bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Interaction between Lyn, Ets1, and Btk in the Control of Antibody Levels
Authors: Mayeux Jessica , Skaug Brian , Luo Wei , Russell Lisa M. , John Shinu , Saelee Prontip , Abbasi Hansaa , Li Quan-Zhen , Garrett-Sinha Lee Ann , Satterthwaite Anne B.
Published: July 2015

Tight control of B cell differentiation into plasma cells (PCs) is critical for proper immune responses and the prevention of autoimmunity. The Ets1 transcription factor acts in B cells to prevent PC differentiation. Ets1−/− mice accumulate PCs and produce autoantibodies. Ets1 expression is downregulated upon B cell activation through the BCR and TLRs and is maintained by the inhibitory signaling pathway mediated by Lyn, CD22 and SiglecG, and SHP-1. In the absence of these inhibitory components, Ets1 levels are reduced in B cells in a Btk-dependent manner. This leads to increased PCs, autoantibodies, and an autoimmune phenotype similar to that of Ets1−/− mice. Defects in inhibitory signaling molecules, including Lyn and Ets1, are associated with human lupus, although the effects are more subtle than the complete deficiency that occurs in knockout mice. In this study, we explore the effect of partial disruption of the Lyn/Ets1 pathway on B cell tolerance and find that Lyn+/−Ets1+/− mice demonstrate greater and earlier production of IgM, but not IgG, autoantibodies compared with Lyn+/− or Ets1+/− mice. We also show that Btk-dependent downregulation of Ets1 is important for normal PC homeostasis when inhibitory signaling is intact. Ets1 deficiency restores the decrease in steady state PCs and Ab levels observed in Btk−/− mice. Thus, depending on the balance of activating and inhibitory signals to Ets1, there is a continuum of effects on autoantibody production and PC maintenance. This ranges from full-blown autoimmunity with complete loss of Ets1-maintaining signals to reduced PC and Ab levels with impaired Ets1 downregulation.
The TNF Family Molecules LIGHT and Lymphotoxin αβ Induce a Distinct Steroid-Resistant Inflammatory Phenotype in Human Lung Epithelial Cells
Authors: da Silva Antunes Ricardo , Madge Lisa , Soroosh Pejman , Tocker Joel , Croft Michael
Published: July 2015

Lung epithelial cells are considered important sources of inflammatory molecules and extracellular matrix proteins that contribute to diseases such as asthma. Understanding the factors that stimulate epithelial cells may lead to new insights into controlling lung inflammation. This study sought to investigate the responsiveness of human lung epithelial cells to the TNF family molecules LIGHT and lymphotoxin αβ (LTαβ). Bronchial and alveolar epithelial cell lines, and primary human bronchial epithelial cells, were stimulated with LIGHT and LTαβ, and expression of inflammatory cytokines and chemokines and markers of epithelial-mesenchymal transition and fibrosis/remodeling was measured. LTβ receptor, the receptor shared by LIGHT and LTαβ, was constitutively expressed on all epithelial cells. Correspondingly, LIGHT and LTαβ strongly induced a limited but highly distinct set of inflammatory genes in all epithelial cells tested, namely the adhesion molecules ICAM-1 and VCAM-1; the chemokines CCL5, CCL20, CXCL1, CXCL3, CXCL5, and CXCL11; the cytokines IL-6, activin A and GM-CSF; and metalloproteinases matrix metalloproteinase-9 and a disintegrin and metalloproteinase domain-8. Importantly, induction of the majority of these inflammatory molecules was insensitive to the suppressive effects of the corticosteroid budesonide. LIGHT and LTαβ also moderately downregulated E-cadherin, a protein associated with maintaining epithelial integrity, but did not significantly drive production of extracellular matrix proteins or α-smooth muscle actin. Thus, LIGHT and LTαβ induce a distinct steroid-resistant inflammatory signature in airway epithelial cells via constitutively expressed LTβ receptor. These findings support our prior murine studies that suggested the receptors for LIGHT and LTαβ contribute to development of lung inflammation characteristic of asthma and idiopathic pulmonary fibrosis.
Selective Targeting of a Disease-Related Conformational Isoform of Macrophage Migration Inhibitory Factor Ameliorates Inflammatory Conditions
Authors: Thiele Michael , Kerschbaumer Randolf J. , Tam Frederick W. K. , Völkel Dirk , Douillard Patrice , Schinagl Alexander , Kühnel Harald , Smith Jennifer , McDaid John P. , Bhangal Gurjeet , Yu Mei-Ching , Pusey Charles D. , Cook H. Terence , Kovarik Josef , Magelky Erica , Bhan Atul , Rieger Manfred , Mudde Geert C. , Ehrlich Hartmut , Jilma Bernd , Tilg Herbert , Moschen Alexander , Terhorst Cox , Scheiflinger Friedrich
Published: July 2015

Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine and counterregulator of glucocorticoids, is a potential therapeutic target. MIF is markedly different from other cytokines because it is constitutively expressed, stored in the cytoplasm, and present in the circulation of healthy subjects. Thus, the concept of targeting MIF for therapeutic intervention is challenging because of the need to neutralize a ubiquitous protein. In this article, we report that MIF occurs in two redox-dependent conformational isoforms. We show that one of the two isoforms of MIF, that is, oxidized MIF (oxMIF), is specifically recognized by three mAbs directed against MIF. Surprisingly, oxMIF is selectively expressed in the plasma and on the cell surface of immune cells of patients with different inflammatory diseases. In patients with acute infections or chronic inflammation, oxMIF expression correlated with inflammatory flare-ups. In addition, anti-oxMIF mAbs alleviated disease severity in mouse models of acute and chronic enterocolitis and improved, in synergy with glucocorticoids, renal function in a rat model of crescentic glomerulonephritis. We conclude that oxMIF represents the disease-related isoform of MIF; oxMIF is therefore a new diagnostic marker for inflammation and a relevant target for anti-inflammatory therapy.
Langerhans Cells Suppress CD49a+ NK Cell–Mediated Skin Inflammation
Authors: Scholz Felix , Naik Shruti , Sutterwala Fayyaz S. , Kaplan Daniel H.
Published: July 2015

Recruitment of innate immune effector cells into sites of infection is a critical component of resistance to pathogen infection. Using a model of intradermal footpad injection of Candida albicans, we observed that inflammation as measured by footpad thickness and neutrophil recruitment occurred independent of adoptive immunity but was significantly reduced in MyD88−/− and IL-6−/− mice. Unexpectedly, huLangerin-DTA mice (ΔLC) that lack Langerhans cells (LC) developed increased skin inflammation and expressed higher amounts of IL-6, suggesting a suppressive role for LC. Increased inflammation also occurred in Rag1−/− ΔLC mice but was reversed by Ab-mediated ablation of NK cells. CXCR6+CD49a+ NK cells are a liver-resident subset that can mediate inflammatory skin responses. We found that exaggerated skin inflammation was absent in ΔLC × CXCR6−/− mice. Moreover, the exaggerated response in ΔLC mice could be adoptively transferred with liver CD49a+ NK cells. Finally, CD49a+ NK cells in ΔLC but not control mice were recruited to the skin, and inhibition of their recruitment prevented the exaggerated response. Thus, in the absence of LC, CD49a+ liver NK cells display an inappropriately proinflammatory phenotype that results in increased local skin inflammation. These data reveal a novel function for LC in the regulation of this recently described subset of skin tropic NK cells.
CXCR3 Polymorphism and Expression Associate with Spontaneous Preterm Birth
Authors: Karjalainen Minna K. , Ojaniemi Marja , Haapalainen Antti M. , Mahlman Mari , Salminen Annamari , Huusko Johanna M. , Määttä Tomi A. , Kaukola Tuula , Anttonen Julia , Ulvila Johanna , Haataja Ritva , Teramo Kari , Kingsmore Stephen F. , Palotie Aarno , Muglia Louis J. , Rämet Mika , Hallman Mikko
Published: July 2015

Spontaneous preterm birth (SPTB) is a major factor associating with deaths and with lowered quality of life in humans. Environmental and genetic factors influence the susceptibility. Previously, by analyzing families with recurrent SPTB in linkage analysis, we identified a linkage peak close to the gene encoding CXCR3. Present objectives were to investigate the association of CXCR3 with SPTB in Finnish mothers (n = 443) and infants (n = 747), to analyze CXCR3 expression levels in human placenta and levels of its ligands in umbilical cord blood, and to verify the influence of Cxcr3 on SPTB-associating cytokines in mice. We detected an association between an intronic CXCR3 polymorphism, rs2280964, and SPTB in infants from families with recurrent preterm births (p = 0.009 versus term controls, odds ratio 0.52, 95% confidence interval 0.32–0.86). The minor allele was protective and undertransmitted to SPTB infants (p = 0.007). In the placenta and fetal membranes, the rs2280964 major allele homozygotes had higher expression levels than minor allele homozygotes; decidual trophoblasts showed strong CXCR3 immunoreactivity. Expression was higher in SPTB placentas compared with those from elective deliveries. Concentration of a CXCR3 ligand, CXCL9, was increased in cord blood from SPTB, and the protective rs2280964 allele was associated with low CXCL9. In CXCR3-deficient mice (Mus musculus), SPTB-associating cytokines were not acutely increased in amniotic fluid after preterm birth–inducing dose of maternal LPS. Our results indicate that CXCR3 contributes to SPTB. Activation of CXCR3 signaling may disturb the maternal–fetal tolerance, and this may promote labor.
Cross-Cultural Comparison of Tamale and Salt Lake City Experience of Unemployed Women With Physical Disabilities
Authors: Naami Augustina
Published: July 2015

Gender and disability interacts to create several challenges and vulnerabilities for women with disabilities. This paper explores and compares the daily experiences of unemployed women with physical disabilities in Tamale-Ghana and Salt Lake City, Utah in the United States.

Face-to-face in-depth interviews were conducted with 15 women with physical disabilities about their experiences with employment, unemployment and how unemployment affects their lives. Outcome suggests that the women encounter several challenges in their daily lives relating to mobility, family relationships, income, social participation and living arrangement. While some of the experiences undoubtedly differ between the two studies, some, interestingly, were similar across the two geographic regions regardless of the cultural differences.
Phosphorus budget in the water‐agro‐food system at nested scales in two contrasted regions of the world (ASEAN‐8 and EU‐27)
Authors: Garnier Josette , Lassaletta Luis , Billen Gilles , Romero Estela , Grizzetti Bruna , Némery Julien , Le Thi Phuong Quynh , Pistocchi Chiara , Aissa‐Grouz Najla , Luu Thi Nguyet Minh , Vilmin Lauriane , Dorioz Jean‐Marcel
Published: July 2015

Phosphorus (P) plays a strategic role in agricultural production as well as in the occurrence of freshwater and marine eutrophication episodes throughout the world. Moreover, the scarcity and uneven distribution of minable P resources is raising concerns about the sustainability of long‐term exploitation. In this paper we analyze the P cycle in anthropic systems with an original multiscale approach (world region, country, and large basin scales) in two contrasting world regions representative of different trajectories in socioeconomic development for the 1961–2009 period: Europe (EU‐27)/France and the Seine River Basin, and Asia (ASEAN‐8)/Vietnam and the Red River Basin. Our approach highlights different trends in the agricultural and food production systems of the two regions. Whereas crop production increased until the 1980s in Europe and France and has stabilized thereafter, in ASEAN‐8 and Vietnam it began to increase in the 1980s and it is still rising today. These trends are related to the increasing use of fertilizers, although in European countries the amount of fertilizers sharply decreased after the 1980s. On average, the total P delivered from rivers to the sea is 3 times higher for ASEAN‐8 (300 kg P km−2 yr−1) than for EU‐27 countries (100 kg P km−2 yr−1) and is twice as high in the Red River (200 kg P km−2 yr−1) than in the Seine River (110 kg P km−2 yr−1), with agricultural losses to water in ASEAN‐8 3 times higher than in EU‐27. Based on the P flux budgets, this study discusses early warnings and management options according to the particularities of the two world regions, newly integrating the perspective of surface water quality with agricultural issues (fertilizers, crop production, and surplus), food/feed exchanges, and diet, defining the so‐called water‐agro‐food system.
Dependence of the dayside magnetopause reconnection rate on local conditions
Authors: Wang Shan , Kistler Lynn M. , Mouikis Christopher G. , Petrinec Steven M.
Published: July 2015

We estimate the reconnection rates for eight dayside magnetopause reconnection events observed by the Cluster spacecraft and compare them with the predictions of the Cassak‐Shay Formula (Rcs) Cassak and Shay (2007). The measured reconnection rate is determined by calculating the product of the inflow velocity and magnetic field in the magnetosheath inflow region. The predicted reconnection rate is calculated using the plasma parameters on both sides of the current layer, including the contributions of magnetosheath H+, magnetospheric hot H+ and O+, and magnetospheric cold ions. The measured reconnection rates show clear correlations with Rcs with an aspect ratio of 0.07. The O+ and cold ions can contribute up to ~30% of the mass density, which may reduce the reconnection rate for individual events. However, the variation of the reconnection rate is dominated by the variation of the magnetosheath parameters. In addition, we calculated the predicted reconnection rate using only magnetosheath parameters (Rsh). The correlation of the measured rate with Rsh was better than the correlation with Rcs, with an aspect ratio of 0.09. This might indicate deviations from the Cassak‐Shay theory caused by the asymmetric reconnection structure and kinetic effects of different inflow populations. A better aspect ratio is expected to be between the ones determined using Rcs and Rsh. The aspect ratio does not show a clear dependence on the O+ concentration, likely because the O+ contribution is too small in these events. The aspect ratio also does not show a clear correlation with density asymmetry or guide field.
Self‐acceleration and instability of gravity wave packets: 1. Effects of temporal localization
Authors: Fritts David C. , Laughman Brian , Lund Thomas S. , Snively Jonathan B.
Published: July 2015

An anelastic numerical model is used to explore the dynamics accompanying the attainment of large amplitudes by gravity waves (GWs) that are localized in altitude and time. GW momentum transport induces mean flow variations accompanying a GW packet that grows exponentially with altitude, is localized in altitude, and induces significant GW phase speed, and phase, variations across the GW packet. These variations arise because the GW occupies the region undergoing accelerations, with the induced phase speed variations referred to as “self‐acceleration.” Results presented here reveal that self‐acceleration of a GW packet localized in time and altitude ultimately leads to stalling of the vertical propagation of the GW packet and accompanying two‐ and three‐dimensional (2‐D and 3‐D) instabilities of the superposed GW and mean motion field. The altitudes at which these effects occur depend on the initial GW amplitude, intrinsic frequency, and degree of localization in time and altitude. Larger amplitudes and higher intrinsic frequencies yield strong self‐acceleration effects at lower altitudes, while smaller amplitudes yield similar effects at higher altitudes, provided the Reynolds number, Re, is sufficiently large. Three‐dimensional instabilities follow 2‐D “self‐acceleration instability” for sufficiently high Re. GW packets can also exhibit self‐acceleration dynamics at more than one altitude because of continued growth of the GW packet leading edge above the previous self‐acceleration event.
Conjoint use of Dibenzosilole and Indan‐1,3‐dione Functionalities to Prepare an Efficient Non‐Fullerene Acceptor for Solution‐Processable Bulk‐Heterojunction Solar Cells
Authors: Patil Hemlata , Gupta Akhil , Alford Ben , Ma Di , Privér Steven H. , Bilic Ante , Sonar Prashant , Bhosale Sheshanath V.
Published: July 2015

A solution‐processable, non‐fullerene electron acceptor, 2,2′‐(((5,5‐dioctyl‐5 H‐dibenzo[b,d]silole‐3,7‐diyl)bis(thiophene‐5,2‐diyl))bis(methanylylidene))bis(1 H‐indene‐1,3(2 H)‐dione) (called N5) comprised of dibenzosilole and 1,3‐indanedione building blocks was designed, synthesized, and fully characterized. N5 is highly soluble in various organic solvents, has high thermal stability, and has energy levels matching those of archetypal donor poly(3‐hexylthiophene). Solution‐processable, bulk‐heterojunction solar cells afforded promising power conversion efficiency of 2.76 % when N5 was used as a non‐fullerene electron acceptor along with the conventional donor polymer poly(3‐hexylthiophene). As per our knowledge, the material reported herein is the first example in the literature where synchronous use of such building blocks is demonstrated in the design an efficient, non‐fullerene acceptor.
Modulation der Stereoselektivität einer DNA‐katalysierten Michael‐Addition durch kovalente Modifizierung
Authors: Dey Surjendu , Jäschke Andres
Published: July 2015

G‐Quadruplex‐DNA fand – im Komplex mit CuII‐Ionen – bereits Anwendung als Katalysator in asymmetrischen Reaktionen. Die größtenteils unspezifische nichtkovalente Wechselwirkung erschwerte jedoch das Verständnis der strukturellen Grundlage der Katalyse. Mit dem Ziel, die Bildung katalytisch aktiver Spezies präziser kontrollieren zu können, beschreiben wir hier die Synthese von DNA‐Quadruplexen, die ortsspezifisch mit Linker‐bpy‐CuII‐Komplexen derivatisiert wurden, sowie ihre Anwendung in asymmetrischen wässrigen Michael‐Additionen. Die modifizierten Quadruplexe zeichnen sich durch eine hohe Reaktionsbeschleunigung und Stereoselektivität aus, wobei unterschiedliche Faktoren das katalytische Verhalten beeinflussen. Dazu zählen unter anderem die Position der Modifizierung, die Topologie der Quadruplexe, die Art des Liganden und die Länge des Linkers zwischen Ligand und DNA. Erstaunlicherweise führte das Versetzen des gleichen Liganden um lediglich zwei Nukleotide zu einer Umkehr der Stereochemie der Reaktion. Während Quadruplexe, die an Position 10 modifiziert wurden, vorzugsweise das (−)‐Enantiomer mit einem Enantiomerenüberschuss von bis zu 92 % bildeten, lieferte die an Position 12 derivatisierte DNA bevorzugt das (+)‐Enantiomer mit bis zu 75 % ee. Diese entgegengesetzte Stereopräferenz wurde auch bei strukturell unterschiedlichen Michael‐Akzeptoren beobachtet. Unsere Arbeit zeigt einen neuen und einfachen Weg auf, die Stereoselektivität in der DNA‐basierten asymmetrischen Katalyse zu modulieren.
Synthetic Enterobacterial Common Antigen (ECA) for the Development of a Universal Immunotherapy for Drug‐Resistant Enterobacteriaceae
Authors: Liu Lin , Zha Jingying , DiGiandomenico Antonio , McAllister Douglas , Stover C. Kendall , Wang Qun , Boons Geert‐Jan
Published: July 2015

All Enterobacteriaceae express a polysaccharide known as enterobacterial common antigen (ECA), which is an attractive target for the development of universally acting immunotherapies. The first chemical synthesis of ECA‐derived oligosaccharides for the development of such therapies is described. A number of synthetic challenges had to be addressed, including the development of concise synthetic procedures for unusual monosaccharides, the selection of appropriate orthogonal protecting groups, the development of stereoselective glycosylation methods, appropriate timing for the introduction of the carboxylic acid groups on the ManpNAcA moieties, and the selection of appropriate conditions for the reduction of multiple azido moieties. The synthetic compounds were employed to uncover immunodominant moieties of ECA. Furthermore, a monoclonal antibody (mAb) was developed that binds to ECA and can selectively recognize a wide range of Enterobacteriaceae species.
Proteome‐Wide Profiling of Targets of Cysteine reactive Small Molecules by Using Ethynyl Benziodoxolone Reagents
Authors: Abegg Daniel , Frei Reto , Cerato Luca , Prasad Hari Durga , Wang Chao , Waser Jerome , Adibekian Alexander
Published: July 2015

In this study, we present a highly efficient method for proteomic profiling of cysteine residues in complex proteomes and in living cells. Our method is based on alkynylation of cysteines in complex proteomes using a “clickable” alkynyl benziodoxolone bearing an azide group. This reaction proceeds fast, under mild physiological conditions, and with a very high degree of chemoselectivity. The formed azide‐capped alkynyl–cysteine adducts are readily detectable by LC‐MS/MS, and can be further functionalized with TAMRA or biotin alkyne via CuAAC. We demonstrate the utility of alkynyl benziodoxolones for chemical proteomics applications by identifying the proteomic targets of curcumin, a diarylheptanoid natural product that was and still is part of multiple human clinical trials as anticancer agent. Our results demonstrate that curcumin covalently modifies several key players of cellular signaling and metabolism, most notably the enzyme casein kinase I gamma. We anticipate that this new method for cysteine profiling will find broad application in chemical proteomics and drug discovery.
Local Joint Inflammation and Histone Citrullination in a Murine Model of the Transition From Preclinical Autoimmunity to Inflammatory Arthritis
Authors: Sohn Dong Hyun , Rhodes Christopher , Onuma Kazuhiro , Zhao Xiaoyan , Sharpe Orr , Gazitt Tal , Shiao Rani , Fert‐Bober Justyna , Cheng Danye , Lahey Lauren J. , Wong Heidi H. , Van Eyk Jennifer , Robinson William H. , Sokolove Jeremy
Published: July 2015

Objective

Anti–citrullinated protein antibodies (ACPAs) are characteristic of rheumatoid arthritis (RA). However, their presence years before the onset of clinical RA is perplexing. Although multiple putative citrullinated antigens have been identified, no studies have demonstrated the specific capacity of these antigens to initiate inflammatory arthritis. This study was undertaken to recapitulate the transition from preclinical to clinical RA and to demonstrate the capacity of local citrullination to facilitate this transition.

Methods

We performed proteomic analysis of activated human neutrophils to identify citrullinated proteins, including those targeted as part of the RA immune response. Using enzyme‐linked immunosorbent assay, we compared RA and osteoarthritis synovial fluid for levels of citrullinated histone H2B and its immune complex. Using macrophage activation assays, we assessed the effect of histone citrullination on immunostimulatory capacity and evaluated the stimulatory capacity of native and citrullinated H2B immune complexes. Finally, we assessed the potential for anti–citrullinated H2B antibodies to mediate arthritis in vivo.

Results

We identified robust targeting of neutrophil‐derived citrullinated histones by the ACPA immune response. More than 90% of the RA patients had anti–citrullinated H2B antibodies. Histone citrullination increased innate immunostimulatory capacity, and immune complexes containing citrullinated histones activated macrophage cytokine production and propagated neutrophil activation. Finally, we demonstrated that immunization with H2B was arthritogenic, but only in the setting of underlying articular inflammation.

Conclusion

Our findings indicate that citrullinated histones, specifically citrullinated H2B, are an antigenic target of the ACPA immune response. Furthermore, local generation of citrullinated antigen during low‐grade articular inflammation provides a mechanistic model for the conversion from preclinical autoimmunity to inflammatory arthritis.
The use of the acute Pd/Pa drop after intracoronary nitroglycerin infusion to rule out significant FFR: CANICA (Can intracoronary nitroglycerin predict fractional flow reserve without adenosine?) multicenter study
Authors: Martin‐Reyes R. , de la Torre Hernandez J.M. , Franco‐Pelaez J. , Lopez‐Palop R. , Telleria Arrieta M. , Amat Santos I.J. , Carrillo Saez P. , Sanchez‐Recalde A. , Sanmartin Pena J.C. , Garcia Camarero T. , Brugaletta S. , Gimeno de Carlos F. , Pinero A. , Sorto Sanchez D.C. , Frutos A. , Lasa Larraya G. , Navarro F. , Farre J.
Published: July 2015

Objective

Functional assessment of coronary artery stenosis is performed by measuring the fractional flow reserve (FFR) under hyperemic conditions (Adenosine). However, the use of adenosine portends limitations.

Objective

We sought to investigate the relationship and correlation between FFR and the Pd/Pa value obtained just after the intracoronary infusion (acute drop) of nitroglycerin (Pd/Pa‐NTG) and if this parameter enhances diagnostic accuracy for FFR prediction compared to the resting baseline Pd/Pa.

Methods

We conducted a multicenter study including prospectively patients presenting intermediate coronary artery stenosis (30–70%) evaluated with pressure wire. Resting baseline Pd/Pa, Pd/Pa‐NTG and FFR were measured.

Results

283 patients (335 lesions) were included. Resting baseline Pd/Pa value was 0.72 to 1.0 (0.93 ± 0.04), Pd/Pa‐NTG was 0.60 to 1.0 (0.87 ± 0.07) and FFR 0.55 to 1.0 (0.83 ± 0.08). The ROC curves for resting baseline Pd/Pa and for Pd/Pa‐NTG, using a FFR ≤ 0.80 showed an AUC of 0.88 (95% CI: 0.84–0.92, P < 0.001) and 0.94 (95% CI: 0.92–0.96, P < 0.001) respectively. The optimal cutoff values of resting baseline Pd/Pa and Pd/Pa‐NTG for an FFR > 0.80, were >0.96 and >0.88, respectively. These values were present in a 29.8% (n = 100) and a 47.1% (n = 158), of the total lesions. Scatter plots showed a better correlation and agreement points with Pd/Pa‐NTG than resting baseline Pd/Pa. The cutoff value of Pd/Pa‐NTG > 0.88 showed an excellent NPV (96.2% for FFR > 0.8 and 100% for FFR > 0.75) and sensitivity (95% for FFR > 0.8 and 100% for FFR > 0.75) which were consistently high across all the subgroups analysis.

Conclusion

The cutoff value of acute Pd/Pa‐NTG > 0.88 has a high NPV meaning adenosine‐FFR can be avoided in almost half of lesions. © 2015 Wiley Periodicals, Inc.
A Striking Case of Enantioinversion in Gold Catalysis and Its Probable Origins
Authors: Ilg Marina K. , Wolf Larry M. , Mantilli Luca , Farès Christophe , Thiel Walter , Fürstner Alois
Published: July 2015

The cyclization of the hydroxy‐allene 2 to the tetrahydrofuran 3 catalyzed by the gold‐phosphoramidite complex 1, after ionization with an appropriate silver salt AgX, is one of the most striking cases of enantioinversion known to date. The major reason why the sense of induction can be switched from (S) to (R) solely by changing either the solvent or the temperature or the nature of the counterion X is likely found in the bias of the organogold intermediates to undergo assisted proto‐deauration. Such assistance can be provided by a protic solvent, a reasonably coordinating counterion or even by a second substrate molecule itself; in this case, the reaction free energy profile gains a strong entropic component that can ultimately dictate the stereochemical course.
Support Hispanic students to ensure college access, success
Authors: Hope Joan
Published: July 2015

As your institution plans for the future, consider your strategy to address changing demographics. Secretary of Education Arne Duncan announced earlier this year that K–12 school enrollment is now majority minority, said Luis Maldonado, chief advocacy officer for the Hispanic Association of Colleges and Universities. The largest group of minority students are Hispanic. They now make up 25 percent of the K–12 population, and they are the only group that is growing.
Morphogenesis of the lymphatic vasculature: A focus on new progenitors and cellular mechanisms important for constructing lymphatic vessels
Authors: Kazenwadel Jan , Harvey Natasha L.
Published: July 2015

Lymphatic vessels serve crucial roles in the regulation of tissue fluid homeostasis, dietary lipid absorption and immune cell trafficking. Defects in lymphatic vessel morphogenesis and function have been associated with lymphedema, obesity, hypertension and tumour metastasis. Morphogenetic events important for construction of the lymphatic vasculature during development include the specification and emergence of lymphatic endothelial progenitor cells, their differentiation and assembly into interconnected vessels and vascular remodeling, ultimately giving rise to a functional vascular network. Despite the embryonic origins of lymphatic endothelial progenitor cells being long debated, work performed over the last decade had overwhelmingly supported at least a great majority of progenitor cells arising from the venous vasculature. Here, we review the most recent advances in the field of lymphatic vessel morphogenesis, with a focus on studies that have identified novel sources of embryonic lymphatic endothelial progenitor cells, together with the cellular mechanisms by which lymphatic vessels are initially assembled. Developmental Dynamics 245:209–219, 2016. © 2015 Wiley Periodicals, Inc.
Epoxidation and polymerization of acrylated castor oil
Authors: Esen Hüseyin , Çayli Gökhan
Published: July 2015

In this study, a new type of bifunctional monomer from castor oil was investigated and the properties of the polymers that were obtained from this monomer were also evaluated and compared with the polymers that were obtained from acrylated epoxidized soybean oil (AESO). Castor oil (CO), first, was reacted with acryloyl chloride in order to obtain acrylated castor oil (ACO). Epoxidized acrylated castor oil (EACO) was obtained after the epoxidation reaction. EACO was characterized by 1H NMR and IR techniques. Viscosity of the monomer was also determined. The viscosity of EACO was found as 1950 centipoise by using Brookfield type viscometer at 20°C. After characterization, homo and block copolymers of the EACO with methyl methacrylate (MMA) and acrylic acid (AA) were synthesized by conventional radical polymerization techniques. Transparent and tough polymers were obtained after polymerization reactions. Thermal and mechanical properties of the polymers synthesized were also evaluated. EACO‐AA (85–15%) copolymer showed 0.7 GPa storage modulus while AESO‐AA (85–15%) copolymer showed only 0.37 GPa modulus. When compared 5% weight loss temperatures as a thermal stability indicator, it was observed at 332°C for AECO‐AA copolymer and 295°C for AESO‐AA copolymer.

Practical applications: Epoxidation and polymerization of EACO was demonstrated in this manuscript. EACO is a new type of monomer that contains a reactive epoxy and acrylate group. This monomer is a versatile monomer and can be applied in a wide variety of areas.

EACO synthesis is completed in two steps. Castor oil is acrylated first at 0°C in the presence of triethyleneamine. The acrylated castor oil is then selectively epoxidized by HCOOH/H2O2 mixture.
Adapting to fill the void: Dynamic group coordination as a function of differing domain roles and instrumentality
Authors: Bonner Bryan L. , Baumann Michael R. , Netchaeva Ekaterina
Published: July 2015

In groups, member coordination is influenced by a complex set of factors including who has what knowledge (which implies who is responsible for different task domains) as well as the differing incentives associated with performing within those domains. We show that the distribution of members' expert roles interacts with the desirability of different task domains to impact member perceptions of the task, coordination, and performance. Group members who have expertise in a highly desirable domain (i.e., key experts) perceive the task differently than members who do not and report that their approach to the task is determined to a greater extent by an attention to capturing highly desirable contributions for the group than do other members. Furthermore, when a group lacks a key expert, groups divide the work involved within a highly desirable domain across multiple members. This results in the group doing well in the highly desirable domain itself, but overlooking other domains and performing poorly, overall. We discuss the theoretical implications of this research as well as its practical applications.
An Ethanol Biosensor Based on Simple Immobilization of Alcohol Dehydrogenase on Fe3O4@Au Nanoparticles
Authors: Samphao Anchalee , Kunpatee Kanjana , Prayoonpokarach Sanchai , Wittayakun Jatuporn , Švorc Ľubomír , Stankovic Dalibor M. , Zagar Kristina , Ceh Miran , Kalcher Kurt
Published: July 2015

An ethanol biosensor based on alcohol dehydrogenase (ADH) attached to Au seeds decorated on magnetic nanoparticles (Fe3O4@Au NPs) is presented. ADH was immobilized on Fe3O4@Au NPs, which were subsequently fixed by a magnet on a carbon paste electrode modified with 5 % (m : m) MnO2. Optimum conditions for the amperometric determination of ethanol with the biosensor were as follows: working potential +0.1 V (vs. Ag/AgCl); supporting electrolyte: 0.1 M phosphate buffer solution at pH 6.8 containing 0.25 mM of the coenzyme (NAD+); working electrode: carbon paste with magnetically attached Fe3O4@Au NPs (0.012 mg ⋅ cm−2 electrode area) with immobilized alcohol dehydrogenase (120 units per cm2 of electrode area). Linearity between signal and concentration was found for the range from 0.1 to 2.0 M ethanol (r2=0.995) with a detection limit of 0.07 M, a sensitivity of 0.02 µA ⋅ mM−1 ⋅ cm−2, a reproducibility of 4.0 % RSD, and a repeatability of 2.7 % RSD. The results for the determination of ethanol in alcoholic beverages showed good agreement with gas chromatography (GC) with recovery of 96.0 – 108.8 %.
Effects of fermentation time on the functional and pasting properties of defatted Moringa oleifera seed flour
Authors: Oloyede Omobolanle O. , James Samaila , Ocheme Ocheme B. , Chinma Chiemela E. , Akpa V. Eleojo
Published: July 2015

Effects of fermentation time on the functional and pasting properties of defatted Moringa oleifera seed flour was examined. Moringa seeds were fermented naturally at 0, 12, 24, 48 and 72 h; oven dried at 60°C for 12 h; milled into five different flour samples for each fermentation time and defatted. The functional and pasting properties of the samples were determined. The result shows significant increase in the water absorption capacity, oil absorption capacity, foaming capacity and emulsifying capacity with increase in fermentation time. However, there was a significant decrease in bulk density (0.53–0.32 g/cm3) and dispersibility (36.00–20.50%) with an increase in fermentation time. There were significant increase in peak viscosity, trough, breakdown, final viscosity, and set back with increasing fermentation time. The swelling power and solubility of fermented Moringa seed flour was significantly affected.
Drug‐metabolism mechanism: Knowledge–based population pharmacokinetic approach for characterizing clobazam drug‐drug interactions
Authors: Tolbert Dwain , Bekersky Ihor , Chu Hui‐May , Ette Ene I.
Published: July 2015

A metabolic mechanism‐based characterization of antiepileptic drug‐drug interactions (DDIs) with clobazam in patients with Lennox‐Gastaut syndrome (LGS) was performed using a population pharmacokinetic (PPK) approach. To characterize potential DDIs with clobazam, pharmacokinetic (PK) data from 153 patients with LGS in study OV‐1012 (NCT00518713) and 18 healthy participants in bioavailability study OV‐1017 were pooled. Antiepileptic drugs (AEDs) were grouped based on their effects on the cytochrome P450 (CYP) isozymes responsible for the metabolism of clobazam and its metabolite,N‐desmethylclobazam (N‐CLB): CYP3A inducers (phenobarbital, phenytoin, and carbamazepine), CYP2C19 inducers (valproic acid, phenobarbital, phenytoin, and carbamazepine), or CYP2C19 inhibitors (felbamate, oxcarbazepine). CYP3A4 inducers—which did not affect the oral clearance of clobazam—significantly increased the formation of N‐CLB by 9.4%, while CYP2C19 inducers significantly increased the apparent elimination rate of N‐CLB by 10.5%, resulting in a negligible net change in the PK of the active metabolite. CYP2C19 inhibitors did not affect N‐CLB elimination. Because concomitant use of AEDs that are either CYP450 inhibitors or inducers with clobazam in the treatment of LGS patients had negligible to no effect on clobazam PK in this study, dosage adjustments may not be required for clobazam in the presence of the AEDs investigated here.
Synthesis of Novel Drug‐Like Small Molecules Based on Quinoxaline Containing Amino Substitution at C‐2
Authors: Rao K. Raghavendra , Raghunadh Akula , Mekala Ramamohan , Meruva Suresh Babu , Ganesh K. Ravi , Krishna T. , Kalita Dipak , Laxminarayana Eppakayala , Pal Manojit
Published: July 2015

A series of novel “drug‐like” small molecules based on quinoxaline containing amino substitution at C‐2 were synthesized. All these molecules were prepared either via the reaction of 2‐phenyl‐3‐(piperazin‐1‐yl)quinoxaline with acyl bromides or benzyl bromides or various carboxylic acids or via the reaction of 2‐chloro‐3‐phenylquinoxaline with various amines. The structures of these novel compounds were confirmed by spectral analysis. The strategy used is simple and efficient and afforded good yields of quinoxaline derivatives.
Treatment rate and factors related to interferon‐based treatment initiation for chronic hepatitis C in South Korea
Authors: Lee Sang Soo , Jeong Sook‐Hyang , Jang Eun Sun , Kim Young Seok , Lee Youn Jae , Jung Eun Uk , Kim In Hee , Bae Si Hyun , Lee Han Chu
Published: July 2015

Under‐recognition and under‐treatment of chronic hepatitis C virus (HCV) infection is an important determinant of the disease outcome. The aim of this study was to investigate the treatment rate and factor of initiation of interferon‐based antiviral treatment for chronic hepatitis C patients in a prospective, multicenter Korean HCV cohort. Treatment‐naïve 759 patients with chronic HCV infection were prospectively followed from January 2007–2013 at six university hospitals during a median (interquartile range) follow‐up of 769 (76–1,427) days. The subjects consisted of patients with chronic hepatitis C (n = 553, 72.9%), liver cirrhosis (n = 127, 16.7%), and hepatocellular carcinoma (n = 79, 10.4%), and were treated usually using pegylated interferon alpha and ribavirin. Treatment initiation rate and its related factors were analysed. The initiation rate of antiviral treatment was 37.3% (n = 273), and the cumulative probability of treatment initiation over 5 years was 39.4%. Multivariate analysis showed that age <58 years (hazard ratio [HR] = 1.588, 95% CI = 1.151–2.193), job employment (HR = 1.737, 95% CI = 1.279–2.363), absence of HCC (chronic hepatitis, HR = 2.534, 95% CI = 1.003–6.400; liver cirrhosis, HR = 2.873, 95% CI = 1.101–7.494), alanine transaminase (ALT) >40 IU/L (HR = 1.682, 95% CI = 1.228–2.303), and genotype 2 (HR = 1.364, 95% CI = 1.034–1.798) were independent factors related to treatment initiation. Interferon‐based antiviral treatment was initiated in more than one third of chronic HCV infected patients visiting university hospitals, who were young, employed, HCV genotype 2, and with abnormal ALT without HCC, in Korea. J. Med. Virol. 88:275–281, 2016. © 2015 Wiley Periodicals, Inc.
Computer‐aided pelvic reduction frame for anatomical closed reduction of unstable pelvic fractures
Authors: Zhang Li‐hai , Zhao Jing‐xin , Zhao Zhe , Su Xiu‐yun , Zhang Li‐cheng , Zhao Yan‐peng , Tang Pei‐fu
Published: July 2015

Traditional closed reductions of unstable pelvic fractures are mainly performed by surgeons using manual manipulation and subjective verification based on intra‐operative roentgenography. It is difficult to perform an accurate closed reduction because of a lack of adequate knowledge of the displacement patterns and an inability to apply the reduction in correct direction. Using the concept of the remote center of motion mechanism and computer‐aided design software, we developed a pelvic reduction frame for use in anatomical closed reductions of unstable pelvic fractures. With three‐dimensional reconstruction technique and the matrix algorithm, the spatial orientation of the displaced hemipelvis can be calculated and deconstructed into several rotational and translational movements that can be completed with the frame. To verify the accuracy of this system, the rotations were repeated 10 times in arbitrary degrees and directions. After the matrix is calculated, the displaced hemipelvis can be reduced to the anatomical position using our frame. The maximum residual translational and rotational displacements were less than 5 mm and 4 degrees, which indicated the accuracy of this system. The maximum average residual translation and rotation were 1.87 mm in Z‐axis (ranging: 4.63–0.1 mm) and 1.1 degrees around Y‐axis (ranging: 3.81–0.13 degrees), respectively. Only the Z‐axial translation showed a statistically significant difference (p < 0.05). In conclusion, the proposed pelvic reduction frame could be a useful tool for the anatomical reduction of unstable pelvic fractures. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:81–87, 2016.
Alleviation effects of calcium and potassium on cadmium rhizotoxicity and absorption by soybean and wheat roots
Authors: Yang Ching‐Ming , Juang Kai‐Wei
Published: July 2015

The objectives of the present study were to investigate the root responses of soybean (Glycine max L.) and wheat (Triticum aestivum L.) seedlings to cadmium (Cd) stress and to investigate the alleviation effects of Ca and K on rhizotoxicity and absorption of Cd by roots. Soybean and wheat seedlings in a hydroponic system were exposed to Cd‐spiked solutions (0, 4, 8, 12, and 16 μM) with different Ca (0.5, 1, and 10 mM) and K (0.3, 1.2, and 9.6 mM) levels for 7 d. The results showed a dramatic reduction in root elongation of soybean due to increased Cd, but increasing Ca and K levels alleviated this reduction in soybean. The amelioration of Cd toxicity by the addition of Ca may be associated with reduced Cd absorption. However, the addition of K in reducing Cd toxicity might not be dependent upon Cd absorption. Compared with soybean, wheat showed a relatively high tolerance to Cd. The alleviation of Cd rhizotoxicity in wheat was more apparent by K than by Ca. We found that the addition of K promoted root elongation but not directly prevent Cd stress, and that the addition of Ca minimized acute rhizotoxicity of Cd in wheat. Moreover, the addition of Ca reduced Cd absorption by soybean and wheat roots. However, the addition of K only reduced Cd absorption by wheat roots.
REMODEL larger cohort with long‐term outcomes and meta‐analysis of standalone balloon dilation studies
Authors: Chandra Rakesh K. , Kern Robert C. , Cutler Jeffrey L. , Welch Kevin C. , Russell Paul T.
Published: July 2015

Objectives/Hypothesis

To provide the final results from the REMODEL (randomized evaluation of maxillary antrostomy versus ostial dilation efficacy through long‐term follow‐up) full‐study cohorts and perform meta‐analyses of standalone balloon sinus dilation studies to explore long‐term outcomes in a large patient sample.

Study Design

Randomized controlled trial and meta‐analysis.

Methods

Final outcomes from the REMODEL randomized trial, including a larger cohort of 135 patients treated with functional endoscopic sinus surgery (FESS) or in‐office balloon dilation, were evaluated. One hundred thirty patients had 12‐month data, 66 had 18‐month data, and 25 had 24‐month data. In addition, a meta‐analysis evaluated outcomes from six studies including 358 standalone balloon dilation patients with up to 24 months follow‐up.

Results

Outcomes out to 2 years from the REMODEL full‐study cohort are consistent with 6‐month and 12‐month outcomes. In the meta‐analysis of standalone balloon dilation studies, technical success is 97.5%, and mean 20‐item Sino‐Nasal Outcomes Test scores are significantly and clinically improved at all time points (P < .0001). There are significant reductions (P < .0001) in work/school days missed, homebound days, physician/nurse visits, acute infections, and antibiotic prescriptions. Mean recovery time is 1.4 days. Comparison of 12‐month symptom improvements and revision rates between the REMODEL FESS arm (n = 59), REMODEL balloon dilation arm (n = 71), and pooled single‐arm standalone balloon dilation studies (n = 243) demonstrated no statistical difference.

Conclusions

All outcomes are comparable between FESS and balloon dilation at all time points from 6 months to 24 months. Balloon dilation produces faster recovery, less postoperative pain, and fewer debridements than FESS. There is significant, durable benefit in a large series of 358 patients undergoing standalone balloon dilation.

Level of Evidence

1b. Laryngoscope, 126:44–50, 2016
Lode's angle effect on the definition of the strength criterion of porous media
Authors: Lemarchand Eric , Dormieux Luc , Kondo Djimedo
Published: July 2015

This paper addresses the open question of the effect of the third invariant in the definition of the strength criterion of porous media. This is here achieved in the context of a porous medium made up of a solid phase, in which strength criterion appears as an explicit function of Lode's angle. Application is provided from the Gurson hollow sphere model for which the macroscopic strength exhibits a lack of symmetry for axisymmetric macroscopic strain rate loadings. Copyright © 2015 John Wiley & Sons, Ltd.
A 3D discrete FEM iterative algorithm for solving the water pipe cooling problems of massive concrete structures
Authors: Cheng Jing , Li T. C. , Liu Xiaoqing , Zhao L. H.
Published: July 2015

Water pipe cooling has been widely used for the temperature control and crack prevention of massive concrete structures such as high dams. Because both under‐cooling and over‐cooling may reduce the efficiency of crack prevention, or even lead to great harm to structures, we need an accurate and robust numerical tool for the prediction of cooling effect. Here, a 3D discrete FEM Iterative Algorithm is introduced, which can simulate the concrete temperature gradient near the pipes, as well as the water temperature rising along the pipes. On the basis of the heat balance between water and concrete, the whole temperature field of the problem can be computed exactly within a few iteration steps. Providing the pipe meshing tool for building the FE model, this algorithm can take account of the water pipe distribution, the variation of water flow, water temperature, and other factors, while the traditional equivalent algorithm based on semi‐theoretical solutions can only solve problems with constant water flow and water temperature. The validation and convergence are proved by comparing the simulated results and analytical solutions of two standard second‐stage cooling problems. Then, a practical concrete block with different cooling schemes is analyzed and the influences of cooling factors are investigated. In the end, detailed guidance for pipe system optimization is provided. Copyright © 2015 John Wiley & Sons, Ltd.
Mechanical properties of poly(l‐lactic acid) composites filled with mesoporous silica
Authors: Liang Ji‐Zhao , Li Feng‐Jiao
Published: July 2015

The mechanical properties of mesoporous silica (MCM‐41) filled poly(l‐lactic acid) (PLA4032D) composites and PLA4032D/poly(ethylene glycol) (PEG) composites were investigated. It was found that the Young's modulus increased while tensile strength decreased with increasing the filler content; the V‐notched impact fracture strengths of both Izod and Charpy for the PLA4032D/PEG/MCM‐41 composites increased while they decreased slightly for the PLA4032D/MCM‐41 composites, the unnotched Charpy impact strength of both the two composites decreased with increasing the filler loading; the flexural modulus increased slightly while the flexural strength decreased slightly with increasing the filler content. The toughening mechanisms of the composites were discussed by means of observing the impact fracture surface with a scanning electronic microscope, and the synergistic effect between the PEG and MCM‐41 should be one of the major toughening mechanisms. POLYM. COMPOS., 38:1118–1126, 2017. © 2015 Society of Plastics Engineers