bluuebunny/crossref_metadata_2025 huggingface dataset:
Secretory leukocyte protease inhibitor promotes the tumorigenic and metastatic potential of cancer cells
Authors: Devoogdt Nick , Hassanzadeh Ghassabeh Gholamreza , Zhang Jing , Brys Lea , De Baetselier Patrick , Revets Hilde
Published: May 2003

Because of their ability to inhibit proteases, protease inhibitors have generally been considered to counteract tumor progression and metastasis. However, expression of serine protease inhibitors (SPIs) in tumors is often associated with poor prognosis of cancer patients. Moreover, there is growing evidence that SPIs may even promote malignancy of cancer cells, opening new avenues for their use as biomarkers in malignancy. To isolate cancer promoting genes, we applied the suppression subtractive hybridization method to low-malignant Lewis Lung Carcinoma 3LL-S versus high-malignant 3LL-S-sc cells. This resulted in the identification of the SPIsecretory leukocyte protease inhibitor(SLPI), as one of the genes whose expression was higher in 3LL-S-sc than in 3LL-S cells. By stable transfection of 3LL-S cells with mouse or humanSLPI, we demonstrated that elevated levels ofSLPIexpression increased both the tumorigenicity and lung-colonizing potential of 3LL-S cells. Moreover, we showed that this function ofSLPIdepended on its protease inhibitory capacity. Our results also reveal that althoughSLPIenhanced the proliferation of 3LL-S cellsin vitro, its promalignant activityin vivowas not solely due to its effect on cell proliferation. In this study, we report a causal role forSLPIin the malignant behavior of cancer cells, underscoring the potential malignancy-promoting activities of SPIs.
Genome Function and Nuclear Architecture: From Gene Expression to Nanoscience
Authors: O'Brien Timothy P. , Bult Carol J. , Cremer Christoph , Grunze Michael , Knowles Barbara B. , Langowski Jörg , McNally James , Pederson Thoru , Politz Joan C. , Pombo Ana , Schmahl Günter , Spatz Joachim P. , van Driel Roel
Published: May 2003

Biophysical, chemical, and nanoscience approaches to the study of nuclear structure and activity have been developing recently and hold considerable promise. A selection of fundamental problems in genome organization and function are reviewed and discussed in the context of these new perspectives and approaches. Advancing these concepts will require coordinated networks of physicists, chemists, and materials scientists collaborating with cell, developmental, and genome biologists.
Overexpression of a Knotted-Like Homeobox Gene of Potato Alters Vegetative Development by Decreasing Gibberellin Accumulation
Authors: Rosin Faye M. , Hart Jennifer K. , Horner Harry T. , Davies Peter J. , Hannapel David J.
Published: May 2003

Potato (Solanum tuberosum) homeobox 1 (POTH1) is a class I homeobox gene isolated from an early-stage tuber cDNA library. The RNA expression pattern ofPOTH1, unlike that of most other class Iknotted-like homeobox genes, is widespread in the cells of both indeterminate and differentiated tissues. Using in situ hybridization, POTH1 transcripts were detected in meristematic cells, leaf primordia, and the vascular procambium of the young stem. Overexpression of POTH1 produced dwarf plants with altered leaf morphology. Leaves were reduced in size and displayed a “mouse-ear” phenotype. The mid-vein was less prominent, resulting in a palmate venation pattern. The overall plant height of overexpression lines was reduced due to a decrease in internode length. Levels of intermediates in the gibberellin (GA) biosynthetic pathway were altered, and the bioactive GA, GA1, was reduced by one-half in sense mutants. Accumulation of mRNA for GA 20-oxidase1, a key biosynthetic enzyme, decreased in overexpression lines. In vitro tuberization was enhanced under both short- and long-day photoperiods in several POTH1 overexpression lines. Sense lines produced more tubers at a faster rate than controls. These results imply that POTH1 mediates the development of potato by acting as a negative regulator of GA biosynthesis.
Cell Death in the Unicellular Chlorophyte Dunaliella tertiolecta. A Hypothesis on the Evolution of Apoptosis in Higher Plants and Metazoans
Authors: Segovia Marı́a , Haramaty Liti , Berges John A. , Falkowski Paul G.
Published: May 2003

Apoptosis is essential for normal growth and development of multicellular organisms, including metazoans and higher plants. Although cell death processes have been reported in unicellular organisms, key elements of apoptotic pathways have not been identified. Here, we show that when placed in darkness, the unicellular chlorophyte alga Dunaliella tertiolecta undergoes a form of cell death reminiscent of apoptosis in metazoans. Many morphological criteria of apoptotic cell death were met, including an increase in chromatin margination, degradation of the nucleus, and DNA fragmentation. Biochemical assays of the activities of cell death-associated proteases, caspases, measured using highly specific fluorogenic substrates, increased with time in darkness and paralleled the morphological changes. The caspase-like activities were inhibited by caspase-specific inhibitors. Antibodies raised against mammalian caspases cross-reacted with specific proteins in the alga. The pattern of expression of these immunologically reactive proteins was correlated with the onset of cell death. The occurrence of key components of apoptosis, and particularly a caspase-mediated cell death cascade in a relatively ancient linage of eukaryotic photoautotrophs, argues against current theories that cell death evolved in multicellular organisms. We hypothesize that key elements of cell death pathways were transferred to the nuclear genome of early eukaryotes through ancient viral infections in the Precambrian Ocean before the evolution of multicellular organisms and were subsequently appropriated in both metazoan and higher plant lineages.
Identification of Novel Mitochondrial Protein Components ofChlamydomonas reinhardtii. A Proteomic Approach
Authors: van Lis Robert , Atteia Ariane , Mendoza-Hernández Guillermo , González-Halphen Diego
Published: May 2003

Pure mitochondria of the photosynthetic algaChlamydomonas reinhardtii were analyzed using blue native-polyacrylamide gel electrophoresis (BN-PAGE). The major oxidative phosphorylation complexes were resolved: F1F0-ATP synthase, NADH-ubiquinone oxidoreductase, ubiquinol-cytochrome c reductase, and cytochrome c oxidase. The oligomeric states of these complexes were determined. The F1F0-ATP synthase runs exclusively as a dimer, in contrast to the C. reinhardtii chloroplast enzyme, which is present as a monomer and subcomplexes. The sequence of a 60-kD protein, associated with the mitochondrial ATP synthase and with no known counterpart in any other organism, is reported. This protein may be related to the strong dimeric character of the algal F1F0-ATP synthase. The oxidative phosphorylation complexes resolved by BN-PAGE were separated into their subunits by second dimension sodium dodecyl sulfate-PAGE. A number of polypeptides were identified mainly on the basis of their N-terminal sequence. Core I and II subunits of complex III were characterized, and their proteolytic activities were predicted. Also, the heterodimeric nature of COXIIA and COXIIB subunits in cytochrome c oxidase was demonstrated. Other mitochondrial proteins like the chaperone HSP60, the alternative oxidase, the aconitase, and the ADP/ATP carrier were identified. BN-PAGE was also used to approach the analysis of the major chloroplast protein complexes of C. reinhardtii.
Towards an Analysis of the Rice Mitochondrial Proteome
Authors: Heazlewood Joshua L. , Howell Katharine A. , Whelan James , Millar A. Harvey
Published: May 2003

Purified rice (Oryza sativa) mitochondrial proteins have been arrayed by isoelectric focusing/polyacrylamide gel electrophoresis (PAGE), by blue-native (BN) PAGE, and by reverse-phase high-performance liquid chromatography (LC) separation (LC-mass spectrometry [MS]). From these protein arrays, we have identified a range of rice mitochondrial proteins, including hydrophilic/hydrophobic proteins (grand average of hydropathicity = −1.27 to +0.84), highly basic and acid proteins (isoelectric point = 4.0–12.5), and proteins over a large molecular mass range (6.7–252 kD), using proteomic approaches. BN PAGE provided a detailed picture of electron transport chain protein complexes. A total of 232 protein spots from isoelectric focusing/PAGE and BN PAGE separations were excised, trypsin digested, and analyzed by tandem MS (MS/MS). Using this dataset, 149 of the protein spots (the products of 91 nonredundant genes) were identified by searching translated rice open reading frames from genomic sequence and six-frame translated rice expressed sequence tags. Sequence comparison allowed us to assign functions to a subset of 85 proteins, including many of the major function categories expected for this organelle. A further six spots were matched to rice sequences for which no specific function has yet been determined. Complete digestion of mitochondrial proteins with trypsin yielded a peptide mixture that was analyzed directly by reverse-phase LC via organic solvent elution from a C-18 column (LC-MS). These data yielded 170 MS/MS spectra that matched 72 sequence entries from open reading frame and expressed sequence tag databases. Forty-five of these were obtained using LC-MS alone, whereas 28 proteins were identified by both LC-MS and gel-based separations. In total, 136 nonredundant rice proteins were identified, including a new set of 23 proteins of unknown function located in plant mitochondria. We also report the first direct identification, to our knowledge, of PPR (pentatricopeptide repeat) proteins in the plant mitochondrial proteome. This dataset provides the first extensive picture, to our knowledge, of mitochondrial functions in a model monocot plant.
Quantitative Trait Loci and Comparative Genomics of Cereal Cell Wall Composition
Authors: Hazen Samuel P. , Hawley Robin M. , Davis Georgia L. , Henrissat Bernard , Walton Jonathan D.
Published: May 2003

Quantitative trait loci (QTLs) affecting sugar composition of the cell walls of maize (Zea mays) pericarp were mapped as an approach to the identification of genes involved in cereal wall biosynthesis. Mapping was performed using the IBM (B73 × Mo17) recombinant inbred line population. There were statistically significant differences between B73 and Mo17 in content of xylose (Xyl), arabinose (Ara), galactose (Gal), and glucose. Thirteen QTLs were found, affecting the content of Xyl (two QTLs), Ara (two QTLs), Gal (five QTLs), Glc (two QTLs), Ara + Gal (one QTL), and Xyl + Glc (one QTL). The chromosomal regions corresponding to two of these, affecting Ara + Gal and Ara on maize chromosome 3, could be aligned with a syntenic region on rice (Oryza sativa) chromosome 1, which has been completely sequenced and annotated. The contiguous P1-derived artificial chromosome rice clones covering the QTLs were predicted to encode 117 and 125 proteins, respectively. Two of these genes encode putative glycosyltransferases, displaying similarity to carbohydrate-active enzyme database family GT4 (galactosyltransferases) or to family GT64 (C-terminal domain of animal heparan synthases). The results illustrate the potential of using natural variation, emerging genomic resources, and homeology within the Poaceae to identify candidate genes involved in the essential process of cell wall biosynthesis.
The Cotton Kinesin-Like Calmodulin-Binding Protein Associates with Cortical Microtubules in Cotton Fibers
Authors: Preuss Mary L. , Delmer Deborah P. , Liu Bo
Published: May 2003

Microtubules in interphase plant cells form a cortical array, which is critical for plant cell morphogenesis. Genetic studies imply that the minus end-directed microtubule motor kinesin-like calmodulin-binding protein (KCBP) plays a role in trichome morphogenesis in Arabidopsis. However, it was not clear whether this motor interacted with interphase microtubules. In cotton (Gossypium hirsutum) fibers, cortical microtubules undergo dramatic reorganization during fiber development. In this study, cDNA clones of the cotton KCBP homolog GhKCBP were isolated from a cotton fiber-specific cDNA library. During cotton fiber development from 10 to 21 DPA, the GhKCBP protein level gradually decreases. By immunofluorescence, GhKCBP was detected as puncta along cortical microtubules in fiber cells of different developmental stages. Thus our results provide evidence that GhKCBP plays a role in interphase cell growth likely by interacting with cortical microtubules. In contrast to fibers, in dividing cells of cotton, GhKCBP localized to the nucleus, the microtubule preprophase band, mitotic spindle, and the phragmoplast. Therefore KCBP likely exerts multiple roles in cell division and cell growth in flowering plants.
Basic skills and small business competitiveness: some conceptual considerations
Authors: Addis Mark
Published: May 2003

Considers how basic skills affect competitiveness, particularly that of small businesses, and the effectiveness of some facets of recent policy initiatives directed at increasing the level of basic skills. Economic performance is seriously threatened by low standards of basic skills. Basic skills are an element of competitiveness because they are connected with personal development, occupational skills, and information technology skills. The application of market and system failure models offers some insight into the levels of basic skills training provided by employers. It is suggested that there is a substantial way to go before employers are firmly persuaded of the competitiveness benefits of undertaking more investment in basic skills training.
The untethered facilities manager
Authors: Finch Edward
Published: May 2003

Facilities managers have a host of skills to sustain the functionality of complex buildings, often not provided by them directly, but by the team of specialists they draw upon to effectively plan for the future, whether the resource be money, space or technology. Building intelligence presents a challenge in terms of understanding a wholly new approach to the building management. This paper asks if the intelligent building of today meets the needs of the facilities management team. Does it enable them to manage their asset more effectively? New technologies are converging that will enable a radically new approach to maintenance, enabling remote smart sensing or remote condition based monitoring (CBM). Some of the design and economic issues that arise from this radically new approach to managing built assets are highlighted and the possibilities for a maintenance environment, where wires, power cables and data loggers become a thing of the past, is described.
“Brain drain” from Turkey: survey evidence of student non‐return
Authors: Tansel Aysit , Demet Güngör Nil
Published: May 2003

Turkey’s first “brain drain” wave began in the 1960s, with doctors and engineers among the first group of emigrants. In recent years, attention has shifted to young university graduates who are seriously contemplating starting their careers abroad as a result of the current economic crisis. Postgraduate studies overseas provide the first step for many in fulfilling this goal. This paper provides an evaluation of the findings of a survey conducted during the first half of 2002 on the return intentions of Turkish students studying abroad. Various factors have been cited as important for student non‐return, including political instability, lower salaries and lack of employment opportunities in the home country when studies are completed, as well as a preference to live abroad. In addition to these factors, several other features of Turkey’s political economy are considered to be important in explaining the Turkish brain drain.
Firm size and recruitment: staffing practices in small and large organisations in north Cyprus
Authors: Tanova Cem
Published: May 2003

This paper investigates the differences between staffing methods used in small and large organisations in north Cyprus. Possible reasons for small organisations preferring some methods over others are discussed, along with the general problems small firms face in recruiting employees. Our survey results show that small organisations are more likely to rely on informal methods of recruitment, but no significant relationship was found between the choice of recruitment method and human resource management outcomes such as employee turnover rate.
A Decade of Europe? Some Reflections on an Aspiration
Authors: Ward Ian
Published: May 2003

This article suggests that Europe faces four primary challenges today. The first relates to democracy, as all the anxieties about the ‘democratic deficit’ in Community are writ even larger in the Union. A second issue is that of liberal legalism. Lawyers have long presumed that the ‘new’ Europe has been integrated ‘through’ law. This article suggests that the role of law is of far less importance to the future of the Union. A third problem, perhaps the most pressing, relates to enlargement. Is the ‘new’ Europe fully prepared for the inevitable shock that will follow the much‐vaunted ‘big bang’? Finally, there is the overarching problem of a continuing lack of ethos, or public philosophy, underpinning public life in the ‘new’ Europe.
Doctors as Good Samaritans: Some Empirical Evidence Concerning Emergency Medical Treatment in Britain
Authors: Williams Kevin
Published: May 2003

This paper reports the results of the first survey of British doctors' attitudes towards the provision of emergency treatment outside the usual confines of a surgery or hospital. The experience and perceptions of NHS doctors practising in Sheffield concerning Good Samaritan behaviour are discussed against the background of the rather uncertain common law of medical rescue. The implications of the survey's findings for the direction of legal policy and the promotion of medical altruism are also considered. Despite the alleged deterioration in standards of social responsibility, the potentially fraught nature of such interventions, and the theoretical possibility of legal liability should any rescue attempt go badly, it seems that the overwhelming majority of doctors (in this survey, at least) are willing Samaritans.
Trends and determinants of managing virtual R&D teams
Authors: Gassmann Oliver , von Zedtwitz Maximilian
Published: May 2003

The past years have seen a decentralization of R&D to local markets and centres‐of‐excellence. Supported by modern information and communication technologies, ‘virtual project teams’ were formed to facilitate transnational innovation processes. With their boundaries expanding and shrinking flexibly with changing project necessities, virtual teams are believed to be an important element in future R&D organization. Based on 204 interviews with R&D directors and project managers in 37 technology‐intensive multinational companies we identify four distinct forms of virtual team organizations used to execute R&D projects across multiple locations. Ordered by increasing degree of central project coordination, these four team concepts are based on: (1) decentralized self‐organization, (2) a system integrator as a coordinator, (3) a core team as a system architect, and (4) a centralized venture team. Our contingency approach for organizing a transnational R&D project is based on four principal determinants: (1) the type of innovation (radical/incremental), (2) the systemic nature of the project (systemic/autonomous), (3) the mode of knowledge involved (tacit/explicit), and (4) the degree of resource bundling (complementary/redundant). According to our analysis, the success of virtual teams depends on the appropriate consideration of these determinants.
Alvin Plantinga's Warranted Christian Belief
Authors: Fales Evan
Published: May 2003

Book reviewed in this article:

Alvin Plantinga, Warranted Christian Belief
Biophysical and Pharmacological Characterization of Voltage‐Gated Calcium Currents in Turtle Auditory Hair Cells
Authors: Schnee M. E. , Ricci A. J.
Published: May 2003

Hair cell calcium channels regulate membrane excitability and control synaptic transmission. The present investigations focused on determining whether calcium channels vary between hair cells of different characteristic frequencies or if multiple channel types exist within a hair cell, each serving a different function. To this end, turtle auditory hair cells from high‐ (317 ± 27 Hz) and low‐frequency (115 ± 6 Hz) positions were voltage clamped using the whole‐cell recording technique, and calcium currents were characterized based on activation, inactivation and pharmacological properties. Pharmacological sensitivity to dihydropyridines (nimodipine, Bay K 8644), benzothiazepines (diltiazem) and acetonitrile derivatives (verapamil, D600) and the insensitivity to non‐L‐type calcium channel antagonists support the conclusion that only L‐type calcium channels were present. Fast activation rise times (< 0.5 ms), hyperpolarized half‐activation potentials and a relative insensitivity to nimodipine suggest the channels were of the α1D (CaV1.3) variety. Although no pharmacological differences were found between calcium currents obtained from high‐ and low‐frequency cells, low‐frequency cells activated slightly faster and at hyperpolarized potentials, with half‐activating voltages of −43 ± 1 mV compared to −35 ± 1 mV. Inactivation was observed in both high‐ and low‐frequency cells. The time course of inactivation required three time constants for a fit. Long depolarizations could result in complete inactivation. The voltage of half‐inactivation was −40 ± 2 mV for high‐frequency cells and −46 ± 2 mV for low‐frequency cells. Calcium channel inactivation did not significantly alter hair cell electrical resonant properties elicited from protocols where the membrane potential was hyperpolarized or depolarized prior to characterizing the resonance. A bell‐shaped voltage dependence and modest sensitivities to intracellular calcium chelators and external barium ions suggest that inactivation was calcium dependent.
Interleukin 1β Modulates Rat Subfornical Organ Neurons as a Result of Activation of a Non‐Selective Cationic Conductance
Authors: Desson Sheana E. , Ferguson Alastair Victor
Published: May 2003

The circumventricular organs (CVOs) are ideal locations at which circulating pyrogens may act to communicate with the CNS during an immune challenge. Their dense vasculature and fenestrated capillaries allow direct access of these pyrogens to CNS tissue without impediment of the blood‐brain barrier (BBB). One such CVO, the subfornical organ (SFO), has been implicated as a site at which the circulating endogenous pyrogen interleukin 1β (IL‐1β) acts to initiate the febrile response. This study was designed to determine the response of rat SFO neurons to IL‐1β (1 nM to 100 fM) using whole‐cell current‐clamp and voltage‐clamp techniques. We found that physiological (subseptic) concentrations of IL‐1β (1 pM, 500 fM, 100 fM) induced a transient depolarization in SFO neurons accompanied by a significant increase in spike frequency. In contrast, pharmacological (septic) concentrations of IL‐1β (1 nM) evoked a sustained hyperpolarization. While depolarizations in response to IL‐1β were abolished by treatment of cells with the IL‐1 receptor antagonist (IL‐1ra), hyperpolarizations were still observed. Voltage‐clamp analysis revealed that the majority (85 %) of SFO neurons responding to IL‐1β with depolarization (29 of 34 cells) exhibited an electrophysiological profile characterized by a dominant delayed rectifier potassium current (DIK), a conductance that we also found to be reduced to 84.4 ± 3.3 % of control by bath application of IL‐1β. In addition, using slow voltage ramps we demonstrated that IL‐1β activates a non‐selective cationic current (INSC) with a reversal potential of −38.8 ± 1.8 mV. These studies identify the cellular mechanisms through which IL‐1β can influence the excitability of SFO neurons and, as a consequence of such actions, initiate the febrile response to exogenous pyrogens.
Insulin Signalling and Resistance in Patients with Chronic Heart Failure
Authors: Kemppainen Jukka , Tsuchida Hiroki , Stolen Kira , Karlsson Håkan , Björnholm Marie , Heinonen Olli J. , Nuutila Pirjo , Krook Anna , Knuuti Juhani , Zierath Juleen R.
Published: May 2003

We investigated whether insulin resistance in patients with chronic heart failure (CHF) is associated with impaired insulin signalling in skeletal muscle and whether exercise training would lead to an improvement in insulin signalling, concomitant with enhanced insulin action. Fourteen men with CHF due to idiopathic dilated cardiomyopathy, with mild‐to‐moderate limitation of physical activity and a left‐ventricular ejection fraction of less than 45 %, were studied before and after either a 5 month exercise training programme (n= 7) or standard care (n= 7). Seven healthy men participated as controls. Whole‐body insulin‐stimulated glucose uptake was determined by the euglycaemic hyperinsulinaemic clamp technique and skeletal muscle biopsy samples were obtained before and after the insulin infusion for insulin signalling measurements. Insulin‐stimulated glucose uptake was 20 % lower in CHF patients versus healthy subjects. Physiological hyperinsulinaemia increased tyrosine phosphorylation of insulin receptor substrate (IRS)‐1 by ≈2.5‐fold, IRS‐1‐associated phosphatidylinositol 3‐kinase (PI‐3‐kinase) activity by ≈2‐fold and Akt (protein kinase B) phosphorylation by ≈3‐fold, with similar responses between healthy subjects and CHF patients. Insulin‐mediated glucose uptake was not altered in patients after standard care, whereas exercise training elicited a 25 % increase in glucose uptake. Neither standard care nor exercise training altered insulin‐stimulated tyrosine phosphorylation of IRS‐1, IRS‐1‐associated PI‐3‐kinase activity or Akt phosphorylation. In conclusion, the CHF patients demonstrated impaired insulin‐stimulated glucose uptake, despite normal signal transduction in skeletal muscle at the level of IRS‐1, PI‐3‐kinase and Akt. Of clinical relevance is the finding that exercise training improves glucose uptake. However, these changes in insulin action after exercise training appear to be independent of enhanced insulin signalling at the level of IRS‐1, PI‐3‐kinase or Akt.
Radio-Frequency Spectroscopy of Ultracold Fermions
Authors: Gupta S. , Hadzibabic Z. , Zwierlein M. W. , Stan C. A. , Dieckmann K. , Schunck C. H. , van Kempen E. G. M. , Verhaar B. J. , Ketterle W.
Published: May 2003

Radio-frequency techniques were used to study ultracold fermions. We observed the absence of mean-field “clock” shifts, the dominant source of systematic error in current atomic clocks based on bosonic atoms. This absence is a direct consequence of fermionic antisymmetry. Resonance shifts proportional to interaction strengths were observed in a three-level system. However, in the strongly interacting regime, these shifts became very small, reflecting the quantum unitarity limit and many-body effects. This insight into an interacting Fermi gas is relevant for the quest to observe superfluidity in this system.
LOW TEMPERATURE PHYSICS AT ROOM TEMPERATURE IN WATER: CHARGE INVERSION IN CHEMICAL AND BIOLOGICAL SYSTEMS
Authors: GROSBERG A. YU. , NGUYEN T. T. , SHKLOVSKII B. I.
Published: May 2003

We review recent advances in the physics of strongly interacting charged systems functioning in water at room temperature. We concentrate on the phenomena which go beyond the framework of mean field theories, whether linear Debye-Hückel or non-linear Poisson-Boltzmann. We place major emphasis on charge inversion - a counterintuitive phenomenon in which a strongly charged particle, called macroion, binds so many counterions that its net charge changes sign. We discuss the universal theory of charge inversion based on the idea of a strongly correlated liquid of adsorbed counterions, similar to a Wigner crystal. This theory has a vast array of applications, particularly in biology and chemistry; for example, the DNA double helix in the presence of positive multivalent ions (e.g., polycations) acquires a net positive charge and drifts as a positive particle in electric field. This simplifies DNA uptake by the cell as needed for gene therapy, because the cell membrane is negatively charged. We discuss also the analogies of charge inversion in other fields of physics.
MOSFET AND FRONT-END PROCESS INTEGRATION: SCALING TRENDS, CHALLENGES, AND POTENTIAL SOLUTIONS THROUGH THE END OF THE ROADMAP
Authors: ZEITZOFF PETER M. , HUTCHBY JAMES A. , HUFF HOWARD R.
Published: May 2003

The development of advanced MOSFETs for future IC technology generations is discussed from the perspective of the 2001 International Technology Roadmap for Semiconductors (ITRS). Starting from overall chip circuit requirements, MOSFET and front-end process integration technology requirements and scaling trends are discussed, as well as some of the key challenges and potential solutions. These include the use of high-k gate dielectrics, metal-gate electrodes, and perhaps the use of non-classical devices such as double-gate MOSFETs in the later stages of the ITRS.
FAR–FUTURE TRENDS IN SOI TECHNOLOGY: A GUESS
Authors: CRISTOLOVEANU SORIN
Published: May 2003

The horizon of the Silicon On Insulator (SOI) technology is explored based on the compilation of many expert viewpoints. An SOI panel was organized at WOFE'02 with the aim of 'guessing' the shape of SOI and its industrial place in 10 years from now. SOI is expected to gradually take the role of bulk-silicon CMOS, reach the final stages of the ITRS roadmap in microelectronics, and enter the nanoelectronics world. The debate exhaustively examined the strategic and critical aspects of SOI technology. Only a few issues were retained as serious challenges.
THE MULTIPLE-GATE MOS-JFET TRANSISTOR
Authors: BLALOCK BENJAMIN J. , CRISTOLOVEANU SORIN , DUFRENE BRIAN M. , ALLIBERT F. , MOJARRADI MOHAMMAD M.
Published: May 2003

A new SOI device, the MOS-JFET, has been developed that combines two different transistors, JFET and MOSFET, superimposed in a single silicon island so that they share the same body. A unique attribute of the MOS-JFET is that it can be viewed as a four gate transistor (two side junction-based gates, the top MOS gate, and the back gate activated by SOI substrate biasing). Each of these four gates can control the conduction characteristics of the transistor. This novel transistor's multiple gate inputs give rise to exciting circuit opportunities for analog, RF, mixed-signal, and digital applications. Measured results of MOS-JFET transistors, fabricated in a conventional partially-depleted SOI technology, demonstrate that the device is fully operational. From the experiments and systematic 2-D simulations, typical regions of operation are identified. These results indicate that optimum performance is reached when the MOS and junction field-effects are combined.
QUANTUM DOT SUPERLATTICES IN A CONSTANT ELECTRIC FIELD: LOCALIZATION AND BLOCH OSCILLATIONS
Authors: SURIS ROBERT A. , DMITRIEV IVAN A.
Published: May 2003

An analysis has been presented of electron localization in ideal 2D and 3D quantum dot superlattices (QDSL) in a homogeneous dc electric field and of Bloch oscillations in such structures. A very strong dependence of the ideal QDSL spectrum and wave functions on the field orientation is demonstrated. Bloch oscillations (BO) in QDSL are performed at two (or three for 3D QDSL) main Stark frequencies, which can be independently tuned by variation of field value and orientation. Due to the strong dependence of spectrum on field orientation, in QDSL intraminiband scattering processes can be almost totally suppressed. That allows to enlarge the BO lifetime by two orders of magnitude as compared with conventional quantum well superlattices.
Molecular Basis of Platelet Granule Secretion
Authors: Flaumenhaft Robert
Published: May 2003

The energy-dependent release of granule contents from activated platelets is a well-established component of normal hemostasis and thrombosis. A role for membrane fusion in this process has been presumed for decades, but only recently have the mechanisms of platelet membrane fusion been investigated at the molecular level. Such studies have demonstrated that platelet membrane fusion is controlled by lipid components of the membrane bilayer, by transmembrane proteins termed SNARE proteins, and by chaperone proteins that interact with SNARE proteins. This core membrane fusion machinery is controlled by activation-dependent changes in cytoskeletal organization, intracellular calcium levels, kinase activity, and intracellular protease activity. Through these mechanisms, interactions of ligands with their cognate cell-surface receptors are transmitted to the membrane fusion machinery to facilitate membrane fusion and secretion of granule contents from platelets.
Biochemical and Genetic Association of Plasma Apolipoprotein A-II Levels With Familial Combined Hyperlipidemia
Authors: Allayee Hooman , Castellani Lawrence W. , Cantor Rita M. , de Bruin Tjerk W.A. , Lusis Aldons J.
Published: May 2003

Apolipoprotein A-II (apoA-II) is a major protein on high-density lipoprotein (HDL) particles, and in mice, its levels are associated with triglyceride and glucose metabolism. In particular, transgenic mice overexpressing apoA-II exhibit hypertriglyceridemia, increased body fat, and insulin resistance, whereas apoA-II-null mice have decreased triglycerides and increased insulin sensitivity. Given the phenotypic overlap between familial combined hyperlipidemia (FCH) and apoA-II transgenic mice, we investigated the relationship of apoA-II to this disorder. Despite having lower HDL-cholesterol (HDL-C), FCH subjects had higher apoA-II levels compared with unaffected relatives (
P
<0.00016). Triglyceride and HDL-C levels were significant predictors of apoA-II, demonstrating that apoA-II variation is associated with several FCH-related traits. After adjustment for multiple covariates, there was evidence for the heritability of apoA-II levels (h
2
=0.15;
P
<0.02) in this sample. A genome scan for apoA-II levels identified significant evidence (LOD=3.1) for linkage to a locus on chromosome 1q41, coincident with a suggestive linkage for triglycerides (LOD score=1.4). Thus, this locus may have pleiotropic effects on apoA-II and FCH traits. Our results demonstrate that apoA-II is biochemically and genetically associated with FCH and may serve as a useful marker for understanding the mechanism by which FCH develops.
Representation of Change: Separate Electrophysiological Markers of Attention, Awareness, and Implicit Processing
Authors: Fernandez-Duque Diego , Grossi Giordana , Thornton Ian M. , Neville Helen J.
Published: May 2003

Awareness of change within a visual scene only occurs in the presence of focused attention. When two versions of a complex scene are presented in alternating sequence separated by a blank mask, unattended changes usually remain undetected, although they may be represented implicitly. To test whether awareness of change and focused attention had the same or separable neurophysiological substrates, and to search for the neural substrates of implicit representation of change, we recorded event-related brain potentials (ERPs) during a change blindness task. Relative to active search, focusing attention in the absence of a change enhanced an ERP component over frontal sites around 100–300 msec after stimulus onset, and in posterior sites at the 150–300 msec window. Focusing attention to the location of a change that subjects were aware of replicated those attentional effects, but also produced a unique positive deflection in the 350–600 msec window, broadly distributed with its epicenter in mediocentral areas. The unique topography and time course of this latter modulation, together with its dependence on the aware perception of change, distinguishes this “awareness of change” electrophysiological response from the electrophysiological effects of focused attention. Finally, implicit representation of change elicited a distinct electrophysiological event: Unaware changes triggered a positive deflection at the 240–300 msec window, relative to trials with no change. Overall, the present data suggest that attention, awareness of change, and implicit representation of change may be mediated by separate underlying systems.
Temporal Modulation of Spatial Tactile Extinction in Right-Brain-Damaged Patients
Authors: Guerrini Chiara , Berlucchi Giovanni , Bricolo Emanuela , Aglioti Salvatore M.
Published: May 2003

Unilateral and bilateral electrotactile stimuli were delivered to both hands of 11 right-brain-damaged (RBD) patients with left tactile extinction and 20 healthy subjects. Bimanual stimuli could be presented simultaneously or with varying stimulus onset asynchronies (SOAs). Subjects indicated their detection of unilateral or bilateral stimuli, their judgements of whether stimuli were simultaneous or successive, and, in the latter case, which side came first. In RBD patients, extinction was maximal with simultaneous presentations and decreased as SOA increased. With short SOAs, omissions of left-sided stimuli occurred with both right-side and left-side stimulus precedence, suggesting a forward and backward interference of the right stimulus on the processing of the left stimulus within a time window of at least 100 msec. In contrast, there was no interference of the left stimulus on the detection of the right stimulus. Unlike controls, extinction patients rarely expressed simultaneity judgements, but those that were produced tended to be veridical or nearly so, like in normal controls. Whereas controls expressed generally accurate judgements of right or left precedence, patients showed a bias toward a right precedence and a maximal uncertainty between left-first and right-first choices when the left stimulus had a lead between 100 and 200 msec. The results are consistent with the hypothesis that, as in other sensory modalities, tactile extinction is associated with an abnormal persistent bias of attention toward the ipsilesional side that delays the processing of contralesional stimuli. However, the finding that both extinction and explicit judgements of simultaneity tended to occur with simultaneous bilateral stimuli suggest the presence of some residual neural capacity to detect precise temporal coincidence.
Contested Images of Femininity
Authors: MILKIE MELISSA A.
Published: May 2003

This research illuminates struggles over cultural definitions of femininity by examining how cultural gatekeepers respond to girls' vocal critique of inauthentic media images. Interviews with 10 editors at two national girls' magazine organizations provide a rare glimpse into their contradictory responses to requests for depicting “real girls.” Editors legitimate and share in the critique, claiming they should change images but cannot. In these accounts, they reveal struggles over altering narrow images of femininity at the organizational and institutional levels. Editors also delegitimate girls' critique as misguided by calling on the media organizations' norms and schemas about how the (good) reader is supposed to understand the images. Paradoxically, here, editors claim that they can change images but should not. Ultimately, the power of girls' resistance is tempered, as both sets of responses lead to the girls' critique being inefficacious in redefining femininity. The study contributes to an understanding of how femininity-defining cultural institutions operate to create and sustain gender stratification.
Dangerous Dependencies
Authors: SCOTT ELLEN K. , LONDON ANDREW S. , MYERS NANCY A.
Published: May 2003

Using longitudinal, ethnographic data, the authors examine how the pursuit of self-sufficiency in the context of welfare reform may unintentionally encourage some women to develop alternative dangerous dependencies on abusive or potentially abusive men. In this article, the authors document how women ended up relying on men who have been abusive to them either for instrumental assistance or for more direct financial assistance as they struggled to move from welfare to work. The authors also document how some extremely disadvantaged and vulnerable women became enmeshed in even more dangerous dependencies as they hit time limits and fell through public and private safety nets into drug addiction and sex work. The authors frame this discussion of dangerous dependencies with the recognition that dependency relations are necessary and inevitable components of carework. They argue that the discourse of self-sufficiency should acknowledge the fact that careworkers are productive citizens to the same extent as paid laborers and grapple with the question of the means through which they can support that productivity when personal resources are limited and paid labor is temporarily or permanently impossible.
Platelet α2β1 integrin activation: contribution of ligand internalization and the α2-cytoplasmic domain
Authors: Wang Zhengyan , Leisner Tina M. , Parise Leslie V.
Published: May 2003

The α2β1 integrin is a major collagen receptor on platelets. Although it has been proposed that α2β1, like αIIbβ3, undergoes agonist-induced activation, neither the potential contributions of α2β1 receptor/ligand internalization to the increase in ligand binding nor the roles of the α2 and β1 cytoplasmic domains in activation of this integrin have been previously explored. Activation of α2β1 was assessed with fluorescein isothiocyanate–labeled soluble type I collagen binding to platelets by flow cytometry. Although collagen internalization in response to agonist activation of platelets was significant, agonist-induced collagen binding still occurred under conditions that block internalization, with minimal changes in cell surface α2β1 expression. Introduction of cell-permeable peptides containing the α2 cytoplasmic tail, and especially the membrane proximal KLGFFKR domain, induced α2β1 activation in resting platelets, whereas a cell-permeable peptide containing the β1 cytoplasmic tail was without effect. Thus, collagen binding to stimulated platelets is increased due to α2β1 activation, in addition to internalization, and the GFFKR motif appears to play an important role in the activation process.
Prior gemtuzumab ozogamicin exposure significantly increases the risk of veno-occlusive disease in patients who undergo myeloablative allogeneic stem cell transplantation
Authors: Wadleigh Martha , Richardson Paul G. , Zahrieh David , Lee Stephanie J. , Cutler Corey , Ho Vincent , Alyea Edwin P. , Antin Joseph H. , Stone Richard M. , Soiffer Robert J. , DeAngelo Daniel J.
Published: May 2003

Gemtuzumab ozogamicin (GO), a monoclonal antibody used in the treatment of acute myelogenous leukemia (AML) has been linked to the development of venoocclusive disease (VOD). We conducted a retrospective study of 62 patients with previously treated AML/MDS (myelodysplastic syndrome) who underwent allogeneic stem cell (SC) transplantation at our institution from December 2000 to October 2002 to determine whether GO exposure prior to allogeneic SC transplantation increases the risk of developing VOD. Fourteen patients received GO prior to SC transplantation. Of 62 patients, 13 (21%) developed VOD; 9 (64%) of 14 with prior GO exposure developed VOD compared with 4 (8%) of 48 without prior GO exposure (P < .0001). Logistic regression controlling for sex, disease status, donor type, and graft-versus-host disease prophylaxis identified prior treatment with GO as a significant risk factor for VOD (odds ratio [OR], 21.6; 95% confidence interval [CI], 4.2-112.2]. Nine of 10 patients who underwent SC transplantation 3.5 months or less following GO developed VOD compared with none of 4 patients who underwent SC transplantation more than 3.5 months from GO administration. Three of 14 patients who received GO prior to SC transplantation died of VOD. We conclude that patients undergoing SC transplantation within a short interval from GO administration are at increased risk of developing VOD.
Granule stores from cellubrevin/VAMP-3 null mouse platelets exhibit normal stimulus-induced release
Authors: Schraw Todd D. , Rutledge Tara W. , Crawford Garland L. , Bernstein Audrey M. , Kalen Amanda L. , Pessin Jeffery E. , Whiteheart Sidney W.
Published: May 2003

It is widely accepted that the platelet release reaction is mediated by heterotrimeric complexes of integral membrane proteins known as SNAREs (SNAP receptors). In an effort to define the precise molecular machinery required for platelet exocytosis, we have analyzed platelets from cellubrevin/VAMP-3 knockout mice. Cellubrevin/VAMP-3 has been proposed to be a critical v-SNARE for human platelet exocytosis; however, data reported here suggest that it is not required for platelet function. Upon stimulation with increasing concentrations of thrombin, collagen, or with thrombin for increasing time there were no differences in secretion of [3H]-5HT (dense core granules), platelet factor IV (alpha granules), or hexosaminidase (lysosomes) between null and wild-type platelets. There were no gross differences in bleeding times nor in agonist-induced aggregation measured in platelet-rich plasma or with washed platelets. Western blotting of wild-type, heterozygous, and null platelets confirmed the lack of cellubrevin/VAMP-3 in nulls and showed that most elements of the secretion machinery are expressed at similar levels. While the secretory machinery in mice was similar to humans, mice did express apparently higher levels of synaptobrevin/VAMP-2. These data show that the v-SNARE, cellubrevin/VAMP-3 is not a requirement for the platelet release reaction in mice.
The role of affect on the perception of disability in multiple sclerosis
Authors: Smith S J , Young C A
Published: May 2003

Objective: To determine the prevalence of depression in multiple sclerosis in the community and to assess how the presence of depression affects patients' perception of their disability.

Design: Consecutive case series.

Setting: The study was carried out at a regional multiple sclerosis (MS) clinic.

Subjects: Eighty-eight patients with MS.

Main outcome measures: Patients were asked to complete the following questionnaires: Hospital Anxiety and Depression Scale (HADS), Beck Depression Inventory (BDI), Rankin Scale of Disability/Handicap (completed by patient and physician to assess relative perceived disability) and two visual analogue scales (coping ability and perceived service adequacy).

Results: Thirty-nine per cent were case level for depression using the BDI criteria of Sullivan; 17% were case level for depression (34% borderline case) and 34% case level for anxiety on HADS. Depressed patients using both BDI and HADS criteria were three times more likely than nondepressed patients to perceive their disability as being greater than the physicians' perception ( p < 0.001).

Conclusion: Depression is common in MS and adversely affects patients' perception of their disability.