bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rational design of a hexameric protein assembly stabilized by metal chelation
Authors: Alcala‐Torano Rafael , Walther Mathieu , Sommer Dayn J. , Park Chad K. , Ghirlanda Giovanna 
Published: September 2018

AbstractProtein‐based self‐assembled nanostructures hold tremendous promise as smart materials. One strategy to control the assembly of individual protein modules takes advantage of the directionality and high affinity bonding afforded by metal chelation. Here, we describe the use of 2,2′‐bipyridine units (Bpy) as side chains to template the assembly of large structures (MW approx. 35 000 Da) in a metal‐dependent manner. The structures are trimers of independently folded 3‐helix bundles, and are held together by 2 Me(Bpy)3 complexes. The assemblies are stable to thermal denaturation, and are more than 90% helical at 90°C. Circular dichroism spectroscopy shows that one of the 2 possible (Bpy)3 enantiomers is favored over the other. Because of the sequence pliability of the starting peptides, these constructs could find use to organize functional groups at controlled positions within a supramolecular assembly.
Animal hoarding: The challenge for mental health, law enforcement, and animal welfare professionals
Authors: Lockwood Randall 
Published: September 2018

AbstractAnimal hoarding has been considered a significant problem by animal welfare and law enforcement professionals for over a century. However, it has only been recognized as an indication of a mental disorder in the last decade. I review the different forms that animal hoarding can take and the current understanding of the prevalence, demographics and possible etiology of this disorder. Conventional animal cruelty laws have often been inadequate to respond to animal hoarding cases until they reach levels that may involve serious harm to animals and people. I document how prosecution of such cases can be difficult and often does not adequately consider the mental health issues underlying the problem or the high likelihood of recidivism. Attempts to solve these problems by enacting new laws specifically addressing animal hoarding have been controversial and ineffective. I explore new approaches that coordinate a variety of community resources in response to hoarding cases that offer the best opportunity to respond to both the human and animal problems associated with animal hoarding.
Strengthening the Combination between Enzymes and Metals in Aqueous Medium: Concurrent Ruthenium‐Catalyzed Nitrile Hydration ‐ Asymmetric Ketone Bioreduction
Authors: Liardo Elisa , González‐Fernández Rebeca , Ríos‐Lombardía Nicolás , Morís Francisco , García‐Álvarez Joaquín , Cadierno Victorio , Crochet Pascale , Rebolledo Francisca , González‐Sabín Javier 
Published: September 2018

AbstractA dual ruthenium/ketoreductase catalytic system has been developed for the conversion of β‐ketonitriles into optically active β‐hydroxyamides through an unprecedented hydration/bioreduction cascade process in aqueous medium working in concurrent mode. The ketoreductase‐mediated ketone reduction took place with exquisite stereoselectivity and it was simultaneous to the nitrile hydration promoted by the ruthenium catalyst. The overall transformation occurred: (i) employing commercially and readily available catalytic systems (ii) under mild reaction conditions, (iii) with high degree of conversion and excellent stereoselectivity, and (iv) without the need to isolate intermediates and with high final product yields. This genuine process demonstrates the benefits of combining metal and enzymatic catalysis to tackle the limitations arising from each field.
CO2 Hydrogenation to Formate with Immobilized Ru‐Catalysts Based on Hybrid Organo‐Silica Mesostructured Materials
Authors: Lo Hung‐Kun , Copéret Christophe 
Published: September 2018

AbstractThe hydrogenation of CO2 to formic acid can be carried out by numerous homogenous catalysts, while efficient heterogeneous catalysts are rare. In this work, we successfully synthesize an immobilized lutidine‐derived pincer‐type N‐heterocyclic carbene ruthenium complex based on a mesoporous organo‐silica hybrid material using sol‐gel direct synthesis in the presence of structure directing agents and click chemistry as the two key pillars of this strategy. This material efficiently catalyzes the hydrogenation of CO2 into formate with turnover numbers reaching 18′000 within 24 hours, surpassing the performance of the corresponding homogeneous complexes.
Ternary WO3/Porous‐BiVO4/FeOOH Hierarchical Architectures: Towards Highly Efficient Photoelectrochemical Performance
Authors: Ma Zizai , Hou Huilin , Song Kai , Fang Zhi , Wang Lin , Gao Fengmei , Yang Zuobao , Tang Bin , Yang Weiyou 
Published: September 2018

AbstractDeveloping photoanodes showing both a high solar harvesting efficiency and efficient charge separation/transfer is recognized as one of the key challenges for water splitting. In the presented work, we report a strongly coupled ternary WO3/porous‐BiVO4/FeOOH hierarchical architecture as photoanode for high PEC performance,which was constructed by unique foaming‐assisted electro‐spraying of porous BiVO4 frameworks and photodeposition of a FeOOH layer, respectively. As a proof of concept, the as‐fabricated WO3/porous‐BiVO4/FeOOH photoanode yielded a photocurrent density of ∼4.4 mA cm−2 at 1.23 V vs. RHE, ∼4 and 10 times higher than that of the BiVO4 and WO3 counterparts, respectively. Because of the surface passivation of FeOOH, the onset potential could be substantially reduced to ∼200 mV in the presence of sacrificial agent under AM 1.5G (100 mW cm−2) simulated sunlight illumination, which was lowered by ∼100 mV in comparison to those of BiVO4 and WO3 analogues. The mechanism for the enhanced PEC activities of ternary WO3/porous‐BiVO4/FeOOH hierarchical architectures was proposed.
Cancer immunophenotyping by seven‐colour multispectral imaging without tyramide signal amplification
Authors: Ijsselsteijn Marieke E , Brouwer Thomas P , Abdulrahman Ziena , Reidy Eileen , Ramalheiro Ana , Heeren A Marijne , Vahrmeijer Alexander , Jordanova Ekaterina S , de Miranda Noel FCC 
Published: September 2018

AbstractCheckpoint blockade immunotherapies have revolutionised cancer treatment in the last decade. Nevertheless, these are only beneficial for a small proportion of cancer patients. Important prognosticators for response to immunotherapy are the mutation burden of tumours as well as the quality and quantity of tumour‐infiltrating immune cells. High‐throughput multiplex immunophenotyping technologies have a central role in deciphering the complexity of anti‐tumour immune responses. Current techniques for the immunophenotyping of solid tumours are held back by the lack of spatial context, limitations in the number of targets that can be visualised simultaneously, and/or cumbersome protocols. We developed a tyramide signal amplification‐free method for the simultaneous detection of seven cellular targets by immunofluorescence. This method overcomes limitations posed by most widespread techniques and provides a unique tool for extensive phenotyping by multispectral fluorescence microscopy. Furthermore, it can be easily implemented as a high‐throughput technology for validation of discovery sets generated by RNA sequencing or mass cytometry and may serve in the future as a complementary diagnostic tool.
High frequency of CD74 expression in lymphomas: implications for targeted therapy using a novel anti‐CD74‐drug conjugate
Authors: Zhao Shuchun , Molina Arturo , Yu Abigail , Hanson Jeff , Cheung Harry , Li Xiaofan , Natkunam Yasodha 
Published: September 2018

AbstractCD74 is a type II transmembrane glycoprotein that functions as an MHC class II chaperone and displays diverse roles in immune responses. Recently, anti‐CD74 immunotherapy has shown promise as an effective treatment strategy for lymphoid neoplasms in preclinical models. Using a human anti‐CD74 antibody (SP7219), we defined the expression of CD74 protein in both normal and over 790 neoplastic hematolymphoid tissue samples. We found that CD74 is expressed broadly in normal B‐cell compartments including primary and secondary lymphoid follicles and in the thymic medulla. The vast majority of lymphomas expressed CD74, including Hodgkin lymphomas (98%), B‐cell lymphomas (96%), extranodal NK/T‐cell lymphomas (88%), mature T‐cell lymphomas (80%), and plasma cell myeloma (75%). Our findings confirm and expand previous observations regarding the expression of CD74 and suggest that CD74 expression on tumor cells may be directly targeted for immunomodulatory therapy for lymphoid and plasma cell malignancies.
Flow immunophenotyping of benign lymph nodes sampled by FNA: Representative with diagnostic pitfalls
Authors: Scott Gregory D. , Lau Hubert D. , Kurzer Jason H. , Kong Christina S. , Gratzinger Dita A. 
Published: September 2018

BackgroundFine‐needle aspiration with flow cytometry (FNA‐FC) is routinely used in the evaluation of lymph nodes suspicious for lymphoma, yet data comparing immunophenotype distributions and outliers in benign lymph nodes sampled by fine‐needle aspiration (FNA) versus excision are lacking.MethodsFlow cytometry data from 289 benign lymph node FNA cases were assessed for the overall antigen distribution, with a focus on outliers relevant to the diagnosis of lymphoma. Distributions and outlier proportions were compared with those of a separate cohort of 298 excisional biopsies.ResultsCompared with excisional biopsies, FNA specimens overrepresented CD3+ events (72% vs 63%), underrepresented CD19+ events (22% vs 29%), and had 25% fewer large cell–gated events. Normalized antigen distributions in FNA were equivalent to those in excisional biopsy. Twenty‐three percent of FNA‐FC cases exhibited an outlier, including a skewed kappa:lambda light‐chain ratio, increased CD5+ or CD10+ B‐cell events, a skewed CD4:CD8 ratio, and increased CD7 loss on T cells, with no significant differences in frequency or type in comparison with excisional specimens. Outliers for the light‐chain ratio and T‐cell antigens were enriched among older patients and included patients with a variety of autoimmune/rheumatologic conditions.ConclusionsBenign lymph node FNA yields flow immunophenotypes remarkably similar to those from excisional biopsies. Outlier flow immunophenotypes are identified in benign lymph nodes sampled by FNA at a frequency similar to that with excisional biopsies. Older patients, who have a higher baseline risk of lymphoma, are more likely to exhibit lymphoma‐mimicking outliers such as a light‐chain predominance on B cells and skewed CD4:CD8 ratios or increased CD7 loss on T cells, and they warrant additional diagnostic caution.
Deciphering Block Copolymers as Carriers of a Pyrazoline Derivative through Its Solvatochromic Behavior: A Spectroscopic and Theoretical Exploration
Authors: Singharoy Dipti , Ghosh Swadesh , Samai Boby , Bhattacharya Subhash Chandra 
Published: September 2018

AbstractMany biologically active water‐insoluble drug molecules have limited clinical application because of strong hydrophobicity. Recently triblock copolymers have attracted enormous interest as potential drug carriers. For the purpose of delivering the 5‐(1‐(bromohexa‐1,3,5‐triyn‐1‐yl)‐3a,4,5,6,7,7a‐hexahydro‐1H‐4,7‐methanoindazol‐3‐yl)‐3‐methyl‐1‐phenyl‐1H‐pyrazole‐4‐carbonitrile (PYZ) molecule, triblock copolymers are used. In order to understand the delivery of this water‐insoluble probe through triblock copolymers (TBP), the solvent‐dependent fluorescence properties of this compound have been examined in different homogeneous solvents. Besides the experimental work, theoretical studies have also been conducted to explain actual orientation of atoms in PYZ through optimized structures to support the experimental findings. Moreover, the three TBP polymers P‐123 (PEO19PPO69PEO19), F‐127 (PEO100PPO65PEO100) and L‐64 (PEO13PPO30PEO13) have been treated here as potential carriers that encapsulate a pyrazoline derivative. The consequence of spatial captivity on the emission properties was systematically visualized by means of steady‐state and time‐resolved fluorescence spectroscopy. From DLS measurements the size variation with the polydispersity index of TBP in the presence and absence of PYZ in different triblock copolymers was also monitored. Furthermore these measurements have been supported by TEM imaging also.
Assessment of baroreflex sensitivity has no prognostic value in contemporary, optimally managed patients with mild‐to‐moderate heart failure with reduced ejection fraction: a retrospective analysis of 5‐year survival
Authors: Paleczny Bartłomiej , Olesińska‐Mader Martyna , Siennicka Agnieszka , Niewiński Piotr , Nowak Krzysztof , Buldańczyk Agnieszka , Jankowska Ewa A. , Banasiak Waldemar , von Haehling Stephan , Ponikowska Beata , Anker Stefan D. , Ponikowski Piotr 
Published: September 2018

ObjectivesWe evaluated the prognostic value of cardiac baroreflex sensitivity (BRS) in contemporary, optimally treated patients with mild‐to‐moderate heart failure with reduced ejection fraction (HFrEF).Methods and resultsData from 97 patients with HFrEF (left ventricular ejection fraction 32 ± 6%, all receiving angiotensin‐converting enzyme inhibitor/angiotensin receptor blocker and beta‐blocker, 85% receiving aldosterone antagonist) were analysed retrospectively. All patients underwent standard clinical assessment, cardiopulmonary exercise testing and BRS evaluation with three methods: the phenylephrine (BRS‐Phe), the sequence (BRS‐Seq) and the controlled breathing (BRS‐CtrBr) method. Data on 5‐year all‐cause mortality and appropriate and documented implantable cardioverter‐defibrillator (ICD) discharges were collected. During a mean follow‐up of 53 ± 15 months, the composite endpoint of all‐cause death and appropriate and documented ICD discharge occurred in 31 (32%) patients. BRS measures assessed using all three methods were not related to survival in univariate Cox proportional hazards analyses (all P >0.25). There were also no differences in survival between low vs. preserved BRS groups, irrespective of the method used for BRS assessment (all P ≥0.15). BRS‐Phe correlated with several clinically important variables (including left ventricular ejection fraction: rS = 0.27, and peak oxygen consumption: rS = 0.32, both P < 0.05), while clinical associations of BRS‐Seq and BRS‐CtrBr were sparse.ConclusionsAssessment of cardiac BRS provides no prognostic information in the contemporary mild‐to‐moderate HFrEF population receiving optimal management.
Toward Understanding the Evaluation Market and its Industry—Advancing a Research Agenda
Authors: Lemire Sebastian , Nielsen Steffen Bohni , Christie Christina A. 
Published: September 2018

AbstractThis chapter reflects on the findings from a comparative analysis of the cases comprising this issue, summarizing and expanding on key findings from these in relation to the evaluation market framework. Major implications of the findings for evaluation practice are considered. The chapter concludes with an outline of a future research agenda for the evaluation marketplace.
A divergence‐free semi‐implicit finite volume scheme for ideal, viscous, and resistive magnetohydrodynamics
Authors: Dumbser M. , Balsara D.S. , Tavelli M. , Fambri F. 
Published: September 2018

SummaryIn this paper, we present a novel pressure‐based semi‐implicit finite volume solver for the equations of compressible ideal, viscous, and resistive magnetohydrodynamics (MHD). The new method is conservative for mass, momentum, and total energy, and in multiple space dimensions, it is constructed in such a way as to respect the divergence‐free condition of the magnetic field exactly, also in the presence of resistive effects. This is possible via the use of multidimensional Riemann solvers on an appropriately staggered grid for the time evolution of the magnetic field and a double curl formulation of the resistive terms. The new semi‐implicit method for the MHD equations proposed here discretizes the nonlinear convective terms as well as the time evolution of the magnetic field explicitly, whereas all terms related to the pressure in the momentum equation and the total energy equation are discretized implicitly, making again use of a properly staggered grid for pressure and velocity. Inserting the discrete momentum equation into the discrete energy equation then yields a mildly nonlinear symmetric and positive definite algebraic system for the pressure as the only unknown, which can be efficiently solved with the (nested) Newton method of Casulli et al. The pressure system becomes linear when the specific internal energy is a linear function of the pressure. The time step of the scheme is restricted by a CFL condition based only on the fluid velocity and the Alfvén wave speed and is not based on the speed of the magnetosonic waves. Being a semi‐implicit pressure‐based scheme, our new method is therefore particularly well suited for low Mach number flows and for the incompressible limit of the MHD equations, for which it is well known that explicit density‐based Godunov‐type finite volume solvers become increasingly inefficient and inaccurate because of the more and more stringent CFL condition and the wrong scaling of the numerical viscosity in the incompressible limit. We show a relevant MHD test problem in the low Mach number regime where the new semi‐implicit algorithm is a factor of 50 faster than a traditional explicit finite volume method, which is a very significant gain in terms of computational efficiency. However, our numerical results confirm that our new method performs well also for classical MHD test cases with strong shocks. In this sense, our new scheme is a true all Mach number flow solver.
Developing a physical influence upwind scheme for pressure‐based cell‐centered finite volume methods
Authors: Vakilipour Shidvash , Mohammadi Masoud , Badrkhani Vahid , Ormiston Scott 
Published: September 2018

SummaryIn the framework of a cell‐centered finite volume method (FVM), the advection scheme plays the most important role in developing FVMs to solve complicated fluid flow problems for a wide range of Reynolds numbers. Advection schemes have been widely developed for FVMs employing pressure‐velocity coupling methodology in the incompressible flow limit. In this regard, the physical influence upwind scheme (PIS) is developed for a cell‐centered finite volume coupled solver (FVCS) using a pressure‐weighted interpolation method for linking the pressure and velocity fields. The well‐known exponential differencing scheme and skew upwind differencing scheme are also deployed in the current FVCS and their numerical results are presented. The accuracy and convergence of the present PIS are evaluated solving flow in a lid‐driven square cavity, a lid‐driven skewed cavity, and over a backward‐facing step (BFS). The flow within the lid‐driven square cavity is numerically solved at Reynolds numbers from 400 to 10 000 on a relatively coarse mesh with respect to other reported solutions. The lid‐driven skewed cavity test case at Reynolds number of 1000 demonstrates the numerical performance of the present PIS on nonorthogonal grids. The flow over a BFS at Reynolds number of 800 is numerically solved to examine capabilities of current FVCS employing the current PIS in inlet‐outlet flow computations. The numerical results obtained by the current PIS are in excellent agreement with those of benchmark solutions of corresponding test cases. Incorporating implicit role of pressure terms in a pressure‐weighted interpolation method and development of PIS provides satisfactory solution convergence alongside the numerical accuracy for the current FVCS. A particular numerical verification is performed for the V velocity calculation within the BFS flow field, which confirms the reliability of present PIS.
Partial‐least‐squares and canonical‐correlation analysis of chemical constituents and active ingredients of new types of Chinese mulberries
Authors: Sun Rui , Sun Lei , Han Chuanming 
Published: September 2018

AbstractObjectiveTo investigate the correlation between chemical constituents and active ingredients of 13 types of Chinese mulberry fruits.MethodsThirteen types mulberry fruits were harvested. The correlation between chemical constituents and active ingredients (primarily anthocyanins and rutins) of 13 new types of Chinese mulberries was assessed using partial‐least‐squares, principle‐component and canonical‐correlation analyses.ResultsVitamin C and titratable acid in the mulberry fruits were critical components that affected the active ingredients, especially anthocyanins and rutins. The content of titratable acid content was related to the fruit flavor and maintained the balance of anthocyanins, vitamin C and rutins. Mineral elements, such as Zn and Cu, also played a vital role in these processes. Low contents of sugar, crude protein, crude fat and pectin were significantly correlated with the mineral elements.ConclusionChemical constituents and mineral elements can mutually affect the concentration. It provides a novel method for any changes in the quality of new types of Chinese mulberries, which can identify the sources of new types of natural antioxidants.
Therapeutic potency of Wnt signaling antagonists in the pathogenesis of prostate cancer, current status and perspectives
Authors: Pashirzad Mehran , Shafiee Mojtaba , Khazaei Majid , Fiuji Hamid , Ryzhikov Mikhail , Soleimanpour Saman , Hesari AmirReza , Avan Amir , Hassanian Seyed Mahdi 
Published: September 2018

AbstractProstate cancer is a major cause of cancer‐related death in males. Wnt/β‐catenin signaling plays a critical role in the pathogenesis of this disease by regulating angiogenesis, drug resistance, cell proliferation, and apoptosis. Suppression of Wnt canonical or noncanonical signaling pathways via Wnt biological or pharmacological antagonists is a potentially novel therapeutic approach for patients with prostate cancer. This review summarizes the role of Wnt signaling inhibitors in the pathogenesis of prostate cancer for a better understanding and hence a better management of this disease.
A Phase 1, Multiple‐Dose Study of Vedolizumab in Japanese Patients With Ulcerative Colitis
Authors: Kobayashi Kiyonori , Suzuki Yasuo , Watanabe Kenji , Oda Kazunori , Mukae Miyuki , Yamada Akihiro , Yamagami Hirokazu , Nishimura Akira , Okamoto Hiroyuki 
Published: September 2018

AbstractAlthough previous studies have shown that patients with ulcerative colitis may benefit from treatment with vedolizumab, a humanized monoclonal antibody targeting the α4β7 integrin heterodimer, no data exist in Japanese populations. The aim of this phase 1, open‐label, multicenter study was to assess the pharmacokinetics, pharmacodynamics, efficacy, and safety of vedolizumab in Japanese patients with ulcerative colitis. Adult patients with confirmed ulcerative colitis received either 150 mg (step 1) or 300 mg (step 2) of intravenous (IV) vedolizumab on days 1, 15, and 43 of the study protocol. Pharmacokinetic, pharmacodynamic, safety, and efficacy parameters were all assessed through study end (day 239). Nine patients were enrolled in this study (150 mg, n = 3; 300 mg, n = 6). Patients who received vedolizumab IV 300 mg had approximately twice the drug exposure of those receiving vedolizumab IV 150 mg (day 1 AUCday14 744 vs 408 μg·d/mL) and a longer‐lasting maximal saturation of α4β7 integrin (155 vs 99 days). The number of treatment‐emergent adverse events, all of which were mild or moderate in intensity, was similar between the 150‐mg (15 events) and 300‐mg (20 events) groups. The 2 patients (150 mg group) not in clinical remission by partial Mayo score at the start of the study met the criteria for clinical remission on days 15 and 155 of the study, respectively. In conclusion, in Japanese patients with ulcerative colitis, vedolizumab showed similar pharmacokinetic and pharmacodynamic results to those seen in non‐Japanese patients. Vedolizumab was well tolerated and demonstrated clinical activity consistent with previous studies.