Investigation of proton-proton short-range correlations via the 12C(e,e'pp) reaction

We investigated simultaneously the 12C(e,e'p) and 12C(e,e'pp) reactions at Q2=2 (GeV/c)2, xB=1.2, and in an (e, e'p) missing-momentum range from 300 to 600 MeV/c. At these kinematics, with a missing momentum greater than the Fermi momentum of nucleons in a nucleus and far from the delta excitation, short-range nucleon-nucleon correlations are predicted to dominate the reaction. For (9.5+/-2)% of the 12C(e,e'p) events, a recoiling partner proton was observed back-to-back to the 12C(e,e'p) missing-momentum vector, an experimental signature of correlations.     

Two-phase flow in heterogeneous porous media III: Laboratory experiments for flow parallel to a stratified system

Two-phase flow in stratified porous media is a problem of central importance in the study of oil recovery processes. In general, these flows are parallel to the stratifications, and it is this type of flow that we have investigated experimentally and theoretically in this study. The experiments were performed with a two-layer model of a stratified porous medium. The individual strata were composed of Aerolith-10, an artificial: sintered porous medium, and Berea sandstone, a natural porous medium reputed to be relatively homogeneous. Waterflooding experiments were performed in which the saturation field was measured by gamma-ray absorption. Data were obtained at 150 points distributed evenly over a flow domain of 0.1 × 0.6 m. The slabs of Aerolith-10 and Berea sandstone were of equal thickness, i.e. 5 centimeters thick. An intensive experimental study was carried out in order to accurately characterize the individual strata; however, this effort was hampered by both local heterogeneities and large-scale heterogeneities.The theoretical analysis of the waterflooding experiments was based on the method of large-scale averaging and the large-scale closure problem. The latter provides a precise method of discussing the crossflow phenomena, and it illustrates exactly how the crossflow influences the theoretical prediction of the large-scale permeability tensor. The theoretical analysis was restricted to the quasi-static theory of Quintard and Whitaker (1988), however, the dynamic effects described in Part I (Quintard and Whitaker 1990a) are discussed in terms of their influence on the crossflow.Roman Letters A interfacial area between the -region and the -region contained within V, m² - a vector that maps onto , m - b vector that maps onto , m - b vector that maps onto , m - B second order tensor that maps onto , m² - C second order tensor that maps onto , m² - E energy of the gamma emitter, keV - f fractional flow of the -phase - g gravitational vector, m/s² - h characteristic length of the large-scale averaging volume, m - H height of the stratified porous medium , m - i unit base vector in the x-direction - K local volume-averaged single-phase permeability, m² - K - {K}, large-scale spatial deviation permeability - { K} large-scale volume-averaged single-phase permeability, m² - K ^* large-scale single-phase permeability, m² - K ^** equivalent large-scale single-phase permeability, m² - K local volume-averaged -phase permeability in the -region, m² - K local volume-averaged -phase permeability in the -region, m² - K - {K } , large-scale spatial deviation for the -phase permeability, m² - K ^* large-scale permeability for the -phase, m² - l thickness of the porous medium, m - l characteristic length for the -region, m - l characteristic length for the -region, m - L length of the experimental porous medium, m - characteristic length for large-scale averaged quantities, m - n outward unit normal vector for the -region - n outward unit normal vector for the -region - n unit normal vector pointing from the -region toward the -region (n = - n ) - N number of photons - p pressure in the -phase, N/m² - p ₀ reference pressure in the -phase, N/m² - local volume-averaged intrinsic phase average pressure in the -phase, N/m² - large-scale volume-averaged pressure of the -phase, N/m² - large-scale intrinsic phase average pressure in the capillary region of the -phase, N/m² - - , large-scale spatial deviation for the -phase pressure, N/m² - p_c , capillary pressure, N/m² - p _c capillary pressure in the -region, N/m² - p capillary pressure in the -region, N/m² - {p _c } ^c large-scale capillary pressure, N/m² - q -phase velocity at the entrance of the porous medium, m/s - q -phase velocity at the entrance of the porous medium, m/s - S_wi irreducible water saturation - S /, local volume-averaged saturation for the -phase - S _i initial saturation for the -phase - S _r residual saturation for the -phase - S ^* { }^*/}^*, large-scale average saturation for the -phase - S saturation for the -phase in the -region - S saturation for the -phase in the -region - t time, s - v -phase velocity vector, m/s - v local volume-averaged phase average velocity for the -phase, m/s - {v } large-scale averaged velocity for the -phase, m/s - v local volume-averaged phase average velocity for the -phase in the -region, m/s - v local volume-averaged phase average velocity for the -phase in the -region, m/s - v -{v } , large-scale spatial deviation for the -phase velocity, m/s - v -{v } , large-scale spatial deviation for the -phase velocity in the -region, m/s - v -{v } , large-scale spatial deviation for the -phase velocity in the -region, m/s - V large-scale averaging volume, m³ - y position vector relative to the centroid of the large-scale averaging volume, m - {y}^c large-scale average of y over the capillary region, m Greek Letters local porosity - local porosity in the -region - local porosity in the -region - local volume fraction for the -phase - local volume fraction for the -phase in the -region - local volume fraction for the -phase in the -region - {}^* { }^*+{ }^*, large-scale spatial average volume fraction - { }^* large-scale spatial average volume fraction for the -phase - mass density of the -phase, kg/m³ - mass density of the -phase, kg/m³ - viscosity of the -phase, N s/m² - viscosity of the -phase, Ns/m² - V /V , volume fraction of the -region ( + =1) - V /V , volume fraction of the -region ( + =1) - attenuation coefficient to gamma-rays, m^-1 - -      

A Hot‐Segment‐Based Approach for the Design of Cross‐Amyloid Interaction Surface Mimics as Inhibitors of Amyloid Self‐Assembly

The design of inhibitors of protein–protein interactions mediating amyloid self‐assembly is a major challenge mainly due to the dynamic nature of the involved structures and interfaces. Interactions of amyloidogenic polypeptides with other proteins are important modulators of self‐assembly. Here we present a hot‐segment‐linking approach to design a series of mimics of the IAPP cross‐amyloid interaction surface with Aβ (ISMs) as nanomolar inhibitors of amyloidogenesis and cytotoxicity of Aβ, IAPP, or both polypeptides. The nature of the linker determines ISM structure and inhibitory function including both potency and target selectivity. Importantly, ISMs effectively suppress both self‐ and cross‐seeded IAPP self‐assembly. Our results provide a novel class of highly potent peptide leads for targeting protein aggregation in Alzheimer’s disease, type 2 diabetes, or both diseases and a chemical approach to inhibit amyloid self‐assembly and pathogenic interactions of other proteins as well.     

Comparative studies of nontoxic and toxic amyloids interacting with membrane models at the air-water interface

Many in vitro studies have pointed out the interaction between amyloids and membranes, and their potential involvement in amyloid toxicity. In a previous study, we generated a yeast toxic mutant (M8) of the harmless model amyloid protein HET-s((218-289)). In this study, we compared the self-assembling process of the nontoxic wild-type (WT) and toxic (M8) protein at the air-water interface and in interaction with various phospholipid monolayers (DOPE, DOPC, DOPI, DOPS and DOPG). We first demonstrate using ellipsometry measurements and polarization-modulated infrared reflection absorption spectroscopy (PMIRRAS) that the air-water interface promotes and modifies the assembly of WT since an amyloid-like film was instantaneously formed at the interface with an antiparallel β-sheet structuration instead of the parallel β-sheet commonly observed for amyloid fibers generated in solution. The toxic mutant (M8) behaves in a similar manner at the air-water interface or in bulk, with a fast self-assembling and an antiparallel β-sheet organization. The transmission electron microscopy (TEM) images established the fibrillous morphology of the protein films formed at the air-water interface. Second, we demonstrate for the first time that the main driving force between this particular fungus amyloid and membrane interaction is based on electrostatic interactions with negatively charged phospholipids (DOPG, DOPI, DOPS). Interestingly, the toxic mutant (M8) clearly induces perturbations of the negatively charged phospholipid monolayers, leading to a massive surface aggregation, whereas the nontoxic (WT) exhibits a slight effect on the membrane models. This study allows concluding that the toxicity of the M8 mutant could be due to its high propensity to interact with membranes.     

Synthesis of 4'-aminopantetheine and derivatives to probe aminoglycoside N-6'-acetyltransferase

A convenient synthesis of 4'-aminopantetheine from commercial D-pantethine is reported. The amino group was introduced by reductive amination in order to avoid substitution at a sterically congested position. Derivatives of 4'-aminopantetheine were also prepared to evaluate the effect of O-to-N substitution on inhibitors of the resistance-causing enzyme aminoglycoside N-6'-acetyltransferase. The biological results combined with docking studies indicate that in spite of its reported unusual flexibility and ability to adopt different folds, this enzyme is highly specific for AcCoA.     

Insights in the rational design of synthetic multivalent glycoconjugates as lectin ligands

Much effort has been made during the last decade to design lectin inhibitors as therapeutics against viral and bacterial adhesion or to control biological functions. The chemical strategy adopted generally consists in the tethering of several binding epitopes on a common scaffold. The resulting multivalent glycoconjugates often display a much higher binding affinity for their targets compared to their monovalent counterparts, a phenomenon designed as the "cluster" or "multivalent effect". Hundreds of multimeric architectures have been designed so far and some of the compounds displayed impressive gains in binding affinity or in vivo efficiency. Progress in this area is, however, hampered by the difficulty to predict the potency of the new multimeric inhibitors. This review presents the recent efforts to probe the important structural features of the synthetic multivalent glycoconjugates for a tight binding with specific lectins. We hope that the reported examples will aid the reader to design efficient multivalent ligands in a more predictable way.     

Poly(D,L-lactide)-block-poly(2-hydroxyethyl acrylate) block copolymers as potential biomaterials for peripheral nerve repair: in vitro and in vivo degradation studies

The properties of poly(D ,L ‐lactide)‐block‐poly(2‐hydroxyethyl acrylate) (PLA‐b‐PHEA) block copolymers by means of in vitro / in vivo (rat) degradation are investigated and compared to those of PLA homopolymer. Over 12 weeks, we observe mass loss and molecular weight decrease. In vitro and in vivo findings are very similar for each polymer tested. When a short PHEA block is used (PLA‐b‐PHEA 15 000–3 000 g · mol^?1, 85/15 wt%), the degradation process is found to be very similar to that of homo‐PLA, and to be typical of a bulk erosion mechanism, with no mass loss observed until week 7 and continuous decrease of molar mass within this timeframe. For a longer PHEA block length within the block copolymer (PLA‐b‐PHEA 15 000–7 500 g · mol^?1, 65/35 wt%), the degradation mechanism is modified, with a significant mass loss observed at early times and only a slight decrease in molar mass. The latter finding is related to the pronounced hydrophilicity and softness of the material induced by the PHEA block, which allow easy diffusion and rapid leakage of the degradation residues from the material towards the aqueous medium. Schwann cells are found to better adhere on spin‐coated films of PLA‐b‐PHEA (85/15 wt%) than on PLA ones. These results show the potential of such hydrophilized PLA‐based copolymers for use in peripheral nerve repair.