bluuebunny/crossref_metadata_2025_split huggingface dataset:
Steroid sulfatase inhibitors
Authors: Nussbaumer Peter , Billich Andreas 
Published: April 2004

AbstractSteroid sulfatase (STS) regulates the local production of estrogens and androgens from systemic precursors in several tissues. The enzyme catalyzes the hydrolysis of the sulfate esters of 3‐hydroxy steroids, which are inactive transport or precursor forms of the active 3‐hydroxy steroids. STS inhibitors are expected to block the local production and, consequently, to reduce the local levels of the hormones. Therefore, they are considered as potential new therapeutic agents for the treatment of estrogen‐ and androgen‐dependent disorders. Indications range from cancers of the breast, endometrium and prostate to androgenetic alopecia and acne. In this review, we give a comprehensive summary of the current knowledge and problems in the field of medicinal chemistry of STS inhibitors. The various types of inhibitors are presented and their structure‐activity relationships are discussed. In addition to potent arylsulfamate‐based, irreversible inhibitors, novel types of reversible inhibitors were recently discovered. The recent publication of the X‐ray structure of STS will further boost research activities on this attractive target. © 2004 Wiley Periodicals, Inc. Med Res Rev, 24, No. 4, 529–576, 2004
Physician adherence to recommendations for duration of empiric antibiotic treatment for uncomplicated urinary tract infection in women: a national drug utilization analysis
Authors: Kahan Natan R. , Chinitz David P. , Kahan Ernesto 
Published: April 2004

AbstractBackgroundCurrent guidelines for the empiric treatment of uncomplicated urinary tract infection in women recommend that first‐line trimethoprim‐sulfamethoxazole (TMP‐SMX) or ofloxacin be given for 3 days and nitrofurantoin for 5 days. Increasing the duration of treatment raises costs, and perhaps, the incidence of adverse effects, without contributing to effectiveness. The aim of this study was to investigate physician adherence to these recommendations.MethodsThe electronic patients record system of a nationwide health management organization in Israel was reviewed for all primary care visits by adult women treated empirically for cystitis or urinary tract infection from January 2001 to June 2002 (n = 7738 patient–physician encounters). The proportion of cases treated according to the guidelines, with regard to duration, was calculated for each drug used.ResultsRate of adherence was 3.36% for cases of TMP‐SMX treatment (95%CI: 2.56%, 4.15%), 22.23% for nitrofurantoin (95%CI: 19.81%, 24.65%) and 4.08% for ofloxacin (95%CI: 2.88%, 5.28%). The crude rate of adherence for all cases of treatment with these drugs was 8.67% (95%CI: 7.82%, 9.52%).ConclusionsThe high rate of nonadherence observed (91.33%) indicate a need for a remedial education program for physicians to improve empiric treatment of urinary tract infection in women. Since this issue is of global importance, we believe our evaluation can serve as model for other settings and countries. Copyright © 2003 John Wiley & Sons, Ltd.
Potential savings from increased use of generic drugs in the elderly: what the experience of Medicaid and other insurance programs means for a Medicare drug benefit
Authors: Fischer Michael A. , Avorn Jerry 
Published: April 2004

AbstractBackgroundGeneric medications provide the same clinical effect at lower cost than brand name drugs but little is known about the extent to which such savings are achieved in drug benefit programs serving the elderly.MethodsUsing patient‐level claims data for participants aged 65 or more in one state Medicaid program and in a non‐Medicaid drug insurance program for the elderly, we compared the expenditures in each program for brand name prescriptions with the amount that would have been paid for generic versions of the same agents. We then estimated potential savings from increased use of substitutable brand name drugs.ResultsThere was an unrealized annual savings of $3.4 million (3.6% of total drug expenditure) in the Medicaid program studied and $13.7 million (9.5% of total drug expenditure) in the non‐Medicaid drug insurance program for the elderly, with corresponding reductions in mean annual per‐patient drug costs.ConclusionsMore widespread use of generic medications represents an important source of unrealized savings in drug coverage programs for the elderly. The Medicaid program limits the excess spending on brand name drugs by imposing pricing restrictions, but many non‐Medicaid programs could realize even larger savings from reducing the use of brand name drugs when identical generic products are available. These findings offer some insight into the potential expense of a Medicare prescription drug benefit. Copyright © 2003 John Wiley & Sons, Ltd.
Novel, biodegradable, functional poly(ester‐carbonate)s by copolymerization of trans‐4‐hydroxy‐L‐proline with cyclic carbonate bearing a pendent carboxylic group
Authors: Lee Ren‐Shen , Yang Jen‐Ming , Lin Tz‐Feng 
Published: April 2004

AbstractWater‐soluble poly(ester‐carbonate) having pendent amino and carboxylic groups on the main‐chain carbon is reported for the first time. This article describes the melt ring‐opening/condensation reaction of trans‐4‐hydroxy‐N‐benzyloxycarbonyl‐L‐proline (N‐CBz‐Hpr) with 5‐methyl‐5‐benzyloxycarbonyl‐1,3‐dioxan‐2‐one (MBC) at a wide range of molar fractions. The influence of reaction conditions such as catalyst concentration, polymerization time, and temperature on the number average molecular weight (Mn) and molecular weight distribution (Mw/Mn) of the copolymers was investigated. The polymerizations were carried out in bulk at 110 °C with 3 wt % stannous octoate as a catalyst for 16 h. The poly(ester‐carbonate)s obtained were characterized by Fourier transform infrared spectroscopy, 1H NMR, differential scanning calorimetry, and gel permeation chromatography. The copolymers synthesized exhibited moderate molecular weights (Mn = 6000–14,700 g mol−1) with reasonable molecular weight distributions (Mw/Mn = 1.11–2.23). The values of the glass‐transition temperature (Tg) of the copolymers depended on the molar fractions of cyclic carbonate. When the MBC content decreased from 76 to 12 mol %, the Tg increased from 16 to 48 °C. The relationship between the poly(N‐CBz‐Hpr‐co‐MBC) Tg and the compositions was in approximation with the Fox equation. In vitro degradation of these poly(N‐CBz‐Hpr‐co‐MBC)s was evaluated from weight‐loss measurements and the change of Mn and Mw/Mn. Debenzylation of 3 by catalytic hydrogenation led to the corresponding linear poly(ester‐carbonate), 4, with pendent amino and carboxylic groups. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 2303–2312, 2004
Facile synthesis of AB2‐type miktoarm star polymers through the combination of atom transfer radical polymerization and ring‐opening polymerization
Authors: Erdogan T. , Ozyurek Z. , Hizal G. , Tunca U. 
Published: April 2004

AbstractA novel miktofunctional initiator (1), 2‐hydroxyethyl 3‐[(2‐bromopropanoyl)oxy]‐2‐{[(2‐bromopropanoyl)oxy]methyl}‐2‐methyl‐propanoate, possessing one initiating site for ring‐opening polymerization (ROP) and two initiating sites for atom transfer radical polymerization (ATRP), was synthesized in a three‐step reaction sequence. This initiator was first used in the ROP of ϵ‐caprolactone, and this led to a corresponding polymer with secondary bromide end groups. The obtained poly(ϵ‐caprolactone) (PCL) was then used as a macroinitiator for the ATRP of tert‐butyl acrylate or methyl methacrylate, and this resulted in AB2‐type PCL–[poly(tert‐butyl acrylate)]2 or PCL–[poly(methyl methacrylate)]2 miktoarm star polymers with controlled molecular weights and low polydispersities (weight‐average molecular weight/number‐average molecular weight < 1.23) via the ROP–ATRP sequence. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 2313–2320, 2004
Distinguish protein decoys by Using a scoring function based on a new AMBER force field, short molecular dynamics simulations, and the generalized born solvent model
Authors: Lee Mathew C. , Duan Yong 
Published: April 2004

AbstractRecent works have shown the ability of physics‐based potentials (e.g., CHARMM and OPLS‐AA) and energy minimization to differentiate the native protein structures from large ensemble of non‐native structures. In this study, we extended previous work by other authors and developed an energy scoring function using a new set of AMBER parameters (also recently developed in our laboratory) in conjunction with molecular dynamics and the Generalized Born solvent model. We evaluated the performance of our new scoring function by examining its ability to distinguish between the native and decoy protein structures. Here we present a systematic comparison of our results with those obtained with use of other physics‐based potentials by previous authors. A total of 7 decoy sets, 117 protein sequences, and more than 41,000 structures were evaluated. The results of our study showed that our new scoring function represents a significant improvement over previously published physics‐based scoring functions. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Is histoaspartic protease a serine protease with a pepsin‐like fold?
Authors: Andreeva N. , Bogdanovich P. , Kashparov I. , Popov M. , Stengach M. 
Published: April 2004

AbstractThe primary structure of the so‐called histoaspartic protease from Plasmodium falciparum has a very high percentage of identity and homology with the pepsin‐like enzyme plasmepsin II. A homology modeling approach was used to calculate the three‐dimensional structure of the enzyme. Molecular dynamics (MD) simulations were applied to find those structural properties of the histoaspartic protease that had a tendency to remain stable during all runs. The results have shown that hydrogen‐bonded residues Ser37–His34–Asp214 are arranged without any strain, in a manner that resembles the active site of a serine protease, while Ser38 and Asn39 take up positions appropriate to formation of an oxyanion hole. Although there are several important differences between the enzyme and plasmepsin II, all of the structural features associated with a typical pepsin‐like aspartic protease are present in the final model of the histoaspartic protease. A possibility that this enzyme may function as a serine protease is discussed. Proteins 2004. © 2004 Wiley‐Liss, Inc.
The low barrier hydrogen bond (LBHB) proposal revisited: The case of the Asp ··· His pair in serine proteases
Authors: Schutz Claudia N. , Warshel Arieh 
Published: April 2004

AbstractThe fact that hydrogen bonds (HBs) can provide major stabilization to transition states (TSs) of enzymatic reactions is well known. However, the nature of HB stabilization has been the subject of a significant controversy. It is not entirely clear if this stabilization is associated with electrostatic effects of preorganized dipoles or with delocalized resonance effects of the so‐called low barrier hydrogen bond (LBHB). One of the best test cases for the LBHB proposal is the complex of chymotrypsin and trifluoromethyl ketone (TFK). It has been argued that the pKa shift in this system provides an experimental evidence for the LBHB proposal. However, this argument could not be resolved by experimental studies. Here we explore the nature of the Asp102–His57 pair in the chymotrypsin‐TFK complex by a systematic computational and conceptual study. We start by defining the LBHB proposal in a unique energy‐based way. We show that a consistent analysis must involve a description in terms of the energy of the two resonance structures and their mixing. It is clarified that LBHBs cannot be defined according to strength or distance, because ionic HBs can also be strong and short. Similarly, NMR chemical shifts and fractionation factors cannot be used to identify LBHBs in a conclusive way. It is also clarified that HBs with a significant asymmetry cannot be classified as LBHBs, because this contradicts the assumption of equal pKa of the donor and acceptor. Thus, the main issue is the ΔpKa and the corresponding energy difference. With this definition in mind, we calculate the free energy surface of proton transfer in this pair and evaluate the energetics of the different ionization states of this system. The calculations are done by both the semimacroscopic version of the protein dipoles Langevin dipoles (PDLD/S‐LRA) model and by the empirical valence bond (EVB) method. The calculations establish that the LBHB proposal is not valid in the chymotrypsin‐TFK complex and in other serine proteases. Although previous theoretical studies reached similar conclusion, this is the first time that the same set of free energy calculations reproduce all the known pKa values and pKa changes in the system, while evaluating the energetics and covalent character of the His–Asp system. The present study provides a support to the idea that enzymes work by creating a preorganized polar environment. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Structure‐based prediction of DNA‐binding sites on proteins Using the empirical preference of electrostatic potential and the shape of molecular surfaces
Authors: Tsuchiya Yuko , Kinoshita Kengo , Nakamura Haruki 
Published: April 2004

AbstractProtein–DNA interactions play an essential role in the genetic activities of life. Many structures of protein–DNA complexes are already known, but the common rules on how and where proteins bind to DNA have not emerged. Many attempts have been made to predict protein–DNA interactions using structural information, but the success rate is still about 80%. We analyzed 63 protein–DNA complexes by focusing our attention on the shape of the molecular surface of the protein and DNA, along with the electrostatic potential on the surface, and constructed a new statistical evaluation function to make predictions of DNA interaction sites on protein molecular surfaces. The shape of the molecular surface was described by a combination of local and global average curvature, which are intended to describe the small convex and concave and the large‐scale concave curvatures of the protein surface preferentially appearing at DNA‐binding sites. Using these structural features, along with the electrostatic potential obtained by solving the Poisson–Boltzmann equation numerically, we have developed prediction schemes with 86% and 96% accuracy for DNA‐binding and non‐DNA‐binding proteins, respectively. Proteins 2004. © 2004 Wiley‐Liss, Inc.
DRESS: a database of REfined solution NMR structures
Authors: Nabuurs Sander B. , Nederveen Aart J. , Vranken Wim , Doreleijers Jurgen F. , Bonvin Alexandre M.J.J. , Vuister Geerten W. , Vriend Gert , Spronk Christian A.E.M. 
Published: April 2004

AbstractSeveral studies have shown that biomolecular NMR structures are often of lower quality when compared to crystal structures, and consequently they are often excluded from structural analyses. We present a publicly available database of re‐refined NMR structures, exhibiting significantly improved quality. This database (available at http://www.cmbi.kun.nl/dress/) presents a uniformly refined and validated set of structural models that improves the value of these NMR structures as input for experimental and theoretical studies in many fields of research. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Primary events in dim light vision: a chemical and spectroscopic approach toward understanding protein/chromophore interactions in rhodopsin
Authors: Fishkin Nathan , Berova Nina , Nakanishi Koji 
Published: April 2004

AbstractThe visual pigment rhodopsin (bovine) is a 40 kDa protein consisting of 348 amino acids, and is a prototypical member of the subfamily A of G protein‐coupled receptors (GPCRs). This remarkably efficient light‐activated protein (quantum yield = 0.67) binds the chromophore 11‐cis‐retinal covalently by attachment to Lys296 through a protonated Schiff base. The 11‐cisgeometry of the retinylidene chromophore keeps the partially active opsin protein locked in its inactive state (inverse agonist). Several retinal analogs with defined configurations and stereochemistry have been incorporated into the apoprotein to give rhodopsin analogs. These incorporation results along with the spectroscopic properties of the rhodopsin analogs clarify the mode of entry of the chromophore into the apoprotein and the biologically relevant conformation of the chromophore in the rhodopsin binding site. In addition, difference UV, CD, and photoaffinity labeling studies with a 3‐diazo‐4‐oxo analog of 11‐cis‐retinal have been used to chart the movement of the retinylidene chromophore through the various intermediate stages of visual transduction. © 2004 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 4: 120–135; 2004: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.20000
Selective aerobic oxidation of hydroxy compounds catalyzed by photoactivated ruthenium‐salen complexes (selective catalytic aerobic oxidation)
Authors: Irie Ryo , Katsuki Tsutomu 
Published: April 2004

AbstractSelective oxidation of alcohols to the corresponding carbonyl compounds is one of the most fundamental reactions in organic synthesis. Traditional methods for this transformation generally rely on stoichiometric amount of oxidants represented by Cr(VI) or DMSO reagents, though their synthetic utility is encumbered by unpleasant waste materials. From ecological and atom‐economic viewpoints, catalytic aerobic oxidation is much more advantageous because molecular oxygen is ubiquitous and the byproduct is basically non‐toxic water or hydrogen peroxide. On the other hand, phenol derivatives undergo oxidative coupling, forming CC or CO bond, through radical intermediates coupled with an electron‐transfer process. Molecular oxygen is also well known to serve as electron acceptor in this reaction. Thus, a variety of transition metal complexes have so far been examined for aerobic oxidations of alcohols and phenols, and high catalytic activities have been achieved in some cases. However, stereo‐ and chemo‐selective aerobic oxidations are still limited in number and are of current interest. Presented in this paper is our recent studies on catalytic aerobic oxidations with photoactivated nitrosyl ruthenium‐salen complexes, including asymmetric oxidation of secondary alcohols to ketones (kinetic resolution), enantioselective oxidative coupling of 2‐naphthols to binaphthols and oxygen‐radical bicyclization of 2,2′‐dihydroxystilbene, chemoselective oxidation of primary alcohols to aldehydes and diols to lactols, and asymmetric desymmetrization of meso‐diols to lactols. © 2004 The Japan Chemical Journal Forum and John Wiley & Sons, Inc. Chem Rec 4: 96–109; 2004: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.20001
Prenatal sonographic appearance of congenital bile duct dilatation associated with renal‐hepatic‐pancreatic dysplasia
Authors: Boopathy Vijayaraghavan S. , Kamalam M. , Raman M. L. 
Published: April 2004

AbstractWe report the prenatal sonographic features of congenital bile duct dilatation associated with renal‐hepatic‐pancreatic dysplasia. The condition was seen at 22 weeks of gestation and led to termination of pregnancy. This is the first description of congenital bile duct dilatation using prenatal sonography. It is also the first report of a case in which the features of dysplasia were evident in all three of the organs which may be affected, the kidneys, liver and pancreas. Copyright © 2004 ISUOG. Published by John Wiley & Sons, Ltd.
Dünne ITO‐Schichten als leitfähige, transparente Elektroden. Thin films of ITO as conductive, transparent electrodes
Authors: Mergel Dieter 
Published: April 2004

AbstractThis article deals with materials science aspects of In2O3:Sn (“ITO”) coatings and with the process technology of variants of sputtering used to obtain thin films with properties desired for specific applications. As an example, antistatic and antireflective coatings of monitor tubes are presented. The influence of sputter parameters such as substrate temperature, plasma excitation mode, sputter pressure and oxygen partial pressure on the quality of the films is discussed. It is shown how application‐oriented basic research helps to obtain recipes for materials design. Two basic aspects are discussed in more detail: the influence of an oxygen surplus in the films on microstructure and electrical properties and the correlation of electrical and optical parameters of the films.
New Turbomolecular Pump with Central Opening for Free Axial Access. Eine neue Turbomolekularpumpe mit zentraler Öffnung für freien axialen Zugang
Authors: Mokler P.H. 
Published: April 2004

AbstractStandard Turbomolekularpumpen haben typischerweise eine kreisringförmige Ansaugöffnung auf der Hochvakuumseite (single‐flow pumps). Die zentrale innere Kreisfläche des Kompressoreingangs der Turbine ist inaktiv für den Pumpvorgang. Das neue Design schlägt eine zentrale Öffnung der Turbomolekularpumpe entlang der ganzen Achse vor. Die zentrale Öffnung kann zur Montage von Durchführungen, Manipulatoren, Fenstern usw. beziehungsweise zum Anschluss weiterer Vakuumeinrichtungen benutzt werden; insbesondere können auch rohrförmige Vakuumsysteme umschlossen werden. Das neue Design erlaubt ein mehrfaches Benutzen eines Pumpflansches einer Vakuumapparatur ohne dort die Pumpleistung zu reduzieren. Außerdem ist das vorgeschlagene Design ideal geeignet für axiale oder radiale differentielle Pumpanordnungen wie sie beispielsweise für alle Gasjet‐ähnlichen Apparaturen oder andere Druckreduktionsstufen benötigt werden.
Die Geschichte der Vakuumkühlung. The History of Vacuum Refrigeration
Authors: Bürger Heinz‐Dieter 
Published: April 2004

AbstractDie Ausnutzung der hohen Verdampfungsenthalpie des Wassers zum Abkühlen und somit Frischhalten von Lebensmitteln ist eine der ältesten, von Menschen eingesetzten Technologien überhaupt. Sie könnte eigentlich ihren 5000. Jahrestag feiern. Die Kühlung durch Verdunsten von Wasser von feuchten Oberflächen nennen wir heute adiabatische Kühlung, diese reguliert z. B. unsere Körpertemperatur beim Schwitzen. Vor 250 Jahren begann nach Einführung einiger Vakuumpumpen in den wissenschaftlichen Experimentalbetrieb in Grossbritannien die moderne Form der “künstlichen” Kühlung, die Verdampfung von Flüssigkeiten unter Abwesenheit von Permanentgasen im Vakuum. Die Vakuumkühlung mit Wasser als Kältemittel wurde ab 1850, also vor ca. 150 Jahren, nahezu jäh gestoppt, durch die Entwicklung von Kompressions‐Kältemaschinen. Seit Ende des 2. Weltkriegs begann eine Wiedereinführung der Vakuumkühlung, und nun, zu Beginn des 2. Jahrtausends stehen die Chancen gut, verlorenes Terrain wieder gutzumachen.