Direct observation of charge inversion by multivalent ions as a universal electrostatic phenomenon

We have directly observed reversal of the polarity of charged surfaces in water upon the addition of tri- and quadrivalent ions using atomic force microscopy. The bulk concentration of multivalent ions at which charge inversion reversibly occurs depends only very weakly on the chemical composition, surface structure, size and lipophilicity of the ions, but is dominated by their valence. These results support the theoretical proposal that spatial correlations between ions are the driving mechanism behind charge inversion.Comment: submitted to PRL, 26-04-2004 Changed the presentation of the theory at the end of the paper. Changed small error in estimate of prefactor ("w" in first version) of equation

Versatile thiol-based reactions for micrometer- and nanometer-scale photopatterning of polymers and biomolecules

Thiol-based chemistry provides a mild and versatile tool for surface functionalization. In the present work, mercaptosilane films were patterned by utilizing UV-induced photo-oxidation of the thiol to yield sulfonate groups via contact and interferometric lithography (IL). These photo-generated sulfonic acid groups were used for selective immobilization of amino-functionalized molecules after activation with triphenylphosphine ditriflate (TPPDF). Moreover, protein-resistant poly(oligoethyleneglycolmethacrylate) (POEGMA) brushes were grown from the intact thiol groups by a surface-induced polymerization reaction. Exploiting both reactions it is possible to couple amino-labelled nitrilotriacetic acid (NH2-NTA) to sulfonate-functionalized regions, enabling the site-specific binding of green fluorescent protein (GFP) to regions defined lithographically, while exploiting the protein-resistant character of POEGMA brushes to prevent non-specific protein adsorption to previously masked areas. The outstanding reactivity of thiol groups paves the way towards novel strategies for the fabrication of complex protein nanopatterns beyond thiol–ene chemistry

One-carbon metabolism in cancer

Cells require one-carbon units for nucleotide synthesis, methylation and reductive metabolism, and these pathways support the high proliferative rate of cancer cells. As such, anti-folates, drugs that target one-carbon metabolism, have long been used in the treatment of cancer. Amino acids, such as serine are a major one-carbon source, and cancer cells are particularly susceptible to deprivation of one-carbon units by serine restriction or inhibition of de novo serine synthesis. Recent work has also begun to decipher the specific pathways and sub-cellular compartments that are important for one-carbon metabolism in cancer cells. In this review we summarise the historical understanding of one-carbon metabolism in cancer, describe the recent findings regarding the generation and usage of one-carbon units and explore possible future therapeutics that could exploit the dependency of cancer cells on one-carbon metabolism

New type of microengine using internal combustion of hydrogen and oxygen

Microsystems become part of everyday life but their application is restricted by lack of strong and fast motors (actuators) converting energy into motion. For example, widespread internal combustion engines cannot be scaled down because combustion reactions are quenched in a small space. Here we present an actuator with the dimensions 100x100x5 um^3 that is using internal combustion of hydrogen and oxygen as part of its working cycle. Water electrolysis driven by short voltage pulses creates an extra pressure of 0.5-4 bar for a time of 100-400 us in a chamber closed by a flexible membrane. When the pulses are switched off this pressure is released even faster allowing production of mechanical work in short cycles. We provide arguments that this unexpectedly fast pressure decrease is due to spontaneous combustion of the gases in the chamber. This actuator is the first step to truly microscopic combustion engines.Comment: Paper and Supplementary Information (to appear in Scientific Reports

Casimir Forces between Spherical Particles in a Critical Fluid and Conformal Invariance

Mesoscopic particles immersed in a critical fluid experience long-range Casimir forces due to critical fluctuations. Using field theoretical methods, we investigate the Casimir interaction between two spherical particles and between a single particle and a planar boundary of the fluid. We exploit the conformal symmetry at the critical point to map both cases onto a highly symmetric geometry where the fluid is bounded by two concentric spheres with radii R_- and R_+. In this geometry the singular part of the free energy F only depends upon the ratio R_-/R_+, and the stress tensor, which we use to calculate F, has a particularly simple form. Different boundary conditions (surface universality classes) are considered, which either break or preserve the order-parameter symmetry. We also consider profiles of thermodynamic densities in the presence of two spheres. Explicit results are presented for an ordinary critical point to leading order in epsilon=4-d and, in the case of preserved symmetry, for the Gaussian model in arbitrary spatial dimension d. Fundamental short-distance properties, such as profile behavior near a surface or the behavior if a sphere has a `small' radius, are discussed and verified. The relevance for colloidal solutions is pointed out.Comment: 37 pages, 2 postscript figures, REVTEX 3.0, published in Phys. Rev. B 51, 13717 (1995

Statistical analysis plan for the LAKANA trial: a cluster-randomized, placebo-controlled, double-blinded, parallel group, three-arm clinical trial testing the effects of mass drug administration of azithromycin on mortality and other outcomes among 1–11-month-old infants in Mali

BACKGROUND:The Large-scale Assessment of the Key health-promoting Activities of two New mass drug administration regimens with Azithromycin (LAKANA) trial in Mali aims to evaluate the efficacy and safety of azithromycin (AZI) mass drug administration (MDA) to 1–11-month-old infants as well as the impact of the intervention on antimicrobial resistance (AMR) and mechanisms of action of azithromycin. To improve the transparency and quality of this clinical trial, we prepared this statistical analysis plan (SAP). METHODS/DESIGN: LAKANA is a cluster randomized trial that aims to address the mortality and health impacts of biannual and quarterly AZI MDA. AZI is given to 1–11-month-old infants in a high-mortality setting where a seasonal malaria chemoprevention (SMC) program is in place. The participating villages are randomly assigned to placebo (control), two-dose AZI (biannual azithromycin-MDA), and four-dose AZI (quarterly azithromycin-MDA) in a 3:4:2 ratio. The primary outcome of the study is mortality among the intention-to-treat population of 1–11-month-old infants. We will evaluate relative risk reduction between the study arms using a mixed-effects Poisson model with random intercepts for villages, using log link function with person-years as an offset variable. We will model outcomes related to secondary objectives of the study using generalized linear models with considerations on clustering. CONCLUSION: The SAP written prior to data collection completion will help avoid reporting bias and data-driven analysis for the primary and secondary aims of the trial. If there are deviations from the analysis methods described here, they will be described and justified in the publications of the trial results. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT04424511. Registered on 11 June 2020

Expression of Luteinizing Hormone Receptor in the Gastrointestinal Tract in Patients with and without Dysmotility

Leuprolide is a gonadotropin-releasing hormone (GnRH) analog which has been shown to reduce symptoms in patients with irritable bowel syndrome (IBS) and chronic intestinal pseudo-obstruction (CIPO). The mechanism is not known, but one hypothesis is through down-modulation of luteinizing hormone (LH) secretion, a hormone whith antagonistic effect on gastrointestinal motility. However, presence of LH receptors in the gastrointestinal tract has never been described. The aim of this study was to find one possible way of action for leuprolide by examining the presence of the LH receptor, and if present, to see whether there was different expression in patients with or without dysmotility. Full-thickness biopsies from the bowel wall of patients with and without severe dysmotility were examined using immunohistochemistry staining. Biopsies showed expression of LH receptors on myenteric neurons and in glial cells, neutrophils, endothelial cells and mast cells. There was no difference in expression between patient groups

Measurement of the adhesion between single melamine-formaldehyde resin microparticles and a flat fabric surface using AFM

An understanding of the adhesion of microparticles, particularly microcapsules, containing a functional component to a fabric surface is crucial to an effective application of this component to the fibre. Fabric surface is very rough; hence, direct measurement of the adhesion of single microparticles to surfaces with a roughness greater than the particle diameter is difficult. In the study reported here, cotton films were generated by dissolving cotton powder in an organic solvent and their properties including surface roughness, thickness, contact angle and purity were characterised. The adhesive forces between single melamineformaldehyde (MF) resin microparticles and a cotton film under ambient conditions with a relative humidity of above 40% were measured using atomic force microscopy; they are considered to be dominated by capillary forces. It was found that there was little adhesion between a MF microparticle and a cotton film in an aqueous solution of sodium dodecylbenzene sulphonate as surfactant. Repulsion between them was observed, but it reduced with increase in the surfactant concentration and decrease in the pH of the solution. The repulsion contributions are thought to originate mainly from electrostatic repulsion. It is believed that the studies on the adhesion between single MF microparticles and a cotton film under ambient conditions or dispersed in surfactant solutions, are beneficial to the attempts to enhance the adhesion of microcapsules to fabric surfaces via a modification of their surface composition and morphology

Photocatalytic Nanolithography of Self-Assembled Monolayers and Proteins

Self-assembled monolayers of alkylthiolates on gold and alkylsilanes on silicon dioxide have been patterned photocatalytically on sub-100 nm length-scales using both apertured near-field and apertureless methods. Apertured lithography was carried out by means of an argon ion laser (364 nm) coupled to cantilever-type near-field probes with a thin film of titania deposited over the aperture. Apertureless lithography was carried out with a helium–cadmium laser (325 nm) to excite titanium-coated, contact-mode atomic force microscope (AFM) probes. This latter approach is readily implementable on any commercial AFM system. Photodegradation occurred in both cases through the localized photocatalytic degradation of the monolayer. For alkanethiols, degradation of one thiol exposed the bare substrate, enabling refunctionalization of the bare gold by a second, contrasting thiol. For alkylsilanes, degradation of the adsorbate molecule provided a facile means for protein patterning. Lines were written in a protein-resistant film formed by the adsorption of oligo(ethylene glycol)-functionalized trichlorosilanes on glass, leading to the formation of sub-100 nm adhesive, aldehyde-functionalized regions. These were derivatized with aminobutylnitrilotriacetic acid, and complexed with Ni2+, enabling the binding of histidine-labeled green fluorescent protein, which yielded bright fluorescence from 70-nm-wide lines that could be imaged clearly in a confocal microscope

Antibodies against gonadotropin-releasing hormone (GnRH) and destruction of enteric neurons in 3 patients suffering from gastrointestinal dysfunction

Background: Antibodies against gonadotropin-releasing hormone (GnRH) and gastrointestinal dysmotility have been found after treatment with GnRH analogues. The aim of this study was to examine the presence of such antibodies in patients with dysmotility not subjected to GnRH treatment and study the anti-GnRH antibody effect on enteric neurons viability in vitro. Methods: Plasma and sera from 3 patients suffering from either enteric dysmotility, irritable bowel syndrome (IBS) or gastroparesis were analysed for C-reactive protein (CRP), and for GnRH antibodies and soluble CD40 by ELISA methods. Primary cultures of small intestinal myenteric neurons were prepared from rats. Neuronal survival was determined after the addition of sera either from the patients with dysmotility, from healthy blood donors, antiserum raised against GnRH or the GnRH analogue buserelin. Only for case 1 a full-thickness bowel wall biopsy was available for immunohistochemical analysis. Results: All 3 patients expressed antibodies against GnRH. The antibody titer correlated to the levels of CD40 (r(s) = 1.000, p < 0.01), but not to CRP. Serum from case 3 with highest anti-GnRH antibody titer, and serum concentrations of sCD40 and CRP, when added to cultured rat myenteric neurons caused remarkable cell death. In contrast, serum from cases 1 and 2 having lower anti-GnRH antibody titer and lower sCD40 levels had no significant effect. Importantly, commercial antibodies against GnRH showed no effect on neuron viability whereas buserelin exerted a protective effect. The full-thickness biopsy from the bowel wall of case 1 showed ganglioneuritis and decrease of GnRH and GnRH receptor. Conclusion: Autoantibodies against GnRH can be detected independently on treatment of GnRH analogue. Whether the generation of the antibody is directly linked to neuron degeneration and chronic gastrointestinal symptoms in patients with intestinal dysmotility, remains to be answered