bluuebunny/crossref_metadata_2025 huggingface dataset:
Fabrication of silicon kinoform lenses for hard x-ray focusing by electron beam lithography and deep reactive ion etching
Authors: Stein Aaron , Evans-Lutterodt Kenneth , Bozovic Natasha , Taylor Ashley
Published: February 2008

The focusing of subnanometer wavelength x rays is limited by the ability to fabricate high-quality optics. In general, the resolution is of the order of the smallest feature of the optic, so nanometer spot sizes are extremely difficult to achieve with lenses made by traditional fabrication methods. In addition, gains in resolution for a given lithography limit are often made at a sacrifice of focusing efficiency. Kinoform lenses offer a compromise position of high resolution and efficiency. The object of this work is to describe the fabrication of kinoform lenses and to show how their unique properties could provide a path toward nanometer scale focusing. Fabrication is made easier by using higher order focusing and larger features. By combining 100keV electron beam lithography and deep reactive ion etching, the authors have fabricated cylindrical kinoform lenses in silicon. These lenses can be used in a crossed pair to produce a two-dimensional focus, but to maintain a large aperture and high resolution this requires etch depths of up to 100μm. Such large etch depths require careful consideration of lens design—feature sizes and densities can be changed with some latitude in the kinoform lens pattern without affecting the lens performance. Multiple lenses are fabricated in serial stacks to increase the resolution and provide a path forward to nanometer resolution.
Photoresist characterization using double exposures with interference lithography
Authors: O’Reilly Thomas B. , Smith Henry I.
Published: February 2008

Photoresist characterization is an important part of process control for any lithography technique. This paper describes a means to experimentally determine how the linewidth in interference lithography varies with characteristics of the exposure, using far fewer exposures than are needed using methods previously described in the literature. In this method, a sample is exposed twice, with the sample rotated a few degrees between the two exposures. From micrographs of the developed resist patterns it is possible to determine how linewidth varies with both average dose and dose modulation, and what dose modulation is required to produce an acceptable pattern for that dose and spatial period. The information generated by this method is directly applicable to interference lithography, but can also be used to study the performance of photoresist for use with other lithography systems.
Ultrashallow junctions formed by C coimplantation with spike plus submelt laser annealing
Authors: Felch S. B. , Collart E. , Parihar V. , Thirupapuliyur S. , Schreutelkamp R. , Pawlak B. J. , Hoffmann T. , Severi S. , Eyben P. , Vandervorst W. , Noda T.
Published: February 2008

A leading candidate for the formation of the ultrashallow junctions needed for Lg⩽45nm devices is the combination of coimplantation of a diffusion-retarding species such as carbon with a high temperature, millisecond annealing process after the conventional spike annealing. C coimplantation with B+ for p-type metal-oxide semiconductor and P+ for n-type metal-oxide semiconductor combined with conventional spike annealing produces reduced junction depths and improved dopant activation and profile abruptness, compared to similar implants without the coimplanted species. Addition of submelt laser annealing may further improve junction activation, but the dominant impact is gate depletion reduction, in that way, delaying the need to introduce metal gates. Devices show that the overlap capacitance is reduced, consistent with the shallower junction depths and reduced lateral diffusion. The improved dopant activation manifests itself in reduced series resistance and improved Ion values. Finally, scanning spreading resistance microscopy measurements confirm the shallow junction depths and reduced lateral diffusion.
Defects in Ge and Si caused by 1MeV Si+ implantation
Authors: Hickey D. P. , Bryan Z. L. , Jones K. S. , Elliman R. G. , Haller E. E.
Published: February 2008

Cross-sectional transmission electron microscopy was used to study defect formation and evolution in the (001) Ge and Si wafers implanted with 1MeV Si+ and 40keV Si+ at a dose of 1×1014cm−2. As expected, upon annealing, the {311} extended defects form and subsequently dissolve at the projected range for nonamorphizing implants into Si. However, in Ge, no {311} defect formation is observed for this nonamorphizing implant after annealing at temperatures between 350 and 850°C. Instead, for the MeV implant, small dotlike defects are observed in Ge, which dissolve upon annealing between 650 and 750°C for 10min.
Application of electron holography to analysis of submicron structures
Authors: Gribelyuk M. A. , Domenicucci A. G. , Ronsheim P. A. , McMurray J. S. , Gluschenkov O.
Published: February 2008

Importance of effects of charging and sample thickness variation across depletion region is discussed using one-dimensional p-n junction in bulk Si and silicon-on-insulator (SOI) structures prepared by mechanical polishing. It is shown that good correlation between results of electron holography and secondary ion mass spectroscopy can be achieved without consideration of “dead layers.” Analysis of laser annealed n-type field-effect transistor (n-FET) devices in SOI structures showed that laser annealing does not cause lateral dopant diffusion of arsenic to resolution of electron holography. It is demonstrated that junction overlap can be achieved with “laser-only” integration scheme. Examples are given on how electron holography can provide insight into integration scheme for development of a p-FET device with embedded SiGe source/drain regions and evaluation of effect of proximity of shallow trench isolation on dopant depletion.
Novel photocurable epoxy siloxane polymers for photolithography and imprint lithography applications
Authors: Wang Pei-I , Nalamasu O. , Ghoshal Rajat , Ghoshal Ram , Schaper Charles D. , Li Andrew , Lu Toh-Ming
Published: February 2008

Polyset epoxy siloxane (PES) polymer is ultraviolet (UV) curable with photoinitiator chemistry based on cationic polymerization. In the present work the authors have investigated the photodefinition characteristics of the epoxy siloxane polymers using photolithography and imprint lithography. The scanning electron microscopic images of the UV-cured patterns exhibit appealing resolution of micrometer scale features for photolithography processes. The imprint lithography has been examined with features smaller than 200 nm. In conjunction with the promising dielectric properties, epoxy siloxane polymers are particularly useful for applications such as the redistribution layer in packaging of integrated circuits.
Description of field emission current/voltage characteristics in terms of scaled barrier field values (f-values)
Authors: Forbes Richard G.
Published: February 2008

The scaled barrier field f is defined as the local field F that determines a field emission tunneling barrier, divided by the critical field needed to reduce to zero a barrier initially of height (for F=0) equal to the local work-function. The description of field emission current-voltage (I−V) characteristics is more universal, and closer to theory, if measured voltages are reassigned as f-values. This paper describes a simple method for directly converting voltage to f-value, using the slope of a Fowler-Nordheim plot of type ln{I/V2} vs 1/V. A short table of characteristic f-values could be helpful for describing typical emission features such as the emission onset, the onset of emitter degradation, or the onset of space-charge effects. For an old-style metal field emitter of moderate to large apex radius, a table based on the systematic work of Dyke and Trolan [Phys. Rev. 89, 799 (1953)] is given. Tables of this kind, if prepared for different categories of field emitter, could be helpful in emitter comparisons. In another use, different individual emitters in emitter arrays can be thought of as operating at different f-values. The use of f-values seems a simple, additional helpful way of describing field emitter behavior, particularly in technological contexts.
Surface plasmon assisted contact scheme nanoscale photolithography using an UV lamp
Authors: Shao Dongbing , Chen Shaochen
Published: February 2008

In this article, we present our study on surface plasmon (SP) assisted contact scheme nanoscale photolithography technique. Sub-100-nm features on a metallic mask, fabricated by e-beam lithography, were successfully transferred to a resist pattern in a setup close to traditional photolithography. Our previous work based on finite difference time domain simulation reveals the mechanism of SP-light coupling in the transferring and confining of light in surface plasmon assisted nanolithography (SPAN), which was demonstrated using 355nm laser light. In this article, we extended our SPAN work to the use of UV light from a mercury lamp, which emits broadband, unpolarized, and incoherent light. Our experimental results show that sub-100-nm features can still be easily transferred using SPAN despite the light source used, proving SPAN to be an alternative nanopatterning technique that is simple, quick, and inexpensive. The experiments also showed interesting SP interference effects at the boundary of the mask.
A Cholesterol Biosynthesis Inhibitor Blocks
Staphylococcus aureus
Virulence
Authors: Liu Chia-I , Liu George Y. , Song Yongcheng , Yin Fenglin , Hensler Mary E. , Jeng Wen-Yih , Nizet Victor , Wang Andrew H.-J. , Oldfield Eric
Published: February 2008

Staphylococcus aureus
produces hospital- and community-acquired infections, with methicillin-resistant
S. aureus
posing a serious public health threat. The golden carotenoid pigment of
S. aureus
, staphyloxanthin, promotes resistance to reactive oxygen species and host neutrophil-based killing, and early enzymatic steps in staphyloxanthin production resemble those for cholesterol biosynthesis. We determined the crystal structures of
S. aureus
dehydrosqualene synthase (CrtM) at 1.58 angstrom resolution, finding structural similarity to human squalene synthase (SQS). We screened nine SQS inhibitors and determined the structures of three, bound to CrtM. One, previously tested for cholesterol-lowering activity in humans, blocked staphyloxanthin biosynthesis in vitro (median inhibitory concentration ∼100 nM), resulting in colorless bacteria with increased susceptibility to killing by human blood and to innate immune clearance in a mouse infection model. This finding represents proof of principle for a virulence factor–based therapy against
S. aureus
.
Generation of Pluripotent Stem Cells from Adult Mouse Liver and Stomach Cells
Authors: Aoi Takashi , Yae Kojiro , Nakagawa Masato , Ichisaka Tomoko , Okita Keisuke , Takahashi Kazutoshi , Chiba Tsutomu , Yamanaka Shinya
Published: February 2008

Induced pluripotent stem (iPS) cells have been generated from mouse and human fibroblasts by the retroviral transduction of four transcription factors. However, the cell origins and molecular mechanisms of iPS cell induction remain elusive. This report describes the generation of iPS cells from adult mouse hepatocytes and gastric epithelial cells. These iPS cell clones appear to be equivalent to embryonic stem cells in gene expression and are competent to generate germline chimeras. Genetic lineage tracings show that liver-derived iPS cells are derived from albumin-expressing cells. No common retroviral integration sites are found among multiple clones. These data suggest that iPS cells are generated by direct reprogramming of lineage-committed somatic cells and that retroviral integration into specific sites is not required.
ISOLATION, PROPERTIES, AND BIOLOGICAL EFFECTS OF PHOMIC ACID
Authors: Lakshmanan M. , Vanterpool T. C.
Published: February 2008

Phomic acid, a toxic metabolic product of Phoma medicaginis, has been isolated from culture filtrates of the fungus. The toxin crystallizes as colorless rectangular plates having a refractive index of 0.56 and melting at 259–260 °C. It has absorption peaks at 208 and 260 mμ. The infrared spectrum of the toxin suggests that it may be an unsaturated aliphatic hydroxy acid.The toxic principle causes discoloration and drying of the leaf tip and leaf margin and a general stunting of the flax plant. It inhibits germination of seeds of flax, alfalfa, rape, and cress. The effect of phomic acid on seed germination can be reversed by glutathione and cysteine. Germination of the conidia of a few fungi is completely inhibited by the toxin, whereas it only retards the growth of the germ tube of Helminthosporium sativum. It inhibits the activity of triosephosphate dehydrogenase but not that of malic dehydrogenase. It is suggested that the toxin might act by inhibiting enzyme systems requiring sulphydryl groups for activity.
GENETICS OF LUPINUS: I. VARIATIONS IN FLOWER COLOR FROM NATURAL POPULATIONS OF LUPINUS NANUS
Authors: Harding James , Mankinen C. B.
Published: February 2008

Methods using natural outcrossing were developed for testing the genetic bases of flower color variants from natural populations of Lupinus nanus. Six flower color variants were described and named white, white-crinkle, faint-blue, light-blue-stripe, pink, and lavender. Each was found to be a simple Mendelian recessive to the dominant blue flower color characteristic of the species. Intercrosses among the six recessive genotypes established that the genes for the different colors were not allelic. The loci were designated B/b for white, Bc/bc for white-crinkle, F/f for faint-blue, A/a for light-blue-stripe, P/p for pink, and L/l for lavender.
KALM'S SPECIMENS OF NORTH AMERICAN GRASSES—THEIR EVALUATION FOR TYPIFICATION
Authors: Baum Bernard R.
Published: February 2008

The value of Kalm's specimens as nomenclatural types of Linnaean species of grasses is evaluated with special reference to a number of species previously typified. A number of these species are retypified according to the "Guide for determination of types" given in the International Code of Nomenclature. As a result of this study one new combination: Trichachne nutans (L.) Baum is made and several other changes in nomenclature are suggested.
BIOLOGICAL CHARACTERISTICS OF FOMES FOMENTARIUS, FOUND ON SPRUCE AND BIRCH
Authors: Suvorov P. A.
Published: February 2008

The comparative growth rates and wood destructive ability of two isolates of Tomes fomentarius (Fries) Kickx. were investigated under laboratory conditions. The pure cultures were obtained from 2-year-old fruiting bodies, growing on stumps of birch (Betula verrucosa Ehrh.) and spruce (Picea excelsa L.) trees situated in the same locality. Comparing the rates of growth of these isolates, on beer-must agar, it was found that isolates from spruce stumps grew faster and covered the entire surface of the medium in 11 days, whereas isolates from birch overgrew the same area in 16 days. The wood-destroying ability of spruce isolates was greater on pine, spruce, and oak wood blocks, whereas birch isolates were more destructive to birch, beech, aspen, alder, linden, and maple. The macro-and micro-scopic characteristics of mycelial mats of both isolates, as well as the fruiting bodies, revealed no difference between them.
Distribution and role of mineral compounds in the haustorium of a parasite of Galium arenarium, Thesium humifusum, before flowering
Authors: Renaudin Serge , Cheguillaume Noelle , Gallant Daniel J.
Published: February 2008

The relations between host and parasite in the haustoria of Thesium humifusum have been studied by scanning electron microscopy combined with an energy dispersive system. The distribution of mineral elements in the connecting tissues binding the host and parasite has been determined. It has been shown that the concentrations of phosphorus and potassium were higher in the hyaline tissue and in the intertracheidal parenchyma; the concentration of silicon was higher in the tracheids of the lignified transfer bridge and the concentration of calcium was higher in the cortical parenchyma and secondary phloem of the host root.These results support the existence of an osmotic gradient in the haustorium and between the two partners in the direction of the parasite. This gradient together with the transpiration pull and the intense acid phosphatase activity in the tissues may explain the movement of water and mineral substances from host to parasite.
A taxonomic survey of some species of Didymella and Didymella-like species
Authors: Corlett Michael
Published: February 2008

Descriptions and illustrations are provided for 15 species of Didymella: D. alectorolophi, D. applanata, D. astragalina, D. bryoniae, D. castillejae, D. delphinii, D. eupyrena, D. exigua, D.festucae, D. glacialis, D. hellebori, D. pedicularis, D. phacae, D. proximella, D. trifolii and for Didymella (?) abieticola, Pseudomassaria corni, Lophiosphaera lophospora comb. nov., and Mycosphaerella prominula. A key to the species and a host index are also provided. Species of Didymella included in this study fall into two small but well-defined subgeneric groups and one large heterogeneous intermediate group.
Ultrastructure of Polyphagus euglenae zoospores
Authors: Powell Martha J.
Published: February 2008

Zoospore ultrastructure of Polyphagus euglenae Nowakowski, a parasite of algae, was studied using transmission electron microscopy. The elongate zoospore contains a centrally located nucleus covered by a ribosomal aggregation. Membranes, continuous with the nuclear envelope, concentrically traverse the ribosomal aggregation and form a lateral membranous labyrinth. In the posterior end of the zoospore, a single prominent microbody–lipid globule complex (MLC) lies adjacent to the nucleus. Oval microbodies cover the anterior aspect of the lipid globule, and a fenestrated cisterna (the rumposome) covers the posterior aspect of the lipid globule. Several of the elongate and branched mitochondria that bind the ribosomal aggregation are near the microbodies, and these mitochondria are also part of the MLC. The flagellar apparatus includes a parallel oriented kinetosome and secondary centriole, as well as a rootlet that extends laterally between the kinetosome and the plasma membrane and passes over a portion of the rumposome. Regularly banded and homogeneous configurations of the rhizoplast are found. Cored vesicles and vesicles containing heterogeneous inclusions are scattered in the outer regions of the cell. In the diaminobenzidine cytochemical technique for the visualization of catalase, microbodies are lightly stained, and this staining is inhibited by aminotriazole. Inflated regions of the nuclear envelope and ribosomal aggregation cisternae also contain electron-dense reaction product. Because staining of endomembranes is inhibited by sodium azide but not by the inhibitor of catalase activity, aminotriazole, it is concluded that catalase, which may have low activity, is present only in microbodies. Because of the distinctive structure of the flagellar apparatus, ribosomal aggregation and cisternal system as well as the position of the MLC, zoospore ultrastructure of P. euglenae is clearly distinct from any other chytrid zoospore that has been studied.
Effect of medium constituents on the viability of immobilized plant cells
Authors: Jones A. , Veliky I. A.
Published: February 2008

Cell suspension cultures of Daucus carota, Cannabis sativa, and Ipomoea sp. were entrapped within a matrix of calcium alginate. Immobilized D. carota cells were chosen as a model system for studies on the effects of medium constituents on the viability (i.e., respiration activity) of the entrapped cells. The 71 V medium could be simplified by omission of hormones, NH4+N, and vitamins, and 2-(N-morpholino)ethanesulphonic acid could substitute for phosphate as the buffering component of the medium. An examination of the effects of varying concentrations of sucrose, KCl, trace elements, and CaCl2 on the viability of the entrapped cells allowed a simple buffer mixture to be formulated. In this mixture, immobilized cells remained viable for at least 24 days and at 12 days could still transform digitoxigenin to periplogenin. Entrapped cells of C. sativa were similarly viable for at least 8 days.
Interactions between nitrogen sources and xylose affecting growth, sporulation, and polyphenoloxidase activity in Bipolaris maydis race T
Authors: Evans Robert C. , Black Candace L.
Published: February 2008

The effect of 23 organic and 3 inorganic nitrogen sources on growth, sporulation, and polyphenoloxidase activity was measured in Bipolaris maydis race T incubated with or without a xylose supplement. Mycelial dry weight tends to be highest on acidic and other polar amino acids and least on nonpolar ones; organic nitrogen sources generally result in greater dry weight than inorganic ones. Changes in nitrogen concentration and pH of media influence growth and sporulation, but only pH alters the relative effectiveness of the nitrogen sources on these processes. The addition of xylose to the growth media has little effect on growth. However, in the presence of lysine, serine, asparagine, glycine, γ-alanine, alanine, and α-aminobutyrate, xylose causes an increase in sporulation and a concomitant decrease in polyphenoloxidase activity. There is no consistent pattern resulting from xylose addition in the presence of the other nitrogen sources.
Entry of Pisolithus tinctorius hyphae into Pinus taeda roots
Authors: Warrington Sarah J. , Black H. Delano , Coons Lewis B.
Published: February 2008

Ectomycorrhizal and nonectomycorrhizal short roots of Pinus taeda were examined by scanning electron microscopy. Hyphae of Pisolithus tinctorius enter primary tissues of lateral and short roots through natural openings several times larger than hyphal diameter. Similar openings appear in roots not exposed to P. tinctorius. Hyphae also enter the root surface through other openings the same diameter as the hyphae. These openings are probably formed by the enzymatic activity of the hyphal tips.
Ecological relationships of wild rice, Zizania aquatica. 1. A model for among-site growth
Authors: Lee P. F. , Stewart J. M.
Published: February 2008

During the 1976 and 1977 growing seasons the growth of wild rice was quantified at four sampling stations on the Mississippi River near the Clay Boswell Steam Electric Station at Cohasset, Minnesota. Cluster analysis was used to illustrate the intercorrelations and seasonal trends which existed among the water and sediment chemical variables. All biological, chemical, and physical variables were corrected for any time dependency, and discriminant analysis isolated those factors which could separate the four sampling stations. The discriminant functions were composed of biological (wild rice density), chemical (alkalinity), and physical (water temperature, water depth) factors previously known to influence wild rice growth. A model of the growth of wild rice was predicted effectively for each of the four sampling stations by combining (i) a time-independent equation formed from a multiple regression analysis of the time-corrected biological, chemical, and physical variables isolated as being significant in the discriminant analysis, versus the time-corrected dry weights per wild rice plant, and (ii) a time-dependent equation formed by fitting a logistic equation to the overall mean weights per wild rice plant at the four sampling stations.
Sample size in studies of geographic variation
Authors: Newman K. W. , Jancey R. C.
Published: February 2008

A procedure is described which provides an objective basis for selecting the number of individuals to sample at each location in studies of geographic variation within species. An example is given using cone data for Pinus contorta.
The mycorrhizal status of boreal plants: species from northeastern Ontario
Authors: Malloch D. , Malloch B.
Published: February 2008

Twenty-nine species of vascular plants commonly occurring in the Boreal Forest Region of northeastern Ontario were examined for the presence of mycorrhizae. Four species were ectomycontiizal, 4 both endo- and ecto-mycorrhizal, and 15 endomycorrhizal. Among the Ericaceae, one had arbutoid mycorrhizae and five ericoid mycorrhizae. The distribution of Cenococcum geophilum among the ectomycorrhizal and arbutoid plants is compared. Selected findings are discussed in relation to reports in the literature.
Ethnobotany in North America: an historical phytogeographic perspective
Authors: Ford Richard I.
Published: February 2008

In 1855 Alphonse de Candolle challenged his contemporaries to describe and to explain the geographical and historical distribution of economic plants. It was only in the 20th century, however, that ethnobotany, the direct interrelationships between human populations and their plant environment, and paleoecology and archaeology could combine to delineate from antiquity the history of economic plant usages, to describe the ecological changes introduced by humans, and to detail the cultural determinants of new plant evolution.The prehistory of plant uses depends upon paleoecological and archaeological data. Pollen and plant macroremains have demonstrated that only during the past 2000 years in North America have humans expanded the number of taxa they used. Ecologically humans have become important agents for transforming the landscape during the same time period in areas where plant food production was practiced. Fire was the principle agent for clearing the land and plant husbandry intensified the disjunction of plant species. Humans, then, became significant ecological and evolutionary factors in the landscape with the introduction of domesticated cucurbits from Mexico in the eastern United States about 5000 years ago. It was not until 3000 years ago that indigenous North American Helianthus and Iva were domesticated and other plants were cultivated and introduced beyond their known ranges. In the Southwest com cultivation started 3000 years ago and spread rapidly as a staple and source of phytogeographical changes. Com-field farming in the past 1000 years by prehistoric Americans created new habitats and had the greatest effect on the geographical distribution of plants. Ethnobotany and its associated discipline, archaeobotany, have brought an indispensible complement to paleoecology and a new dimension to historical phytogeography.
A FRAMEWORK FOR TOOL SELECTION AND USE IN INTEGRATED ASSESSMENT FOR SUSTAINABLE DEVELOPMENT
Authors: DE RIDDER WOUTER , TURNPENNY JOHN , NILSSON MÅNS , VON RAGGAMBY ANNEKE
Published: February 2008

Integrated assessment is rapidly developing in the scientific as well as policy community. Different methods, techniques and procedures (i.e., tools) are used in these assessments. Often, the choice for using certain tools in an assessment is not well founded. This paper presents a framework that scientifically underpins the role of, and thus choice for, tools within an integrated assessment. The framework identifies four phases in an integrated assessment, which are derived from the complementarities between various forms of integrated assessments. Tasks have to be done within each of the four phases. Seven types of tools with similar characteristics are matched to those tasks. The tool framework is a theoretical construct, developed whilst keeping in mind perceptions and suggestions from eventual users. It is a first step in the development of an overarching framework for finding appropriate tools for different tasks in an assessment, and justifying the use of those tools.
A QUALITY AND EFFECTIVENESS REVIEW PROTOCOL FOR STRATEGIC ENVIRONMENTAL ASSESSMENT (SEA) IN DEVELOPING COUNTRIES
Authors: RETIEF FRANCOIS
Published: February 2008

The need for empirical research and systematic performance evaluation of SEA, to advance theoretical understandings as well as practice, has been widely expressed. To promote such research any performance evaluation has to ensure that it is conceptually justified, methodologically sound, practically viable and tailored to the local context. This paper describes a SEA quality and effectiveness review protocol for application within the South African context. Based on international perspectives and debates it provides a description of the conceptual thinking underpinning the structure of the protocol in terms of its approach and framework as well as methodological justification on how the review areas and indicators were designed. Finally a critical evaluation of its application to selected case studies is presented. It concludes that the conceptual framework and methodology could be applied in any context although the contents in terms of review areas and indicators needs to be adapted to accommodate different understandings and perspectives on SEA.
TOWARDS A FRAMEWORK FOR SEA FOLLOW-UP: THEORETICAL ISSUES AND LESSONS FROM POLICY EVALUATION
Authors: PERSSON ÅSA , NILSSON MÅNS
Published: February 2008

Most SEA practice and research has focused on the pre-decision stages, whereas post-decision follow-up stages such as monitoring, evaluation, and management have been given far less attention. These stages, referred to as SEA follow-up, are integral to making SEA effective and learning-oriented. This paper takes the first step towards a framework for conducting SEA follow-up, by analysing the requirements for ex post activities according to the European SEA Directive (2001/42/EC), reviewing existing experiences and literature on how to perform SEA follow-up, and exploring lessons to be learnt from the adjacent fields of EIA follow-up and policy evaluation. The directive, along with most mainstream applications of SEA, is based on EIA follow-up concepts. However, SEA follow-up displays a number of critical differences, including: an enhanced risk of implementation gaps; a focus on performance rather than compliance; and less direct linkages between decisions and impacts. The paper argues that the SEA Directive is seriously constrained and that a more ambitious interpretation of SEA follow-up is necessary to enable strategic decision making and learning. Lessons from the policy/programme evaluation literature could strengthen SEA follow-up by giving it analytical rigour in relation to establishing causality and providing insights into the use and acceptance of SEA follow-up among decision makers and stakeholders. Further explorations into policy evaluation toolkits, and practical experiences in applying them, are needed to enhance the potential of SEA follow-up in supporting strategic decision making.
Regulation of caveolar cardiac sodium current by a single Gsα histidine residue
Authors: Palygin Oleg A. , Pettus Janette M. , Shibata Erwin F.
Published: February 2008

Cardiac sodium channels (voltage-gated Na+ channel subunit 1.5) reside in both the plasmalemma and membrane invaginations called caveolae. Opening of the caveolar neck permits resident channels to become functional. In cardiac myocytes, caveolar opening can be stimulated by applying β-receptor agonists, which initiates an interaction between the stimulatory G protein subunit-α (Gsα) and caveolin-3. This study shows that, in adult rat ventricular myocytes, a functional Gsα-caveolin-3 interaction occurs, even in the absence of the caveolin-binding sequence motif of Gsα. Consistent with previous data, whole cell experiments conducted in the presence of intracellular PKA inhibitor stimulation with β-receptor agonists increased the sodium current ( INa) by 35.9 ± 8.6% ( P < 0.05), and this increase was mimicked by application of Gsα protein. Inclusion of anti-caveolin-3 antibody abolished this effect. These findings suggest that Gsα and caveolin-3 are components of a PKA-independent pathway that leads to the enhancement of INa. In this study, alanine scanning mutagenesis of Gsα (40THR42), in conjunction with voltage-clamp studies, demonstrated that the histidine residue at position 41 of Gsα (H41) is a critical residue for the functional increase of INa. Protein interaction assays suggest that GsαFL (full length) binds to caveolin-3, but the enhancement of INa is observed only in the presence of Gsα H41. We conclude that Gsα H41 is a critical residue in the regulation of the increase in INa in ventricular myocytes.
Arachidonic acid in postshock mesenteric lymph induces pulmonary synthesis of leukotriene B4
Authors: Jordan Janeen R. , Moore Ernest E. , Sarin Eric L. , Damle Sagar S. , Kashuk Sara B. , Silliman Christopher C. , Banerjee Anirban
Published: February 2008

Mesenteric lymph is the mechanistic link between splanchnic hypoperfusion and acute lung injury (ALI), but the culprit mediator(s) remains elusive. Previous work has shown that administration of a phospholipase A2(PLA2) inhibitor attenuated postshock ALI and also identified a non-ionic lipid within the postshock mesenteric lymph (PSML) responsible for polymorphonuclear neutrophil (PMN) priming. Consequently, we hypothesized that gut-derived leukotriene B4(LTB4) is a key mediator in the pathogenesis of ALI. Trauma/hemorrhagic shock (T/HS) was induced in male Sprague-Dawley rats and the mesenteric duct cannulated for lymph collection/diversion. PSML, arachidonic acid (AA), and a LTB4receptor antagonist were added to PMNs in vitro. LC/MS/MS was employed to identify bioactive lipids in PSML and the lungs. T/HS increased AA in PSML and increased LTB4and PMNs in the lung. Lymph diversion decreased lung LTB4by 75% and PMNs by 40%. PSML stimulated PMN priming (11.56 ± 1.25 vs. 3.95 ± 0.29 nmol O2−/min; 3.75 × 105cells/ml; P < 0.01) that was attenuated by LTB4receptor blockade (2.64 ± 0.58; P < 0.01). AA stimulated PMNs to produce LTB4, and AA-induced PMN priming was attenuated by LTB4receptor antagonism. Collectively, these data indicate that splanchnic ischemia/reperfusion activates gut PLA2-mediated release of AA into the lymph where it is delivered to the lungs, provoking LTB4production and subsequent PMN-mediated lung injury.
Effect of training in the fasted state on metabolic responses during exercise with carbohydrate intake
Authors: De Bock K. , Derave W. , Eijnde B. O. , Hesselink M. K. , Koninckx E. , Rose A. J. , Schrauwen P. , Bonen A. , Richter E. A. , Hespel P.
Published: February 2008

Skeletal muscle gene response to exercise depends on nutritional status during and after exercise, but it is unknown whether muscle adaptations to endurance training are affected by nutritional status during training sessions. Therefore, this study investigated the effect of an endurance training program (6 wk, 3 day/wk, 1–2 h, 75% of peak V̇o2) in moderately active males. They trained in the fasted (F; n = 10) or carbohydrate-fed state (CHO; n = 10) while receiving a standardized diet [65 percent of total energy intake (En) from carbohydrates, 20%En fat, 15%En protein]. Before and after the training period, substrate use during a 2-h exercise bout was determined. During these experimental sessions, all subjects were in a fed condition and received extra carbohydrates (1 g·kg body wt−1 ·h−1). Peak V̇o2 (+7%), succinate dehydrogenase activity, GLUT4, and hexokinase II content were similarly increased between F and CHO. Fatty acid binding protein (FABPm) content increased significantly in F ( P = 0.007). Intramyocellular triglyceride content (IMCL) remained unchanged in both groups. After training, pre-exercise glycogen content was higher in CHO (545 ± 19 mmol/kg dry wt; P = 0.02), but not in F (434 ± 32 mmol/kg dry wt; P = 0.23). For a given initial glycogen content, F blunted exercise-induced glycogen breakdown when compared with CHO ( P = 0.04). Neither IMCL breakdown ( P = 0.23) nor fat oxidation rates during exercise were altered by training. Thus short-term training elicits similar adaptations in peak V̇o2 whether carried out in the fasted or carbohydrate-fed state. Although there was a decrease in exercise-induced glycogen breakdown and an increase in proteins involved in fat handling after fasting training, fat oxidation during exercise with carbohydrate intake was not changed.
Food restriction and simulated microgravity: effects on bone and serum leptin
Authors: Baek Kyunghwa , Barlow Alicia A. , Allen Matt R. , Bloomfield Susan A.
Published: February 2008

Leptin is responsible for linking energy metabolism to bone mass. Because astronauts are commonly in negative energy balance during spaceflight, this study was designed to assess individual and combined effects of food restriction and simulated microgravity on bone mass and serum leptin. Six-month-old male Sprague-Dawley rats were randomly assigned to four groups ( n = 12 each): two hindlimb-unloading (HU) groups fed 100% (HU100) and 70% (HU70) and two cage-activity control (CC) groups fed 100% (CC100) and 70% (CC70) of their baseline food requirement. After 28 days, CC100 rats gained body weight, whereas all other groups lost body weight; this loss was greater in HU70 than in CC70 and HU100 rats. Serum leptin decreased in CC70 and HU100 (−60% and −27%, respectively) and was not detectable in HU70 animals. Percent osteoid surface in CC70 and HU100 was lower than that of CC100 (7.80%, 8.60% vs. 10.70%, respectively), and this decrease was more pronounced in HU70 animals (4.38%). Mineral apposition rate of CC70, HU100, and HU70 rats was lower than that of CC100 (1.5, 1.6, and 1.5 vs. 2.1 μm/day, respectively). Bone formation rate of CC70, HU100, and HU70 rats was lower than that of CC100 (13.4, 13.1, and 12.2 vs. 40.8 mm3·mm−2·day−1, respectively). The change in bone formation rate was correlated with the change in serum leptin value over 28 days ( r2 = 0.69, P = 0.0007). We conclude that moderate caloric restriction may cause bone loss at susceptible bone sites to a similar degree as does the unloading effect of microgravity; serum leptin may be an important endocrine regulator contributing to this change in skeletal integrity.
Epithelial-Mesenchymal Transition in Breast Cancer Relates to the Basal-like Phenotype
Authors: Sarrió David , Rodriguez-Pinilla Socorro María , Hardisson David , Cano Amparo , Moreno-Bueno Gema , Palacios José
Published: February 2008

Epithelial-mesenchymal transition (EMT) is defined by the loss of epithelial characteristics and the acquisition of a mesenchymal phenotype. In carcinoma cells, EMT can be associated with increased aggressiveness, and invasive and metastatic potential. To assess the occurrence of EMT in human breast tumors, we conducted a tissue microarray–based immunohistochemical study in 479 invasive breast carcinomas and 12 carcinosarcomas using 28 different markers. Unsupervised hierarchical clustering of the tumors and statistical analysis showed that up-regulation of EMT markers (vimentin, smooth-muscle-actin, N-cadherin, and cadherin-11) and overexpression of proteins involved in extracellular matrix remodeling and invasion (SPARC, laminin, and fascin), together with reduction of characteristic epithelial markers (E-cadherin and cytokeratins), preferentially occur in breast tumors with the “basal-like phenotype.” Moreover, most breast carcinosarcomas also had a basal-like phenotype and showed expression of mesenchymal markers in their sarcomatous and epithelial components. To assess whether basal-like cells have intrinsic phenotypic plasticity for mesenchymal transition, we performed in vitro studies with the MCF10A cell line. In response to low cell density, MCF10A cells suffer spontaneous morphologic and phenotypic EMT-like changes, including cytoskeleton reorganization, vimentin and Slug up-regulation, cadherin switching, and diffuse cytosolic relocalization of the catenins. Moreover, these phenotypic changes are associated with modifications in the global genetic differentiation program characteristic of the EMT process. In summary, our data indicate that in breast tumors, EMT likely occurs within a specific genetic context, the basal phenotype, and suggests that this proclivity to mesenchymal transition may be related to the high aggressiveness and the characteristic metastatic spread of these tumors. [Cancer Res 2008;68(4):989–97]
Synergistic Damage of Tumor Vessels with Ultra Low-Dose Endothelial-Monocyte Activating Polypeptide-II and Neovasculature-Targeted Tumor Necrosis Factor-α
Authors: Crippa Luca , Gasparri Anna , Sacchi Angelina , Ferrero Elisabetta , Curnis Flavio , Corti Angelo
Published: February 2008

High-dose endothelial-monocyte activating polypeptide II (EMAP-II), a tumor-derived antiangiogenic cytokine, can sensitize tumor vasculature to the damaging activity of high-dose tumor necrosis factor (TNF)-α. However, this combination cannot be used for systemic treatment of patients because of prohibitive toxicity. We have found that this limitation can be overcome by combining a TNF-targeting strategy with the use of ultra low-dose EMAP-II. Coadministration of 0.1 ng of EMAP-II and 0.1 ng of CNGRCG-TNF (NGR-TNF), a peptide-TNF conjugate able to target tumor blood vessels, inhibited lymphoma and melanoma growth in mice, with no evidence of toxicity. This drug combination induced endothelial cell apoptosis in vivo and, at later time points, caused reduction of vessel density and massive apoptosis of tumor cells. Ligand-directed targeting of TNF was critical because the combination of nontargeted TNF with EMAP-II was inactive in these murine models. The synergism was progressively lost when the dose of EMAP-II was increased in the nanogram to microgram range, supporting the concept that the use of low-dose EMAP-II is critical. Studies on the mechanism of this paradoxical behavior showed that EMAP-II doses >1 ng induce the release of soluble TNF receptor 1 in circulation, a strong counter-regulatory inhibitor of TNF. Tumor vascular targeting with extremely low amounts of these cytokines may represent a new strategy for cancer treatment. [Cancer Res 2008;68(4):1154–61]
Association of Genetic Variation in the Transforming Growth Factor β-1 Gene with Serum Levels and Risk of Colorectal Neoplasia
Authors: Saltzman Barbara S. , Yamamoto Jennifer F. , Decker Robert , Yokochi Lance , Theriault Andre G. , Vogt Thomas M. , Le Marchand Loïc
Published: February 2008

In the normal intestinal epithelium transforming growth factor β-1 (TGFβ-1) acts as a growth inhibitor, but in malignant cells it may act as a tumor promoter. However, only limited information is available on genetic variation in the TGFB1 gene and its relationship to circulating levels and risk of colorectal cancer. To characterize associations of genetic variation [tagging single-nucleotide polymorphisms (tagSNP) and haplotypes with frequency >0.05] at the TGFB1 locus with circulating TGFβ-1 and risk of colorectal neoplasia, we conducted two case-control studies (including 271 colorectal adenoma cases and 544 controls, and 535 colorectal adenocarcinoma cases and 656 controls) among Japanese Americans, Caucasians, and Native Hawaiians in Hawaii. Serum TGFβ-1 was measured by sandwich ELISA among the subjects of the first study. The variant A allele for tagSNP rs6957 was associated with higher serum TGFβ-1 [means (in ng/mL) and 95% confidence interval (95% CI) for AA or AG, 32.6 (30.6–34.7); GG, 29.0 (25.1–32.9); Pdifference = 0.05] after adjusting for age and other factors. Homozygous carriers of the variant G allele for tagSNP rs11466345 had a statistically significantly lower risk of adenocarcinoma [AG versus AA: odds ratio (OR), 0.9 (95% CI, 0.7–1.2); GG versus AA: OR, 0.4 (95% CI, 0.2–0.7); Ptrend = 0.01]. The haplotype carrying both variants was also statistically significantly associated with a reduced risk of adenocarcinoma (OR, 0.3; 95% CI, 0.1–0.8). Although not statistically significant, the direction and magnitude of the corresponding ORs were similar for adenoma. These results suggest that a haplotype containing SNP rs11466345 at the 3′ end of TGFB1 is associated with genetic susceptibility to colorectal neoplasia. [Cancer Res 2008;68(4):1236–44]
A Selective Phosphatase of Regenerating Liver Phosphatase Inhibitor Suppresses Tumor Cell Anchorage-Independent Growth by a Novel Mechanism Involving p130Cas Cleavage
Authors: Daouti Sherif , Li Wen-hui , Qian Hong , Huang Kuo-Sen , Holmgren Janna , Levin Wayne , Reik Linda , McGady Debra Lucas , Gillespie Paul , Perrotta Agostino , Bian Hongjin , Reidhaar-Olson John F. , Bliss Sarah A. , Olivier Andree R. , Sergi Joseph A. , Fry David , Danho Waleed , Ritland Steve , Fotouhi Nader , Heimbrook David , Niu Huifeng
Published: February 2008

The phosphatase of regenerating liver (PRL) family, a unique class of oncogenic phosphatases, consists of three members: PRL-1, PRL-2, and PRL-3. Aberrant overexpression of PRL-3 has been found in multiple solid tumor types. Ectopic expression of PRLs in cells induces transformation, increases mobility and invasiveness, and forms experimental metastases in mice. We have now shown that small interfering RNA–mediated depletion of PRL expression in cancer cells results in the down-regulation of p130Cas phosphorylation and expression and prevents tumor cell anchorage-independent growth in soft agar. We have also identified a small molecule, 7-amino-2-phenyl-5H-thieno[3,2-c]pyridin-4-one (thienopyridone), which potently and selectively inhibits all three PRLs but not other phosphatases in vitro. The thienopyridone showed significant inhibition of tumor cell anchorage-independent growth in soft agar, induction of the p130Cas cleavage, and anoikis, a type of apoptosis that can be induced by anticancer agents via disruption of cell-matrix interaction. Unlike etoposide, thienopyridone-induced p130Cas cleavage and apoptosis were not associated with increased levels of p53 and phospho-p53 (Ser15), a hallmark of genotoxic drug-induced p53 pathway activation. This is the first report of a potent selective PRL inhibitor that suppresses tumor cell three-dimensional growth by a novel mechanism involving p130Cas cleavage. This study reveals a new insight into the role of PRL-3 in priming tumor progression and shows that PRL may represent an attractive target for therapeutic intervention in cancer. [Cancer Res 2008;68(4):1162–9]
Differential Effects of Interleukin-2 and Interleukin-15 versus Interleukin-21 on CD4+ Cutaneous T-Cell Lymphoma Cells
Authors: Marzec Michal , Halasa Krzysztof , Kasprzycka Monika , Wysocka Maria , Liu Xiaobin , Tobias John W. , Baldwin Donald , Zhang Qian , Odum Niels , Rook Alain H. , Wasik Mariusz A.
Published: February 2008

In this study, we compared the effects of interleukin-2 (IL-2), IL-15, and IL-21 on gene expression, activation of cell signaling pathways, and functional properties of cells derived from CD4+ cutaneous T-cell lymphoma (CTCL). Whereas both IL-2 and IL-15 modulated, in a CTCL cell line, the expression of >1,000 gene transcripts by at least 2-fold, IL-21 up-regulated <40 genes. All three cytokines induced tyrosine phosphorylation of Jak1 and Jak3 in CTCL cell lines and native leukemic (Sezary) cells. However, only IL-2 and IL-15 strongly activated signal transducers and activators of transcription 5, phosphoinositide 3-kinase/Akt, and mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase/ERK signaling pathways in the cell lines and mitogen-primed native cells. In contrast, IL-21 selectively activated signal transducers and activators of transcription 3. Whereas all three cytokines protected CTCL cells from apoptosis, only IL-2 and IL-15 promoted their proliferation. The effects of the cytokine stimulation were Jak3 kinase– and Jak1 kinase– dependent. These findings document the vastly different effect of IL-2 and IL-15 versus IL-21 on CTCL cells. They also suggest two novel therapeutic approaches to CTCL and, possibly, other CD4+ T-cell lymphomas: inhibition of the Jak1/Jak3 kinase complex and, given the known strong immunostimulatory properties of IL-21 on CD8+ T, natural killer, and B cells, application of this cytokine to boost an immune response against malignant CD4+ T cells. [Cancer Res 2008;68(4):1083–90]