bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of SH3 Domain–Binding Protein 2 Function Suppresses Bone Destruction in Tumor Necrosis Factor–Driven and Collagen‐Induced Arthritis in Mice
Authors: Mukai Tomoyuki , Gallant Richard , Ishida Shu , Kittaka Mizuho , Yoshitaka Teruhito , Fox David A. , Morita Yoshitaka , Nishida Keiichiro , Rottapel Robert , Ueki Yasuyoshi 
Published: December 2014

ObjectiveSH3 domain–binding protein 2 (SH3BP2) is a signaling adapter protein that regulates the immune and skeletal systems. The present study was undertaken to investigate the role of SH3BP2 in arthritis using 2 experimental mouse models, i.e., human tumor necrosis factor α–transgenic (hTNF‐Tg) mice and mice with collagen‐induced arthritis (CIA).MethodsFirst, Sh3bp2−/− and wild‐type (Sh3bp2+/+) mice were crossed with hTNF‐Tg mice. Inflammation and bone loss were examined by clinical inspection and histologic and micro−computed tomography analysis, and osteoclastogenesis was evaluated using primary bone marrow–derived macrophage colony‐stimulating factor–dependent macrophages (BMMs). Second, CIA was induced in Sh3bp2−/− and Sh3bp2+/+ mice, and the incidence and severity of arthritis were evaluated. Anti–mouse type II collagen (CII) antibody levels were measured by enzyme‐linked immunosorbent assay, and lymph node cell responses to CII were determined.ResultsSH3BP2 deficiency did not alter the severity of joint swelling but did suppress bone erosion in the hTNF‐Tg mouse model. Bone loss at the talus and tibia was prevented in Sh3bp2−/−/hTNF‐Tg mice compared to Sh3bp2+/+/hTNF‐Tg mice. RANKL‐ and TNFα‐induced osteoclastogenesis was suppressed in Sh3bp2−/− mouse BMM cultures. NF‐ATc1 nuclear localization in response to TNFα was decreased in Sh3bp2−/− mouse BMMs compared to Sh3bp2+/+ mouse BMMs. In the CIA model, SH3BP2 deficiency suppressed the incidence of arthritis and this was associated with decreased anti‐CII antibody production, while antigen‐specific T cell responses in lymph nodes were not significantly different between Sh3bp2+/+ and Sh3bp2−/− mice.ConclusionSH3BP2 deficiency prevents loss of bone via impaired osteoclastogenesis in the hTNF‐Tg mouse model and suppresses the induction of arthritis via decreased autoantibody production in the CIA model. Therefore, SH3BP2 could potentially be a therapeutic target in rheumatoid arthritis.
Internationale Wasserbauprojekte: Entwicklung von Häfen und Transportwegen
Authors: Unger Jens , Galipp Karsten , Krebs Hauke 
Published: December 2014

AbstractDie Hafenwirtschaft steht in einem weltweiten Wettbewerb. Immer größere Schiffe müssen in immer kürzeren Zeiten weltweit abgefertigt werden. Fachingenieure planen die Hafenanlagen und alle zugehörigen Infra‐ und Suprastruktureinrichtungen und bieten Beratungsleistungen für die Umstrukturierung vorhandener Anlagen zur Anpassung an sich ändernde Anforderungen an. Beispielhaft wird ein Einblick in aktuelle internationale Projekte gegeben. Der erste Beitrag befasst sich mit der Entwicklung eines Masterplanes für den rumänischen Schwarzmeerhafen Constanta, der größte Seehafen Rumäniens und ein bedeutendes Drehkreuz für den Warenumschlag zwischen dem Schwarzmeer‐Raum, der Europäischen Union und Zentralasien. Die Modernisierung des Hafens Freetown, der als größter Naturhafen Afrikas eine wichtige wirtschaftliche Rolle einnimmt, steht im Fokus des zweiten Beitrages und es wird über neue Anlagen und Reparaturflächen für die größte Schiffswerft in Indien berichtet.International projects of water engineering: Development of harbours and transport waysThe port industry is subject to global competition. All over the world, increasingly large ships have to be served in ever shorter time frames. Specialist engineers are not only planning port facilities and their related infrastructure and suprastructure, but are also offering consulting services for the restructuring of existing facilities in order to have them adapted to changing requirements. An insight into our current international projects is being provided. The first contribution deals with the development of a master plan for the port of Constanta on the Black Sea, Romania's largest sea port and an important hub for cargo handling between the Black Sea area, the European Union and Central Asia. The focus of the second contribution is on the modernisation of the port of Freetown which, as the largest natural port in Africa, plays an essential economic role. Furthermore, new facilities and repair surfaces for the largest shipyard in India are being presented.
Reconstructing the Discontinuous and Conformational β1/β3‐Loop Binding Site on hFSH/hCG by Using Highly Constrained Multicyclic Peptides
Authors: Smeenk Linde E. J. , Timmers‐Parohi Drohpatie , Benschop Joris J. , Puijk Wouter C. , Hiemstra Henk , van Maarseveen Jan H. , Timmerman Peter 
Published: December 2014

AbstractMaking peptide‐based molecules that mimic functional interaction sites on proteins remains a challenge in biomedical sciences. Here, we present a robust technology for the covalent assembly of highly constrained and discontinuous binding site mimics, the potential of which is exemplified for structurally complex binding sites on the “Cys‐knot” proteins hFSH and hCG. Peptidic structures were assembled by Ar(CH2Br)2‐promoted peptide cyclizations, combined with oxime ligation and disulfide formation. The technology allows unprotected side chain groups and is applicable to peptides of different lengths and nature. A tetracyclic FSH mimic was constructed, showing >600‐fold improved binding compared to linear or monocyclic controls. Binding of a tricyclic hCG mimic to anti‐hCG mAb 8G5 was identical to hCG itself (IC50=260 vs. 470 pM), whereas this mimic displayed an IC50 value of 149 nM for mAb 3468, an hCG‐neutralizing antibody with undetectable binding to either linear or monocyclic controls.
Conformation of Inhibitor‐Free HIV‐1 Protease Derived from NMR Spectroscopy in a Weakly Oriented Solution
Authors: Roche Julien , Louis John M. , Bax Ad 
Published: December 2014

AbstractFlexibility of the glycine‐rich flaps is known to be essential for catalytic activity of the HIV‐1 protease, but their exact conformations at the different stages of the enzymatic pathway remain subject to much debate. Although hundreds of crystal structures of protease–inhibitor complexes have been solved, only about a dozen inhibitor‐free protease structures have been reported. These latter structures reveal a large diversity of flap conformations, ranging from closed to semi‐open to wide open. To evaluate the average structure in solution, we measured residual dipolar couplings (RDCs) and compared these to values calculated for crystal structures representative of the closed, semi‐open, and wide‐open states. The RDC data clearly indicate that the inhibitor‐free protease, on average, adopts a closed conformation in solution that is very similar to the inhibitor‐bound state. By contrast, a highly drug‐resistant protease mutant, PR20, adopts the wide‐open flap conformation.
The Synthesis and STM/AFM Imaging of ‘Olympicene’ Benzo[cd]pyrenes
Authors: Mistry Anish , Moreton Ben , Schuler Bruno , Mohn Fabian , Meyer Gerhard , Gross Leo , Williams Antony , Scott Peter , Costantini Giovanni , Fox David J. 
Published: December 2014

AbstractH‐Benzo[cd]pyrene (‘Olympicene′) is a polyaromatic hydrocarbon and non‐Kekulé fragment of graphene. A new synthetic method has been developed for the formation of 6H‐benzo[cd]pyrene and related ketones including the first time isolation of the unstable alcohol 6H‐benzo[cd]pyren‐6‐ol. Molecular imaging of the reaction products with scanning tunnelling microscopy (STM) and non‐contact atomic force microscopy (NC‐AFM) characterised the 6H‐benzo[cd]pyrene as well as the previously intangible and significantly less stable 5H‐benzo[cd]pyrene, the fully conjugated benzo[cd]pyrenyl radical and the ketones as oxidation products.
Active‐Site‐Matched Fluorescent Probes for Rapid and Direct Detection of Vicinal‐Sulfydryl‐Containing Peptides/Proteins in Living Cells
Authors: Pan Xiaohong , Liang Ziye , Li Jing , Wang Shanshan , Kong Fanpeng , Xu Kehua , Tang Bo 
Published: December 2014

AbstractVicinal‐sulfydryl‐containing peptides/proteins (VSPPs) play a crucial role in human pathologies. Fluorescent probes that are capable of detecting intracellular VSPPs in vivo would be useful tools to explore the mechanisms of some diseases. In this study, by regulating the spatial separation of two maleimide groups in a fluorescent dye to match that of two active cysteine residues contained in the conserved amino acid sequence (–CGPC–) of human thioredoxin, two active‐site‐matched fluorescent probes, o‐Dm‐Ac and m‐Dm‐Ac, were developed for real‐time imaging of VSPPs in living cells. As a result, the two probes can rapidly respond to small peptide models and reduced proteins, such as WCGPCK (W‐6), WCGGPCK (W‐7), and WCGGGPCK (W‐8), reduced bovine serum albumin (rBSA), and reduced thioredoxin (rTrx). Moreover, o‐Dm‐Ac displays a higher binding sensitivity with the above‐mentioned peptides and proteins, especially with W‐7 and rTrx. Furthermore, o‐Dm‐Ac was successfully used to rapidly and directly detect VSPPs both in vitro and in living cells. Thus, a novel probe‐design strategy was proposed and the synthesized probe applied successfully in imaging of target proteins in situ.
Mechanism of Redox‐Active Ligand‐Assisted Nitrene‐Group Transfer in a ZrIV Complex: Direct Ligand‐to‐Ligand Charge Transfer Preferred
Authors: Ghosh Soumya , Baik Mu‐Hyun 
Published: December 2014

AbstractThe mechanism of the nitrene‐group transfer reaction from an organic azide to isonitrile catalyzed by a ZrIV d0 complex carrying a redox‐active ligand was studied by using quantum chemical molecular‐modeling methods. The key step of the reaction involves the two‐electron reduction of the azide moiety to release dinitrogen and provide the nitrene fragment, which is subsequently transferred to the isonitrile substrate. The reducing equivalents are supplied by the redox‐active bis(2‐iso‐propylamido‐4‐methoxyphenyl)‐amide ligand. The main focus of this work is on the mechanism of this redox reaction, in particular, two plausible mechanistic scenarios are considered: 1) the metal center may actively participate in the electron‐transfer process by first recruiting the electrons from the redox‐active ligand and becoming formally reduced in the process, followed by a classical metal‐based reduction of the azide reactant. 2) Alternatively, a non‐classical, direct ligand‐to‐ligand charge‐transfer process can be envisioned, in which no appreciable amount of electron density is accumulated at the metal center during the course of the reaction. Our calculations indicate that the non‐classical ligand‐to‐ligand charge‐transfer mechanism is much more favorable energetically. Utilizing a series of carefully constructed putative intermediates, both mechanistic scenarios were compared and contrasted to rationalize the preference for ligand‐to‐ligand charge‐transfer mechanism.
Iodine(III)‐Catalyzed Rearrangements of Imides: A Versatile Route to α,α‐Dialkylated α‐Hydroxy Carboxylamides
Authors: Ulmer Anna , Stodulski Maciej , Kohlhepp Stefanie V. , Patzelt Christoph , Pöthig Alexander , Bettray Wolfgang , Gulder Tanja 
Published: December 2014

AbstractA tertiary hydroxy group α to a carboxyl moiety comprises a key structural motif in many bioactive substances. With the herein presented metal‐free rearrangement of imides triggered by hypervalent λ3‐iodane, an easy and selective way to gain access to such a compound class, namely α,α‐disubstituted‐α‐hydroxy carboxylamides, was established. Their additional methylene bromide side chain constitutes a useful handle for rapid diversification, as demonstrated by a series of further functionalizations. Moreover, the in situ formation of an iodine(III) species under the reaction conditions was proven. Our findings clearly corroborate that hypervalent λ3‐benziodoxolones are involved in these organocatalytic reactions.
Zirconium‐Mediated Multicomponent Reactions of 1,3‐Butadiynes with Ylidenemalononitriles to Form Functionalized 1,8‐Naphthyridine and Cyclopenta[b]pyridine Derivatives
Authors: Yu Shasha , Sun Renhong , Chen Haoyi , Xie Xin , Liu Yuanhong 
Published: December 2014

AbstractZirconocene‐mediated multicomponent reactions of 1,3‐butadiynes with ylidenemalononitriles in the absence or presence of CuCl have been developed. In the absence of CuCl, 1,3‐butadiyne couples with three molecules of ylidenemalononitriles to yield azazirconacycles bearing a hexahydro‐1,8‐naphthyridine skeleton with high stereoselectivity. In the presence of CuCl, cyclopenta[b]pyridine or cyclopenta[b]quinolin‐1‐one derivatives are obtained via transmetalation of ZrC bond to CuC bond as the key reaction step. These domino‐type reactions proceed with high chemo‐, regio‐ and/or stereoselectivities, and allowing the formation of multiple CN and CC bonds in a single operation.
Gold(I)‐Catalyzed 1,2‐Acyloxy Migration/[3+2] Cycloaddition of 1,6‐Diynes with an Ynamide Propargyl Ester Moiety: Highly Efficient Synthesis of Functionalized Cyclopenta[b]indoles
Authors: Liu Jun , Chen Ming , Zhang Liangwei , Liu Yuanhong 
Published: December 2014

AbstractA gold‐catalyzed cycloisomerization of 1,6‐diynes containing an ynamide propargyl ester or carbonate moiety has been developed that provides an attractive route to a diverse‐substituted 3‐acyloxy‐1,4‐dihydrocyclopenta[b]indoles. Mechanistic studies indicate that the reaction likely proceeds through a competitive 1,2‐OAc migration followed by [3+2] cycloaddition of the vinyl gold–carbenoid intermediate with the pendant triple bond. The synthetic utility of the obtained cyclopenta[b]indole products was demonstrated by their efficient transformations by deprotection or double‐bond isomerization reactions.
Solvent Choice and Kinetic Isotope Effects (KIEs) Dramatically Alter Regioselectivity in the Directed ortho Metalation (DoM) of 1,5‐Dichloro‐2,4‐dimethoxybenzene
Authors: Farmer Jennifer L. , Froese Robert D. J. , Lee‐Ruff Edward , Organ Michael G. 
Published: December 2014

AbstractThe regioselective formation of the 6‐lithio derivative of 1,5‐dichloro‐2,4‐dimethoxybenzene (i.e., 12) by directed ortho metalation (DoM) with nBuLi in THF is described. Although literature reports suggest direct deprotonation at C6, a series of time‐course and labelling studies has revealed that deprotonation rather occurs exclusively at C3 followed by isomerization of the anion to C6. By contrast, when DoM was performed in Et2O, deprotonation again occurred selectively at C3, but now no isomerization occurs, and electrophilic capture produces the regioisomer of that produced in THF. In these labeling studies, it has been found that deuterium has an enormous kinetic isotope effect (KIE) that suppresses not only the original DoM reaction at C3 when deuterium is present there, but also suppresses isomerization to C6 when the label is at that site. Remarkably, this “protecting‐group” role of the deuterium is unique to THF; in ether, full deprotonation of the deuterium at C3 was observed.
Lyapunov‐based offset‐free model predictive control of nonlinear process systems
Authors: Das Buddhadeva , Mhaskar Prashant 
Published: December 2014

AbstractThis work considers the problem of control of nonlinear systems subject to uncertainty. To this end, a Lyapunov‐based robust model predictive controller (MPC) design is integrated with a moving horizon based offset‐free mechanism to enable improved closed–loop performance. Simulation results are presented to illustrate the key ideas of the proposed design.
SIS.NET: A randomized controlled trial evaluating a web‐based system for symptom management after treatment of breast cancer
Authors: Wheelock Alyse E. , Bock Meredith A. , Martin Eva L. , Hwang Jimmy , Ernest Mary Lou , Rugo Hope S. , Esserman Laura J. , Melisko Michelle E. 
Published: December 2014

BACKGROUNDAs cancer survivorship increases, health care systems will be challenged to meet patient needs. With the limited availability of clinician time and resources, novel methods of using patient‐reported outcomes may improve the quality and efficiency of follow‐up care in patients with breast cancer.METHODSThe authors conducted a randomized trial in patients with TNM stage I to III breast cancer comparing standard care with SIS.NET (System for Individualized Survivorship Care, based on patient self‐reported data, with review by Nurse practitioners, targeted Education, and Triage), a follow‐up protocol including integration of online health questionnaires at 3‐month intervals and the evaluation of self‐reported symptoms monitored and addressed remotely by a nurse practitioner (NP). The primary endpoint was to quantify the time between symptom reporting and remote evaluation of symptoms. The secondary endpoint was to compare use of health care resources (breast cancer‐related visits, total medical appointments, and laboratory and imaging studies) over an 18‐month period.RESULTSA total of 102 participants were enrolled; 2 patients were excluded due to cancer recurrence. In the SIS.NET arm, 74% of new or changed self‐reported symptoms were reviewed by a NP in <3 days. SIS.NET patients reported more new or changed symptoms compared with standard care patients (7.36 vs 3.2; P = .0045). During the 18‐month trial, there were no statistically significant differences noted between the SIS.NET and standard care arms with regard to oncology‐related appointments (mean, 4.2 vs 4.1 appointments), number of physician visits (mean, 10.8 vs 9.6 visits), or medical tests (mean, 5.5 vs 5 tests).CONCLUSIONSIntegration of online health questionnaires with remote review by a NP facilitated symptom reporting and may provide a means of convenient symptom assessment, but it did not appear to reduce health care resource use. Cancer 2015;121:893–899. © 2014 American Cancer Society.
The Influence of Cu Lattices on the Structure and Electrical Properties of Graphene Domains during Low‐Pressure Chemical Vapor Deposition
Authors: Kim Dae Woo , Kim Seon Joon , Kim Jae Sung , Shin Minju , Kim Gyu‐Tae , Jung Hee‐Tae 
Published: December 2014

AbstractThe influence of various Cu lattices on the texturing of graphene domains during low‐pressure chemical vapor deposition was investigated in a large area. The results show that the sizes and shapes of graphene domains grown on Cu(111) substrates match well with those of the underlying Cu(111) domains, which seem to be quasi‐single‐crystalline. In contrast, on other Cu substrates such as (100) and more intermediate domains, graphene islands with poly‐domains (ca. 85 %) are significantly nucleated, eventually merging into polycrystalline graphene. Within the overall channel‐length range, graphene from a Cu foil shows a higher resistance compared to graphene from a Cu(111) domain, with the extracted average channel resistances being 34.51 Ω μm−1 for Cu(111) and 66.17 Ω μm−1 for the Cu foil.
Enhanced Performance of Bioelectrochemical Hydrogen Production using a pH Control Strategy
Authors: Ruiz Yolanda , Baeza Juan A. , Guisasola Albert 
Published: December 2014

AbstractThe use of membranes in microbial electrolysis cells (MEC) is required to obtain high‐purity hydrogen and to avoid the consumption of hydrogen by undesired microorganisms. However, its utilization results in pH gradients across the membrane that contribute to potential losses and reduce the efficiency of MEC. Several pH‐controlled and noncontrolled scenarios were evaluated in this work, which evidenced that pH control is beneficial for the MEC performance. The best results were obtained if the anodic and cathodic pH were controlled at 7.5 and 2.0, respectively, to produce 0.58 m3 m−3 d−1 of hydrogen at an applied voltage of only 0.2 V. The energy efficiency with respect to the electrical input was increased up to 883 %. Anodic pH control allowed us to maintain a stable exoelectrogenic activity with practically constant current intensity, whereas cathodic pH control at 2.0 allowed a fivefold decrease of the required electrical input, which opens new opportunities for the economy of its full‐scale application.
Different health behaviours and clinical factors associated with bone mineral density and bone turnover in premenopausal women with and without type 1 diabetes
Authors: Kujath Amber S. , Quinn Lauretta , Elliott Mary E. , LeCaire Tamara J. , Binkley Neil , Molino Andrea R. , Danielson Kirstie K. 
Published: December 2014

AbstractBackgroundWomen with type 1 diabetes (T1DM) have an elevated fracture risk. We therefore compared the associations of health behaviours and clinical factors with bone mineral density (BMD) and bone remodelling between premenopausal women with and without T1DM to inform potential interventions.MethodsParticipants included women with T1DM (n = 89) from the Wisconsin Diabetes Registry Study and age‐matched and race‐matched controls without diabetes (n = 76). Peripheral (heel and forearm) and central (hip and spine) BMD, markers of bone resorption and formation, bone cell signalling, glycaemic control, and kidney function were assessed. Health behaviours and medical history were self‐reported.ResultsIn controls, but not in women with T1DM, older age was associated with lower bone resorption (p ≤ 0.006) and formation (p = 0.0007). Body mass index was positively associated with heel and forearm BMD in both controls and T1DM women (all p < 0.0001), but with hip and spine BMD only in controls (p ≤ 0.005). Worse glycaemic control during the previous 10 years, greater alcohol intake, history of smoking, and lack of physical activity were associated with poorer bone outcomes only in women with T1DM (all p ≤ 0.002), whereas use of hormonal contraceptives was related to low bone formation in both women with and without T1DM (all p ≤ 0.006). Diabetes duration, insulin dose, residual C‐peptide, and kidney function were not associated with bone in T1DM.ConclusionsAge and body mass index may not predict bone health in T1DM women. However, modifiable behaviours such as optimizing glycaemic control, limiting substance and hormonal contraceptive use, and increasing physical activity may improve bone health in T1DM women. Copyright © 2014 John Wiley & Sons, Ltd.