bluuebunny/crossref_metadata_2025 huggingface dataset:
Gender differences in self‐reported late effects, quality of life and satisfaction with clinic in survivors of lymphoma
Authors: Arden‐Close E. , Absolom K. , Greenfield D. M. , Hancock B. W. , Coleman R. E. , Eiser C. ,   and on behalf of the Late Effects Group Sheffield
Published: September 2010

Objectives: Gender differences in perceived vulnerability to late effects and views about follow‐up among cancer survivors have received little attention. As lymphoma affects both genders similarly, we compared the consequences of cancer (late effects, perceived vulnerability and quality of life (health‐related quality of life (HRQoL)), and satisfaction with clinic visits between genders.

Methods: A cohort of 115 younger adults (18–45 years, >5 years disease‐free survival), who had been treated for lymphoma participated. Questionnaires (n = 91) were completed before and after (n = 62) routine consultant‐led appointments. Survivors (n = 24) without appointments were recruited by post. Questionnaires included HRQoL, late effects, perceived vulnerability, issues survivors wanted to discuss and reported discussing in clinic, time waiting in clinic and consultation satisfaction.

Results: There were no gender differences in number of self‐reported late effects or perceived vulnerability. Men with more late effects reported worse psychological HRQoL (r = 0.50, p<0.001). While men wanted to discuss more topics than they did, women were able to discuss the topics they wanted (ANOVA, p = 0.01). Multiple regression analyses showed a shorter wait in clinic (r = −0.46, p = 0.009) and discussing more topics (r = 0.34, p = 0.06) explained 30.6% of the variance in consultation satisfaction for men.

Conclusions: Issues surrounding follow‐up provision are increasingly important given the length of survival in young adults following treatment for lymphoma. Men may experience poor psychological well‐being due to distress about unanswered concerns. Consideration of their concerns should be prioritised, given that satisfaction and ultimately continued attendance at clinic and HRQoL may be dependent on the extent to which follow‐up meets survivors' expectations. Copyright © 2010 John Wiley & Sons, Ltd.
Proposed ToF‐SIMS/XPS standardization methods for bonding wires in electronic packaging applications
Authors: Sodhi R. , Gallaugher M. , Wang Z. , Koo J.
Published: September 2010

Time of Flight Secondary Ion Mass Spectrometry (ToF‐SIMS) and XPS were utilized to assess the surface characteristics of the bonding wire generally used in electronic packaging applications. This paper outlines the proposed standard methodologies for the analysis of the high‐curvature surfaces of the fine bonding wires (less than 1.2 mil (30 micron) in diameter) using specially designed stages and systematic data acquisition and analysis. Examples are given to showcase the effectiveness of the methodology, which is able to differentiate various industrial process residues and contaminants on the bonding wire. A preliminary draft of the proposed standard surface characterization methods is presented. Copyright © 2010 John Wiley & Sons, Ltd.
Beyond the Caster Semenya Controversy: The Case of the Use of Genetics for Gender Testing in Sport
Authors: Wonkam Ambroise , Fieggen Karen , Ramesar Raj
Published: September 2010

Caster Semenya won the eight‐hundred‐meter title in the Berlin World Athletics Championships in 2009. Few hours after, Caster was at the center of a harsh contestation on gender. The International Association of Athletics Federations started an investigation, which was not respectful of her privacy. Caster's case highlights the need for an improvement in the awareness of genetic counseling principles amongst professionals, the public and various stakeholders. We critically examine the historical steps of gender verification in the Olympics, the violation of genetic counseling principles in Caster's case and outline some reflections on the complexity of the genetics of Disorders of sex development (DSD). Variability in both genotypes and phenotypes in DSD may not allow any etiological or functional classification at this point in time that could permit uncontroversial gender verification for fairer sport participation. We strongly suggest revisiting the pertinence of gender verification, and the process whereby this is done.
Gender Verification: A Term Whose Time has Come and Gone
Authors: Hercher Laura
Published: September 2010

The process of testing to determine gender in putatively female athletes was developed in order to prevent cheating, but has devolved instead into a clumsy mechanism for detecting disorders of sexual development (DSD's). In over thirty years of compulsory testing, individuals with DSD's have been stigmatized and some have been denied the right to compete, although frequently their condition provided no competitive advantage. More recent guidelines require testing only on a case‐by‐case basis; the South African runner Caster Semenya was the first major test of this policy, and her experience points to the need for a more sensitive and confidential process. In addition, her case dramatizes the inadequacy of the term “gender verification.” Gender identity is a complex entity and resists simple classification. Sports authorities may set guidelines for who can compete, but they should refrain from taking on themselves the authority to decide who is and who is not a female.
Engkabang Fat Esters for Cosmeceutical Formulation
Authors: Abd Gani Siti Salwa , Basri Mahiran , Abdul Rahman Mohd Basyaruddin , Kassim Anuar , Raja Abd Rahman Raja Noor Zaliha , Salleh Abu Bakar , Ismail Zahariah
Published: September 2010

Engkabang fat esters were synthesized from engkabang fat using an enzyme as catalyst. The main composition of the fat esters were oleyl palmitate, oleyl stearate and oleyl oleate. The percentage yield was 93.67%. Ternary phase diagrams systems containing fat esters/surfactant/water were constructed. Several regions appeared in the ternary phase diagrams such as isotropic, homogenous, liquid crystal, two‐phase and three‐phase regions. Increasing the hydrophilic‐lipophilic balance value of the used surfactants gave a larger homogenous and isotropic region in ternary phase diagrams of engkabang fat esters/nonionic surfactant/deionized water. Isotropic and homogenous regions in the ternary phase diagram of engkabang fat esters: PEG‐40 hydrogenated castor oil (2:1)/polyoxyethylene(20) sorbitan tri‐oleate/deionized water, was the largest when compared to the other ternary phase diagrams. The isotropic and homogenous region can be used as a medium in formulation of cosmetics and pharmaceutical products such as creams, lotions, balms and lipsticks.
Host-parasite relationships in flatfish (Pleuronectiformes) – the relative importance of host biology, ecology and phylogeny
Authors: MARQUES J. F. , SANTOS M. J. , TEIXEIRA C. M. , BATISTA M. I. , CABRAL H. N.
Published: September 2010

The extent to which host biology, ecology and phylogeny determine the diversity of macroparasite assemblages has been investigated in recent years in several taxa, including fish. However, consensus has not been reached probably as a result of data being collected from different sources, different temporal scales or host and parasite biogeography and phylogeny having greater influence than expected. The present study evaluates the relative importance of 27 biological, ecological and phylogenetic characteristics of 14 flatfish species on the diversity of their ecto- and endoparasite assemblages, comprising a total of 53 taxa. Redundancy analyses were applied to the mean abundance of each parasite taxa infecting each host and to the richness, taxonomic distinctness and variance in taxonomic distinctness calculated for each assemblage within each host. Only a few host characteristics contributed significantly to the observed patterns: host distribution was more important in determining the type and mean abundance of ectoparasites present in an assemblage, whereas diversity of these assemblages were mainly related to the host's maximum size. Endoparasite mean abundance and diversity were mostly influenced by the number of food items ingested and by the presence of Crustacea and Polychaeta in the diet. However, the sympatric occurrence of related hosts also played an important role in the diversity values found in macroparasite assemblages. Results showed that a host characteristic has different importance according to the host-parasite relationship being examined, suggesting an important role for host-parasite co-evolution on the diversity of extant macroparasite assemblages.
Protein functional landscapes, dynamics, allostery: a tortuous path towards a universal theoretical framework
Authors: Zhuravlev Pavel I. , Papoian Garegin A.
Published: September 2010

Energy landscape theories have provided a common ground for understanding the protein folding problem, which once seemed to be overwhelmingly complicated. At the same time, the native state was found to be an ensemble of interconverting states with frustration playing a more important role compared to the folding problem. The landscape of the folded protein – the native landscape – is glassier than the folding landscape; hence, a general description analogous to the folding theories is difficult to achieve. On the other hand, the native basin phase volume is much smaller, allowing a protein to fully sample its native energy landscape on the biological timescales. Current computational resources may also be used to perform this sampling for smaller proteins, to build a ‘topographical map’ of the native landscape that can be used for subsequent analysis. Several major approaches to representing this topographical map are highlighted in this review, including the construction of kinetic networks, hierarchical trees and free energy surfaces with subsequent structural and kinetic analyses. In this review, we extensively discuss the important question of choosing proper collective coordinates characterizing functional motions. In many cases, the substates on the native energy landscape, which represent different functional states, can be used to obtain variables that are well suited for building free energy surfaces and analyzing the protein's functional dynamics. Normal mode analysis can provide such variables in cases where functional motions are dictated by the molecule's architecture. Principal component analysis is a more expensive way of inferring the essential variables from the protein's motions, one that requires a long molecular dynamics simulation. Finally, the two popular models for the allosteric switching mechanism, ‘preexisting equilibrium’ and ‘induced fit’, are interpreted within the energy landscape paradigm as extreme points of a continuum of transition mechanisms. Some experimental evidence illustrating each of these two models, as well as intermediate mechanisms, is presented and discussed.
Collisional and collisionless beam plasma instabilities
Authors: Bret Antoine
Published: September 2010

Collisions are a key issue regarding the instabilities involved in the fast ignition scenario for inertial confinement fusion. Because of the plasma density gradient through which the relativistic electron beam travels, unstable modes are collisionless at the beginning of the path, and collisional near the target core. While some works have been done on both regimes, the transition from the former to the later remains unclear. By implementing a hot fluid model accounting for a collisional return current, a theory is presented which bridges between the two regimes. The transition from one regime to the other is detailed in terms of the beam-to-plasma density ratio and the collision frequency. Purely collisional modes are found to arise at very low k, compared to the collisionless ones, and generate beam skin-depth size structures in accordance to previous works on resistive filamentation.
Interaction of two plasma jets produced successively from Cu target
Authors: Kasperczuk A. , Pisarczyk T. , Badziak J. , Borodziuk S. , Chodukowski T. , Parys P. , Ullschmied J. , Krousky E. , Masek K. , Pfeifer M. , Rohlena K. , Skala J. , Pisarczyk P.
Published: September 2010

Our earlier papers demonstrate a very simple method of plasma jet formation, consisting in irradiating a massive planar target of a relatively high atomic number by a partly defocused laser beam. Our present interest is concentrated on interaction of the plasma jet with other media. This paper is aimed at investigations of interaction of two jets launched successively on Cu target. Our attention was paid to the role of radiative cooling in the plasma jet formation. The experiment was carried out at the PALS iodine laser facility. The laser provided a 250-ps (full width at half maximum) pulse with energy of 130 J at the third harmonic frequency (λ3 = 0.438 µm). Two successive jets were produced on a massive flat Cu target provided with a cylindrical channel 5 mm long and 400 µm in diameter. Since the focal spot diameter of the laser beam on the target surface was larger than that of the channel (800 µm), the annular irradiation of the target face resulted in creation of the first plasma jet, whereas the second jet was produced by action of the central part of laser beam on the channel wall. Three-frame interferometric system, X-ray streak camera, and a set of ion collectors were used as diagnostic tools.
New micro-cones targets can efficiently produce higher energy and lower divergence particle beams
Authors: Renard-Le Galloudec N. , D'Humieres E.
Published: September 2010

Small conical targets have been used in high intensity laser target interaction mostly in the context of fast ignition. We demonstrate that when cone targets are shaped appropriately and used with specific interaction conditions, they can produce particle beams of higher maximum energy and number in a lower angular divergence than flat targets. This is relevant to fast ignition, small compact particle beams, medical applications, focused ion and/or electron beam microscopes. This fact carries the potential to produce particle beams that are no longer limited by the characteristics of the laser. Note that for fast ignition, reducing the divergence of the beam lowers the energy requirement and enhances the energy deposition into the compressed fuel.
Policy prospects for the hills and uplands
Authors: Harvey D. R.
Published: September 2010

The arguments presented in this paper strongly support the stated intention of the European Commission that farm product prices must be set more competitively with the world market. Indeed, they go further. The only long-term sustainable agricultural policy for the European Community is to let farm products compete unsupported on a free-trade world market (the ultimate objective of the GATT negotiations). This does not deny either justification or need for some form of compensation to the present industry for the loss of support. However, the argument does clearly require that such compensation should be ‘neutral’ — that it should not distort or alter production and allocation decisions from those which would be taken in the absence of such compensation. The only genuinely neutral compensation would be single lump sum capital transfer through a government bond issue. However, failing this, definitely limited annual support payments independent of current production decisions and relating to past production quantities less than those which would be produced under uncompensated free-trade would be ‘quasi neutral’, and might as a result be acceptable as non-distorting under GATT. In this sense, the price reduction proposals currently being discussed are a definite step in the right direction, especially for cereals.

Nevertheless, agriculture faces a continued period of difficult adjustment, especially difficult in the hill and upland areas. As far as conventional agriculture is concerned, there is little prospect of these areas being able to compete directly in the final consumer markets at world price competitive levels. Their comparative advantage will lie with the production of breeding and store animals, to be finished on grass or grain in more productive locations. Fewer people will be able to earn a full-time living from agriculture in these areas and other things being equal, hill and upland farms seem likely to become even more extensive ranching operations than is the case at present. However, other things are not equal. It seems likely that society will continue to value the non-productive elements of hill and upland agriculture, which in many cases are seen as adding to the amenity and landscape qualities of these regions. Since the demand for these features will grow, ways will be found to supplement farming incomes in these areas (especially) in order to conserve the landscape, wildlife and amenity characteristics.
Practical pasture management in hill and upland systems
Authors: Johnson J. , Merrell B. G.
Published: September 2010

The imbalance in area of conservation to grazing has resulted in systems which attempt to maximize grazing and minimize winter feeding. This is rendered more difficult by the short growing season and generally poorer quality of indigenous vegetation when compared with, for example, perennial ryegrass and white clover. Recent changes in government policy discourage land improvement and emphasis nowadays concentrates on maximizing use of, for example, moorland whilst at the same time maintaining its longer-term production and environmental quality. Sward height guidelines can be used to optimize production and utilization of sown grassland for sheep and cattle. Information is also available to integrate heather moorland into farming systems, as a result of an increased understanding of grazing preferences. It remains as important as ever to maintain production from the limited area of improved ground, and improvements in perennial ryegrass and white clover varieties can be introduced successfully into hill and upland systems. Change in such systems however is often constrained by both social and economic factors and this needs to be acknowledged if the agricultural emphasis in the hills and uplands is to have proper direction.
Future of animal production in hill and upland areas
Authors: Maxwell T. J.
Published: September 2010

Together hill and upland agriculture (LFA) currently utilizes from 44% of the land area of the UK and employs directly some 126,000 people. An estimate of gross output from these sectors in 1990 was around £1.3 billion. These data indicate that there can be little doubt about the significance of agriculture and livestock production in hill and upland areas. Since the Second World War output has increased substantially by virtue of a better control of sheep diseases, improved grazing management, sheep and cattle husbandry and the financial incentives offered by successive governments for land improvement, fencing and buildings. However, these incentives have not in themselves led to an economically viable agriculture for most hill and upland areas.

It is questionable if it was ever the intention of any UK government that financial support for the hill and upland livestock industries to improve productivity was the sole objective of their policies for hill and upland areas. While it has always been the case that Agricultural Departments have had the major responsibility for administering the major financial support, the reason for doing so has been as much to do with a social policy of making it possible for people to live in the remoter countryside as it has been to do with improving the output and viability of agriculture.

It is therefore inconceivable that support for hill and upland economies will be withdrawn. It may be, however, that the amount of support will become less as the Common Agriculture Policy is reformed and that element of support which is currently attached to product price is progressively removed. For the future, the indications are that support is much more likely to continue on the basis of headage payments related to breeding livestock quotas and linked to specific management protocols to meet conservation and wider environmental objectives.

Even with the levels of financial support that can be reasonably expected over the next decade, the financial constraints upon, or the opportunities that may arise for individual land owners will inevitably lead to land being removed from agriculture.

However, it is likely that livestock production will continue to dominate much of the hill and upland areas within a management context which will reflect the size of the business, the need to meet specific environmental objectives and the range of other activities and employment opportunities with which the farm household is involved.

Although we must expect that the economics of animal production in the hill and upland areas of the UK will no longer justify a continuation of farming in some areas, the great majority of farms will continue to adopt more efficient technologies, improve their breeding programme and adapt their land management rôle to meet the needs of conservation and the maintenance and enhancement of landscape quality.
A life-course approach to co-residence in the Netherlands, 1850–1940
Authors: KOK JAN , MANDEMAKERS KEES
Published: September 2010

In this article, we study variations in co-residence with kin in the Netherlands in the late nineteenth and early twentieth centuries. We use the reconstructed life courses of 17,527 individuals derived from the Historical Sample of the Netherlands (HSN) database. The life-course approach allows us to look at co-residence from the perspectives of both the receiving households and the co-resident kin. What made households take in relatives and do we find a preference for one type of relative over another? What was the background of people who decided to co-reside in another household? How important were family-related ‘altruistic’ motives compared with economic ones? The outcomes suggest the predominance of altruistic motives for co-residence, apart from persistent inheritance customs in the eastern part of the country.
Nun apothecaries and the impact of the Secularization in Southwest Germany
Authors: MAEGRAITH JANINE CHRISTINA
Published: September 2010

This article examines the interplay of the Secularization of 1803, the ‘professionalisation’ of pharmacy, and increasing state control in Württemberg after 1806 by looking at convent pharmacies and their destiny after the secularization of the convents in 1803. This interplay consequently led to the temporary abolition of convent pharmacies and with them an important occupational niche for female apothecaries was thus lost. The research is based on a detailed case study of the convent pharmacy in Gutenzell in Upper Swabia, 50 kilometres south of Ulm.
Anthropogenic forcing of the Northern Annular Mode in CCMVal‐2 models
Authors: Morgenstern O. , Akiyoshi H. , Bekki S. , Braesicke P. , Butchart N. , Chipperfield M. P. , Cugnet D. , Deushi M. , Dhomse S. S. , Garcia R. R. , Gettelman A. , Gillett N. P. , Hardiman S. C. , Jumelet J. , Kinnison D. E. , Lamarque J.‐F. , Lott F. , Marchand M. , Michou M. , Nakamura T. , Olivié D. , Peter T. , Plummer D. , Pyle J. A. , Rozanov E. , Saint‐Martin D. , Scinocca J. F. , Shibata K. , Sigmond M. , Smale D. , Teyssèdre H. , Tian W. , Voldoire A. , Yamashita Y.
Published: September 2010

We address the question of how ozone and long‐lived greenhouse gas changes impact the Northern Annular Mode (NAM). Using reanalyses and results from the Chemistry‐Climate Model Validation 2 (CCMVal‐2) initiative, we calculate seasonal NAM indices from geopotential height for winter and spring. From these, we determine the strength of stratosphere‐troposphere coupling in the model simulations and the reanalyses. For both seasons, we find a large spread in the ability of models to represent the vertical coherence of the NAM, although most models are within the 95% confidence interval. In winter, many models underestimate the vertical coherence derived from the reanalyses. Some models exhibit substantial differences in vertical coherence between simulations driven with modeled and observed ocean conditions. In spring, in the simulations using modeled ocean conditions, models with poorer horizontal or vertical resolution tend to underestimate the vertical coupling, and vice versa for models with better resolution. Accounting for model deficits in producing an appropriate troposphere‐stratosphere coupling, we show significant correlations of the NAM in winter with three indices representing the anthropogenic impact. Analysis of cross‐correlations between these indices suggests that increasing CO2 is the main reason for these correlations in this season. In the CCMVal‐2 simulations, CO2 increases are associated with a weakening of the NAM in winter. For spring, we show that the dominant effect is chemical ozone depletion leading to a transient strengthening of the NAM, with CO2 changes playing an insignificant role.
Ensemble spread and its implication for the evaluation of temperature trends from multiple radiosondes and reanalyses products
Authors: Xu Jianjun , Powell Alfred M.
Published: September 2010

Based on the ensemble spread, a methodology of measuring uncertainty in weather forecasts, the temperature trend and spread have been estimated using five radiosonde data sets and seven reanalysis products beginning in 1989. The results show that the magnitude of warming or cooling depends on the data sources, atmospheric heights, and geophysical latitudes. Over low‐middle latitudes, the cooling varies from −2.6 K/decade in NCEP‐DOE to −0.8 K/decade in HADAT2 in the lower stratosphere. The warming weakly changes from 0.2 through 0.4 K/decade in the middle troposphere. Over Antarctica, there is a pronounced warming in the low‐middle troposphere in the three NCEP reanalyses and the RATPAC radiosonde data sets, and cooling in the other eight products. Over the Arctic, the warming is observed from the lower troposphere to the lower stratosphere in all twelve data sets. Significant cooling is identified over the middle stratosphere (above 50 hPa) in all five radiosondes. For global mean temperature, the trend is approximately 0.2 K/decade in the troposphere and −0.8 K/decade in the stratosphere. The spread increases significantly with atmospheric height from approximately 0.1 K/decade at 850hPa to 0.8 K/decade at 30hPa. The spread in the reanalysis data sets is much larger than in the radiosondes in the stratosphere. In contrast, the spread in both the reanalysis and radiosondes data sets is very small and shows the trend in better agreement with each other in the troposphere.
Computational reconstruction of tissue‐specific metabolic models: application to human liver metabolism
Authors: Jerby Livnat , Shlomi Tomer , Ruppin Eytan
Published: September 2010

The computational study of human metabolism has been advanced with the advent of the first generic (non‐tissue specific) stoichiometric model of human metabolism. In this study, we present a new algorithm for rapid reconstruction of tissue‐specific genome‐scale models of human metabolism. The algorithm generates a tissue‐specific model from the generic human model by integrating a variety of tissue‐specific molecular data sources, including literature‐based knowledge, transcriptomic, proteomic, metabolomic and phenotypic data. Applying the algorithm, we constructed the first genome‐scale stoichiometric model of hepatic metabolism. The model is verified using standard cross‐validation procedures, and through its ability to carry out hepatic metabolic functions. The model's flux predictions correlate with flux measurements across a variety of hormonal and dietary conditions, and improve upon the predictive performance obtained using the original, generic human model (prediction accuracy of 0.67 versus 0.46). Finally, the model better predicts biomarker changes in genetic metabolic disorders than the generic human model (accuracy of 0.67 versus 0.59). The approach presented can be used to construct other human tissue‐specific models, and be applied to other organisms.
HepatoNet1: a comprehensive metabolic reconstruction of the human hepatocyte for the analysis of liver physiology
Authors: Gille Christoph , Bölling Christian , Hoppe Andreas , Bulik Sascha , Hoffmann Sabrina , Hübner Katrin , Karlstädt Anja , Ganeshan Ramanan , König Matthias , Rother Kristian , Weidlich Michael , Behre Jörn , Holzhütter Herrmann‐Georg
Published: September 2010

We present HepatoNet1, the first reconstruction of a comprehensive metabolic network of the human hepatocyte that is shown to accomplish a large canon of known metabolic liver functions. The network comprises 777 metabolites in six intracellular and two extracellular compartments and 2539 reactions, including 1466 transport reactions. It is based on the manual evaluation of >1500 original scientific research publications to warrant a high‐quality evidence‐based model. The final network is the result of an iterative process of data compilation and rigorous computational testing of network functionality by means of constraint‐based modeling techniques. Taking the hepatic detoxification of ammonia as an example, we show how the availability of nutrients and oxygen may modulate the interplay of various metabolic pathways to allow an efficient response of the liver to perturbations of the homeostasis of blood compounds.
Emergent cooperation in microbial metabolism
Authors: Wintermute Edwin H , Silver Pamela A
Published: September 2010

Mixed microbial communities exhibit emergent biochemical properties not found in clonal monocultures. We report a new type of synthetic genetic interaction, synthetic mutualism in trans (SMIT), in which certain pairs of auxotrophic Escherichia coli mutants complement one another's growth by cross‐feeding essential metabolites. We find significant metabolic synergy in 17% of 1035 such pairs tested, with SMIT partners identified throughout the metabolic network. Cooperative phenotypes show more growth on average by aiding the proliferation of their conjugate partner, thereby expanding the source of their own essential metabolites. We construct a quantitative, predictive, framework for describing SMIT interactions as governed by stoichiometric models of the metabolic networks of the interacting strains.
Resolution of disulfide heterogeneity in Nogo receptor 1 fusion proteins by molecular engineering
Authors: Weinreb Paul H. , Wen Dingyi , Qian Fang , Wildes Craig P. , Garber Ellen A. , Walus Lee , Jung Mi‐young , Wang Joy , Relton Jane K. , Amatucci Joseph , Wang Ruizhong , Porreca Frank , Silvian Laura , Meier Werner , Pepinsky R. Blake , Lee Daniel H. S.
Published: September 2010

NgR1 (Nogo‐66 receptor) is part of a signalling complex that inhibits axon regeneration in the central nervous system. Truncated soluble versions of NgR1 have been used successfully to promote axon regeneration in animal models of spinal‐cord injury, raising interest in this protein as a potential therapeutic target. The LRR (leucine‐rich repeat) regions in NgR1 are flanked by N‐ and C‐terminal disulfide‐containing ‘cap’ domains (LRRNT and LRRCT respectively). In the present work we show that, although functionally active, the NgR1(310)‐Fc fusion protein contains mislinked and heterogeneous disulfide patterns in the LRRCT domain, and we report the generation of a series of variant molecules specifically designed to prevent this heterogeneity. Using these variants we explored the effects of modifying the NgR1 truncation site or the spacing between the NgR1 and Fc domains, or replacing cysteines within the NgR1 or IgG hinge regions. One variant, which incorporates replacements of Cys266 and Cys309 with alanine residues, completely eliminated disulfide scrambling while maintaining functional in vitro and in vivo efficacy. This modified NgR1‐Fc molecule represents a significantly improved candidate for further pharmaceutical development, and may serve as a useful model for the optimization of other IgG fusion proteins made from LRR proteins.
Characterization of a novel peroxisome membrane protein essential for conversion of isopenicillin N into cephalosporin C
Authors: Ullán Ricardo V. , Teijeira Fernando , Guerra Susana M. , Vaca Inmaculada , Martín Juan F.
Published: September 2010

The mechanisms of compartmentalization of intermediates and secretion of penicillins and cephalosporins in β-lactam antibiotic-producing fungi are of great interest. In Acremonium chrysogenum, there is a compartmentalization of the central steps of the CPC (cephalosporin C) biosynthetic pathway. In the present study, we found in the ‘early’ CPC cluster a new gene named cefP encoding a putative transmembrane protein containing 11 transmembrane spanner. Targeted inactivation of cefP by gene replacement showed that it is essential for CPC biosynthesis. The disrupted mutant is unable to synthesize cephalosporins and secretes a significant amount of IPN (isopenicillin N), indicating that the mutant is blocked in the conversion of IPN into PenN (penicillin N). The production of cephalosporin in the disrupted mutant was restored by transformation with both cefP and cefR (a regulatory gene located upstream of cefP), but not with cefP alone. Fluorescence microscopy studies with an EGFP (enhanced green fluorescent protein)–SKL (Ser-Lys-Leu) protein (a peroxisomal-targeted marker) as a control showed that the red-fluorescence-labelled CefP protein co-localized in the peroxisomes with the control peroxisomal protein. In summary, CefP is a peroxisomal membrane protein probably involved in the import of IPN into the peroxisomes where it is converted into PenN by the two-component CefD1/CefD2 protein system.
Two routes of iron accumulation in astrocytes: ascorbate-dependent ferrous iron uptake via the divalent metal transporter (DMT1) plus an independent route for ferric iron
Authors: Lane Darius J.R. , Robinson Stephen R. , Czerwinska Hania , Bishop Glenda M. , Lawen Alfons
Published: September 2010

Astrocytes are central to iron and ascorbate homoeostasis within the brain. Although NTBI (non-transferrin-bound iron) may be a major form of iron imported by astrocytes in vivo, the mechanisms responsible remain unclear. The present study examines NTBI uptake by cultured astrocytes and the involvement of ascorbate and DMT1 (divalent metal transporter 1). We demonstrate that iron accumulation by ascorbate-deficient astrocytes is insensitive to both membrane-impermeant Fe(II) chelators and to the addition of the ferroxidase caeruloplasmin. However, when astrocytes are ascorbate-replete, as occurs in vivo, their rate of iron accumulation is doubled. The acquisition of this additional iron depends on effluxed ascorbate and can be blocked by the DMT1 inhibitor ferristatin/NSC306711. Furthermore, the calcein-accessible component of intracellular labile iron, which appears during iron uptake, appears to consist of only Fe(III) in ascorbate-deficient astrocytes, whereas that of ascorbate-replete astrocytes comprises both valencies. Our data suggest that an Fe(III)-uptake pathway predominates when astrocytes are ascorbate-deficient, but that in ascorbate-replete astrocytes, at least half of the accumulated iron is initially reduced by effluxed ascorbate and then imported by DMT1. These results suggest that ascorbate is intimately involved in iron accumulation by astrocytes, and is thus an important contributor to iron homoeostasis in the mammalian brain.
Epigenetic regulation of V(D)J recombination
Authors: Johnson Kristen , Chaumeil Julie , Skok Jane A.
Published: September 2010

Chromosome breaks are dangerous business, carrying the risk of loss of genetic information or, even worse, misrepair of the break, leading to outcomes such as dicentric chromosomes or oncogenic translocations. Yet V(D)J recombination, a process that breaks, rearranges and repairs chromosomes, is crucial to the development of the adaptive immune system, for it gives B- and T-cells the capacity to generate a virtually unlimited repertoire of antigen receptor proteins to combat an equally vast array of antigens. To minimize the risks inherent in chromosomal breakage, V(D)J recombination is carefully orchestrated at multiple levels, ranging from DNA sequence requirements all the way up to chromatin conformation and nuclear architecture. In the present chapter we introduce various regulatory controls, with an emphasis on epigenetic mechanisms and recent work that has begun to elucidate their interdependence.
Density functional calculations of the structural, electronic, and ferroelectric properties of high-k titanate Re2Ti2O7 (Re=La and Nd)
Authors: Bruyer Emilie , Sayede Adlane
Published: September 2010

We have studied the structural, electronic, and ferroelectric properties of La2Ti2O7 (LTO) and Nd2Ti2O7 (NTO) by first-principles density functional theory calculations. The computed structural parameters are found to be in good agreement with experimental findings. In particular, the P21 phase is confirmed to be energetically preferred over the other configurations for both titanates. The calculations revealed the possible existence of an unidentified phase, namely, the P21/m paraelectric structure. From the modern theory of polarization the spontaneous polarization of LTO and NTO was calculated to be 7.72 μC/cm2 and 7.42 μC/cm2, respectively, in accordance with experimental findings. Its origin is ascribed to the displacement of the rare earth (Re) cations in the [100] cleavage plane and parallel to the b axis. Electronic charge density distributions and Bader’s topological analysis indicates that the bonding interactions between Re and O as well as Ti and O are not purely ionic, a noticeable covalent bonding is identified between Ti and O. Band structure calculations using a generalized gradient approximation (GGA) approach predicted insulating ground state for LTO with band gap energy of about 2.84 eV. Conversely, a half-metallic ground state was predicted for NTO. Using GGA+U approach, an appropriate insulating ground state was found with band gap energy of 1.63 eV. Density of states analysis suggest that the localized Nd 4f levels act as charge-trapping sites, explaining the reduced photocatalytic activity of NTO.
Core-valence double photoionization of the CS2 molecule
Authors: Andersson E. , Niskanen J. , Hedin L. , Eland J. H. D. , Linusson P. , Karlsson L. , Rubensson J.-E. , Carravetta V. , Ågren H. , Feifel R.
Published: September 2010

Double photoionization spectra of the CS2 molecule have been recorded using the TOF-PEPECO technique in combination with synchrotron radiation at the photon energies hν=220, 230, 240, 243, and 362.7 eV. The spectra were recorded in the S 2p and C 1s inner-shell ionization regions and reflect dicationic states formed out of one inner-shell vacancy and one vacancy in the valence region. MCSCF calculations were performed to model the energies of the dicationic states. The spectra associated with a S 2p vacancy are well structured and have been interpreted in some detail by comparison to conventional S 2p and valence photoelectron spectra. The lowest inner-shell-valence dicationic state is observed at the vertical double ionization energy 188.45 eV and is associated with a (2p3/2)−1(2πg)−1 double vacancy. The spectrum connected to the C 1s vacancy shows a distinct line at 310.8 eV, accompanied by additional broad features at higher double ionization energies. This line is associated with a (C 1s)−1(2πg)−1 double vacancy.
The entropy in finite N-unit nonextensive systems: The normal average and q-average
Authors: Hasegawa Hideo
Published: September 2010

We discuss the Tsallis entropy in finite N-unit nonextensive systems by using the multivariate q-Gaussian probability distribution functions (PDFs) derived by the maximum entropy methods with the normal average and the q-average (q: the entropic index). The Tsallis entropy obtained by the q-average has an exponential N dependence: Sq(N)/N≃e(1−q)NS1(1) for large N (⪢1/(1−q)>0). In contrast, the Tsallis entropy obtained by the normal average is given by Sq(N)/N≃[1/(q−1)N] for large N (⪢1/(q−1)>0). N dependences of the Tsallis entropy obtained by the q- and normal averages are generally quite different, although both results are in fairly good agreement for |q−1|⪡1.0. The validity of the factorization approximation (FA) to PDFs, which has been commonly adopted in the literature, has been examined. We have calculated correlations defined by Cm=⟨(δxiδxj)m⟩−⟨(δxi)m⟩⟨(δxj)m⟩ for i≠j where δxi=xi−⟨xi⟩, and the bracket ⟨⋅⟩ stands for the normal and q-averages. The first-order correlation (m=1) expresses the intrinsic correlation and higher-order correlations with m≥2 include nonextensivity-induced correlation, whose physical origin is elucidated in the superstatistics.
Correcting hot-wire measurements of stream-wise turbulence intensity in boundary layers
Authors: Monkewitz P. A. , Duncan R. D. , Nagib H. M.
Published: September 2010

The current experimental activity aimed at resolving the scaling of stream-wise turbulence intensity profiles uu¯+(y+) with Reynolds number in turbulent flat plate boundary layers has brought the largely unresolved issue of correcting systematic errors in hot-wire measurements of uu¯+(y+) into focus. Here, a heuristic scheme is proposed to generate unique uu¯+(y+;Reδ∗) profiles from data obtained with single hot wires of widely different length, aspect ratio and construction over a large Reynolds number range of 4000≲Reδ∗≲50 000. A comparison with LDA data and other checks suggest that the present correction scheme produces uu¯+(y+;Reδ∗) profiles close to the (unknown) true profiles.
Si-based ultrasmall multiswitching single-electron transistor operating at room-temperature
Authors: Shin S. J. , Jung C. S. , Park B. J. , Yoon T. K. , Lee J. J. , Kim S. J. , Choi J. B. , Takahashi Y. , Hasko D. G.
Published: September 2010

An ultrasmall single-electron transistor has been made by scaling the size of a fin field-effect transistor structure down to an ultimate limiting form, resulting in the reliable formation of a sub-5 nm Coulomb island. The charge stability data feature the first exhibition of three and a half clear Coulomb diamonds at 300 K, each showing a high peak-to-valley current ratio. Its charging energy is estimated to be more than one order magnitude larger than the thermal energy at room-temperature. The hybrid literal gate integrated by this single-electron transistor combined with a field-effect transistor displays >5 bit multiswitching behavior at 300 K with a large voltage swing of ∼1 V.
Polarization dependent two-photon properties in an organic crystal
Authors: Fang Hong-Hua , Yang Jie , Ding Ran , Chen Qi-Dai , Wang Lei , Xia Hong , Feng Jing , Ma Yu-Guang , Sun Hong-Bo
Published: September 2010

The dependence of the fluorescence on the excitation beam polarization under two-photon excitation was studied in a 1,4-bis(R-cyano-4-diphenylaminostyryl)-2,5-diphenylbenzene organic crystal. The crystal shows strong response to the polarization, especially when the pump intensity was increased. The polarization plays an important role on the threshold of amplified spontaneous emission (ASE) and the ΔGASE under two-photon excitation (TPE). Moreover, the polarization distribution between the TPE (800 nm) and one-photon excitation (400 nm) are very different. The former generates a cos4 θ distribution, while the later gives rise to cos2 θ distribution in different orientation.
Structural aspects in the dielectric properties of pentyl alcohols
Authors: Kaatze Udo , Behrends Ralph , von Roden Kerstin
Published: September 2010

At temperatures between 0 and 60 °C densities, shear viscosities and dielectric spectra have been measured for isomers 1-pentanol, 2-pentanol, 3-pentanol, isopentylalcohol, and tert-pentanol, as well as for mixtures of these alcohols. The density and shear viscosity data are discussed in terms of deviations from ideal mixing behavior. The dielectric spectra are evaluated to yield the extrapolated static permittivity and the relaxation time of the principal (low-frequency) relaxation term. The former parameter is analyzed in view of dipole orientation correlations, the latter one is discussed in terms of the activation enthalpy controlling the relaxation process. A noticeable result is the effect of isomer structure on both the dipole orientation correlation and the dielectric relaxation. Especially the dielectric parameters of tert-pentanol deviate significantly from the relevant parameters of the other pentanols. Such deviations are considered in the light of models of hydrogen network structure and fluctuations.
A simple method of fabricating mask-free microfluidic devices for biological analysis
Authors: Yi Xin , Kodzius Rimantas , Gong Xiuqing , Xiao Kang , Wen Weijia
Published: September 2010

We report a simple, low-cost, rapid, and mask-free method to fabricate two-dimensional (2D) and three-dimensional (3D) microfluidic chip for biological analysis researches. In this fabrication process, a laser system is used to cut through paper to form intricate patterns and differently configured channels for specific purposes. Bonded with cyanoacrylate-based resin, the prepared paper sheet is sandwiched between glass slides (hydrophilic) or polymer-based plates (hydrophobic) to obtain a multilayer structure. In order to examine the chip’s biocompatibility and applicability, protein concentration was measured while DNA capillary electrophoresis was carried out, and both of them show positive results. With the utilization of direct laser cutting and one-step gas-sacrificing techniques, the whole fabrication processes for complicated 2D and 3D microfluidic devices are shorten into several minutes which make it a good alternative of poly(dimethylsiloxane) microfluidic chips used in biological analysis researches.
Maximum likelihood estimation of locus-specific mutation rates in Y-chromosome short tandem repeats
Authors: Ravid-Amir Osnat , Rosset Saharon
Published: September 2010

Motivation: Y-chromosome short tandem repeats (Y-STRs) are widely used for population studies, forensic purposes and, potentially, the study of disease, therefore knowledge of their mutation rate is valuable. Here we show a novel method for estimation of site-specific Y-STR mutation rates from partial phylogenetic information, via the maximum likelihood framework.

Results: Given Y-STR data classified into haplogroups, we de-scribe the likelihood of observed data, and develop optimization strategies for deriving maximum likelihood estimates of mutation rates. We apply our method to Y-STR data from two recent papers. We show that our estimates are comparable, often more accurate than those obtained in familial studies, although our data sample is much smaller, and was not collected specifically for our study. Furthermore, we obtain mutation rate estimates for DYS388, DYS426, DYS457, three STRs for which there were no mutation rate measures until now.

Contact:  saharon@post.tau.ac.il