bluuebunny/crossref_metadata_2025 huggingface dataset:
Introducing sustainability into the architecture curriculum in the United States
Authors: Wright James
Published: April 2003

A brief review of the five collateral organizations that influence architectural education in the USA and their priorities indicate they may have reached the point of recognizing that sustainability is a core issue of architecture. To reflect this recognition, sustainability will need to be integrated into the architecture curriculum. The question is now one of how to achieve integration. Differing approaches to introducing sustainability into an architectural program are proposed and examined. They range from assuming sustainability already permeates the curriculum by its nature and therefore is integrated, expanding the existing courses concerning environmental systems, and revising the entire curriculum to fully integrate into each subject. To assist in the task of integration, criteria are proposed. The task of integrating sustainability is not to be understated, but if architectural education and practice is to focus beyond state and national levels a global responsibility will need to be assumed.
Applying ISO 14001 as a business tool for campus sustainability
Authors: Fisher Richard M.
Published: April 2003

Environmental education at post‐secondary levels throughout the world has come to be predicated on, at least in part, the greening of campuses where the courses are taught. Green practices provide legitimacy to environmental education programmes. A number of resources are available to assist staff and students in getting sustainability initiatives off the ground. One in particular holds special promise, from the International Organisation for Standardisation (ISO). Although directed largely towards the business community, the ISO 14000 series of environmental standards may be very useful to campuses when initiating an environmental review, or contemplating the adoption of an Environmental Management Systems (EMS). The standards provide methodological assistance to organisations, including academic institutions, which seek to establish a workable EMS. Use of the ISO standards has the added benefit of bringing the business world into the campus classroom, which may provide a useful counterpoint for environmental education. A case study is included which describes the experience of a New Zealand tertiary college using ISO 14001 in its first environmental review.
Conformational states of the switch I region of Ha‐ras‐p21 in hinge residue mutants studied by fluorescence lifetime and fluorescence anisotropy measurements
Authors: Kuppens Steven , Hellings Mario , Jordens Jan , Verheyden Stefan , Engelborghs Yves
Published: April 2003

The hinge residues (Val29 and Ile36) of the switch I region (also known as the effector loop) of the Ha‐ras‐p21 protein have been mutated to glycines to accelerate the conformational changes typical for the effector loop. In this work, we have studied the influence of the combined mutations on the steady‐state structure of the switch I region of the protein in both the inactive GDP‐bound conformation as in the active GTP‐bound conformation. Here, we use the fluorescence properties of the single tryptophan residue in the Y32W mutant of Ha‐ras‐p21. This mutant has already been used extensively as a reference form of the protein. Reducing the size of the side chains of the hinge residues not only accelerates the conformational changes but also affects the steady‐state structures of the effector loop as indicated by the changes in the fluorescence properties. A thorough analysis of the fluorescence changes (quantum yield, lifetimes, etc.) proves that these changes are from a reshuffling between the rotamer populations of Trp. The population reshuffling is caused by the overall structural rearrangement along the switch I region. The effects are clearly more pronounced in the inactive GDP‐bound conformation than in the active GTP‐bound conformation. The effect of both mutations seems to be additive in the GDP‐bound state, but cooperative in the GTP‐bound state.
The catalytic mechanism of galactose mutarotase
Authors: Thoden James B. , Kim Jungwook , Raushel Frank M. , Holden Hazel M.
Published: April 2003

Galactose mutarotase catalyzes the first step in normal galactose metabolism by catalyzing the conversion of β‐d‐galactose to α‐d‐galactose. The structure of the enzyme from Lactococcus lactis was recently solved in this laboratory and shown to be topologically similar to domain 5 of β‐galactosidase. From this initial X‐ray analysis, four amino acid residues were demonstrated to be intimately involved in sugar binding to the protein: His 96, His 170, Asp 243, and Glu 304. Here we present a combined X‐ray crystallographic and kinetic analysis designed to examine the role of these residues in the reaction mechanism of the enzyme. For this investigation, the following site‐directed mutant proteins were prepared: H96N, H170N, D243N, D243A, E304Q, and E304A. All of the structures of these proteins, complexed with either glucose or galactose, were solved to a nominal resolution of 1.95 Å or better, and their kinetic parameters were measured against d‐galactose, d‐glucose, l‐arabinose, or d‐xylose. From these studies, it can be concluded that Glu 304 and His 170 are critical for catalysis and that His 96 and Asp 243 are important for proper substrate positioning within the active site. Specifically, Glu 304 serves as the active site base to initiate the reaction by removing the proton from the C‐1 hydroxyl group of the sugar substrate and His 170 functions as the active site acid to protonate the C‐5 ring oxygen.
Numerical Investigation of Heat Transfer in Turbine Cascades With Separated Flows
Authors: de la Calzada P. , Alonso A.
Published: April 2003

Modern design of turbine blades usually requires highly loaded, very thin profiles in order to save weight and cost. If local leading edge incidence is kept close to zero, then flow separation might occur on the pressure side. Although it is known that flow separation, flow reattachment, and the associated zones of recirculation have a major impact on the heat transfer to the wall, the turbomachinery community needs an understanding of the heat transfer mechanisms in separated flows as well as models and correlations to predict them. The aim of the present investigation is a detailed study by means of an in-house CFD code, MU2S2T, of the heat transfer mechanisms in separated flows, in particular in separation and reattachment point regions. Furthermore, an attempt is made to identify a limited number of parameters (i.e., Re, M, inlet flow angle, etc.) whose influence on the heat flux would be critical. The identification of these parameters would be the starting point to develop special correlations to estimate the heat transfer in separated flow regions.
Combustor Turbine Interface Studies—Part 1: Endwall Effectiveness Measurements
Authors: Colban W. F. , Thole K. A. , Zess G.
Published: April 2003

Improved durability of gas turbine engines is an objective for both military and commercial aeroengines as well as for power generation engines. One region susceptible to degradation in an engine is the junction between the combustor and first vane given that the main gas path temperatures at this location are the highest. The platform at this junction is quite complex in that secondary flow effects, such as the leading edge vortex, are dominant. Past computational studies have shown that the total pressure profile exiting the combustor dictates the development of the secondary flows that are formed. This study examines the effect of varying the combustor liner film-cooling and junction slot flows on the adiabatic wall temperatures measured on the platform of the first vane. The experiments were performed using large-scale models of a combustor and nozzle guide vane in a wind tunnel facility. The results show that varying the coolant injection from the upstream combustor liner leads to differing total pressure profiles entering the turbine vane passage. Endwall adiabatic effectiveness measurements indicate that the coolant does not exit the upstream combustor slot uniformly, but instead accumulates along the suction side of the vane and endwall. Increasing the liner cooling continued to reduce endwall temperatures, which was not found to be true with increasing the film-cooling from the liner.
Micellar Nanocontainers Distribute to Defined Cytoplasmic Organelles
Authors: Savić Radoslav , Luo Laibin , Eisenberg Adi , Maysinger Dusica
Published: April 2003

Block copolymer micelles are water-soluble biocompatible nanocontainers with great potential for delivering hydrophobic drugs. An understanding of their cellular distribution is essential to achieving selective delivery of drugs at the subcellular level. Triple-labeling confocal microscopy in live cells revealed the localization of micelles in several cytoplasmic organelles, including mitochondria, but not in the nucleus. Moreover, micelles change the cellular distribution of and increase the amount of the agent delivered to the cells. These micelles may thus be worth exploring for their potential to selectively deliver drugs to specified subcellular targets.
Adaptation in a Plant-Hummingbird Association
Authors: Temeles Ethan J. , Kress W. John
Published: April 2003

Sexual dimorphism in bill morphology and body size of the Caribbean purple-throated carib hummingbird is associated with a reversal in floral dimorphism of its
Heliconia
food plants. This hummingbird is the sole pollinator of
H. caribaea
and
H. bihai
, with flowers of the former corresponding to the short, straight bills of males, the larger sex, and flowers of the latter corresponding to the long, curved bills of females. On St. Lucia,
H. bihai
compensates for the rarity of
H. caribaea
by evolving a second color morph with flowers that match the bills of males, whereas on Dominica,
H. caribaea
evolves a second color morph with flowers that match the bills of females. The nectar rewards of all
Heliconia
morphs are consistent with each sex's choice of the morph that corresponds to its bill morphology and energy requirements, supporting the hypothesis that feeding preferences have driven their coadaptation.
TUNING MESSAGE AGGREGATION ON HIGH PERFORMANCE CLUSTERS FOR EFFICIENT PARALLEL SIMULATIONS
Authors: PHAM CONGDUC , ALBRECHT CARSTEN
Published: April 2003

High performance clusters (HPCs) based on commodity hardware are becoming more and more popular in the parallel computing community. These new platforms offer a hardware capable of very low latency and very high throughput at an unbeatable cost, making them attractive for a large variety of parallel and distributed applications. With adequate communication software, HPCs have the potential to achieve a level of performance similar to massively parallel computers. However, for parallel applications that present a high communication/computation ratio, it is still essential to provide the lowest latency in order to minimize the communication overhead. In this paper, we are investigating message aggregation techniques to improve parallel simulations of fine-grain ATM communication network models. Even if message aggregation is a well-known solution for improving the communication perfomance of high latency interconnection networks, the complex interaction between message aggregation and the underlying communication software is often ignored. We show that message aggregation must carefully take into account the characteristics of the communication software to be efficient on an HPC. This methodology can be applied as a preliminary step to tune a message aggregation algorithm for a given combination of hardware architecture and communication software layer.
NON-ABELIAN GENERALIZATION OF ELECTRIC–MAGNETIC DUALITY — A BRIEF REVIEW
Authors: CHAN HONG-MO , TSOU SHEUNG TSUN
Published: April 2003

A loop space formulation of Yang–Mills theory highlighting the significance of monopoles for the existence of gauge potentials is used to derive a generalization of electric–magnetic duality to the non-Abelian theory. The result implies that the gauge symmetry is doubled from SU (N) to [Formula: see text], while the physical degrees of freedom remain the same, so that the theory can be described in terms of either the usual Yang–Mills potential Aμ(x) or its dual Ãμ(x). Non-Abelian "electric" charges appear as sources of Aμ but as monopoles of Ãμ, while their "magnetic" counterparts appear as monopoles of Aμ but sources of Ãμ. Although these results have been derived only for classical fields, it is shown for the quantum theory that the Dirac phase factors (or Wilson loops) constructed out of Aμ and Ãμ satisfy the 't Hooft commutation relations, so that his results on confinement apply. Hence one concludes, in particular, that since colour SU (3) is confined, dual colour [Formula: see text] is broken. Such predictions can lead to many very interesting physical consequences, which are explored in a companion paper.
HOMOCLINIC BIFURCATIONS IN A PLANAR DYNAMICAL SYSTEM
Authors: GIANNAKOPOULOS FOTIOS , KÜPPER TASSILO , ZOU YONGKUI
Published: April 2003

The homoclinic bifurcation properties of a planar dynamical system are analyzed and the corresponding bifurcation diagram is presented. The occurrence of two Bogdanov–Takens bifurcation points provides two local existing curves of homoclinic orbits to a saddle excluding the separatrices not belonging to the homoclinic orbits. Using numerical techniques, these curves are continued in the parameter space. Two further curves of homoclinic orbits to a saddle including the separatrices not belonging to the homoclinic orbits are calculated by numerical methods. All these curves of homoclinic orbits have a unique intersection point, at which there exists a double homoclinic orbit. The local homoclinic bifurcation diagram of both the double homoclinic orbit point and the points of homoclinic orbits to a saddle-node are also gained by numerical computation and simulation.
CHAOTIC ATTITUDE MOTION OF GYROSTAT SATELLITE VIA MELNIKOV METHOD
Authors: KUANG JINLU , TAN SOONHIE , ARICHANDRAN KANDIAN , LEUNG A. Y. T.
Published: April 2003

In this paper Deprit's variables are used to describe the Hamiltonian equations for attitude motions of a gyrostat satellite spinning about arbitrarily body-fixed axes. The Hamiltonian equations for the attitude motions of the gyrostat satellite in terms of the Deprit's variables and under small viscous damping and nonautonomous perturbations are suitable for the employment of the Melnikov's integral. The torque-free homoclinic orbits to the symmetric Kelvin gyrostat are derived by means of the elliptic function integral theory. With the help of residue theory of complex functions, the Melnikov's integral is utilized to analytically study the criterion for chaotic oscillations of the attitude motions of the symmetric Kelvin gyrostat under small, damping and periodic external disturbing torques. The Melnikov's integral yields an analytical criterion for the chaotic oscillations of the attitude motions in the form of an inequality that gives a necessary condition for chaotic dynamics in terms of the physical parameters. The dependence of the onset of homoclinic orbits on quantities such as body shapes, the initial conditions of the angular velocities or the two constants of motions of the torque-free gyrostat satellite is investigated in details. The dependence of the onset of chaos on quantities such as the amplitudes of the external excitation and the damping coefficients' matrix is discussed. The bifurcation curves based upon the Melnikov's integral are computed by using the combined parameters versus the frequency of the external excitation. The theoretical criterion agrees with the result of the numerical simulation of the gyrostat satellite by using the fourth-order Runge–Kutta integration algorithm. The numerical solutions show that the motions of the perturbed symmetric gyrostat satellite possess a lot of "random" characteristic associated with a nonperiodic solution.
TOPOLOGICAL ENTROPY FOR MULTIDIMENSIONAL PERTURBATIONS OF ONE-DIMENSIONAL MAPS
Authors: MISIUREWICZ MICHAŁ , ZGLICZYŃSKI PIOTR
Published: April 2003

We prove that if an interval map of positive entropy is perturbed to a compact multidimensional map then the topological entropy cannot drop down considerably if the perturbation is small.
ANALYTIC INTEGRABILITY OF NILPOTENT CUBIC SYSTEMS WITH DEGENERATE INFINITY
Authors: GINÉ JAUME
Published: April 2003

In this paper we study the cubic nilpotent systems having an isolated singular point at the origin with degenerate infinity and give a characterization of those that accept a certain type of analytical first integrals. For these systems we give, also, a characterization of the singular point at the origin; in particular we see that the origin is never a center.
THE EFFECT OF MEMORY IN THE SPATIAL CONTINUOUS-VALUED PRISONER'S DILEMMA
Authors: ALONSO-SANZ RAMÓN , MARTÍN M. CARMEN , MARTÍN MARGARITA
Published: April 2003

The standard spatial formulation of the Prisoner's Dilemma is a historic (memoryless, i.e. only results generated in the last round are taken into account in deciding the next choice), and binary (players are confined to fully cooperating or defecting). The spatial historic model admitting intermediate degrees of cooperation (fuzzy model) is studied in this work. Comparisons are made between the binary and fuzzy models. The effect of errors and discounting is also assessed.
Presence of ADAMTS13 Activity in a Patient with Metastatic Cancer and Thrombotic Microangiopathy
Authors: Forman Robin B. , Benkel Seth A. , Novik Yelena , Tsai Han-Mou
Published: April 2003

Patients with metastatic cancers occasionally present with microangiopathic hemolysis and thrombocytopenia. A patient with metastatic adenocarcinoma of the colon and microangiopathic hemolysis was treated with plasma exchange for a presumptive diagnosis of thrombotic thrombocytopenic purpura (TTP). However, her condition continued to deteriorate and a determination of ADAMTS13 activity revealed that she did not have TTP. Despite similarity in clinical manifestation, microangiopathic hemolysis in patients with metastatic cancers may not be caused by ADAMTS13 deficiency and the role of plasma exchange in such patients should be reevaluated.
Urinary and Plasma Homocysteine and Cysteine Levels during Prolonged Oral N-Acetylcysteine Therapy
Authors: Ventura Paolo , Panini Rossana , Abbati Gianluca , Marchetti Germano , Salvioli Gianfranco
Published: April 2003

Acute administration of N-acetylcysteine (NAC) may induce alterations in plasma and urinary levels of homocysteine (Hcy) and cysteine (Cys). We studied the effects of continuous oral NAC therapy on different Hcy and Cys plasma and urinary forms in 40 healthy subjects assigned to three groups (groups A: n = 13, no therapy; group B: n = 14, NAC 600 mg/day, and group C: n = 14, NAC 1,800 mg/day) for 1 month (T1). After a 1-month washout period without therapy (T2), all subjects were treated with oral NAC (1,800 mg/day) for 2 months and (T3 and T4) reassessed monthly for plasma and urinary thiols. The treated subjects showed a significant decrease in plasma total Hcy and a slight increase in total Cys levels; the alterations of different forms of plasma thiols suggested an NAC-induced increase in disulfide forms and an increase in urinary Hcy and Cys excretion as disulfide forms. The effects appeared to be dose dependent, being more marked in subjects treated with higher dosages. This approach may be important, as an association or alternative therapy in hyperhomocysteinemic conditions of poor responses to vitamins.
Long-Term Prognosis of Patients with Acute Coronary Syndrome and Moderate Coronary Artery Stenosis
Authors: Maurin Thierry , Zeller Marianne , Cottin Yves , Touzery Claude , Beer Jean Claude , L’Huillier Isabelle , Fraison Michel , Buffet Philippe , Louis Pierre , Wolf Jean Eric
Published: April 2003

We evaluated the clinical outcome and the prognostic factors at 6-year follow-up of patients with acute coronary syndrome without critical coronary arterial narrowing. The mean follow-up was 73 ± 19 months. Mortality rate was 13%, and 20 patients (12%) had major cardiac event, 8 patients (5%) had stroke and 10 patients (6%) underwent revascularization. Multivariate analysis matched for age and ejection factor showed that moderate disease (stenosis 40–59%) (OR = 2.713, p < 0.024) was an independent predictive factor of major cardiac event.
Electrophysiological Mapping and Histological Examinations of the Swine Atrium with Sustained (≥24 h) Atrial Fibrillation: A Suitable Animal Model for Studying Human Atrial Fibrillation
Authors: Lin Jiunn-Lee , Lai Ling-Ping , Lin Chih-Shen , Du Chao-Cheng , Wu Tsu-Juey , Chen Shih-Ping , Lee Wen-Chuan , Yang Ping-Cheng , Tseng Yung-Zu , Lien Wen-Pin , Huang Shoei K. Stephen
Published: April 2003

Objectives: Interventional elimination of chronic persistent atrial fibrillation (AFib) remains difficult. An animal model mimicking the clinical situation is important. Methods and Results: Twenty-five adult pigs were implanted with a high-speed atrial pacemaker. After continuous pacing at 600 bpm for 6 weeks, 20 (91%) of the 22 survivals developed sustained AFib lasting for at least 24 h. Epicardial dense mapping revealed multiple coexisting reentrant wavelets in the left and the right atrium (LA and RA, respectively; 10.6 ± 2.9 vs. 7.6 ± 2.4 wavelets/cm2/s; p < 0.002). The mean local A-A intervals were 87.2 ± 14.6 ms in the LA and 103.3 ± 19.0 ms in the RA (p < 0.0002). Acute termination of sustained AFib was successful in 3 of the 5 pigs by propafenone, but in none of the 6 by dl-sotalol. Epicardial cryothermal ablation failed to terminate any AFib by compartmentalization of the RA free wall alone (4 pigs) or together with the LA appendage (4 pigs). Electron microscopic examination demonstrated diffuse perinuclear myolysis, myofibrillar fragmentation and mitochondrial crystal disruption in the atrium. Conclusions: Pacing-induced sustained AFib (≧24 h) in adult pigs is a feasible and efficient animal model with electrophysiological and histological characteristics closely similar to those seen in humans.
Biochemical and Clinical Aspects of Methotrexate Neurotoxicity
Authors: Vezmar Sandra , Becker Achim , Bode Udo , Jaehde Ulrich
Published: April 2003

Acute, subacute and chronic neurotoxicity have been observed after the administration of high-dose and/or intrathecal methotrexate (MTX). Acute toxicity is usually transient without permanent damage. Subacute and chronic toxicity are associated with changes in the brain and/or the spinal cord which may be progressive and even lead to coma and death in severe cases. It is believed that MTX can induce direct toxic effects to the CNS by damaging the neuronal tissue. Moreover, MTX interferes with the metabolic pathways of folates, excitatory amino acids, homocysteine, S-adenosylmethionine/S-adenosylhomocysteine, adenosine and biopterins, inducing biochemical alterations which have been associated with neurotoxic symptoms. It has been suggested that acute toxicity is partly mediated by adenosine, whereas homocysteine, S-adenosylmethionine/S-adenosylhomocysteine, excitatory amino acids and biopterins may play an important role in the development of subacute and chronic toxicity. A better understanding of the pathogenesis of MTX neurotoxicity would offer the possibility of developing new therapeutic strategies for its treatment or prevention.
Comparison of a 48-Hour Infusion of 5-Fluorouracil without Folinic Acid with 24-Hour Folinic Acid/5-Fluorouracil in Patients with Metastatic Colorectal Cancer Refractory to Bolus Folinic Acid/5-Fluorouracil
Authors: Moehler Markus , Gutzler Frank , Steinmann Silke , Boehme Michael , Raeth Ulrich , Stremmel Wolfgang , Galle Peter R. , Rudi Jochen
Published: April 2003

Background: Out of various high-dose 5-fluorouracil (5-FU) regimens given with or without folinic acid (FA), the optimal 5-FU schedule has still to be defined as treatment for metastatic colorectal cancer (CRC). Consequently, we compared toxicity, response and survival following two FA/5-FU regimens in 55 CRC patients refractory to bolus FA/5-FU. Methods: Twenty-eight patients (group A) received 5-FU (60 mg/kg body weight) for 48 h, and 27 (group B) received 2-hour infusions of FA (500 mg/m2) and 24-hour infusions of 5-FU (2,600 mg/m2) until disease progression. Results: Both groups were adequately matched with respect to patient characteristics. While overall toxicities were rare, hand-foot syndrome was more common in A. Tumor control was achieved in 57 and 44%, for A and B, respectively. Survival times were 16 months in A and 9 months in B. Conclusions: Since both 5-FU infusion protocols showed equivalent palliative effects, FA may be questioned in second-line 5-FU regimens.
Assessment of Antibiotic Susceptibility of Ureaplasma urealyticum from Prostitutes and Outpatient Clinic Patients Using the E-Test and Agar Dilution Method
Authors: Çakan Hüseyin , Polat Erdal , Kocazeybek Bekir , Öcal Pelin , Çepni İsmail , Aslan Mustafa , Salihoğlu Funda , Altaş Kemal
Published: April 2003

In this study, a total of 647 vaginal discharge samples were examined. Ureaplasma urealyticum growth was seen in 68 samples (10.5%). The antibiotic sensitivity of 30 types of U.urealyticum was determined with the E-test and agar dilution method. With the agar dilution method, all types were sensitive to ciprofloxacin and ofloxacin (MIC 0.94 µg/ml), tetracycline (MIC 0.125 µg/ml) and doxycycline (MIC 0.125 and 0.190 µg/ml). Furthermore, with the agar dilution method, 18 types (60%) were resistant to roxithromycin and 12 (40%) were sensitive (MIC 12 µg/ml); 3 types (10%) were resistant to erythromycin and 27 (90%) were sensitive (MIC 12 µg/ml); 9 types (30%) were resistant to clarithromycin and 21 (70%) were sensitive (MIC 12 µg/ml), and all types were sensitive to azithromycin (MIC 14 µg/ml).
Differential Effect of HIV-1 Protease Inhibitors on P-Glycoprotein Function in Multidrug-Resistant Variants of the Human CD4+ T Lymphoblastoid CEM Cell Line
Authors: Dupuis Maria Luisa , Tombesi Marina , Sabatini Marco , Cianfriglia Maurizio
Published: April 2003

Background: P-glycoprotein causing multidrug resistance (MDR) and limiting the efficacy of antineoplastic drugs and protease inhibitors (PIs) is expressed in human CD4+ T lymphocytes, one of the main targets of HIV, in a range of pharmacological barriers and at varying degrees in non-Hodgkin’s lymphoma and Kaposi’s sarcoma. Methods: The differential effect of PIs on P-glycoprotein function was studied by measuring drug efflux inhibition, MDR-reversing ability and MAb UIC2 epitope modulation in MDR variants of the human T lymphoblastoid CEM cell line. Results: The treatment of MDR cells with PIs induces different UIC2 epitope modulations indicating a differential recognition and binding of these antiviral drugs by MDR1 P-glycoprotein. In fact, ritonavir, saquinavir and indinavir act differently to the P-glycoprotein blocker in CEM-VBL10 cells. The MDR level of these cells was markedly affected by ritonavir and saquinavir in the order, while the PI indinavir does not seem to compete with the P-glycoprotein drug transport function. In CEM-VBL100 cells, expressing a very high number of P-glycoprotein molecules, only ritonavir acts as an efficient drug efflux inhibitor and MDR-reversing agent. Conclusion: TheHIV-1 PIs ritonavir and saquinavir even at different levels act as genuine P-glycoprotein substrates by inhibiting dye substrate efflux, modulating UIC2 epitope and reversing drug resistance. Conversely, at least in the in vitrosystem used in the present study, the PI indinavir does not significantly alter P-glycoprotein drug transport activities and function.
Treatment with Simvastatin in Patients with Alzheimer’s Disease Lowers Both α- and β-Cleaved Amyloid Precursor Protein
Authors: Sjögren Magnus , Gustafsson Kina , Syversen Steinar , Olsson Annika , Edman Åke , Davidsson Pia , Wallin Anders , Blennow Kaj
Published: April 2003

We investigated the clinical and biological effects of cholesterol-lowering treatment with a statin in 19 patients with Alzheimer’s disease. They received simvastatin 20 mg/day for 12 weeks in an open trial. Primary efficacy parameters were the changes after 12 weeks in the cerebrospinal fluid (CSF) levels of β-amyloid42 (Aβ42), α-secretase-cleaved amyloid precursor protein (α-sAPP), β-secretase-cleaved APP (β-sAPP), tau, phospho-tau and the plasma levels of Aβ42. A secondary efficacy parameter was the change in the Alzheimer’s Disease Assessment Scale-Cognition (ADAS-cog) score. After 12 weeks, CSF α-sAPP and CSF β-sAPP were significantly reduced (p < 0.001), but the CSF levels of tau, phospho-tau, Aβ42 and the plasma levels of Aβ42 were unchanged. The ADAS-cog score was slightly increased (p < 0.05). The results suggest that simvastatin acts directly on the processing of APP by inhibiting both the α- and the β-secretase pathways.
Profile of Neuropsychological Deficits in Older Stroke Survivors without Dementia
Authors: Ballard Clive , Stephens Sally , Kenny RoseAnne , Kalaria Raj , Tovee Martin , O’Brien John
Published: April 2003

Background: Few studies have examined the profile of cognitive impairments in older stroke patients without dementia. Method: A standardized evaluation including a detailed neuropsychological assessment [Cambridge Examination for Mental Disorders in the Elderly – cognitive subscale (CAMCOG)] and computerised tests of attention and working memory from the Cognitive Drug Research battery were undertaken in 150 stroke survivors of >75 years of age and 30 elderly controls. Results: The stroke survivors without dementia had significantly greater overall impairment on the CAMCOG, as well as significantly greater impairment in memory, simple reaction time, choice reaction time (CRT), vigilance accuracy, CRT variability, spatial working memory reaction time (SWMRT) and numerical working memory than the elderly controls (e.g. CRT ↑ 33%, SWMRT ↑ 61%, memory ⇓ 11%). Conclusion: Impairments of cognitive processing speed, working memory and executive functions are frequent in elderly stroke patients without dementia and represent the main cognitive components of early cognitive impairments.
Multilayer Primary Epithelial Cell Culture from Bovine Conjunctiva as a Model for in vitro Toxicity Tests
Authors: Civiale Claudine , Paladino Grazia , Marino Clara , Trombetta Francesco , Pulvirenti Teodoro , Enea Vincenzo
Published: April 2003

Objective: The purpose of this study was to obtain a primary cell culture of bovine origin similar to the conjunctiva in terms of morphology and cell types, which could be of use for in vitro toxicity studies. Methods: After separation from the stroma by enzymatic treatment, conjunctival epithelial cells were dissociated and plated onto collagen-coated Transwell® filters (1.13 cm2 area). One group of plates was maintained in immersion and another was cultured under air-lifted conditions. Anti-epithelial keratin antibodies (AE1/AE3, K4) and antidesmoplakin 1 and 2 were used to characterize the cells by indirect immunofluorescence. The cell layer was examined after histological processing of the Transwell filter. Ultrastructural analysis was carried out by scanning electron microscopy (SEM). The bioelectric parameters transepithelial electrical resistance (TEER), potential difference (PD), short circuit current and paracellular permeability profile of carboxyfluorescein were monitored as indices of the functional characteristics of these cultures. Cytotoxicity was evaluated on morphological and functional (TEER) grounds after treating the cultures with several test substances. Results: Morphological studies showed pure and homogeneous cell cultures. In the SEM analysis, we observed contiguous polygonal cells with numerous short microvilli, a characteristic proportion of light, medium and dark cells and a sparse population of rounded PAS-positive cells, i.e. resembling goblet cells. Air-lifted cultures also showed a tissue-like cellular organization (8–9 layers). Immersion cultures reached a maximum TEER value of around 2.95 kΩ·cm2 7 days after plating while in air-lifted cultures TEER peaked up to 5.59 kΩ·cm2 11 days after plating. With regard to the use of bovine conjunctival epithelial cells (BCECs) for cytotoxicity screening, the system responded finely to the insults and yielded morphological and functional results in accordance with data obtained in vivo. Conclusions: BCECs reproduce cell morphology and differentiation of the original tissue and should prove a useful tool for initial studies of drug toxicity.
Hydrogel Tissue Adhesive for Sealing Corneal Incisions
Authors: Kalaycı Defne , Fukuchi Toshio , Edelman Peter G. , Sawhney Amarpreet S. , Mehta Mehul C. , Hirose Tatsuo
Published: April 2003

The purpose of the study was to assess the efficacy of a newly developed hydrogel tissue adhesive for sealing corneal incisions in ex vivo rabbit eyes. Simple through-and-through central linear corneal incisions measuring 1–5 mm were created in enucleated rabbit eyes. As controls, the leaking pressures were measured immediately after the incisions had been made. Afterwards, the incisions were sealed with hydrogel adhesive in group 1 and with a single 10-0 nylon suture in group 2. The leaking pressure of each incision was measured after the wounds had been sealed in both groups. The leaking pressures of the controls and the sealed incisions were compared for statistical significance using the Wilcoxon signed rank test. The difference between the leaking pressures before and after sealing the incisions in groups 1 and 2 were compared using the Mann-Whitney rank sum test. The leaking pressures were significantly higher after sealing in both groups 1 and 2 compared to the controls for all incision sizes. The differences in the leaking pressures before and after adhesive application were higher than before and after suturing in all incision sizes. The differences were all statistically significant except for the 1-mm incisions. We conclude that the hydrogel glue has the potential to be used for sealing corneal incisions measuring up to 5 mm.
Adulthood in Women with Turner Syndrome
Authors: Ostberg Julia E. , Conway Gerard S.
Published: April 2003

Turner syndrome, resulting from a complete or partial absence of one X chromosome, is the most commonly occurring chromosomal abnormality in females. Patients have traditionally been carefully followed in paediatric practice during childhood, but were often discharged to primary care on reaching adulthood. Adults with Turner syndrome are thought to have a reduced life expectancy, mainly due to excess cardiovascular risk, but they may also have multiple comorbidities including hypothyroidism, deafness, osteoporosis and the attendant problems of oestrogen deficiency and infertility. A multidisciplinary approach to focused adult care is needed, with consideration of how to optimise surveillance strategies in these women.
GH Values after Clonidine Stimulation Measured by Immunofluorometric Assay in Normal Prepubertal Children and GH-Deficient Patients
Authors: Silva Eveline G.P. , Slhessarenko Natasha , Arnhold Ivo J.P. , Batista Marcelo C. , Estefan Vivian , Osorio Maria G.F. , Marui Suemi , Mendonca Berenice B.
Published: April 2003

Objective: To establish the cut-off values of GH measured by immunofluorometric assay, a more sensitive and specific assay, in normal prepubertal children and compare their values with those of proven GH-deficient patients. Methods: 30 normal children (20 males) and 26 patients with known causes of GH deficiency were submitted to the clonidine test and their GH values were compared. A powdered clonidine tablet (0.1 mg/m2) was given orally and blood samples for GH measurements were drawn at times –30, 0, 60, 90 and 120 min. Results: GH peak values presented a wide variation ranging from 1.7 to 25 µg/l (mean ± SD = 12.87 ± 5.8 µg/l) in the normal group. The cut-off values for the 5th and 10th percentiles of the distribution curve were 3.3 and 5.5 µg/l, respectively. In the GH deficiency group, maximum GH levels after clonidine stimulation ranged from <0.1 to 2.1 µg/l (0.56 ± 0.58 µg/l). Conclusions: The cut-off values obtained with the immunofluorometric method are lower than the ones obtained by radioimmunoassay. We suggest a cut-off value of 3.3 µg/l (5th percentile) that ensures 100% of sensitivity along with 93% of specificity to exclude the diagnosis of GH deficiency when using this immunofluorometric method.
Carbohydrate Metabolism Is Not Impaired after 3 Years of Growth Hormone Therapy in Children with Prader-Willi Syndrome
Authors: l’Allemand Dagmar , Eiholzer Urs , Schlumpf Michael , Torresani Toni , Girard Jürg
Published: April 2003

Background/Aim: In children with Prader-Labhart-Willi syndrome (PWS), the insulin secretion is reduced, despite obesity, being ascribed to the growth hormone (GH) deficiency of hypothalamic origin. Besides, an increased prevalence of diabetes mellitus was described in this syndrome. Hence, we addressed the questions of how body composition and insulin secretion are interrelated and what impact GH therapy has on the carbohydrate metabolism in PWS. Methods: We measured weight, lean and fat mass (by dual-energy X-ray absorptiometry), triglycerides, HbA1c, and fasting insulin and glucose levels in 17 children (age range 1.5–14.6 years) with PWS to examine whether the carbohydrate metabolism is altered during 36 months of therapy with 8 mg GH/m2 body surface/week. In a subgroup of 8 children, the insulin secretion was longitudinally assayed during oral glucose tolerance at 0 and 12 months of therapy. Results: Before therapy, the insulin secretion was lower and markedly delayed as compared with reference data and did not rise during therapy. The glucose tolerance was impaired in 2 of 12 children examined by oral glucose tolerance test before therapy and normalized during therapy. Fasting insulin and insulin resistance being normal at the beginning, significantly increased at 12 months and returned to initial levels at 36 months of GH therapy. Fasting glucose as well as HbA1c and triglyceride levels were always normal. The fat mass before GH therapy was increased (39.5%) and dropped into the upper normal range (28.3%) during 3 years of therapy, being correlated with fasting insulin concentration and indices of insulin sensitivity before and after 1 year of therapy. Conclusions: Children with PWS are characterized by an intact insulin sensitivity with a decrease and a delay of insulin secretion, regardless of moderate obesity or GH treatment. In the present setting, the carbohydrate metabolism is not impaired by GH therapy, but by the excessively increased fat mass.
Characterization of Empathy Deficits following Prefrontal Brain Damage: The Role of the Right Ventromedial Prefrontal Cortex
Authors: Shamay-Tsoory S. G. , Tomer R. , Berger B. D. , Aharon-Peretz J.
Published: April 2003

Impaired empathic response has been described in patients following brain injury, suggesting that empathy may be a fundamental aspect of the social behavior disturbed by brain damage. However, the neuroanatomical basis of impaired empathy has not been studied in detail. The empathic response of patients with localized lesions in the prefrontal cortex (n = 25) was compared to responses of patients with posterior (n = 17) and healthy control subjects (n = 19). To examine the cognitive processes that underlie the empathic ability, the relationships between empathy scores and the performance on tasks that assess processes of cognitive flexibility, affect recognition, and theory of mind (TOM) were also examined. Patients with prefrontal lesions, particularly when their damage included the ventromedial prefrontal cortex, were significantly impaired in empathy as compared to patients with posterior lesions and healthy controls. However, among patients with posterior lesions, those with damage to the right hemisphere were impaired, whereas those with left posterior lesions displayed empathy levels similar to healthy controls. Seven of nine patients with the most profound empathy deficit had a right ventromedial lesion. A differential pattern regarding the relationships between empathy and cognitive performance was also found: Whereas among patients with dorsolateral prefrontal damage empathy was related to cognitive flexibility but not to TOM and affect recognition, empathy scores in patients with ventromedial lesions were related to TOM but not to cognitive flexibility. Our findings suggest that prefrontal structures play an important part in a network mediating the empathic response and specifically that the right ventromedial cortex has a unique role in integrating cognition and affect to produce the empathic response.
Variability of the Indian Ocean: Relation to monsoon and ENSO
Authors: Krishnamurthy V. , Kirtman Ben P.
Published: April 2003

Recent years have brought renewed interest in Indian Ocean variability and its relationship with both Australasian monsoon variability and the El Niño–Southern Oscillation (ENSO). There is an ongoing debate as to whether the Indian Ocean is entirely a ‘slave’ to ENSO or whether it has its own modes of coupled variability that are independent of ENSO. The objective of this observational study is to document the variability of the Indian Ocean, to examine its relationship to variability in the tropical Pacific, and to investigate the potential influence of the Australasian monsoon on the variability in both basins. Indian Ocean variability is shown to be strongly seasonal and related to ENSO variability. In fact, when seasonality is carefully considered, the link between ENSO and the Indian Ocean becomes quite robust. This does not imply that the Indian Ocean does not have any variability on seasonal‐to‐interannual time‐scales that is independent of ENSO. It does, however, suggest that a preponderance of this variability is related to ENSO variability. Cause and effect is not be determined here. A significant fraction of the variability in the tropical Indian and Pacific Oceans is related to variations with three centres of action: cold (warm) sea surface temperature anomalies (SSTA) in the western Indian Ocean, warm (cold) anomalies in the eastern Indian and western Pacific Oceans, and cold (warm) anomalies in the eastern Pacific. These three centres of action have a distinct annual march so that the SSTA in the Indian Ocean is of one sign during December to May, and a so‐called dipole structure develops during June to November. The Indian monsoon is shown to be strongly connected to the annual march of this Indo–Pacific SST variability. Copyright © 2003 Royal Meteorological Society
Factors associated with accurate self-reported adherence to HIV antiretrovirals
Authors: Kimmerling Mina , Wagner Glenn , Ghosh-Dastidar Bonnie
Published: April 2003

The purpose of this study was to determine the conditions in which self-reports provide an accurate assessment of adherence to HIV antiretrovirals. In a sample of 58 participants, self-reported and electronically monitored adherence to antiretroviral therapy were compared over a three-day period. Of the 16 who reported missed doses, only six (38%) accurately reported the number of doses they took, although the electronic monitoring data confirmed that all but one (94%) did in fact miss at least one dose. In contrast, 25 (60%) of the 42 participants who reported no missed doses were accurate. Nearly all (96%) participants who actually did take all their doses accurately reported their adherence compared to only 20% of those who missed at least one dose ( P<0.001). Cognitive functioning was marginally associated with self-report accuracy, but all other baseline factors were not associated with accuracy. Our findings highlight the need for more effective self-report methodology and a better understanding of the circumstances in which self-reports are valid measures of adherence.
Hierarchical Pattern Replication by Polymer Demixing
Authors: Sprenger M. , Walheim S. , Schäfle C. , Steiner U.
Published: April 2003

Structures with a lateral size of ≈ 100 nm have been created using a new replication method based on the demixing of a ternary polymer mixture during spin‐coating. The technique, which relies on the interfacial wetting of one of the polymer components at the interface of the other two, produces structures (see Figure) that are significantly smaller than the lateral dimensions of the substrate prepattern.
Solid‐state polymerization of poly(ethylene terephthalate). III. Thermal stabilities in terms of the vinyl ester end group and acetaldehyde
Authors: Kim T. Y. , Jabarin S. A.
Published: April 2003

Poly(ethylene terephthalate) (PET), precursors, and solid‐stated samples were evaluated in terms of changing vinyl ester (VE) concentrations. The results obtained through the application of reaction kinetics gave VE contents ranging from 0.7 to 5.5 mmol/kg of PET. As the initial intrinsic viscosity (IV) of the precursor increased, the VE content also increased, representing the different thermal histories of the samples during melt‐phase polymerization. The VE contents decreased as the solid‐state polymerization (SSP) time increased from 0 to 12 h and as the temperature of SSP increased up to 220°C. A series of acetaldehyde (AA) generation experiments were conducted from 270 to 300°C with samples solid‐stated from three precursors with different initial IVs. The rate of AA generation decreased as the final IV of the solid‐stated PET increased, and this showed that the SSP process improved the thermal stability of PET. The AA generation rates of samples that had similar final IVs but were solid‐stated from different IV precursors were also compared. When the heating temperature was low, the amount and rate of AA generation were higher for samples with higher initial precursor IVs. This tendency, however, became less clear as the generation temperatures increased, probably because interference from the dissociation reactions (occurring between the polymer chains to produce VE) increased with increasing temperature. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 228–237, 2003