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International audience; Conventional measurements of kinetic constants currently in use are performed at equilibrium and may require large volumes, especially at low association rate constant k on. If the measurements are made out of equilibrium, the values obtained may be biased by dilution of the sample with the flow of the running buffer. In some applications, the available sample volume can be very critical and requires the developmentof tools to measure kinetic constants with low volumes. In this paper, through ex-perimental, numerical simulation and a modeling combined approach, we propose aSPR-based method that relies on an out-of-equilibrium measurement, using the effectof dilution by flow to its advantage. This new method should have a significant impactin biochemistry and medical research

Gold nanorods (GNRs) can be functionalized with multiple biomolecules allowing efficient cell targeting and delivery into specific cells. However, various issues have to be addressed prior to any clinical applications. They involve controlled biofunctionalization to be able to deliver a known dose of drug by immobilizing a known number of active molecules to GNRs while protecting their surface from degradation. The most widely used synthesis method of GNRs is seed-mediated growth. It requires the use of cetyltrimethylammonium bromide (CTAB) that acts as a strong capping agent stabilizing the colloidal solution. The problem is that not only is CTAB cytotoxic to most cells but it also induces the sequestration of biomolecules in solution during the functionalization steps of GNRs. The presence of CTAB therefore makes it difficult to control the immobilization of biomolecules to GNRs while removing CTAB from the colloidal solution, leading to the aggregation of GNRs. The sequestration effect of ssDNA in solution by CTAB was studied in detail as a function of the CTAB concentration and the nature of the solution (water or buffer) using Forster resonance energy transfer as a detection tool. The conditions in which DNA sequestration did and did not occur could be clearly defined. Using gel electrophoresis, we could demonstrate how strongly the ssDNA sequestration effect in solution impacts the GNR surface biofunctionalization.

Nucleosome assembly and disassembly play a central role in the regulation of gene expression. Here we use PhAST (Photochemical Analysis of Structural Transitions) to monitor at the base pair level, structural alterations induced all along DNA upon histone binding or release. By offering the first consistent, detailed comparison of nucleosome assembly and disassembly in vitro, we are able to reveal similarities and differences between the two processes. We identify multiple intermediate states characterised by specific PhAST signatures; revealing a complexity that goes beyond the known sequential events involving (H3-H4)2 tetramer and H2A-H2B heterodimers. Such signatures localise and quantify the extent of the asymmetry of DNA/histone interactions with respect to the nucleosome dyad. This asymmetry is therefore defined by the localisation and amplitude of the signals. The localisation of the signal is consistent between assembly and disassembly and dictated by the DNA sequence. However, the amplitude component of this asymmetry not only evolves during the assembly and disassembly but does so differently between the two processes.Understanding the regulation of gene expression requires a complete knowledge of nucleosome dynamics. Our unexpected observation of differences between assembly and disassembly opens up new avenues to define the role of the DNA sequence in these processes. Overall, we provide new insights into how the intrinsic properties of DNA are integrated into a holistic mechanism that controls chromatin structure.Statement of SignificanceThis manuscript addresses the question of nucleosome dissociation compares with association. We used PhAST which is a non-intrusive photochemical technique to follow nucleosome dynamics at base pair resolution. We observed structural asymmetry during nucleosome turnover. We also showed for the first time that the process of nucleosome dissociation is not a reversal of association. This asymmetry favours intermediate states involved in chromatin organisation suggesting novel models for the role of nucleosome turnover in the epigenetic regulation of gene expression.

Funding: Royal Society (Grant Number(s): IE160703); Engineering and Physical Sciences Research Council (Grant Number(s): EP/L015110/1). Conventional fluorescence sensing equipment for disease detection is expensive and bulky, restricting access of patients to accurate diagnosis. Organic light-emitting diodes (OLEDs) have the potential to enable compact fluorescence sensing compatible with point-of-care (POC) testing. However, the limited brightness and broad emission spectra of OLEDs can be a challenge for achieving good sensitivity. Here, co-host microcavity OLEDs with narrowed spectra, high conductivity, and high brightness are developed for fluorescence sensing. The OLEDs are driven in pulsed mode for achieving higher brightness and stable light output. To sense the presence of single-stranded DNA (ssDNA), two complementary ssDNA labelled with Cyanine dyes – Cy3 (ssDNA-Cy3) or Cy5 (ssDNA-Cy5) are used to form a Förster resonance energy transfer (FRET) pair when the DNA hybridized. The dye-labelled DNA is then excited by the OLED at the Cy3 excitation wavelength, and the fluorescence is detected at the emission wavelength of Cy5. As a result, the device shows a very high sensitivity that can detect as low as 1 × 10−9 m of ssDNA-Cy5 in fetal bovine serum (FBS). This work shows a simple approach to highly sensitive fluorescence sensing with OLED light sources that is promising for use in POC diagnostics. Publisher PDF

The anisotropic shape of DNA molecules allows them to form lyotropic liquid crystals (LCs) at high concentrations. This liquid crystalline arrangement is also found in vivo (e.g., in bacteriophage capsids, bacteria or human sperm nuclei). However, the role of DNA liquid crystalline organization in living organisms still remains an open question. Here we show that in vitro, the DNA spatial structure is significantly changed in mesophases compared to non-organized DNA molecules. DNA LCs were prepared from pBluescript SK (pBSK) plasmid DNA and investigated by photochemical analysis of structural transitions (PhAST). We reveal significant differences in the probability of UV-induced pyrimidine dimer photoproduct formation at multiple loci on the DNA indicative of changes in major groove architecture.

International audience; SU-8 photoresist polymer is widely used in the fabrication of microdevices. However, for biological applications , the problem of efficiently modifying SU-8 surfaces without perturbing roughness has not been successfully resolved. We present UV/ozone (UVO) surface pre-treatment as an effective method to increase the hydrophilicity of SU-8 films without affecting surface roughness, thus improving specific covalent binding of bio-molecules. We demonstrate that 30 s UVO treatment suffices to create carboxyl groups at the surface that can then be used for high density binding of molecules via amide bond formation. We further demonstrate that a two-step surface modification where the surface is first protected with an ethylene glycol monolayer leads to an increase in binding specificity. Finally, to illustrate the controlled binding and accessibility of immobilized molecules, we show three cycles of reversible interactions between anti-tamra antibody and tamra-cadaverine immobilized on the surface of SU-8.

Rapid detection of Mycobacterium tuberculosis (Mtb), an etiological agent of tuberculosis (TB), is important for global control of this disease. Aptamers have emerged as a potential rival for antibodies in therapeutics, diagnostics and biosensing due to their inherent characteristics. The aim of the current study was to select and characterize single-stranded DNA aptamers against MPT64 protein, one of the predominant secreted proteins of Mtb pathogen. Aptamers specific to MPT64 protein were selected in vitro using systematic evolution of ligands through exponential enrichment (SELEX) method. The selection was started with a pool of ssDNA library with randomized 40-nucleotide region. A total of 10 cycles were performed and seventeen aptamers with unique sequences were identified by sequencing. Dot Blot analysis was performed to monitor the SELEX process and to conduct the preliminary tests on the affinity and specificity of aptamers. Enzyme linked oligonucleotide assay (ELONA) showed that most of the aptamers were specific to the MPT64 protein with a linear correlation of R2 = 0.94 for the most selective. Using Surface Plasmon Resonance (SPR), dissociation equilibrium constant KD of 8.92 nM was obtained. Bioinformatics analysis of the most specific aptamers revealed the existence of a conserved as well as distinct sequences and possible binding site on MPT64. The specificity was determined by testing non-target ESAT-6 and CFP-10. Negligible cross-reactivity confirmed the high specificity of the selected aptamer. The selected aptamer was further tested on clinical sputum samples using ELONA and had sensitivity and specificity of 91.3% and 90%, respectively. Microscopy, culture positivity and nucleotide amplification methods were used as reference standards. The aptamers studied could be further used for the development of medical diagnostic tools and detection assays for Mtb.

We describe a biophysical approach that enables changes in the structure of DNA to be followed during nucleosome formation in in vitro reconstitution with either the canonical “Widom” sequence or a judiciously mutated sequence. The rapid non-perturbing photochemical analysis presented here provides ‘snapshots’ of the DNA configuration at any given moment in time during nucleosome formation under a very broad range of reaction conditions. Changes in DNA photochemical reactivity upon protein binding are interpreted as being mainly induced by alterations in individual base pair roll angles. The results strengthen the importance of the role of an initial (H3/H4)2 histone tetramer-DNA interaction and highlight the modulation of this early event by the DNA sequence. (H3/H4)2 binding precedes and dictates subsequent H2A/H2B-DNA interactions, which are less affected by the DNA sequence, leading to the final octameric nucleosome. Overall, our results provide a novel, exciting way to investigate those biophysical properties of DNA that constitute a crucial component in nucleosome formation and stabilization.

After having presented the organization and self-assembly of alkanethiols on zinc substrates, we focus here on the bond between the thiol sulfur and the metal. The interfacial bond between decanethiol and bulk Zn platelet has been investigated by X-ray photoelectron spectroscopy. In the presence of traces of oxygen, the Zn is oxidized and subsequently the thiolate –Zn(II)–SR is formed whatever the adsorption time tads and ageing conditions. This is attributed to the inability of the thiol to reduce the Zn(II). Results for the Zn substrate are discussed and we put into perspective the behaviour of Zn compared to other metals in the light of its great affinity towards sulfur and its complexing, soft acid and reducing properties.

International audience; VirE2 is the major secreted protein of Agrobacterium tumefaciens in its genetic transformation of plant hosts. It is co-expressed with a small acidic chaperone VirE1, which prevents VirE2 oligomerization. After secretion into the host cell, VirE2 serves functions similar to a viral capsid in protecting the single-stranded transferred DNA en route to the nucleus. Binding of VirE2 to ssDNA is strongly cooperative and depends moreover on protein-protein interactions. In order to isolate the protein-DNA interactions , imaging surface plasmon resonance (SPRi) studies were conducted using surface-immobilized DNA substrates of length comparable to the protein-binding footprint. Binding curves revealed an important influence of substrate rigidity with a notable preference for poly-T sequences and absence of binding to both poly-A and double-stranded DNA fragments. Dissociation at high salt concentration confirmed the electrostatic nature of the interaction. VirE1-VirE2 heterodimers also bound to ssDNA, though by a different mechanism that was insensitive to high salt. Neither VirE2 nor VirE1-VirE2 followed the Lang-muir isotherm expected for reversible monomeric binding. The differences reflect the cooperative self-interactions of VirE2 that are suppressed by VirE1.

The electrical conduction through three short oligomers (26 base pairs, 8 nm long) with differing numbers of GC base pairs was measured. One strand is poly(A)-poly(T), which is entirely devoid of GC base pairs. Of the two additional strands, one contains 8 and the other 14 GC base pairs. The oligomers were adsorbed on a gold substrate on one side and to a gold nanoparticle on the other side. Conducting atomic force microscope was used for obtaining the current versus voltage curves. We found that in all cases the DNA behaves as a wide band-gap semiconductor, with width depending on the number of GC base pairs. As this number increases, the band-gap narrows. For applied voltages exceeding the band-gap, the current density rises dramatically. The rise becomes sharper with increasing number of GC base pairs, reaching more than 1 nA/nm2 for the oligomer containing 14 GC pairs.

A simple and reproducible method for the preparation of gold films on mica with large (typically 0.8–1.0 μm) atomically flat (1 1 1) terraces is described. The procedure involves thin gold film evaporation onto freshly cleaved mica substrates, followed by 1 min annealing at 650 °C under nitrogen. The annealed gold surfaces are compared to those of freshly evaporated gold films on mica using cyclic voltammetry and atomic force microscopy. Our results favorably compare to other published annealing techniques, with minimal equipment and time necessary to reproducibly obtain atomically flat gold terraces.

SAMs (self-assembled monolayers) of alkanethiols functionalized by α-terthienyl (3T-SAMs) and α-quaterthienyl (4T-SAMs) were formed on a gold surface presenting (111) terraces and studied by high-resolution electron energy loss spectroscopy (HREELS). The angular width of the elastic peak leads to a domain size of ca. 90 A, comparable to that of the Au(111) terraces of the substrate. Enhancement of the spectral resolution by using a new generation spectrometer enables the improvement of the spectral analysis in the energy range of the vibrational losses. A detailed analysis of the differential cross sections of the different vibrational peaks indicates the nature of their mechanisms: impact mechanisms show that the extreme surface of the monolayers is mainly constituted by thienyl moieties with the thienyl density in 3T-SAMs higher than that in 4T-SAMs; dipolar mechanisms show that molecules are standing up slightly tilted on the substrate; a resonance via a negative ion formation was detected around 4.5 ...

A model of polythiophene grafting on a SAM functionalised by α-quaterthiophene is presented. The elaboration and characterisation of the dodecanethiol monolayer terminated by α-quaterthiophene are reported. Blocking level of substrates, structure of the alkyl chains and organisation of the quaterthiophene units as well as their chemical behaviour are analysed. HREELS spectra showed that the extreme surface of the monolayers is entirely covered by quaterthiophene units after typical adsorption times of 12 h. PM-IRRAS spectra allow to follow the orientation of molecules within the monolayer versus adsorption time. It is shown that the long axis of quaterthienyl groups stand slightly tilted with respect to the perpendicular. In addition, interfacial reactions of the SAM layer with a model molecule, the end-capped terthiophene, were electrochemically induced via the formation of radical cations. The number of grafted molecules that depends on the 4T film structure is discussed in regard to the 4T moiety reactivity.

International audience; This work describes the interaction between femtosecond laser pulses (B130 fs, 800 nm) and gold nanorods (NRs) leading to reshaping of the NRs. We focus on the investigation of structural changes of the NRs and the parameters influencing the reshaping, like surface modification using sodium sulphide, laser power and the position of the longitudinal surface plasmon resonance band (l-SPR) with respect to the laser wavelength. A thermogravimetric analysis experiment is performed to examine changes in the composition of NRs upon heating. A new type of banana-shaped NPs is described and the conditions of their appearance are discussed.

We previously demonstrated that vertically-coupled polymer microring resonators are good candidates as transducers in label-free biosensing instruments, for several reasons: good optical performances, low production costs, excellent biocompatibility and state-of-the-art surface sensitivity. We later presented the association of our original opto-electronic setup to microfluidics to perform homogeneous optofluidic detection, using glucose solutions to characterize the behavior of the microring transducer. In parallel, the same transducer devices have been associated to another detection scheme, phase-sensitive OLCI, with promising results.

We synthesized a mixture composed of gold nanoparticles of various shapes using the wet chemistry method. The final solution contained long nanorods, balls, disks and different spherical nanoparticles. To separate particles of individual shapes from the reaction mixture, the solution was centrifuged in a glucose density gradient. A distribution of nanoparticles based on their diameters was observed and each section was collected independently and each type of nanoobjects was characterised separately. Finally, the difference in nanoparticle shapes depending on the presence of Ag+ ions in the growth solution is reported and its influence on the separation is discussed.

It is well known that the heart releases a factor called ANF (atrial natriuretic factor) or ANP (atrial natriuretic peptide) capable of inducing rapid diuretic and natriuretic actions. This factor is stored in secretory granules mainly located in myocytes in both atria. The main secretory stimulus is the distention of the atrial cavity resulting, for example, from enhanced venous return. However, the cellular events which occur after the stimulation remain to be clarified. The aim of this investigation was to study the intra-cellular events preceding the ANF release, using the rat hindlimb suspension as model of stimulation. In this model, Wistar rats were placed in a 30 degrees anti-orthostatic position and a blood shift towards the heart was obtained. Different durations (1/4 h, 1/2 h, 3/4 h, 1 h, 2 h and 6 h) were studied. The ANF plasma level was investigated by Radio Immuno Assay and granule immunoreactivity was measured by counting gold particles on micrographs. The ANF plasma level was significantly increased (+60%) after 1 h of suspension. The response was transient and then decreased to basal values. Morphological criteria established at the beginning of this study, and measured throughout the experiment, were found transiently modified after suspension. The surface of the perinuclear area was transitory enlarged by 36% 30 min after suspension. Moreover, in the same time immunoreactivity of the secretory granules was enhanced without changes in granule size. These results suggest an increase in the ANF synthesis and storage in the granules during the stimulation. However, the cellular regulatory mechanism of the ANF synthesis which could explain the transitory aspect of these events, requires further investigation.

International audience; We report on the efficient design and fabrication of polymeric microracetrack optical resonators for label-free biosensing purposes. Vertically-coupled microresonators immersed in deionised water display high Q-factors (>35000) and finesses up to 25. A surface sensing experiment performed with these microresonators using 5-TAMRA cadaverine as a test molecule demonstrated both the high sensitivity and low detection limit of our device.

International audience; Natural RNAs, unlike many proteins, have never been reported to form extended nanostructures, despite their wide variety of cellular functions. This is all the more striking, as synthetic DNA and RNA forming large nanostructures have long been successfully designed. Here, we show that DsrA, a 87-nt noncoding RNA of Escherishia coli, self-assembles into a hierarchy of nanostructures through antisense interactions of three contiguous self-complementary regions. Yet, the extended nanostructures, observed using atomic force microscopy (AFM) and fluorescence-microscopy, are easily disrupted into >100 nm long helical bundles of DsrA filaments, including hundreds of DsrA monomers, and are surprisingly resistant to heat and urea denaturation. Molecular modeling demonstrates that this structural switch of DsrA nanostructures into filament bundles results from the relaxation of stored torsional constraints and suggests possible implications for DsrA regulatory function.

We investigated the fine structure of a self-assembled monolayer of dodecanethiol functionalized by alpha-quaterthiophene on gold (alpha-4TC 12H 24SH). The molecular orientation, quantified using polarization modulation infrared reflection-absorption spectroscopy, was studied as a function of the adsorption time. The alpha-4T moieties arrange in the upright position on the surface as the adsorption time increases, while the alkyl chain organization remains poor. Here we quantify the orientation of the self-assembled monolayer and, more significantly, reveal through surface X-ray diffraction that after a long incubation period (12 h) the alpha-4T on the gold surface adopts a 2D crystal structure.

International audience; We present results from high-resolution electron energy loss spectroscopy (HREELS) and XPS studies of self-assembled monolayers of DNA. The monolayers are well-organized and display sharp vibrational peaks in the HREEL spectra. The electrons interact mainly with the backbone of the DNA. The XPS results indicate that, in most of the samples studied, the phosphates on the DNA are not charged.

This work concerns a first step toward the use of self-assembled monolayers derived from thiols as coupling layers between a zinc surface and organic coatings. The adsorption, structure, and aging of alkanelthiol monolayers on zinc substrates have been studied by contact angle measurements, infrared spectroscopy, and electrochemistry. The thiols self-assemble on the zinc surface to form a highly hydrophobic monolayer. The molecules are well organized with very few gauche defects, oriented nearly normal to the surface, and protect the zinc from oxidation in a neutral aqueous medium.

We recently reported electrical transport measurements through double-stranded (ds)DNA molecules that are embedded in a self-assembled monolayer of single-stranded (ss)DNA and attached to a metal substrate and to a gold nanoparticle (GNP) on opposite ends. The measured current flowing through the dsDNA amounts to 220 nA at 2 V. In the present report we compare electrical transport through an ssDNA monolayer and dsDNA monolayers with and without upper thiol end-groups. The measurements are done with a conductive atomic force microscope (AFM) using various techniques. We find that the ssDNA monolayer is unable to transport current. The dsDNA monolayer without thiols in the upper end can transport low current on rare occasions and the dsDNA monolayer with thiols on both ends can transport significant current but with a much lower reliability and reproducibility than the GNP-connected dsDNA. These results reconfirm the ability of dsDNA to transport electrical current under the appropriate conditions, demonstrate the efficiency of an ssDNA monolayer as an insulating layer, and emphasize the crucial role of an efficient charge injection through covalent bonding for electrical transport in single dsDNA molecules.

Seemingly contradicting results raised a debate over the ability of DNA to transport charge and the nature of the conduction mechanisms through it. We developed an experimental approach for measuring current through DNA molecules, chemically connected on both ends to a metal substrate and to a gold nanoparticle, by using a conductive atomic force microscope. Many samples could be made because of the experimental approach adopted here, which enabled us to obtain reproducible results with various samples, conditions, and measurement methods. We present multileveled evidence for charge transport through 26-bp-long dsDNA of a complex sequence, characterized by S-shaped current–voltage curves that show currents >220 nA at 2 V. This significant observation implies that a coherent or band transport mechanism takes over for bias potentials leading to high currents (>1 nA).

Self assembled monolayers (SAMs) of thiols functionalised with oligothiophene functions were used as models for polymer surfaces. Thienyl functionalisation simulates the surface region and demonstrates that the analysed depth is of the order of 10 A. Spectra of polystyrene (PS) films were recorded and show that impact mechanism dominates, which corroborates the high sensitivity of HREELS applied to polymer surfaces. Different orientation of phenyl groups is unravel for PS films deposited on platinum and silicon substrates, which is here related to a different conformation of the PS chains in the surface region of the film. To illustrate the state of the art of HREELS applied to organic films, spectra were recorded with old and new generation spectrometers.

International audience; Background: Heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 is a target for antinuclear autoantibodies in systemic Lupus erythematosus (SLE), rheumatoid arthritis (RA), and autoimmune hepatitis (AIH).Aim: To monitor molecular interactions between peptides spanning the entire sequence of hnRNP A2/B1 and sera from patients and healthy controls.Methods: Sera from 8 patients from each pathology and controls were passed across a surface plasmon resonance Imagery (SPRi) surface containing 39 overlapping peptides of 17 mers covering the human hnRNP B1. Interactions involving the immobilised peptides were followed in real time and dissociation rate constants koff for each interaction were calculated.Results: Several significant interactions were observed: i) high stability (lower koff values) between P55-70 and the AIH sera compared to controls (p= 0.003); ii) lower stability (higher koff values) between P118-133 and P262-277 and SLE sera, P145-160 and RA sera compared to controls (p=0.006, p=0.002, p=0.007). The binding curves and koff values observed after the formation of complexes with anti-IgM and anti-IgG antibodies and after nuclease treatment of the serum indicate that i) IgM isotypes are prevalent and ii) nucleic acids participate in the interaction between anti-hnRNAP B1 and P55-70 and also between controls and the peptides studied.Conclusions: These results indicate that P55-70 of hnRNP B1 is a potential biomarker for AIH in immunological tests and suggest the role of circulating nucleic acids, (eg miRNA), present or absent according to the autoimmune disorders and involved in antigen-antibody stability.

International audience; Non-specific binding to biosensor surfaces is a major obstacle to quantitative analysis of selective retention of analytes at immobilized target molecules. Although a range of chemical antifouling monolayers has been developed to address this problem, many macromolecular interactions still remain refractive to analysis due to the prevalent high degree of non-specific binding. In this manuscript we explore the dynamic process of the formation of self-assembled monolayers and optimize physical and chemical properties thus reducing considerably non-specific binding while maintaining the integrity of the immobilized biomolecules. As a result, analysis of specific binding of analytes to immobilized target molecules is significantly facilitated.

We study second-harmonic generation from single CdTe/CdS core/shell rod-on-dot nanocrystals with different geometrical parameters, which allow to fine tune the nonlinear properties of the nanostructure. These hybrid semiconductor-semiconductor nanoparticles exhibit extremely strong and stable second-harmonic emission, although the size of CdTe core is still within the strong quantum confinement regime. The orientation sensitive polarization response is analyzed by means of a pointwise additive model of the third-order tensors associated to the nanoparticle components. These findings prove that engineering of semiconducting complex heterostructures at the single nanoparticle scale can lead to extremely bright nanometric nonlinear light sources.

Oligothiophenes carrying an alkylthiol group on one of the internal β-positions have been synthesized and adsorbed onto platinum and gold. The adsorbed assemblies are not very well organized, probably due to the geometry of the single molecules. The thiophene-based layers exhibit electrochemical activity in non aqueous electrolytes. The monomer units within the layers can be polymerized by a single anodic sweep. The obtained polymers show a high electrochemical and thermal stability. In some cases the polymer shows an increase of the structural order compared to the monomer layers.

A method for work-function evaluation is proposed, based on recording the shift of x-ray photoelectron signals from a surface irradiated by low-energy electrons. The method is capable of measuring samples with very low conductivity, poor back contacts, and high dielectric constants. The method is also applicable to magnetic materials and can be particularly effective for studies of multilayer and heterogeneous systems.

Complementary, single-strands of DNA (ssDNA), one bound to a gold electrode and the other to a gold nanoparticle were hybridized on the surface to form a self-assembled, dsDNA bridge between the two gold contacts. The adsorption of a ssDNA monolayer at each gold interface eliminates non-specific interactions of the dsDNA with the surface, allowing bridge formation only upon hybridization. The technique used, in addition to providing a good electrical contact, offers topographical contrast between the gold nanoparticles and the non-hybridized surface and enables accurate location of the bridge for the electrical measurements. Reproducible AFM conductivity measurements have been performed and significant qualitative differences were detected between conductivity in single- and double-strand DNA. The ssDNA was found to be insulating over a 4 eV range between ±2 V under the studied conditions, while the dsDNA, bound to the gold nanoparticle, behaves like a wide band gap semiconductor and passes significant current outside of a 3 eV gap.

Alkylthiol functionalized quaterthiophene has been synthesized and adsorbed onto gold an platinum substrates. The obtained layers (SAMs) are densely packed and highly ordered. The assemblies show remarkable electrochemical and thermal stability and are elctroactive in nonaqueous media.

Summary Expression of HLADR, I, i blood group antigen and T6 antigen were studied in Histiocytosis X cells and pulmonary alveolar macrophages using double labelling immunofluorescence technique or immuno-peroxydase procedure. Alveolar macrophages express simultaneously HLADR and i blood group antigen. Histiocytosis X cells, caracterized by HLADR and T6 antigens, and by their ultra-structural marker do not express i antigen. These results confirm the hypothesis that histiocytosis X cells constitute a specialized sub-population of the mononuclear phagocyte system.

Irradiations of rat's brain with heavy ionized particles ( 291 Mev/nucleon, 100 to 300 ions/mm2) have been carried out at the Lawrence Berkeley Laboratory. Exposures were made with slowed ions which stopped within the brain as well as with more energetic particles which passed through. Histological examination of irradiated encephalons by optical microscopy showed zones of glial reaction and an increased number of darkly staining cells. By electron microscopy, intercellular edema, various alterations of nervous cells and macrophagy were observed, especially with stopped ions.