bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sensitive detection of glucagon aggregation using amyloid fibril‐specific antibodies
Authors: Stimple Samuel D. , Kalyoncu Sibel , Desai Alec A. , Mogensen Jesper E. , Spang Lotte T. , Asgreen Désirée J. , Staby Arne , Tessier Peter M. 
Published: April 2019

AbstractSensitive detection of protein aggregates is important for evaluating the quality of biopharmaceuticals and detecting misfolded proteins in several neurodegenerative diseases. However, it is challenging to detect extremely low concentrations (<10 ppm) of aggregated protein in the presence of high concentrations of soluble protein. Glucagon, a peptide hormone used in the treatment of extreme hypoglycemia, is aggregation‐prone and forms amyloid fibrils. Detection of glucagon fibrils using conformation‐specific antibodies is an attractive approach for identifying such aggregates during process and formulation development. Therefore, we have used yeast surface display and magnetic‐activated cell sorting to sort single‐chain antibody libraries to identify antibody variants with high conformational specificity for glucagon fibrils. Notably, we find several high‐affinity antibodies that display excellent selectivity for glucagon fibrils, and we have integrated these antibodies into a sensitive immunoassay. Surprisingly, the sensitivity of our assay—which involves direct (nonantibody mediated) glucagon immobilization in microtiter plates—can be significantly enhanced by pretreating the microtiter plates with various types of globular proteins before glucagon immobilization. Moreover, increased total concentrations of glucagon peptide also significantly improve the sensitivity of our assay, which appears to be due to the strong seeding activity of immobilized fibrils at high glucagon concentrations. Our final assay is highly sensitive (fibril detection limit of ~0.5–1 ppm) and is >20 times more sensitive than detection using a conventional, amyloid‐specific fluorescent dye (Thioflavin T). We expect that this type of sensitive immunoassay can be readily integrated into the drug development process to improve the generation of safe and potent peptide therapeutics.
Exploring the molecular genetic foundations of cancer biology and how biomedical advances are made in an advanced undergraduate course
Authors: Alexander Stephen , Hannink Mark 
Published: April 2019

AbstractWe describe an advanced, inquiry driven undergraduate course in Cancer Biology that combines faculty lectures typical of undergraduate courses with literature‐driven discussions typical of graduate courses. As a capstone course, one goal of this course is to integrate knowledge from previous coursework in physiology, cell and molecular biology, genetics, and chemistry, so that students acquire a state‐of‐the‐art understanding of cancer and cancer treatment. A related goal is for students to learn, from the primary literature, how science is performed and how new scientific knowledge is used to improve cancer treatment. We report on the development of this course and the methods used to accomplish the course goals. We present the results of a 5‐year survey that provides a detailed picture of the demographics of the class and demonstrates that the course results in improved understanding of both cancer biology and how science is performed. Student responses to our survey strongly support the use of original literature as a teaching tool. We suggest that incorporation of primary literature into advanced undergraduate science courses is an effective approach for improving scientific literacy. © 2019 International Union of Biochemistry and Molecular Biology, 47(4):408–416, 2019.
Major hemorrhage in chronic lymphocytic leukemia patients in the US Veterans Health Administration system in the pre‐ibrutinib era: Incidence and risk factors
Authors: Georgantopoulos Peter , Yang Huiying , Norris LeAnn B. , Bennett Charles L. 
Published: April 2019

AbstractChronic lymphocytic leukemia (CLL) patients are at increased risk for major hemorrhage (MH). We examined incidence of and risk factors for MH in CLL patients before introduction of newer CLL therapies such as ibrutinib, which includes bleeding risk. This study included 24 198 CLL patients treated in the VA system before FDA approval of ibrutinib as CLL therapy. Data came from VA databases from 1999 to 2013. MH incidence was 1.9/100 person‐years (95% CI: 1.8‐1.9), with cumulative incidences of 2.3%, 5.2%, and 7.3% by year 1, 3, and 5, respectively. Median time from CLL diagnosis to MH was 2.8 years (range: 0‐15.7 years). In multivariate analyses, concurrent anticoagulant and antiplatelet use (HR: 4.2; 95% CI: 3.2‐5.6), anticoagulant use only (HR: 2.6; 95% CI: 2.3‐3.1), and antiplatelet use only (HR: 1.5; 95% CI: 1.3‐1.7) increased MH risk vs not receiving those medications; being nonwhite, male, having MH history, renal impairment, anemia, thrombocytopenia, and alcohol abuse were associated with increased MH risk. These pre‐ibrutinib data are important for providing context for interpreting MH risk in ibrutinib‐treated patients. As ibrutinib clinical use is increasing, updated analyses of MH risk among ibrutinib‐treated VA patients with CLL may provide additional useful insight.
The impact of husbands' involvement in goal‐setting training on women's empowerment: First evidence from an intervention among female microfinance borrowers in Sri Lanka
Authors: Huis Marloes Anne , Hansen Nina , Otten Sabine , Lensink Robert 
Published: April 2019

AbstractOffering women access to microcredit and business training is a prominent approach to stimulate women's empowerment. Whereas men seem to profit from business training, women do not. We adjusted a goal‐setting training session on the basis of women's needs in collaboration with a women organization in Sri Lanka. We invited female microfinance borrowers and their husbands to the training as both parties should be involved to change existing gender roles with respect to their income‐generating activity. We investigated the impact of the training on goal‐setting skills, self‐esteem, and the couples' interaction in a subsequent task. In two field experiments, female borrowers and their husbands (nstudy1 = 68; nstudy2 = 76) were randomly assigned to one of three conditions: (a) goal‐setting training and setting goals as couple, (b) goal‐setting training and setting goals individually, or (c) no training (control condition). Participation in the training increased women's SMART (specific, measurable, achievable, realistic, time bound) goal‐setting skills. We coded couples' interactions in a subsequent decision‐making task to assess signs of women's empowerment. Descriptively, we found some initial evidence of increased women's empowerment in the interaction (Study 2). We critically discuss results and how gendered power imbalances may need to be addressed to stimulate social change towards gender equity.
Considerations on Probe Design for Affinity‐Guided Protein Conjugation
Authors: Mortensen Michael R. , Skovsgaard Mikkel B. , Gothelf Kurt V. 
Published: April 2019

AbstractThe plethora of methods developed for the creation of protein conjugates often differs significantly with regard to the heterogeneity of the resulting products, in the degree of genetic manipulation of the protein required, and in the technical skills required to perform the conjugation procedure. Affinity‐guided protein conjugation is a protein labeling methodology based on noncovalent binding interactions between a labeling probe and the protein of interest. These interactions increase the local concentration of a reactive group in the probe on the protein surface thus facilitating the conjugation in proximity of the complexation site. The ability to produce high‐quality conjugates from nongenetically modified proteins both in vitro, but also in cells, demonstrates the power of affinity‐guided protein conjugation. Here, we present the progress of affinity‐guided protein conjugation in relation to selective protein labeling in living systems and the formation of high‐quality protein conjugates. Furthermore, the probe design will be discussed in relation to the utility of the probe for labeling in vitro or in living systems.
ATP Inhibits the Transcription Factor STAT5b
Authors: Berg Angela , Sperl Bianca , Berg Thorsten 
Published: April 2019

AbstractAlthough naturally occurring low‐molecular‐weight compounds have many known roles within the cell, these do not usually involve the direct inhibition of protein–protein interactions. Based on the results of high‐throughput screening of a library of bioactive compounds and neurotransmitters, we report here that the four nucleoside triphosphates ATP, GTP, CTP and UTP inhibit the SH2 domain of the tumor‐related transcription factor STAT5b. ATP and GTP are the most active nucleoside triphosphates and show specificity for STAT5b over STAT5a, STAT3, STAT6 and the p53‐binding protein HDM2. As the inhibition constant of ATP against STAT5b is significantly lower than published values for the intracellular ATP concentration, our data suggest that ATP might inhibit the protein–protein interactions of STAT5b in living cells.
Chemoenzymatic Synthesis of Fragrance Compounds from Stearic Acid
Authors: Meng Shuaiqi , Guo Jia , Nie Kaili , Tan Tianwei , Xu Haijun , Liu Luo 
Published: April 2019

AbstractFatty acids are versatile precursors for fuels, fine chemicals, polymers, perfumes, etc. The properties and applications of fatty acid derivatives depend on chain length and on functional groups and their positions. To tailor fatty acids for desired properties, an engineered P450 monooxygenase has been employed here for enhanced selective hydroxylation of fatty acids. After oxidation of the hydroxy groups to the corresponding ketones, Baeyer–Villiger oxidation could be applied to introduce an oxygen atom into the hydrocarbon chains to form esters, which were finally hydrolyzed to afford either hydroxylated fatty acids or dicarboxylic fatty acids. Using this strategy, we have demonstrated that the high‐value‐added flavors exaltolide and silvanone supra can be synthesized from stearic acid through a hydroxylation/carbonylation/esterification/hydrolysis/lactonization reaction sequence with isolated yields of about 36 % (for ω−1 hydroxylated stearic acid; 100, 60, 80, 75 % yields for the individual reactions, respectively) or 24 % (for ω−2 hydroxylated stearic acid). Ultimately, we obtained 7.91 mg of exaltolide and 13.71 mg of silvanone supra from 284.48 mg stearic acid.
Adverse events and modes of failure related to the FilterWire EZ Embolic Protection System: Lessons learned from an analytic review of the FDA MAUDE database
Authors: Khalid Nauman , Javed Hasan , Rogers Toby , Hashim Hayder , Shlofmitz Evan , Chen Yuefeng , Khan Jaffar M. , Musallam Anees , Torguson Rebecca , Bernardo Nelson L. , Waksman Ron 
Published: April 2019

AbstractObjectivesTo assess the commonly reported complications and failure modes for FilterWire EZ Embolic Protection Devices (EPD) by analyzing the postmarketing surveillance data from the Food and Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database.BackgroundEPDs prevent distal embolization of atheroembolic materials during percutaneous interventions resulting in reduced microvascular obstruction and improved microcirculation while maintaining tissue perfusion. The FilterWire EZ EPD (Boston Scientific, Natick, MA) is approved for use in interventions of de novo saphenous vein grafts (SVG) and carotid artery stenosis. Robust data on the commonly reported complications and failure modes associated with the FilterWire EZ device are limited.MethodsThe MAUDE database was queried from September 1, 2008, through September 30, 2018, for FilterWire EZ system, yielding 474 reports. After exclusion of duplicate and incomplete reports, 464 device reports were included in the final analysis.ResultsDevice‐related adverse events were most commonly reported for carotid (n = 281) and SVG (n = 101) interventions. The most commonly reported major complications were: ischemic stroke (n = 57), vessel perforation or dissection (n = 12), death (n = 8), and myocardial infarction (n = 5). Minor complications included: hypotension (n = 68), bradycardia (n = 41), and vasospasm (n = 27). The most commonly reported failure modes were: detachment and/or damage of the device components (n = 118), device entrapment (n = 90), and stent‐related issues (n = 46).ConclusionsAnalysis of the MAUDE dataset is helpful in identifying the commonly reported adverse events and failure modes of FilterWire EZ devices. This platform serves as an important tool for both physicians and manufacturers to optimize device performance and clinical outcomes.
Blend Time Measurement in the Confined Impeller Stirred Tank
Authors: Jairamdas Khilesh , Bhalerao Akshay , Machado Marcio Bezerra , Kresta Suzanne M. 
Published: April 2019

AbstractAn image processing technique is applied to measure the blend time in a confined impeller stirred tank (CIST). An acid‐base reaction is used to track mixing. The blend time is defined as the time taken to 95 % or 99 % of the pixels change color from purple to yellow. Six sets of impellers are employed: Rushtons, A310s, pitched‐blade turbines (PBTs; three different combinations of up‐ and down‐pumping), and Intermigs. Variation of the Reynolds number Re showed that the blend time becomes shorter with increasing Re and longer with higher viscosity. As Re drops below 225, compartmentalization becomes apparent and the decolorization percentage increases suddenly when the acid reaches each communication point between the impellers.
Intramolecular [2+2] Photocycloaddition of Cyclic Enones: Selectivity Control by Lewis Acids and Mechanistic Implications
Authors: Poplata Saner , Bauer Andreas , Storch Golo , Bach Thorsten 
Published: April 2019

AbstractThe intramolecular [2+2] photocycloaddition of 3‐alkenyl‐2‐cycloalkenones was performed in an enantioselective fashion (nine representative examples, 54–86 % yield, 76–96 % ee) upon irradiation at λ=366 nm in the presence of an AlBr3‐activated oxazaborolidine as the Lewis acid. An extensive screening of proline‐derived oxazaborolidines showed that the enantioface differentiation depends strongly on the nature of the aryl group at the 3‐position of the heterocycle. DFT calculations of the Lewis acid–substrate complex indicate that attractive dispersion forces may be responsible for a change of the binding mode. The catalytic [2+2] photocycloaddition was shown to proceed on the triplet hypersurface with a quantum yield of 0.05. The positive effect of Lewis acids on the outcome of a given intramolecular [2+2] photocycloaddition was illustrated by optimizing the key step in a concise total synthesis of the sesquiterpene (±)‐italicene.
Synthesis and Thermal Decomposition of Heavy Tetrylenes Bearing N‐Aminocarbazolyl Substituents
Authors: Hinz Alexander 
Published: April 2019

AbstractThe synthesis of the N‐aminocarbazole R‐NH2 (2) is reported. Subsequent reaction with bis[bis(trimethylsilyl)amido]tetrylenes E[N(SiMe3)2]2 (E=Ge, Sn, or Pb) allowed the isolation of formal hydrazidotetrylene derivatives, R−N(H)EN(SiMe3)2 (3) that includes the first example of a hydrazidoplumbylene to date. Thermal decomposition of these compounds resulted in the elimination of “NH” and afforded the tetrylenes R‐EN(SiMe3)2 (4).
Intramolecular Hydroamination of Selenoalkynes to 2‐Selenylindoles in the Absence of Catalyst
Authors: Coelho Felipe L. , Gil Eduarda S. , Gonçalves Paulo F. B. , Campo Leandra F. , Schneider Paulo H. 
Published: April 2019

AbstractIn this work, a series of 2‐chalcogenylindoles was synthesized by an efficient methodology, starting from chalcogenoalkynes, including a previously unreported tellurium indole derivative. For the first time, these 2‐substituted chalcogenylindoles were obtained in the absence of metal catalyst or base, under thermal conditions only. In addition, the results described herein represent a methodology with inverse regioselectivity for the chalcogen functionalization of indoles.
Work‐related medical rehabilitation in patients with cancer—Postrehabilitation results from a cluster‐randomized multicenter trial
Authors: Fauser David , Wienert Julian , Beinert Thomas , Schmielau Jan , Biester Irene , Krüger Hans‐Ulrich , Presl Angelika , Bethge Matthias 
Published: April 2019

BackgroundEffective multidisciplinary rehabilitation programs supporting the return to work have become increasingly relevant for cancer survivors. In Germany, inpatient work‐related medical rehabilitation programs consider treatment modules of work‐related diagnostics, work‐related functional capacity training, psychosocial groups, and intensified social counseling. The authors tested the effectiveness of a work‐related medical rehabilitation program compared with conventional medical rehabilitation using a cluster‐randomized multicenter trial (German Clinical Trial Register: DRKS00007770).MethodsIn total, 484 patients with cancer were recruited at 4 rehabilitation centers. Patients at a center who started their rehabilitation in the same week represented a cluster. These clusters were randomly assigned using computer‐generated randomization schedules either to an intervention group (IG) or to a control group (CG). The primary outcome was role functioning. Secondary outcomes were other quality‐of‐life domains and the return to work.ResultsIn total, 425 patients (210 in the IG) were included in the analysis at the 3‐month follow‐up. There was no significant difference between the IG and CG in role functioning (b = 3.55; 95% CI, −1.18 to 8.29; P = .142). Participants in the IG reported better physical functioning (b = 5.99; 95% CI, 3.33‐8.65; P < .001), less physical fatigue (b = −5.09; 95% CI, −9.62 to −0.56; P = .028), and less pain (b = −6.24; 95% CI, −11.24 to −1.23; P = .015).ConclusionsWork‐related medical rehabilitation had no effect on the primary outcome compared with conventional medical rehabilitation but may enhance physical functioning and reduce physical fatigue and pain.
Optoelectronic Properties of A‐π‐D‐π‐A Thiophene‐Based Materials with a Dithienosilole Core: An Experimental and Theoretical Study
Authors: Caselli Monica , Vanossi Davide , Buffagni Mirko , Imperato Manuel , Pigani Laura , Mucci Adele , Parenti Francesca 
Published: April 2019

AbstractTwo A‐π‐D‐π‐A thiophene‐based small molecules with a central dithienosilole core and dicyanovinyl (DCV) end groups were synthesized. These compounds differ only by the presence of alkyl and alkylsulfanyl chains, respectively, on the thiophene beta positions. Computational data together with the spectroscopic and electrochemical findings (obtained by means of absorption, steady‐state/time‐resolved emission techniques, and cyclic voltammetry) revealed that both molecules possess low electronic and optical band gaps, broad absorption spectra, and good stability both in p and n‐doping states, which make them suitable for optoelectronic applications. In both compounds, the HOMO–LUMO transition involves an intramolecular charge transfer from the electron‐donor dithienosilole unit to the two terminal electron‐acceptor DCV groups. A marked positive emission solvatochromism was observed for both molecules and was interpreted on the basis of the symmetry breaking in the S1 excited state. The two synthesized compounds were also compared to their shorter precursors and to similar oligothiophenes to understand how the nature of the building block influences the characteristics of the final materials. Furthermore, it was possible to better understand the contribution of the sulfur atom in modulating the optical properties of the small molecules studied.
Nonlinear Nonacenes with a Dithienothiophene Substructure: Multifunctional Compounds that Act as Columnar Mesogens, Luminophores, π Gelators, and p‐Type Semiconductors
Authors: Ma Tao , Wang Hai‐Feng , Zhao Ke‐Qing , Wang Bi‐Qin , Hu Ping , Monobe Hirosato , Heinrich Benoît , Donnio Bertrand 
Published: April 2019

AbstractBoard‐like liquid‐crystalline semiconductors based on the dithieno[3,2‐b;2′,3′‐d]thiophene (DTT) substructure were synthesized and their thermal, self‐assembly, optical, and semiconducting properties investigated. These sanidic compounds, bearing eight peripheral chains, are mesomorphic and spontaneously self‐assemble into columnar hexagonal mesophases (Colhex) over broad temperature ranges, as confirmed by polarized optical microscopy, differential scanning calorimetry, and small‐angle X‐ray scattering. Strong blue photoluminescence with absolute quantum yields up to 33 % were measured. These compounds also form blue‐light emitting gels in various organic solvents. The fibrillar‐like morphology of these gels, reminiscent of the columnar structure, and stabilized by efficient intermolecular interactions, was characterized by scanning electron microscopy. The charge carrier mobility of these π‐extended mesogens was measured by time‐of‐flight transient photocurrent technique in the Colhex mesophase, and showed good hole‐transport performance with charge carrier mobility of 10−3 cm2 V−1 s−1.
Design of Two‐Photon‐Excited Fluorescent Dyes Containing Fluoroborylene Groups
Authors: Zaleśny Robert , Szczotka Nina , Grabarz Anna , Ośmiałowski Borys , Jacquemin Denis 
Published: April 2019

AbstractAiming at establishing structure‐property relationships for two‐photon absorption, we present the results of an in silico investigation of dyes containing fluoroborylene (BF) groups. More specifically, we analyze the electronic properties corresponding to the one‐ and two‐photon excitation to two lowest‐lying singlet states (
and
) using TD‐DFT and CC2 methods. BF‐ and BF2‐containing fluorescent dyes are in the limelight, but it remains challenging to reach the larger electronic two‐photon transition strengths needed in bioimaging applications. Hence, we put an emphasis on maximizing those strengths through structural variations. To this end, we consider 138 unique molecules deriving from five different structural cores presenting BF/BF2 groups. This molecular set encompasses representatives of three architectures, built with different arrangements of electron‐donating (D) and electron‐withdrawing (A) moieties: D‐A, D‐A‐D and D‐A‐A‐D. In addition, we consider several π‐conjugated linkers of different lengths, composed of ethylene (en) and 1,4‐phenylene (PH) units (up to ‐enPHenPH‐), and a panel of substituents (R=H, OMe, NMe2 and NPh2). For the two‐photon transitions, it is shown that not only the linker extension and the strength of the electron‐donating substituent are crucial for maximizing the two‐photon activity but also the central core possessing fluoroborylene unit. The results have been rationalized by using a generalized three‐level model.
Creating shared value using materiality analysis: Strategies from the mining industry
Authors: Saenz Cesar 
Published: April 2019

AbstractMateriality reflects an organization's significant social, economic, and environmental impacts, together with their influence on stakeholders' assessments and decisions. The Global Reporting Initiative's G4 Guidelines describe a four‐step process for an organization to follow to determine the specific content to be included in its social responsibility report. However, there are no recommendations regarding what types of strategies should be used for each social issue depending on their materiality. The main aims of this paper are to explain the material issues and to identify what creating shared value (CSV) strategies can be applied to address each social issue according to a materiality analysis. For this purpose, a sample of 27 mining companies is obtained. Based on secondary sources, a content analysis is prepared. The resulting framework provides CSV theory with a guide to what CSV strategy is recommended according to the location of each social issue in the materiality matrix.