bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of the tetracycline repressor: Characterization by molecular‐dynamics simulations
Authors: Haberl Florian , Lanig Harald , Clark Timothy 
Published: June 2009

AbstractExtensive molecular‐dynamics simulations show that the distance between the centers of gravity of the two equivalent helices 3 in the DNA‐binding heads of the dimer of the tetracycline‐repressor protein (TetR) can be used as a reliable diagnostic of induction. This is not, however, true for X‐ray structures, but only for molecular‐dynamics simulations. This is suggested to be because TetR is inherently flexible along the coordinate of the allosteric change (as is always likely to be the case for allosteric proteins), so that crystal‐packing forces can determine the conformation of the protein. However, the time scale of the allosteric rearrangement in the absence of DNA‐complexationis found to be of the order of tens of nanoseconds, so that rearrangements can be observed reproducibly in 100 ns simulations. Metastable (pre‐equilibrium) conformations of TetR have been observed for up to 60 ns. The likely equilibrium processes and key features of the TetR system are discussed. Proteins 2009. © 2009 Wiley‐Liss, Inc.
Muscle FBPase is targeted to nucleus by its 203KKKGK207 sequence
Authors: Gizak Agnieszka , Maciaszczyk‐Dziubinska Ewa , Jurowicz Magdalena , Rakus Dariusz 
Published: June 2009

AbstractIt has been recently found that muscle fructose 1,6‐bisphosphatase (FBPase) is actively transported into cells' nuclei. Results of an analysis in silico of muscle FBPase structure gave rise to a hypothesis that sequence 203KKKGK207 is responsible for nuclear targeting of the enzyme. To test this, HL‐1 cardiomyocytes were transfected with FITC‐labeled muscle FBPase constructs, bearing mutations within the putative nuclear localization signal (NLS). Results revealed that integrity of the 203KKKGK207 motif is critical to nuclear targeting of muscle FBPase and even a single amino‐acid change within this sequence results in significant decrease of nuclear accumulation of the enzyme. Although it has long been recognized as a canonical NLS in theoretical and computational research, to the best of our knowledge this is the first experimental evidence confirming that the KKKGK motif can act as a functional NLS in a protein. Proteins 2009. © 2009 Wiley‐Liss, Inc.
GPCR 3D homology models for ligand screening: Lessons learned from blind predictions of adenosine A2a receptor complex
Authors: Katritch Vsevolod , Rueda Manuel , Lam Polo Chun‐Hung , Yeager Mark , Abagyan Ruben 
Published: June 2009

AbstractProteins of the G‐protein coupled receptor (GPCR) family present numerous attractive targets for rational drug design, but also a formidable challenge for identification and conformational modeling of their 3D structure. A recently performed assessment of blind predictions of adenosine A2a receptor (AA2AR) structure in complex with ZM241385 (ZMA) antagonist provided a first example of unbiased evaluation of the current modeling algorithms on a GPCR target with ∼ 30% sequence identity to the closest structural template. Several of the 29 groups participating in this assessment exercise (Michino et al., doi: 10.1038/nrd2877) successfully predicted the overall position of the ligand ZMA in the AA2AR ligand binding pocket, however models from only three groups captured more than 40% the ligand‐receptor contacts. Here we describe two of these top performing approaches, in which all‐atom models of the AA2AR were generated by homology modeling followed by ligand guided backbone ensemble receptor optimization (LiBERO). The resulting AA2AR‐ZMA models, along with the best models from other groups are assessed here for their vitual ligand screening (VLS) performance on a large set of GPCR ligands. We show that ligand guided optimization was critical for improvement of both ligand‐receptor contacts and VLS performance as compared to the initial raw homology models. The best blindly predicted models performed on par with the crystal structure of AA2AR in selecting known antagonists from decoys, as well as from antagonists for other adenosine subtypes and AA2AR agonists. These results suggest that despite certain inaccuracies, the optimized homology models can be useful in the drug discovery process. Proteins 2010. © 2009 Wiley‐Liss, Inc.
Applying Undertaker to quality assessment
Authors: Archie John G. , Paluszewski Martin , Karplus Kevin 
Published: June 2009

AbstractOur group tested three quality assessment functions in CASP8: a function which used only distance constraints derived from alignments (SAM‐T08‐MQAO), a function which added other single‐model terms to the distance constraints (SAM‐T08‐MQAU), and a function which used both single‐model and consensus terms (SAM‐T08‐MQAC). We analyzed the functions both for ranking models for a single target and for producing an accurate estimate of GDT_TS. Our functions were optimized for the ranking problem, so are perhaps more appropriate for metaserver applications than for providing trustworthiness estimates for single models. On the CASP8 test, the functions with more terms performed better. The MQAC consensus method was substantially better than either single‐model function, and the MQAU function was substantially better than the MQAO function that used only constraints from alignments. Proteins 2009. © 2009 Wiley‐Liss, Inc.
Cancer‐associated mutations are preferentially distributed in protein kinase functional sites
Authors: Izarzugaza Jose M. G. , Redfern Oliver C. , Orengo Christine A. , Valencia Alfonso 
Published: June 2009

AbstractProtein kinases are a superfamily involved in many crucial cellular processes, including signal transmission and regulation of cell cycle. As a consequence of this role, kinases have been reported to be associated with many types of cancer and are considered as potential therapeutic targets. We analyzed the distribution of pathogenic somatic point mutations (drivers) in the protein kinase superfamily with respect to their location in the protein, such as in structural, evolutionary, and functionally relevant regions. We find these driver mutations are more clearly associated with key protein features than other somatic mutations (passengers) that have not been directly linked to tumor progression. This observation fits well with the expected implication of the alterations in protein kinase function in cancer pathogenicity. To explain the relevance of the detected association of cancer driver mutations at the molecular level in the human kinome, we compare these with genetically inherited mutations (SNPs). We find that the subset of nonsynonymous SNPs that are associated to disease, but sufficiently mild to the point of being widespread in the population, tend to avoid those key protein regions, where they could be more detrimental for protein function. This tendency contrasts with the one detected for cancer associated‐driver‐mutations, which seems to be more directly implicated in the alteration of protein function. The detailed analysis of protein kinase groups and a number of relevant examples, confirm the relation between cancer associated‐driver‐mutations and key regions for protein kinase structure and function. Proteins 2009. © 2009 Wiley‐Liss, Inc.
Prediction of ligand binding sites using homologous structures and conservation at CASP8
Authors: Wass Mark N. , Sternberg Michael J. E. 
Published: June 2009

AbstractThe critical assessment of protein structure prediction experiment is a blind assessment of the prediction of protein structure and related topics including function prediction. We present our results in the function/binding site prediction category. Our approach to identify binding sites combined the use of the predicted structure of the targets with both residue conservation and the location of ligands bound to homologous structures. We obtained an average coverage of 83% and 56% accuracy. Analysis of our predictions suggests that overprediction reduces the accuracy obtained due to large areas of conservation around the binding site that do not bind the ligand. In some proteins such conserved residues may have a functional role. A server version of our method will soon be available. Proteins 2009. © 2009 Wiley‐Liss, Inc.
Inhibition of P‐glycoprotein function by procyanidine on blood–brain barrier
Authors: He Ling , Zhao Chuan , Yan Ming , Zhang Lu‐Yong , Xia Yuan‐Zheng 
Published: June 2009

AbstractThe inhibitory effects of procyanidine, one of the components from the bark ofPinus massonianaLamb, on the P‐glycoprotein (P‐gp) function of the blood–brain barrier (BBB) were studied usingin vitrorat brain microvessel endothelial cells (RBMECs) and nude mice transplanted with human cerebroma. Quantitative accumulation and efflux of rhodamine 123 (Rh123), a P‐gp substrate, were determined using a fluorescence spectrophotometer as a measure of P‐gp function. Procyanidine markedly increased the accumulation of Rh123 by inhibiting its efflux in a dose‐dependent manner. A 5‐fold increase in cellular Rh123 was observed for procyanidine at 10 µmol/L. The verapamil‐stimulated ATPase activity in plasma membrane vesicles from the RBMECs was estimated by measuring inorganic phosphate liberation. Procyanidine significantly inhibited the verapamil‐induced P‐gp ATPase activity by 78% when pretreated with 10 µmol/L in a concentration‐dependent manner. The inhibition of P‐gp by procyanidine was suggested to be at least partly due to its inhibition of P‐gp ATPase. Procyanidine markedly improved the therapeutic effects of adriamycin (ADM) on nude mice transplanted with human cerebroma, compared with solitary treatment of ADM. The combination of 80 mg/kg procyanidine with 2 mg/kg ADM significantly elevated the days of survival with an increase in life span of 76%. The findings suggested that procyanidine was a potent inhibitor of P‐gp on BBB and could improve the therapeutic effects on cerebral tumors of some drugs which are difficult to accumulate in the brain. Copyright © 2009 John Wiley & Sons, Ltd.
The super‐droplet method for the numerical simulation of clouds and precipitation: a particle‐based and probabilistic microphysics model coupled with a non‐hydrostatic model
Authors: Shima S. , Kusano K. , Kawano A. , Sugiyama T. , Kawahara S. 
Published: June 2009

AbstractA novel, particle‐based, probabilistic approach for the simulation of cloud microphysics is proposed, which is named the super‐droplet method (SDM). This method enables the accurate simulation of cloud microphysics with a less demanding cost in computation. SDM is applied to a warm‐cloud system, which incorporates sedimentation, condensation/evaporation and stochastic coalescence. The methodology to couple super‐droplets and a non‐hydrostatic model is also developed. It is confirmed that the result of our Monte Carlo scheme for the stochastic coalescence of super‐droplets agrees fairly well with the solutions of the stochastic coalescence equation. The behaviour of the model is evaluated using a simple test problem, that of a shallow maritime cumulus formation initiated by a warm bubble. Possible extensions of SDM are briefly discussed. A theoretical analysis suggests that the computational cost of SDM becomes lower than the spectral (bin) method when the number of attributes—the variables that identify the state of each super‐droplet—becomes larger than some critical value, which we estimate to be in the range$2\sim4$. Copyright © 2009 Royal Meteorological Society
Organizational attributes of Highly Reliable complex systems
Authors: Gifun J. F. , Karydas D. M. 
Published: June 2009

AbstractOrganizations that effectively anticipate, resist, and recover from disasters and system disturbances follow the successful practices of organizations that embody high organizational quality, reliability, disaster resistance, and resilience as a precondition for product or service quality and reliability. The model proposed herein was developed and derived from acomprehensive examination of the following organizational models: the High Reliability Organization, the Disaster Resistant University, the Resilient Enterprise, Enterprise Risk Management, Risk‐Based Process Safety, Reactor Oversight Process, Hearts and Minds, and Business Continuity Planning. The proposed model, named the Highly Reliable Resilient Organization, integrates the common attributes of each these models and optimizes the balance of complexity and simplicity to ensure that the model is comprehensive enough to reflect reality and yet manageable within the operational systems of the organization. This balance provides value to the organization and ensures sustained use of the model. A case study describing the method used by a stakeholder group to verify the model and assign weights to the criteria therein is included. Copyright © 2009 John Wiley & Sons, Ltd.
Cumulative impacts of river engineering, Mississippi and Lower Missouri rivers
Authors: Pinter Nicholas , Jemberie Abebe A. , Remo Jonathan W. F. , Heine Reuben A. , Ickes Brian S. 
Published: June 2009

AbstractThe goal of this study was to construct a large, data‐rich model to test hydrological responses to engineering modifications on over 3200 km of the Mississippi and Lower Missouri Rivers. We compiled model explanatory variables from a geospatial database quantifying construction of all bridges, wing dikes, bendway weirs, levees, artificial meander cutoffs, channel constriction and navigational dams over the past 100–150 years. Response variables were derived from 68 rated and un‐rated hydrologic stations in the study area, with responses analysed across a range of discharges from within‐channel flows up to moderate floods. Correlation analysis, multiple linear regression and stepwise regression analyses document strong and consistent responses to construction history, both in individual reach‐scale models and systemwide. Meander cutoffs are associated with degradation and acceleration of flow that has reduced stages across the full discharge range. Navigational dams on the Upper Mississippi River increased low‐flow stages and flood levels to a lesser extent, with little or no post‐dam change. One of the strongest signals was the hydrologic response to wing‐dike construction, which resulted in large back‐water increases in stage upstream of wing dikes and mixed effects downstream, including the overlapping effects of incision and velocity losses. Levees were associated with local flow concentration, overbank storage loss and floodplain conveyance loss depending on reach‐scale conditions. The results presented here (1) quantify incremental and cumulative hydrologic responses to a range of engineering activities and (2) provide an empirical tool for verifying and assessing hydraulic and other models of river‐system change. Copyright © 2009 John Wiley & Sons, Ltd.
Cotransplantation of Placental Mesenchymal Stromal Cells Enhances Single and Double Cord Blood Engraftment in Nonobese Diabetic/Severe Combined Immune Deficient Mice
Authors: Hiwase Smita D , Dyson Pamela G , To L. Bik , Lewis Ian D. 
Published: June 2009

Abstract
Limited cell numbers in a unit restricts cord blood transplantation (CBT) in adults. We evaluated whether cotransplantation of placental mesenchymal stromal cells (MSCs) would enhance engraftment. Plastic adherent cells from placenta demonstrated typical characteristics of MSCs. In six individual experiments, 4 cohorts of 24 nonobese diabetic/severe combined immune deficient (NOD/SCID) mice were evaluated. Cohort 1 received 5 × 104 CD34+ cells from unit (U) one (SCBT); cohort 2 received 5 × 104 CD34+ cells from U1 + 4 × 104 MSCs (SCBT+MSCs); cohort 3 received 2.5 × 104 CD34+ cells from U1 + 2.5 × 104 CD34+ cells from U2 (double cord blood transplant [DCBT]); cohort 4 received 2.5 × 104 CD34+ cells from U1 + 2.5 × 104 CD34+ cells from U2 + 4 × 104 MSCs (DCBT+MSCs). Hematopoietic engraftment evaluated after 6 to 8 weeks, was similar in recipients of SCBT and DCBT. MSC cotransplantation demonstrated enhanced engraftment in DCBT (51.8 ± 6.8% versus 14.9 ± 6.5%; p = .04) with an increased trend in SCBT (48.7 ± 7.7% versus 17.5 ± 6.1%; p = .07). In DCBT, cotransplantation of placental MSCs reduced single cord dominance. Self-renewal capacity was assessed by serial transplantation in secondary recipients infused with engrafted human cells from primary mice transplanted with or without MSCs. In secondary transplant experiments, 13 of 17 evaluable mice engrafted at levels of 1% to 6.5%. Despite enhanced engraftment in primary mice, long-term engraftment capacity was unaltered with MSC cotransplantation. Imaging studies showed MSCs migrated to pelvic region and improved cord blood (CB) CD34+ homing. Cotransplantation of placental MSCs enhanced cord blood engraftment and may act by improving homing of CD34+ cells.
Disclosure of potential conflicts of interest is found at the end of this article.
Species composition, diversity, and abundance of lianas in different secondary and primary forests in a subtropical mountainous area, SW China
Authors: Yuan Chun‐ming , Liu Wen‐yao , Tang Cindy Q. , Li Xiao‐shuang 
Published: June 2009

AbstractThe species composition, diversity, and abundance of lianas were studied in four secondary forests (a 100‐year‐old forest, a middle‐aged forest, and two younger secondary forests), and compared with an undisturbed primary forest in the Ailao Mountains of subtropical SW China. The results showed that the species composition of lianas differed greatly from the secondary forests to the primary forest, which exhibit early and late‐successional species. The abundance of lianas was relatively higher in the two younger and middle‐aged secondary forests than in the old‐growth secondary and primary forests. However, liana species richness was very limited in the four secondary forests as compared to the primary forest. Root climbers mainly grew in the primary forest, whereas tendril and hook climbers predominated in the four secondary forests, while stem twiners were common in both. The majority of lianas recorded in this study reproduced by animal dispersal, and there was no variation in dispersal modes across the five forest types. A step‐wise regression showed that the abundance of small lianas (dbh <4 cm) was positively correlated with the abundance of small‐ and medium‐sized tree stems and negatively correlated with the abundance of large‐sized tree stems, whereas there is a strong positive correlation between the abundance of large lianas (dbh ≥4 cm) and large tree stems. Results from the CCA indicate that canopy openness, soil moisture, and average canopy height were the most important factors that influenced the abundance and distribution of lianas.
Preparation and Characterization of Silica-Coated Magnetic–Fluorescent Bifunctional Microspheres
Authors: Xiao Qi , Xiao Chong 
Published: June 2009

Abstract
Bifunctional magnetic–fluorescent composite nanoparticles (MPQDs) with Fe3O4MPs and Mn:ZnS/ZnS core–shell quantum dots (QDs) encapsulated in silica spheres were synthesized through reverse microemulsion method and characterized by X-ray powder diffraction, scanning electron microscopy, transmission electron microscopy, vibration sample magnetometer, and photoluminescence (PL) spectra. Our strategy could offer the following features: (1) the formation of Mn:ZnS/ZnS core/shell QDs resulted in enhancement of the PL intensity with respect to that of bare Mn:ZnS nanocrystals due to the effective elimination of the surface defects; (2) the magnetic nanoparticles were coated with silica, in order to reduce any detrimental effects on the QD PL by the magnetic cores; and (3) both Fe3O4MPs and Mn:ZnS/ZnS core–shell QDs were encapsulated in silica spheres, and the obtained MPQDs became water soluble. The experimental conditions for the silica coating on the surface of Fe3O4nanoparticles, such as the ratio of water to surfactant (R), the amount of ammonia, and the amount of tetraethoxysilane, on the photoluminescence properties of MPQDs were studied. It was found that the silica coating on the surface of Fe3O4could effectively suppress the interaction between the Fe3O4and the QDs under the most optimal parameters, and the emission intensity of MPQDs showed a maximum. The bifunctional MPQDs prepared under the most optimal parameters have a typical diameter of 35 nm and a saturation magnetization of 4.35 emu/g at room temperature and exhibit strong photoluminescence intensity.
Synthesis of Tin Nitride Sn
x
N
y
Nanowires by Chemical Vapour Deposition
Authors: Zervos Matthew , Othonos Andreas 
Published: June 2009

Abstract
Tin nitride (Sn
x
N
y
) nanowires have been grown for the first time by chemical vapour deposition on n-type Si(111) and in particular by nitridation of Sn containing NH4Cl at 450 °C under a steady flow of NH3. The Sn
x
N
y
nanowires have an average diameter of 200 nm and lengths ≥5 μm and were grown on Si(111) coated with a few nm’s of Au. Nitridation of Sn alone, under a flow of NH3is not effective and leads to the deposition of Sn droplets on the Au/Si(111) surface which impedes one-dimensional growth over a wide temperature range i.e. 300–800 °C. This was overcome by the addition of ammonium chloride (NH4Cl) which undergoes sublimation at 338 °C thereby releasing NH3and HCl which act as dispersants thereby enhancing the vapour pressure of Sn and the one-dimensional growth of Sn
x
N
y
nanowires. In addition to the action of dispersion, Sn reacts with HCl giving SnCl2which in turn reacts with NH3leading to the formation of Sn
x
N
y
NWs. A first estimate of the band-gap of the Sn
x
N
y
nanowires grown on Si(111) was obtained from optical reflection measurements and found to be ≈2.6 eV. Finally, intricate assemblies of nanowires were also obtained at lower growth temperatures.
Metabolites from an Endophytic Fungus Sphaceloma sp. LN‐15 Isolated from the Leaves of Melia azedarach
Authors: Zhang An‐Ling , He Li‐Ying , Gao Jin‐Ming , Xu Xu , Li Shi‐Qing , Bai Ming‐Sheng , Qin Jian‐Chun 
Published: June 2009

AbstractTwo new natural compounds, a symmetrical disulfide dimer didodecyl 3,3″‐dithiodipropionate (1) and a pregnane steroid 5,16‐pregnadien‐3β‐ol‐20‐one acetate (2), were isolated together with two known compounds, ergosta‐4,6,8(14),22‐tetraen‐3‐one (3) and ergosterol peroxide (4), from the ethyl acetate soluble extract of fermentation broth of an endophytic fungus, Sphaceloma sp. LN‐15 isolated from the leaves of Melia azedarach L. and grown in pure culture. Their structures were determined on the basis of spectroscopic methods including 1D and 2D nuclear magnetic resonance spectroscopy (NMR) experiments and by mass spectrometric measurements (MS). These fungal metabolites were isolated for the first time from the genus Sphaceloma. The structure of 1 was also confirmed by chemical synthesis.
Differential Scanning Calorimetry Analysis of Goat Fats: Comparison of Chemical Composition and Thermal Properties
Authors: Yılmaz Mustafa Tahsin , Karakaya M. 
Published: June 2009

AbstractThe physical–chemical properties, fatty acid composition and thermal properties of goat subcutaneous (SF), tallow (TF) and intestinal (IF) fats were determined. SF differed from other fat types with respect to its lower melting (41.6 °C), lower saponification (190.3 mg KOH/g) and higher iodine (40.4) values as compared to those of other fats. Goat fat types contained palmitic acid (C16:0), stearic acid (C18:0), oleic acid (C18:1ω9) and linoleic acid (C18:2ω6) as the major components of the fatty acid composition (23.06–23.52, 22.95–39.03, 21.94–36.16 and 1.96–2.22%, respectively). A differential scanning calorimetry (DSC) study revealed that two characteristic peaks were detected in both crystallization and melting curves. Major peaks (Tpeak) of TF and IF were similar and determined as 34.02–35.24 and 9.95–10.72 °C, respectively for the crystallization peaks and 15.11–18.26 and 50.70–52.76 °C, respectively for the melting peaks in the DSC curves; but those of SF (27.14 and 4.36 °C for crystallization peaks and 8.39 and 44.93 °C for melting peaks) differed remarkably from those of other fat types.