bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neural networks as data mining tools in drug design
Authors: Gasteiger Johann , Teckentrup Andreas , Terfloth Lothar , Spycher Simon 
Published: March 2003

AbstractNeural networks are powerful data mining tools with a wide range of applications in drug design. This paper largely concentrates on self‐organizing neural networks that can be used for investigating datasets both by unsupervised and by supervised learning. The representation of chemical structures is the key to success in establishing useful relationships. Applications are shown for exploring different structure representations, for establishing quantitative structure–activity relationships and for handling compounds having multicategory activities. The applications comprise the separation of compounds according to different biological activities, the location of biologically active compounds in large chemical spaces, the analysis of high‐throughput screening data and the classification of compounds according to mode of toxic action. Copyright © 2003 John Wiley & Sons, Ltd.
Synthesis and UV/Vis spectroscopic properties of new [2‐(N,N‐dialkylamino)‐1,3‐dithiolium‐4‐yl]phenolates
Authors: Birsa Mihail Lucian , Ganju Dumitru 
Published: March 2003

AbstractIn weak alkaline aqueous medium, 4‐(hydroxyphenyl)‐2‐(N,N‐dialkylamino)‐1,3‐dithiolium salts led to the corresponding dipolar betaines. These compounds were described as zwitterionic phenolates with an intramolecular charge‐transfer UV/Vis absorption and represent useful precursors for the preparation of the first 1,3‐dithiolium chlorides. Copyright © 2003 John Wiley & Sons, Ltd.
Effect of carbonyls on the reactivity of polyenes in autoxidation
Authors: Krasnokutskaya I. S. , Leontieva S. V. , Finkelshtein E. I. , Khodonov A. A. , Shvets V. I. 
Published: March 2003

AbstractAutoxidation of the biologically active polyenes β‐carotene, canthaxanthin, retinyl acetate, methyl retinoate, retinal and 3,7,11,11‐tetramethyl‐10,15‐dioxo‐2,4,6,8‐hexadecatetraenal (diketoretinal) in solid amorphous films was investigated. The course of the process was followed by electronic and IR spectroscopy. The overall activation energies were obtained. It was shown that insertion in the polyene molecule of a carbonyl group conjugated with polyene chain results in a drastic decrease in the reactivity towards molecular oxygen. The results are discussed and explained on the basis of radical stabilization energy, ES(R·), as a driving force of the autoxidation process. Semi‐empirical AM1 calculations of ΔHf of some retinyl polyenes and polyenyl radicals were carried out and the C—H bond strengths and ES(R·) values of corresponding polyenyl radicals were evaluated. It was shown that the incorporation of a carbonyl group in the polyene results in a decrease in the overall autoxidation rate due to the decrease in both the initiation and propagation rates. Copyright © 2003 John Wiley & Sons, Ltd.
Competing nature of intramolecular [4 + 2] and [3 + 2] cycloaddition reactions: a theoretical study
Authors: Ananikov Valentine P. 
Published: March 2003

AbstractComparative study of the intramolecular alkyne triple bond addition reaction to the conjugated ­C≡C—CHX moiety (X = CH2,O,S,NH) revealed that two different pathways are possible in the system, namely [4 + 2] and [3 + 2] cycloaddition reactions. The energetically preferred pathway for enynes (X = CH2) involves [4 + 2] cycloaddition leading to benzene derivatives, whereas heteroatom‐substituted substrates undergo [3 + 2] cycloaddition resulting in an five‐membered aromatic ring in the final product. This paper reports a detailed mechanistic study based on full potential energy surface calculations at the MP2 and B3LYP theory levels, with MP4(SDTQ) energy evaluation. The effect of solvent was included within the PCM approach. Copyright © 2003 John Wiley & Sons, Ltd.
Three power‐aware routing algorithms for sensor networks
Authors: Aslam Javed , Li Qun , Rus Daniela 
Published: March 2003

AbstractThis paper discusses online power‐aware routing in large wireless ad hoc networks (especially sensor networks) for applications in which the message sequence is not known. We seek to optimize the lifetime of the network. We show that online power‐aware routing does not have a constant competitive ratio to the off‐line optimal algorithm. We develop an approximation algorithm calledmax–minzPminthat has a good empirical competitive ratio. To ensure scalability, we introduce a second online algorithm for power‐aware routing. This hierarchical algorithm is called zone‐based routing. Our experiments show that its performance is quite good. Finally, we describe a distributed version of this algorithm that does not depend on any centralization. Copyright © 2003 John Wiley & Sons, Ltd.
Media access using dynamic bandwidth system to improve satellite network uplink performance
Authors: Foudriat Edwin C. , Maly Kurt J. , Olariu Stephan , Todorova Petia 
Published: March 2003

AbstractThe paper describes a media access system for satellite network uplinks. The media access protocol is designed to support a range of low‐level protocols using a dual‐framing system, that is, there is a synchronous traffic subframe in which registered station requests are assigned fixed blocks or slots and an asynchronous traffic subframe for unregistered station random access on a contention basis. Slots for the registered stations are assigned through request to the satellite; the remaining frame time is assigned to unregistered stations. Capacity waste through contention resulting in collisions is minimized. The system uses dynamic bandwidth (bit rate) allocation for each channel, that is, the base frequency and bandwidth are changed for each channel at frame boundaries. The total bandwidth for the sum of all uplink channels is fixed. Channels that have low load based upon their request in a prior uplink frame are assigned lower bandwidth, while those with higher loading are provided larger bandwidth. By sharing bandwidth over channels at frame boundaries, overall network efficiency and fairness are significantly enhanced. Bandwidth allocation is decided in the satellite. It allocates sufficient bandwidth for all synchronous traffic and then commits the remaining bandwidth to asynchronous traffic. Here, the allocation for asynchronous traffic provides each channel with sufficient slots so that equal probability of success for stations sharing the channel can be expected. The combination of traffic assignment and bandwidth allocation provides significant improvement in overall network efficiency and fairness for all traffic types. The hardware implementation of media access for variable bandwidth sharing between channels use the concepts of Digital Software Radio. Copyright © 2003 John Wiley & Sons, Ltd.
An Ecologically Differentiated, Multifactor Model of Adolescent Network Orientation
Authors: Barone Charles , Iscoe Ellen , Trickett Edison J. , Schmid Kathy D. 
Published: March 2003

AbstractThe paper presents a test of an ecologically differentiated model of social network orientation for adolescents that distinguished between different social network reference groups (family, peers, and nonfamily adults). The model was tested in two consecutive studies. Study 1 describes initial model development (N = 120). Study 2 presents a confirmatory factor analysis with a second sample (N = 430) to replicate the factor structure developed in Study 1. Results supported a three‐factor model of network orientation that differentiated between network reference groups. Analyses of concurrent and predictive validity indicated that orientation to network reference groups was differentially related to the perceived quality and frequency of support from members of respective social network groups. Group differences (gender, race) regarding network orientation to different network reference groups were consistent with studies of other social network processes. Implications for the study of the network orientation and the study of social networks more generally are discussed.
Clopidogrel but not aspirin reduces P‐selectin expression and formation of platelet‐leukocyte aggregates in patients with atherosclerotic vascular disease*
Authors: Klinkhardt Ute , Bauersachs Rupert , Adams Jan , Graff Jochen , Lindhoff‐Last Edeltraud , Harder Sebastian 
Published: March 2003

Formation of platelet‐leukocyte aggregates via the CD62 ligand represents an important mechanism by which leukocytes contribute to thrombotic events. In a cross‐sectional study, we investigated platelet‐leukocyte aggregate formation and markers indicative for platelet, leukocyte, and endothelial activation (CD62, activated fibrinogin receptor glycoprotein IIb/IIIA [PAC‐1], CD11b/CD18 [MAC‐1], and soluble intercellular adhesion molecule 1) in 44 patients with atherosclerotic vascular disease and peripheral occlusions receiving clopidogrel (n = 12), aspirin (n = 17), their combination (n = 8), or no treatment (n = 7), as well as in a group of healthy subjects (n = 9). Whole‐blood flow cytometry was performed before (baseline) and after stimulation with thrombin receptor‐activating peptide or adenosine diphosphate. Both at baseline and after stimulation, untreated patients and those receiving aspirin monotherapy exhibited significantly higher levels of platelet CD62 expression (baseline CD62: untreated, 22% [median]; with aspirin, 16%) and had higher rates of platelet‐leukocyte aggregate formation (monocyte‐platelet‐leukocyte aggregates at baseline: untreated, 27%; with aspirin, 16%) when compared with patients receiving clopidogrel alone (baseline CD62: 10% [P < .05]; monocyte‐platelet‐leukocyte aggregates: 13% [P < .05]) or combined with aspirin (baseline CD62: 5% [P < .05]; monocyte‐platelet‐leukocyte aggregates: 7% [P < .05]). Up‐regulation of MAC‐1 on monocytes after stimulation with thrombin receptor‐activating peptide and adenosine diphosphate was significantly lower in patients treated with clopidogrel and aspirin. Plasma levels of soluble intercellular adhesion molecule 1 were significantly lower in the group of healthy subjects (median, 186 ng/mL) when compared with those in untreated patients (median, 352 ng/mL) (P < .05), whereas intercellular adhesion molecule 1 levels in treated patients were similar for any antiplatelet regimen (aspirin, 262 ng/mL; clopidogrel, 274 ng/mL; combination therapy, 273 ng/mL) but significantly lower than those in untreated patients. This is the first report showing that platelet‐leukocyte aggregate formation is enhanced in atherosclerotic vascular disease but was found to be reduced in patients receiving clopidogrel.Clinical Pharmacology & Therapeutics (2003) 73, 232–241; doi: 10.1067/mcp.2003.13
Population differences in S‐warfarin metabolism between CYP2C9 genotype‐matched Caucasian and Japanese patients
Authors: Takahashi Harumi , Wilkinson Grant R. , Caraco Yoseph , Muszkat Mordechai , Kim Richard B. , Kashima Toshitaka , Kimura Sosuke , Echizen Hirotoshi 
Published: March 2003

ObjectiveOur objective was to investigate population differences in the metabolic activity of cytochrome P450 (CYP) 2C9 between genotypically matched Caucasian and Japanese patients by using the unbound oral clearance of S‐warfarin as an in vivo phenotypic trait measure.MethodsNinety Japanese and 47 Caucasian patients receiving maintenance warfarin therapy were studied. Steady‐state plasma unbound concentrations of S‐warfarin were measured by a chiral HPLC method coupled with an ultrafiltration technique, and unbound oral clearance for S‐warfarin was estimated. By combining plasma unbound concentrations of S‐warfarin with the urinary excretion rates of S‐7‐hydroxywarfarin, the formation clearance of S‐7‐hydroxywarfarin was also determined. Genotyping of CYP2C9 was performed for 6 distinct alleles (CYP2C9*1, CYP2C9*2, CYP2C9*3, CYP2C9*4, CYP2C9*5, and a T/C transition in intron 2).ResultsThe frequency distribution of unbound oral clearance for S‐warfarin obtained from Japanese patients was shifted toward higher values as compared with that in Caucasian patients. Japanese patients had lower allelic frequencies for the 5 variants than Caucasian patients. When interpopulation comparisons of CYP2C9 activity were made for genotype‐matched subjects, Japanese patients with the homozygous CYP2C9*1 (wild‐type) genotype (n = 85) had significantly (P < .01) greater median values for unbound oral clearance and formation clearance than Caucasian patients with the corresponding genotype (n = 26), 10.4 mL × min−1 × kg−1 versus 4.25 mL × min−1 × kg−1 and 0.015 mL × min−1 × kg−1 versus 0.010 mL × min−1 × kg−1, respectively. In addition, Japanese patients heterozygous for the CYP2C9*3 genotype (n = 4) showed a significantly (P < .05) reduced unbound oral clearance for S‐warfarin, by 63%, as compared with Japanese patients possessing the homozygous CYP2C9*1 genotype. By contrast, in Caucasian patients, no significant differences were observed in this parameter between CYP2C9*1 homozygous subjects and those with heterozygous CYP2C9*2 or CYP2C9*3 genotypes.ConclusionsThese findings indicate that population differences in the frequencies of known variant CYP2C9 alleles account only in part for the variability observed in in vivo CYP2C9 activity in different populations. In addition, a gene‐dose effect of defective CYP2C9 alleles on the in vivo CYP2C9 activity is evident in Japanese patients but not in Caucasian patients. Further studies are required to identify currently unknown factor(s) (eg, transcriptional regulation) responsible for the large intrapopulation and interpopulation variability in CYP2C9 activity.Clinical Pharmacology & Therapeutics (2003) 73, 253–263; doi: 10.1067/mcp.2003.26
Duloxetine is both an inhibitor and a substrate of cytochrome P4502D6 in healthy volunteers
Authors: Skinner Michael H. , Kuan Han‐Yi , Pan Alan , Sathirakul Korbtham , Knadler Mary Pat , Gonzales Celedon R. , Yeo Kwee Poo , Reddy Shobha , Lim Maggie , Ayan‐Oshodi Mosun , Wise Stephen D. 
Published: March 2003

Background and ObjectivesDuloxetine, a potent dual reuptake inhibitor of serotonin and norepinephrine currently undergoing clinical investigation for treatment of depression and stress urinary incontinence, has the potential to act as both a substrate and an inhibitor of cytochrome P4502D6 (CYP2D6). Our objectives were to determine the effect of duloxetine on the pharmacokinetics of desipramine, a tricyclic antidepressant metabolized by CYP2D6 (study 1), and the effect of paroxetine, a potent CYP2D6 inhibitor, on duloxetine pharmacokinetics (study 2).MethodsSubjects were healthy men and women between 21 and 63 years old. All subjects were genotypically CYP2D6 extensive metabolizers. In study 1, 50 mg of desipramine was administered as a single dose alone and in the presence of steady‐state duloxetine 60 mg twice daily. In study 2, steady‐state pharmacokinetics of duloxetine 40 mg once daily were determined in the presence and absence of steady‐state paroxetine 20 mg once daily.ResultsDuloxetine increased the maximum plasma concentration of desipramine 1.7‐fold and the area under the concentration‐time curve 2.9‐fold. Paroxetine increased the maximum plasma concentration of duloxetine and the area under the concentration‐time curve at steady state 1.6‐fold. Reports of adverse events were similar whether duloxetine was administered alone or in combination with desipramine or paroxetine.ConclusionDuloxetine 60 mg twice daily is a moderately potent CYP2D6 inhibitor, intermediate between paroxetine and sertraline. The potent CYP2D6 inhibitor paroxetine has a moderate effect on duloxetine concentrations. The results of these 2 studies suggest that caution should be used when CYP2D6 substrates and inhibitors are coadministered with duloxetine.Clinical Pharmacology & Therapeutics (2003) 73, 170–177; doi: 10.1067/mcp.2003.28
Dizziness: Relating the Severity of Vertigo to the Degree of Handicap by Measuring Vestibular Impairment
Authors: Pérez Nicolás , Martin Eduardo , Garcia‐Tapia Rafael 
Published: March 2003

OBJECTIVEWe sought to correlate the severity of vertigo and handicap in patients with vestibular pathology according to measures of impairment.STUDY DESIGN AND SETTINGWe conducted a prospective assessment of patients with dizziness by means of caloric, rotatory test, and computerized dynamic posturography to estimate impairment. Handicap and severity of vertigo were determined with specific questionnaires (Dizziness Handicap Inventory and UCLA‐DQ).RESULTSA fair relationship were found between severity of dizziness and vestibular handicap. When impairment was taken into consideration, values were still fair and only moderate for a group of patients with an abnormal caloric test as the only pathologic finding. The composite score from the sensory organization test portion of the computerized dynamic posturography is fairly correlated to severity of vertigo and handicap in the whole population of patients, but no correlation was found when they were assigned to groups of vestibular impairment.CONCLUSIONTo assess vestibular impairment, the results from several tests must be taken into account. However, vestibular handicap is not solely explained with measurements of impairment and/or severity.
Jugular Bulb Diverticula: Clinical and Radiologic Aspects
Authors: Bilgen Cem , Kirazli Tayfun , Ogut Fatih , Totan Secil 
Published: March 2003

OBJECTIVEThis study was performed to determine the clinical presentation of jugular diverticulum and its relevance with the extension of the lesion.STUDY DESIGNThe records and high‐resolution CT scans of 1474 patients, with otologic symptoms or related clinical findings, were evaluated retrospectively. In 17 cases in which CT scans revealed the presence of jugular diverticulum, sensorineural symptoms were evaluated with respect to a reference line, perpendicular to the basal turn of the cochlea and tangent to the vestibule in axial CT scan images.RESULTSWhen the extension of jugular diverticulum was posterior to the reference line, sensorineural symptoms with vertigo were dominant in most patients (72.7%) in this group. On the other hand, for the patients with anterior‐extending jugular diverticulum, sensorineural symptoms without vertigo were detected in 50% of patients, whereas 33.3% had sensorineural symptoms with vertigo.CONCLUSIONThis study revealed a relationship between the extension of jugular diverticulum and clinical symptoms. However, this relationship lacks statistical evidence because of the limited number of patients.
Functional Comparison after Reconstruction with a Radial Forearm Free Flap or a Pectoralis Major Flap for Cancer of the Tongue
Authors: Su Wan‐Fu , Hsia Yi‐Jan , Chang Yen‐Chine , Chen Shyi‐Gen , Sheng Hwa 
Published: March 2003

OBJECTIVENumerous patients in Taiwan with tongue carcinoma require tongue reconstruction. We compared the abilities of 2 methods of tongue reconstruction to reserve tongue function.STUDY DESIGN AND SETTINGSixty patients underwent resection of the tumors and reconstruction with a pectoralis major flap or a radial forearm flap. The Chinese articulation test was used to evaluate the place and manner of error production, and a questionnaire on dietary habits was used to evaluate deglutition 6 months to 10 years after reconstruction.RESULTSPatients with the free flap had more intelligible speech. The questionnaire study showed no significant difference between the 2 groups in swallowing rating. Motility caused by flap pliability increased speech intelligibility more than it did on swallowing function.CONCLUSIONOur experience in a few selected patients shows that the functional outcome of tongue surgery is related to the reconstruction methods used (for speech) and to the extent of tongue resection (for swallowing).
Evaluation of Sleep‐Disordered Breathing in Children
Authors: Sohn Han , Rosenfeld Richard M. 
Published: March 2003

OBJECTIVEWe evaluated changes in disease‐specific quality of life (QOL) for children with sleep‐disordered breathing (SDB).PATIENTS, DESIGN, AND SETTINGWe conducted a cohort study in 69 children (age range, 6 months to 13 years; median age, 6.1 years) from a hospital‐based pediatric otolaryngology practice in a metropolitan area. We used the OSA‐18, an 18‐item QOL survey with known test‐retest reliability, internal consistency, and construct validity. Survey domains included sleep disturbance, physical suffering, emotional distress, daytime problems, and caregiver concerns.INTERVENTIONTonsillectomy or adenoidectomy was performed as part of routine clinical care. The OSA‐18 was completed at entry by the child's caregiver and again at least 4 weeks after surgery.MAIN OUTCOME MEASURESThe validity of the OSA‐18 change score was assessed by comparison with multiple external constructs, including a validated measure of longitudinal change (OSD‐6 survey). Responsiveness was assessed by the standardized response mean (SRM).RESULTSThe mean baseline OSA‐18 survey score was 3.1 (SD, 0.9) of a maximum 7.0, with higher values indicating poorer QOL. Change scores were available for all children, with a mean interval between preoperative and postoperative surveys of 61 days (range, 42 to 92 days). The mean OSA‐18 change score of 1.14 (SD, 0.71) showed significant correlation with tonsil size (r = 0.40), adenoid size (r = 0.31), OSD‐6 change scores (r = 0.71), and the direct caregiver estimates of change (r = 0.34). OSA‐18 change scores showed large responsiveness to change (SRM 1.44; 95% confidence interval, 1.16 to 69), with the most responsive domains being sleep disturbance, physical suffering, and care‐giver concerns. Significant responsiveness was also demonstrated for the domains of daytime problems and emotional distress.CONCLUSIONSThe OSA‐18 is a valid, reliable, and responsive QOL measure that combines the advantages of a discriminative and evaluative survey in a single instrument. The OSA‐18 is a useful measure of patient‐based outcomes for clinical trials, health services research, and routine clinical care.
Revisiting Outpatient Tonsillectomy in Young Children
Authors: Ross Adam T. , Kazahaya Ken , Tom Lawrence W. C. 
Published: March 2003

OBJECTIVEPostoperative same‐day discharge is safe for most children undergoing tonsillectomy. However, young children with upper airway obstruction have a higher risk of postoperative complications. We review our tonsillectomy experience in children under 36 months to evaluate the safety of outpatient tonsillectomy in this population.STUDY DESIGN AND SETTINGWe conducted a retrospective study of all children under 36 months who underwent tonsillectomy during a recent 2‐year period at The Children's Hospital of Philadelphia.RESULTSThe indication for tonsillectomy in 96% of 421 children was upper airway obstruction. Eighteen percent required postoperative treatment to prevent respiratory compromise; 56% of these patients had no associated medical comorbidity. Patients younger than 24 months and those with medical comorbidities were more likely to require intervention.CONCLUSION AND SIGNIFICANCEIt is not possible to preoperatively anticipate which children will have postsurgical complications. We recommend planning an overnight admission for children younger than 36 months undergoing tonsillectomy.