bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of gemcitabine and docetaxel in combination for the treatment of metastatic breast cancer
Authors: GOEL Shom , ABDI Ehtesham , LEWIS Craig R , LINKS Matthew , BEGBIE Steven , CLINGAN Philip , GANJU Vinod , BEITH Jane 
Published: February 2009

AbstractAim:  Gemcitabine (G) and docetaxel (D) have both shown activity in the treatment of anthracycline‐pretreated patients with metastatic breast cancer. This phase II study was designed to evaluate the safety and efficacy of the GD combination.Methods:  Patients with measurable locally advanced or metastatic breast cancer who had previously received anthracycline‐based therapy were eligible. The patients received D 40 mg/m2 followed by G 800 mg/m2 IV on days 1 and 8 every 3 weeks for a maximum of eight cycles.Results:  Thirty patients were enrolled and received a median of five cycles (range 0–8). Of these, 24 were evaluable for efficacy, with an overall response rate of 29.2% (95% CI, 12.6–51.1%). An additional 36.7% had a stable disease for an overall clinical benefit of 65.9%. The median duration of response was 2.1 months (95% CI, 2.0–3.6 months) and the median time to disease progression was 5.5 months (95% CI, 2.0–8.9 months). The median survival time was 16.7 months (95% CI, 7.3–32.0 months). Myelosuppression was the major toxicity, with grade 3/4 neutropenia in 73.3% of patients and febrile neutropenia in 6.7%.Conclusion:  Weekly G and D is an active and safe regimen in treating metastatic breast cancer. The response rate was lower than that previously reported for this combination, which may relate to the lower doses used and the weekly D schedule. It may be worthwhile to further explore this combination to determine the optimal dosing schedule.
Randomized phase II trial of gemcitabine and either day 1 or day 8 carboplatin for advanced non‐small‐cell lung cancer: Is thrombocytopenia predictable?
Authors: CROMBIE Cathy , BURNS W Ivon , KARAPETIS Christos , LOWENTHAL Ray M , KIRSTEN Fred , DAVIDSON J Andrew , ABELL Fiona , REECE William HH , IGLESIAS Jose , DE SOUZA Paul 
Published: February 2009

AbstractAim:  Two 21‐day gemcitabine–carboplatin schedules were evaluated in patients with advanced non‐small cell lung cancer in order to assess the effect of timing of the carboplatin dose on toxicity and efficacy.Methods:  Patients were randomized to gemcitabine (1000 mg/m2 on days 1 and 8 of a 21‐day cycle) and carboplatin (AUC 5, on day 1) (Carbo d1 arm) or the same gemcitabine schedule with carboplatin given on day 8 (Carbo d8 arm). Twenty patients with Stage IIIB or IV non‐small‐cell lung cancer were enrolled in each arm.Results:  The achieved dose intensities of both gemcitabine and carboplatin were significantly higher in the Carbo d1 arm. The total rates of grade 3 or 4 hematological and non‐hematological toxicities (any toxicity, any cycle) were 80% and 65%, respectively, with no significant differences between the two arms. Nine patients in the Carbo d1 arm, but only one patient in the Carbo d8 arm, required a platelet transfusion. There were 10 partial responses (four Carbo d1 arm, six Carbo d8 arm), giving an overall response rate of 25% (95% CI 13–41%).Conclusion:  Administration of carboplatin on day 8 of this regimen confers no clear advantage compared with day 1 carboplatin, with similar toxicity but lower dose intensity. A formula for the prediction of thrombocytopenia is proposed.
The transition disc frequency in M stars
Authors: Ercolano B. , Clarke C. J. , Robitaille T. P. 
Published: February 2009

Abstract
We re-examine the recent suggestion of a high fraction of transition discs (i.e. those with a cleared inner hole) in M stars, motivated by the fact that we expect that, for M stars, even discs without inner holes should exhibit very weak excess shortwards of around 10 μm. Our analysis of spectral energy distribution models suggests that this indeed means that M stars where a detectable excess begins at around 6 μm may be misclassified as transition discs when in fact they have optically thick dust extending in to the dust sublimation radius. Consequently, we estimate that the transition disc fraction among M stars in the Coronet cluster is ∼15 ± 10 per cent (rather than the recently claimed value of 50 per cent). This revised figure would imply that the transition disc fraction is not after all markedly higher in later type stars. We suggest that, for M stars, transition discs can only be readily identified if they have emission that is close to photospheric out to &gt;10 μm.
AMP‐activated protein kinase in contraction regulation of skeletal muscle metabolism: necessary and/or sufficient?
Authors: Jensen T. E. , Wojtaszewski J. F. P. , Richter E. A. 
Published: February 2009

AbstractIn skeletal muscle, the contraction‐activated heterotrimeric 5′‐AMP‐activated protein kinase (AMPK) protein is proposed to regulate the balance between anabolic and catabolic processes by increasing substrate uptake and turnover in addition to regulating the transcription of proteins involved in mitochondrial biogenesis and other aspects of promoting an oxidative muscle phenotype. Here, the current knowledge on the expression of AMPK subunits in human quadriceps muscle and evidence from rodent studies suggesting distinct AMPK subunit expression pattern in different muscle types is reviewed. Then, the intensity and time dependence of AMPK activation in human quadriceps and rodent muscle are evaluated. Subsequently, a major part of this review critically examines the evidence supporting a necessary and/or sufficient role of AMPK in a broad spectrum of skeletal muscle contraction‐relevant processes. These include glucose uptake, glycogen synthesis, post‐exercise insulin sensitivity, fatty acid (FA) uptake, intramuscular triacylglyceride hydrolysis, FA oxidation, suppression of protein synthesis, proteolysis, autophagy and transcriptional regulation of genes relevant to promoting an oxidative phenotype.
AMP‐activated protein kinase and cancer
Authors: Wang W. , Guan K.‐L. 
Published: February 2009

AbstractAMP‐activated protein kinase (AMPK) is a cellular energy sensor that is conserved in eukaryotes. Elevated AMP/ATP ratio activates AMPK, which inhibits energy‐consuming processes and activates energy‐producing processes to restore the energy homeostasis inside the cell. AMPK activators, metformin and thiazolidinediones, are used for the treatment of type II diabetes. Recently, reports have indicated that AMPK may also be a beneficial target for cancer treatment. Cancer cells have characteristic metabolic changes different from normal cells and, being a key metabolic regulator, AMPK may regulate the switch. AMPK may act to inhibit tumorigenesis through regulation of cell growth, cell proliferation, autophagy, stress responses and cell polarity.
Vulnerability as a Regulatory Category in Human Subject Research
Authors: Coleman Carl H. 
Published: February 2009

The concept of vulnerability has long played a central role in discussions of research ethics. In addition to its rhetorical use, vulnerability has become a term of art in U.S. and international research regulations and guidelines, many of which contain specific provisions applicable to research with vulnerable subjects. Yet, despite the frequency with which the term vulnerability is used, little consensus exists on what it actually means in the context of human subject protection or, more importantly, on how a finding of vulnerability should affect the process of research ethics review.The Common Rule, the centerpiece of the U.S. human subject protection regulations, uses the word vulnerable three times. First, it provides that institutional review boards (IRBs) that regularly review research involving a vulnerable category of subjects should consider including one or more individuals who are knowledgeable about and experienced in working with these subjects.
Limited English Proficiency and Disparities in Clinical Research
Authors: Bustillos Dan 
Published: February 2009

Imagine that you possess an indicator for a disease or illness that has nothing to do with your body. It is not a genetic predisposition to acquire cancer or a vice that raises the probability of contracting some dread disease, though estimates of its health risks have placed it on par with having diabetes. It has nothing to do with the environmental pollutants you are exposed to or whether you can afford health care. It is not a physical susceptibility that renders you more easily reachable by the clutches of pathology. No, this indicator of health hinges on certain learned abilities and skills, and it is a barrier to health that is totally within the health field's power and resources to lift.The condition hinted at above is the inability to speak English proficiently in the United States. Today, more than one-sixth of the United States population speaks a language other than Englishat home,and this number (approximately 50 million people) is increasing rapidly.
Rhodopsin Activation Switches in a Native Membrane Environment†
Authors: Lüdeke Steffen , Mahalingam Mohana , Vogel Reiner 
Published: February 2009

AbstractThe elucidation of structure–function relationships of membrane proteins still poses a considerable challenge due to the sometimes profound influence of the lipid bilayer on the functional properties of the protein. The visual pigment rhodopsin is a prototype of the family of G protein‐coupled transmembrane receptors and a considerable part of our knowledge on its activation mechanisms has been derived from studies on detergent‐solubilized proteins. This includes in particular the events associated with the conformational transitions of the receptor from the still inactive Meta I to the Meta II photoproduct states, which are involved in signaling. These events involve disruption of an internal salt bridge of the retinal protonated Schiff base, movement of helices and proton uptake from the solvent by the conserved cytoplasmic E(D)RY network around Glu134. As the equilibria associated with these events are considerably altered by the detergent environment, we set out to investigate these equilibria in the native membrane environment and to develop a coherent thermodynamic model of these activating steps using UV–visible and Fourier‐transform infrared spectroscopy as complementary techniques. Particular emphasis is put on the role of protonation of Glu134 from the solvent, which is a thermodynamic prerequisite for full receptor activation in membranes, but not in detergent. In view of the conservation of this carboxylate group in family A G protein‐coupled receptors, it may also play a similar role in the activation of other family members.
pH‐dependent Interaction of Rhodopsin with Cyanidin‐3‐glucoside. 2. Functional Aspects†
Authors: Tirupula Kalyan C. , Balem Fernanda , Yanamala Naveena , Klein‐Seetharaman Judith 
Published: February 2009

AbstractAnthocyanins are a class of phytochemicals that confer color to flowers, fruits, vegetables and leaves. They are part of our regular diet and serve as dietary supplements because of numerous health benefits, including improved vision. Recent studies have shown that the anthocyanin cyanidin‐3‐O‐glucoside (C3G) increased regeneration of the dim‐light photoreceptor rhodopsin (Matsumotoet al. [2003]J.Agric.Food Chem.,51, 3560–3563). In an accompanying study (Yanamalaet al. [2009]Photochem.Photobiol.), we show that C3G directly binds to rhodopsin in a pH‐dependent manner. In this study, we investigated the functional consequences of C3G binding to rhodopsin. As observed previously in rod outer segments, regeneration of purified rhodopsin in detergent micelles is also accelerated in the presence of C3G. Thermal denaturation and stability studies using circular dichroism, fluorescence and UV/visible absorbance spectroscopy show that C3G exerts a destabilizing effect on rhodopsin structure while it only modestly alters G‐protein activation and the rates at which the light‐activated Metarhodopsin II state decays to opsin and free retinal. These results indicate that the mechanism of C3G‐enhanced regeneration may be based on changes in opsin structure promoting access to the retinal binding pocket.
Role of Arg123 in Light‐driven Anion Pump Mechanisms of pharaonis Halorhodopsin†
Authors: Kubo Megumi , Kikukawa Takashi , Miyauchi Seiji , Seki Akiteru , Kamiya Masakatsu , Aizawa Tomoyasu , Kawano Keiichi , Kamo Naoki , Demura Makoto 
Published: February 2009

AbstractHalorhodopsin (HR) acts as a light‐driven chloride pump which transports a chloride ion from the extracellular (EC) to the cytoplasmic space during a photocycle reaction that includes some photointermediates initiated by illumination. To understand the chloride uptake mechanisms, we focused on a basic residue Arg123 of HR from Natronomonas pharaonis (NpHR), which is the only basic residue located in the EC half ion channel. By the measurements of the visible absorption spectra in the dark and the light‐induced inward current through the membrane, it was shown that the chloride binding and transport ability of NpHR completely disappeared by the change of arginine to glutamine. From flashphotolysis analysis, the photocycle of R123Q differed from that of wildtype NpHR completely. The response of the R123H mutant depended on pH. These facts imply that the positive charge at position 123 is essential for chloride binding in the ground state and for the chloride uptake under illumination. On the basis of the molecular structures of HR and the anion‐transportable mutants of bacteriorhodopsin, the effects of the positive charge and the conformational change of the Arg123 side chain as well as the chloride‐pumping mechanism are discussed.
Additive Effects of Chlorin E6 and Metal Ion Binding on the Thermal Stability of RhodopsinIn Vitro†
Authors: Balem Fernanda , Yanamala Naveena , Klein‐Seetharaman Judith 
Published: February 2009

AbstractZinc (Zn2+) deficiency causes retinal dysfunctions such as night blindness and neurodegeneration. Because Zn2+binds directly to the photoreceptor rhodopsin and alters its stability, the stabilization of rhodopsin may be key to prevention and treatment of retinal dysfunctions. In this paper, we investigated if not only trace metals but also other nutrients may stabilize rhodopsin structurein vitro. Detailed studies of the thermal stability of secondary and tertiary structure of rhodopsin in the presence and absence of the chlorophyll derivative chlorin e6 alone and together with bivalent metal ions Zn2+, Cu2+, Fe2+, Ni2+, Mg2+and Mn2+over a temperature range 5–100°C were conducted using circular dichroism and fluorescence spectroscopy. When both chlorin e6 and Zn2+are present, a pronounced increase in the thermal stability of overall secondary structure content is observed compared to either compound alone. This additive capacity is also noted with Cu2+, but not when other metal ions and chlorin e6 are combined.
Geology and Origin of Supergene Ore at the Lavrion Pb‐Ag‐Zn Deposit, Attica, Greece
Authors: Skarpelis Nikos , Argyraki Ariadne 
Published: February 2009

AbstractThe Lavrion carbonate‐hosted Pb‐Ag‐Zn deposit in southeast Attica, Greece, consisted of significant non‐sulfide ore bodies. The polymetallic sulfide mineralization was subjected to supergene oxidation, giving rise to gossan. The principal non‐sulfide minerals of past economic importance were smithsonite, goethite and hematite. The supergene mineral assemblages occupy secondary open spaces and occur as replacement pods within marble. Calamine and iron ore mainly filled open fractures. X‐ray diffraction and scanning electron microscopy of samples of oxidized ore indicate complex gossan mineralogy depending on the hypogene mineralogy, the degree of oxidation and leaching of elements, and the local hydrologic conditions. Bulk chemical analysis of the samples indicated high ore‐grade variability of the supergene mineralization. On multivariate cluster analysis of geochemical data the elements were classified into groups providing evidence for their differential mobilization during dissolution, transport and re‐precipitation. The mode of occurrence, textures, mineralogy and geochemistry of the non‐sulfide mineralization confirm that it is undoubtedly of supergene origin: the product of influx into open fractures in the country rock of highly acidic, metal‐rich water resulting from the oxidation of pyrite‐rich sulfide protore. Dissolution of carbonates led to opening of the fractures. Mineral deposition in the supergene ore took place under near‐neutral to mildly acidic conditions. The supergene dissolution and re‐precipitation of Fe and Zn in the host marble increased metal grades and separated iron and zinc from lead, thereby producing economically attractive deposits; it further contributed to minimization of pollution impact on both soil and ground water.
FeO*‐Al2O3‐TiO2‐Rich Rocks of the Tertiary Bana Igneous Complex, West Cameroon
Authors: Kuepouo Gilbert , Sato Hiroaki , Tchouankoue Jean‐Pierre , Murata Mamoru 
Published: February 2009

AbstractFeO*‐Al2O3‐TiO2‐rich rocks are found associated with transitional tholeiitic lava flows in the Tertiary Bana plutono‐volcanic complex in the continental sector of the Cameroon Line. These peculiar rocks consist principally of iron‐titanium oxides, aluminosilicates and phosphates, and occur as layers 1–3 m thick occupying the upper part of lava flows on the southwest (site 1) and northwest (site 2) sites of the complex. Mineral constituents of the rocks include magnetite, ilmenite, hematite, rutile, corundum, andalusite, sillimanite, cordierite, quartz, plagioclase, alkali feldspar, apatite, Fe‐Mn phosphate, Al phosphate, micas and fine mixtures of sericite and silica. Texturally and compositionally, the rocks can be subdivided into globular type, banded type, and Al‐rich fine‐gained massive type. The first two types consist of dark globule or band enriched in Fe‐Ti oxides and apatite and lighter colored groundmass or bands enriched in aluminosilicates and quartz, respectively. The occurrence of andalusite and sillimanite and the compositional relations of magnetite and ilmenite in the FeO*‐Al2O3‐TiO2‐rich rocks suggest temperatures of crystallization in a range of 690–830°C at low pressures. The Bana FeO*‐Al2O3‐TiO2‐rich rocks are characterized by low concentrations of SiO2 (25–54.2 wt%), Na2O + K2O (0–1%), CaO (0–2%) and MgO (0–0.5%), and high concentrations of FeO* (total iron as FeO, 20–42%), Al2O3 (20–42%), TiO2 (3–9.2%), and P2O5 (0.26–1.30%). TiO2 is positively correlated with Al2O3 and inversely correlated with FeO*. The bulk rock compositions cannot be derived from the associated basaltic magma by crystal fractionation or by partial melting of the mantle or lower crustal materials. In ternary diagrams of (Al2O3)−(CaO + Na2O + K2O)−(FeO*+ MnO + MgO) and (SiO2)−(FeO*)−(Al2O3), the compositional field of the rocks is close to that of laterite and is distinct from the common volcanic rocks, suggesting that the rocks are derived from lateritic materials by recrystallization when the materials are heated by the basaltic magmas. A hydrothermal origin is discounted because the rocks contain high‐temperature mineral assemblages and lack sulfide minerals. It is proposed that the FeO*‐Al2O3‐TiO2‐rich rocks of the Bana complex were formed by pyrometamorphism of laterite by the heat of basaltic magmas.
Isolation of polymorphic microsatellite loci from the Chinese alligator (Alligator sinensis)
Authors: ZHU HAITAO , WU XIAOBING , XUE HUI , WEI LEI , HU YULING 
Published: February 2009

AbstractTen microsatellite loci were isolated from the Chinese alligator (Alligator sinensis), using a partial genomic DNA library and an enrichment method. Fifty microsatellite repeats were screened from the library of 888 positive clones, 10 of which were polymorphic. These microsatellite loci developed here are another set of novel molecular markers for A. sinensis, and they will be suitable for population genetic studies as well as for kinship analysis.
Microsatellite markers for the silver arowana (Osteoglossum bicirrhosum, Osteoglossidae, Osteoglossiformes)
Authors: DE JESUS DA SILVA THEMIS , HRBEK TOMAS , FARIAS IZENI P. 
Published: February 2009

Abstract Osteoglossum bicirrhosum (silver arowana) is an important fish for the economy of the Amazon region, both as an ornamental fish and as a food fish. To provide tools for addressing ecological and genetic questions, we developed 19 polymorphic microsatellite markers that had between 2 and 7 alleles per locus in the 24 tested individuals. The transferability of many of the loci was confirmed for Osteoglossum ferreirai (black arowana) and Arapaima gigas, and for three African osteoglossiform species.
FLOCK: a method for quick mapping of admixture without source samples
Authors: DUCHESNE P. , TURGEON J. 
Published: February 2009

AbstractIdentifying and estimating individual and/or population admixture is a very common objective in evolution and conservation biology. There are many situations where samples from one or many of the putatively hybridizing entities are not available or easily identified. Here we describe FLOCK, a new method especially designed to provide spatial and/or temporal admixture maps in the absence of one or several source samples. FLOCK is a non‐Bayesian method and therefore differs substantially from previous clustering algorithms. Its working principle is repeated re‐allocation of all collected specimens (total sample) to the k subsamples, each re‐allocation being more effective than the previous one in attracting genetically similar individuals. This snowball effect, more formally referred to as a positive feedback mechanism, makes FLOCK an efficient and quick sorting process. The usage of FLOCK is illustrated with two empirical situations which have been thoroughly analysed previously with other approaches. A number of simulations were run to better assess the power of the FLOCK algorithm. Performance comparisons were made between the FLOCK and Structure algorithms. When non‐negligible numbers of pure genotypes were present, the two performed equally well. However, FLOCK proved significantly more powerful in the absence of pure genotypes. Moreover, FLOCK showed more potential for fast processing. Run times were shown to increase linearly with size of total sample and with size of k, the number of reference samples from which admixture mapping is performed.