bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Tax protein in human T-cell leukemia virus type-I leukemogenicity
Authors: Azran Inbal , Schavinsky-Khrapunsky Yana , Aboud Mordechai
Published: August 2004

HTLV-1 is the etiological agent of adult T-cell leukemia (ATL), the neurological syndrome TSP/HAM and certain other clinical disorders. The viral Tax protein is considered to play a central role in the process leading to ATL. Tax modulates the expression of many viral and cellular genes through the CREB/ATF-, SRF- and NF-κB-associated pathways. In addition, Tax employs the CBP/p300 and p/CAF co-activators for implementing the full transcriptional activation competence of each of these pathways. Tax also affects the function of various other regulatory proteins by direct protein-protein interaction. Through these activities Tax sets the infected T-cells into continuous uncontrolled replication and destabilizes their genome by interfering with the function of telomerase and topoisomerase-I and by inhibiting DNA repair. Furthermore, Tax prevents cell cycle arrest and apoptosis that would otherwise be induced by the unrepaired DNA damage and enables, thereby, accumulation of mutations that can contribute to the leukemogenic process. Together, these capacities render Tax highly oncogenic as reflected by its ability to transform rodent fibroblasts and primary human T-cells and to induce tumors in transgenic mice. In this article we discuss these effects of Tax and their apparent contribution to the HTLV-1 associated leukemogenic process. Notably, however, shortly after infection the virus enters into a latent state, in which viral gene expression is low in most of the HTLV-1 carriers' infected T-cells and so is the level of Tax protein, although rare infected cells may still display high viral RNA. This low Tax level is evidently insufficient for exerting its multiple oncogenic effects. Therefore, we propose that the latent virus must be activated, at least temporarily, in order to elevate Tax to its effective level and that during this transient activation state the infected cells may acquire some oncogenic mutations which can enable them to further progress towards ATL even if the activated virus is re-suppressed after a while. We conclude this review by outlining an hypothetical flow of events from the initial virus infection up to the ultimate ATL development and comment on the risk factors leading to ATL development in some people and to TSP/HAM in others.
Critical care procedure logging using handheld computers
Authors: Carlos Martinez-Motta J , Walker Robin , Stewart Thomas E , Granton John , Abrahamson Simon , Lapinsky Stephen E
Published: August 2004

Introduction

We conducted this study to evaluate the feasibility of implementing an internet-linked handheld computer procedure logging system in a critical care training program.

Methods

Subspecialty trainees in the Interdepartmental Division of Critical Care at the University of Toronto received and were trained in the use of Palm handheld computers loaded with a customized program for logging critical care procedures. The procedures were entered into the handheld device using checkboxes and drop-down lists, and data were uploaded to a central database via the internet. To evaluate the feasibility of this system, we tracked the utilization of this data collection system. Benefits and disadvantages were assessed through surveys.

Results

All 11 trainees successfully uploaded data to the central database, but only six (55%) continued to upload data on a regular basis. The most common reason cited for not using the system pertained to initial technical problems with data uploading. From 1 July 2002 to 30 June 2003, a total of 914 procedures were logged. Significant variability was noted in the number of procedures logged by individual trainees (range 13–242). The database generated by regular users provided potentially useful information to the training program director regarding the scope and location of procedural training among the different rotations and hospitals.

Conclusion

A handheld computer procedure logging system can be effectively used in a critical care training program. However, user acceptance was not uniform, and continued training and support are required to increase user acceptance. Such a procedure database may provide valuable information that may be used to optimize trainees' educational experience and to document clinical training experience for licensing and accreditation.
Novel applications of therapeutic hypothermia: report of three cases
Authors: Hartemink Koen J , Wisselink Willem , Rauwerda Jan A , Girbes Armand RJ , Polderman Kees H
Published: August 2004

Therapeutic hypothermia can provide neuroprotection in various situations where global or focal neurological injury has occurred. Hypothermia has been shown to be effective in a large number of animal experiments. In clinical trials, hypothermia has been used in patients with postanoxic injury following cardiopulmonary resuscitation, in traumatic brain injury with high intracranial pressure, in the perioperative setting during various surgical procedures and for various other indications. There is thus evidence that hypothermia can be effective in various situations of neurological injury, although a number of questions remain unanswered. We describe three patients with unusual causes of neurological injury, whose clinical situation was in fundamental aspects analogous to conditions where hypothermia has been shown to be effective.
The child as agent for change in therapy for phonological disorders
Authors: Weiss Amy L.
Published: August 2004

All speech and language therapists want to determine which strategies facilitate improvement of their clients' communication skills and to delineate the most efficacious of these. Although laudable preliminary efforts have been made, the field of speech-language pathology is in its nascent period of data gathering regarding efficacy. Determining best practices for young children presenting with speech production disorders represents one necessary area of efficacy research, given their prevalence in the population. Borrowing from literature outside the speech therapy field, suggestions are made in this paper for capitalizing on the young child's own contribution to the therapy process, as an avenue for utilizing techniques that will be both effective and efficient for children receiving therapy for multiple misarticulations.
The role of families in optimizing phonological therapy outcomes
Authors: Bowen Caroline , Cupples L.
Published: August 2004

Developed in Australia, Parents and Children Together (PACT) is a broad-based, family-centred phonological therapy. It is a treatment approach for developmental phonological disorders in the course of whose implementation speech and language therapists enlist the active participation of parents and significant others. It requires family members to learn technical information and develop novel skills to use, with professional guidance, in relation to their own child and his or her specific speech clarity issues. In this paper we review the family education and “homework’ aspects of PACT and explore, with brief case illustrations, the participation of 13 families involved in its administration.
From hindsight to foresight: working around barriers to success in phonological intervention
Authors: Baker Elise , Bernhardt Barbara
Published: August 2004

A major goal of phonological intervention is to help bring a child's speech development to within normal range for his or her developmental stage. Reaching that goal may take longer than anticipatedfor some children. This paper illustrates an in–depth retrospective evaluation of assessment data from one child with a phonological impairment, who progressed slowly during intervention (Baker and McLeod, 2004). An alternative intervention plan is suggested that takes key factors from the assessment data into account, and utilizes a nonlinear phonologicalframework to set up the goal sequence. The insights gained from hindsight in this case may lead to foresight for other children s intervention programmes.
Power, difference and mobility: feminist advances in migration studies
Authors: Silvey Rachel
Published: August 2004

The feminist migration literature in geography has contributed to bringing several critical social theoretical themes to the forefront of migration studies. Specifically, feminists have foregrounded the politics of scale, mobility as political process, questions of subjectivity/identity and critical theorizations of space and place. This article provides an overview of the feminist migration literature organized around these themes. In addition, it argues that feminist migration studies can play a pivotal role in the ongoing project of marrying the materialist concerns of political economy to those of critical social theorists.
Convergence, the institutional turn and workplace regimes: the case of lean production
Authors: Rutherford Tod D.
Published: August 2004

The principal focus in this paper is a sympathetic critique of the institutional turn in economic geography and its analysis of convergence in contemporary capitalism. While insightful, this perspective does not fully capture the dynamic and contradictions of capitalist development and has tended to neglect the role of labor-capital relations in how systems of work organization develop. Following Jessop (1999; 2001), I argue that macroeconomic competition driven by the law of value disrupts institutions and acts as a ‘disembedding’ force for convergence within capitalism. In the workplace these tendencies are mediated by labor's ability to resist capital through what Burawoy (1985) terms the production politics of workplace regimes. I then illustrate these general points via an analysis of lean production in the automobile industry. Lean production is associated with strong convergence tendencies, because TNC reorganization facilitates the increased comparability of work quality and intensity across space. However, drawing upon the research of Lewchuck et al. (2001) and others on lean production and workers in Canada, the UK and Germany, I argue that, while national regimes are declining relative to firm-specific ones, workplace regimes continue to be an active force for divergence.
Europe's eastern expansion and the reinscription of otherness in East-Central Europe
Authors: Kuus Merje
Published: August 2004

This article examines how EU and NATO enlargement is framed by the dichotomy of Europe versus Eastern Europe, and how the enlargement process simultaneously transforms that dichotomy. I argue that the double enlargement is underpinned by a broadly orientalist discourse that assumes essential difference between Europe and Eastern Europe and frames difference from Western Europe as a distance from and a lack of Europeanness. I suggest that in order to expose and undercut this reinscription of otherness, research on East-Central Europe should engage with postcolonial theory in a more direct and sustained fashion.
Detection of antigen-specific lymphocytes/Detektion von Antigen-spezifischen Lymphozyten
Authors: Scheffold Alexander , Thiel Andreas
Published: August 2004

Abstract Antigen-specific lymphocytes are the cellular basis for the unique features of the adaptive immune system and are critically involved in both immune protection and immune pathology. Their low frequency and technical limitations with respect to specific labeling methods have prevented their in-depth analysis on the cellular level until only a few years ago. For a long time, most of our knowledge about the antigen-specific cells was obtained from indirect assays measuring antigen-induced effector functions of whole lymphocyte populations. During the last few years, several developments in flow-cytometry and cell sorting have been made which now allow to correlate phenotype and function on the single cell level. These new technologies allowed us to obtain a more detailed view of the role of antigen-specific lymphocytes for immune protection from infectious diseases as well as for immune pathology like autoimmunity or allergy. Information about frequency and function of antigen-specific lymphocytes in vivo will not only lead to improved diagnostic tools but also open up new avenues for the specific treatment of various immune-mediated disorders. Here, we give an overview of the state-of-the-art in antigen-specific cytometry.
Telomere length analysis by fluorescence in situ hybridization and flow cytometry (Flow-FISH)/Telomerlängen-Messung mittels Fluoreszenz-in-situ-Hybridisierung und Durchflusszytometrie (Flow-FISH)
Authors: Hartmann Ulrike , Beier Fabian , Brümmendorf Tim H.
Published: August 2004

Abstract Telomeres are located at the ends of chromosomes and consist of non-coding TTAGGG repeats and telomere-binding proteins. Telomeres protect the chromosomal ends from degradation, aberrant recombination and end-to-end fusion. Due to the end-replication problem, telomeres shorten with each round of replication in vitro and in vivo, eventually leading to genetic instability and cellular senescence. In germline cells and in the majority of human cancers studied, telomere length is maintained by the enzyme telomerase, which adds terminal TTAGGG repeats onto the chromosome ends and thus counteracts replication-dependent telomere shortening.

Assessment of telomere length is of value to study the mitotic history as well as the proliferative potential of cells both in vitro and in vivo. In the hematopoietic system, telomere length has been found to be correlated with disease progression and response to specific treatment in a variety of diseases, that are associated with increased cellular (e.g. stem cell) turnover. Therefore, telomere biology might potentially provide prognostic information that may help to guide the direction and intensity of therapeutic strategies in the future. Based on these considerations, it is obligatory to be able to use reliable, fast and sensitive technology for the accurate assessment of telomere length. In this review, we will characterize the most commonly used methodes to measure telomere length in cells, with particular focus on fluorescence in situ hybridization and flow cytometry (Flow-FISH).
Laboratoriumsdiagnostik bei Diabetes mellitus/Laboratory diagnostics in patients with diabetes mellitus
Authors: Truschnig-Wilders Martie , Boehm Bernhard O. , März Winfried
Published: August 2004

Zusammenfassung Diabetes mellitus umfasst eine Gruppe von metabolischen Störungen, welche durch eine Hyperglykämie als Folge von Störungen der Insulinsekretion, der Insulinaktivität oder von beidem charakterisiert sind.

Die diagnostischen Kriterien - und damit auch die Prävalenz - wurden im Laufe der Zeit unterschiedlich definiert. In Europa liegt die Prävalenz des Diabetes nach den gängigen Einteilungen, welche hier beschrieben werden, zwischen 5 und 10 Prozent. Screening-Kriterien sowie die Begriffe Mikroalbuminurie, postprandialer Blutzucker, HbA1c, C-Peptid und Proinsulin werden beschrieben.
Evaluation of automated sample preparation for quantitative detection of human immunodeficiency virus type 1 RNA/Evaluierung einer automatisierten Probenvorbereitung zum quantitativen Nachweis von HIV-1 RNA
Authors: Stelzl Evelyn , Baumert Rita , Haas Josef , Marth Egon , Kessler Harald H.
Published: August 2004

Abstract The COBAS AMPLIPREP instrument for automated sample preparation has recently been introduced. The COBAS AMPLIPREP/COBAS AMPLICOR HIV-1 MONITOR Ultrasensitive test, version 1.5, which includes this new molecular device, was evaluated and compared to the COBAS AMPLICOR HIV-1 MONITOR test, version 1.5, which includes a manual extraction protocol. Accuracy, linearity, interassay variation, and intra-assay variation were determined and a total of 126 clinical specimens were investigated. When the accuracy of the COBAS AMPLIPREP/COBAS AMPLICOR HIV-1 MONITOR test was examined, all but one result were found within ± 0.5 logs of the expected results. Furthermore, one of two samples containing 1.0 × 102 HIV-1 RNA copies ml–1 could not be detected. The determination of linearity resulted in a quasi-linear curve over at least 3 logs. For the determination of interassay variation, coefficients of variation were found between 15 and 43% for the COBAS AMPLIPREP/COBAS AMPLICOR HIV-1 MONITOR test and between 14 and 39% for the COBAS AMPLICOR HIV-1 MONITOR test. For the determination of intra-assay variation, coefficients of variation were found between 11 and 30% for the COBAS AMPLIPREP/COBAS AMPLICOR HIV-1 MONITOR test and between 13 and 30% for the COBAS AMPLICOR HIV-1 MONITOR test. When 126 clinical samples were tested with the COBAS AMPLIPREP/COBAS AMPLICOR HIV-1 MONITOR test and compared with the COBAS AMPLICOR HIV-1 MONITOR test, 93% of all samples yielded comparable results. Nine samples containing HIV-1 RNA concentrations close to the detection limit of the assays produced discrepant results. The new assay, which included the automated sample preparation, proved to be suitable for the routine molecular laboratory. It was found to be labor-saving and easy to handle.
Evaluation of a new assay for detection of herpes simplex virus type 1 and type 2 DNA by real-time PCR/Evaluierung eines neuen Tests zur Detektierung von Herpes simplex Virus Typ 1 und Typ 2 DNA mittels Real-time PCR
Authors: Haas Ingrid , Mühlbauer Gerhard , Bozic Michael , Stelzl Evelyn , Koidl Christoph , Berger Annemarie , Berg Jörg , Vince Adriana , Rabenau Holger , Kessler Harald H.
Published: August 2004

Abstract Molecular detection of herpes simplex virus (HSV) DNA is recognized as reference standard assay for the sensitive and specific diagnosis of central nervous system and genital infections caused by HSV. In this study, a qualitative molecular assay based on automated DNA extraction on the MagNA Pure LC (Roche Applied Science, Mannheim, Germany) and a commercially available kit, the LightCycler – HSV 1/2 Detection Kit (Roche), were evaluated. This kit includes a homologous internal control. The accuracy and the detection limit of the new molecular assay were determined with samples from European Union Concerted Action HSV Proficiency Panels. A total of 153 clinical specimens including cerebrospinal fluids, genital swabs, and oral swabs were investigated and the results were compared to those obtained from a home-brew molecular assay based on manual DNA extraction and real-time polymerase chain reaction (PCR). When the accuracy of the new molecular assay was tested, all positive samples except for the one containing 3.0 × 102–9.0 × 102 HSV type 1 (HSV-1) genome equivalents (GE) per ml could be detected. All negative samples tested negative. When the detection limit was determined, 6.0 × 102–1.8 × 103 HSV-1 GE per ml, i.e. 12 to 36 GE per LightCycler (LC) capillary and 2.0 × 102–6.0 × 102 HSV type 2 (HSV-2) GE per ml, i.e. 4 to 12 GE per LC capillary could consistently be detected. Results obtained from clinical specimens corresponded to 100% to those obtained by the molecular assay based on manual DNA extraction and real-time PCR. In seven clinical samples, an unexpected melting peak was detected. In conclusion, the new molecular assay allows rapid detection of HSV-1 and HSV-2 DNA in the routine diagnostic laboratory. The inclusion of a homologous internal control ensures accurate interpretation of negative results.
Experimental studies and nuclear model calculations on (p,xn) and (p,pxn) reactions on85Rb from their thresholds up to 100 MeV
Authors: Kastleiner S. , Shubin Yu. N. , Nortier F. M. , van der Walt T.N. , Qaim Syed M.
Published: August 2004

Excitation functions were measured by the stacked-foil technique for the reactions85Rb(p,pxn)84m, g,83, 82m, 81Rb from their thresholds up to 100 MeV. Nuclear model calculations were performed using the code ALICE-IPPE both on (p,xn) reactions reported earlier and (p,pxn) reactions described here. The experimental excitation curves and the results of nuclear model calculations were found to be qualitatively in agreement. With the exception of the (p,n) reaction above 40 MeV, the theory appears to reproduce all the experimental data within deviations of about 50 %. The cross section ratios for the isomeric pairs85m,gSr and84m,gRb are discussed qualitatively in terms of the spins of the states involved and the increasing projectile energy.
Theoretical treatment of the complexation of element 106, Sg, in HF solutions
Authors: Pershina V.
Published: August 2004

Fully relativistic density-functional calculations of the electronic structures of various oxo-fluoro-complexes were performed for group-6 elements Mo, W, and element 106, Sg. Based on the electronic density distribution data, relative values of the free energy change of complex formation reactions in HF solutions have been defined. On their basis, sequences in the sorption of Mo, W, and Sg by an anion exchange resin (Kdvalues) have been predicted. The results show a complex situation depending on the acid concentration and pH of the solution. The predicted trends are in agreement with the known data for Mo and W. The following sequence in the sorption of Mo, W, and Sg by an anion exchange resin from 5×10-3HF/0.1 M HNO3solutions is predicted: Mo>Sg>W. A very good separation of Sg from Mo and W is expected at concentrated HF solutions, where MOF5-is formed. The sequence of the sorption in this case should be Sg ≫W > Mo.
Advanced aqueous reprocessing in P&T strategies: Process demonstrations on genuine fuels and targets
Authors: Christiansen Birgit , Apostolidis C. , Carlos R. , Courson O. , Glatz J.-P. , Malmbeck R. , Pagliosa G. , Römer K. , Serrano-Purroy D.
Published: August 2004

In the present work the performance of several processes used for advanced reprocessing of commercial LWR fuels as well as transmutation targets is compared. As a first step uranium and plutonium were recovered by PUREX type reprocessing. The raffinate, containing fission products including lanthanides and the minor actinides (MA) was used as feed for the second step in which minor actinides and lanthanides were separated from the bulk of the fission products. The five different processes tested use CMPO, DIDPA, TRPO, Diamide and CYANEX 923 as extractants. In the third step MA are separated from lanthanides. Here three processes were tested, i.e. using CYANEX 301, the synergistic mixture of di-chloro substituted CYANEX 301 and TOPO, and BTP solvents. Column-, batch- and continuous counter-current extraction techniques were used for the tests. The different processes will be described and discussed in terms of performances and efficiencies for Am and Cm separation. Efficient separation of MA from different genuine fuel solutions could be demonstrated and thereby also the possibility of closing a future transmutation fuel cycle. The combination of Diamide and BTP seems to be the best, among extractants tested, to achieve an efficient MA recovery from spent fuel.
Uranium association with halophilic and non-halophilic bacteria and archaea
Authors: Francis Arokiasamy J. , Gillow J. B. , Dodge Cleveland J. , Harris R. , Beveridge T. J. , Papenguth H. W.
Published: August 2004

We determined the association of uranium with bacteria isolated from the Waste Isolation Pilot Plant (WIPP), Carlsbad, New Mexico, and compared this with known strains of halophilic and non-halophilic bacteria and archaea. Examination of the cultures by transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy (EDS) showed uranium accumulation extracellularly and/or intracellularly to a varying degree. In Pseudomonas fluorescens and Bacillus subtilis uranium was associated with the cell surface and in the latter it was present as irregularly shaped grains. In Halobacterium halobium, the only archeon studied here, uranium was present as dense deposits and with Haloanaerobium praevalens as spikey deposits. Halomonas sp. isolated from the WIPP site accumulated uranium both extracellularly on the cell surface and intracellularly as electron-dense discrete granules. Extended X-ray absorption fine structure (EXAFS) analysis of uranium with the halophilic and non-halophilic bacteria and archaea showed that the uranium present in whole cells was bonded to an average of 2.4±0.7 phosphoryl groups at a distance of 3.65±0.03 Å. Comparison of whole cells of Halomonas sp. with the cell wall fragments of lysed cells showed the presence of a uranium bidentate complex at 2.91±0.03 Å with the carboxylate group on the cell wall, and uranyl hydroxide with U-U interaction at 3.71±0.03 Å due to adsorption or precipitation reactions; no U-P interaction was observed. Addition of uranium to the cell lysate of Halomonas sp. resulted in the precipitation of uranium due to the inorganic phosphate produced by the cells. These results show that the phosphates released from bacteria bind a significant amount of uranium. However, the bacterially immobilized uranium was readily solubilized by bicarbonate with concurrent release of phosphate into solution.
Fluorescence and IR studies on the hydration state of lanthanides(III) and curium(III) in the complexes extracted with purified Cyanex301, Cyanex302 and Cyanex272
Authors: Tian Guoxin , Kimura Takaumi , Yoshida Zenko , Zhu Yongjun , Rao Linfeng
Published: August 2004

The hydration number of lanthanides, Ln(III) (Ln = Sm, Eu, Tb, Dy), and Cm(III) in the extracted complexes with purified Cyanex301, Cyanex302 and Cyanex272 was investigated using time-resolved laser-induced fluorescence spectroscopy (TRLFS) and FT-IR spectroscopy. The results, in conjunction with the previous results on the Ln(III) and Am(III) complexes, provide insight into the composition of the extracted complexes. No difference has been observed in the hydration number or the composition between the Ln(III) and Cm(III) complexes with Cyanex302 or Cyanex272. The extracted complexes of Ln(III) and Cm(III) with Cyanex302 have the formula, ML(HL2)2·nH2O, where L stands for the anion of Cyanex302 andn=3-5. No water molecules are found in the first coordination shell of Ln(III) or Cm(III) complexes with Cyanex272. In contrast to the extraction with Cyanex302 or Cyanex272, the composition of the Ln(III) complexes is different from that of the Cm(III) complex in the extraction with Cyanex301. The Ln(III) complex with Cyanex301 has one or two H2O molecules with a molecular formula of LnL3·2H2O or HLnL4·H2O, where L stands for the anion of Cyanex301. However, the Cm(III) complex with Cyanex301 does not contain H2O with the molecular formula of HCmL4, in which only the 8 sulfur atoms from Cyanex301 coordinate to Cm(III). The results for Cm(III) agree with the previous data for Am(III) from EXAFS and IR measurements.
Investigations on adsorption and transport behaviour of carrier-free silver, gold and platinum in quartz columns under vacuum conditions
Authors: Hohn Alexander , Eichler R. , Eichler B.
Published: August 2004

The adsorption enthalpy of silver and gold atoms on fused silica surfaces was measured using vacuum-thermochromatography. Carrier-free silver, gold and platinum nuclides were produced by irradiation of cadmium, lead and mercury targets at the Swiss Spallation Neutron Source SINQ, followed by a thermochromatographic separation. For the calculation of the adsorption enthalpy from experimental data a thermodynamic model and a kinetic model (Monte Carlo simulation) were used. Our measurements revealed an adsorption enthalpy of -279±10 kJ/mol for gold, -232±13 kJ/mol for silver and an upper limit of -430 kJ/mol for platinum. These values, determined by the thermodynamic model, are in good agreement with literature values based on the same model. Additionally, Monte Carlo simulations have been performed to demonstrate the influence of temperature and size of quartz columns on the transport of model-isotopes with different half-lives.
Observer design for reverse flow reactor
Authors: Edouard D. , Schweich D. , Hammouri H.
Published: August 2004

A medium‐scale reverse flow reactor for VOC combustion is considered. Heat loss and forced dilution by fresh air at the core of the reactor are accounted for. A countercurrent pseudohomogeneous model with frequency correction is proposed. This model is then used to synthesize an observer. This observer allows an on‐line inlet estimate of inlet VOC concentration, and of the temperature profiles in the monoliths. © 2004 American Institute of Chemical Engineers AIChE J, 50: 2155–2166, 2004
Fast process security assessment theory
Authors: Uygun Korkut , Huang Yinlun , Lou Helen H.
Published: August 2004

This communication introduces a comprehensive theory for process security assessment. The theory can quickly provide mathematically proven upper and lower bounds on minimum time to disaster (the time disaster conditions will be reached in worst‐case scenarios). Computational efficiency and reliability are achieved by performing process security assessment based on a time‐derivative–based approach, rather than conducting massive process dynamic simulations. Further, the methodology enables prioritizing the process variables critical to plant security. This facilitates pinpointing the possible reasons of a security‐threatening situation, quantifying the importance of each disturbance factor on the system's vulnerability, and creating a prioritized list of improvements/counteractions for ensuring process security. Two runaway reactor examples are studied to demonstrate the methodology for security‐threat analysis. © 2004 American Institute of Chemical Engineers AIChE J, 50: 2187–2202, 2004
Steady‐state multiplicity, flashback, and control issues in CH4 radiant burners
Authors: Bizzi M. , Saracco G. , Specchia V.
Published: August 2004

Methane is widely employed as a source of energy in combustion systems. Among the currently available technologies, radiant heaters offer high thermal efficiency and low environmental impact in comparison with atmospheric burners. The present work deals with the modeling of methane combustion in a noncatalytic metal fiber burner, represented by means of one‐dimensional transient equations. The model accounts for a detailed reaction mechanism, radiation within the porous medium, longitudinal heat and mass transfer. After its validation, the model was employed to analyze a typical stability problem that affects these systems: under given operating conditions (low specific power inputs and excess of air) the occurrence of flashback may in fact preclude the safe operation of the system. As a consequence of energy radiation in the upstream direction, the burner upstream surface and the plenum chamber might become hot enough to heat in turn the gas feedstock, thus eventually determining flashback. In this paper, the mechanism of flashback is numerically investigated as a function of the burner structure and operating conditions by means of a model analysis so as to single out regions of flashback occurrence and a criterion for safe operation. Finally, some guidelines are outlined for a cheap and effective control of the system, paving the way for possible improvement of currently adopted control systems. © 2004 American Institute of Chemical Engineers AIChE J, 50: 2276–2286, 2004
Distributed midpoint chain scission in ultrasonic degradation of polymers
Authors: Sivalingam G. , Agarwal Nitin , Madras Giridhar
Published: August 2004

The ultrasonic degradation of poly(bisphenol A carbonate), poly(ε‐caprolactone), and poly(vinyl acetate) was investigated with various solvents such as benzene, monochlorobenzene, and dichlorobenzene. The time evolution of molecular weight was determined using gel permeation chromatography. A limiting molecular weight was observed for all the systems and was a function of solvent properties. The degradation rates increased with increase in viscosity and decrease in vapor pressure. The polydispersity reached a maximum before reaching a constant value at longer times. The experimental data indicate that the breakage of the polymer is around midpoint, with a distribution rather than an ideal midpoint scission. A continuous distribution model with a stoichiometric kernel based on Lorentzian probability distribution function was developed to satisfactorily model the experimental data. © 2004 American Institute of Chemical Engineers AIChE J, 50: 2258–2265, 2004
Modeling wood gasification in a countercurrent fixed‐bed reactor
Authors: Di Blasi Colomba
Published: August 2004

A one‐dimensional, unsteady mathematical model is presented of fixed‐bed countercurrent wood gasifiers, which couples heat and mass transport with wood drying and devolatilization, char gasification, and combustion of both char and gas‐phase species. The model is used to simulate the structure of the reaction fronts and the gasification behavior of a laboratory‐scale plant as the reactor throughput and the air‐to‐wood (or char) weight ratio are varied. It is observed that a wide zone, acting essentially as a countercurrent heat exchanger, separates combustion/gasification from devolatilization/drying. Moreover, the former zone presents interesting dynamic patterns driven by the highly variable solid/gas heat transfer rates. For a constant air‐to‐wood weight ratio, the gasification process is improved by increasing the reactor throughput as a result of higher temperatures, in spite of the simultaneous reduction in the amount of char generated from wood devolatilization. In fact, an increase in the air‐to‐wood (or char) ratio always lowers the efficiency of the gasification process. Finally, good agreement is obtained between predictions and experiments for the axial temperature profiles and the composition of the producer gas. © 2004 American Institute of Chemical Engineers AIChE J, 50: 2306–2319, 2004
Analysis of the reverse flow chromatographic reactor
Authors: Caram Hugo S. , Viecco Guillermo A.
Published: August 2004

A reverse flow chromatographic reactor with side feed (RFCR) can be used to improve the conversion and selectivity for irreversible and reversible reaction systems beyond the values obtained from conventional steady‐state reactors in the case where the reactants are more strongly adsorbed than the products. It is also simpler than conventional chromatographic, moving, and simulated moving beds and other systems that combine reaction and adsorption separation. The results of the study show the robustness and stability of the system, as well as its capacity to significantly improve conversion and selectivity for several reaction systems, including consecutive reactions. Simulation results of this mathematical model for the hydrogenation of 1,3,5‐trymethylbenzene (MES) compare well with previous studies, using countercurrent moving‐bed reactors and simulated countercurrent bed reactors. © 2004 American Institute of Chemical Engineers AIChE J, 50: 2266–2275, 2004
Formation of electric potential during the oxidation of a metal particle
Authors: Filimonov Igor , Luss Dan
Published: August 2004

Experiments revealed that a transient electric voltage of the order of 1 V may form during the combustion of a single metal particle. We present a model showing that such an electrical field may form as a result of the different diffusion rates of the positive and negative charge carriers through a growing mixed‐ionic‐electronic‐conducting oxide shell. Simulations of the evolution of the electric charge carriers and temporal potential distribution reveal that three key parameters affect the voltage formation. The ratio of the characteristic oxygen ion diffusion rate within the particle to the maximum oxygen transport rate to the particle surface affects the formation of a diffusion layer and the carrier distributions inside the oxide shell. The ratio between the thickness of an exterior oxide layer, formed before the reaction has started, and the Debye screening length has a strong impact on the amplitude and temporal evolution of the voltage. The thinner this initial oxide shell is, the larger is the voltage amplitude. The ratio between the diffusion coefficients of the positive and negative charge carriers determines the sign of the excess electrical charge on the surface. © 2004 American Institute of Chemical Engineers AIChE J, 50: 2287–2296, 2004
On the modeling assessment of thermal styrene polymerization
Authors: López‐Serrano F. , Puig J. E. , Alvarez J.
Published: August 2004

In this work the problem of determining the dependencies on conversion of the initiation rate (Ri), the propagation (kp), termination (kt), and transfer to monomer (ktr) kinetic constants in the thermally initiated free‐radical polymerization of styrene is addressed. A nonlinear observability analysis establishes that the parameter groupings Ri, κ = kt/k, and Cm = ktr/kp dependencies on conversion can be determined on the basis of the species conservation balances in conjunction with conversion and (number‐ and weight‐) average molecular weight experimental measurements, without making any a priori kinetic modeling assumption. Then, the differential estimation technique associated with the observability property is applied to previously reported experimental runs at 100, 120, 170, and 200°C, yielding the following results: (1) for the two lower temperature runs, Ri exhibits a nearly quadratic dependency on monomer concentration, and for the higher temperature the overall dependency is about cubic or quartic, and this behavior differs from that of the standard cubic‐dependency model; (2) κ shows an exponential‐like decay with conversion that agrees with previous reports, and (3) Cm exhibits a quadratic‐like increase with conversion that disagrees with the linear decay assumed before. © 2004 American Institute of Chemical Engineers AIChE J, 50: 2246–2257, 2004
Crystallographic report: 1,4‐Bis(carboxymethyldiphenylphosphonio)butane dibromide, (CH2)4[(HOOCCH2)Ph2P(+)]2 ·2Br(−)
Authors: Du Miao , Zhao Xiao‐Jun
Published: August 2004

The centrosymmetric cation {[(HOOCCH2PPh2)]2(CH2)4}2+ adopts an extended conformation. The phosphorus atom shows a tetrahedral coordination and each OH of the carboxylic group is hydrogen bonded to a bromide ion. Copyright © 2004 John Wiley & Sons, Ltd.
Pharmacokinetics and splenic accumulation of N‐acetylamino‐3‐chloro‐N‐(2‐diethylamino‐ethyl) benzamide after a single administration to rats
Authors: Hua Jianyi , Sheng Yezhou , Olin Magnus , Pero Ronald , Edvardsen Klaus
Published: August 2004

The purpose of this study was to measure the pharmacokinetics and tissue accumulation of N‐acetylamino‐3‐chloro‐N‐(2‐diethylamino‐ethyl) benzamide (NACPA) after oral or intravenous administration at a single dose of 25 mg/kg to female W/Fu rats. The serum pharmacokinetics of NACPA were characterized by rapid absorption, distribution and elimination. However, in comparison with its parent compound, 4‐amino‐3‐chloro‐N‐(2‐diethylamino‐ethyl) benzamide (3‐CPA), NACPA displayed a higher Cmax (mean±SD, 201±21 vs 33.6±0.5 nmol/ml, p<0.05), and a longer elimination half‐life (50±0.8 vs 36.6±1.1 min, p<0.05) following intravenous administration. Bioavailability of NACPA was significantly greater than that of 3‐CPA (50% compared with 14%, p<0.05). The tissue accumulation of NACPA was generally higher than that of 3‐CPA. NACPA was deposited at higher concentrations in the spleen than in the kidney and liver. Cellular pharmacokinetics indicated that NACPA accumulated more readily in lymphocyte related cells than in liver related cells. Furthermore, incubation of human peripheral lymphocytes with NACPA resulted in inhibition of lymphocyte proliferation, INF‐γ production and chemotaxis. All these results suggest that NACPA may be a good candidate drug for oral administration for immune modulation. Copyright © 2004 John Wiley & Sons, Ltd.
Trafficking and signaling pathways of nuclear localizing protein ligands and their receptors
Authors: Johnson Howard M. , Subramaniam Prem S. , Olsnes Sjur , Jans David A.
Published: August 2004

Interaction of ligands such as epidermal growth factor and interferon‐γ with the extracellular domains of their plasma membrane receptors results in internalization followed by translocation into the nucleus of the ligand and/or receptor. There has been reluctance, however, to ascribe signaling importance to this, the focus instead being on second messenger pathways, including mobilization of kinases and inducible transcription factors (TFs). The latter, however, fails to explain the fact that so many ligands stimulate the same second messenger cascades/TFs, and yet show distinct gene activation profiles. This is particularly apt in the case of the seven STAT TFs that are held to be the mediators of the distinct cellular functions of over 60 ligands. The current review focuses on five representative nuclear localizing ligands for which there is documentation of translocation into the cytosol and nucleus through well‐characterized pathways, in addition to a role in gene activation by ligand/receptor in the nucleus. BioEssays 26:993‐1004, 2004. © 2004 Wiley Periodicals, Inc.
Molecular mechanisms for organizing the neuronal cytoskeleton
Authors: Mukhopadhyay Rajendrani , Kumar Sanjay , Hoh Jan H.
Published: August 2004

Neurofilaments and microtubules are important components of the neuronal cytoskeleton. In axons or dendrites, these filaments are aligned in parallel arrays, and separated from one another by nonrandom distances. This distinctive organization has been attributed to cross bridges formed by NF side arms or microtubule‐associated proteins. We recently proposed a polymer‐brush‐based mechanism for regulating interactions between neurofilaments and between microtubules. In this model, the side arms of neurofilaments and the projection domains of microtubule‐associated proteins are highly unstructured and exert long‐range repulsive forces that are largely entropic in origin; these forces then act to organize the cytoskeleton in axons and dendrites. Here, we review the biochemical, biophysical, genetic and cell biological data for the polymer‐brush and cross‐bridging models. We explore how the data traditionally used to support cross bridging may be reconciled with a polymer‐brush mechanism and compare the implications of recent experimental insights into axonal transport and physiology for each model. BioEssays 26:1017–1025, 2004. © 2004 Wiley Periodicals, Inc.
PML nuclear bodies: dynamic sensors of DNA damage and cellular stress
Authors: Dellaire Graham , Bazett‐Jones David P.
Published: August 2004

Promyelocytic leukaemia nuclear bodies (PML NBs) are generally present in all mammalian cells, and their integrity correlates with normal differentiation of promyelocytes. Mice that lack PML NBs have impaired immune function, exhibit chromosome instability and are sensitive to carcinogens. Although their direct role in nuclear activity is unclear, PML NBs are implicated in the regulation of transcription, apoptosis, tumour suppression and the anti‐viral response. An emerging view is that they represent sites where multi‐subunit complexes form and where post‐translational modification of regulatory factors, such as p53, occurs in response to cellular stress. Following DNA damage, several repair factors transit through PML NBs in a temporally regulated manner implicating these bodies in DNA repair. We propose that PML NBs are dynamic sensors of cellular stress, which rapidly disassemble following DNA damage into large supramolecular complexes, dispersing associated repair factors to sites of damage. The dramatically increased total surface area available would enhance interactions between PML‐associated factors regulating DNA repair and apoptosis. BioEssays 26:963–977, 2004. © 2004 Wiley Periodicals, Inc.
VEGF: once regarded as a specific angiogenic factor, now implicated in neuroprotection
Authors: Storkebaum Erik , Lambrechts Diether , Carmeliet Peter
Published: August 2004

Both blood vessels and nerves are guided to their target. Vascular endothelial growth factor (VEGF)A is a key signal in the induction of vessel growth (a process termed angiogenesis). Though initial studies, now a decade ago, indicated that VEGF is an endothelial cell‐specific factor, more recent findings revealed that VEGF also has direct effects on neural cells. Genetic studies showed that mice with reduced VEGF levels develop adult‐onset motor neuron degeneration, reminiscent of the human neurodegenerative disorder amyotrophic lateral sclerosis (ALS). Additional genetic studies confirmed that VEGF is a modifier of motor neuron degeneration in humans and in SOD1G93A mice—a model of ALS. Reduced VEGF levels may promote motor neuron degeneration by limiting neural tissue perfusion and VEGF‐dependent neuroprotection. VEGF also affects neuron death after acute spinal cord or cerebral ischemia, and has also been implicated in other neurological disorders such as diabetic and ischemic neuropathy, nerve regeneration, Parkinson's disease, Alzheimer's disease and multiple sclerosis. These findings have raised growing interest in assessing the therapeutic potential of VEGF for neurodegenerative disorders. BioEssays 26:943–954, 2004. © 2004 Wiley Periodicals, Inc.
Dynamic cross‐talk between cells and the extracellular matrix in the testis
Authors: Siu Michelle K.Y. , Cheng C. Yan
Published: August 2004

In the seminiferous tubule of the mammalian testis, one type A1 spermatogonium (diploid, 2n) divides and differentiates into 256 spermatozoa (haploid, n) during spermatogenesis. To complete spermatogenesis and produce ∼150 × 106 spermatozoa each day in a healthy man, germ cells must migrate progressively across the seminiferous epithelium yet remain attach to the nourishing Sertoli cells. This active cell migration process involves precisely controlled restructuring events at the tight (TJ) and anchoring junctions at the cell–cell interface. While the hormonal events that regulate spermatogenesis by follicle‐stimulating hormone and testosterone from the pituitary gland and Leydig cells, respectively, are known, less is known about the mechanism(s) that regulates junction restructuring during germ cell movement in the seminiferous epithelium. The relative position of tight (TJs) and anchoring junctions in the testis is of interest. Sertoli cell TJs that constitute the blood–testis barrier (BTB) are present side by side with anchoring junctions and are adjacent to the basement membrane. This intimate physical association with the TJs, the anchoring junctions and the basement membrane (a modified form of extracellular matrix, ECM) suggests a role for the ECM in the junction dynamics of the testis. Indeed, evidence is accumulating that ECM proteins are crucial to Sertoli cell TJ dynamics. In this review, we discuss the pivotal role of tumor necrosis factor α (TNFα) on BTB dynamics via its effects on the homeostasis of ECM proteins. In addition, discussion will also be focused on the novel findings regarding the role of non‐basement‐membrane‐associated ECM proteins and components of focal adhesion (a cell–matrix anchoring junction type) in the regulation of junction dynamics in the testis. BioEssays 26:978–992, 2004. © 2004 Wiley Periodicals, Inc.
Model systems in stem cell biology
Authors: Robert Jason Scott
Published: August 2004

Stem cell scientists and ethicists have focused intently on questions relevant to the developmental stage and developmental capacities of stem cells. Comparably less attention has been paid to an equally important set of questions about the nature of stem cells, their common characteristics, their non‐negligible differences and their possible developmental species specificity. Answers to these questions are essential to the project of justly inferring anything about human stem cell biology from studies in non‐human model systems—and so to the possibility of eventually developing human therapies based on stem cell biology. After introducing and discussing these questions, I conclude with a brief discussion of the creation of novel model systems in stem cell biology: human‐to‐animal embryonic chimeras. Such novel model systems may help to overcome obstacles to extrapolation, but they are also scientifically and ethically contentious. BioEssays 26:1005‐1012, 2004. © 2004 Wiley Periodicals, Inc.