma chromogranin A were suggestive of a gastrinoma or NET. Pernicious anemia was unlikely. Imaging studies did not reveal any tumor. Random colonic biopsy was compatible with LC, possibly explaining her diarrhea, although we also considered excessive histamine from elevated gastrin, bacterial overgrowth, and pentosan polysulfate which can cause diarrhea and be misleading in this setting, pointing to the diagnosis of gastrinoma. At 4year follow-up in 2012, fasting serum gastrin was 1097pg/ml and the patient asymptomatic taking only cetirizine for nasal allergies. This case illustrates that diarrhea may be associated with very high serum gastrin levels in the setting of chronic gastritis, LC, and interstitial cystitis (pentosan use), without clear evidence for a gastrinoma or NET. If no history of ulcers or liver metastases is present in such cases, watchful observation rather than an extensive/invasive and costly search for a NET may be justified. Considering the various forms of polyglandular syndrome, this may represent a variant and we here provide an algorithm for working up such patients, while also reviewing literature on the intertwined relationship between the immune and endocrine systems.
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Control of epigenetic states by WT1 via regulation of de novo DNA methyltransferase 3A.
Hum. Mol. Genet.
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Although tumour suppressor gene hypermethylation is a universal feature of cancer cells, little is known about the necessary molecular triggers. Here, we show that Wilms tumour 1 (WT1), a developmental master regulator that can also act as a tumour suppressor or oncoprotein, transcriptionally regulates the de novo DNA methyltransferase 3A (DNMT3A) and that cellular WT1 levels can influence DNA methylation of gene promoters genome-wide. Specifically, we demonstrate that depletion of WT1 by short-interfering RNAs leads to reduced DNMT3A in Wilms tumour cells and human embryonal kidney-derived cell lines. Chromatin immunoprecipitation assays demonstrate WT1 recruitment to the DNMT3A promoter region and reporter assays confirm that WT1 directly transactivates DNMT3A expression. Consistent with this regulatory role, immunohistochemical analysis shows co-expression of WT1 and DNMT3A proteins in nuclei of blastemal cells in human fetal kidney and Wilms tumours. Using genome-wide promoter methylation arrays, we show that human embryonal kidney cells over-expressing WT1 acquire DNA methylation changes at specific gene promoters where DNMT3A recruitment is increased, with hypermethylation being associated with silencing of gene expression. Elevated DNMT3A is also demonstrated at hypermethylated genes in Wilms tumour cells, including a region of long-range epigenetic silencing. Finally, we show that depletion of WT1 in Wilms tumour cells can lead to reactivation of gene expression from methylated promoters, such as TGFB2, a key modulator of epithelial-mesenchymal transitions. Collectively, our work defines a new regulatory modality for WT1 involving elicitation of epigenetic alterations which is most likely crucial to its functions in development and disease.
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Chromosomal evolution in the South American Riodinidae (Lepidoptera: Papilionoidea).
Hereditas
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We give the haploid chromosome numbers of 173 species or subspecies of Riodinidae as well as of 17 species or subspecies of neotropical Lycaenidae for comparison. The chromosome numbers of riodinids have thus far been very poorly known. We find that their range of variation extends from n =?9 to n =?110 but numbers above n =?31 are rare. While lepidopterans in general have stable chromosome numbers, or variation is limited at most a subfamily or genus, the entire family Riodinidae shows variation within genera, tribes and subfamilies with no single modal number. In particular, a stepwise pattern with chromosome numbers that are about even multiples is seen in several unrelated genera. We propose that this variation is attributable to the small population sizes, fragmented populations with little migration, and the behavior of these butterflies. Small and isolated riodinid populations would allow for inbreeding to take place. Newly arisen chromosomal variants could become fixed and contribute to reproductive isolation and speciation. In contrast to the riodinids, the neotropical Lycaenidae (Theclinae and Polyommatinae) conform to the modal n =?24 that characterizes the family.
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Dispersible surface-enhanced Raman scattering nanosheets.
Adv. Mater. Weinheim
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Ultrathin and flexible silica nanosheets, synthesized with gold nanorod dimers embedded uniformly throughout, can be dispersed in solution and deposited onto arbitrary surfaces. These novel materials conform and maintain the as-synthesized density of dimers, allowing them to be used reliably in labeling and detection applications.
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OWL-based nanomasks for preparing graphene ribbons with sub-10 nm gaps.
Nano Lett.
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We report a simple and highly efficient method for creating graphene nanostructures with gaps that can be controlled on the sub-10 nm length scale by utilizing etch masks comprised of electrochemically synthesized multisegmented metal nanowires. This method involves depositing striped nanowires with Au and Ni segments on a graphene-coated substrate, chemically etching the Ni segments, and using a reactive ion etch to remove the graphene not protected by the remaining Au segments. Graphene nanoribbons with gaps as small as 6 nm are fabricated and characterized with atomic force microscopy, scanning electron microscopy, and Raman spectroscopy. The high level of control afforded by electrochemical synthesis of the nanowires allows us to specify the dimensions of the nanoribbon, as well as the number, location, and size of nanogaps within the nanoribbon. In addition, the generality of this technique is demonstrated by creating silicon nanostructures with nanogaps.
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American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: Part 2--guidance.
Pain Physician
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Part 2 of the guidelines on responsible opioid prescribing provides the following recommendations for initiating and maintaining chronic opioid therapy of 90 days or longer. 1. A) Comprehensive assessment and documentation is recommended before initiating opioid therapy, including documentation of comprehensive history, general medical condition, psychosocial history, psychiatric status, and substance use history. (Evidence: good) B) Despite limited evidence for reliability and accuracy, screening for opioid use is recommended, as it will identify opioid abusers and reduce opioid abuse. (Evidence: limited) C) Prescription monitoring programs must be implemented, as they provide data on patterns of prescription usage, reduce prescription drug abuse or doctor shopping. (Evidence: good to fair) D) Urine drug testing (UDT) must be implemented from initiation along with subsequent adherence monitoring to decrease prescription drug abuse or illicit drug use when patients are in chronic pain management therapy. (Evidence: good) 2. A) Establish appropriate physical diagnosis and psychological diagnosis if available prior to initiating opioid therapy. (Evidence: good) B) Caution must be exercised in ordering various imaging and other evaluations, interpretation and communication with the patient, to avoid increased fear, activity restriction, requests for increased opioids, and maladaptive behaviors. (Evidence: good) C) Stratify patients into one of the 3 risk categories - low, medium, or high risk. D) A pain management consultation, may assist non-pain physicians, if high-dose opioid therapy is utilized. (Evidence: fair) 3. Essential to establish medical necessity prior to initiation or maintenance of opioid therapy. (Evidence: good) 4. Establish treatment goals of opioid therapy with regard to pain relief and improvement in function. (Evidence: good) 5. A) Long-acting opioids in high doses are recommended only in specific circumstances with severe intractable pain that is not amenable to short-acting or moderate doses of long-acting opioids, as there is no significant difference between long-acting and short-acting opioids for their effectiveness or adverse effects. (Evidence: fair) B) The relative and absolute contraindications to opioid use in chronic non-cancer pain must be evaluated including respiratory instability, acute psychiatric instability, uncontrolled suicide risk, active or history of alcohol or substance abuse, confirmed allergy to opioid agents, coadministration of drugs capable of inducing life-limiting drug interaction, concomitant use of benzodiazepines, active diversion of controlled substances, and concomitant use of heavy doses of central nervous system depressants. (Evidence: fair to limited) 6. A robust agreement which is followed by all parties is essential in initiating and maintaining opioid therapy as such agreements reduce overuse, misuse, abuse, and diversion. (Evidence: fair) 7. A) Once medical necessity is established, opioid therapy may be initiated with low doses and short-acting drugs with appropriate monitoring to provide effective relief and avoid side effects. (Evidence: fair for short-term effectiveness, limited for long-term effectiveness) B) Up to 40 mg of morphine equivalent is considered as low dose, 41 to 90 mg of morphine equivalent as a moderate dose, and greater than 91 mg of morphine equivalence as high dose. (Evidence: fair) C) In reference to long-acting opioids, titration must be carried out with caution and overdose and misuse must be avoided. (Evidence: good) 8. A) Methadone is recommended for use in late stages after failure of other opioid therapy and only by clinicians with specific training in the risks and uses. (Evidence: limited) B) Monitoring recommendation for methadone prescription is that an electrocardiogram should be obtained prior to initiation, at 30 days and yearly thereafter. (Evidence: fair) 9. In order to reduce prescription drug abuse and doctor shopping, adherence monitoring by UDT and PMDPs provide evidence that is essential to the identification of those patients who are non-compliant or abusing prescription drugs or illicit drugs. (Evidence: fair) 10. Constipation must be closely monitored and a bowel regimen be initiated as soon as deemed necessary. (Evidence: good) 11. Chronic opioid therapy may be continued, with continuous adherence monitoring, in well-selected populations, in conjunction with or after failure of other modalities of treatments with improvement in physical and functional status and minimal adverse effects. (Evidence: fair).
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Characterization of 17.94, a novel anaplastic Wilms tumor cell line.
Cancer Genet
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Despite considerable advances in understanding the molecular pathogenesis of Wilms tumor (WT), its cell biology is less well understood, partly due to the paucity of established WT cell lines. We report here the establishment of a new anaplastic WT cell line, 17.94, which expressed NCAM, SALL1, and CITED1-phenotypic features expected of metanephric blastema-derived cells. Treatment of 17.94 cells with 12-O-Tetradecanoylphorbol 13-acetate caused morphological changes, which led to reduced NCAM and SALL1 expression, but expression of vimentin was maintained, indicating a potential for stromal differentiation. The 17.94 cell line contained a TP53 mutation, consistent with the anaplastic histology of the original tumor, but lacked mutations in WT1, WTX, or CTNNB1, which are the other genes involved in WT pathogenesis. The 17.94 cells showed no loss of heterozygosity at 7p, 11p, or 16q; however, DNA hypermethylation was detected at several loci, including the H19 differentially methylated region (indicative of loss of imprinting of IGF2 at 11p15) and at the PCDH@ gene clusters at 5q31. The derivation of the 17.94 cell line should help to further dissect the genetic-epigenetic interactions involved in the pathogenesis of WT.
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Preferential electrical coupling regulates neocortical lineage-dependent microcircuit assembly.
Nature
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Radial glial cells are the primary neural progenitor cells in the developing neocortex. Consecutive asymmetric divisions of individual radial glial progenitor cells produce a number of sister excitatory neurons that migrate along the elongated radial glial fibre, resulting in the formation of ontogenetic columns. Moreover, sister excitatory neurons in ontogenetic columns preferentially develop specific chemical synapses with each other rather than with nearby non-siblings. Although these findings provide crucial insight into the emergence of functional columns in the neocortex, little is known about the basis of this lineage-dependent assembly of excitatory neuron microcircuits at single-cell resolution. Here we show that transient electrical coupling between radially aligned sister excitatory neurons regulates the subsequent formation of specific chemical synapses in the neocortex. Multiple-electrode whole-cell recordings showed that sister excitatory neurons preferentially form strong electrical coupling with each other rather than with adjacent non-sister excitatory neurons during early postnatal stages. This preferential coupling allows selective electrical communication between sister excitatory neurons, promoting their action potential generation and synchronous firing. Interestingly, although this electrical communication largely disappears before the appearance of chemical synapses, blockade of the electrical communication impairs the subsequent formation of specific chemical synapses between sister excitatory neurons in ontogenetic columns. These results suggest a strong link between lineage-dependent transient electrical coupling and the assembly of precise excitatory neuron microcircuits in the neocortex.
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High spatial resolution Kelvin probe force microscopy with coaxial probes.
Nanotechnology
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Kelvin probe force microscopy (KPFM) is a widely used technique to measure the local contact potential difference (CPD) between an AFM probe and the sample surface via the electrostatic force. The spatial resolution of KPFM is intrinsically limited by the long range of the electrostatic interaction, which includes contributions from the macroscopic cantilever and the conical tip. Here, we present coaxial AFM probes in which the cantilever and cone are shielded by a conducting shell, confining the tip-sample electrostatic interaction to a small region near the end of the tip. We have developed a technique to measure the true CPD despite the presence of the shell electrode. We find that the behavior of these probes agrees with an electrostatic model of the force, and we observe a factor of five improvement in spatial resolution relative to unshielded probes. Our discussion centers on KPFM, but the field confinement offered by these probes may improve any variant of electrostatic force microscopy.
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DNA demethylation increases sensitivity of neuroblastoma cells to chemotherapeutic drugs.
Biochem. Pharmacol.
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Neuroblastoma is a common embryonal malignancy in which high-stage cases have a poor prognosis, often associated with resistance to chemotherapeutic drugs. DNA methylation alterations are frequent in neuroblastoma and can modulate sensitivity to chemotherapeutic drugs in other cancers, suggesting that manipulation of epigenetic modifications could provide novel treatment strategies for neuroblastoma. We evaluated neuroblastoma cell lines for DNA demethylation induced by 5-Aza-2-deoxycytidine, using genome-wide and gene-specific assays. Cytotoxic effects of chemotherapeutic agents (cisplatin, doxorubicin and etoposide), with and without 5-Aza-2-deoxycytidine, were determined by morphological and biochemical apoptosis assays. We observed that the extent of genome-wide DNA demethylation induced by 5-Aza-2-deoxycytidine varied between cell lines and was associated with expression differences of genes involved in the uptake and metabolism of 5-Aza-2-deoxycytidine. Treatment of neuroblastoma cells with a combination of chemotherapeutic drugs and 5-Aza-2-deoxycytidine significantly increased the levels of apoptosis induced by cisplatin, doxorubicin and etoposide, compared to treatment with chemotherapeutic drugs alone. The variable demethylation of cell lines in response to 5-Aza-2-deoxycytidine suggests that epigenetic modifiers need to be targeted to suitably susceptible tumours for maximum therapeutic benefit. Epigenetic modifiers, such as 5-Aza-2-deoxycytidine, could be used in combination with chemotherapeutic drugs to enhance their cytotoxicity, providing more effective treatment options for chemoresistant neuroblastomas.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.