bluuebunny/crossref_metadata_2025 huggingface dataset:
Using inexpensive temperature sensors to monitor the duration and heterogeneity of snow‐covered areas
Authors: Lundquist Jessica D. , Lott Fred
Published: December 2008

Small, self‐recording temperature sensors can be deployed quickly and inexpensively to monitor spatial and temporal patterns of snow accumulation and melt in complex environments. Burying these sensors slightly below the soil surface provides a record of the presence or absence of snow cover because near‐surface soil temperatures only experience diurnal temperature oscillations when they are not covered by an insulating layer of snow. When combined with an air temperature record and snowmelt model, the date snow cover disappears can be used to approximate the amount of snow that accumulated at the start of the melt season.
Combining multiobjective optimization and Bayesian model averaging to calibrate forecast ensembles of soil hydraulic models
Authors: Wöhling Thomas , Vrugt Jasper A.
Published: December 2008

Most studies in vadose zone hydrology use a single conceptual model for predictive inference and analysis. Focusing on the outcome of a single model is prone to statistical bias and underestimation of uncertainty. In this study, we combine multiobjective optimization and Bayesian model averaging (BMA) to generate forecast ensembles of soil hydraulic models. To illustrate our method, we use observed tensiometric pressure head data at three different depths in a layered vadose zone of volcanic origin in New Zealand. A set of seven different soil hydraulic models is calibrated using a multiobjective formulation with three different objective functions that each measure the mismatch between observed and predicted soil water pressure head at one specific depth. The Pareto solution space corresponding to these three objectives is estimated with AMALGAM and used to generate four different model ensembles. These ensembles are postprocessed with BMA and used for predictive analysis and uncertainty estimation. Our most important conclusions for the vadose zone under consideration are (1) the mean BMA forecast exhibits similar predictive capabilities as the best individual performing soil hydraulic model, (2) the size of the BMA uncertainty ranges increase with increasing depth and dryness in the soil profile, (3) the best performing ensemble corresponds to the compromise (or balanced) solution of the three‐objective Pareto surface, and (4) the combined multiobjective optimization and BMA framework proposed in this paper is very useful to generate forecast ensembles of soil hydraulic models.
Pathways for remodelling chromatin
Authors: Owen-Hughes T.
Published: December 2008

The alteration of chromatin structure plays an integral role in gene regulation. One means by which eukaryotes manipulate chromatin structure involves the use of ATP-dependent chromatin-remodelling enzymes. It appears likely that these enzymes play a widespread role in the regulation of many nuclear processes. Recently, significant progress has been made in defining the alterations to chromatin structure that these enzymes generate. The ability to alter nucleosome positioning may be a common feature of all ATP-dependent remodelling enzymes, but the spectrum of positions to which nucleosomes are relocated varies. Mounting evidence supports the ability of remodelling enzymes to translocate along DNA. This provides a means by which they could alter both the twist and writhe of DNA on the surface of nucleosomes, and so accelerate nucleosome repositioning.
Molecular and cellular requirements for the regulation of adenylate cyclases by calcium
Authors: Cooper D.M.F.
Published: December 2008

Calcium-sensitive adenylate cyclases provide a key regulatory device for integrating the activities of the two major signalling systems, Ca2+ and cAMP. Recent experiments have brought us closer to understanding the molecular mechanisms whereby Ca2+ either stimulates or inhibits susceptible adenylate cyclases in vitro. However, in the intact cell an additional layer of sophistication is evident whereby Ca2+-sensitive adenylate cyclases are juxtaposed with Ca2+-entry channels, such that the cyclases respond selectively to capacitative Ca2+ entry. Part of this dependency is enforced by the placement of Ca2+-sensitive adenylate cyclases (AC5, AC6 and AC8) in caveolae, from which at least one Ca2+-insensitive adenylate cyclase (AC7) is excluded. However, additional protein–protein interactions are also required to ensure the dependency of these cyclases on capacitative Ca2+ entry. Recent findings in this area and their implications for ‘local cAMP signals’ will be discussed.
Cardiac calcium signalling
Authors: Berridge M.J.
Published: December 2008

Calcium regulates three different aspects of cardiac contraction. It drives pacemaker activity, excitation–contraction coupling and the transcriptional events that remodel the Ca2+ signalling system in both health and disease.
Regulation of [Ca2+]c oscillations by plasma membrane Ca2+ fluxes: a role for natriuretic peptides
Authors: Green A.K. , Zolle O. , Simpson A.W.M.
Published: December 2008

We have investigated the effects of natriuretic peptides on oscillations in [Ca2+]c (cytosolic free Ca2+ concentration) in two different cell types: freshly isolated rat hepatocytes and the ECV304 cell line. Our data, from both cell types, suggest that natriuretic peptides modulate the frequency of [Ca2+]c oscillations through alterations in plasma membrane Ca2+ fluxes. Here, we review evidence for a role for plasma membrane Ca2+ fluxes in the control of the frequency of [Ca2+]c oscillations. We describe a hypothetical mechanism through which this might be achieved. We propose a physiological role for regulated control of Ca2+ efflux in modulating [Ca2+]c oscillations.
Anti-arrhythmic actions of polyunsaturated fatty acids in cardiac muscle exerted via the sarcoplasmic reticulum
Authors: O'Neill S.
Published: December 2008

Cardiac arrhythmias can be triggered from ischaemic cardiac muscle due to the damage inflicted on individual myocytes. During an ischaemic episode free fatty acids accumulate in the ischaemic tissue. The importance of these fatty acids lies in the apparent ability of some classes of fatty acid to protect against cardiac arrhythmias. As cardiac sudden death is a likely cause of death in patients who have suffered an initial ischaemic insult, protection against such arrhythmias may be of crucial importance. The following review discusses how this protection may be produced, dealing specifically with changes in electrophysiological properties of cells and intracellular calcium regulation.
Bi-directional signalling from the InsP3 receptor: regulation by calcium and accessory factors
Authors: Roderick H.L. , Bootman M.D.
Published: December 2008

Calcium is a pleiotropic messenger controlling a diverse array of intracellular events from fertilization to cell death. One of the main mechanisms by which intracellular calcium is elevated is through InsP3 [Ins(1,4,5)P3]-induced mobilization of calcium from its receptor on the endoplasmic reticulum calcium store. The activity of the InsP3R (InsP3 receptor) is subject to regulation by many factors other than InsP3, most notably calcium itself, which regulates the channel in a bell-shaped dependent manner. InsP3R sensitivity is also regulated by post-translational modifications such as phosphorylation and by binding of accessory proteins. Taken together it appears that the InsP3R can be regarded as a cellular sensor for many signalling pathways, qualitatively and quantitatively regulating intracellular calcium signals with consequences for downstream cellular physiology.
Ins(1,4,5)P3-mediated calcium signals and apoptosis: is there a role for Bcl-2?
Authors: Distelhorst C.W. , Roderick H.L.
Published: December 2008

In this review we speculate that the anti-apoptotic protein Bcl-2 may regulate calcium signals involved in mediating cell death. Evidence that Ins(1,4,5)P3-mediated calcium release from the endoplasmic reticulum triggers apoptosis in response to diverse signals is summarized. Also, we review evidence that Bcl-2 regulates calcium release from the endoplasmic reticulum, and speculate that Bcl-2 may interact either functionally or physically with Ins(1,4,5)P3 receptors to modulate calcium signals that determine life or death decisions.
Introductory remarks
Authors: Harding S.E. , O'Shea P.
Published: December 2008

An overview is given of a stimulating Meeting held at the University of Nottingham in June 2003 focusing on molecular interactions occurring in membranes or ‘2D’ and those occurring in aqueous solution or ‘3D’. It was held jointly between the Biochemical Society and the British Biophysical Society. The 80 or so delegates who attended benefitted from an exciting exchange of ideas between researchers from a wide spectrum of backgrounds. It is hoped the collection of papers which follow this Introductory paper will provide a useful summary of the state of the art and help stimulate collaboration across the wide range of disciplines represented.
Molecular modelling probes: docking and scoring
Authors: Kroemer R.T.
Published: December 2008

A general introduction to molecular modelling techniques in the area of protein–ligand interactions is given. Methods covered range from binding-site analysis to statistical treatment of sets of ligands. The main focus of this paper is on docking and scoring. After an outline of the main concepts, two specific application examples are given.
Intermolecular interactions with/within cell membranes and the trinity of membrane potentials: kinetics and imaging
Authors: O'Shea P.
Published: December 2008

The interactions of (macro-)molecules with biological membranes underlies much of cell biology. This paper outlines many of the factors that must be taken into account in order to understand fully the nature of these interactions. These include some roles of the membrane potentials including features of the surface and dipole potentials. Several fluorescence detection technologies directed towards these are outlined that offer high-resolution experimental determination of the intermolecular interactions by measuring small changes of these potentials resulting from specific interactions of many kinds of molecular species. The possibilities for making single-cell spatial imaging measurements of such interactions is also described. Examples are used to indicate the feasibility of identifying and tracking localized interactions on the membrane surface in real-time. Some of this work points to the possibility that the membrane dipole potential spatially varies about the cell surface, particularly within membrane microdomains such as ‘rafts’. Such variation is suggested to underlie the altered behaviour of signalling systems within rafts and offer the means of an additional level of biological control.
Studies of protein–ligand interactions by NMR
Authors: Clarkson J. , Campbell I.D.
Published: December 2008

Solution-state NMR has become an accepted method for studying the structure of small proteins in solution. This has resulted in over 3000 NMR-based co-ordinate sets being deposited in the Protein Databank. It is becoming increasingly apparent, however, that NMR is also a very powerful tool for accessing interactions between macromolecules and various ligands. These interactions can be assessed at a wide variety of levels, e.g. qualitative screening of libraries of pharmaceuticals and ‘chemical shift mapping’. Dissociation constants can sometimes be obtained in such cases. Another example would be the complete three-dimensional structure determination of a protein–ligand complex. Here we briefly describe a few of the principles involved and illustrate the method with recent examples.
Measurements of associations of cell-surface receptors by single-particle fluorescence imaging
Authors: Cherry R.J. , Morrison I.E.G. , Karakikes I. , Barber R.E. , Silkstone G. , Fernández N.
Published: December 2008

SPFI (single-particle fluorescence imaging) uses the high sensitivity of fluorescence to visualize individual molecules that have been selectively labelled with small fluorescent particles. The images of particles are diffraction-limited spots that are analysed by fitting with a two-dimensional Gaussian function. The spot intensities depend on whether they arise from one or more particles; this provides the basis for determining self-association of cell-surface receptors. We have used this approach to determine dimerization of MHC class II molecules and its disruption by interface peptides. We have also exploited the positional information obtained from SPFI to detect co-localization of cell-surface molecules. This involves labelling two different molecules with different coloured fluorophores and determining their positions separately by dual wavelength imaging. The images are analysed to quantify the overlap of the particle images and hence determine the extent of co-localization of the labelled molecules. The technique provides quantification of the extent of co-localization and can detect whether co-localized molecules occur singly or in clusters. We have obtained preliminary data for co-localization of lipopolysaccharide and CD14 on intact cells. We also show that HLA-DR (human leukocyte antigen-DR) and CD74 are partially co-localized and that interaction between these molecules involves the peptide-binding groove of HLA-DR.
Binding properties and anti-bacterial activities of V-region identical, human IgG and IgM antibodies, against group B Neisseria meningitidis
Authors: Michaelsen T.E. , Ihle Ø. , Beckstrøm K.J. , Herstad T.K. , Sandin R.H. , Kolberg J. , Aase A.
Published: December 2008

We have constructed chimaeric (ch) mouse/human antibodies with identical binding regions isolated from the V-genes of two mouse parent hybridoma cell lines, with specificity against the P1.7 and P1.16 epitopes on the outer-membrane protein PorA on meningococci. The chimaeric antibodies can be used to analyse relationships between specificity, binding activity (avidity and kinetics), isotype (antibody class and antibody subclass) and in vitro anti-bacterial activity of meningococcal antibodies. The antibody sets represented the human isotypes IgG1, IgG3 and IgM, which dominate during immune response against protein antigens. The binding activities were quite similar for all these isotypes, surprisingly also for the pentameric IgM. Interestingly, monomeric IgM, prepared from pentameric IgM by partially reduction and alkylation, had similar binding activities as the original pentameric IgM. Regarding in vitro anti-bacterial activity, chIgG1 was superior in SBA (serum bactericidal activity) compared with chIgG3, while chIgG3 was more efficient in OP (opsonophagocytosis; measured by flow cytometry) than chIgG1. ChIgM showed slightly higher SBA than chIgG1 on molar basis, and much higher OP than chIgG3 and chIgG1. A lower concentration of antibodies was needed against the P1.16 than against the P1.7 epitope to induce SBA, but this was not the case for OP.
The androgen receptor transactivation domain: the interplay between protein conformation and protein–protein interactions
Authors: Reid J. , Betney R. , Watt K. , McEwan I.J.
Published: December 2008

The AR (androgen receptor) belongs to the nuclear receptor superfamily and directly regulates patterns of gene expression in response to the steroids testosterone and dihydrotestosterone. Sequences within the large N-terminal domain of the receptor have been shown to be important for transactivation and protein–protein interactions; however, little is known about the structure and folding of this region. Folding of the AR transactivation domain was observed in the presence of the helix-stabilizing solvent trifluorethanol and the natural osmolyte TMAO (trimethylamine N-oxide). TMAO resulted in the movement of two tryptophan residues to a less solvent-exposed environment and the formation of a protease-resistant conformation. Critically, binding to a target protein, the RAP74 subunit of the general transcription factor TFIIF, resulted in a similar resistance to protease digestion, consistent with induced folding of the receptor transactivation domain. Our current hypothesis is that the folding of the transactivation domain in response to specific protein–protein interactions creates a platform for subsequent interactions, resulting in the formation of a competent transcriptional activation complex.
Measuring and visualizing single molecular interactions in biology
Authors: Allen S. , Rigby-Singleton S.M. , Harris H. , Davies M.C. , O'Shea P.
Published: December 2008

In recent years, considerable attention has focused upon the biological applications of the atomic force microscope (AFM), and in particular in its ability to explore biomolecular interaction events at the single molecule level. Such measurements can provide considerable advantages, as they remove the data averaging inherent in other biophysical/biochemical approaches that record measurements over large ensembles of molecules. To this end AFM has been used for both the high-resolution imaging of a range of individual biological molecules and their complexes, and to record interaction forces between single interacting molecules. In a recently initiated project we have begun to utilize these approaches to explore the interactions of a range of biologically important peptides with model and cell membrane surfaces. In this review, the potential value of AFM for the investigation of a range of biomolecular interaction events will be discussed, but highlighting in particular its potential for the study of interactions of peptides/proteins with biological membranes.
Oxidant stress: a key determinant of atherothrombosis
Authors: Loscalzo J.
Published: December 2008

ROS (reactive oxygen species) are normal products of oxidative cellular metabolism. These biochemically active free-radical derivatives of molecular oxygen serve as normal signalling molecules in the vasculature; however, an excess of vascular ROS flux occurs in the setting of risk factors for atherothrombosis or established atherothrombosis. The oxidant stress that ROS generate promotes endothelial dysfunction, causes oxidative injury to vascular cells, oxidizes lipoproteins and accelerates atherothrombogenesis. Antioxidant enzymes that are important in limiting vascular oxidant stress include the superoxide dismutases, catalase, glutathione peroxidases and glucose-6-phosphate dehydrogenase. The consequences of acquired and inherited deficiencies of these antioxidant enzymes for vascular oxidant stress, endothelial dysfunction and atherothrombosis will be reviewed.
Triacylglycerol-rich lipoproteins and the generation of small, dense low-density lipoprotein
Authors: Packard C.J.
Published: December 2008

LDL (low-density lipoprotein) is the major carrier of cholesterol in human plasma, and as such is intimately involved in the process of atherosclerosis. The lipoprotein class comprises a number of distinct subfractions, and is commonly divided into large, intermediate and small sized particles. Small, dense LDLs are held to be particularly atherogenic, since these particles are retained preferentially by the artery wall, are readily oxidized and carry an enzyme believed to have an important role in atherosclerosis, i.e. lipoprotein-associated phospholipase A2. Generation of small, dense LDL occurs by intravascular lipoprotein remodelling as a result of disturbances such as Type II diabetes, metabolic syndrome, renal disease and pre-eclampsia. The key predisposing factor is the development of hypertriglyceridaemia, in particular elevation in the plasma concentration of large, triacylglycerol-rich VLDL (very-low-density lipoprotein). This leads to the formation of slowly metabolized LDL particles (5-day residence time), which are subject to exchange processes that remove cholesteryl ester from the particle core and replace it with triacylglycerol. LDL, so altered, is a potential substrate for hepatic lipase; if the activity of the enzyme is high enough, lipolysis will generate smaller, denser particles. Correction of the dyslipidaemia associated with small, dense LDL is possible using fibrates and statins, and this may contribute to the clinical benefits seen with these drugs. Fibrates act to lower plasma triacylglycerol (VLDL) levels, and so correct the underlying metabolic disturbance. Statins remove VLDL particles via receptor-mediated pathways and reduce the residence time (and hence limit the potential for remodelling) of LDL in the circulation.
Relevance of hepatic lipase to the metabolism of triacylglycerol-rich lipoproteins
Authors: Zambon A. , Bertocco S. , Vitturi N. , Polentarutti V. , Vianello D. , Crepaldi G.
Published: December 2008

HL (hepatic lipase) is a glycoprotein that is synthesized and secreted by the liver, and which binds to heparan sulphate proteoglycans on the surface of sinusoidal endothelial cells and on the external surface of parenchymal cells in the space of Disse. HL catalyses the hydrolysis of triacylglycerols and phospholipids in different lipoproteins, contributing to the remodelling of VLDL (very-low-density lipoprotein) remnants, as well as IDL, LDL and HDL (intermediate-, low- and high-density lipoprotein respectively). HL deficiency in humans is associated with diminished conversion of VLDL remnants into IDL and a near-complete absence of IDL-to-LDL conversion. Remnant lipoproteins and IDL are major determinants of coronary artery disease risk, and accumulation of these lipoproteins in the presence of low HL activity might lead to increased atherosclerosis. In addition to and independently of its lipolytic activity, HL participates as a ligand in promoting the hepatic uptake of remnants and IDL particles, and the latter may represent an additional mechanism linking low HL levels to plasma accumulation of these atherogenic lipoproteins. On the other hand, high HL activity may also result in an increased atherosclerotic risk by promoting the formation of atherogenic small, dense LDL particles. Finally, HL is also synthesized by human macrophages, suggesting that, at the arterial wall site, HL may also contribute locally to promote atherosclerosis by enhancing the formation and retention in the subendothelial space of the arterial wall of VLDL remnants, IDL and small, dense LDL. In conclusion, by interfering with the metabolism of apolipoprotein B100-containing lipoproteins, HL may have pro- as well as anti-atherogenic effects. The anti- or pro-atherogenic role of HL is likely to be modulated by the concurrent presence of other lipid abnormalities (i.e. LDL-cholesterol levels), as well as by the genetic regulation of other enzymes involved in lipoprotein metabolism.
Triacylglycerol-rich lipoproteins and atherosclerosis – where is the link?
Authors: Cullen P.
Published: December 2008

The link between raised levels of LDL (low-density lipoprotein) cholesterol in the blood and atherosclerosis is incontrovertible. The situation with regard to TRLs (triacylglycerol-rich lipoproteins) is not as clear. Nevertheless, there is substantial evidence that TRLs may in some cases be just as atherogenic as triacylglycerol-poor LDL. This review focuses on three aspects of the link between TRLs and atherosclerosis: (i) the epidemiological evidence for an association between raised levels of TRLs and atherosclerosis, with particular reference to the results of the PROCAM study; (ii) the possible pathophysiological contribution of TRL to atherogenesis at the level of the arterial wall; and (iii) the case for specific lowering of triacylglycerol levels to prevent atherosclerosis.
IR/UV spectroscopy on jet cooled 3-hydroxyflavone (H2O)n (n=1,2) clusters along proton transfer coordinates in the electronic ground and excited states
Authors: Bartl K. , Funk A. , Gerhards M.
Published: December 2008

The structure and reactivity of isolated 3-hydroxyflavone (3-HF) aggregates with one and two water molecules has been investigated by applying combined infrared/ultraviolet (IR/UV) spectroscopy in a supersonic jet both for the electronic ground and excited states. In combination with density functional theory (DFT) calculations, the IR spectra of the S0 states recorded from the upper fingerprint region to the OH stretching vibrations are assigned to the most stable isomers of the clusters. For the first electronically excited (ππ∗) state of the 3-HF(H2O)2 cluster structural information are obtained from the IR spectra in combination with time-dependent-DFT (TD-DFT) calculations. No proton transfer structure is observed in the case of a low excess energy within the electronically excited state. By raising the excitation energy, additional bands appear that can be assigned to a tautomeric form indicating the induction of a proton transfer reaction.
Slow trap charging and detrapping in the negative bias temperature instability in HfSiON dielectric based field effect transistors
Authors: Devine R. A. B. , Alshareef H. N. , Quevedo-Lopez M. A.
Published: December 2008

Negative bias temperature instability in HfSiON gate dielectric based p-channel transistors has been studied at 293, 363, 398, and 433 K and the “slow trap” creation and relaxation has been investigated. Analysis of transistor characteristics suggests that slow trapping in this case is almost entirely related to positive charge trapping in the dielectric as opposed to the dielectric/semiconductor interface. A linear threshold voltage shift versus fractional mobility variation relationship is established as expected. A simplified approach is used to crudely estimate the importance of fast relaxing trapped charges and its magnitude estimated for the four temperatures studied in this work.
Block correlated coupled cluster method with a complete-active-space self-consistent-field reference function: The implementation for low-lying excited states
Authors: Fang Tao , Shen Jun , Li Shuhua
Published: December 2008

Block correlated coupled cluster theory with the complete-active-space self-consistent-field reference function (CAS-BCCC) is generalized for low-lying electronic excited states. By truncating the cluster operator up to the four-block correlation level, the corresponding CAS-BCCC4 method for excited states has been efficiently implemented. The approach is applied to study the excited-state potential energy surfaces for HF and C2 and to evaluate adiabatic or vertical excitation energies for CH2, N2, and trans-1,3-butadiene. The results are compared with those from the full configuration interaction, the internally contracted multireference configuration interaction with singles and doubles, the complete active space with second-order perturbation theory, and other theoretical methods (if available). The CAS-BCCC4 approach is found to provide high accuracy calculations for the low-lying excited states of the systems under study.
Optical properties, structural parameters, and bonding of highly textured rocksalt tantalum nitride films
Authors: Matenoglou G. M. , Koutsokeras L. E. , Lekka Ch. E. , Abadias G. , Camelio S. , Evangelakis G. A. , Kosmidis C. , Patsalas P.
Published: December 2008

Tantalum nitride is an interesting solid with exceptional properties and it might be considered as a representative model system of the d3s2 transition metal nitrides. In this work highly textured, stoichiometric, rocksalt TaN(111) films have been grown on Si(100) by pulsed laser deposition. The films were under a triaxial stress, which has been determined by the sin2 ψ method. The stress-free lattice parameter was found to be 0.433±0.001 nm, a value which has been also determined by ab initio calculations within the local spin density approximation. The optical properties of TaN have been studied using spectroscopic ellipsometry and detailed band structure calculations. The electron conductivity of TaN is due to the Ta 5dt2g band that intercepts the Fermi level and is the source of intraband absorption. The plasma energies of fully dense rocksalt TaN were found to be 9.45 and 9.7 eV based on the experimental results and ab initio calculations, respectively. Additional optical absorption bands were also observed around 1.9 and 7.3 eV and attributed to be due to crystal field splitting of the Ta 5d band (t2g→eg transition) and the N p→Ta d interband transition, respectively.
Aperture effects and mismatch oscillations in an intense electron beam
Authors: Harris John R. , O’Shea Patrick G.
Published: December 2008

When an electron beam is apertured, the transmitted beam current is the integral of the incident beam current density over the aperture area. Space charge forces generally cause an increase in incident beam current to result in an increase in incident beam spot size. Under certain circumstances, the spot size will increase faster than the current, resulting in a decrease in current extracted from the aperture. When using a gridded electron gun, this can give rise to negative transconductance. Here, this effect is explored in the case of an intense beam propagating in a uniform focusing channel. It is shown that proper placement of the aperture can decouple the current extracted from the aperture from fluctuations in the source current, thereby isolating systems downstream of the aperture from upstream current fluctuations. It is also shown that apertures can serve to alter longitudinal space charge wave propagation by changing the relative contribution of velocity and current modulation present in the beam.
Phase separation in SiGe nanocrystals embedded in SiO2 matrix during high temperature annealing
Authors: Mogaddam N. A. P. , Alagoz A. S. , Yerci S. , Turan R. , Foss S. , Finstad T. G.
Published: December 2008

SiGe nanocrystals have been formed in SiO2 matrix by cosputtering Si, Ge, and SiO2 independently on Si substrate. Effects of the annealing time and temperature on structural and compositional properties are studied by transmission electron microscopy, x-ray diffraction (XRD), and Raman spectroscopy measurements. It is observed that Ge-rich Si(1−x)Gex nanocrystals do not hold their compositional uniformity when annealed at high temperatures for enough long time. A segregation process leading to separation of Ge and Si atoms from each other takes place. This process has been evidenced by a double peak formation in the XRD and Raman spectra. We attributed this phase separation to the differences in atomic size, surface energy, and surface diffusion disparity between Si and Ge atoms leading to the formation of nonhomogenous structure consist of a Si-rich SiGe core covered by a Ge-rich SiGe shell. This experimental observation is consistent with the result of reported theoretical and simulation methods.
Influence of exposure to 980 nm laser radiation on the luminescence of Si:Er/O light-emitting diodes
Authors: Karim A. , Du C.-X. , Hansson G. V.
Published: December 2008

Erbium (Er) codoping with oxygen (O) in Si is a well-known method for producing electroluminescent material radiating at 1.54 μm through a 4f shell transition of Er3+ ions. In this work the influence of exposure to 980 nm radiation on the electroluminescence (EL) of reverse biased Si:Er/O light-emitting diodes (LEDs), which give a strong room temperature 1.54 μm intensity, is presented and discussed. All the device layers, including Er/O doped Si sandwiched between two Si0.82Ge0.18 layers, have been grown on silicon on insulator substrates using molecular beam epitaxy and processed to fabricate edge emitting Si:Er/O waveguide LEDs. Electromagnetic mode confinement simulations have been performed to optimize the layer parameters for waveguiding. The temperature dependence of the 1.54 μm EL intensity exhibits an abnormal temperature quenching with a peak near −30 °C, and at −160 °C it has decreased by a factor of 5. However, irradiating the devices with a 980 nm laser gives an enhancement of the 1.54 μm EL intensity, which is more dramatic at low temperatures (e.g., −200 °C) where the quenched EL signal is increased up to almost the same level as at room temperature. The enhancement of the EL intensity is attributed to the photocurrent generated by the 980 nm laser, reducing the detrimental avalanche current.
The neuronal connexin36 interacts with and is phosphorylated by CaMKII in a way similar to CaMKII interaction with glutamate receptors
Authors: Alev Cantas , Urschel Stephanie , Sonntag Stephan , Zoidl Georg , Fort Alfredo G. , Höher Thorsten , Matsubara Mamoru , Willecke Klaus , Spray David C. , Dermietzel Rolf
Published: December 2008

Electrical synapses can undergo activity-dependent plasticity. The calcium/calmodulin-dependent kinase II (CaMKII) appears to play a critical role in this phenomenon, but the underlying mechanisms of how CaMKII affects the neuronal gap junction protein connexin36 (Cx36) are unknown. Here we demonstrate effective binding of
35
S-labeled CaMKII to 2 juxtamembrane cytoplasmic domains of Cx36 and in vitro phosphorylation of this protein by the kinase. Both domains reveal striking similarities with segments of the regulatory subunit of CaMKII, which include the pseudosubstrate and pseudotarget sites of the kinase. Similar to the NR2B subunit of the NMDA receptor both Cx36 binding sites exhibit phosphorylation-dependent interaction and autonomous activation of CaMKII. CaMKII and Cx36 were shown to be significantly colocalized in the inferior olive, a brainstem nucleus highly enriched in electrical synapses, indicating physical proximity of these proteins. In analogy to the current notion of NR2B interaction with CaMKII, we propose a model that provides a mechanistic framework for CaMKII and Cx36 interaction at electrical synapses.
Preclinical evaluation of multiple species of PEGylated recombinant phenylalanine ammonia lyase for the treatment of phenylketonuria
Authors: Sarkissian Christineh N. , Gámez Alejandra , Wang Lin , Charbonneau Marilyse , Fitzpatrick Paul , Lemontt Jeffrey F. , Zhao Bin , Vellard Michael , Bell Sean M. , Henschell Carroll , Lambert Amy , Tsuruda Laurie , Stevens Raymond C. , Scriver Charles R.
Published: December 2008

Phenylketonuria (PKU) is a metabolic disorder, in which loss of phenylalanine hydroxylase activity results in neurotoxic levels of phenylalanine. We used the

Pah
enu2/enu2

PKU mouse model in short- and long-term studies of enzyme substitution therapy with PEGylated phenylalanine ammonia lyase (PEG-PAL conjugates) from 4 different species. The most therapeutically effective PAL (
Av, Anabaena variabilis
) species was one without the highest specific activity, but with the highest stability; indicating the importance of protein stability in the development of effective protein therapeutics. A PEG-
Av
-p.C503S/p.C565S-PAL effectively lowered phenylalanine levels in both vascular space and brain tissue over a >90 day trial period, resulting in reduced manifestations associated with PKU, including reversal of PKU-associated hypopigmentation and enhanced animal health. Phenylalanine reduction occurred in a dose- and loading-dependent manner, and PEGylation reduced the neutralizing immune response to the enzyme. Human clinical trials with PEG-
Av
-p.C503S/p.C565S-PAL as a treatment for PKU are underway.
White spot syndrome virus protein ICP11: A histone-binding DNA mimic that disrupts nucleosome assembly
Authors: Wang Hao-Ching , Wang Han-Ching , Ko Tzu-Ping , Lee Yu-May , Leu Jiann-Horng , Ho Chun-Han , Huang Wei-Pang , Lo Chu-Fang , Wang Andrew H.-J.
Published: December 2008

White spot syndrome virus (WSSV) is a large (≈300 kbp), double-stranded DNA eukaryotic virus that has caused serious disease in crustaceans worldwide. ICP11 is the most highly expressed WSSV nonstructural gene/protein, which strongly suggests its importance in WSSV infection; but until now, its function has remained obscure. We show here that ICP11 acts as a DNA mimic. In crystal, ICP11 formed a polymer of dimers with 2 rows of negatively charged spots that approximated the duplex arrangement of the phosphate groups in DNA. Functionally, ICP11 prevented DNA from binding to histone proteins H2A, H2B, H3, and H2A.x, and in hemocytes from WSSV-infected shrimp, ICP11 colocalized with histone H3 and activated-H2A.x. These observations together suggest that ICP11 might interfere with nucleosome assembly and prevent H2A.x from fulfilling its critical function of repairing DNA double strand breaks. Therefore, ICP11 possesses a functionality that is unique among the handful of presently known DNA mimic proteins.
Abusive interactions with embodied agents
Authors: Creed Chris , Beale Russell
Published: December 2008

Numerous research groups around the world are attempting to build realistic and believable autonomous embodied agents that attempt to have natural interactions with users. Research into these entities has primarily focused on their potential to enhance human–computer interaction. As a result, there is little understanding of the potential for embodied entities to abuse and manipulate users for questionable purposes. We highlight the potential opportunities for abuse when interacting with embodied agents in virtual worlds and discuss how our social interactions with such entities can contribute to abusive behaviour. Suggestions for reducing such risks are also provided, along with suggestions for important future research areas.
Our deepest sympathy
Authors: Ruzich Constance M.
Published: December 2008

This research provides a qualitative elaboration of the research of Reeves and Nass (1996) and Ferdig and Mishra (2004), examining the ways in people relate to computers as social agents. Specifically, this paper investigates the ways in which humans, due to a natural tendency to anthropomorphize computers, may experience significant emotions of grief and loss when computers crash. A content analysis of narratives describing human reactions to computer crashes demonstrates that the metaphoric language used to describe computer failure frames humans’ experience with computer loss in language that highlights the negative impact of human/computer interaction and that references Kubler-Ross’s (1969) stage theory of grief: denial, bargaining, anger, depression, and acceptance.
Learning new words for objects and nonobjects
Authors: Barcroft Joe , Sunderman Gretchen
Published: December 2008

In this study we compared second language (L2) vocabulary learning with real objects versus nonobjects as referents (a) to test the effects of increased semantic processing (when learning nonobjects) and (b) to assess the viability of using L2 vocabulary learning with nonobjects (which forces learners toward concept mediation) for future studies on the development of conceptual mediation. Native English speakers attempted to learn 24 pseudowords using real objects and nonobjects as referents. After the learning phase, they completed two posttests: picture-to-L2 recall (productive) and word-picture verification (receptive). Scores were submitted to analyses of variance with condition (object, nonobject) as a within-subject independent variable. Other analyses tested whether object familiarity and nonobject similarity ratings had an effect on participants’ ability to learn the words. Regression analyses were used to test whether condition (object, nonobject) affected the participants’ accuracy in learning the words on the word-picture verification task. Additional analyses were also performed on the extent to which the mismatch between learning and testing as objects and nonobjects affected accuracy. The results of the study suggest that (a) the additional semantic processing involved in learning with nonobjects decreases learners’ ability to learn new word forms and that (b) L2 vocabulary learning with objects and nonobjects is a viable experimental paradigm for measuring the extent to which L2 vocabulary learning involves L1 lexical mediation.
Reproducibility of dynamic computed tomography brain perfusion measurements in patients with significant carotid artery stenosis
Authors: Serafin Z. , Kotarski M. , Karolkiewicz M. , Mindykowski R. , Lasek W. , Molski S. , Gajdzińska M. , Nowak-Nowacka A.
Published: December 2008

Background: Perfusion computed tomography (PCT) determination is a minimally invasive and widely available technique for brain blood flow assessment, but its application may be restricted by large variation of results.

Purpose: To determine the intraobserver, interobserver, and interexamination variability of brain PCT absolute measurements in patients with significant carotid artery stenosis (CAS), and to evaluate the effect of the use of relative perfusion values on PCT reproducibility.

Material and Methods: PCT imaging was completed in 61 patients before endarterectomy, and in 38 of these within 4 weeks after treatment. Cerebral blood flow (CBF), cerebral blood volume (CBV), time to peak (TTP), and peak enhancement intensity (PEI) were calculated with the maximum slope method. Interexamination variability was evaluated based on perfusion of hemisphere contralateral to the treated CAS, from repeated examinations. Interobserver and intraobserver variability were established for the untreated side, based on pretreatment examination.

Results: Interobserver and intraobserver variability were highest for CBF measurement (28.8% and 32.5%, respectively), and interexamination variability was the highest for CBV (24.1%). Intraobserver and interobserver variability were higher for absolute perfusion values compared with their respective ratios for CBF and TTP. The only statistically significant difference between perfusion values measured by two observers was for CBF (mean 78.3 vs. 67.5 ml/100 g/min). The interexamination variability of TTP (12.1%) was significantly lower than the variability of other absolute perfusion measures, and the interexamination variability of ratios was significantly lower than absolute values for all the parameters.

Conclusion: In longitudinal studies of patients with chronic cerebral ischemia, PCT ratios and either TTP or CBV are more suitable measures than absolute CBF values, because of their considerably lower inter- and intraobserver variability. Differences in CBF between two examinations as high as 30% may be considered as significant in such patients.
The contribution of familiarity to recognition memory is a function of test format when using similar foils
Authors: Migo Ellen , Montaldi Daniela , Norman Kenneth A. , Quamme Joel , Mayes Andrew
Published: December 2008

Patient Y.R., who suffered hippocampal damage that disrupted recollection but not familiarity, was impaired on a yes/no (YN) object recognition memory test with similar foils. However, she was not impaired on a forced-choice corresponding (FCC) version of the test that paired targets with corresponding similar foils (Holdstock et al., 2002). This dissociation is explained by the Complementary Learning Systems (CLS) neural-network model (Norman & O'Reilly, 2003) if recollection is impaired but familiarity is preserved. The CLS model also predicts that participants relying exclusively on familiarity should be impaired on forced-choice noncorresponding (FCNC) tests, where targets are presented with foils similar to other targets. The present study tests these predictions for all three test formats (YN, FCC, FCNC) in normal participants using two variants of the remember/know procedure. As predicted, performance using familiarity alone was significantly worse than standard recognition on the YN and FCNC tests, but not on the FCC test. Recollection in the form of recall-to-reject was the major process driving YN recognition. This adds support to the interpretation of patient data, according to which hippocampal damage causes a recollection deficit that leads to poor performance on the YN test relative to FCC.
Selective interference with image retention and generation: Evidence for the workspace model
Authors: van der Meulen Marian , Logie Robert H. , Sala Sergio Della
Published: December 2008

We address three types of model of the relationship between working memory (WM) and long-term memory (LTM): (a) the gateway model, in which WM acts as a gateway between perceptual input and LTM; (b) the unitary model, in which WM is seen as the currently activated areas of LTM; and (c) the workspace model, in which perceptual input activates LTM, and WM acts as a separate workspace for processing and temporary retention of these activated traces. Predictions of these models were tested, focusing on visuospatial working memory and using dual-task methodology to combine two main tasks (visual short-term retention and image generation) with two interference tasks (irrelevant pictures and spatial tapping). The pictures selectively disrupted performance on the generation task, whereas the tapping selectively interfered with the retention task. Results are consistent with the predictions of the workspace model.
Multiphoton time-domain fluorescence lifetime imaging microscopy: practical application to protein–protein interactions using global analysis
Authors: Barber P.R , Ameer-Beg S.M , Gilbey J , Carlin L.M , Keppler M , Ng T.C , Vojnovic B
Published: December 2008

Förster resonance energy transfer (FRET) detected via fluorescence lifetime imaging microscopy (FLIM) and global analysis provide a way in which protein–protein interactions may be spatially localized and quantified within biological cells. The FRET efficiency and proportion of interacting molecules have been determined using bi-exponential fitting to time-domain FLIM data from a multiphoton time-correlated single-photon counting microscope system. The analysis has been made more robust to noise and significantly faster using global fitting, allowing higher spatial resolutions and/or lower acquisition times. Data have been simulated, as well as acquired from cell experiments, and the accuracy of a modified Levenberg–Marquardt fitting technique has been explored. Multi-image global analysis has been used to follow the epidermal growth factor-induced activation of Cdc42 in a short-image-interval time-lapse FLIM/FRET experiment. Our implementation offers practical analysis and time-resolved-image manipulation, which have been targeted towards providing fast execution, robustness to low photon counts, quantitative results and amenability to automation and batch processing.
Critical superparamagnetic/single-domain grain sizes in interacting magnetite particles: implications for magnetosome crystals
Authors: Muxworthy Adrian R. , Williams Wyn
Published: December 2008

Magnetotactic bacteria contain chains of magnetically interacting crystals (magnetosome crystals), which they use for navigation (magnetotaxis). To improve magnetotaxis efficiency, the magnetosome crystals (usually magnetite or greigite in composition) should be magnetically stable single-domain (SSD) particles. Smaller single-domain particles become magnetically unstable owing to thermal fluctuations and are termed superparamagnetic (SP). Previous calculations for the SSD/SP threshold size or blocking volume did not include the contribution of magnetic interactions. In this study, the blocking volume has been calculated as a function of grain elongation and separation for chains of identical magnetite grains. The inclusion of magnetic interactions was found to decrease the blocking volume, thereby increasing the range of SSD behaviour. Combining the results with previously published calculations for the SSD to multidomain threshold size in chains of magnetite reveals that interactions significantly increase the SSD range. We argue that chains of interacting magnetosome crystals found in magnetotactic bacteria have used this effect to improve magnetotaxis.