bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II Study of Temsirolimus (CCI-779), a Novel Inhibitor of mTOR, in Heavily Pretreated Patients With Locally Advanced or Metastatic Breast Cancer
Authors: Chan Stephen , Scheulen Max E. , Johnston Stephen , Mross Klaus , Cardoso Fatima , Dittrich Christian , Eiermann Wolfgang , Hess Dagmar , Morant Rudolph , Semiglazov Vladimir , Borner Markus , Salzberg Marc , Ostapenko Valerijus , Illiger Hans-Joachim , Behringer Dirk , Bardy-Bouxin Nathalie , Boni Joseph , Kong Steven , Cincotta Maria , Moore Laurence 
Published: June 2005

Purpose In this study, two doses of temsirolimus (CCI-779), a novel inhibitor of the mammalian target of rapamycin, were evaluated for efficacy, safety, and pharmacokinetics in patients with locally advanced or metastatic breast cancer who had been heavily pretreated. Patients and Methods Patients (n = 109) were randomly assigned to receive 75 or 250 mg of temsirolimus weekly as a 30-minute intravenous infusion. Patients were evaluated for tumor response, time to tumor progression, adverse events, and pharmacokinetics of temsirolimus. Results Temsirolimus produced an objective response rate of 9.2% (10 partial responses) in the intent-to-treat population. Median time to tumor progression was 12.0 weeks. Efficacy was similar for both dose levels but toxicity was more common with the higher dose level, especially grade 3 or 4 depression (10% of patients at the 250-mg dose level, 0% at the 75-mg dose level). The most common temsirolimus-related adverse events of all grades were mucositis (70%), maculopapular rash (51%), and nausea (43%). The most common, clinically important grade 3 or 4 adverse events were mucositis (9%), leukopenia (7%), hyperglycemia (7%), somnolence (6%), thrombocytopenia (5%), and depression (5%). Conclusion In heavily pretreated patients with locally advanced or metastatic breast cancer, 75 and 250 mg temsirolimus showed antitumor activity and 75 mg temsirolimus showed a generally tolerable safety profile.
Zoledronic Acid and Renal Toxicity: Data from French Adverse Effect Reporting Database
Authors: Munier Aline , Gras Valerie , Andrejak Michel , Bernard Nathalie , Jean-Pastor Marie-Josephe , Gautier Sophie , Biour Michel , Massy Ziad 
Published: June 2005

BACKGROUND Zoledronic acid–associated renal impairment leading to renal failure has been recently reported in a cohort of US patients. However, the presence of such toxicity in other populations has not yet been determined. OBJECTIVE To analyze French cases of zoledronic acid–associated nephrotoxicity. METHODS We evaluated available cases with acute deterioration of renal function associated with zoledronic acid therapy drawn from the French Adverse Event Reporting System database until July 1, 2004. RESULTS We identified 4 men and 3 women between the ages of 52 and 70 years, with multiple myeloma or different types of metastatic cancer, who had experienced renal impairment during zoledronic acid therapy. Four patients developed de novo acute renal failure, while the other 3 patients experienced acute deterioration of preexisting chronic renal failure. Renal failure occurred after various durations of zoledronic acid therapy (1–120 days). Three patients completely recovered and one partially recovered their previous renal function after discontinuation of zoledronic acid, but renal impairment was associated with a fatal outcome in 2 cases; the outcome of the other case was unknown. Our data confirm the previously reported risk factors for zoledronic acid–associated nephrotoxicity such as advanced cancer, multiple myeloma, preexisting renal failure, diabetes, hypertension, and concomitant use of nephrotoxic drugs. CONCLUSIONS These cases emphasize the need for regular monitoring of renal function during zoledronic acid treatment, with particular attention to patients with preexisting impaired renal function.
Use of the Transtheoretical Model in the Medication Use Process
Authors: Ficke Danielle L , Farris Karen B 
Published: June 2005

OBJECTIVE To review articles published during the past 10 years relating to the transtheoretical model (TTM) and the medication use process, focusing on prescribing, dispensing, and using prescription and nonprescription medications for legitimate purposes. DATA SOURCES MEDLINE, Cochrane database, PsychINFO, International Pharmaceutical Abstracts, and PubMed were searched from 1995 to August 2004 using the key terms models, psychological; prescriptions, drug; drugs, nonprescription; models, theoretical; self medication; patient compliance; medication compliance; decision making; drug therapy and behavior change. Additional searches included the following terms: pharmacists, community; TTM; transtheoretical model, pharmacy services, new practice patterns and physician practice patterns. STUDY SELECTION AND DATA EXTRACTION Studies with empirical application of any aspect of TTM were included. Abstracts were reviewed by both authors, and data were independently abstracted including, for example, specific aspects of TTM used or tested, context for model use or setting, and results and authors' suggestions for future use of TTM. The reviewers came to consensus on all abstracted information. DATA SYNTHESIS Eleven articles were identified that contained TTM and drug use; however, only 5 were empirical applications. There were 2 types of applications of TTM in medication use: measurement of stage of change regarding adherence and prediction of adherence using TTM concepts. A 1- and 2-item measure of adherence stage of change have been validated. Medication adherence stage of change varied by type of drug. The pros and cons of taking the medicine and stage of change were useful in predicting adherence. No intervention studies to improve adherence were identified. CONCLUSIONS TTM has not been used extensively to examine the medication use process. Without further research, no clear recommendation can be provided as to the effectiveness of TTM in improving the drug use process, but it remains promising.
Carotenoid-chlorophyll complexes: Ready-to-harvest
Authors: Vaswani Harsha M. , Holt Nancy E. , Fleming Graham R. 
Published: June 2005

Abstract
The fundamental interactions between naturally occurring pigments in light-harvesting systems are responsible for the high efficiency of the photosynthetic apparatus. We describe the role of carotenoids (Cars) in light-harvesting systems, including our work elucidating the mechanism of energy transfer from the optically dark Car singlet excited state (S1) to chlorophyll (Chl) and calculations on the electronic structure of Cars by means of time-dependent density functional theory (TDDFT). We highlight new studies on the charge-transfer state of the Car, peridinin (Per), which enhances the light-harvesting efficiency of the Car by increasing the electronic coupling to Chl. The role of another Car, zeaxanthin (Zea), is discussed with respect to its role in the mechanism of the feedback deexcitation quenching in green plants, a vital regulation process under light conditions which exceed photosynthetic capacity. Lastly, we provide insight on how the 96 Chls in Photosystem I are optimized to generate a pigment-protein complex which utilizes solar energy with near unit efficiency.
UVB and UVA radiation-mediated damage to isolated and cellular DNA
Authors: Cadet Jean , Courdavault Sophie , Ravanat Jean-Luc , Douki Thierry 
Published: June 2005

Abstract
The effects of solar light on cellular DNA are mostly explained by both direct excitation of nucleobases and photosensitized reactions that are mediated by UVB and UVA radiation, respectively. A large body of information is now available on the main photodynamic reactions to DNA, which involve guanine as the preferential target of both one-electron oxidation and singlet oxygen oxidation, as the result of type I and type II mechanisms. Most of the final products of the photosensitized reactions of guanine base in isolated DNA have been characterized, and comprehensive mechanisms for their formation have been proposed. Further insights into the mechanisms of solar radiation-induced modifications within cellular DNA have been gained from accurate measurement of the main photoproducts using recently designed sensitive chromatographic and biochemical methods. Thus, the distribution pattern of the 12 possible bipyrimidine photoproducts has been shown to be similar in the DNA of UVB-irradiated rodent and human cells. Cyclobutyl pyrimidine dimers are also generated at di-thymine and thymine-cytosine sites within nuclear DNA upon exposure to UVA radiation as the likely result of triplet energy transfer. In addition, oxidative reactions that involved mostly singlet oxygen, and to a lesser extent, .OH radicals are also implicated, although less efficiently.
Toward a computational photobiology
Authors: Sinicropi Adalgisa , Andruniow Tadeusz , De Vico Luca , Ferré Nicolas , Olivucci Massimo 
Published: June 2005

Abstract
In this paper, we discuss the results of our recent studies on the molecular mechanism, which stand at the basis of the photochemical processes occurring in photobiological systems. These results are obtained using modern, robust, and fairly accurate high-level quantum chemical methods.
Fluorescence sensor applications as detectors for DNA damage, free radical formation, and in microlithography
Authors: Scaiano J. C. , Aliaga C. , Chrétien M. N. , Frenette M. , Focsaneanu K. S. , Mikelsons L. 
Published: June 2005

Abstract
Fluorescence sensors have been developed to monitor radical reactions, DNA damage, acid-catalyzed processes, detection of electron-deficient molecules, and zeolite applications. The examples presented emphasize applications in polymer and supramolecular systems.
Rotaxane-based molecular machines operated by photoinduced electron transfer
Authors: Credi Alberto , Ferrer Belén 
Published: June 2005

Abstract
A molecular machine is an assembly of a definite number of molecular components designed to perform mechanical motions as a result of an appropriate external stimulation. Like their macroscopic counterparts, nanoscale machines need energy to operate. Energy can be supplied through (i) chemical reactions, (ii) electrochemical processes, and (iii) photoinduced processes. Although most molecular motors of the biological world are fueled by chemical reactions, for several reasons light is a very good choice to operate artificial molecular machines. Rotaxanes, owing to their peculiar architecture, are attractive candidates for the construction of artificial nanoscale machines. By adopting an incrementally staged design strategy, photoinduced electron-transfer processes have been engineered within rotaxane-type structures with the purpose of obtaining light-powered molecular machines. Such an approach is illustrated by describing the behavior of prototypes investigated in our laboratories.
Return electron transfer in radical ion pairs of triplet multiplicity
Authors: Roth Heinz D. 
Published: June 2005

Abstract
Return electron transfer (RET) in radical ion pairs may populate the reagent ground states or, in the case of triplet pairs, one reagent triplet state. The efficiency of triplet RET is governed by the free energies of singlet and triplet RET and by the topologies of the potential surfaces of parent molecules, radical ions, and accessible triplet states or biradicals. RET in triplet radical ion pairs is exemplified for two distinct relationships between the three potential surfaces.
Genome-Wide Characterization of Tetrahymena thermophila Chromosome Breakage Sites. II. Physical and Genetic MappingSequence data from this article have been deposited with the EMBL/GenBank Data Libraries under accession nos. AY653004, AY653005, AY653006, AY653007, AY653008, AY653009, AY653010, AY653011, AY653012, AY653013, AY653014, AY653015, AY653016, AY653017, AY653018, AY653019, AY653020, AY653021, AY653022, AY653023, AY653024, AY653025, AY653026, AY653027, AY653028, AY653029.
Authors: Cassidy-Hanley Donna , Bisharyan Yelena , Fridman Vladimir , Gerber Joseph , Lin Cindy , Orias Eduardo , Orias Judith D , Ryder Hilary , Vong Linh , Hamilton Eileen P 
Published: June 2005

Abstract
The chromosomes of the macronuclear (expressed) genome of Tetrahymena thermophila are generated by developmental fragmentation of the five micronuclear (germline) chromosomes. This fragmentation is site specific, directed by a conserved chromosome breakage sequence (Cbs element). An accompanying article in this issue reports the development of a successful scheme for the genome-wide cloning and identification of functional chromosome breakage sites. This article reports the physical and genetic characterization of 30 functional chromosome breakage junctions. Unique sequence tags and physical sizes were obtained for the pair of macronuclear chromosomes generated by fragmentation at each Cbs. Cbs-associated polymorphisms were used to genetically map 11 junctions to micronuclear linkage groups and macronuclear coassortment groups. Two pairs of junctions showed statistically significant similarity of the sequences flanking the Cbs, suggestive of relatively recent duplications of entire Cbs junctions during Tetrahymena genome evolution. Two macronuclear chromosomes that lose at least one end in an age-related manner were also identified. The whole-genome shotgun sequencing of the Tetrahymena macronucleus has recently been completed at The Institute for Genome Research (TIGR). By providing unique sequence from natural ends of macronuclear chromosomes, Cbs junctions will provide useful sequence tags for relating macro- and micronuclear genetic, physical, and whole-genome sequence maps.
A Comparison of Three Estimators of the Population-Scaled Recombination Rate: Accuracy and Robustness
Authors: Smith Nick G C , Fearnhead Paul 
Published: June 2005

Abstract
We have performed simulations to assess the performance of three population genetics approximate-likelihood methods in estimating the population-scaled recombination rate from sequence data. We measured performance in two ways: accuracy when the sequence data were simulated according to the (simplistic) standard model underlying the methods and robustness to violations of many different aspects of the standard model. Although we found some differences between the methods, performance tended to be similar for all three methods. Despite the fact that the methods are not robust to violations of the underlying model, our simulations indicate that patterns of relative recombination rates should be inferred reasonably well even if the standard model does not hold. In addition, we assess various techniques for improving the performance of approximate-likelihood methods. In particular we find that the composite-likelihood method of Hudson (2001) can be improved by including log-likelihood contributions only for pairs of sites that are separated by some prespecified distance.
Adult Myogenesis in Drosophila melanogaster Can Proceed Independently of Myocyte Enhancer Factor-2
Authors: Baker Phillip W , Tanaka Kathleen K Kelly , Klitgord Niels , Cripps Richard M 
Published: June 2005

Abstract
Myocyte enhancer factor-2 (MEF2) is a transcription factor that is necessary for embryonic muscle development in Drosophila and vertebrates; however, whether this factor is required during later muscle development remains largely unknown. Using heteroallelic combinations of different Mef2 mutant alleles, we isolated and characterized a temperature-sensitive combination. Through temperature-shift experiments, we obtained adult animals that were lacking proper MEF2 function. Many of these individuals died as mature pupae, and those that eclosed showed poor locomotion and an inability to fly. Histological analysis of these animals revealed a requirement for MEF2 in skeletal muscle patterning, although these animals had strikingly normal amounts of muscle tissue. Using quantitative polymerase chain reaction, we determined that expression of the MEF2-regulated actin gene Act57B was severely reduced in these animals. By contrast myofibrillar actin genes unique to the adult stage were only mildly affected. Since MEF2 mutant adults were still capable of forming muscle tissue, we conclude that MEF2 is required for the expression of only a subset of muscle structural genes in the adult. These results indicate that additional muscle-specific factors function to control the myogenesis of complex and diverse muscle in the adult.
NinR- and Red-Mediated Phage-Prophage Marker Rescue Recombination in Escherichia coli
Authors: Hayes Sidney , Asai Kengo , Chu Audrey M , Hayes Connie 
Published: June 2005

Abstract
We examined the requirement of λ recombination functions for marker rescue of cryptic prophage genes within the Escherichia coli chromosome. We infected lysogenic host cells with λimm434 phages and selected for recombinant immλ phages that had exchanged the imm434 region of the infecting phage for the heterologous 2.6-kb immλ region from the prophage. Phage-encoded activity, provided by either Red or NinR functions, was required for the substitution. Red− phages with ΔNinR, internal NinR deletions of rap-ninH, or orf-ninC were 117-, 12-, and 5-fold reduced for immλ rescue in a Rec+ host, suggesting the participation of several NinR activities. RecA was essential for NinR-dependent immλ rescue, but had slight influence on Red-dependent rescue. The host recombination activities RecBCD, RecJ, and RecQ participated in NinR-dependent recombination while they served to inhibit Red-mediated immλ rescue. The opposite effects of several host functions toward NinR- and Red-dependent immλ rescue explains why the independent pathways were not additive in a Rec+ host and why the NinR-dependent pathway appeared dominant. We measured the influence of the host recombination functions and DnaB on the appearance of oriλ-dependent replication initiation and whether oriλ replication initiation was required for immλ marker rescue.
Portrait of a Species
Authors: Pröschold Thomas , Harris Elizabeth H , Coleman Annette W 
Published: June 2005

AbstractChlamydomonas reinhardtii, the first alga subject to a genome project, has been the object of numerous morphological, physiological, and genetic studies. The organism has two genetically determined mating types (plus and minus) and all stages of the simple life cycle can be evoked in culture. In the nearly 60 years since the first standard laboratory strains were isolated, numerous crosses and exchanges among laboratories have led to some confusion concerning strain genealogy. Here we use analyses of the nuclear internal transcribed spacer regions and other genetic traits to resolve these issues, correctly identify strains currently available, and analyze phylogenetic relationships with all other available similar chlamydomonad types. The presence of a 10-bp indel in ITS2 in some but not all copies of the nuclear ribosomal cistrons of an individual organism, and the changing ratios of these in crosses, provide a tool to investigate mechanisms of concerted evolution. The standard C. reinhardtii strains, plus C. smithii +, plus the new eastern North American C. reinhardtii isolates, comprise one morphological species, one biological species of high sexual intercompatibility, and essentially identical ITS sequences (except the tip of helix I of ITS2). However, variant RFLP patterns characterize strains from each geographic site.
Preliminary Assessment of Refrigerated and Frozen Storage of Sperm of the Coppernose Bluegill
Authors: Bates Mark C , Williams Casey S , Lang R Paul , Tiersch Terrence R 
Published: June 2005

Abstract
The coppernose bluegill (CBG) Lepomis macrochirus purpurescens is a bluegill subspecies that is native to Florida. The CBGs and their hybrids are of interest as potential food fish. Our objectives were to (1) develop an osmolality activation curve for CBG sperm, (2) determine suitable cryoprotectants for the cryopreservation of CBG sperm, and (3) demonstrate the ability of cryopreserved CBG sperm to fertilize eggs. Sperm were stripped from mature CBGs (mean ± SD = 113 ± 35 g, n = 10), diluted in Hanks' balanced salt solution (HBSS; osmolality = 300 mosmols/kg), and stored at 4°C. An activation curve was generated by exposing the sperm to solutions prepared by serial dilution of HBSS with de-ionized water. The sperm remained inactive at osmolalities above 265 mosmols/kg. Dilution below 115 mosmols/kg was required for complete activation. The motility of sperm stored in these solutions was estimated at 24-h intervals. Stripped sperm motility (mean ± SD) declined from 90 ± 7% initially to 26 ± 11% after 6 d of storage at 4°C. Motility of sperm from crushed testes declined from 80 ± 8% at collection to 28 ± 10% at 1 d of storage. By day 5, motility of sperm from crushed testes was 9 ± 9%; no motility was observed at 6 d. Sperm were exposed to 10% concentrations of the cryoprotectants dimethyl acetamide (DMA), dimethyl sulfoxide (DMSO), and methanol (MeOH), and motility was evaluated at 15-min intervals for 60 min. Initially, motility was 81 ± 11% for the control sperm. At 60 min, motility was 0% for DMA, 30 ± 24% for DMSO, 78 ± 10% for MeOH, and unchanged for the control. For samples frozen in a controlled-rate freezer (CRF), post-thaw motility was 26 ± 10% for samples with 10% DMSO and 51 ± 18% for samples with 10% MeOH. For samples frozen by means of dairy industry technology (DIT), post-thaw motility was 46 ± 21% for samples with 10% DMSO and 56 ± 13% for samples with 10% MeOH. Overall, samples frozen in 10% MeOH had significantly higher post-thaw motility (P = 0.043) than did those frozen in 10% DMSO. However, post-thaw motility did not differ between samples frozen by use of the CRF and DIT (P = 0.13). For sperm frozen in the CRF, fertilization was 15% for samples with 10% DMSO and 50% for samples with 10% MeOH. For sperm frozen by means of DIT, fertilization was 50% for samples with 10% DMSO and 75% for samples with 10% MeOH.
Evaluation of Hatchery versus Wild Sockeye Salmon Fry Growth and Survival in Two British Columbia Lakes
Authors: Hyatt Kim D. , Mathias Karin L. , McQueen Donald J. , Mercer Brian , Milligan Patrick , Rankin D. Paul 
Published: June 2005

Abstract
We evaluated the relative success of sockeye salmon hatchery fry stocking in two British Columbia–Alaska transboundary lakes (1,622-ha Tatsamenie Lake and 492-ha Tahltan Lake). Fry stocking began in the late 1980s and is still under way. During the study period, survival patterns in the two lakes were different. At Tatsamenie Lake, wild egg-to-fry survival was higher than hatchery egg-to-fry survival (11.3% versus 4.3%) and wild egg-to-smolt survival was higher than hatchery egg-to-smolt survival (5.8% versus 2.5%). We found no relationship between fry survival and stocking date, spawner abundance, or food availability in Tatsamenie Lake, but we did find a significant positive relationship between early-spring fry length and egg-to-fry survival. Also, we found that in net-pen experiments, larger fry survived better. From this, we concluded that hatchery fry stocked into Tatsamenie Lake may suffer from size-mediated mortality and that net-pen supplemental feeding could be used to overcome this problem. However, because eggs used for hatchery production come from the lake, fry stocking can only be justified when hatchery fry survival exceeds wild fry survival. At Tatsamenie Lake, this goal has not yet been attained. At Tahltan Lake, wild egg-to-fry survival was lower than hatchery egg-to-fry survival (1.5% versus 6.3%) and wild egg-to-smolt survival was lower than hatchery egg-to-smolt survival (3.6% versus 12.8%). Hatchery fry release date and food availability both failed to explain these differences in fry and smolt survival at Tahltan Lake. However, there was a strong negative relationship between total female escapement and wild egg-to-smolt survival. This supported the results of an earlier investigation, which suggested that Tahltan Lake was spawning-site limited. We concluded that at Tahltan Lake, hatchery fry stocking increased smolt numbers, is biologically justified, and should be continued.