bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insights into the potential function and membrane organization of the TP0435 (Tp17) lipoprotein from Treponema pallidum derived from structural and biophysical analyses
Authors: Brautigam Chad A. , Deka Ranjit K. , Liu Wei Z. , Norgard Michael V. 
Published: October 2014

AbstractThe sexually transmitted disease syphilis is caused by the bacterial spirochete Treponema pallidum. This microorganism is genetically intractable, accounting for the large number of putative and undercharacterized members of the pathogen's proteome. In an effort to ascribe a function(s) to the TP0435 (Tp17) lipoprotein, we engineered a soluble variant of the protein (rTP0435) and determined its crystal structure at a resolution of 2.42 Å. The structure is characterized by an eight‐stranded β‐barrel protein with a shallow “basin” at one end of the barrel and an α‐helix stacked on the opposite end. Furthermore, there is a disulfide‐linked dimer of the protein in the asymmetric unit of the crystals. Solution hydrodynamic experiments established that purified rTP0435 is monomeric, but specifically forms the disulfide‐stabilized dimer observed in the crystal structure. The data herein, when considered with previous work on TP0435, imply plausible roles for the protein in either ligand binding, treponemal membrane architecture, and/or pathogenesis.
Computational de novo design of a four‐helix bundle protein—DND_4HB
Authors: Murphy Grant S. , Sathyamoorthy Bharatwaj , Der Bryan S. , Machius Mischa C. , Pulavarti Surya V. , Szyperski Thomas , Kuhlman Brian 
Published: October 2014

AbstractThe de novo design of proteins is a rigorous test of our understanding of the key determinants of protein structure. The helix bundle is an interesting de novo design model system due to the diverse topologies that can be generated from a few simple α‐helices. Previously, noncomputational studies demonstrated that connecting amphipathic helices together with short loops can sometimes generate helix bundle proteins, regardless of the bundle's exact sequence. However, using such methods, the precise positions of helices and side chains cannot be predetermined. Since protein function depends on exact positioning of residues, we examined if sequence design tools in the program Rosetta could be used to design a four‐helix bundle with a predetermined structure. Helix position was specified using a folding procedure that constrained the design model to a defined topology, and iterative rounds of rotamer‐based sequence design and backbone refinement were used to identify a low energy sequence for characterization. The designed protein, DND_4HB, unfolds cooperatively (Tm >90°C) and a NMR solution structure shows that it adopts the target helical bundle topology. Helices 2, 3, and 4 agree very closely with the design model (backbone RMSD = 1.11 Å) and >90% of the core side chain χ1 and χ2 angles are correctly predicted. Helix 1 lies in the target groove against the other helices, but is displaced 3 Å along the bundle axis. This result highlights the potential of computational design to create bundles with atomic‐level precision, but also points at remaining challenges for achieving specific positioning between amphipathic helices.
Design and characterization of ebolavirus GP prehairpin intermediate mimics as drug targets
Authors: Clinton Tracy R. , Weinstock Matthew T. , Jacobsen Michael T. , Szabo‐Fresnais Nicolas , Pandya Maya J. , Whitby Frank G. , Herbert Andrew S. , Prugar Laura I. , McKinnon Rena , Hill Christopher P. , Welch Brett D. , Dye John M. , Eckert Debra M. , Kay Michael S. 
Published: October 2014

AbstractEbolaviruses are highly lethal filoviruses that cause hemorrhagic fever in humans and nonhuman primates. With no approved treatments or preventatives, the development of an anti‐ebolavirus therapy to protect against natural infections and potential weaponization is an urgent global health need. Here, we describe the design, biophysical characterization, and validation of peptide mimics of the ebolavirus N‐trimer, a highly conserved region of the GP2 fusion protein, to be used as targets to develop broad‐spectrum inhibitors of ebolavirus entry. The N‐trimer region of GP2 is 90% identical across all ebolavirus species and forms a critical part of the prehairpin intermediate that is exposed during viral entry. Specifically, we fused designed coiled coils to the N‐trimer to present it as a soluble trimeric coiled coil as it appears during membrane fusion. Circular dichroism, sedimentation equilibrium, and X‐ray crystallography analyses reveal the helical, trimeric structure of the designed N‐trimer mimic targets. Surface plasmon resonance studies validate that the N‐trimer mimic binds its native ligand, the C‐peptide region of GP2. The longest N‐trimer mimic also inhibits virus entry, thereby confirming binding of the C‐peptide region during viral entry and the presence of a vulnerable prehairpin intermediate. Using phage display as a model system, we validate the suitability of the N‐trimer mimics as drug screening targets. Finally, we describe the foundational work to use the N‐trimer mimics as targets in mirror‐image phage display, which will be used to identify D‐peptide inhibitors of ebolavirus entry.
Synthesis of nitrogen‐containing porous carbon using calcium oxide nanoparticles
Authors: Shlyakhova E. V. , Bulusheva L. G. , Kanygin M. A. , Plyusnin P. E. , Kovalenko K. A. , Senkovskiy B. V. , Okotrub A. V. 
Published: October 2014

Nitrogen‐containing porous carbon has been produced by acetonitrile vapor deposition at 700 and 800 °C on the products of thermolysis of calcium tartrate doped by iron. The template was removed by dilute HCl acid treatment, and the samples obtained were comparatively studied using transmission electron microscopy, N2 adsorption measurements, thermogravimetric analysis (TGA), X‐ray photoelectron and near‐edge X‐ray absorption fine structure spectroscopy. It was found that increase in the synthesis temperature results in an extension of the specific surface area from ∼640 to ∼670 m2/g, enlargement in the average pore size from ∼9 to ∼13 nm, and a decrease in the nitrogen content from ∼4.4 to 2.7 at%. TGA revealed that the samples differ by ∼80 °C in the temperature of nitrogen loss, which was desorbed as the NO species mainly.Scheme of nitrogen‐doped porous carbon synthesis.
Design and implementation of an efficient hybrid dynamic and static typing language
Authors: Garcia Miguel , Ortin Francisco , Quiroga Jose 
Published: October 2014

SummaryDynamic languages are suitable for developing specific applications where runtime adaptability is an important issue. On the contrary, statically typed languages commonly provide better compile‐time type error detection and more opportunities for compiler optimizations. Because both approaches offer different benefits, there exist programming languages that support hybrid dynamic and static typing. However, the existing hybrid typing languages commonly do not gather type information of dynamic references at compile time, missing opportunities for improving compile‐time error detection and runtime performance. Therefore, we propose some design principles to implement hybrid typing languages that continue gathering type information of dynamically typed references. This type information is used to perform compile‐time type checking of the dynamically typed code and improve its runtime performance. As an example, we have implemented a hybrid typing language following the proposed design principles. We have evaluated the runtime performance and memory consumption of the generated code. The average performance of the dynamic and hybrid typing code is at least 2.53× and 4.51× better than the related approaches for the same platform, consuming less memory resources. Copyright © 2014 John Wiley & Sons, Ltd.
Nerve Growth Factor and proNGF Simultaneously Promote Symmetric Self-Renewal, Quiescence, and Epithelial to Mesenchymal Transition to Enlarge the Breast Cancer Stem Cell Compartment
Authors: Tomellini Elisa , Touil Yasmine , Lagadec Chann , Julien Sylvain , Ostyn Pauline , Ziental-Gelus Nathalie , Meignan Samuel , Lengrand Justine , Adriaenssens Eric , Polakowska Renata , Le Bourhis Xuefen 
Published: October 2014

Abstract
The discovery of cancer stem cells (CSCs) fundamentally advanced our understanding of the mechanisms governing breast cancer development. However, the stimuli that control breast CSC self-renewal and differentiation have still not been fully detailed. We previously showed that nerve growth factor (NGF) and its precursor proNGF can stimulate breast cancer cell growth and invasion in an autocrine manner. In this study, we investigated the effects of NGF and proNGF on the breast CSC compartment and found that NGF or proNGF enrich for CSCs in several breast cancer cell lines. This enrichment appeared to be achieved by increasing the number of symmetric divisions of quiescent/slow-proliferating CSCs. Interestingly, in vitro NGF pretreatment of MCF-7 luminal breast cancer cells promoted epithelial to mesenchymal transition in tumors of severe combined immunodeficient mice. Furthermore, p75NTR, the common receptor for both neurotrophins and proneurotrophins, mediated breast CSC self-renewal by regulating the expression of pluripotency transcription factors. Our data indicate, for the first time, that the NGF/proNGF/p75NTR axis plays a critical role in regulating breast CSC self-renewal and plasticity. Stem Cells 2015;33:342–353
The Orphan Nuclear Receptor NR4A1 Specifies a Distinct Subpopulation of Quiescent Myeloid-Biased Long-Term HSCs
Authors: Land Ruben H. , Rayne Anna K. , Vanderbeck Ashley N. , Barlowe Trevor S. , Manjunath Shwetha , Gross Matthew , Eiger Sophie , Klein Peter S. , Cunningham Nicole R. , Huang Jian , Emerson Stephen G. , Punt Jennifer A. 
Published: October 2014

Abstract
Hematopoiesis is maintained throughout life by self-renewing hematopoietic stem cells (HSCs) that differentiate to produce both myeloid and lymphoid cells. The NR4A family of orphan nuclear receptors, which regulates cell fate in many tissues, appears to play a key role in HSC proliferation and differentiation. Using a NR4A1GFP BAC transgenic reporter mouse we have investigated NR4A1 expression and its regulation in early hematopoiesis. We show that NR4A1 is most highly expressed in a subset of Lin−Sca-1+c-Kit+ CD48−CD150+ long-term (LT) HSCs, and its expression is tightly associated with HSC quiescence. We also show that NR4A1 expression in HSCs is induced by PGE2, a known enhancer of stem cell engraftment potential. Finally, we find that both NR4A1GFP+ and NR4A1GFP− HSCs successfully engraft primary and secondary irradiated hosts; however, NR4A1GFP+ HSCs are distinctly myeloid-biased. These results show that NR4A1 expression identifies a highly quiescent and distinct population of myeloid-biased LT-HSCs. Stem Cells 2015;33:278–288
RepOK‐based reduction of bounded exhaustive testing
Authors: Bengolea Valeria , Aguirre Nazareno , Marinov Darko , Frias Marcelo 
Published: October 2014

SUMMARYWhile the effectiveness of bounded exhaustive test suites increases as one increases the scope for the bounded exhaustive generation, both the time for test generation and the time for test execution grow exponentially with respect to the scope. In this article, a set of techniques for reducing the time for bounded exhaustive testing, by either reducing the generation time or reducing the obtained bounded exhaustive suites, is proposed. The representation invariant of the software under test's input, implemented as a repOK routine, is exploited for these reductions in two ways: (i) to factor out separate representation invariants for disjoint structures of the inputs; and (ii) to partition valid inputs into equivalence classes, according to how these exercise the repOK code. The first is used in order to split the test input generation process, as disjoint substructures can be independently generated. The second is used in order to reduce the size of a bounded exhaustive test suite, by removing from the suite those tests that are equivalent to some tests already present in the suite. Copyright © 2014 John Wiley & Sons, Ltd.
Coupled flexural–torsional dynamic stiffness matrix of an elastically supported axially loaded beam with shear resistant in‐fill
Authors: Ghandi E. , Rafezy B. , Abedi K. , Howson W. P. 
Published: October 2014

SummaryThe dynamic stiffness matrix of an axially loaded elastically supported uniform beam with doubly asymmetric cross‐section that exhibits coupling between flexural and torsional motions is developed and subsequently used to investigate its free vibration characteristics. The beam comprises a thin‐walled outer section that encloses, and works compositely with, a core of shear resistant in‐fill material. The outer layer provides flexure, warping and Saint–Venant rigidity, while the inner layer provides both Saint–Venant and shear rigidity. A three‐parameter Winkler model is used to describe the distributed elastic support. Hamilton's principle is used to derive the partial differential equations governing the free vibration of the beam, together with the associated natural boundary conditions. This gives rise to three coupled equations that are subsequently combined into a single, 12th order, ordinary differential equation. Throughout the process, the uniform distribution of mass in the member is accounted for exactly and thus necessitates the solution of a transcendental eigenvalue problem. This is accomplished using the Wittrick–Williams algorithm, which enables the required natural frequencies to be converged upon to any required accuracy with the certain knowledge that none have been missed. Finally, in order to verify the accuracy of the presented theory, the numerical solutions are given and compared with the results that are available in the literature and finite element solutions using abaqus software. Copyright © 2014 John Wiley & Sons, Ltd.
Spitzenwirkungsgrade bei sinkenden Herstellungskosten
Authors: Strauch Kerstin , Schwarz Florian , Gatz Sebastian , Rack Andreas 
Published: October 2014

AbstractDie Manz AG kommt mit der neuen Beschichtungsanlage VCS1200 der Forderung der PV‐Industrie nach immer höheren Wirkungsgraden bei gleichzeitig sinkenden Produktionskosten nach. Mittels neuartiger HP‐ICP Technologie konnten bereits Wirkungsgrade über 20% erreicht werden. Die hohe Gaszersetzung, die mit diesem Verfahren erreicht wird, sorgt für kompakte Schichten mit sehr guten Passiviereigenschaften. Das ebenfalls neu entwickelte elektrostatische Carriersystem sorgt für eine geringe mechanische Belastung der Wafer bei gleichzeitig vollflächig homogener Abscheidung. Die VCS1200 kann sowohl für Rückseiten‐Passivierungen als auch für Vorderseiten‐Antireflexbeschichtungen eingesetzt werden.
Glass meets flexibility
Authors: Junghähnel Manuela , Garner Sean 
Published: October 2014

AbstractFlexible glass, such as ultra‐slim Corning® Willow® Glass, produced at thicknesses lower than 200 micron has the ability to bend, while maintaining perfect barrier properties, superior surface quality, greater transparency, and high temperature processing, outperforming polymers. At the same time it has the potential to be used in roll‐to‐roll large area processing. These qualities make flexible glass an outstanding material for displays, touch panels, thinfilm batteries and photovoltaic (PV) products.
Stochastic climate theory and modeling
Authors: Franzke Christian L. E. , O'Kane Terence J. , Berner Judith , Williams Paul D. , Lucarini Valerio 
Published: October 2014

Stochastic methods are a crucial area in contemporary climate research and are increasingly being used in comprehensive weather and climate prediction models as well as reduced order climate models. Stochastic methods are used as subgrid‐scale parameterizations (SSPs) as well as for model error representation, uncertainty quantification, data assimilation, and ensemble prediction. The need to use stochastic approaches in weather and climate models arises because we still cannot resolve all necessary processes and scales in comprehensive numerical weather and climate prediction models. In many practical applications one is mainly interested in the largest and potentially predictable scales and not necessarily in the small and fast scales. For instance, reduced order models can simulate and predict large‐scale modes. Statistical mechanics and dynamical systems theory suggest that in reduced order models the impact of unresolved degrees of freedom can be represented by suitable combinations of deterministic and stochastic components and non‐Markovian (memory) terms. Stochastic approaches in numerical weather and climate prediction models also lead to the reduction of model biases. Hence, there is a clear need for systematic stochastic approaches in weather and climate modeling. In this review, we present evidence for stochastic effects in laboratory experiments. Then we provide an overview of stochastic climate theory from an applied mathematics perspective. We also survey the current use of stochastic methods in comprehensive weather and climate prediction models and show that stochastic parameterizations have the potential to remedy many of the current biases in these comprehensive models. WIREs Clim Change 2015, 6:63–78. doi: 10.1002/wcc.318This article is categorized under:

Climate Models and Modeling > Model Components
Reduction of Metal Coordinated N2 to NH3 with H2 by Heterolytic Hydrogen Cleavage induced by External Lewis Bases – a DFT Study
Authors: Hölscher Markus , Leitner Walter 
Published: October 2014

AbstractThe synthesis of NH3 from N2 and H2 employing molecular ruthenium pincer complexes as catalysts was investigated by DFT calculations for an hitherto unusual type of outer sphere mechanism in N2 chemistry. The mechanistic approach relies on the heterolytic cleavage of a H2 molecule between the sterically demanding P(tBu)3 as a Lewis base and the dicationic ruthenium pincer complex [Ru(PNP)(N2)(CO)2]2+ [PNP = 2,6‐bis(diisopropylphosphanyl)lutidin] as a Lewis acid. Cleavage of the H2 molecule results in a hydride, which is transferred onto the external N atom of the N2 molecule coordinated at the metal complex, while the proton binds to the base. In a subsequent step the proton is also transferred to the HNN unit. Repetition of these two reaction steps with two more H2 molecules results in the formation of two NH3 molecules. Closed catalytic cycles could be calculated, which proves that this concept is applicable in principle. However, some activation barriers in the middle stages of the catalytic cycle are too high to envision practical realization with this particular acid‐base combination. Low lying intermediates, which occur in late stages of the catalytic cycle, are another challenge as they increase the overall activation barrier significantly. As a result it is suggested that this novel approach of hydrogen transfer onto N2 should be extended to other complexes.
Novel [{Cp(CO)2Mo}2ESb]+ Clusters with Tetrahedral Mo2SbE Core. Synthesis and Crystal Structures of [{Cp(CO)2Mo}2ESb][GaCl4] (E = S, Se)
Authors: Wagner Christoph , Merzweiler Kurt 
Published: October 2014

AbstractTreatment of the cluster compounds [Cp2(CO)4Mo2ESbCl] (E = S, Se) with GaCl3 in thf as solvent leads to the compounds [Cp2(CO)4Mo2ESb]GaCl4. [Cp2(CO)4Mo2SSb]GaCl4 crystallizes in the monoclinic system, space group P21/c with a = 815.64(6), b = 1094.31(5), c = 2503.7(2) pm, and β = 92.505(6)°. The selenium derivative [Cp2(CO)4Mo2SeSb]GaCl4 forms isotypic crystals with a = 811.53(4), b = 1103.90(6), c = 2511.2(1) pm, and β = 92.704(4)°. Both the derivatives display ionic structures consisting of separated [Cp2(CO)4Mo2ESb]+ cations and GaCl4– anions. According to the 18 electron rule the [Cp2(CO)4Mo2ESb]+ cations can be considered as electron precise tetrahedral clusters, which are closely related to the well‐known dipnictogen complexes [Cp2(CO)4Mo2E2] (E = P, As, Sb, Bi).
Observer reliability of CT angiography in the assessment of acute ischaemic stroke: data from the Third International Stroke Trial
Authors: Mair Grant , von Kummer Rüdiger , Adami Alessandro , White Philip M. , Adams Matthew E. , Yan Bernard , Demchuk Andrew M. , Farrall Andrew J. , Sellar Robin J. , Ramaswamy Rajesh , Mollison Daisy , Boyd Elena V. , Rodrigues Mark A. , Samji Karim , Baird Andrew J. , Cohen Geoff , Sakka Eleni , Palmer Jeb , Perry David , Lindley Richard , Sandercock Peter A. G. , Wardlaw Joanna M. ,   The IST-3 Collaborative Group
Published: October 2014

Abstract

Introduction
CT angiography (CTA) is often used for assessing patients with acute ischaemic stroke. Only limited observer reliability data exist. We tested inter- and intra-observer reliability for the assessment of CTA in acute ischaemic stroke.

Methods
We selected 15 cases from the Third International Stroke Trial (IST-3, ISRCTN25765518) with various degrees of arterial obstruction in different intracranial locations on CTA. To assess inter-observer reliability, seven members of the IST-3 expert image reading panel (>5 years experience reading CTA) and seven radiology trainees (<2 years experience) rated all 15 scans independently and blind to clinical data for: presence (versus absence) of any intracranial arterial abnormality (stenosis or occlusion), severity of arterial abnormality using relevant scales (IST-3 angiography score, Thrombolysis in Cerebral Infarction (TICI) score, Clot Burden Score), collateral supply and visibility of a perfusion defect on CTA source images (CTA-SI). Intra-observer reliability was assessed using independently repeated expert panel scan ratings. We assessed observer agreement with Krippendorff’s-alpha (K-alpha).

Results
Among experienced observers, inter-observer agreement was substantial for the identification of any angiographic abnormality (K-alpha = 0.70) and with an angiography assessment scale (K-alpha = 0.60–0.66). There was less agreement for grades of collateral supply (K-alpha = 0.56) or for identification of a perfusion defect on CTA-SI (K-alpha = 0.32). Radiology trainees performed as well as expert readers when additional training was undertaken (neuroradiology specialist trainees). Intra-observer agreement among experts provided similar results (K-alpha = 0.33–0.72).

Conclusion
For most imaging characteristics assessed, CTA has moderate to substantial observer agreement in acute ischaemic stroke. Experienced readers and those with specialist training perform best.
Effects of Postoperative Morbidity on Long‐Term Outcome Following Surgery for Colorectal Liver Metastases
Authors: Lodewick T. M. , de Jong M. C. , van Dam R. M. , Bemelmans M. H. A. , Neumann U. P. , Olde Damink S. W. M. , Dejong C. H. C. 
Published: October 2014

AbstractBackgroundThe impact of postoperative complications on long‐term outcomes after surgery for colorectal liver metastases (CRLM) remains controversial. During the last decade, advances in surgical as well as non‐surgical treatment have increased resectability and altered outcomes. We sought to determine the influence of postoperative morbidity on disease‐free (DFS) and overall survival (OS).MethodsAll patients undergoing liver resection for CRLM for the first time between 2000 and 2011 were retrospectively identified from a prospective database. Postoperative morbidity was classified according to Dindo–Clavien grade. A Dindo–Clavien grade ≥3a was considered a major complication. Primary outcomes were DFS and OS depending on the presence or absence of postoperative morbidity.ResultsOf the 266 included patients, 97 patients (37 %) developed postoperative complications, of whom 61 (23 %) had major complications. Median DFS and OS (5‐year) were 17 and 53 months (42 %). The occurrence of postoperative morbidity did not significantly shorten OS (p = 0.130) and DFS (p = 0.101). However, major morbidity reduced DFS significantly (p < 0.05).ConclusionIn the present study, the occurrence of major postoperative complications was associated with diminished DFS. However, the effect of (major) complications on OS did not reach statistical significance.