bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trastuzumab Triggers Phagocytic Killing of High HER2 Cancer Cells In Vitro and In Vivo by Interaction with Fcγ Receptors on Macrophages
Authors: Shi Yun , Fan Xuejun , Deng Hui , Brezski Randall J. , Rycyzyn Michael , Jordan Robert E. , Strohl William R. , Zou Quanming , Zhang Ningyan , An Zhiqiang 
Published: March 2015

Abstract
Trastuzumab has been used for the treatment of HER2-overexpressing breast cancer for more than a decade, but the mechanisms of action for the therapy are still being actively investigated. Ab-dependent cell-mediated cytotoxicity mediated by NK cells is well recognized as one of the key mechanisms of action for trastuzumab, but trastuzumab-mediated Ab-dependent cellular phagocytosis (ADCP) has not been established. In this study, we demonstrate that macrophages, by way of phagocytic engulfment, can mediate ADCP and cancer cell killing in the presence of trastuzumab. Increased infiltration of macrophages in the tumor tissue was associated with enhanced efficacy of trastuzumab whereas depletion of macrophages resulted in reduced antitumor efficacy in mouse xenograft tumor models. Among the four mouse FcγRs, FcγRIV exhibits the strongest binding affinity to trastuzumab. Knockdown of FcγRIV in mouse macrophages reduced cancer cell killing and ADCP activity triggered by trastuzumab. Consistently, an upregulation of FcγRIV expression by IFN-γ triggered an increased ADCP activity by trastuzumab. In an analogous fashion, IFN-γ priming of human macrophages increased the expression of FcγRIII, the ortholog of murine FcγRIV, and increased trastuzumab-mediated cancer cell killing. Thus, in two independent systems, the results indicated that activation of macrophages in combination with trastuzumab can serve as a therapeutic strategy for treating high HER2 breast cancer by boosting ADCP killing of cancer cells.
Induction of an Altered CD40 Signaling Complex by an Antagonistic Human Monoclonal Antibody to CD40
Authors: Bankert Katherine C. , Oxley Kyp L. , Smith Sonja M. , Graham John P. , de Boer Mark , Thewissen Marielle , Simons Peter J. , Bishop Gail A. 
Published: March 2015

Abstract
Blocking the interaction of CD40 with its ligand CD154 is a desirable goal of therapies for preventing and/or ameliorating autoimmune diseases and transplant rejection. CD154-blocking mAbs used in human clinical trials resulted in unanticipated vascular complications, leading to heightened interest in the therapeutic potential of antagonist mAbs specific for human CD40. Abs that do not require physical competition with CD154 to inhibit CD40 signaling have particular therapeutic promise. In this study, we demonstrate that the antagonist anti-human CD40 mAb PG102 fails to trigger CD40-mediated activation, as well as impairs CD154-mediated CD40 activation, via a distinct nonstimulatory CD40 signaling mechanism. PG102 did not induce early CD40-induced signaling events, and it inhibited early kinase and transcription factor activation by CD154 or agonist anti-CD40 mAbs. However, PG102 stimulated normal CD40-mediated TNFR-associated factor (TRAF)2 and TRAF3 degradation. PG102 induced the formation of a CD40 signaling complex that contained decreased amounts of both TRAF2 and TRAF3 and TRAF2-associated signaling proteins. Additionally, PG102-induced CD40 signaling complexes failed to recruit TRAF6 to detergent-insoluble membrane fractions. Fab fragments of PG102, while retaining CD40 binding, did not induce TRAF degradation, nor could they inhibit CD154-stimulated B cell signaling, indicating that CD40 aggregation is required for the signaling inhibition induced by PG102. The antagonistic impact of PG102 on CD40 signaling reveals that the manner of CD40 ligation can determine sharply different outcomes for CD40 signaling and suggests that such information can be used to therapeutically manipulate these outcomes.
The Role of PTPN22 Risk Variant in the Development of Autoimmunity: Finding Common Ground between Mouse and Human
Authors: Rawlings David J. , Dai Xuezhi , Buckner Jane H. 
Published: March 2015

Abstract
The PTPN22 1858T variant was among the first single nucleotide polymorphisms to be associated with multiple autoimmune diseases. Lymphocyte tyrosine phosphatase, a coding variant within the tyrosine phosphatases, is known to participate in AgR signaling; the impact of this variant on the immune response and its role in the development of autoimmunity have been a focus of study. These studies used a series of approaches, including transfected cell lines, animal models, and primary human lymphocytes, and identified multiple alterations in cell signaling and function linked to the PTPN22 variant. Conflicting findings led to questions of how best to study the role of this variant in human autoimmunity. In this review, we discuss these differences and the factors that may account for them, as well as show how an integrated approach can lead to a more complete understanding of the mechanisms that promote autoimmunity in the context of the PTPN22 1858T risk variant.
Tumor-Infiltrating Dendritic Cells in Cancer Pathogenesis
Authors: Tran Janco Jo Marie , Lamichhane Purushottam , Karyampudi Lavakumar , Knutson Keith L. 
Published: March 2015

AbstractDendritic cells (DCs) play a pivotal role in the tumor microenvironment, which is known to affect disease progression in many human malignancies. Infiltration by mature, active DCs into the tumors confers an increase in immune activation and recruitment of disease-fighting immune effector cells and pathways. DCs are the preferential target of infiltrating T cells. However, tumor cells have means of suppressing DC function or of altering the tumor microenvironment in such a way that immune-suppressive DCs are recruited. Advances in understanding these changes have led to promising developments in cancer-therapeutic strategies targeting tumor-infiltrating DCs to subdue their immunosuppressive functions and enhance their immune-stimulatory capacity.
IFN-α/β Receptor Signaling Promotes Regulatory T Cell Development and Function under Stress Conditions
Authors: Metidji Amina , Rieder Sadiye Amcaoglu , Glass Deborah Dacek , Cremer Isabelle , Punkosdy George A. , Shevach Ethan M. 
Published: March 2015

Abstract
Type I IFNs are a family of cytokines with antiviral and immunomodulatory properties. Although the antiviral effects of IFNs are well characterized, their immunomodulatory properties are less clear. To specifically address the effects of type I IFNs on T regulatory cells (Tregs), we studied mixed bone marrow chimeras between wild-type and IFN-α/β receptor (IFNAR) knockout (KO) mice, and heterozygous female mice expressing a Treg-specific deletion of the IFNAR. In these two models, IFNAR signaling promotes the development of the Treg lineage in the thymus and their survival in the periphery. IFNAR KO Tregs had a higher expression of the proapoptotic gene Bim and higher frequency of active caspase-positive cells. IFNAR KO Tregs from chimeric mice displayed a more naive phenotype, accompanied by lower levels of CD25 and phosphorylated STAT5. Therefore, in Tregs, IFNAR signaling may directly or indirectly affect phosphorylation of STAT5. In mixed chimeras with Scurfy fetal liver, Tregs derived from IFNAR KO bone marrow were unable to control T effector cell activation and tissue inflammation. Under stress conditions or in a competitive environment, IFNAR signaling may be required to maintain Treg homeostasis and function.
Changes in seismicity and stress loading on subduction faults in the Kanto region, Japan, 2011–2014
Authors: Gardonio Blandine , Marsan David , Lengliné Olivier , Enescu Bogdan , Bouchon Michel , Got Jean‐Luc 
Published: March 2015

AbstractSeismic activity has increased in the Kanto region, Japan, following the 2011 M9.0 Tohoku earthquake. We here reassess this increase up to June 2014, to show that normal, Omori‐like relaxation characterizes the activity on crustal faults as well as on the Philippine Sea plate, but not on the deeper Pacific plate. There repeating earthquakes display a twofold rate of occurrence (still ongoing in June 2014) as compared to the pre‐Tohoku rate, suggesting enhanced creep. We compute the Coulomb stress changes on the upper locked portion of the Philippine Sea plate, which last ruptured in 1923. We find that this fault was little affected by either the coseismic, the postseismic, the accelerated creep, or the 2011 Boso silent slip event.
Tropical rainforest response to marine sky brightening climate engineering
Authors: Muri Helene , Niemeier Ulrike , Kristjánsson Jón Egill 
Published: March 2015

AbstractTropical forests represent a major atmospheric carbon dioxide sink. Here the gross primary productivity (GPP) response of tropical rainforests to climate engineering via marine sky brightening under a future scenario is investigated in three Earth system models. The model response is diverse, and in two of the three models, the tropical GPP shows a decrease from the marine sky brightening climate engineering. Partial correlation analysis indicates precipitation to be important in one of those models, while precipitation and temperature are limiting factors in the other. One model experiences a reversal of its Amazon dieback under marine sky brightening. There, the strongest partial correlation of GPP is to temperature and incoming solar radiation at the surface. Carbon fertilization provides a higher future tropical rainforest GPP overall, both with and without climate engineering. Salt damage to plants and soils could be an important aspect of marine sky brightening.
Nonlinear interactions of waves and tides in a subterranean estuary
Authors: Xin Pei , Wang Shen S. J. , Lu Chunhui , Robinson Clare , Li Ling 
Published: March 2015

AbstractPrevious studies have revealed hysteretic behavior in subterranean estuaries in response to intensified wave conditions caused by offshore storm events, showing dependence of submarine groundwater discharge (SGD) and subsurface salt distribution on historic wave conditions. Although most shorelines worldwide are also exposed to tidal fluctuations, it is unclear how tides moderate wave‐induced SGD and salinity distribution in subterranean estuaries. This study presents numerical simulations that explore the combined influence of intensified wave conditions and tides on groundwater flow and salt transport in a subterranean estuary. The results show that tides weaken the hysteretic wave effect on SGD, suggesting that a tidally influenced subterranean estuary is less sensitive to intensified wave conditions with respect to the water fluxes across the aquifer‐sea interface. However, due to enhancement of salt‐freshwater mixing, tides strengthen the hysteretic wave effect on the salt fluxes across the aquifer‐sea interface, prolonging the recovery of salt distribution in the subterranean estuary to the prestorm state. These findings reveal the nonlinear, coupling nature of processes driven by oceanic oscillations at different time scales in subterranean estuaries.
Disappearance of plasmaspheric hiss following interplanetary shock
Authors: Su Zhenpeng , Zhu Hui , Xiao Fuliang , Zheng Huinan , Wang Yuming , Shen Chao , Zhang Min , Wang Shui , Kletzing C. A. , Kurth W. S. , Hospodarsky G. B. , Spence H. E. , Reeves G. D. , Funsten H. O. , Blake J. B. , Baker D. N. , Wygant J. R. 
Published: March 2015

AbstractPlasmaspheric hiss is one of the important plasma waves controlling radiation belt dynamics. Its spatiotemporal distribution and generation mechanism are presently the object of active research. We here give the first report on the shock‐induced disappearance of plasmaspheric hiss observed by the Van Allen Probes on 8 October 2013. This special event exhibits the dramatic variability of plasmaspheric hiss and provides a good opportunity to test its generation mechanisms. The origination of plasmaspheric hiss from plasmatrough chorus is suggested to be an appropriate prerequisite to explain this event. The shock increased the suprathermal electron fluxes, and then the enhanced Landau damping promptly prevented chorus waves from entering the plasmasphere. Subsequently, the shrinking magnetopause removed the source electrons for chorus, contributing significantly to the several‐hours‐long disappearance of plasmaspheric hiss.
Ruthenium Complex‐Catalyzed Domino Addition/exo‐ Cycloisomerization of Propargylic Alcohols and Tosyl Isocyanate to Form Oxazolidinones
Authors: Li Deng Yuan , Chen Hao Jie , Liu Pei Nian 
Published: March 2015

AbstractA ruthenium complex with a tetradentate nitrogen–phosphorus mixed ligand is shown to be an efficient catalyst for domino addition/exo‐cycloisomerization of propargylic alcohols and tosyl isocyanate. In the presence of 2–5 mol% ruthenium complex, a range of terminal propargylic alcohols were reacted with tosyl isocyanate to furnish the corresponding oxazolidinone product exclusively in moderate to excellent yields. Mechanistic studies suggest that propargylic alcohol and tosyl isocyanate undergo addition firstly to generate propargylic carbamate, which is then activated by the ruthenium complex to form an η2‐alkyne complex, rather than the ruthenium vinylidene intermediate, to afford the final oxazolidinone product.magnified image
Palladium on Carbon‐Catalyzed Aqueous Transformation of Primary Alcohols to Carboxylic Acids Based on Dehydrogenation under Mildly Reduced Pressure
Authors: Sawama Yoshinari , Morita Kosuke , Asai Shota , Kozawa Masami , Tadokoro Shinsuke , Nakajima Junichi , Monguchi Yasunari , Sajiki Hironao 
Published: March 2015

AbstractThe catalytic dehydrogenation of alcohols to carbonyl products is a green sustainable oxidation with no production of waste except for hydrogen, which can be an energy source. Additionally, a reusable heterogeneous catalyst is valuable from the viewpoint of process chemistry and water is a green solvent. We have accomplished the palladium on carbon (Pd/C)‐catalyzed dehydrogenation of primary alcohols to carboxylic acids in water under a mildly reduced pressure (800 hPa). The reduced pressure can be easily controlled by the vacuum controller of the rotary evaporator to remove the excess of generated hydrogen, which causes the reduction (reverse reaction) of aldehydes to alcohols (starting materials) and other undesirable side reactions. The present method is applicable to the reaction of various aliphatic and benzylic alcohols to the corresponding carboxylic acids, and the Pd/C could be reused at least 5 times.magnified image
Very Important Publication: Iridium‐Catalyzed Intramolecular Enantioselective CH Alkylation at the C‐2 Position of N‐Alkenylindoles
Authors: Shibata Takanori , Ryu Naoto , Takano Hideaki 
Published: March 2015

AbstractIntramolecular enantioselective alkylation of N‐alkenylindoles proceeded via CH bond cleavage at the C‐2 position in the presence of a cationic iridium catalyst with a diphosphine ligand. Aroyl groups at the C‐3 position of the indoles operated as effective directing groups, and chiral 1‐substituted‐2,3‐dihydro‐1H‐pyrrolo[1,2‐a]indoles were obtained in high yield with excellent ee.magnified image
Being born after your brother is not a disadvantage: Reproductive success does not depend on the sex of the preceding sibling
Authors: Puskarczyk Karolina , Galbarczyk Andrzej , Klimek Magdalena , Nenko Ilona , Odrzywołek Ludwik , Jasienska Grazyna 
Published: March 2015

ObjectivesThe aim of the present study is to examine whether being born after a brother versus after a sister differentially impacts reproductive outcomes in a contemporary population. The sex of the preceding sibling may influence an individual's fitness, and, in fact, individuals born after a brother have been shown to have lower reproductive success in historical populations. Males, as the more expensive sex, constitute a drain on maternal resources and elicit an immune response during pregnancy, which may have negative consequences on subsequent siblings.MethodsA questionnaire was used to collect data on reproductive health and family history from 951 women and 380 men between 20 and 92 years of age in villages throughout the Mogielica Human Ecology Study Site in southern Poland. Number of children, number of sons and daughters, age at menarche, age at marriage, age at menopause, and age at first and last reproduction were tested as components of reproductive success.ResultsThe sex of one's preceding sibling had no statistically significant impact on any of the reproductive characteristics tested.ConclusionsOur results suggest that potential immunological and nutritional disadvantages experienced during prenatal life by individuals born after male siblings do not have long‐lasting effects in modern, well‐nourished populations. Am. J. Hum. Biol. 27:731–733, 2015. © 2015 Wiley Periodicals, Inc.
Theory and Practice: Bulk Synthesis of C3B and its H2‐ and Li‐Storage Capacity
Authors: King Timothy C. , Matthews Peter D. , Glass Hugh , Cormack Jonathan A. , Holgado Juan Pedro , Leskes Michal , Griffin John M. , Scherman Oren A. , Barker Paul D. , Grey Clare P. , Dutton Siân E. , Lambert Richard M. , Tustin Gary , Alavi Ali , Wright Dominic S. 
Published: March 2015

AbstractPrevious theoretical studies of C3B have suggested that boron‐doped graphite is a promising H2‐ and Li‐storage material, with large maximum capacities. These characteristics could lead to exciting applications as a lightweight H2‐storage material for automotive engines and as an anode in a new generation of batteries. However, for these applications to be realized a synthetic route to bulk C3B must be developed. Here we show the thermolysis of a single‐source precursor (1,3‐(BBr2)2C6H4) to produce graphitic C3B, thus allowing the characteristics of this elusive material to be tested for the first time. C3B was found to be compositionally uniform but turbostratically disordered. Contrary to theoretical expectations, the H2‐ and Li‐storage capacities are lower than anticipated, results that can partially be explained by the disordered nature of the material. This work suggests that to model the properties of graphitic materials more realistically, the possibility of disorder must be considered.
Multifunctional Reagents for Quantitative Proteome‐Wide Analysis of Protein Modification in Human Cells and Dynamic Profiling of Protein Lipidation During Vertebrate Development
Authors: Broncel Malgorzata , Serwa Remigiusz A. , Ciepla Paulina , Krause Eberhard , Dallman Margaret J. , Magee Anthony I. , Tate Edward W. 
Published: March 2015

AbstractNovel multifunctional reagents were applied in combination with a lipid probe for affinity enrichment of myristoylated proteins and direct detection of lipid‐modified tryptic peptides by mass spectrometry. This method enables high‐confidence identification of the myristoylated proteome on an unprecedented scale in cell culture, and allowed the first quantitative analysis of dynamic changes in protein lipidation during vertebrate embryonic development.
1D NMR Homodecoupled 1H Spectra with Scalar Coupling Constants from 2D NemoZS‐DIAG Experiments
Authors: Cotte Axelle , Jeannerat Damien 
Published: March 2015

AbstractA two‐dimensional liquid‐state NMR experiment cleanly separating chemical shifts and scalar couplings information is introduced. This DIAG experiment takes advantage of a drastic reduction of the spectral window in the indirect dimension to be quickly recorded and of a new non‐equidistant modulation of the selective pulse to improve the sensitivity of the broadband homodecoupling Zangger–Sterk sequence element by one order of magnitude. A simple automatic analysis results in 1D spectra displaying singlets and lists of the scalar couplings for first‐order multiplets. This facilitates the analysis of 1D spectra by resolving multiplets based on their differences in chemical shifts and coupling structures.
Organocatalytic Enantioselective Oxidative CH Alkenylation and Arylation of N‐Carbamoyl Tetrahydropyridines and Tetrahydro‐β‐carbolines
Authors: Liu Xigong , Meng Zhilin , Li Chengkun , Lou Hongxiang , Liu Lei 
Published: March 2015

AbstractThe first organocatalytic enantioselective CH alkenylation and arylation reactions of N‐carbamoyl tetrahydropyridines and tetrahydro‐β‐carbolines (THCs) are described. The metal‐free processes represent an efficient and straightforward approach to a variety of structurally and electronically diverse α‐substituted tetrahydropyridines and THCs in good yields with excellent regio‐ and enantioselectivities. Preliminary control experiments provide important insights into the reaction mechanism.
Formation of BN Isosteres of Azo Dyes by Ring Expansion of Boroles with Azides
Authors: Braunschweig Holger , Celik Mehmet Ali , Hupp Florian , Krummenacher Ivo , Mailänder Lisa 
Published: March 2015

AbstractHerein, we present the results of our investigations on the effect of ortho substitution of aryl azides on the ring‐expansion reaction of boroles, five‐membered unsaturated boron heterocycles. These studies led to the isolation of the first 1,2‐azaborinine‐substituted azo dyes, which are bright yellow solids. One of the derivatives, (E)‐2‐mesityl‐1‐(mesityldiazenyl)‐3,4,5,6‐tetraphenyl‐1,2‐azaborinine, was found to be unstable in solution and to transform through a Jacobsen‐like reaction into an indazole and 1‐hydro‐1,2‐azaborinine. DFT calculations were performed to shed light on possible mechanisms to rationalize the unexpected azo‐azaborinine formation and to draw conclusions about the role played by the ortho substituents in the reaction.
A mixed complementarity model for the US biofuel market with federal policy interventions
Authors: Christensen Adam , Siddiqui Sauleh 
Published: March 2015

AbstractPolicymakers in the USA have provided various mechanisms to grow the domestic biofuel industry. One of the most significant policies in the USA is the volume mandate specified within the Renewable Fuel Standard (RFS). There are a number of other overlapping factors that impact the use of biofuels, namely the so‐called blend wall, or the 10% blend limit of ethanol in gasoline, along with a complex system of tax credits. All of these policies directly affect the value of a Renewable Identification Number (RIN), the tradable compliance certificate created as part of the RFS. Regulators track RIN prices carefully because they are a measure of the cost of compliance. In this work a mixed complementarity problem (MCP) is presented to combine these market dynamics into one model. This tool was specifically designed for policymakers to compare scenarios and study the effects on key market variables including RIN, gasoline, and diesel prices, along with production quantities for a number of different finished blended fuels. Our results suggest that RIN prices will increase with an increase in the volume of biofuel mandated by the Environmental Protection Agency (EPA); however the behavior of the different RIN prices depends on how the biofuel volumes are assigned among all the subcategories. Under scenarios investigated in this study, it is likely that a primary compliance strategy is to blend more biodiesel into diesel fuel. This behavior would increase the price of the D4 RIN but the premium could be mitigated by reinstating the biodiesel production tax credit. © 2015 Society of Chemical Industry and John Wiley & Sons, Ltd