bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maximization of cell viability rather than biocatalyst activity improves whole‐cell ω‐oxyfunctionalization performance
Authors: Kadisch Marvin , Julsing Mattijs K. , Schrewe Manfred , Jehmlich Nico , Scheer Benjamin , von Bergen Martin , Schmid Andreas , Bühler Bruno 
Published: November 2016

ABSTRACTIt is a common misconception in whole‐cell biocatalysis to refer to an enzyme as the biocatalyst, thereby neglecting the structural and metabolic framework provided by the cell. Here, the low whole‐cell biocatalyst stability, that is, the stability of specific biocatalyst activity, in a process for the terminal oxyfunctionalization of renewable fatty acid methyl esters was investigated. This reaction, which is difficult to achieve by chemical means, is catalyzed by Escherichia coli featuring the monooxygenase system AlkBGT and the uptake facilitator AlkL from Pseudomonas putida GPo1. Corresponding products, that is, terminal alcohols, aldehydes, and acids, constitute versatile bifunctional building blocks, which are of special interest for polymer synthesis. It could clearly be shown that extensive dodecanoic acid methyl ester uptake mediated by high AlkL levels leads to whole‐cell biocatalyst toxification. Thus, cell viability constitutes the primary factor limiting biocatalyst stability and, as a result, process durability. Hence, a compromise had to be found between low biocatalyst activity due to restricted substrate uptake and poor biocatalyst stability due to AlkL‐mediated toxification. This was achieved by the fine‐tuning of heterologous alkL expression, which, furthermore, enabled the identification of the alkBGT expression level as another critical factor determining biocatalyst stability. Controlled synthesis of AlkL and reduced alkBGT expression finally enabled an increase of product titers by a factor of 4.3 up to 229 g Lorg−1 in a two‐liquid phase bioprocess setup. Clearly, ω‐oxyfunctionalization process performance was determined by cell viability and thus biocatalyst stability rather than the maximally achievable specific biocatalyst activity. Biotechnol. Bioeng. 2017;114: 874–884. © 2016 Wiley Periodicals, Inc.
A Thioacetal Photocage Designed for Dual Release: Application in the Quantitation of Therapeutic Release by Synchronous Reporter Decaging
Authors: Wong Pamela T. , Tang Shengzhuang , Cannon Jayme , Mukherjee Jhindan , Isham Danielle , Gam Kristina , Payne Michael , Yanik Sean A. , Baker James R. , Choi Seok Ki 
Published: November 2016

AbstractDespite the immense potential of existing photocaging technology, its application is limited by the paucity of advanced caging tools. Here, we report on the design of a novel thioacetal ortho‐nitrobenzaldehyde (TNB) dual arm photocage that enabled control of the simultaneous release of two payloads linked to a single TNB unit. By using this cage, which was prepared in a single step from commercial 6‐nitroverataldehyde, three drug–fluorophore conjugates were synthesized: Taxol‐TNB‐fluorescein, Taxol‐TNB‐coumarin, and doxorubicin‐TNB‐coumarin, and long‐wavelength UVA light‐triggered release experiments demonstrated that dual payload release occurred with rapid decay kinetics for each conjugate. In cell‐based assays performed in vitro, dual release could also be controlled by UV exposure, resulting in increased cellular fluorescence and cytotoxicity with potency equal to that of unmodified drug towards the KB carcinoma cell line. The extent of such dual release was quantifiable by reporter fluorescence measured in situ and was found to correlate with the extent of cytotoxicity. Thus, this novel dual arm cage strategy provides a valuable tool that enables both active control and real‐time monitoring of drug activation at the delivery site.
An Overview of Structural Features of Antibacterial Glycoconjugate Vaccines That Influence Their Immunogenicity
Authors: Khatun Farjana , Stephenson Rachel J. , Toth Istvan 
Published: November 2016

AbstractBacterial cell‐surface‐derived or mimicked carbohydrate moieties that act as protective antigens are used in the development of antibacterial glycoconjugate vaccines. The carbohydrate antigen must have a minimum length or size to maintain the conformational structure of the antigenic epitope(s). The presence or absence of O‐acetate, phosphate, glycerol phosphate and pyruvate ketal plays a vital role in defining the immunogenicity of the carbohydrate antigen. The nature of the carrier protein, spacer and conjugation pattern used to develop the glycoconjugate vaccine also defines its overall spatial orientation which in turn affects its avidity and selectivity of interaction with the desired target(s). In addition, the ratio of carbohydrate to protein in glycoconjugate vaccines also makes an important contribution in determining the optimum immunological response. This Review article presents the importance of these variables in the development of antibacterial glycoconjugate vaccines and their effects on immune efficacy.
TiO2‐Supported Re as a General and Chemoselective Heterogeneous Catalyst for Hydrogenation of Carboxylic Acids to Alcohols
Authors: Toyao Takashi , Siddiki S. M. A. Hakim , Touchy Abeda S. , Onodera Wataru , Kon Kenichi , Morita Yoshitsugu , Kamachi Takashi , Yoshizawa Kazunari , Shimizu Ken‐ichi 
Published: November 2016

AbstractTiO2‐supported Re, Re/TiO2, was found to promote selective hydrogenation of carboxylic acids having aromatic and aliphatic moieties to the corresponding alcohols. Re/TiO2 showed superior results compared to other transition‐metal‐loaded TiO2 and supported Re catalysts for selective hydrogenation of 3‐phenylpropionic acid. 3‐phenylpropanol was produced in 97 % yield under mild conditions (5 MPa H2 at 140 °C). Contrary to typical heterogeneous catalysts, Re/TiO2 does not lead to the formation of dearomatized byproducts. The catalyst is recyclable and shows a wide substrate scope in the synthesis of alcohols (22 examples; up to 97 % isolated yield).
Zur Bindung bereit: Wie der T‐Zell‐Rezeptor aktiviert wird
Authors: Tetsch Larissa 
Published: November 2016

AbstractT‐Zellen gehören zur erworbenen Immunabwehr und erkennen Fremdstoffe über ihren T‐Zell‐Rezeptor. Dieser liegt, wie man seit kurzem weiß, in zwei Zuständen vor, die spontan in einander umwandelbar sind: einem ruhenden, inaktiven und einem voraktivierten Zustand. Nur voraktivierte Rezeptoren können Fremdstoffe binden und eine Immunantwort auslösen. Eine vorzeitige Aktivierung wird durch die Bindung des inaktiven Rezeptors an Membranlipide verhindert.
Wie entstanden und funktionierten die ersten Nucleinsäuren?
Authors: Groß Michael 
Published: November 2016

AbstractDass Ribonucleinsäure (RNA) in der Urzeit des Lebens auf der Erde eine zentrale Rolle spielte und sowohl als Erbmaterial als auch als Katalysator diente, ist inzwischen mit vielen Indizien belegt und weithin anerkannt, aber viele wichtige Details bleiben noch offen. Eine neue Arbeit zeigt, wie die allerersten Nucleotide das in allen Nucleinsäuren als Kettenglied vorhandene Phosphat rekrutiert haben könnten. Eine weitere demonstriert erstmals eine allein auf RNA beruhende exponentielle Vervielfältigung von RNA‐Genen und deren Umsetzung in funktionale RNA‐Moleküle.
Papierbasierte mikrofluidische Systeme
Authors: Ruffert Christine 
Published: November 2016

AbstractDie Mikrofluidik ist ein interdisziplinäres Forschungsgebiet, das sich mit der Untersuchung des Strömungsverhaltens flüssiger und gasförmiger Stoffe in Systemen mit mikrometerkleinen Strukturen befasst. Einen Teilbereich der Mikrofluidik bilden papierbasierte Schnelltests. Prominente Beispiele für solche Schnelltests sind der Schwangerschaftstest und Tests zum Drogennachweis. Die in diesem Beitrag vorgestellte Lehr‐/Lerneinheit ist Teil einer Lehrveranstaltung, in der Studierende mit Konzepten der Fertigung und des Einsatzes einfacher, aus Papier bestehender Analysesysteme vertraut gemacht werden. Durch Medieneinsatz und die aktive Beteiligung des Auditoriums wird der Unterricht lernorientiert gestaltet und die Inhalte durch die Einbindung praktischer Elemente in der technischen Übung vertieft. Diese Lehr‐/Lerneinheit wurde im Rahmen der zweisemestrigen Vorlesung Mikrofluidik an der Leibniz Universität Hannover eingesetzt und ist in modifizierter Form auch für den Sekundarbereich II im Schulunterricht geeignet.
Results of a randomized, prospective clinical trial evaluating metronomic chemotherapy in nonmetastatic patients with high‐grade, operable osteosarcomas of the extremities: A report from the Latin American Group of Osteosarcoma Treatment
Authors: Senerchia Andreza A. , Macedo Carla Renata , Ferman Sima , Scopinaro Marcelo , Cacciavillano Walter , Boldrini Erica , Lins de Moraes Vera Lúcia , Rey Guadalupe , de Oliveira Claudia T. , Castillo Luis , Almeida Maria Tereza , Borsato Maria Luisa , Lima Eduardo , Lustosa Daniel , Barreto José Henrique , El‐Jaick Tatiana , Aguiar Simone , Brunetto Algemir , Greggiani Lauro , Cogo‐Moreira Hugo , Atallah Alvaro , Petrilli Antonio Sergio 
Published: November 2016

BACKGROUNDMetronomic chemotherapy (MC) consists of the administration of a low dose of chemotherapy on a daily or weekly basis without a long break to achieve an antitumoral effect through an antiangiogenic effect or stimulation of the immune system. The potential effect of MC with continuous oral cyclophosphamide and methotrexate in patients with high‐grade operable osteosarcomas (OSTs) of the extremities was investigated.METHODSPatients with high‐grade OSTs who were 30 years old or younger were eligible for registration at diagnosis. Eligibility for randomization included 1) nonmetastatic disease and 2) complete resection of the primary tumor. The study design included a backbone of 10 weeks of preoperative therapy with methotrexate, adriamycin, and platinum (MAP). After surgery, patients were randomized between 2 arms to complete 31 weeks of MAP or receive 73 weeks of MC after MAP. The primary endpoint was event‐free survival (EFS) from randomization.RESULTSThere were 422 nonmetastatic patients registered (May 2006 to July 2013) from 27 sites in 3 countries (Brazil, Argentina and Uruguay), and 296 were randomized to MAP plus MC (n = 139) or MAP alone (n = 157). At 5 years, the EFS cumulative proportions surviving in the MAP‐MC group and the MAP‐alone group were 61% (standard error [SE], 0.5%) and 64% (SE, 0.5%), respectively, and they were not statistically different (Wilcoxon [Gehan] statistic = 0.724; P =.395). The multivariate analysis showed that necrosis grades 1 and 2, tumor size, and amputation were associated with shorter EFS.CONCLUSIONSAccording to the current follow‐up, EFS with MAP plus MC is not statistically superior to EFS with MAP alone in patients with high‐grade, resectable OSTs of the extremities. Cancer 2017;123:1003–10. © 2016 American Cancer Society.
Intraoperative near‐infrared fluorescence imaging targeting folate receptors identifies lung cancer in a large‐animal model
Authors: Keating Jane J. , Runge Jeffrey J. , Singhal Sunil , Nims Sarah , Venegas Ollin , Durham Amy C. , Swain Gary , Nie Shuming , Low Philip S. , Holt David E. 
Published: November 2016

BACKGROUNDComplete tumor resection is the most important predictor of patient survival with non–small cell lung cancer. Methods for intraoperative margin assessment after lung cancer excision are lacking. This study evaluated near‐infrared (NIR) intraoperative imaging with a folate‐targeted molecular contrast agent (OTL0038) for the localization of primary lung adenocarcinomas, lymph node sampling, and margin assessment.METHODSTen dogs with lung cancer underwent either video‐assisted thoracoscopic surgery or open thoracotomy and tumor excision after an intravenous injection of OTL0038. Lungs were imaged with an NIR imaging device both in vivo and ex vivo. The wound bed was re‐imaged for retained fluorescence suspicious for positive tumor margins. The tumor signal‐to‐background ratio (SBR) was measured in all cases. Next, 3 human patients were enrolled in a proof‐of‐principle study. Tumor fluorescence was measured both in situ and ex vivo.RESULTSAll canine tumors fluoresced in situ (mean Fluoptics SBR, 5.2 [range, 2.7‐8.1]; mean Karl Storz SBR 1.9 [range, 1.4‐2.6]). In addition, the fluorescence was consistent with tumor margins on pathology. Three positive lymph nodes were discovered with NIR imaging. Also, a positive retained tumor margin was discovered upon NIR imaging of the wound bed. Human pulmonary adenocarcinomas were also fluorescent both in situ and ex vivo (mean SBR, > 2.0).CONCLUSIONSNIR imaging can identify lung cancer in a large‐animal model. In addition, NIR imaging can discriminate lymph nodes harboring cancer cells and also bring attention to a positive tumor margin. In humans, pulmonary adenocarcinomas fluoresce after the injection of the targeted contrast agent. Cancer 2017;123:1051–60. © 2016 American Cancer Society.
Flow cytometry based rapid duplexed immunoassay for fusarium mycotoxins
Authors: Czéh Árpád , Mézes Miklós , Mandy Francis , Szőke Zsuzsanna , Nagyéri György , Laufer Noémi , Kőszegi Balázs , Koczka Tamás , Kunsági‐Máté Sándor , Lustyik György 
Published: November 2016

AbstractAt small food processing facilities, the most frequently used test to determine if grain‐derived mycotoxin concentrations are compliant with legal limits is the enzyme‐linked immunosorbent assay (ELISA). Each kit is designed to detect one of the six dangerous mycotoxins. With the increasing occurrence of coinfection of grain with multiple‐mycotoxins in the field and/or during storage, ELISA is no longer a cost effective best assay option. With ELISA, each species of mycotoxin requires different sample preparation/extraction and a 45 min incubation. The alternative multiplexed assay presented here, the competitive fluorescent microsphere immunoassay (CFIA), follows current food safety standards. It handles several toxins simultaneously with a single universal extraction protocol. The authors' objective was to modify an existing commercial CFIA kit developed for bench top flow cytometry and extend its utility for point‐of‐need (PON) applications. The accelerated protocol offers over 60% reduction in total processing time and it detects dual mycotoxin contamination simultaneously. The observed enhanced binding kinetics equations reported here utilizing suspended solid phase particles in liquid phase, are also supported by published theoretical calculations. In the near future portable cytometry may bring rapid multiplexed PON testing to assure the safety of small food processing installations. © 2016 International Society for Advancement of Cytometry
In the absence of a “landscape of fear”: How lions, hyenas, and cheetahs coexist
Authors: Swanson Alexandra , Arnold Todd , Kosmala Margaret , Forester James , Packer Craig 
Published: November 2016

AbstractAggression by top predators can create a “landscape of fear” in which subordinate predators restrict their activity to low‐risk areas or times of day. At large spatial or temporal scales, this can result in the costly loss of access to resources. However, fine‐scale reactive avoidance may minimize the risk of aggressive encounters for subordinate predators while maintaining access to resources, thereby providing a mechanism for coexistence. We investigated fine‐scale spatiotemporal avoidance in a guild of African predators characterized by intense interference competition. Vulnerable to food stealing and direct killing, cheetahs are expected to avoid both larger predators; hyenas are expected to avoid lions. We deployed a grid of 225 camera traps across 1,125 km2 in Serengeti National Park, Tanzania, to evaluate concurrent patterns of habitat use by lions, hyenas, cheetahs, and their primary prey. We used hurdle models to evaluate whether smaller species avoided areas preferred by larger species, and we used time‐to‐event models to evaluate fine‐scale temporal avoidance in the hours immediately surrounding top predator activity. We found no evidence of long‐term displacement of subordinate species, even at fine spatial scales. Instead, hyenas and cheetahs were positively associated with lions except in areas with exceptionally high lion use. Hyenas and lions appeared to actively track each, while cheetahs appear to maintain long‐term access to sites with high lion use by actively avoiding those areas just in the hours immediately following lion activity. Our results suggest that cheetahs are able to use patches of preferred habitat by avoiding lions on a moment‐to‐moment basis. Such fine‐scale temporal avoidance is likely to be less costly than long‐term avoidance of preferred areas: This may help explain why cheetahs are able to coexist with lions despite high rates of lion‐inflicted mortality, and highlights reactive avoidance as a general mechanism for predator coexistence.
Utility function design for strategic radio resource management games: An overview, taxonomy, and research challenges
Authors: Yang Chungang , Li Jiandong , Ejaz Waleed , Anpalagan Alagan , Guizani Mohsen 
Published: November 2016

AbstractRadio resource management is important for wireless communication networks. Game theory has been extensively used to model, analyze, and design interactive behaviors and the strategic decision‐making for radio resource management. It is known that utility function is one of the critical elements in a game, which characterizes the preferred relationship of the rational players and is a function of the action of players and their opponents. We first overview the basics of game theory and utility functions. We then present a taxonomy of utility functions with respect to different types of players, the nature of actions, and preferences in terms of the fairness, quality of service, and quality of experience. We provide some insights based on the taxonomy of utility functions, which provides the readers with a comprehensive view. Following that, we also discuss other types of traffic‐aware utility functions with different fairness and the potential and super modular game‐theoretic utility functions. In addition, we summarize the desired properties and observations for the design of suitable utility functions. Finally, we investigate impacts of the pricing in utility functions. This article ends with the conclusions and a promising view on open problems and challenges with possible future research directions.
Ascending stair evacuation: walking speed as a function of height
Authors: Delin Mattias , Norén Johan , Ronchi Enrico , Kuklane Kalev , Halder Amitava , Fridolf Karl 
Published: November 2016

SummaryThere is reason to believe that factors such as physical exertion and behavioural changes will influence the ascending walking speed and ultimately the possibility of satisfactory evacuation. To study these effects, a 2‐year research project was initiated with the focus on effects of physical exertion on walking speeds, physiological performance and behaviours during long ascending evacuations. Two sets of experiments on human performance during ascending long stairs, with a height of 48 and 109 m, were performed. The results include aspects such as walking speeds, physical exertion (oxygen consumption, heart rates and electromyography data), perceived exertion and behavioural changes, showing that physical work capacity affects walking speeds in case of long ascending evacuation and should be considered while using long ascending evacuation. Analysis of both walking and vertical speeds is recommended because it provides additional insights on the impact of stair configuration on vertical displacement and the importance of not using the same value for walking speed for different stairs because the design of the stairs has an impact. The novel datasets presented in this paper are deemed to provide useful information for fire safety engineers both for assisting fire safety design as well as the calibration of evacuation modelling tools. Copyright © 2016 John Wiley & Sons, Ltd.
Patterns of late‐life depressive symptoms and subsequent declines in cognitive domains
Authors: Gillis J. Cai , Chang Shun‐Chiao , Devore Elizabeth E. , Rosner Bernard A. , Grodstein Francine , Okereke Olivia I. 
Published: November 2016

BackgroundDepression frequently co‐occurs with cognitive decline, but the nature of this association is unclear. We examined relations of late‐life depressive symptom patterns to subsequent domain‐specific cognitive changes.MethodsDepressive symptoms were measured at up to 3 timepoints among 11,675 Nurses' Health Study participants prior to cognitive testing. Depressive symptom patterns were categorized as non‐depressed, variable or persistent, based on published severity cutpoints. Outcomes were global, verbal, and executive function‐attention composite scores.ResultsParticipants with persistent depressive symptoms had worse executive function‐attention decline compared with non‐depressed participants (multivariable‐adjusted mean difference = −0.03 units/year, 95% CI: −0.05, −0.01; p = 0.003); this difference was comparable with 8 years of aging. However, being in the persistent versus non‐depressed group was not significantly related to verbal (p = 0.71) or global score (p = 0.09) decline. By contrast, compared with the non‐depressed group, those with variable depressive symptoms had worse verbal memory decline (multivariable‐adjusted mean difference = −0.01 units/year, 95% CI: −0.02, −0.002; p = 0.03); this group showed no differences for global or executive function‐attention decline.ConclusionsA variable pattern of depressive symptom severity related to subsequent decline in verbal memory, while a persistent pattern related to decline in executive function‐attention. Findings could signal differences in underlying neuropathologic processes among persons with differing depression patterns and late‐life cognitive decline. Copyright © 2016 John Wiley & Sons, Ltd.
Banking and Currency Crises: Differential Diagnostics for Developed Countries
Authors: Joy Mark , Rusnák Marek , Šmídková Kateřina , Vašíček Bořek 
Published: November 2016

AbstractWe identify a set of ‘rules of thumb’ that characterize economic, financial and structural conditions preceding the onset of banking and currency crises in 36 advanced economies over 1970–2010. We use the classification and regression tree methodology and its random forest extension, which permits the detection of key variables driving binary crisis outcomes, allows for interactions among key variables and determines critical tipping points. We distinguish between basic country conditions, country structural characteristics and international developments. We find that crises are more varied than they are similar. For banking crises, we find that low net interest rate spreads in the banking sector and a shallow, or inverted, yield curve is their most important forerunners in the short term. In the longer term, it is high house price inflation. For currency crises, high domestic short‐term rates coupled with overvalued exchange rates are the most powerful short‐term predictors. We find that both country structural characteristics and international developments are relevant banking‐crisis predictors. Currency crises, however, seem to be driven more by country idiosyncratic, short‐term developments. We find that some variables, such as the domestic credit gap, provide important unconditional signals, but it is difficult to use them as conditional signals and, more importantly, to find relevant threshold values. Copyright © 2016 John Wiley & Sons, Ltd.