bluuebunny/crossref_metadata_2025 huggingface dataset:
Blood Pressure Control and Factors Predicting Control in a Treatment‐Compliant Male Veteran Population
Authors: Bizien Marcel D. , Jue Sandra G. , Panning Chad , Cusack Barry , Peterson Teri
Published: May 2004

Study Objective. To estimate blood pressure control and identify treatment variables predicting control in treatment‐compliant, hypertensive, male veterans.

Setting. Outpatient clinic of a Veterans Affairs medical center.

Design. Retrospective review of computerized patient records over a 12‐month period for demographics, comorbidities, patient‐specific blood pressure goals, blood pressure history, antihypertensive therapy, and refill history.

Patients. Two hundred fifty hypertensive men aged 39–90 years whose antihypertensive regimen remained unchanged over 12 months.

Measurements and Main Results. The proportion of patients with blood pressures below 160/90 mm Hg was 86%; only 34.8% had pressures below 140/90 mm Hg. Blood pressure control was less common with advancing age (42.1%, 33.7%, and 29.4% for patients aged < 60, 60–75, and > 75 yrs, respectively, p=0.057 for trend). Treatment intensity was highest in obese men, those aged 60–75 years, and those with a history of chronic heart failure or angina, and lowest in men older than 75 years or with a history of stroke. Blood pressure control was independently associated with therapy with β‐blockers (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.5–10.2, p=0.005), loop diuretics (OR 4.3, 95% CI 1.6–12.1, p=0.005), angiotensin‐converting enzyme inhibitors (OR 3.1, 95% CI 1.2–8.2, p=0.025), and long‐term simvastatin therapy (OR 3.7, 95% CI 1.9–7.4, p=0.0001), and with a diagnosis of coronary artery disease (OR 3.2, 95% CI 1.35–7.69, p=0.009). The relationship between simvastatin therapy and blood pressure control persisted after controlling for the higher treatment intensity in patients taking the drug. Factors predicting poor control included a history of stroke (OR for control 0.36, 95% CI 0.19–0.69, p=0.002), age over 75 years (OR 0.43, 95% CI 0.18–0.98, p=0.046), highest low‐density lipoprotein tertile (OR 0.37, 95% CI 0.17–0.80, p=0.013), highest body mass index tertile (OR 0.46, 95% CI 0.21–1.00, p=0.05), and therapy with two or fewer antihypertensives (OR 0.14, 95% CI 0.04–0.61, p=0.009).

Conclusion. In a compliant veteran population, control of blood pressure appeared inadequate but was significantly more likely in those receiving at least three antihypertensive agents. Long‐term therapy with simvastatin was independently associated with increased odds of control.
Determination of the Lack of a Drug Interaction Between Azithromycin and Warfarin
Authors: McCall Kenneth L. , H. Glenn Anderson Jr. Pharm.D.  , Jones Angela D.
Published: May 2004

Study Objective. To determine the effect on the international normalized ratio (INR) of adding azithromycin to patients receiving stable dosages of warfarin.

Design. Retrospective chart review.

Setting. Outpatient clinic.

Patients. Ambulatory patients receiving warfarin and azithromycin concurrently who had a documented therapeutic INR value before the start of azithromycin therapy (pre‐INR) and a documented INR value within 30 days after the start of azithromycin therapy (post‐INR).

Measurements and Main Results. Patients given felodipine during long‐term warfarin therapy formed a comparative control group. Patient demographics were similar in both treatment groups. Mean age of the azithromycin group (17 patients) was 59 ± 13 years and of the control group (20 patients) 65 ± 12 years. All 17 patients in the azithromycin group and 16 of the controls were women. Mean change from pre‐INR to post‐INR in the azithromycin and control groups, respectively, was 0.14 ± 0.64 (pre‐INR 2.46, post‐INR 2.61) and 0.19 ± 0.54 (pre‐INR 2.46, post‐INR 2.66) (p=0.74). A post hoc power analysis based on a pooled standard deviation of 0.60 revealed that the study had 68% power to detect a 0.5 change in the INR value.

Conclusion. No interaction between azithromycin and warfarin was observed in ambulatory patients with therapeutic baseline INR values.
Enfuvirtide, a New Fusion Inhibitor for Therapy of Human Immunodeficiency Virus Infection
Authors: Hardy Hélène , Skolnik Paul R.
Published: May 2004

Enfuvirtide is the first fusion inhibitor to be approved by the Food and Drug Administration for the treatment of chronic human immunodeficiency virus (HIV) infection in adults and children 6 years and older. The drug is a synthetic peptide derived from a naturally occurring amino acid sequence known as heptad repeat 2 (HR2) found in gp41, a viral transmembrane glycoprotein that facilitates fusion with host cells. By mimicking the activity of HR2 and competitively binding to a second region of gp41, heptad repeat 1 (HR1), enfuvirtide prevents interaction between HR1 and HR2 and inhibits the conformational change of gp41 that is necessary for fusion of virions to host cells. The safety and efficacy of enfuvirtide have been studied only in antiretroviral‐experienced persons. Preliminary data from two multicenter phase III clinical trials (T‐20 versus Optimized Regimen Only [TORO 1, TORO 2]) suggest that the drug is safe and efficacious in heavily pretreated subjects through 24 weeks. By week 24, in TORO 1 and TORO 2, respectively, mean changes in HIV RNA concentrations of −1.7 and −1.4 log10 copies/ml were observed in subjects receiving enfuvirtide plus an optimized background (OB) regimen, compared with changes of −0.8 and −0.7 log10 copies/ml in subjects receiving an OB regimen alone. Resistance to enfuvirtide has been identified in vitro and in vivo. Most resistant variants contain mutations in the HR1 region of gp41 (positions 36–45). In phase III clinical trials, numerous substitutions within this critical region were associated with faster time to virologic failure over 24 weeks. Overall, enfuvirtide appears to be well tolerated and acceptable to patients despite a high rate of injection site reactions (> 90%). Bacterial pneumonia and eosinophilia occurred more frequently in subjects taking enfuvirtide than in those taking an OB regimen alone in phase III trials; however, no causal relationship was established. Like most drugs with peptide structures, enfuvirtide appears to have a low potential for metabolic drug‐drug interactions. The approved dosage is 90 mg twice/day by subcutaneous injection in adults and 2 mg/kg twice/day in children older than 6 years. Enfuvirtide is an addition to antiretroviral therapy since it targets a new step in the HIV life cycle. Given the complexity of its production and administration, however, it is likely to be most useful in antiretroviral‐experienced patients.
The Antipyretic Effect of Ibuprofen and Acetaminophen in Children
Authors: Wahba Haney
Published: May 2004

Objective. To determine whether evidence in the medical literature supports ibuprofen or acetaminophen for reducing fever in children.

Methods. Both MEDLINE and the Science Citation Index were searched using various medical subject headings for all articles published worldwide from 1966–2000. The language of publication was not restricted.

Results. Initially, 4132 articles were found that dealt with either ibuprofen or acetaminophen. Limiting these articles to humans and children, and cross‐referencing with the Science Citation Index resulted in 68 articles; 22 satisfied the inclusion criteria and were further assessed for validity, design, and methods of reporting data.

Conclusion. Acetaminophen and ibuprofen have equal tolerability. Acetaminophen produced a greater body temperature reduction at 0.5 hour after intervention compared with ibuprofen. However, ibuprofen provides a longer duration of antipyretic effect than acetaminophen 4 hours after intervention, and the initial temperature decrement lasts longer.
Assessment of Hypothyroidism in Patients with Chronic Heart Failure
Authors: Middleton Sarah C. , Spencer Anne P.
Published: May 2004

Study Objective. To determine whether appropriate thyroid function measurements were being conducted in patients receiving care at a multidisciplinary heart failure clinic.

Design. Retrospective chart review.

Setting. University‐affiliated outpatient clinic.

Patients. One hundred ninety‐three patients with heart failure.

Intervention. Patients enrolled in the heart failure clinic at the Medical University of South Carolina from January 2000‐April 2003 were identified. Their medical records were reviewed for demographics, New York Heart Association (NYHA) functional classification, laboratory data, and date of most recent heart failure clinic appointment.

Measurements and Main Results. The records of 193 patients (43% women) were reviewed. Overall and subgroup analyses were performed based on patient characteristics such as presence of thyroid‐stimulating hormone (TSH) level, interval since last heart failure clinic appointment, presence of thyroid replacement therapy, amiodarone use, NYHA functional class, and attending physician. Of the 193 patients, 77 (40%) had appropriate TSH monitoring, whereas 10 (32%) of 31 patients receiving amiodarone had appropriate monitoring. Forty‐four (27%) patients not receiving amiodarone had no record of a TSH level. In 22 patients (11%), hypothyroidism was diagnosed and treated, whereas 16 patients (8%) had an abnormal TSH level but received no therapy.

Conclusion. Forty percent of the 193 patients at this outpatient heart failure clinic received appropriate TSH monitoring. An opportunity exists for protocol implementation and education of pharmacists, nurse practitioners, and physicians concerning appropriate thyroid function monitoring in the heart failure population.
Pharmacist Compensation for Cognitive Services: Focus on the Physician Office and Community Pharmacy
Authors: Snella Kathleen A. , Trewyn Renee R. , Hansen Laura B. , Bradberry J. Chris
Published: May 2004

We provide a stepwise approach for the clinical pharmacy practitioner in the physician clinic or community pharmacy setting to secure compensation for cognitive services. How to establish compensation for pharmacist services is explored, including evaluating the payer mix, developing a relationship with the first‐ or third‐party payer, becoming credentialed with a third‐party payer, and creating a fee structure. We detail the physical process of billing, which involves completing appropriate billing forms, appropriately using billing codes, documenting cognitive services in the patient record, and obtaining the proper waivers and/or approvals to provide specific services such as laboratory services and immunizations. This comprehensive review of compensation for cognitive services available in the community pharmacy and physician office environment is designed to be a template for pharmacists to further develop specific strategies, implement fee structures, and obtain compensation in their pharmacy environment and payer mix. Exploration into these innovative markets will enable pharmacists to increase revenue as they enhance and expand their cognitive services for patients.
VBCI
: A Valence Bond Configuration Interaction Method that Includes Dynamic Correlation
Authors: Wu Wei , Song Lingchun , Zhang Qianer , Shaik Sason
Published: May 2004

Valence bond configuration interaction (VBCI) is introduced in this paper. The method adds the dynamic correlation contribution by use of configuration interaction (CI) following a VBSCF calculation. The VBCI method allows various approaches with different structure selection procedures. VBCIS involves only single excitations, while VBCISD involves also doubles, and so on. VBCI(D, S) includes doubly excited structures for the active electron shell and singly excited structures for inactive pairs. Using perturbation theory, VBCIPT truncates less important excitations and estimates their contribution by an approximate perturbation theoretic formula. The methods were tested by calculating the bond energies of H
2
, LiH, HF, HCl, F
2
, and Cl
2
as well as the barriers of identity hydrogen abstraction reactions, X• + X′H → XH + X′• (X, X′ = CH
3
, SiH
3
, GeH
3
, SnH
3
, PbH
3
). Test calculations show the VBCISD results match those of the MO‐based CCSD method. The computational results of VBCI(D, S) and VBCIPT match those of VBCISD with much less computational effort. As a demonstration of the potential of the VBCI method, we calculated the barrier of the hydrogen exchange reaction. The value of 10.0 kcal mol
−1
of the VBCI barrier is in very good agreement with the most accurate barrier of MO–based methods.
NMR
Scalar Couplings and Molecular Interactions
Authors: Barone Verónica , Peralta Juan E , Contreras Rubén H
Published: May 2004

In this work, a description is given of the possibilities that, at present, can be envisioned for using NMR scalar spin–spin couplings for studying molecular systems. Such possibilities are based both on the application of computational chemistry approaches to calculate them and on the using of modern experimental techniques to measure them. This article intends to be useful to scientists who are not familiar with the theoretical background of scalar couplings. The organization of this work proceeds as follows: First, a short description is given of the nucleus–electron magnetic interactions that originate these spectral parameters. Second, some comments on the current approaches to calculate them are quoted, and adequate references are given for readers interested in deepening their theoretical background. Third, the potential of scalar couplings to study inter‐ and intramolecular interactions is illustrated. This is accomplished by discussing how the Fermi contact contribution to

${}^{1}J_{\rm CH}$

as well as to several types of
geminal
scalar couplings is influenced by hyperconjugative interactions. A qualitative analysis is presented for geminal couplings involving nuclei of lone‐pair–bearing atoms in order to explain under which conditions their paramagnetic spin‐orbital contribution could be substantial. Two different examples are presented in which, for similar configurations of lone pairs, the roles played by such lone pairs in coupling transmission are quite different.
The Hamiltonian particle‐mesh method for the spherical shallow water equations
Authors: Frank J. , Reich S.
Published: May 2004

The Hamiltonian particle‐mesh (HPM) method is generalized to the spherical shallow‐water equations, utilizing constrained particle dynamics on the sphere and Merilees pseudospectral method (complexity 𝒪(J2logJ) in the latitudinal gridsize) to approximate the inverse modified Helmholtz regularization operator. The time step for the explicit, symplectic integrator depends only on a uniform physical smoothing length. Copyright © 2004 Royal Meteorological Society
Ten-year experience of carbon dioxide laser ablation as treatment for cutaneous recurrence of malignant melanoma
Authors: Gibson S C , Byrne D S , McKay A J
Published: May 2004

Background

Cutaneous recurrence of malignant melanoma is distressing for the patient, can be difficult to palliate and is resistant to treatment by conventional methods. Experience with carbon dioxide laser ablation was reviewed to determine the initial efficacy, time to recurrence, number of treatments required and length of palliation achieved.

Methods

Using a departmental database and case notes, a review was carried out of all patients undergoing laser ablation in the authors' unit between September 1992 August 2002.

Results

Forty-two patients received 105 (mean 2·5) treatments. The median time to recurrence was 5·2 (range 1·2–72·0) months. Twenty-three patients were still alive, with a median time from first laser ablation of 5·4 (range 0·5–10·0) years. Nineteen patients had died, a median of 0·8 (range 0·1–5·3) years after the first ablation. Ten of the 23 patients were disease-free for more than 1 year. No limbs were amputated because of failure to control disease.

Conclusion

Laser ablation is a practical and useful method of palliating recurrent cutaneous malignant melanoma.
Randomized clinical trial of the effect of pneumoperitoneum on cardiac function and haemodynamics during laparoscopic cholecystectomy
Authors: Larsen J F , Svendsen F M , Pedersen V
Published: May 2004

Background

Conventional laparoscopic cholecystectomy (CLC) with carbon dioxide pneumoperitoneum may cause major cardiovascular changes. The aim of this study was to evaluate the effect of carbon dioxide pneumoperitoneum and positional changes on haemodynamics and cardiac function in patients assigned randomly to CLC or gasless laparoscopic cholecystectomy (GLC).

Methods

Fifty patients with American Society of Anesthesiologists physical status I and II were randomly allocated to CLC (28 patients) or GLC (22). Left ventricular end-diastolic and end-systolic diameters, fractional shortening and cardiac output were determined by transoesophageal echocardiography. Measurements were performed before (phase 1) and 10 and 30 min (phases 2 and 3 respectively) after pneumoperitoneum or abdominal wall traction, and after desufflation or release of abdominal wall traction (phase 4) in supine, Trendelenburg and reverse Trendelenburg positions.

Results

Mean diastolic diameter, systolic diameter, mean arterial pressure and heart rate were significantly higher, and fractional shortening was significantly lower, with carbon dioxide pneumoperitoneum than with the gasless procedure during phases 2 and 3. There were no significant differences in cardiac output between the two groups.

Conclusion

Carbon dioxide pneumoperitoneum was associated with increased preload and afterload in patients undergoing laparoscopic cholecystecomy. It also decreased heart performance (fractional shortening), but did not affect cardiac output.
Reactive Ion Surface Scattering as an Eley–Rideal Process: A Molecular Dynamics Study into the Abstraction Reaction Mechanism by Low Energy Cs+ From Pt(111)
Authors: Lahaye Rob J. W. E. , Kang Heon
Published: May 2004

We have employed a classical molecular dynamics simulation for the direct pick‐up reaction of adsorbates by very low energy (1–60 eV) ions scattered at a surface. The system investigated is the reactive ion scattering (RIS) of Cs+ with an adsorbate on a Pt(111) surface. The ion–dipole attraction between the projectile and the physisorbed adsorbate drives the abstraction reaction, in which the ion projectile at first collides with the surface to release a substantial amount of its kinetic energy, and subsequently pulls the adsorbate along in the outgoing trajectory. Desorption induced by the ion–dipole attraction is a precursor to the formation of the Cs+–adsorbate product. This Eley–Rideal‐type mechanism must accommodate the inertia of the adsorbate. Consequently, a successful abstraction works well only for low mass adsorbates and slow outgoing Cs+ ions. The efficient energy transfer to the Pt(111) surface makes Cs+ a better candidate for RIS than lighter projectile ions. Optimal conditions for the efficient RIS abstraction mechanism are found for physisorbed adsorbates with a mass below 32 amu, and for 10 eV Cs+ ions at a 45° incidence.
High‐performance liquid chromatography and capillary electrophoresis: Methodological challenges for the determination of biologically relevant low‐aliphatic aldehydes in human saliva
Authors: Annovazzi Laura , Cattaneo Vitaliano , Viglio Simona , Perani Eleonora , Zanone Chiara , Rota Chiara , Pecora Fabio , Cetta Giuseppe , Silvestri Maurizio , Iadarola Paolo
Published: May 2004

Tobacco smoke is involved in the pathogenesis of cardiovascular and respiratory diseases and also has a local toxic effect in the oral cavity. Low‐aliphatic aldehydes, such as formaldehyde, acetaldehyde and acrolein, are among the main components of mainstream cigarette smoke and their local noxious and carcinogenic effects in the oral cavity and upper gastrointestinal tract are well‐known. Although various studies have been performed so far to determine their content in cigarette smoke, none has included the direct measurement of these compounds in the saliva of smoking and nonsmoking subjects. Thus, in an attempt to verify whether typical chromatographic (high‐performance liquid chromatography, HPLC) and/or electrophoretic (capillary electrophoresis, CE) techniques could be reliable methods for determining the levels of these analytes in human saliva, we submitted specimens obtained from a selected population of heavy, moderate, and nonsmoking subjects to HPLC and CE analyses. Both methods showed good reproducibility in terms of migration times and peak height and/or areas and had comparable linearity. Quantitative analyses performed on the specimens investigated evidenced a 3.5‐fold increase of low‐aliphatic aldehydes in saliva of nonsmoking subjects after they have smoked a single cigarette and a further 2‐fold increase of these compounds in saliva of smokers with a daily consumption of 10 or more cigarettes.
Low‐molecular‐weight human serum proteome using ultrafiltration, isoelectric focusing, and mass spectrometry
Authors: Harper Robert G. , Workman Sarah R. , Schuetzner Shayne , Timperman Aaron T. , Sutton Jennifer N.
Published: May 2004

Identification of the serum proteome is a daunting analytical task due to the complex nature of the sample which has an extremely large dynamic range of protein components. This report addresses this issue by using centrifugal ultrafiltration to enrich the low‐molecular‐weight (LMW) serum proteome while decreasing the amount of abundant high‐molecular‐weight proteins. Reduction of the complex nature of the sample was achieved by fractionation of the LMW serum proteins using solution‐phase isoelectric focusing (IEF). Multiple enzyme digestions are performed and analyzed by liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). Analysis of the tandem mass spectra resulted in the identification of 262 proteins belonging to LMW serum proteome. Our results demonstrate the effectiveness of this methodology to isolate and identify LMW proteins with improved confidence in the MS data acquired. In addition, our methodology can be combined with other multidimensional chromatography techniques performed on the peptide level to increase the number of identified proteins.
Proteomic analysis of detergent‐resistant membrane rafts
Authors: Blonder Josip , Hale Martha L. , Lucas David A. , Schaefer Carl F. , Yu Li‐Rong , Conrads Thomas P. , Issaq Haleem J. , Stiles Bradley G. , Veenstra Timothy D.
Published: May 2004

A combined, detergent‐ and organic solvent‐based proteomic method for the analysis of detergent‐resistant membrane rafts (DRMR) is described. These specialized domains of the plasma membrane contain a distinctive and dynamic protein and/or lipid complement, which can be isolated from most mammalian cells. Lipid rafts are predominantly involved in signal transduction and adapted to mediate and produce different cellular responses. To facilitate a better understanding of their biology and role, DRMR were isolated from Vero cells as a Triton X‐100 insoluble fraction. After detergent removal, sonication in 60% buffered methanol was used to extract, solubilize and tryptically digest the resulting protein complement. The peptide digestate was analyzed by microcapillary reversed‐phase liquid chromatography‐tandem mass spectrometry. Gas‐phase fractionation in the mass‐to‐charge range was employed to broaden the selection of precursor ions and increase the number of identifications in an effort to detect less abundant proteins. A total of 380 proteins were identified including all known lipid raft markers. A total of 91 (24%) proteins were classified as integral α‐helical membrane proteins, of which 51 (56%) were predicted to have multiple transmembrane domains.
Quantitative proteomic analysis of inorganic phosphate‐induced murine MC3T3‐E1 osteoblast cells
Authors: Conrads Kelly A. , Yu Li‐Rong , Lucas David A. , Zhou Ming , Chan King C. , Simpson Kerri A. , Schaefer Carl F. , Issaq Haleem J. , Veenstra Timothy D. , Beck George R. , Conrads Thomas P.
Published: May 2004

Cleavable isotope‐coded affinity tag (cICAT) reagents were utilized to identify and quantitate protein expression differences in control and inorganic phosphate‐treated murine MC3T3‐E1 osteoblast cells. Proteins extracted from control and treated cells were labeled with the light and heavy isotopic versions of cICAT reagents, respectively. The cICAT‐labeled samples were combined, proteolytically digested, and the cICAT‐derivatized peptides isolated using immobilized avidin chromatography. The cICAT‐labeled peptides were resolved into 96 fractions by strong cation‐exchange (SCX) liquid chromatography (LC). Analysis of the SCX‐LC cICAT peptide fractions by microcapillary reversed‐phase LC‐tandem mass spectrometry resulted in the identification and quantitation of 7227 unique peptides corresponding to 2501 proteins, or roughly 9% of the proteins currently predicted to be encoded by the mouse genome. A false positive analysis indicated a 98% confidence in the peptide identifications. To corroborate changes in abundance measured by cICAT with those detectable in traditionally prepared cell lysate, we chose to analyze cyclin D1. Cyclin D1 has been previously identified as a phosphate‐responsive gene and was likewise identified as a phosphate‐responsive protein in the current analysis. The 1.76‐fold increase in abundance in cyclin D1 determined from cICAT corresponds well with the 2.41‐fold increase as determined by Western blotting. These results demonstrate that quantitative proteomics is capable of providing a quantitative view of thousands of proteins in mammalian cells within a defined set of experiments.
Open‐tubular electrochromatographic characterization of synthetic peptides
Authors: Pesek Joseph J. , Matyska Maria T. , Dawson G. Brent , Chen Jenny I‐Chen , Boysen Reinhard I. , Hearn Milton T. W.
Published: May 2004

The open‐tubular electrochromatographic (OT‐CEC) migration behavior of a series of peptides, based on a common structural feature, has been characterized using two different types of chemically modified etched capillaries. The organic moieties immobilized onto the capillary inner surface were n‐butylphenyl and cholesterol‐10‐undecenaoate, respectively. The structure‐migration behavior of this set of peptides has been studied at several pH values and with methanol at different concentrations as an organic solvent modifier of the buffer electrolyte composition. By comparing the structural properties of the peptides, such as their amino acid sequences, charge‐to‐mass ratios and intrinsic hydrophobicities to their migrational behavior, the relative contribution of electrophoretic and chromatographic mobility to the overall migration times, elution order, and selectivity has been determined. Moreover, the experimental data provide important insight into procedures that can be used to modulate the separation of peptides in OT‐CEC through variation of the composition of the electrolyte buffer as well as via the properties of the bonded organic moiety.
Product stewardship in the flame retardant industry
Authors: TerHaar Gary L.
Published: May 2004

The products of the flame retardant industry are very important to the fire safety of the consumer. As with any product, there are issues that must be addressed by the producers and users to ensure the continued safe use of the materials. While most flame retardants are quite nonreactive and of low toxicity, the presence of them in the environment could threaten their future use. The producers and users alike should have the goal of keeping them out of the air, water and land. To this end, an aggressive product stewardship program is in order. This paper will review the steps needed to have a meaningful program. This activity should include evaluating the amount of material entering the air, water and land, deciding how to reduce that amount, putting in place practices to reduce the level and reporting to our stakeholders. By working together as producers and users, we can ensure that flame retardants will continue to save lives and have a long commercial future. Copyright © 2004 John Wiley & Sons, Ltd.
Flame retardancy of nanocomposites
Authors: Okoshi Masayuki , Nishizawa Hitoshi
Published: May 2004

Nishizawa Technical Institute (NTI) and Kyoto Institute of Technology (KIT) have developed EVA‐clay nanocomposites with excellent mechanical and flame retardant properties by a reactive process and have succeeded in a novel method to synthesize an aluminium hydroxide nanoparticle, which has the effect of improving the flame retardancy of nanocomposites with EVA. About the EVA‐clay nanocomposites, the peak heat release rate (HRR) of sample MM2 (EVA‐clay partially processed nanocomposites) and sample MM3 (EVA‐clay completely processed nanocomposites) was reduced from 1/3 (one third) to 1/4 (one fourth) compared with EVA only. Sample AL‐1 (EVA‐aluminium nanocomposites) showed a more effective reduction of HRR than sample AL‐2 (EVA‐normal aluminium hydroxide). Beside these experiments, the orientation of the nanofiller MMT (montmorillonite) by a 2‐axis extruder equipped a special novel kneading roll head and the flame retardancy of silica nanocomposite coating materials (Sol‐Gel process) is discussed. Copyright © 2004 John Wiley & Sons, Ltd.
Parallel‐in‐time simulation of the unsteady Navier–Stokes equations for incompressible flow
Authors: Trindade J. M. F. , Pereira J. C. F.
Published: May 2004

In this paper, we present an application of a parallel‐in‐time algorithm for the solution of the unsteady Navier–Stokes model equations that are of parabolic–elliptic type. This method is based on the alternated use of a coarse global sequential solver and a fine local parallel one. A standard finite volume/finite differences first‐order approach is used for discretization of the unsteady two‐dimensional Navier–Stokes equations. The Taylor vortex decay problem and the confined flow around a square cylinder were selected as unsteady flow examples to illustrate and analyse the properties of the parallel‐in‐time method through numerical experiments. The influence of several parameters on the computing time required to perform a parallel‐in‐time calculation on a PC cluster was verified. Among them we have analysed the influence of the number of processors, the number of iterations for convergence, the resolution of the spatial domain and the influence of the time‐step sizes ratio between the coarse and fine grids. Significant computer time saving was achieved when compared with the single processor computing time, particularly when the spatial dimension of the problem is low and the temporal scale is large. Copyright © 2004 John Wiley & Sons, Ltd.
On the structural age of the Rhoscolyn antiform, Anglesey, North Wales
Authors: Hassani Hossein , Covey‐Crump Stephen J. , Rutter Ernest H.
Published: May 2004

In the Rhoscolyn area of Anglesey, the late Precambrian interbedded psammites and pelites of the Monian Supergroup are folded into a kilometre‐scale antiform, plunging about 25°NE and with an axial surface dipping about 40°NW. Numerous folds of up to a few tens of metres in wavelength are present on both limbs of this antiform. These smaller‐scale folds also plunge about 25°NE but clearly belong to two separate episodes of folding, and it has become a matter of longstanding controversy as to whether the larger antiform belongs to the first or second of these episodes. Close examination of the cleavage/bedding asymmetries from all the lithologies, however, shows that the large antiform is a second‐generation structure, and that on the gently dipping northwest limb, the sense of cleavage/bedding asymmetry of the earlier cleavage in the psammitic units has been almost uniformly and homogeneously reversed (so that it appears to be axial planar to the antiform), while in the pelitic units the sense of cleavage/bedding asymmetry of the earlier cleavage has been preserved. Many of the small‐scale complexities of the observed cleavage/bedding relationships may be explained by appealing to differences in the timing of the formation of buckling instabilities relative to this reorientation of the early cleavage in the psammites during the second deformation. A first‐order analysis of the finite strains from around the large‐scale antiform shows that the orientation of the first cleavage prior to the second deformation was steeply dipping to the southeast. The second deformation correlates with the southeast‐verging Caledonian deformation affecting the Monian and Ordovician units elsewhere in northwest Anglesey, while the northwest‐verging first deformation event, which is not present in the Ordovician rocks, must have occurred before they were deposited. Copyright © 2004 John Wiley & Sons, Ltd.
Major neotectonic features of eastern Marmara region, Turkey: development of the Adapazarı–Karasu corridor and its tectonic significance
Authors: Yi̇ği̇tbaş Erdi̇nç , Elmas Ali̇ , Sefunç Ati̇lla , Özer Naşi̇de
Published: May 2004

Eastern Marmara region consists of three different morphotectonic units: Thrace–Kocaeli Peneplain (TKP) and Çamdağ–Akçakoca Highland (ÇAH) in the north, and Armutlu–Almacık Highland in the south of the North Anatolian Fault Zone (NAFZ). The geologic‐morphologic data and seismic profiles from the Sakarya River offshore indicate that the boundary between the TKP in the west and ÇAH in the east is a previously unrecognized major NNE–SSW‐trending strike‐slip fault zone with reverse component. The fault zone is a distinct morphotectonic corridor herein named the Adapazarı–Karasu corridor (AKC) that runs along the Sakarya River Valley and extends to its submarine canyon along the southern margin of the Black Sea in the north. It formed as a transfer fault zone between the TKP and ÇAH during the Late Miocene; the former has been experiencing extensional forces and the latter compressional forces since then. East–West‐trending segments of the NAFZ cuts the NE–SW‐trending AKC and their activity has resulted in the formation of a distinct fault‐bounded morphology, which is characterized by alternating E–W highlands and lowlands in the AKC. Furthermore, this activity has resulted in the downward motion of an ancient delta and submarine canyon of the Sakarya River in the northern block of the NAFZ below sea level so that the waters of the Black Sea invaded them. The NE–SW‐trending faults in the AKC were reactivated with the development of the NAFZ in the Late Pliocene, which then caused block motions and microseismic activities throughout the AKC. Copyright © 2004 John Wiley & Sons, Ltd.
Telomerase as an independent prognostic factor in head and neck squamous cell carcinoma
Authors: Liao Chun‐Ta , Tung‐Chieh Chang Joseph , Wang Hung‐Ming , Chen I‐How , Lin Chien‐Yu , Chen Tsung‐Ming , Hsieh Ling‐Ling , Cheng Ann‐Joy
Published: May 2004

Background.

Telomerase activity has been found to be associated with many cancers, including head and neck squamous cell carcinoma (HNSCC). We examined the association of telomerase activity with the clinical outcome of patients with HNSCC.

Methods.

A PCR‐based enzyme immunoassay method was used to measure telomerase activity in 217 matched (grossly normal and cancerous) tissues from patients with HNSCC. Pearson chi‐square test was used to analyze the correlation of telomerase activity with clinicopathologic parameters. Kaplan‐Meier method and Cox logistic regression model were used for prognostic analysis.

Results.

Of the 217 tissues assayed, 4.1% of the normal and 63.3% of the cancer tissues had high levels of telomerase activity. Telomerase activity was shown to be statistically correlated with extracapsule spreading (ECS) of lymph nodes (p = .005) and overall survival (p = .003). On multivariant analysis, overall stage (p = .007), tumor depth (p = .045), and telomerase activity (p = .008) showed independent variables associated with poor survival.

Conclusions.

Telomerase activity has been shown to be an independent prognostic factor for survival in cases of HNSCC. Telomerase may be a potential molecular target for clinical use in prognostication and therapy in cases of the disease. © 2004 Wiley Periodicals, Inc. Head Neck 26: XXX–XXX, 2004
Depression in the early postpartum period and attachment to children—in mothers of NICU infants
Authors: Nagata Masako , Nagai Yukiyo , Sobajima Hisanori , Ando Tsunesaburo , Honjo Shuji
Published: May 2004

Depression in early puerperium was evaluated in terms of maternal attachment in mothers of children admitted to the neonatal intensive care unit (NICU) in comparison to a control group of mothers of full‐term infants.

A survey including Zung's self‐rating depression scale (ZSDS), a postpartum maternal attachment scale and items addressing the mother's feelings and peripheral conditions was conducted on mothers of children admitted to the NICU.

Among the 153 mothers who gave valid responses, positive ZSDS scores of over 40 were seen in 61.8%. In terms of the children's disorder, strong depressive tendency was noted among mothers of low birth weight infants. Significant correlation was noted between the ZSDS and the ‘core maternal attachment’ (negative correlation) and ‘anxiety regarding children’ (positive correlation) subscales of postpartum maternal attachment. Path analysis revealed the father's positive reaction in learning of the pregnancy resulted in elevation of the ‘core maternal attachment’ score, in contrast to the control group mothers. Copyright © 2003 John Wiley & Sons, Ltd.
The influence of intercalator binding on DNA triplex stability: correlation with effects on A‐tract duplex structure
Authors: Sandström Karin , Wärmländer Sebastian , Bergman Jan , Engqvist Robert , Leijon Mikael , Gräslund Astrid
Published: May 2004

The triplex form of DNA is of interest because of a possible biological role as well as the potential therapeutic use of this structure. In this paper the stabilizing effects of two intercalating drugs, ethidium and the quinoxaline derivative 9‐OH‐B220, on DNA triplexes have been studied by thermal denaturation measurements. The corresponding duplex structures of the DNA triplex systems investigated are either A‐tract or normal B‐DNA. The largest increases in the triplex melting temperatures caused by the intercalators were found for sequences having A‐tract duplex structures. Inserting a single base pair with an N2‐amino group in the minor groove, e.g. a G–C pair, breaks up the A‐tract duplex structure and also reduces the stabilizing effect of the drugs on the triplex melting temperatures. The large drug‐induced increase in triplex melting temperature for complexes having an original duplex A‐tract structure is correlated with a low initial melting point of the triplex, not with the triplex being unusually stable in the presence of the drug. Hence, we conclude that the large thermal stabilizing effect exhibited by ethidium and 9‐OH‐B220 on dTn·dAn–dTn triplexes is partly caused by the intercalators breaking up the intrinsic A‐tract structure of the underlying duplex. Copyright © 2004 John Wiley & Sons, Ltd.
A novel mammalian display system for the selection of protein–protein interactions by decoy receptor engagement
Authors: Ellmark Peter , Ohlin Mats , Borrebaeck Carl A. K. , Furebring Christina
Published: May 2004

The emerging field of proteomics has created a need for new high‐throughput methodologies for the analysis of gene products. An attractive approach is to develop systems that allow for clonal selection of interacting protein pairs from large molecular libraries. In this study, we have characterized a novel approach for identification and selection of protein–protein interactions, denoted SPIRE (selection of protein interactions by receptor engagement), which is based on a mammalian expression system. We have demonstrated proof of concept by creating a general plasma membrane bound decoy receptor, by displaying a protein or a peptide genetically fused to a trunctated version of the CD40 molecule. When this decoy receptor is engaged by a ligand to the displayed protein/peptide, the receptor expressing cell is rescued from apoptosis. To design a high‐throughput system with a highly parallel capacity, we utilized the B cell line WEHI‐231, as carrier of the decoy receptor. One specific peptide‐displaying cell could be identified and amplified, based on a specific receptor engagement, in a background of 12 500 wild‐type cells after four selections. This demonstrates that the approach may serve as a tool in post‐genomic research for identifying protein–protein interactions, without prior knowledge of either component. Copyright © 2004 John Wiley & Sons, Ltd.
Structural basis of light chain amyloidogenicity: comparison of the thermodynamic properties, fibrillogenic potential and tertiary structural features of four Vλ6 proteins
Authors: Wall Jonathan S. , Gupta Vibha , Wilkerson Matthew , Schell Maria , Loris Remy , Adams Paul , Solomon Alan , Stevens Fred , Dealwis Chris
Published: May 2004

Primary (AL) amyloidosis results from the pathologic deposition of monoclonal light chains as amyloid fibrils. Studies of recombinant‐derived variable region (VL) fragments of these proteins have shown an inverse relationship between thermodynamic stability and fibrillogenic potential. Further, ionic interactions within the VL domain were predicted to influence the kinetics of light chain fibrillogenicity, as evidenced from our analyses of a relatively stable Vλ6 protein (Jto) with a long range electrostatic interaction between Asp and Arg side chains at position 29 and 68, respectively, and an unstable, highly fibrillogenic Vλ6 protein (Wil) that had neutral amino acids at these locations. To test this hypothesis, we have generated two Jto‐related mutants designed to disrupt the interaction between Asp 29 and Arg 68 (JtoD29A and JtoR68S). Although the thermodynamic stabilities of unfolding for these two molecules were identical, they exhibited very different kinetics of fibril formation: the rate of JtoD29A fibrillogenesis was slow and comparable to the parent molecule, whereas that of JtoR68S was significantly faster. High‐resolution X‐ray diffraction analyses of crystals prepared from the two mutants having the same space group and unit cell dimensions revealed no significant main‐chain conformational changes. However, several notable side‐chain alterations were observed in JtoR68S, as compared with JtoD29A, that resulted in the solvent exposure of a greater hydrophobic surface and modifications in the electrostatic potential surface. We posit that these differences contributed to the enhanced fibrillogenic potential of the Arg 68 mutant, since both Jto mutants lacked the intrachain ionic interaction and were equivalently unstable. The information gleaned from our studies has provided insight into structural parameters that in addition to overall thermodynamic stability, contribute to the fibril forming propensity of immunoglobulin light chains. Copyright © 2004 John Wiley & Sons, Ltd.
Synthetic peptide vaccine development: measurement of polyclonal antibody affinity and cross‐reactivity using a new peptide capture and release system for surface plasmon resonance spectroscopy
Authors: Cachia Paul J. , Kao Daniel J. , Hodges Robert S.
Published: May 2004

A method has been developed for measurement of antibody affinity and cross‐reactivity by surface plasmon resonance spectroscopy using the EK‐coil heterodimeric coiled‐coil peptide capture system. This system allows for reversible capture of synthetic peptide ligands on a biosensor chip surface, with the advantage that multiple antibody‐antigen interactions can be analyzed using a single biosensor chip. This method has proven useful in the development of a synthetic peptide anti‐Pseudomonas aeruginosa (PA) vaccine. Synthetic peptide ligands corresponding to the receptor binding domains of pilin from four strains of PA were conjugated to the E‐coil strand of the heterodimeric coiled‐coil domain and individually captured on the biosensor chip through dimerization with the immobilized K‐coil strand. Polyclonal rabbit IgG raised against pilin epitopes was injected over the sensor chip surface for kinetic analysis of the antigen‐antibody interaction. The kinetic rate constants, k(on) and k(off), and equilibrium association and dissociation constants, KA and KD, were calculated. Antibody affinities ranged from 1.14 × 10−9 to 1.60 × 10−5 M. The results suggest that the carrier protein and adjuvant used during immunization make a dramatic difference in antibody affinity and cross‐reactivity. Antibodies raised against the PA strain K pilin epitope conjugated to keyhole limpet haemocyanin using Freund's adjuvant system were more broadly cross‐reactive than antibodies raised against the same epitope conjugated to tetanus toxoid using Adjuvax adjuvant. The method described here is useful for detailed characterization of the interaction of polyclonal antibodies with a panel of synthetic peptide ligands with the objective of obtaining high affinity and cross‐reactive antibodies in vaccine development. Copyright © 2004 John Wiley & Sons, Ltd.
Remote weather associated with South Pacific subtropical sea‐level high properties
Authors: Grotjahn Richard
Published: May 2004

The subtropical highs in sea‐level pressure (SLP) are little studied and incompletely understood. In recent years, three groups of theories, i.e. tropical divergent circulations, subtropical Rossby wavetrains, and midlatitude frontal cyclone interactions, have been proposed for remote maintenance of these highs. The latter is presented here as a remote forcing of these highs for the first time in the reviewed literature. The focus of the study is upon illuminating associations between these mechanisms and the South Pacific subtropical high in SLP (SP high). Precipitation, outgoing longwave radiation, velocity potential, and divergent winds are used as proxy markers for the remote forcing mechanisms. The tools used include composites, one‐point correlations, autocorrelations, cross‐correlations, and cross‐spectra. Observational evidence, in monthly and daily data, is examined that appears to support each mechanism. Associations seen in monthly data are better understood in daily data at various lags. Convection over Amazonia, coordinated with suppressed convection in the western tropical Pacific, leads to enhanced SLP on the tropical side of the high. Midlatitude weather systems are the strongest influence upon the maximum SLP and the SLP on the higher latitude side of the high. The western side is associated with both middle‐and lower‐latitude phenomena, such as the South Pacific convergence zone. Various properties of the high have a strong period around 45 days. Associations to the Madden–Julian oscillation and El Niño–southern oscillation are explored and are strong only for the tropical side of the SP high. Copyright © 2004 Royal Meteorological Society