A Variable Neighbourhood Descent Heuristic for Conformational Search Using a Quantum Annealer.

Discovering the low-energy conformations of a molecule is of great interest to computational chemists, with applications in in silico materials design and drug discovery. In this paper, we propose a variable neighbourhood search heuristic for the conformational search problem. Using the structure of a molecule, neighbourhoods are chosen to allow for the efficient use of a binary quadratic optimizer for conformational search. The method is flexible with respect to the choice of molecular force field and the number of discretization levels in the search space, and can be further generalized to take advantage of higher-order binary polynomial optimizers. It is well-suited for the use of devices such as quantum annealers. After carefully defining neighbourhoods, the method easily adapts to the size and topology of these devices, allowing for seamless scaling alongside their future improvements.

A process efficiency assessment of serum protein removal from milk using ceramic graded permeability microfiltration membrane.

Microfiltration (MF) is a well-known process that can be used in the dairy industry to separate caseins from serum proteins (SP) in skim milk using membranes with a pore diameter of 0.1µm. Graded permeability ceramic membranes have been studied widely as means of improving milk fractionation by overcoming problems encountered with other MF membranes. The ideal operating parameters for process efficiency in terms of membrane selectivity, permeate flux, casein loss, SP transmission, energy consumption, and dilution with water remain to be determined for this membrane. Our objective was to evaluate the effects of transmembrane pressure (TMP), volumetric concentration factor (VCF), and diafiltration on overall process efficiency. Skim milk was processed using a pilot-scale MF system equipped with 0.72-m(2) graded permeability membranes with a pore size of 0.1µm. In the first experiment, in full recycle mode, TMP was set at 124, 152, 179, or 207 kPa by adjusting the permeate pressure at the outlet. Whereas TMP had no significant effect on permeate and retentate composition, 152 kPa was found to be optimal for SP removal during concentration and concentration or diafiltration experiments. When VCF was increased to 3×, SP rejection coefficient increased along with energy consumption and total casein loss, whereas SP removal rate decreased. Diafiltering twice allowed an increase in total SP removal but resulted in a substantial increase in energy consumption and casein loss. It also reduced the SP removal rate by diluting permeate. The membrane surface area required for producing cheese milk by blending whole milk, cream, and MF retentate (at different VCF) was estimated for different cheese milk casein concentrations. For a given casein concentration, the same quantity of permeate and SP would be produced, but less membrane surface area would be needed at a lower retentate VCF. Microfiltration has great potential as a process of adding value to conventional cheesemaking processes, but its cost-effectiveness at a large scale remains to be demonstrated.

Contributions to reversed-phase column selectivity. II. Cation exchange.

The contribution of cation exchange to solute retention for type-B alkylsilica columns (made from high-purity silica) has been examined in terms of the hydrophobic-subtraction (H-S) model of reversed-phase column selectivity. The relative importance of cation exchange in the separation of ionized bases by reversed-phase chromatography (RPC) varies with (a) column acidity (values of the column cation-exchange capacity C), (b) mobile-phase pH and buffer concentration, and (c) the nature of the buffer cation. The effects of each of these separation variables on cation retention were examined. The contribution of cation exchange (and other ionic interactions) to solute retention is represented in the H-S model by properties of the solute (κ') and column (C), respectively. Values of κ' for 87 solutes have been examined as a function of solute molecular structure, and values of C for 167 type-B alkylsilica columns have been related to various column properties: ligand length (e.g., C(8) vs. C(18)) and concentration (µmol/m(2)), pore diameter (nm), and end-capping. These results contribute to a more detailed picture of the retention of cationic solutes in RPC as a function of separation conditions. While previous work suggests that the ionization of type-B alkylsilica columns is generally negligible with mobile-phase pH<7 (as a result of which cation exchange then becomes insignificant), the present study provides evidence for cation exchange (and presumably silanol ionization) at a pH as low as 3 for most columns.

Sharp transition for single polarons in the one-dimensional Su-Schrieffer-Heeger model.

We study a single polaron in the Su-Schrieffer-Heeger (SSH) model using four different techniques (three numerical and one analytical). Polarons show a smooth crossover from weak to strong coupling, as a function of the electron-phonon coupling strength λ, in all models where this coupling depends only on phonon momentum q. In the SSH model the coupling also depends on the electron momentum k; we find it has a sharp transition, at a critical coupling strength λ(c), between states with zero and nonzero momentum of the ground state. All other properties of the polaron are also singular at λ=λ(c). This result is representative of all polarons with coupling depending on k and q, and will have important experimental consequences (e.g., in angle-resolved photoemission spectroscopy and conductivity experiments).

[Atopic dermatitis aggravates the allergic airways inflammation in acute viral bronchiolitis]. / La dermatite atopique aggrave l'inflammation allergique dans la bronchiolite aiguë virale.

INTRODUCTION: Exhaled nitric oxide (FeNO) is a putative non-invasive marker of eosinophilic airway inflammation with a good predictive value for allergic asthma in preschool children. The aim of the present study was to compare FeNO after acute viral bronchiolitis (AVB) in children aged less than 2 years without atopic dermatitis (AD) vs those with atopic dermatitis, as well as children with AD without any history of AVB. METHODS: Forty-two children (mean age +/- SD: 12.3 +/- 5.2 months; range 5.0-23.5; sex-ratio M: F=1.3: 1) were included in this prospective study, > 8 wks after an episode of AVB. The patients' atopic status was assessed both by clinical phenotype and IgE- mediated response to inhaled and/or food allergens. FeNO (ppb) was measured off-line by the chemoluminescence method on samples obtained from gas collected in a balloon during tidal breathing. RESULTS: There was a significant difference between the AVB/AD (23.4 +/- 14.3 ppb, n=15) vs the AVB without AD group (13.5 +/- 10. 1 ppb, n=13) or the AD without AVB group (11.0 +/- 8.3 ppb, n=14). Maternal feeding for more than 2 months decreased FeNO by 50%. CONCLUSION: Atopic children below 2 years with AD produce more NO after AVB than non-atopic children or atopic children without any history of AVB. Maternal feeding decreases FeNO.

Anion-exchange behavior of several alkylsilica reversed-phase columns.

Some alkylsilica columns carry a positive charge at low pH, as determined by anion-exchange with nitrate ion. In the present study, the relative positive charge for 14 alkylsilica columns was measured for a mobile-phase pH 3.0. All but 3 of these columns were found to carry a significant positive charge under these conditions. The relative positive charge on these columns was found to correlate approximately with two other column characteristics: relative cation-exchange behavior as measured by the hydrophobic-subtraction model (values of C-2.8), and slow equilibration of the column to changes in the mobile-phase-as evidenced by a slow change in the retention of anionic and cationic solutes with time. The origin of this positive charge may arise from the bonding process, with incorporation of some cationic entity into the stationary phase.

Characterization and applications of reversed-phase column selectivity based on the hydrophobic-subtraction model.

A total of 371 reversed-phase columns have now been characterized in terms of selectivity, based on five solute-column interactions (the hydrophobic-subtraction model). The present study illustrates the use of these data for interpreting peak-tailing and column stability. New insights are also provided concerning column selectivity as a function of ligand and silica type, and the selection of columns for orthogonal separations is re-examined. Some suggestions for the quality control of reversed-phase columns during manufacture are offered.

Relevance of pi-pi and dipole-dipole interactions for retention on cyano and phenyl columns in reversed-phase liquid chromatography.

Previous work suggests that pi-pi interactions between certain solutes and both phenyl and cyano columns can contribute to sample retention and the selectivity of these two column types versus alkylsilica columns. Recent studies also suggest that dipole-dipole interactions are generally unimportant for retention on cyano columns. The present study presents data for 44 solutes, three columns and two different mobile phases that were selected to further test these conclusions. We find that pi-pi interactions can contribute to retention on both cyano and phenyl columns, while dipole-dipole interactions are likely to be significant for the retention of polar aliphatic solutes on cyano columns. When acetonitrile/water mobile phases are used, both pi-pi and dipole-dipole interactions are suppressed, compared to the use of methanol/water.

Column selectivity in reversed-phase liquid chromatography. VII. Cyanopropyl columns.

Eleven cyanopropyl ("cyano") columns were characterized by means of a relationship developed originally for alkyl-silica columns. Compared to type-B alkyl-silica columns (i.e., made from pure silica), cyano columns are much less hydrophobic (smaller H), less sterically restricted (smaller S*), and have lower hydrogen-bond acidity (smaller A). Because sample retention is generally much weaker on cyano versus other columns (e.g., C8, C18), a change to a cyano column usually requires a significantly weaker mobile phase in order to maintain comparable values of k for both columns. For this reason, practical comparisons of selectivity between cyano and other columns (i.e., involving different mobile phases for each column) must take into account possible changes in separation due to the change in mobile phase, as well as change in the column.

Column selectivity in reversed-phase liquid chromatography. VIII. Phenylalkyl and fluoro-substituted columns.

As reported previously, five solute-column interactions (hydrophobicity, steric resistance, hydrogen-bond acidity and basicity, ionic interaction) quantitatively describe column selectivity for 163 alkyl-silica, polar-group and cyano columns. In the present study, solute retention and column selectivity for 11 phenyl and 5 fluoro-substituted columns were compared with alkyl-silica columns of similar ligand length. It is concluded that two additional solute-column interactions may be significant in affecting retention and selectivity for the latter columns: (a) dispersion interactions of varying strength as a result of significant differences in bonded-phase polarizability or refractive index and (b) pi-pi interactions in the case of phenyl columns and aromatic solutes. These 16 phenyl and fluoro columns were also characterized in terms of hydrophobicity, steric resistance, hydrogen-bond acidity and basicity, and ionic interaction.

Measurement of strange-quark contributions to the nucleon's form factors at Q(2) = 0.230 (GeV/c)(2).

We report on a measurement of the parity-violating asymmetry in the scattering of longitudinally polarized electrons on unpolarized protons at a Q2 of 0.230 (GeV/c)(2) and a scattering angle of theta (e) = 30 degrees - 40 degrees. Using a large acceptance fast PbF2 calorimeter with a solid angle of delta omega = 0.62 sr, the A4 experiment is the first parity violation experiment to count individual scattering events. The measured asymmetry is A(phys)=(-5.44+/-0.54(stat)+/-0.26(sys))x10(-6). The standard model expectation assuming no strangeness contributions to the vector form factors is A(0) = (-6.30+/-0.43) x 10(-6). The difference is a direct measurement of the strangeness contribution to the vector form factors of the proton. The extracted value is G(s)(E) + 0.225G(s)(M) = 0.039+/-0.034 or F(s)(1) + 0.130F(s)(2) = 0.032+/-0.028.

Biological activity of silylated amino acid containing substance P analogues.

The need to replace natural amino acids in peptides with nonproteinogenic counterparts to obtain new medicinal agents has stimulated a great deal of innovation on synthetic methods. Here, we report the incorporation of non-natural silylated amino acids in substance P (SP), the binding affinity for the two hNK-1 binding sites and, the potency to stimulate phospholipase C (PLC) and adenylate cyclase of the resulting peptide. We also assess the improvement of their stability towards enzyme degradation. Altogether, we found that replacing glycine with silaproline (Sip) in position 9 of SP leads to a potent analogue exhibiting an increased resistance to angiotensin-converting enzyme hydrolysis.

Slow equilibration of reversed-phase columns for the separation of ionized solutes.

Reversed-phase columns that have been stored in buffer-free solvents can exhibit pronounced retention-time drift when buffered, low-pH mobile phases are used with ionized solutes. Whereas non-ionized compounds exhibit constant retention times within 20 min of the beginning of mobile phase flow, the retention of ionized compounds can continue to change (by 20% or more) for several hours. If mobile phase pH is changed from low to high and back again, an even longer time may be required before the column reaches equilibration at low pH. The speed of column equilibration for ionized solutes can vary significantly among different reversed-phase columns and is not affected by flow rate.

The effect of the descent technique and truck cabin layout on the landing impact forces.

The majority of injuries to truckers are caused by falls during the descent from the cab of the truck. Several studies have shown that the techniques used to descend from the truck and the layout of the truck's cabin are the principal cause of injury. The goal of the present study was to measure the effects of the descent techniques used by the trucker and the layout of the truck's cabin on the impact forces absorbed by the lower limbs and the back. Kinematic data, obtained with the aid of a video camera, were combined with the force platform data to allow for calculation of the lower limb and L5-S1 torques as well as L5-S1 compressive forces. The trucker descended from two different conventional tractor cabin layouts. Each trucker descended from cabin using either "facing the truck" (FT) or "back to the truck" (BT) techniques. The results demonstrate that the BT technique produces greater ground impact forces than the FT technique, particularly when the truck does not have a handrail. The BT technique also causes an increase in the compressive forces exerted on the back. In conclusion, the use of the FT technique along with the aids (i.e., handrails and all the steps) help lower the landing impact forces as well as the lumbosacral compressive forces.

[The supra-occipital bone in cetaceans and burrowing rodents. morphological convergence induced by the post-cephalic pole?]. / Le supra-occipital des Cétacés et des Rongeurs fouisseurs. Une convergence morphologique induite par le pôle post-céphalique?

A comparative study of the cranial morphologies of cetaceans and of rodents that use their incisors for burrowing brings out morphological convergences concerning the supra-occipital bone. These phyletically very remote groups are both subject to the same mechanical constraint, viz. the need for the spinal column to be aligned with the anteroposterior axis of the skull. This constraint, which is related to swimming in cetaceans and burrowing in rodents, entails three major points of convergence: 1) a clearly backward facing foramen magnum; 2) a shortened or even greatly shortened neck, sometimes with cervical vertebrae fused together; and 3) an uprighted or even forward tilted supra-occipital bone.

Assessment of wood utility pole climbability using psychophysical and mechanical measurements.

The issue of climbability has been raised on several occasions for more than a decade in North America. Presently, climbability is estimated from the pole hardness measured by the Pilodyn measurements (6 J). However, the use of Pilodyn measurements to discriminate the pole hardness value is criticized by climbers, who claim that the Pilodyn hardness measurement is affected by species-treatment combinations and that it does not reflect gaff penetration or climbability. Furthermore, climbability evaluations have been conducted in which test poles were climbed by linemen, and corresponding subjective ratings were recorded. However, the ability of psychophysical measurements to accurately discriminate close hardness pole values and to differentiate species-treatment combinations at specific hardness levels have not yet been fully documented. The aim of this study is to evaluate the psychophysical perception of linemen and the mechanical measurements of gaff penetration and gaff impact during the climbing of different wood species and treatment combinations in order to compare these results with Pilodyn measurements within a precise range of pole hardnesses, to study the relationships between these variables, and, finally, to propose various design guidelines for the development of a better tool for the evaluation of climbability.

Heterogeneity of antigen expression among human umbilical cord vascular endothelial cells: identification of cell subsets by co-expression of haemopoietic antigens.

First described as an interface between blood and tissues, the endothelial cells are now known to be also involved in haemostasis, inflammatory and immune responses. Recent studies have reported that the endothelial cells represent a heterogeneous population of cells with organ-specific properties. This report describes the phenotype analyzed by flow cytometry of human umbilical vascular endothelial cells (HUVEC). For this purpose, we use monoclonal antibodies (Mabs) recognizing B cell antigens (CD10, 19, 20, 21, 22, 23, 24, 38, 40), T cell antigens (CD1, 2, 3, 4, 5, 6, 7, 8), myeloid antigens (CD13, 14, 15, 34, 35, 64), platelet antigens (CD9, 31, 51, 62P), NK and non-lineage cell antigens (CD16, 45, 56, 57), activation antigens (CD25, 30, 69, 71) and adhesion molecules (CD11a, CD11b, 29, 44, 54, 62E, 102, 106). Mabs recognizing MHC ClI or ClII molecules are also tested. Firstly, we show that HUVEC co-express some haemopoietic antigens with different levels of expression. Secondly, this study reveals that the HUVEC population does not represent a homogeneous cell population. Different endothelial cell subsets are identified. These phenotypical differences could reflect specialization of HUVEC performing different functions. The significant of haemopoietic antigen expression on the HUVEC surface will be discussed.

Brazilian daycares: weighing the risks and benefits.

PIP: The number of day care centers in Brazil has doubled over the last few years; with this increase has come a rise in the numbers of cases of communicable disease, particularly pneumonia (the main cause of child mortality in Brazil). A study by Dr. Walter V.C. da Fonseca states that a day care child is 5 times more likely to contact pneumonia. However, since the income earned by women in Brazil today is necessary to meet basic needs, children must be left at home with relatives or sent to day care. Most of the centers taking in children under 6 years of age are urban; they care for, on average, 125-200 children. These children are usually from low income families who live on the outskirts of cities; free day care is only provided to working mothers. There are 3 social factors involved: the greater number of single-parent families, more households supported solely by the mother, and an economic crisis that has hit the poor particularly hard. Financial and administrative responsibility for these centers varies. The centers provide meals, baths, rest, education (including some special education services), and health care (doctors, dentists, and nurses). Some accept abandoned children, who are cared for until they are adopted. However, new studies indicate that the centers represent the primary risk factor for respiratory illnesses and were, until recently, the principal causes of diarrhea and child mortality. An ongoing comparative study by da Fonseca is analyzing the incidence rates of respiratory and infectious diseases among 400 children attending a nursery in Fortaleza in comparison to those for 400 cared for at home by family. Doctor Aluiso Barros, in another study, is observing 1000 children in 40 nurseries in Campinas. For 8 weeks, data was collected on the health, socioeconomic situation, medical history, and family medical history of each child. The nurseries were examined and information was collected regarding the number of diseases reported each month, their causes, possible associations with services provided, and possibilities of transmission. Dr. Barros' research is supported by IDRC; Dr. da Fonseca's is supported by the British Overseas Development Agency.^ieng