bluuebunny/crossref_metadata_2025 huggingface dataset:
Levofloxacin Disposition in Cerebrospinal Fluid in Patients with External Ventriculostomy
Authors: Pea Federico , Pavan Federica , Nascimben Ennio , Benetton Claudio , Scotton Pier Giorgio , Vaglia Alberto , Furlanut Mario
Published: September 2003

In vitro levofloxacin exhibits both potent or intermediate activity against most of the pathogens frequently responsible for acute bacterial meningitis and synergistic activity with some beta-lactams. Since levofloxacin was shown to penetrate the cerebrospinal fluid (CSF) during meningeal inflammation both in animals and in humans, the disposition of levofloxacin in CSF was studied in 10 inpatients with external ventriculostomy because of communicating hydrocephalus related to subarachnoid occlusion due to cerebral accidents who were treated with 500 mg of levofloxacin intravenously twice a day because of extracerebral infections. Plasma and CSF concentration-time profiles and pharmacokinetics were assessed at steady state. Plasma and CSF levofloxacin concentrations were analyzed by high-pressure liquid chromatography. The peak concentration of levofloxacin at steady state (Cmax ss)was 10.45 mg/liter in plasma and 4.06 mg/liter in CSF, respectively, with the ratio of theCmax ssin CSF to theCmax ssin plasma being 0.47. The areas under the concentration-time curves during the 12-h dosing interval (AUC0-τs) were 47.69 mg · h/liter for plasma and 33.42 mg · h/liter for CSF, with the ratio of the AUC0-τfor CSF to the AUC0-τfor plasma being 0.71. The terminal-phase half-life of levofloxacin in CSF was longer than that in plasma (7.02 ± 1.57 and 5.51 ± 1.36 h, respectively;P= 0.034). The ratio of the levofloxacin concentration in CSF to the concentration in plasma progressively increased with time, from 0.30 immediately after dosing to 0.99 at the end of the dosing interval. In the ventricular CSF of patients with uninflamed meninges, levofloxacin was shown to provide optimal exposure, which approximately corresponded to the level of exposure of the unbound drug in plasma. The findings provide support for trials of levofloxacin with twice-daily dosing in combination with a reference beta-lactam for the treatment of bacterial meningitis in adults. This cotreatment could be useful both for overcomingStreptococcus pneumoniaeresistance and for enabling optimal exposure of the CSF to at least one antibacterial agent for the overall treatment period.
Identifying Antimicrobial Resistance Genes with DNA Microarrays
Authors: Call Douglas R. , Bakko Marlene K. , Krug Melissa J. , Roberts Marilyn C.
Published: September 2003

We developed and tested a glass-based microarray suitable for detecting multiple tetracycline (
tet
) resistance genes. Microarray probes for 17
tet
genes, the β-lactamase
bla
TEM-1
gene, and a 16S ribosomal DNA gene (
Escherichia coli
) were generated from known controls by PCR. The resulting products (ca. 550 bp) were applied as spots onto epoxy-silane-derivatized, Teflon-masked slides by using a robotic spotter. DNA was extracted from test strains, biotinylated, hybridized overnight to individual microarrays at 65°C, and detected with Tyramide Signal Amplification, Alexa Fluor 546, and a microarray scanner. Using a detection threshold of 3× the standard deviation, we correctly identified
tet
genes carried by 39 test strains. Nine additional strains were not known to harbor any genes represented on the microarray, and these strains were negative for all 17
tet
probes as expected. We verified that R741a, which was originally thought to carry a novel
tet
gene,
tet
(I), actually harbored a
tet
(G) gene. Microarray technology has the potential for screening a large number of different antibiotic resistance genes by the relatively low-cost methods outlined in this paper.
Glutathione Peroxidase Overexpression Inhibits Cytochrome
c
Release and Proapoptotic Mediators to Protect Neurons From Experimental Stroke
Authors: Hoehn B. , Yenari M.A. , Sapolsky R.M. , Steinberg G.K.
Published: September 2003

Background and Purpose—

Ischemic injury and reperfusion increases superoxide (O
2
−
) production and reduces the ability of neurons to scavenge free radicals, leading to the release of cytochrome
c
and apoptosis. Here we test whether overexpression with the use of gene therapy of the antioxidant glutathione peroxidase (Gpx), delivered before or after experimental stroke, is protective against ischemic injury.

Methods—

Sixty-two rats underwent middle cerebral artery occlusion for 1 hour. Defective herpes simplex viral vectors expressing
Gpx/lacZ
or
lacZ
alone (control) were delivered into each striatum 12 hours before or 2 or 5 hours after ischemia onset.

Results—

Striatal neuron survival at 2 days was improved by 36% when Gpx was delivered 12 hours before ischemia onset, 26% with a 2-hour delay, and 25% when delayed 5 hours. After ischemia, Gpx overexpression significantly reduced cytosolic translocation of cytochrome
c
and increased the proportion of Bcl-2–positive cells compared with cells transfected with control vector. Bax and activated caspase-3, while present in control-transfected neurons after ischemia, were rarely noted in Gpx-transfected cells.

Conclusions—

Expression from these herpes simplex viral vectors begins 4 to 6 hours after injection, which suggests a 9- to 11-hour temporal therapeutic window for Gpx. This is the first study to show that overexpression of Gpx with the use of gene therapy protects against experimental stroke, even with postischemic transfection, and the neuroprotective mechanism involves attenuation of apoptosis-related events.
Protection from endotoxemia by adenoviral-mediated gene transfer of human bactericidal/permeability-increasing protein
Authors: Alexander Scott , Bramson Jonathan , Foley Ronan , Xing Zhou
Published: September 2003

Sepsis represents a growing concern in high-risk patients and there has been a lack of effective preventives and therapies. Bacterial/permeability increasing protein (BPI) is a human neutrophil granule-associated defense molecule specific for Gram-negative bacteria and their products. To develop a BPI-transgene–based prophylactic or therapeutic modality, we have developed a recombinant, replication-deficient adenoviral vector expressing full-length human BPI protein (AdhBPI). The expression of BPI is under control of a murine cytomegalovirus (CMV) promoter. Using in vitro and in vivo systems, AdhBPI-mediated gene transfer led to extracellular secretion of BPI protein, which effectively neutralized endotoxin (lipopolysaccharide [LPS]) and markedly reduced the production of proinflammatory cytokines tumor necrosis factor α (TNF-α) and macrophage inflammatory protein 2 (MIP-2) by freshly isolated murine alveolar macrophages. By using a mouse model of nonlethal sepsis elicited with LPS, we demonstrated that in vivo gene transfer of BPI was able to markedly inhibit the effect of a large dose of LPS on cytokine responses when injected intraperitoneally. Furthermore, such in vivo BPI gene transfer also improved the survival of mice suffering from lethal septic shock elicited by intraperitoneal injection of d-galactosamine and LPS. Thus, our results suggest that human BPI gene transfer vector has the potential to be used as a therapeutic agent for septic conditions.
Antimalarial drug discovery: old and new approaches
Authors: Rosenthal Philip J.
Published: September 2003

New drugs against malaria are greatly needed. Many approaches to antimalarial drug discovery are available. These approaches must take into account specific concerns, in particular the requirement for very inexpensive and simple to use new therapies and the need to limit the cost of drug discovery. Among important efforts that are currently ongoing are the optimization of therapy with available drugs, including the use of combination therapy, the development of analogs of existing agents, the discovery of natural products, the use of compounds that were originally developed against other diseases, the evaluation of drug resistance reversers, and the consideration of new chemotherapeutic targets. The last category benefits from recent advances in malaria research technologies and genomics and is most likely to identify new classes of drugs. A number of new antimalarial therapies will likely be needed over the coming years, so it is important to pursue multiple strategies for drug discovery.
Laxity of the elbow after experimental excision of the radial head and division of the medial collateral ligament
Authors: Jensen S. L. , Deutch S. R. , Olsen B. S. , Søjbjerg J. O. , Sneppen O.
Published: September 2003

We studied the stabilising effect of prosthetic replacement of the radial head and repair of the medial collateral ligament (MCL) after excision of the radial head and section of the MCL in five cadaver elbows. Division of the MCL increased valgus angulation (mean 3.9 ± 1.5°) and internal rotatory laxity (mean 5.3 ± 2.0°). Subsequent excision of the radial head allowed additional valgus (mean 11.1 ± 7.3°) and internal rotatory laxity (mean 5.7 ± 3.9°). Isolated replacement of the radial head reduced valgus laxity to the level before excision of the head, while internal rotatory laxity was still greater (2.8 ± 2.1°). Isolated repair of the MCL corrected internal rotatory laxity, but a slight increase in valgus laxity remained (mean 0.7 ± 0.6°). Combined replacement of the head and repair of the MCL restored stability completely.

We conclude that the radial head is a constraint secondary to the MCL for both valgus displacement and internal rotation. Isolated repair of the ligament is superior to isolated prosthetic replacement and may be sufficient to restore valgus and internal rotatory stability after excision of the radial head in MCL-deficient elbows.
Thermomechanical properties, phase structure, and conductivity of organic/inorganic hybrid material filled with a conductive filler
Authors: Matsumura Tomoyuki , Ochi Mitsukazu , Nagata Kazuya
Published: September 2003

Novel epoxy‐based organic/inorganic hybrid materials filled with carbon black (CB) were synthesized from an epoxy resin and silane alkoxide via a sol–gel process. The phase structure and thermal and mechanical properties of the hybrid materials were studied in detail. It was revealed by transmission electron microscope observations that the filled CB particles formed a secondary aggregation structure and were uniformly dispersed in the aggregate. The storage modulus in the rubbery region increased and the peak area of the tan δ curve in the glass‐transition region decreased with the hybridization of silica. Moreover, the conductive properties of the CB‐filled hybrid systems were investigated. In the same volume fraction of CB, the conductivity of the hybrid systems was much higher than that of the unmodified system. This result was attributed to the excluded volume effect of the silica network. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 1980–1984, 2003
Chain extension and mechanical properties of unsaturated aliphatic copolyesters based on poly(L‐lactic acid)
Authors: Park Eun‐Soo , Cho Hae‐Chul , Kim Mal‐Nam , Yoon Jin‐San
Published: September 2003

Chain extension of poly(L‐lactic acid) (PLLA) with unsaturated groups (PLBM) was attempted using benzoyl peroxide (BPO) and the resulting variation in molecular weight and mechanical properties was explored. Bulk copolymerization of L‐lactic acid (LA)/1,4‐butanediol (BD)/maleic acid (MA) (100/1/1) isomerized some of the cis‐structured maleate units into trans‐structured fumarate units. The optically active LA promoted isomerization during the condensation polymerization. Chain extension of PLBM with BPO did not bring about a discernible increase in the molecular weight when the chain extension was carried out in various solvents with different radical abstraction abilities. In contrast, the hot pressing of PLBM containing BPO increased the molecular weight and sometimes produced chloroform‐insoluble gels depending on the BPO concentration and temperature. The chain extension at low temperatures increased the flexibility of PLBM considerably. However, PLBM lost the flexibility precipitously as the chain‐extension temperature increased above 120°C. The biodegradation rate of PLBM was much slower than that of PLLA. The biodegradation rate was further lowered by the chain extension. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 90: 1802–1807, 2003
Lay rationalism and inconsistency between predicted experience and decision
Authors: Hsee Christopher K. , Zhang Jiao , Yu Fang , Xi Yiheng
Published: September 2003

Decision‐makers are sometimes depicted as impulsive and overly influenced by ‘hot’, affective factors. The present research suggests that decision‐makers may be too ‘cold’ and overly focus on rationalistic attributes, such as economic values, quantitative specifications, and functions. In support of this proposition, we find a systematic inconsistency between predicted experience and decision. That is, people are more likely to favor a rationalistically‐superior option when they make a decision than when they predict experience. We discuss how this work contributes to research on predicted and decision utilities; we also discuss when decision‐makers overweight hot factors and when they overweight cold factors. Copyright © 2003 John Wiley & Sons, Ltd.
Improvement of the digestibility of the proteins of the red alga Palmaria palmata by physical processes and fermentation
Authors: Marrion Olivier , Schwertz Annie , Fleurence Joël , Guéant Jean Louis , Villaume Christian
Published: September 2003

Palmaria palmata (dulse) is an edible red alga constituting a potential protein source in human diet. However, previous studies showed that the digestibility of dulse proteins is bad because of the cell‐wall encapsulating cytoplasmic proteins and the presence of fibers. The water‐soluble xylan, present in high proportions in dulse, could be involved to explain the weak digestibility of proteins. To limit the influence of fibers and to improve the nutritional quality of these proteins, we have treated dulse by physical processes or by fermentation by moulds. After a 30 min predigestion by pepsin followed by a 6 h digestion into a cell dialysis containing porcine pancreatin, the correctedin vitro digestibility of crude dulse was very low (about 1.5% after correction by digestibility blank). Thein vitro protein digestibility was estimated to 58% of that of casein for dulse samples obtained after washing in demineralized water and grinding in liquid nitrogen. Thein vitro protein digestibility of fermented samples was 45%–65% of that of casein. After physical treatment, the digestibility improvement was related to the elimination of soluble molecules such as xylan and mineral salts. The improvement observed after fermentations seemed due to the degradation of insoluble fibers.
Towards the Synthesis of Azoacetylenes
Authors: Denonne Frédéric , Seiler Paul , Diederich François
Published: September 2003

The synthesis of azoacetylenes (=dialkynyldiazenes) 1 and 2 has been investigated. They represent a still elusive class of chromophores with potentially very interesting applications as novel bistable photochemical molecular switches or as antitumor agents (Fig. 1). Our synthetic efforts have led us alongside three different approaches (Scheme 1). In a first route, it was envisioned to generate the azo (=diazene) bond by photolysis of N,N′‐dialkynylated 1,3,4‐thiadiazolidine‐2,5‐diones that are themselves challenging targets (Scheme 2). Attempts are described to obtain the latter by alkynylation of the parent heterocycle with substituted alkynyliodonium salts. In a conceptually similar approach, the no‐less‐challenging dialkynylated 9,10‐dihydro‐9,10‐diazanoanthracene (29) was to be generated by alkynylation of the unsubstituted hydrazine 28 (Scheme 6). In a second route, the generation of the NN bond from Br‐substituted divinylidenehydrazines (ketene‐azines) 35 was attempted in a synthetic scheme involving an aza‐Wittig reaction between azinobis(phosphorane) 36 and (triisopropylsilyl)ketene 37 (Scheme 7). Finally, a third approach, based on the formation of the central azo bond as the key step, was explored. This route involved the extrapolation of a newly discovered condensation reaction of N,N‐disilylated anilines with nitroso compounds (Scheme 11, and Tables 1 and 2) to the transformation of N,N‐disilylated ynamine 55 and nitroso‐alkyne 54 (Scheme 13).
Phenanthrene‐Derived DNA Hairpin Mimics
Authors: Stutz Alfred , Langenegger Simon M. , Häner Robert
Published: September 2003

Self‐complementary oligodeoxynucleotides containing 3,6‐disubstituted phenanthrenes adopt highly stable, hairpin‐like structures. The thermodynamic stability of the hairpin mimics depends on the overall length of the phenanthrene building block. Hairpin loops composed of a phenanthrene‐3,6‐dicarboxamide and ethylene linkers were found to be optimal. The hairpin mimics are more stable than the analogous hairpins containing either a dT4 or dA4 tetraloop. Model studies indicate that the thermodynamic stability of the hairpin mimics is primarily due to aromatic stacking of the phenanthrene‐3,6‐dicarboxamide onto the adjoining base pair of the DNA duplex.
Preschoolers' and adults' attributions of who causes interpersonal events
Authors: Corrigan Roberta
Published: September 2003

Adults and 4‐year‐olds explained who caused prosocial or antisocial interactions between two characters who differed in two dimensions that underlie interpersonal traits. Participants saw pictures depicting every pairwise combination of four characters (good/powerful, good/weak, bad/powerful or bad/weak) as initiators or recipients of six actions. Both children and adults made causal attributions to ‘good’ characters for prosocial behaviours and to ‘bad’ characters for antisocial behaviours. Potency influenced the frequency of attributions. Adults and children differed in the justifications of their attributions and in their reconciliations of contradictory information, e.g. a positive character initiating an antisocial act. Explanations of social events are based on characteristics of both interactants in combination with whether the event is prosocial or antisocial. The findings thus extend work on children's ‘theory‐of‐mind’ to the realm of interpersonal interactions, where beliefs, desires or dispositions of either of two characters can cause an event. Copyright © 2003 John Wiley & Sons, Ltd.
The Late‐glacial reoccupation of the British Isles and the Creswellian
Authors: Barton R. N. E. , Jacobi R. M. , Stapert D. , Street M. J.
Published: September 2003

This paper presents a review of AMS radiocarbon dating evidence for human occupation of Britain during the Late‐glacial Interstadial. The dates are all on humanly modified materials, including artefacts, and on human bone. The CalPal program is used to test whether the earliest evidence of human presence shows any correlation with more widespread climatic events, and if the British chronology differs significantly from that of neighbouring regions of northwest Europe. In the second part of the paper a number of well‐dated sites with British Late Upper Palaeolithic ‘Creswellian’ technology are examined and compared with lithic assemblages from The Netherlands and Belgium. The main conclusions of this work are that expansion of human populations into the northern edge of the upland zone just before or at the beginning of GI‐1 was followed by repopulation of the British Isles possibly with very little time‐lag. The British Creswellian sites offer evidence of this earliest resettlement, which is mainly focused on the upland margins of western and central Britain. Copyright © 2003 John Wiley & Sons, Ltd.
Reactive intermediates of the reduction of SO2 on activated carbon
Authors: Humeres Eduardo , Peruch Maria da Gloria B. , Moreira Regina F. P. M. , Schreiner Wido
Published: September 2003

The reduction of SO2 on activated carbon was studied in the range of 600–700°C in a differential reactor under steady‐state conditions and under chemically controlled kinetics. Initial rates of carbon conversion and gas reagent were calculated from the mass balance of the gaseous products. The kinetics was first‐order with respect to carbon and first‐order with respect to the partial pressure of SO2. The activation parameters were ΔH≠= 21.5 kcal mol−1 and ΔS≠=−211 cal mol−1 K−1. The activated carbon was ca. 105 times more reactive than graphite, and determined by the enthalpy of activation. The main reaction products were CO2 and sulfur. CO and COS were produced from consecutive reactions of the primary products. During the pre‐steady state, the sulfur content of the carbon increased to a plateau where the reaction reached the steady state condition. This sulfur was shown to be chemically bound to the carbon matrix and represents the stable reactive intermediates of the reduction of SO2. The XPS spectrum of the residual carbon C(S) showed two forms of sulfur bound to carbon: non‐oxidized sulfur (sulfide and/or disulfide) and oxidized sulfur (sulfone, sulfoxide, sulfenate, sulfinate). The sulfur intermediates C(S) reacted with SO2 at the same rate as pure activated carbon and with CO2 to produce SO2 by the reverse reaction. The reaction of C(S) with CO produced COS. Copyright © 2003 John Wiley & Sons, Ltd.
Language evolution in apes and autonomous agents
Authors: Cangelosi Angelo
Published: September 2003

Computational approaches based on autonomous agents share with new ape language research the same principles of dynamical system paradigms. A recent model for the evolution of symbolization and language in autonomous agents is briefly described in order to highlight the similarities between these two methodologies. The additional benefits of autonomous agent modeling in the field of language origin research are highlighted.
The residual normality assumption and models of cognition in schizophrenia
Authors: Condray Ruth , Steinhauer Stuart R.
Published: September 2003

Thomas & Karmiloff-Smith’ (T&K-S’) argument that the Residual Normality assumption is not valid for developmental disorders has implications for models of cognition in schizophrenia, a disorder that may involve a neurodevelopmental pathogenesis. A limiting factor for such theories is the lack of understanding about the nature of the cognitive system (modular components versus global processes). Moreover, it is unclear how the proposal that modularization emerges from developmental processes would change that fundamental question.
On the public nature of communication
Authors: Leavens David A.
Published: September 2003

Comparative and developmental psychology are engaged in a search for the evolutionary and developmental origins of the perceptions of “intentions” and “desires,” and of epistemic states such as “ignorance” and “false belief.” Shanker & King (S&K) remind us that these are merely words to describe public events: All organisms that can discriminate states of “knowledge” in others have learned to do this through observation of publicly available information.
No conceptual thought without language
Authors: Gauker Christopher
Published: September 2003

Carruthers labels as “too strong” the thesis that language is necessary for all conceptual thought. Languageless creatures certainly do think, but when we get clear about what is meant by “conceptual thought,” it appears doubtful that conceptual thought is possible without language.
Doesn't a dance require dancers?
Authors: Thompson N. S. , Valsiner Jaan
Published: September 2003

The dance metaphor of ape-human communication is valuable and needs to be pressed to its logical conclusion. When couples dance, they are both choreographers and dancers, and the dance arises dialectically out of the “peractions” of the dancers. We suppose that the way in which scientists communicate with their apes emerges by an analogous process.
What domain integration could not be
Authors: Robbins Philip
Published: September 2003

Carruthers argues that natural language is the medium of non-domain-specific thought in humans. The general idea is that a certain type of thinking is conducted in natural language. It’ not exactly clear, however, what type of thinking this is. I suggest two different ways of interpreting Carruthers’ thesis on this point and argue that neither of them squares well with central-process modularism.
A SUBJECT-OBJECT ASYMMETRY IN THE ACQUISITION OF RELATIVE CLAUSES IN KOREAN AS A SECOND LANGUAGE
Authors: O'Grady William , Lee Miseon , Choo Miho
Published: September 2003

A variety of studies have reported that learners of English as a second language find subject relative clauses easier to produce and comprehend than direct object relatives, but it is unclear whether this preference should be attributed to structural factors or to a linear distance effect. This paper seeks to resolve this issue and to extend our understanding of SLA in general by investigating the interpretation of subject and direct object relative clauses by English-speaking learners of Korean, a left-branching language in which subject gaps in relative clauses are more distant from the head than are object gaps. The results of a comprehension task conducted with 53 beginning and intermediate learners point toward a strong preference for subject relative clauses, favoring the structural account.
RESEARCHING AND APPLYING METAPHOR. Lynn Cameron and Graham Low (Eds.). New York: Cambridge University Press, 1999. Pp. 311. $59.95 cloth, $22.95 paper.
Authors: Kramsch Claire
Published: September 2003

Whether they are collecting data from spoken or written sources, learners or teachers, English corpora or academic essays, or talk about disease and illness, applied linguists are confronted with the pervasive use of metaphor. Metaphor, as a mode of talk and thought, is a way of making meaning that is particularly linked to the sociocultural context. What counts as a metaphor? How can we operationalize, analyze, and categorize it? What research methodology is best suited for the study of metaphor? Cameron and Low's timely collection of papers is a first attempt to put metaphor research on the map of applied linguistics.
PROCESSES OF LANGUAGE CONTACT: STUDIES FROM AUSTRALIA AND THE SOUTH PACIFIC. Jeff Siegel (Ed.). Saint-Laurent, Canada: Fides, 2000. Pp. xvi + 320. $34.95 paper.
Authors: Clements J. Clancy
Published: September 2003

The present volume highlights studies of languages created by contact-induced language change in Australia and the Pacific. Editor Jeff Siegel identifies six processes involved in the formation of pidgins, creoles, and other such language contact varieties: reanalysis, simplification, leveling, diffusion, language shift, and depidginization/decreolization. The process of reanalysis is the focus of four chapters: “The Role of Australian Aboriginal Language in the Formation of Australian Pidgin Grammar: Transitive Verbs and Adjectives” by Koch; “‘Predicate Marking' in Bislama” by Crowley; “Predicting Substrate Influence: Tense-Modality-Aspect Marking in Tayo” by Siegel, Sandeman, and Corne; “My Nephew Is My Aunt: Features and Transformation of Kinship Terminology in Solomon Islands Pijin” by Jourdan; and “Na pa kekan, na person: The Evolution of Tayo Negatives” by Corne.
UNITED STATES CONGRESS AND BILINGUAL EDUCATION. Abdul Karim Bangura and Martin C. Muo. Bern: Peter Lang, 2001. Pp. 159. $24.95 paper.
Authors: González Gustavo
Published: September 2003

The purpose of this book is to “fill a gap in the literature of the politics of bilingual education in the United States: the role of the legislature in the passage of the 1968 Bilingual Education Act and its aftermath” (p. xi). The authors use Easton's “framework for political analysis” to trace the passage of this legislation. Examined as part of the framework are the environment, inputs, legislative system, and outputs, each of which is covered in separate chapters.
“Respect for Autonomy” in Genetic Counseling: An Analysis and a Proposal
Authors: White Mary Terrell
Published: September 2003

Respect for autonomy in genetic counseling is generally understood as a negative right: as clients' right to noninterference in decision‐making. In order to promote client autonomy, genetic counseling is nondirective, an approach that minimizes risks of counselor influence in the decision‐making process. But by minimizing counselor involvement, nondirective counseling may permit clients to make decisions that are partially informed or poorly reasoned. Alternatively, clients may be better served if autonomy is construed as a positive right: as clients' right to a maximally enhanced decision‐making process. This interpretation of autonomy suggests a counseling approach in which the deliberative process is central and takes place through dialogue. Dialogical counseling remains nonprescriptive but holds counselors responsible for ensuring that decisions are thoroughly and carefully considered. The goal is a good decision, defined as one in which clients' values and goals, identified through the deliberative approaches of authenticity, effective deliberation, and moral reflection, are in equilibrium. By this means, counselors may more reliably meet clients' needs while simultaneously demonstrating a limited degree of professional accountability.
An electron heating mechanism in the outflow region from the X‐type neutral line
Authors: Fujimoto K. , Machida S.
Published: September 2003

A linear analysis and 2 1/2‐dimensional full‐particle simulations are performed to investigate mechanisms of an electron heating due to a strong Hall current, which is caused by a large velocity difference between electrons and ions in the outflow region inside the diffusion region of the magnetic reconnection process. The numerical solution of the kinetic dispersion relation indicates that the prospective unstable mode varies according to the electron‐ion relative velocity Vd; the kinetic cross‐field streaming instability (KCSI) is dominant when Vd is under the substantial fraction of the electron thermal velocity ve, while the electron cyclotron drift instability (ECDI) is first excited for the case where Vd exceeds that critical velocity. We show that electrons are heated parallel to the ambient magnetic field due to the KCSI and perpendicularly due to the ECDI. In particular, electrons are very quickly heated up to a high temperature when the ECDI is dominant. However, the electron heating is ineffective when Vd/ve < 1.
High resolution FUV observations of proton aurora
Authors: Chua D. H. , Dymond K. F. , Budzien S. A. , McCoy R. P. , Gérard J.‐C. , Coumans V. , Bisikalo D. , Shematovich V.
Published: September 2003

We present new FUV observations of Doppler‐shifted Lyman‐α emissions from proton aurora obtained from the High Resolution Ionospheric and Thermospheric Spectrograph (HITS) aboard the Advanced Research and Global Observation Satellite (ARGOS). The HITS instrument observes the Doppler‐shifted H Lyman‐α emissions from proton precipitation with 1.5 Å resolution. The high spectral resolution of these measurements allows the auroral Lyman‐α emissions to be separated from the intense geocoronal background. The measured proton aurora Doppler spectra are modeled using a Monte Carlo simulation of proton flux transport. The forward modeling performed with this code allows us to infer the characteristic energies of the incident protons from the measured Lyman‐α Doppler spectra. The inferred characteristics of dayside versus nightside proton precipitation are compared and used to identify the magnetospheric regions from which the particles likely originated.
Changes of lymphocyte apoptosis associated with sequential introduction of highly active antiretroviral therapy
Authors: Wasmuth J‐C , Hackbarth F , Rockstroh JK , Sauerbruch T , Spengler U
Published: September 2003

Objective

To assess the effect of highly active antiretroviral therapy (HAART) on surrogate markers of lymphocyte apoptosis in HIV 1‐infected individuals.

Methods

Ex vivo apoptosis was studied prospectively in 26 antiretroviral naive HIV‐positive patients up to 12 weeks after sequential initiation of HAART [phase I: nucleoside reverse transcriptase inhibitor (NRTI), phase II: NRTI + protease inhibitor (PI)]. Apoptosis was assessed via CD95‐, Apo2.7‐expression and annexin‐V‐binding in peripheral CD4, CD8, B and NK‐cells, and compared to changes in activation markers (HLA‐DR, CD38) and viral loads.

Results

After introduction of HAART CD4‐counts rose significantly mainly through cell redistribution, while activation markers decreased. Although Apo2.7 expression decreased throughout the study period, it was not possible to establish a correlation to the rise in CD4 cells. Unexpectedly, CD95 expression and annexin V binding were elevated during phase I of treatment without PI and began to decline only after the addition of a PI in phase II. Poor responders to antiretroviral therapy had significantly higher CD95 expression and annexin V binding in the initial phase of antiretroviral regimen.

Conclusion

These data show divergent effects of HAART on surrogate markers of apoptosis, when treatment is initiated sequentially with NRTIs first. Partial suppression of HIV replication during treatment without PI may be associated with increased rates of apoptosis.
Prophylactic Anticoagulation for Venous Thromboembolic Disease in Geriatric Patients
Authors: Jacobs Laurie G.
Published: September 2003

Venous thromboembolic disease (VTED) occurs commonly in geriatric medical patients, causing significant morbidity and mortality. Although VTED is preventable, prophylactic anticoagulation is underused. Awareness of the clinical risk factors that contribute to VTED in the elderly is essential for identifying candidates for prophylaxis. Iatrogenic risk factors include venous catheterization, transvenous pacemaker placement, hormone replacement therapy, and immobilization or prolonged bed rest. Medical conditions associated with increased risk include a previous episode of VTED, myocardial infarction, heart failure, severe lung disease, cancer, and neurological conditions associated with paresis. Obstacles to the widespread usage of VTED prophylaxis in geriatric medical patients include the clinically silent nature of VTED, underestimation of the risk and clinical effect of VTED in this population, and concerns about the cost and safety of anticoagulant therapy in this population. Clinical practice guidelines devised specifically for geriatric medical patients facilitate rational use of thromboprophylaxis in this population. The safety, efficacy, cost‐effectiveness, and convenience of low‐molecular‐weight heparins for thromboprophylaxis are reflected in their increasing prominence in clinical practice guidelines and clinical use.
Timing and Sequence of Differentiation of Embryonic Rat Hepatocytes Along the Biliary Epithelial Lineage
Authors: Notenboom Robbert G.E. , van den Bergh Weerman Marius A. , Dingemans Koert P. , Vermeulen Jacqueline L.M. , van den Eijnde Stefan , Reutelingsperger Chris P. , Hut Hans , Willemsen Rob , Offerhaus Johan G.A. , Lamers Wouter H.
Published: September 2003

To study the differentiation of hepatocytes along the biliary epithelial lineage in vivo, embryonic day 14 (E14) rat hepatocytes were isolated by differential centrifugation and transplanted as single–cell suspensions into the spleen of adult syngeneic rats. Hepatocytes and cholangiocytes were identified and their maturation characterized by the level of expression of α–fetoprotein (AFP), glutamate dehydrogenase (GDH), and carbamoyl phosphate synthetase I (CPS); annexin IV, annexin V, cytokeratin 19 (CK–19), and cystic fibrosis transmembrane conductance regulator (CFTR); and electron microscopy. By correlating morphologic changes with the timing in the expression of these markers, we show that the organization of the transplanted E14 hepatocytes into lobular structures is accompanied by the formation and maturation of bile ducts around these developing lobules. Morphologic differentiation of the emerging bile ducts was accompanied by a gradual loss of hepatocyte markers and a gradual acquisition of cholangiocyte markers, with markers identifying a large–cholangiocyte phenotype appearing latest. Once fully differentiated, the intrasplenic liver lobules developed cholestatic features. The accompanying proliferation of bile ducts was due to cholangiocyte proliferation, but ductular transformation of hepatocytes was also observed. In conclusion, (1) bile duct formation at the interface between hepatocytes and connective tissue is an inherent component of liver development and (2) the susceptibility of developing hepatocytes to bile duct–inducing signals is highest in the fetal liver but that (3) this capacity is not irreversibly lost in otherwise mature hepatocytes.
Viral and Clinical Factors Associated With the Fulminant Course of Hepatitis A Infection
Authors: Rezende Guilhermo , Roque-Afonso Anne Marie , Samuel Didier , Gigou Michele , Nicand Elisabeth , Ferre Virginie , Dussaix Elisabeth , Bismuth Henri , Féray Cyrille
Published: September 2003

Fulminant hepatitis is a severe complication of hepatitis A virus infection. Its mechanism is unknown. Liver transplantation can be necessary, but spontaneous recovery is frequent. There are no data on the level of viral replication according to the clinical form of hepatitis A. We reviewed the files of 50 patients with acute hepatitis A. Nineteen patients had fulminant hepatitis (defined by encephalopathy and factor V <50%), and, from them, 10 patients underwent transplantation. Hepatitis A virus (HAV) RNA was quantified by real–time PCR on sera obtained at admission. The genotype was determined by phylogenetic analysis of HAV RNA. HAV RNA was detected in serum by RT–PCR in 39 out of 50 patients. Encephalopathy and low factor V level were significantly related to female gender, HAV PCR negativity (9/19 vs. 5/31, respectively; P = .03), a low serum HAV RNA level (log, 3.6 ± 0.6 vs. 4.4 ± 0.9, respectively; P = .02), genotypes other than IA, and acetaminophen intake. In multivariate analysis, low or undetectable HAV viral load and a high bilirubin level were independently associated with both low factor V levels and fulminant hepatitis and also with death or transplantation. In conclusion, HAV–related liver failure is due to an excessive host response associated with a marked reduction in viral load. Serum HAV RNA assay could be of help in the management of severe hepatitis A.
Modulation of the Outcome and Severity of Hepadnaviral Hepatitis in Woodchucks by Antibodies to Hepatic Asialoglycoprotein Receptor
Authors: Diao Jingyu , Slaney Darlene M. , Michalak Tomasz I.
Published: September 2003

Viral hepatitis is frequently accompanied by humoral autoimmune responses toward both organ–nonspecific and liver–specific antigens, but contribution of these reactivities to liver injury remains unrecognized. Infection with woodchuck hepatitis virus (WHV) has been identified as a potent inducer of autoantibodies against asialoglycoprotein receptor (anti–ASGPR), a molecule essentially unique to hepatocytes that mediates clearance of desialylated serum proteins. In this study, we applied the WHV–woodchuck model of hepatitis B to examine the effect of experimentally elicited anti–ASGPR on the progression and the severity of WHV hepatitis in initially healthy animals immunized with the receptor and then infected with WHV and in woodchucks with ongoing chronic WHV hepatitis. The results implied that the induction of anti–ASGPR prior to WHV infection tends to modulate acute viral hepatitis toward chronic outcome and, in animals with established chronic WHV infection, exacerbates histologic severity of liver lesions. The findings also suggest that the liver compromised by chronic hepadnavirus infection might be prone to anti–ASGPR–directed complement–mediated hepatocellular injury and that this is associated with formation of the ASGPR–anti–ASGPR immune complexes on hepatocyte surface. In conclusion, the host's immune response mounted against a hepatocyte–specific autoantigen may modulate both the outcome and the severity of liver injury in viral hepatitis.
Sfi1p has conserved centrin-binding sites and an essential function in budding yeast spindle pole body duplication
Authors: Kilmartin John V.
Published: September 2003

Centrins are calmodulin-like proteins present in microtubule-organizing centers. The Saccharomyces cerevisiae centrin, Cdc31p, was functionally tagged with a single Z domain of protein A, and used in pull-down experiments to isolate Cdc31p-binding proteins. One of these, Sfi1p, localizes to the half-bridge of the spindle pole body (SPB), where Cdc31p is also localized. Temperature-sensitive mutants in SFI1 show a defect in SPB duplication and genetic interactions with cdc31-1. Sfi1p contains multiple internal repeats that are also present in a Schizosaccharomyces pombe protein, which also localizes to the SPB, and in several human proteins, one of which localizes close to the centriole region. Cdc31p binds directly to individual Sfi1 repeats in a 1:1 ratio, so a single molecule of Sfi1p binds multiple molecules of Cdc31p. The centrosomal human protein containing Sfi1 repeats also binds centrin in the repeat region, showing that this centrin-binding motif is conserved.
Truly European: interlending and document supply in Belgium at the beginning of the twenty‐first century
Authors: Van Borm Julien , Corthouts Jan
Published: September 2003

Belgium, one of the smaller European Union countries, has long since integrated its interlending and document supply in a truly European context and 20 per cent of all supplies come from the document supply centres of neighbouring countries. The Belgian electronic document‐ordering system, IMPALA, is the heart of the system. New ICT developments in communication technology will render traditional ILL and document supply partly obsolete by making available full text databases.
Multi‐domain DRM boundary element method for non‐isothermal non‐Newtonian Stokes flow with viscous dissipation
Authors: Florez W. , Power H. , Chejne F.
Published: September 2003

This paper presents a boundary element method (BEM) based on a subdomain approach for the solution of non‐Newtonian fluid flow problems which include thermal effects and viscous dissipation. The volume integral arising from non‐linear terms is converted into equivalent boundary integrals by the multi‐domain dual reciprocity method (MD‐DRM) in each subdomain. Augmented thin plate splines interpolation functions are used for the approximation of field variables. The iterative numerical formulation is achieved by viewing the material as divided into small elements and on each of them the integral representation formulae for the velocity and temperature are applied and discretised using linear boundary elements. The final system of non‐linear algebraic equations is solved by a modified Newton's method. The numerical examples include non‐Newtonian problems with viscous dissipation, temperature‐dependent viscosity and natural convection due to bouyancy forces.
The career development and aspirations of women in middle management – revisited
Authors: Mary Wentling Rose
Published: September 2003

This article reports the results of the second phase of a research study on the career development and aspirations of women in middle management in business firms in the USA. The major method of this research study was the individual case study. Case studies relied on in‐person and/or telephone interviews with the same 30 women managers who participated in the first phase of the study in 1995. The majority of the women managers worked forFortune500 companies and were located throughout the USA. The findings of the study revealed that the majority of the women managers have not attained the positions to which they ultimately aspire. The majority do not believe they are progressing as rapidly as they think they should. However, the majority of the women managers continue to aspire to top level management positions and they believe that it is very realistic that they will attain these positions.
Exploring e‐education applications: a framework for analysis
Authors: Helen Fagan Mary
Published: September 2003

As a result of the convergence of computing and communications in the information age, there have been repeated calls for institutions of higher education to embark on needed changes. Some believe that higher education must transform itself, or make radical shifts, to operate effectively in this era. Much has been learned from the business and government sectors about the power of information technology to improve organizational efficiency and effectiveness, and to enable radical transformation. This study looks at approaches that have been used to classify e‐commerce and e‐government IT applications and explores their relevance to higher education. The study develops an e‐education framework that analyzes applications in higher education in terms of their application category and phase. By developing a framework for analysis based upon lessons learned in e‐commerce and e‐government, the study can provide another way of viewing an institution’s IT portfolio and for mapping future application possibilities.
Effects of tropomyosin internal deletion Δ23Tm on isometric tension and the cross‐bridge kinetics in bovine myocardium
Authors: Lu Xiaoying , Tobacman Larry S. , Kawai Masataka
Published: September 2003

Tropomyosin (Tm) spans seven actin monomers and contains seven quasi‐repeating, loosely similar regions, 1–7. Deletion of regions 2–3 decreases the in vitro sliding speed of synthetic filaments of actin‐Tm‐Troponin (Tn), and weakens Tm binding to the actin‐myosin subfragment 1 (S1) complex (acto‐S1). The thin filament was selectively removed from bovine myocardium by gelsolin, and the actin filament was reconstituted, followed by further reconstitution with Tm and Tn. In this reconstitution, full‐length Tm (control) was compared with Tm internal deletion mutant Δ23Tm, which lacks residues 47–123 (regions 2–3). The effects of phosphate, MgATP, MgADP and Ca2+ were studied in Tm‐reconstituted myocardium and Δ23Tm‐reconstituted myocardium at pH 7.00 and 25 °C. In Δ23Tm, both isometric tension and stiffness were about 40 % of the control. The Hill factor with Δ23Tm, deduced from the pCa‐tension plot, was 1.4 times that of the control, but the Ca2+ sensitivity was the same. Sinusoidal analysis indicated that the cross‐bridge number in force‐generating states was not decreased with Δ23Tm. We conclude that the thin filament cooperativity is increased with Δ23Tm, presumably because of the increased density of the Ca2+‐binding sites. We further conclude that tension per cross‐bridge is 40 % of control and stiffness per cross‐bridge is 40 % of control in Δ23Tm. These results are consistent with the idea that Tm modifies the actin‐myosin interface so as to increase the stereospecific interaction between moieties of actin and myosin. In Δ23Tm, the interface may not have a perfect stereospecific match so that the tension‐ and stiffness‐generating capacity is greatly diminished.
Rusty Hatches
Authors: Beckman Mary
Published: September 2003

Doors on old houses tend to stick shut. Similarly, entryways into the energy-producing factories of older cells seize up, according to new research. The jam prevents at least one molecular mechanic from getting inside to fix DNA damage, allowing faults to accumulate with age.