bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational protein design suggests that human PCNA‐partner interactions are not optimized for affinity
Authors: Fridman Yearit , Gur Eyal , Fleishman Sarel J. , Aharoni Amir 
Published: January 2013

AbstractIncreasing the affinity of binding proteins is invaluable for basic and applied biological research. Currently, directed protein evolution experiments are the main approach for generating such proteins through the construction and screening of large mutant libraries. Proliferating cell nuclear antigen (PCNA) is an essential hub protein that interacts with many different partners to tightly regulate DNA replication and repair in all eukaryotes. Here, we used computational design to generate human PCNA mutants with enhanced affinity for several different partners. We identified double mutations in PCNA, outside the main partner binding site, that were predicted to increase PCNA‐partner binding affinities compared to the wild‐type protein by forming additional hydrophobic interactions with conserved residues in the PCNA partners. Affinity increases were experimentally validated with four different PCNA partners, demonstrating that computational design can reveal unexpected regions where affinity enhancements in natural systems are possible. The designed PCNA mutants can be used as a valuable tool for further examination of the regulation of PCNA‐partner interactions during DNA replication and repair both in vitro and in vivo. More broadly, the ability to engineer affinity increases toward several PCNA partners suggests that interaction affinity is not an evolutionarily optimized trait of this system. Proteins 2013. © 2012 Wiley Periodicals, Inc.
Simulation of the mutation F76del on the von Hippel–Lindau tumor suppressor protein: Mechanism of the disease and implications for drug development
Authors: Limaverde‐Sousa Gabriel , de Andrade Barreto Ester , Ferreira Carlos Gil , Cláudio Casali‐da‐Rocha José 
Published: January 2013

AbstractThe von Hippel–Lindau tumor suppressor protein (pVHL) plays a central role in the oxygen‐sensing pathway by regulating the degradation of the hypoxia‐inducible factor (HIF‐1α). The capture of HIF‐1α by pVHL is regulated by an oxygen‐dependent hydroxylation of a specific conserved prolyl residue. The VHL gene is mutated in the von Hippel–Lindau cancer predisposition syndrome, which is characterized by the development of highly vascularized tumors and is associated with constitutively high levels of HIF‐1α. The disturbance of the dynamic coupling between HIF‐1α and pVHL bearing the commonly found mutation F76del was experimentally confirmed but the mechanism of such complex disruption is still not clear. Performing unbiased molecular dynamics simulations, we show that the F76del mutation may enlarge the HIF binding pocket in pVHL and induce the formation of an internal cavity in the hydrophobic core of the β‐domain, which can lead to a partial destabilization of the β‐sheets S1, S4, and S7 and a consequent loss of hydrogen bonds with a conserved recognition motif in HIF. The newly formed cavity has a significant druggability score and may be a suitable target for stabilizing ligands. Studies of this nature may help to fill the information gap between genotype–phenotype correlations with details obtained at atomic level and provide basis for future development of drug candidates, such as pharmacological chaperones, with the specific aim of reverting the dysfunction of such pathological protein complexes found in patients with VHL. Proteins 2013. © 2012 Wiley Periodicals, Inc.
Enhanced critical current density in MgB2 prepared by reaction of MgB4 and Mg
Authors: Tan K. L. , Lim K. P. , Halim A. S. , Chen S. K. 
Published: January 2013

AbstractInstead of reacting B and Mg powders, MgB4 was used as precursor to react with Mg to obtain the polycrystalline samples of nominal composition MgxB2 (x = 1.2, 1.5, and 1.7). Upon increasing the sintering temperature to 750 °C, the reaction between MgB4 and Mg was thermodynamically intensified leading to the formation of larger MgB2 weight fraction as estimated from X‐ray diffraction (XRD) data using the Rietveld method. Despite no further improvement to the weight fraction of this phase by increasing the excess nominal Mg, it was shown that the critical current density (Jc) was enhanced by almost one order of magnitude. At 5 K, 2 T, Jc for the sample Mg1.5B2 is estimated to be 4.5 × 105 A cm−2. The enhancement of Jc is attributed to the collective effect of improved grain connectivity and flux pinning by unreacted Mg. Incorporation of nano‐SiC for reaction resulted in a more gradual drop of Jc with applied magnetic field. Hence, Jc can be tailored to meet the range of fields intended for various applications via optimization of excess nominal Mg and dopant additions.
Defect and analysis effects in the infrared optical properties of silicon
Authors: Smith D. Y. , Karstens W. , Shiles E. , Inokuti Mitio 
Published: January 2013

AbstractThe infrared optical properties of silicon reported by different workers disagree by far more than the precision of the measurements. Further, their extrapolations conflict with THz measurements. These inconsistencies are commonly attributed to crystal defects or impurities, but lack of reliable intrinsic silicon values hampers separation of host and defect effects. We have developed tests based on linear‐response theory to address this. Tests include requiring that the refractive index is an even function of photon energy, and comparing the coefficients of a Taylor expansion of the IR index with the moments of the electronic absorption above the band gap. The latter is sufficiently well known for silicon that predictions for the intercept, slope, and curvature, of the index may be used to test infrared measurements for consistency. Thus, we identified the sources of conflict as: (i) A physically inconsistent assumption for index parity commonly made in analysis of channel‐spectra. (ii) Defect and free‐carrier absorption. Eliminating data sets with these shortcomings resolved the conflict between measurements and allowed us to develop a composite set of IR optical constants for silicon that is a best fit to reliable measurements from microwaves to the visible.
Valence‐band effective‐potential evolution for coupled holes
Authors: Flores‐Godoy J. J. , Mendoza‐Álvarez A. , Diago‐Cisneros L. , Fernández‐Anaya G. 
Published: January 2013

AbstractWe present the metamorphosis in the effective‐potential profile of layered heterostructures, for several III–V semiconductor binary compounds, when the band mixing of light and heavy holes increases. A root‐locus‐like procedure is directly applied to an eigenvalue quadratic problem obtained from a multichannel system of coupled modes, in the context of the multiband effective mass approximation. By letting grow valence‐band mixing, it is shown that the standard fixed‐height rectangular potential energy for the scatterer distribution is a reliable test‐run input for heavy holes. On the contrary, this scheme is no longer valid for light holes and a mutable effective band offset profile has to be considered instead whenever the in‐plane kinetic energy changes.
Vibrational spectroscopic studies on pure and metal‐covered metal oxide surfaces
Authors: Noei Heshmat , Jin Lanying , Qiu Hengshan , Xu Mingchun , Gao Youkun , Zhao Jianli , Kauer Max , Wöll Christof , Muhler Martin , Wang Yuemin 
Published: January 2013

AbstractMetal oxides and metal nanoparticles dispersed on oxide substrates have gained increasing interest in surface science because of their widespread applications, especially in heterogeneous catalysis. In this review we summarize our recent vibrational spectroscopic studies on pure and metal‐covered oxide surfaces (ZnO, TiO2, Au/ZnO and Cu/ZnO) using a number of small molecules (H2, CO, CO2, NO and HCOOH) as probes and/or reactants. High‐resolution electron energy loss spectroscopy (HREELS) turned out to be a powerful tool to investigate well‐defined oxide and metal/oxide model systems. The application of a novel ultrahigh vacuum IR spectroscopy (UHV‐FTIRS) apparatus allowed us to record high‐quality IR data on oxide surfaces of both single crystals and polycrystalline powder particles. We will particularly focus on following important issues: (i) the interaction of hydrogen with ZnO; (ii) structure and reactivity of polar and nonpolar ZnO surfaces; (iii) the role of defects in surface chemistry of oxides; (iv) the origin of significant difference in photocatalytic activity between anatase and rutile TiO2 and (v) the interaction between metal nanoparticles and oxide supports. We will demonstrate that the data from HREELS and UHV‐FTIRS provide detailed insight into structural, electronic and chemical properties of the studied systems.
Failure mode and effects analysis in designing a virtual reality‐based training simulator for bilateral sagittal split osteotomy
Authors: Sofronia R. E. , Knott T. , Davidescu A. , Savii G. G. , Kuhlen T. , Gerressen M. 
Published: January 2013

AbstractBackgroundVirtual reality‐based simulators offer a cost‐effective and efficient alternative to traditional medical training and planning. Developing a simulator that enables the training of medical skills and also supports recognition of errors made by the trainee is a challenge. The first step in developing such a system consists of error identification in the real procedure, in order to ensure that the training environment covers the most significant errors that can occur. This paper focuses on identifying the main system requirements for an interactive simulator for training bilateral sagittal split osteotomy (BSSO).MethodsAn approach is proposed based on failure mode and effects analysis (FMEA), a risk analysis method that is well structured and already an approved technique in other domains.ResultsBased on the FMEA results, a BSSO training simulator is currently being developed, which centres upon the main critical steps of the procedure (sawing and splitting) and their main errors.ConclusionsFMEA seems to be a suitable tool in the design phase of developing medical simulators. Herein, it serves as a communication medium for knowledge transfer between the medical experts and the system developers. The method encourages a reflective process and allows identification of the most important elements and scenarios that need to be trained. Copyright © 2013 John Wiley & Sons, Ltd.
An efficient online trajectory generating method for underactuated crane systems
Authors: Sun Ning , Fang Yongchun 
Published: January 2013

SUMMARYIn this paper, a trajectory planning approach is proposed for underactuated overhead cranes. Different from existing trajectory planning methods, the presented approach generates trajectory commands online without the necessity of iterative optimization, which is convenient for practical implementation. We demonstrate the performance of the proposed method, including swing elimination and precise trolley positioning, with rigorous Lyapunov‐based mathematical analysis. Both numerical simulation and experimental results suggest that the presented method is feasible and efficient for practical applications. Copyright © 2013 John Wiley & Sons, Ltd.
Self‐Organized Graphene Nanosheets with Corrugated, Ordered Tip Structures for High‐Performance Flexible Field Emission
Authors: Jeong Hee Jin , Jeong Hae Deuk , Kim Ho Young , Jeong Seung Yol , Han Joong Tark , Lee Geon‐Woong 
Published: January 2013

AbstractPatterned reduced graphene oxide (rGO) films with vertically aligned tip structures are fabricated by a straightforward self‐assembly method. The size, uniformity of the patterns, and alignment of the tips are successfully controlled according to the concentration of a GO/octadecylamine (ODA)‐dispersed solution. The surface energy difference between the GO/ODA solution and a self‐assembled water droplet is a critical parameter for determining the pattern structure. Numerous rGO nanosheets are formed so as to be vertically aligned with respect to the substrate during film fabrication at GO concentrations below 2.0 g/L. These samples provide high field‐emission characteristics. The patterned rGO arrays are highly flexible with preservation of the field emission properties, even at large bending angles. This is attributed to the high crystallinity, emitter density, and good chemical stability of the rGO arrays, as well as the strong interactions between the rGO arrays and the substrate.
Dynamic Migration and Cell-Cell Interactions of Early Reprogramming Revealed by High-Resolution Time-Lapse Imaging
Authors: Megyola Cynthia M. , Gao Yuan , Teixeira Alexandra M. , Cheng Jijun , Heydari Kartoosh , Cheng Ee-Chun , Nottoli Timothy , Krause Diane S. , Lu Jun , Guo Shangqin 
Published: January 2013

Abstract
Discovery of the cellular and molecular mechanisms of induced pluripotency has been hampered by its low efficiency and slow kinetics. Here, we report an experimental system with multicolor time-lapse microscopy that permits direct observation of pluripotency induction at single cell resolution, with temporal intervals as short as 5 minutes. Using granulocyte-monocyte progenitors as source cells, we visualized nascent pluripotent cells that emerge from a hematopoietic state. We engineered a suite of image processing and analysis software to annotate the behaviors of the reprogramming cells, which revealed the highly dynamic cell-cell interactions associated with early reprogramming. We observed frequent cell migration, which can lead to sister colonies, satellite colonies, and colonies of mixed genetic makeup. In addition, we discovered a previously unknown morphologically distinct two-cell intermediate of reprogramming, which occurs prior to other reprogramming landmarks. By directly visualizing the reprogramming process with E-cadherin inhibition, we demonstrate that E-cadherin is required for proper cellular interactions from an early stage of reprogramming, including the two-cell intermediate. The detailed cell-cell interactions revealed by this imaging platform shed light on previously unappreciated early reprogramming dynamics. This experimental system could serve as a powerful tool to dissect the complex mechanisms of early reprogramming by focusing on the relevant but rare cells with superb temporal and spatial resolution.
Protein O-GlcNAcylation Is a Novel Cytoprotective Signal in Cardiac Stem Cells
Authors: Zafir Ayesha , Readnower Ryan , Long Bethany W. , McCracken James , Aird Allison , Alvarez Alejandro , Cummins Timothy D. , Li Qianhong , Hill Bradford G. , Bhatnagar Aruni , Prabhu Sumanth D. , Bolli Roberto , Jones Steven P. 
Published: January 2013

Abstract
Clinical trials demonstrate the regenerative potential of cardiac stem cell (CSC) therapy in the postinfarcted heart. Despite these encouraging preliminary clinical findings, the basic biology of these cells remains largely unexplored. The principal requirement for cell transplantation is to effectively prime them for survival within the unfavorable environment of the infarcted myocardium. In the adult mammalian heart, the β-O-linkage of N-acetylglucosamine (i.e., O-GlcNAc) to proteins is a unique post-translational modification that confers cardioprotection from various otherwise lethal stressors. It is not known whether this signaling system exists in CSCs. In this study, we demonstrate that protein O-GlcNAcylation is an inducible stress response in adult murine Sca-1+/lin− CSCs and exerts an essential prosurvival role. Posthypoxic CSCs responded by time-dependently increasing protein O-GlcNAcylation upon reoxygenation. We used pharmacological interventions for loss- and gain-of-function, that is, enzymatic inhibition of O-GlcNAc transferase (OGT) (adds the O-GlcNAc modification to proteins) by TT04, or inhibition of OGA (removes O-GlcNAc) by thiamet-G (ThG). Reduction in the O-GlcNAc signal (via TT04, or OGT gene deletion using Cre-mediated recombination) significantly sensitized CSCs to posthypoxic injury, whereas augmenting O-GlcNAc levels (via ThG) enhanced cell survival. Diminished O-GlcNAc levels render CSCs more susceptible to the onset of posthypoxic apoptotic processes via elevated poly(ADP-ribose) polymerase cleavage due to enhanced caspase-3/7 activation, whereas promoting O-GlcNAcylation can serve as a pre-emptive antiapoptotic signal regulating the survival of CSCs. Thus, we report the primary demonstration of protein O-GlcNAcylation as an important prosurvival signal in CSCs, which could enhance CSC survival prior to in vivo autologous transfer.
IGF1 Receptor Signaling Regulates Adaptive Radioprotection in Glioma Stem Cells
Authors: Osuka Satoru , Sampetrean Oltea , Shimizu Takatsune , Saga Isako , Onishi Nobuyuki , Sugihara Eiji , Okubo Jun , Fujita Satoshi , Takano Shingo , Matsumura Akira , Saya Hideyuki 
Published: January 2013

Abstract
Cancer stem cells (CSCs) play an important role in disease recurrence after radiation treatment as a result of intrinsic properties such as high DNA repair capability and antioxidative capacity. It is unclear, however, how CSCs further adapt to escape the toxicity of the repeated irradiation regimens used in clinical practice. Here, we have exposed a population of murine glioma stem cells (GSCs) to fractionated radiation in order to investigate the associated adaptive changes, with the ultimate goal of identifying a targetable factor that regulates acquired radioresistance. We have shown that fractionated radiation induces an increase in IGF1 secretion and a gradual upregulation of the IGF type 1 receptor (IGF1R) in GSCs. Interestingly, IGF1R upregulation exerts a dual radioprotective effect. In the resting state, continuous IGF1 stimulation ultimately induces downregulation of Akt/extracellular-signal-regulated kinases (ERK) and FoxO3a activation, which results in slower proliferation and enhanced self-renewal. In contrast, after acute radiation, the abundance of IGF1R and increased secretion of IGF1 promote a rapid shift from a latent state toward activation of Akt survival signaling, protecting GSCs from radiation toxicity. Treatment of tumors formed by the radioresistant GSCs with an IGF1R inhibitor resulted in a marked increase in radiosensitivity, suggesting that blockade of IGF1R signaling is an effective strategy to reverse radioresistance. Together, our results show that GSCs evade the damage of repeated radiation not only through innate properties but also through gradual inducement of resistance pathways and identify the dynamic regulation of GSCs by IGF1R signaling as a novel mechanism of adaptive radioprotection.
The CD44+ALDH+ Population of Human Keratinocytes Is Enriched for Epidermal Stem Cells with Long-Term Repopulating Ability
Authors: Szabo Akos Z. , Fong Stephen , Yue Lili , Zhang Kai , Strachan Lauren R. , Scalapino Kenneth , Mancianti Maria Laura , Ghadially Ruby 
Published: January 2013

Abstract
Like for other somatic tissues, isolation of a pure population of stem cells has been a primary goal in epidermal biology. We isolated discrete populations of freshly obtained human neonatal keratinocytes (HNKs) using previously untested candidate stem cell markers aldehyde dehydrogenase (ALDH) and CD44 as well as the previously studied combination of integrin α6 and CD71. An in vivo transplantation assay combined with limiting dilution analysis was used to quantify enrichment for long-term repopulating cells in the isolated populations. The ALDH+CD44+ population was enriched 12.6-fold for long-term repopulating epidermal stem cells (EpiSCs) and the integrin α6hiCD71lo population was enriched 5.6-fold, over unfractionated cells. In addition to long-term repopulation, CD44+ALDH+ keratinocytes exhibited other stem cell properties. CD44+ALDH+ keratinocytes had self-renewal ability, demonstrated by increased numbers of cells expressing nuclear Bmi-1, serial transplantation of CD44+ALDH+ cells, and holoclone formation in vitro. CD44+ALDH+ cells were multipotent, producing greater numbers of hair follicle-like structures than CD44−ALDH− cells. Furthermore, 58% ± 7% of CD44+ALDH+ cells exhibited label-retention. In vitro, CD44+ALDH+ cells showed enhanced colony formation, in both keratinocyte and embryonic stem cell growth media. In summary, the CD44+ALDH+ population exhibits stem cell properties including long-term epidermal regeneration, multipotency, label retention, and holoclone formation. This study shows that it is possible to quantify the relative number of EpiSCs in human keratinocyte populations using long-term repopulation as a functional test of stem cell nature. Future studies will combine isolation strategies as dictated by the results of quantitative transplantation assays, in order to achieve a nearly pure population of EpiSCs.
The need for a canopy perspective to understand the importance of phenotypic plasticity for promoting species coexistence and light‐use complementarity in forest ecosystems
Authors: Ishii Hiroaki , Azuma Wakana , Nabeshima Eri 
Published: January 2013

AbstractBecause of their overwhelming size over other organisms, trees define the structural and energetic properties of forest ecosystems. From grasslands to forests, leaf area index, which determines the amount of light energy intercepted for photosynthesis, increases with increasing canopy height across the various terrestrial ecosystems of the world. In vertically well‐developed forests, niche differentiation along the vertical gradient of light availability may promote species coexistence. In addition, spatial and temporal differentiation of photosynthetic traits among the coexisting tree species (functional diversity) may promote complementary use of light energy, resulting in higher biomass and productivity in multi‐species forests. Trees have evolved retaining high phenotypic plasticity because the spatial/temporal distribution of resources in forest ecosystems is highly heterogeneous and trees modify their own environment as they increase nearly 1,000 times in size through ontogeny. High phenotypic plasticity may enable coexistence of tree species through divergence in resource‐rich environments, as well as through convergence in resource‐limited environments. We propose that the breadth of individual‐level phenotypic plasticity, expressed at the metamer level (leaves and shoots), is an important factor that promotes species coexistence and resource‐use complementarity in forest ecosystems. A cross‐biome comparison of the link between plasticity of photosynthesis‐related traits and stand productivity will provide a functional explanation for the relationship between species assemblages and productivity of forest ecosystems.