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In our study, we hypothesized that sternum-mental angle (SMA) was a totally new preoperative predictor of difficult laryngeal exposure (DLE). The main objective of this study was to evaluate the diagnostic utility of SMA in predicting DLE in patients undergoing suspension microlaryngeal surgery, and we also searched for risk factors among the selected parameters.

When protons and neutrons (nucleons) are bound into atomic nuclei, they are close enough to feel significant attraction, or repulsion, from the strong, short-distance part of the nucleon–nucleon interaction. These strong interactions lead to hard collisions between nucleons, generating pairs of highly energetic nucleons referred to as short-range correlations (SRCs). SRCs are an important but relatively poorly understood part of nuclear structure1–3, and mapping out the strength and the isospin structure (neutron–proton (np) versus proton–proton (pp) pairs) of these virtual excitations is thus critical input for modelling a range of nuclear, particle and astrophysics measurements3–5. Two-nucleon knockout or ‘triple coincidence’ reactions have been used to measure the relative contribution of np-SRCs and pp-SRCs by knocking out a proton from the SRC and detecting its partner nucleon (proton or neutron). These measurements6–8have shown that SRCs are almost exclusively np pairs, but they had limited statistics and required large model-dependent final-state interaction corrections. Here we report on measurements using inclusive scattering from the mirror nuclei hydrogen-3 and helium-3 to extract the np/pp ratio of SRCs in systems with a mass number of three. We obtain a measure of the np/pp SRC ratio that is an order of magnitude more precise than previous experiments, and find a marked deviation from the near-total np dominance observed in heavy nuclei. This result implies an unexpected structure in the high-momentum wavefunction for hydrogen-3 and helium-3. Understanding these results will improve our understanding of the short-range part of the nucleon–nucleon interaction.

Quantitative assessments of liver fibrosis using second-harmonic generation/two-photon excited fluorescence microscopy provide greater sensitivity and accuracy than collagen proportionate area while eliminating operator-dependent variation in the staining process. In conjunction with sophisticated image analysis algorithms and feature selection, we might reduce the computation cost in future and narrow down the candidates for further clinical studies.

AimsWe aimed to determine the effect of dementia and Parkinson’s disease on one, three and 12-month mortality following surgery for fracture of the hip in elderly patients from an Asian population.Patients and MethodsUsing a random sample of patients taken from the Taiwan National Health Insurance Research Database, this retrospective cohort study analyzed the data on 6626 elderly patients who sustained a fracture of the hip between 1997 and 2012 who had ICD-9 codes within the general range of hip fracture (820.xx). We used Cox regression to estimate the risk of death associated with dementia, Parkinson’s disease or both, adjusting for demographic, clinical, treatment, and provider factors.ResultsAmong 6626 hip fracture patients, 10.20% had dementia alone, 5.60% had Parkinson’s disease alone, and 2.67% had both. Corresponding one-year mortality rates were 15.53%, 11.59%, and 15.82%, compared with 9.22% for those without neurological illness. Adjusted hazard ratio for one-year mortality was 1.45 (95% confidence intervals (CI) 1.17 to 1.79) for those with dementia, and 1.57 (95% CI 1.07 to 2.30) with both dementia and Parkinson’s disease versuspatients with neither. There was no significant association with death for Parkinson’s disease alone. Age, male gender and comorbidities were also associated with a higher risk of mortality.ConclusionDementia, with or without Parkinson’s disease, is an independent predictor of mortality following surgery for fractures of the hip. Age, male gender and comorbidities also increase the risk of death. Parkinson’s disease alone has no significant effect.Cite this article: Bone Joint J2018;100-B:1220–6.

Previous studies have identified education as an important indicator of future psychological outcomes through the lens of parental education level. Here, we seek to understand how education affects suicide through the perspective of the child's education.

The effects of tensile stresses on isothermal bainitic transformation were studied in the case of a 35MV7 steel. The modification of transformation kinetics and the presence of transformation plasticity is shown in a first step. Furthermore, the effect of stress on the morphological modifications of the ferrite laths is illustrated. The role of the stress on these changes is analysed.

We present results from an experimental and numerical investigation on the compression, and consequent buckling, of a slender rod constrained inside a horizontal cylinder. An experimental model system is developed to systematically study the sequence of instabilities from straight-to-sinusoidal and sinusoidal-to-helical configurations. We quantify the associated buckling loads as a function of the radial clearance between the rod and cylindrical constraint. These results are compared to existing theoretical predictions. While good agreement is obtained for large values of the radial clearance, significant deviations are found when the geometric imperfections of the setup are comparable to the radial clearance. Due to this imperfection sensitivity, the critical buckling loads can be reduced significantly by up to a factor of three. The findings from this model system can be applied to practical applications across a range of length scales due to the geometric (rather than material) nonlinearities involved in the deformations of rods.

Dry sliding wear tests were performed on AZ31 alloy using a pin-on-disc configuration under the loads of 5–360 N and sliding speeds of 0.1–1.5 m/s. Friction and wear characteristics of AZ31 alloy were investigated as a function of the load and sliding speed. Wear mechanisms for AZ31 alloy were characterized by scanning electron microscopy. The wear behavior in mild and severe wear regimes was described in terms of plastic deformation and microstructure evolution in subsurface, and surface hardness change and temperature rise of worn surfaces. The results revealed that surface strain hardening caused by large plastic deformation played an important role in maintaining a low slope of wear rate in mild wear regime, while surface thermal softening originating from dynamic recrystallization and surface melting were responsible for a rapid wear in severe wear regime.

A warmer climate impacts streamflows and these changes need to be quantified to assess future risk, vulnerability, and to implement efficient adaptation measures. The climate simulations from the fifth phase of the Coupled Model Intercomparison Project (CMIP5), which have been the basis of most such assessments over the past decade, are being gradually superseded by the more recent Coupled Model Intercomparison Project Phase 6 (CMIP6). Our study portrays the added value of the CMIP6 ensemble over CMIP5 in a first North America wide comparison using 3,107 catchments. Results show a reduced spread of the CMIP6 ensemble compared to the CMIP5 ensemble for temperature and precipitation projections. In terms of flow indicators, the CMIP6 driven hydrological projections result in a smaller spread of future mean and high flow values, except for mountainous areas. Overall, we assess that the CMIP6 ensemble provides a narrower band of uncertainty of future climate projections, bringing more confidence for hydrological impact studies. Greenhouse gas emissions are causing the climate to warm significantly, which in turn impacts flows in rivers worldwide. To adapt to these changes, it is essential to quantify them and assess future risk and vulnerability. Climate models are the primary tools used to achieve this. The main data set that provides scientists with state‐of‐the‐art climate model simulations is known as the Coupled Model Intercomparison Project (CMIP). The fifth phase of that project (CMIP5) has been used over the past decade in multiple hydrological studies to assess the impacts of climate change on streamflow. The more recent sixth phase (CMIP6) has started to generate projections, which brings the following question: is it necessary to update the hydrological impact studies performed using CMIP5 with the new CMIP6 models? To answer this question, a comparison between CMIP5 and CMIP6 using 3,107 catchments over North America was conducted. Results show that there is less spread in temperature and precipitation projections for CMIP6. This translates into a smaller spread of future mean, high and low flow values, except for mountainous areas. Overall, we assess that using the CMIP6 data set would provide a more concerted range of future climate projections, leading to more confident hydrological impact studies. A comparison of hydrological impacts using Coupled Model Intercomparison Project version 5 (CMIP5) and Coupled Model Intercomparison Project Phase 6 (CMIP6) ensembles is performed over 3,107 catchments in North AmericaThe CMIP6 ensembles provide a narrower band of uncertainty for hydrological indicators in the futureIt is recommended to update hydrological impact studies performed using CMIP5 with the CMIP6 ensemble A comparison of hydrological impacts using Coupled Model Intercomparison Project version 5 (CMIP5) and Coupled Model Intercomparison Project Phase 6 (CMIP6) ensembles is performed over 3,107 catchments in North America The CMIP6 ensembles provide a narrower band of uncertainty for hydrological indicators in the future It is recommended to update hydrological impact studies performed using CMIP5 with the CMIP6 ensemble

Zr–TiO2synthesized heterogeneous catalysts could efficiently convert ethyl levulinates (ELs) to γ-valerolactone (GVL) using isopropanol (2-PrOH) as H-donor. Obtained catalysts were characterized by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Scanning electron microscope (SEM), High revolution transmission electron microscope (HR-TEM), Fourier transform infrared spectroscopy (FT-IR), inductively coupled plasma optical emission spectroscopy (ICP-OES), NH3/CO2temperature programmed desorption (NH3/CO2-TPD), pyridine-infrared spectroscopy, H2temperature-programmed reduction (H2-TPR), and N2adsorption and desorption measurements. In total, 10 wt% Zr–TiO2with average nanoparticle sizes (ca. 4–6 nm) exhibited optimum catalytic activity after optimization of reaction temperature, reaction time, catalyst loading, as well as solvent effect. GVL yield reached 74% with 79% EL conversion at 190 °C for 5 h over 10 wt% Zr–TiO2in 2-PrOH. The high catalytic activity could be attributed to an appropriate proportion of acidic/basic sites, high Brønted/Lewis acid ratio, and large surface areas. Both acidic and basic sites lead to a synergistic effect on the concurrent activation of H-donor and substrate. The major side product ethyl 4-hydroxypentanoate (EHP) and other byproducts were found. GVL yield achieved from methyl levulinate (ML) and levulinic acid (LA) were 65% and 20%, respectively. Catalyst deactivation was observed due to coke deposits on the catalyst’s surface. The spent catalyst proved to be reusable to recover almost completely its initial activity after calcination (300 °C, 2 h). A plausible reaction mechanism is presented on the basis of characterization results.

In this work, a monopole antenna with defect ground is proposed for ultra wideband EMC measurement in communication system. The antenna is fed by micro-strip. It is demonstrated that the antenna provides an impedance bandwidth ranging from 2.5 GHz to 13.5 GHz (for VSWR < 2) and supports an adequate pattern.

Hydrogenated nanocrystalline silicon (nc-Si:H) is a promising candidate to replace the hydrogenated amorphous silicon-germanium alloy (a-SiGe:H) in multijunction thin-film silicon solar cells due to its superior long-wavelength response and stability against light-induced degradation. Due to its indirect bandgap, the absorbing nc-Si:H layer needs to be much thicker than its amorphous counterpart. For nc-Si:H-based solar cells to be commercially viable, the challenge is to deposit the nc-Si:H layer at a high rate with good quality. In this paper, we report on the development of our proprietary high-frequency glow discharge deposition technology to fabricate high-efficiency, large-area, a-Si:H/nc-Si:H/nc-Si:H triple-junction solar cells at a high deposition rate >;1 nm/s. The National Renewable Energy Laboratory (NREL) has confirmed stable efficiency of 12.41% on a 1.05-cm2 solar cell. We have attained initial efficiency of 12.33% on an encapsulated cell of aperture area ~400 cm2 ; the corresponding stable efficiency is projected to be 11.7-11.9%.

We explored the concentration gradient effects of the sodium and lithium ions and the deuterium isotope's effects on the activities of H+-ATP synthase from chloroplasts (CF0F1). We found that the sodium concentration gradient can drive the ATP synthesis reaction of CF0F1. In contrast, the lithium ion can be an efficient enzyme-inhibitor by blocking the entrance channel of the ion translocation pathway in CF0. In the presence of sodium or lithium ions and with the application of a membrane potential, unexpected enzyme behaviors of CF0F1were evident. To account for these observations, we propose that both of the sodium and lithium ions could undergo localized hydrolysis reactions in the chemical environment of the ion channel of CF0. The protons generated locally could proceed to complete the ion translocation process in the ATP synthesis reaction of CF0F1. Experimental and theoretical deuterium isotope effects of the localized hydrolysis on the activities of CF0F1, and the energetics of these related reactions, support this proposed mechanism. Our experimental observations could be understood in the framework of the well-established ion translocation models for the H+-ATP synthase from Escherichia coli,and the Na+-ATP synthase from Propionigenium modestumand Ilyobacter tartaricus.

Abstract: Conformational transitions in a 4-way DNA junction when titrated with ionic solutions are studied using time-resolved fluorescence resonance energy transfer. Parameters characterising the transition in terms of critical ion concentration (c 1/2) and the Hill coefficient for ion binding are obtained by fitting a simple two-state model using steady-state spectra. Data obtained from a fluorescence lifetime plate reader and analysed by fitting a single exponential to donor fluorescence lifetime decays are shown to be in good agreement with the parameters obtained from steady-state measurements. Fluorescence lifetimes, however, offer advantages, particularly in being independent of fluorophore concentration, output intensity, inhomogeneity in the excitation source and output wavelength. We demonstrate preliminary FRET-FLIM images of DNA junction solutions obtained using a picosecond gated CCD which are in agreement with results from a fluorescence lifetime plate reader. The results suggest that time-resolved FRET-FLIM is sensitive to subtle structural changes and may be useful in assays based on 4-way DNA junctions.

Although originally proposed as a subtype of opioid receptors, the sigma receptor is now confirmed to be a non-opioid receptor that binds diverse classes of psychotropic drugs. Sigma receptors are subdivided into two subtypes, sigma-1 and sigma-2. The sigma-1 receptor is a 25-kDa protein possessing one putative transmembrane domain and an endoplasmic reticulum retention signal. Sigma-1 receptors are highly expressed in deeper laminae of the cortex, olfactory bulb, nuclei of mesencephalon, hypothalamus, and Purkinje cells in the brain. Sigma-1 receptors are predominantly localized at the endoplasmic reticulum of both neurons and oligodendrocytes. From behavioral studies, sigma-1 receptors were shown to be involved in higher-ordered brain functions including memory and drug dependence. The actions mediated by sigma-1 receptors at the cellular level can be considered either as acute or chronic. The acute actions include the modulation of ion channels (i.e., K+ channel, NMDA receptors, IP3 receptors) and the sigma-1 receptor translocation. Chronic actions of sigma-1 receptors are basically considered to be the result of an up- or down regulation of the sigma-1 receptor itself. For example, the upregulation of sigma-1 receptors per se, even without exogenous ligands, promotes cellular differentiation and reconstitution of lipid microdomains (lipid rafts) in cultured cells. These findings together suggest that sigma-1 receptors might possess a constitutive biological activity, and that sigma-1 receptor ligands might merely work as modulators of the innate activity of this protein. Recent in vitro and in vivo studies strongly point to the possibility that sigma-1 receptors participate in membrane remodeling and cellular differentiation in the nervous system.

Pregabalin (PGB) is a novel drug under development for the treatment of epilepsy, neuropathic pain, fibromyalgia, and generalized anxiety disorder. In this study, we investigated PGB transport in rats, mammalian cell lines, and Xenopus laevis oocytes. In contrast to gabapentin (GBP), PGB absorption in rats showed unique linear pharmacokinetics. PGB entered CHO and Caco-2 cells predominately via Na(+)-independent processes. Uptake of PGB was mutually exclusive with leucine, GBP and 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid, the substrates preferential for system L. The preloaded PGB in CHO cells was exchangeable with leucine, but at a lower exchange rate than that of leucine and GBP. Dixon plots showed competitive inhibition of leucine uptake by PGB, with a K(i) value very close to the K(m) value for PGB uptake (377 versus 363 microM). At an extracellular concentration of 300 microM, the intracellular PGB concentration in CHO cells reached 1.5- and 23-fold higher than that of GBP and leucine, respectively. In contrast, at clinically relevant concentrations, PGB seemed not to interact with GABA transport in GAT1, GAT2, and GAT3 cell lines, system y(+), b(0,+), B(0,+), and B(0) transport activities in Caco-2 and NBL-1 cells, and the b(0,+)-like transport activity in rBAT cRNA-injected X. laevis oocytes. Taken together, these results suggest that L-type transport is the major transport route for PGB and GBP uptake in mammalian cells. The differential affinity of PGB and GBP at L-type system leads to more concentrative accumulation of PGB than GBP, which may facilitate PGB transmembrane absorption in vivo.

As part of a program aimed at generating compounds with affinity for the α2-δ subunit of voltage-gated calcium channels, several novel β-amino acids were prepared using an efficient nitroalkane-mediated cyclopropanation as a key step. Depending on the ester that was chosen, the target amino acids could be prepared in as few as three steps. The cyclopropyl amino acids derived from ketones proved to be potent binders of the α2-δ subunit of voltage-gated calcium channels, but did not interact with the large neutral amino acid system L (leucine) transporter. Anticonvulsant effects were observed in vivo with compound 34 but only after intracerebroventricular (icv) administration, presumably due to inadequate brain concentrations of the drug being achieved following oral dosing. However, pregabalin 1 was active in the DBA/2 model after oral (and icv) dosing, supporting a hypothesis that active transport is a prerequisite for such zwitterionic species to cross the blood−brain barrier.

Pregabalin exhibits robust activity in preclinical assays indicative of potential antiepileptic, anxiolytic, and antihyperalgesic clinical efficacy. It binds with high affinity to the α2-δ subunit of voltage-gated calcium channels and is a substrate of the system L neutral amino acid transporter. A series of pregabalin analogues were prepared and evaluated for their α2-δ binding affinity as demonstrated by their ability to inhibit binding of [³H]gabapentin to pig brain membranes and for their potency to inhibit the uptake of [³H]leucine into CHO cells, a measure of their ability to compete with the endogenous substrate at the system L transporter. Compounds were also assessed in vivo for their ability to promote anxiolytic, analgesic, and anticonvulsant actions. These studies suggest that distinct structure activity relationships exist for α2-δ binding and system L transport inhibition. However, both interactions appear to play an important role in the in vivo profile of these compounds.

A new triphenylamine-containing aromatic diamine, N,N-bis(4-aminophenyl)-N‘,N‘-diphenyl-1,4-phenylenediamine, was synthesized from the amination reaction between 4-aminotriphenylamine and 4-fluoronitrobenzene and subsequent reduction of the dinitro intermediate. A series of novel aromatic poly(amine-imide)s with pendent triphenylamine units were prepared from the newly synthesized diamine and various tetracarboxylic dianhydrides by either a one-step or a conventional two-step polymerization process. All the poly(amine-imide)s were amorphous and readily soluble in many organic solvents such as N-methyl-2-pyrrolidone (NMP), N,N-dimethylacetamide, and chloroform. These polymers could be solution cast into transparent, tough, and flexible films with good mechanical properties. They had useful levels of thermal stability associated with relatively high glass transition temperatures (264−352 °C), 10% weight-loss temperatures in excess of 568 °C, and char yields at 800 °C in nitrogen higher than 63%. These polymers exhibited strong UV−vis absorption bands at 311−330 nm in NMP solution. The photoluminescence spectra showed maximum bands around 545−562 nm in the green region. The hole-transporting and electrochromic properties are examined by electrochemical and spectroelectrochemical methods. Cyclic voltammograms of the poly(amine-imide) films cast onto an indium−tin oxide (ITO)-coated glass substrate exhibited two reversible oxidation redox couples at 0.78 and 1.14 V versus Ag/AgCl in acetonitrile solution. The poly(amine-imide) films revealed excellent stability of electrochromic characteristics, with a color change from the pale yellowish neutral form to the green and blue oxidized forms at applied potentials ranging from 0.78 to 1.14 V.

Single molecule fluorescence imaging incorporated with optical tweezers and a laminar flow cell has been used to monitor the kinetic process of DNA condensation induced by spermidine. It was found that at least two steps were involved in the condensation process of the hydrodynamically-stretched linear DNA; a lag period followed by a rapid collapse of DNA. The lag time increased with the flow speed and the collapse time remained short within the range of the flow speed studied. The effect of salt concentration on the condensation process was examined, and the results suggest that the longer lag time observed in the higher salt buffer probably results from the displacement of bound cations and rearrangement of spermidine on the DNA. The flow-speed dependence of the lag time suggests that a nucleation event at the free end of the DNA, i.e. formation of a loop, may play a vital role in the kinetic process of condensation.

Neutron reflectivity (NR) has been used to determine the structure of dry and swollen PC100B biocompatible phosphorylcholine (PC) polymer films coated on the optically flat silicon oxide surfaces. Deuterium labeling to the dodecyl chain of PC100B polymer was found to be effective at highlighting the interfacial structure of dry PC100B films while the swelling with D2O into the fully hydrogenated PC100B polymer produced sufficient isotopic contrast for revealing structural features within the swollen films. The main structural characteristics of the dry PC films were found to consist of alternate layers at the SiO2/polymer and polymer/air interfaces, indicating that thermal annealing promoted segregation of hydrophilic and hydrophobic moieties within the polymer. The thicknesses of these sublayers were between 10 and 30 Å, and the layering feature gradually became diminished into the middle film region which is characterized by a uniform scattering length density (SLD) determined by NR. It was further observed that the outer surfaces of the dry polymer films contained a significant fraction of hydrophobic moiety as a result of surface energy minimization during annealing, but upon swelling in water this structural feature was deteriorated by fragment motions and redistributions. In contrast to the greater structural variation on the outer film surface, swelling had relatively less effect on the internal layering structure at the SiO2/polymer interface due to the structural constraints imposed by silyl cross-linking and the hydrophobic barrier to water diffusion. The thickness of the middle part of uniform region increases with dry film thickness, but the alternate layering at the interfaces was largely unaffected. The increase in annealing temperature enhanced silyl cross-linking, resulting in the reduced equilibrium water content across the films and the slowdown of the rate of swelling.

The adsorption of glucose oxidase (GOx) was studied at the interface between two immiscible electrolyte solutions (ITIES) by interfacial capacitance and surface tension measurements and at the air/water (phosphate buffer) interface by surface tension and neutron reflection measurements. The adsorption at both interfaces was found to be time, enzyme concentration, and ionic strength dependent. There was a switch from one interfacial adsorption state to another, as the enzyme concentration was increased. At the ITIES, there was evidence of an interaction between the adsorbed enzyme and the hydrophobic cation in the organic phase (1,2-dichloroethane). The enzyme adsorbed at the air/water interface was found to dissociate into monomers at the lower buffer total concentration of 2 mM while, at the higher buffer concentration of 0.2 M, the adsorbed enzyme retained its dimer structure. The adsorption mostly formed monolayers and the layer thickness varied with bulk concentration, indicating deformation related to the packing of the enzyme at the interface. For enzyme concentrations above 1 μM, in high ionic strength medium, bilayers of enzyme started to form, and the interlayer interactions resulted in a less densely packed second layer forming on the aqueous side of the first one. The switch in properties of the adsorbed layer observed in interfacial tension and capacitance measurements at the ITIES occurred over the same enzyme concentration range as the formation of a more densely packed layer detected from neutron reflection at the air/water interface.

Abstract: The interfacial reactions of liquid Sn and Sn-3.5Ag solders with Ag thick films are investigated in the temperature range from 250–325 �C, and the morphology of intermetallic compounds formed after such soldering reactions is observed. In kinetics analysis of the growths of intermetallic compounds, it was found that both Sn/Ag and Sn-3.5Ag/Ag reactions were interfacial-controlled, and the growth rates for both cases were similar. The rate of Ag dissolution into liquid solder attendant on the formation of interfacial intermetallic compounds after Sn/Ag reaction was about four times higher than that after Sn-3.5Ag/Ag reaction, as evidenced by experimental results.

DNA minor groove binder hybrid molecules, netropsin derivatives such as N-[2-(dimethylamino)ethyl]-1-methyl-4-aminopyrrolo-2-carboxamide (MePy) or its derivatives containing two units of N-methylpyrrolecarboxamide (diMePy) and bisbenzimidazole (Ho33258), were linked to the NH2 function of AHMA or to the CH2OH group of AHMA-ethylcarbamate to form AHMA−N-netropsins (13−16) and AHMA−ethylcarbamate-O-netropsins (19−22), and AHMA−bisbenzimidazole (AHMA−Ho33258, 25), respectively. These conjugates' in vitro antitumor activity, inhibition of a variety of human tumor cell growth, revealed that AHMA−ethylcarbamate-O-netropsin derivatives were more cytotoxic than AHMA−N-netropsin compounds. In the same studies, all compounds bearing MePy were more potent than those compounds linked with diMePy. Moreover, AHMA−netropsin derivatives bearing a succinyl chain as the linking spacer were more potent than those compounds having a glutaryl bridge. Among these hybrid molecules, AHMA−ethylcarbamate-O-succinyl-MePy (19) was 2- to 6-fold more cytotoxic than the parent compound AHMA (5) in various cell lines, whereas compound 25 had very poor solubility and was inactive. Studies on the inhibitory effect against topoisomerase II (Topo II) and DNA interaction of these conjugates showed no correlation between the potency of DNA binding and inhibitory activity against Topo II.

β(25–35) is a fragment of β-amyloid that retains its wild-type properties. N-methylated derivatives of β(25–35) can block hydrogen bonding on the outer edge of the assembling amyloid, so preventing the aggregation and inhibiting the toxicity of the wild-type peptide. The effects are assayed by Congo Red and thioflavin T binding, electron microscopy and an MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] toxicity assay. N-methyl-Gly-25 has similar properties to the wild-type, while five other methylation sites have varying effects on prefolded fibrils and fibril assembly. In particular, N-methyl-Gly-33 is able to completely prevent fibril assembly and reduces the toxicity of prefolded amyloid. With N-methyl-Leu-34 the fibril morphology is altered and toxicity reduced. A preliminary study of β(25–35) structure in aqueous solution was made by small-angle neutron scattering (SANS). The protofibrillar aggregates are best described as a disc of radius 140 å and height 53 å (1 å = 0.1 nm), though the possibility of polydisperse aggregates cannot be ruled out. No aggregates form in the presence of N-methyl-Gly-33. We suggest that the use of N-methylated derivatives of amyloidogenic peptides and proteins could provide a general solution to the problem of amyloid deposition and toxicity and that SANS is an important technique for the direct observation of protofibril formation and destruction in solution.

For the soldering of recycled Ag sputtering targets, the interfacial reaction between liquid Sn and an Ag substrate at temperatures ranging from 250 –425°C has been investigated. Experimental results show that a scallop-shaped layer of Ag3Sn intermetallic compounds formed during the soldering reaction. Kinetics analysis indicated that the growth of such interfacial Ag3Sn intermetallic compounds is diffusion-controlled with activation energy of 70.3kJ/mol. During the reaction, the Ag substrate dissolves into the molten Sn solder and causes the appearance of needle-shaped Ag3Sn precipitates in the Sn matrix.

Abstract: The corrosion behaviors of a series of Al-Si-Cu-based filler metals and the 6061-T6 butt joints brazed with these filler metals are evaluated by polarization tests and immersion tests in a 3.5% NaCl aqueous solution. For comparison, a traditional Al-12Si filler metal is also employed. The results indicate that the Al-Si-Cu-based filler metals before brazing possess much higher corrosion current densities and pitting tendencies than the Al-12Si filler metal. However, brazing of the 6061-T6 alloy with an Al-12Si filler metal produces a wider butt joint, which, in this case, creates a more extensive corrosion region. Severe galvanic corrosion occurs at the 6061-T6 joints when brazed with Al-Si-Cu-based filler metals. However, in the case of the 6061-T6/Al-12Si brazements, selective corrosion of the Al-12Si eutectic phase can be observed. The bonding strengths of the 6061-T6 butt joints brazed with various filler metals are also measured before and after the immersion tests.

Drosophila 14-3-3 epsilon and 14-3-3 zeta proteins have been shown to function in RAS/MAP kinase pathways that influence the differentiation of the adult eye and the embryo. Because 14-3-3 proteins have a conserved involvement in cell cycle checkpoints in other systems, we asked (1) whether Drosophila 14-3-3 proteins also function in cell cycle regulation, and (2) whether cell proliferation during Drosophila development has different requirements for the two 14-3-3 proteins. We find that antibody staining for 14-3-3 family members is cytoplasmic in interphase and perichromosomal in mitosis. Using mutants of cyclins, Cdk1 and Cdc25(string) to manipulate Cdk1 activity, we found that the localization of 14-3-3 proteins is coupled to Cdk1 activity and cell cycle stage. Relocalization of 14-3-3 proteins with cell cycle progression suggested cell-cycle-specific roles. This notion is confirmed by the phenotypes of 14-3-3 epsilon and 14-3-3 zeta mutants: 14-3-3 epsilon is required to time mitosis in undisturbed post-blastoderm cell cycles and to delay mitosis following irradiation; 14-3-3 zeta is required for normal chromosome separation during syncytial mitoses. We suggest a model in which 14-3-3 proteins act in the undisturbed cell cycle to set a threshold for entry into mitosis by suppressing Cdk1 activity, to block mitosis following radiation damage and to facilitate proper exit from mitosis.

Neutron reflectometry was used to investigate the time-dependent β-casein adsorption at the silica−aqueous solution interface. The transient and steady-state structural characteristics of the adsorbed layer were determined from reflectivity curves, fitted to three-layer and two-layer models. The results show that the β-casein adsorption to silica is very slow. The adsorption process involves the formation of an inner dense protein layer with a mean thickness of about 30 Å onto which a more hydrated outer layer is self-associated. The surface excess and the total layer thickness of the asymmetric bilayer were, after 5 h adsorption time, estimated to be about 6.5 mg/m² and 105 Å, respectively. The adsorption behavior observed on silica contrasts with that previously reported for hydrophobic substrates, where β-casein adsorption is much more rapid and the final surface excess is less than half of that observed for silica. Rinsing the silica surface with protein-free buffer resulted in a substantial desorption; much more pronounced than observed for hydrophobic substrates. This behavior suggests a weak adsorption affinity for a fraction of the adsorbed casein molecules; most likely the outer self-associated casein molecules in the adsorbed bilayer. The comparative desorption from hydrophobic surfaces was shown to be marginal. The difference between the layer structures adopted on hydrophobic and hydrophilic surfaces is also mirrored in the effects that the addition of a specific proteolytic enzyme (endoproteinase Asp-N) has on the adsorbed layer properties. The rinsing and endoproteinase cleavage processes result together in more than 80% reduction of the originally adsorbed mass at the silica surface. Only a thin but dense adsorbed layer remains after these treatments. The corresponding reduction reported for the hydrophobic adsorbent system was only about 20%. It is concluded that β-casein adsorption on silica results in the formation of an asymmetric surface bound bilayer that stands in strong contrast to the monolayer structure formed at hydrophobic surfaces. This finding support the previous results obtained by using ellipsometry. The study also shows that neutron reflection, despite its limitations in time resolution, can be used for studying dynamic interfacial phenomena in protein systems.

The interaction of neuroactive steroids with the sigma(1)-receptor was investigated in Swiss mice submitted to the forced swimming test. The sigma(1)-agonists igmesine and (+)-SKF-10,047 and the steroid dehydroepiandrosterone sulfate (DHEAS) showed some antidepressant-like activity by shortening the immobility time, these effects being blocked by the sigma(1)-antagonist BD1047 or progesterone. The sigma(1)-agonist PRE-084 or pregnenolone sulfate failed to affect the immobility time. In adrenalectomized/castrated (AdX/CX) mice, the effects of igmesine and DHEAS were significantly potentiated, and PRE-084 or pregnenolone sulfate induced significant decreases of immobility time. The augmented effects in AdX/CX were fully blocked by BD1047. The effects of the classical antidepressants, desipramine or fluoxetine, were unchanged in AdX/CX mice. The effect of stress on the sigma(1)-receptor binding and neurosteroid levels was then examined in different brain structures, in terms of in vivo (+)-[(3)H]SKF-10,047 binding to sigma(1)-sites and neurosteroids levels. In the hippocampus, but not in the cortex or cerebellum, inhibition of in vivo (+)-[(3)H]SKF-10,047 binding was measured in parallel to the extent of progesterone levels according to the endocrine conditions. These data confirmed the antidepressant ability of sigma(1)-receptor agonists and revealed that the endogenous steroidal levels tonically interfere with the efficacy of the sigma(1)-system. It was observed that local modifications in progesterone levels are directly related to the changes of in vivo sigma(1)-binding. Such observations may be of major importance in view of the therapeutic use of selective sigma(1)-agonists in depression.

Neutron reflectivity has been used to investigate the interaction between the cationic surfactant dodecyltrimethylammonium bromide (C12TAB) and preadsorbed lysozyme layers at the hydrophilic silica−water interface. Reflectivity measurements were carried out with two different concentrations of lysozyme and a range of C12TAB concentrations at a solution pH of 7. A preadsorbed lysozyme layer was prepared by adsorption from 0.03 or 1 g dm^-3 protein solutions. The effect on the adsorbed protein layer structure upon addition of a range of surfactant concentrations, from 0.2 to 14 mM, was determined and the surface excesses of both protein and surfactant within the adsorbed layers calculated. The surface composition of the mixed layers and their structural distributions were identified with the help of the variation of hydrogen/deuterium labeling to the surfactant. It was found that upon increasing surfactant concentration the protein was gradually replaced by the surfactant at the interface. However, a simple replacement mechanism was not observed. Protein removal over the low surfactant concentration range was accompanied by little surfactant adsorption, showing that the desorption was likely to be caused by the formation of highly soluble protein/surfactant complex. At the high surfactant concentration, protein removal was driven by the interplay of the interactions involving the protein, surfactant, and substrate, as evidenced from the coadsorption of surfactant and protein at the interface and the variation of interfacial composition with surfactant concentration. These results, together with previous measurements using sodium dodecyl sulfate (SDS) suggest that for surfactants with the same alkyl chain length the fraction of protein removal is dictated by the nature of the surfactant headgroups. These studies have shown that neutron reflectivity has distinct advantages over other techniques in investigating multicomponent interfacial systems involving biomolecules.

Exogenous application of transforming growth factors-β (TGFβ) family proteins, including glial cell line-derived neurotrophic factor (GDNF), neurturin, activin, and bone morphogenetic proteins, has been shown to protect neurons in many models of neurological disorders. Finding a tissue source containing a variety of these proteins may promote optimal beneficial effects for treatment of neurodegenerative diseases. Because fetal kidneys express many TGFβ trophic factors, we transplanted these tissues directly into the substantia nigra after a unilateral 6-hydroxydopamine lesion. We found that animals that received fetal kidney tissue grafts exhibited (1) significantly reduced hemiparkinsonian asymmetrical behaviors, (2) a near normal tyrosine hydroxylase immunoreactivity in the lesioned nigra and striatum, (3) a preservation of K+-induced dopamine release in the lesioned striatum, and (4) high levels of GDNF protein within the grafts. In contrast, lesioned animals that received grafts of adult kidney tissues displayed significant behavioral deficits, dopaminergic depletion, reduced K+-mediated striatal dopamine release, and low levels of GDNF protein within the grafts. The present study suggests that fetal kidney tissue grafts can protect the nigrostriatal dopaminergic system against a neurotoxin-induced parkinsonism, possibly through the synergistic release of GDNF and several other neurotrophic factors.

Hybrid differential evolution (HDE) is applied to estimate the kinetic model parameters of batch fermentation for ethanol and glycerol production using Saccharomyces diastaticus LORRE 316. In this study, we considered two kinetic models for describing the dynamic behaviors of S. diastaticus LORRE 316. In the parameter estimation problem, we used the worst observed error for all experiments as an objective function so that the parameter estimation problem becomes the min−max estimation problem. Several numerical methods have been employed to solve the min−max estimation problem for comparison. HDE could use a small population size to obtain a more satisfied solution as compared from these computations. To validate the two kinetic models, we respectively used the two kinetic models to determine the optimal feed rates for the fedbatch optimization problem. Because the fedbatch optimization problem was a constrained dynamic optimization problem, we introduced the HDE with a multiplier updating method including adaptive penalty parameters to obtain the feasible feed rates. Such feed rates are then applied for fedbatch experiments in a 5 L fermenter for model validation. From the comparison of batch and fedbatch experiments, we observed that the proposed kinetic model was more adequate than Monod's model.

New stability criteria are provided for a class of uncertain linear time-delay systems with time-varying delays. Based on Lyapunov–Krasovskii functionals combined with LMI techniques, simple and improved delay-dependent robust stability criteria given in terms of quadratic forms of state and LMI are derived. Examples show the performance of the application of the results presented.

We have modified the surface of hydrophilic silicon oxide by chemically anchoring an organic monolayer bearing terminal phosphorylcholine (PC) groups and subsequently characterized the structure of the PC layers and their effectiveness in inhibiting the deposition of a range of model proteins. The PC compound was synthesized through coupling of 3-aminopropyl trimethoxysilane with acryloyloxyethylphosphorylcholine in 2-propanol. The presence of the labile hydrogen on the secondary amine group of the monomer allowed a subsequent coupling of two monomers with a bridging spacer such as a diisocyanate to form a dimer. The PC dimer was coated onto a silicon substrate via dip coating, and the chemical grafting with the substrate was strengthened by annealing the coated layers at 150 °C under vacuum. Neutron reflection measurements showed that upon the formation of a well-packed monolayer, the small PC molecular coatings were as effective as the PC polymer coatings in reducing protein adsorption in vitro.

The effect of the presence of NaCl, CaCl2, or MgCl2 at the same ionic strength on the structure of β-casein layers adsorbed on hydrophobic surfaces has been investigated by neutron reflectivity measurements. The data were fitted to a four-layer model. The volume fraction versus distance profiles have a similar shape whether β-casein is adsorbed from NaCl, CaCl2, and MgCl2 of the same ionic strength or whether the protein concentration is lowered 10 times. In particular at larger distances from the surface, the volume fraction values are low and similar. However, close to the hydrophobic surface the volume fraction of protein decreases in the order CaCl2 > MgCl2 > NaCl. We have also used a specific proteolytic enzyme, endoproteinase Asp-N, which cleaves off the hydrophilic part of β-casein, as a tool to reveal the interfacial structure of the protein. For all the different types of added electrolytes, endoproteinase Asp N only affects the outermost β-casein layer. Subsequent addition of β-casein in all cases led to large increases in amounts adsorbed and in the thickness of the outer layers.

The interaction between sodium dodecyl sulfate (SDS) and preadsorbed lysozyme at the hydrophilic silicon oxide−water interface has been studied using specular neutron reflection. Measurements were carried out using two different solution concentrations of lysozyme and a range of SDS solution concentrations between 0.2 and 2 mM. The surface composition and the adsorbed layer structure were determined by varying H/D labeling of SDS. Initially, a uniform layer or bilayer of protein was formed at the interface by adsorption from either 0.03 or 1 g/L lysozyme solution concentrations. The SDS was then added to the system and the neutron reflectivity measured. It was found that this method of studying the SDS/lysozyme system produced highly repeatable neutron reflectivity profiles. On addition of intermediate SDS concentrations, cooperative binding of the SDS to the protein layer was observed, without any evidence of removal of the preadsorbed protein layer. On increasing the SDS concentration, to above 0.5 mM SDS, partial removal of the protein layer occurred. A concentration of 2 mM SDS was required to completely remove all traces of adsorbed material from the interface. These results suggest that the mechanism for protein elution from the interface is via the coadsorption of SDS to the protein layer and the formation of a SDS/protein complex whose surface activity varies with the extent of SDS binding.