bluuebunny/crossref_metadata_2025_split huggingface dataset:
(R)‐Metacycloprodigiosin‐HCl: Chiroptical properties and structure
Authors: Peixoto Daniela , Ferreira Elisabete P. , Lourenço Ana M. , Johnson Jordan L. , Lobo Ana M. , Polavarapu Prasad L. 
Published: May 2018

Abstract(R)‐Metacycloprodigiosin can exist in three different tautomeric forms, each with hydrogens at C9′ and C12 in syn or anti orientation. With the addition of HCl, this structural diversity reduces to syn‐(R)‐metacycloprodigiosin‐HCl (1a) and anti‐(R)‐metacycloprodigiosin‐HCl (1b), each with multiple conformers. Energetics and chiroptical properties, namely, electronic circular dichroism (ECD) and specific optical rotation (SOR), of (R)‐metacycloprodigiosin‐HCl have been investigated at B3LYP/6‐311++G(2d,2p) level. The experimental ECD spectra of (R)‐metacycloprodigiosin‐HCl have also been measured. Calculations indicated that the lowest energy conformer of 1b is approximately 2.7 kcal/mol lower in energy than that of 1a, and the energy barrier for anti to syn conversion is approximately 13 kcal/mol. The population weighted calculated SORs of 1a and 1b are, respectively, positive and negative. The respective calculated ECD spectra of these pseudoenantiomers show an almost mirror image relationship between them. The experimental SOR and ECD compare well with those predicted for 1b. Thus, 1b is expected to be predominant, a situation confirmed also by nuclear Overhauser effect (NOE) data, with a similar conclusion reached for prodigiosin R1.
Chiral Cliffs: Investigating the Influence of Chirality on Binding Affinity
Authors: Schneider Nadine , Lewis Richard A. , Fechner Nikolas , Ertl Peter 
Published: May 2018

AbstractChirality is understood by many as a binary concept: a molecule is either chiral or it is not. In terms of the action of a structure on polarized light, this is indeed true. When examined through the prism of molecular recognition, the answer becomes more nuanced. In this work, we investigated chiral behavior on protein–ligand binding: when does chirality make a difference in binding activity? Chirality is a property of the 3D structure, so recognition also requires an appreciation of the conformation. In many situations, the bioactive conformation is undefined. We set out to address this by defining and using several novel 2D descriptors to capture general characteristic features of the chiral center. Using machine‐learning methods, we built different predictive models to estimate if a chiral pair (a set of two enantiomers) might exhibit a chiral cliff in a binding assay. A set of about 3800 chiral pairs extracted from the ChEMBL23 database was used to train and test our models. By achieving an accuracy of up to 75 %, our models provide good performance in discriminating chiral cliffs from non‐cliffs. More importantly, we were able to derive some simple guidelines for when one can reasonably use a racemate and when an enantiopure compound is needed in an assay. We critically discuss our results and show detailed examples of using our guidelines. Along with this publication we provide our dataset, our novel descriptors, and the Python code to rebuild the predictive models.
Universal screening of both endometrial and colon cancers increases the detection of Lynch syndrome
Authors: Adar Tomer , Rodgers Linda H. , Shannon Kristen M. , Yoshida Makoto , Ma Tianle , Mattia Anthony , Lauwers Gregory Y. , Iafrate Anthony J. , Hartford Nicole M. , Oliva Esther , Chung Daniel C. 
Published: May 2018

BACKGROUNDLynch syndrome (LS) is the most common hereditary cause of colorectal cancer (CRC) and endometrial cancer (EC). Screening of all CRCs for LS is currently recommended, but screening of ECs is inconsistent. The objective of this study was to determine the added value of screening both CRC and EC tumors in the same population.METHODSA prospective, immunohistochemistry (IHC)‐based screening program for all patients with newly diagnosed CRCs and ECs was initiated in 2011 and 2013, respectively, at 2 centers (primary and tertiary). Genetic testing was recommended for those who had tumors with absent mutS homolog 2 (MSH2), MSH6, or postmeiotoic segregation increased 2 (PMS2) expression and for those who had tumors with absent mutL homolog 1 (MLH1) expression and no v‐Raf murine sarcoma viral oncogene homolog B (BRAF) mutation or MLH1 promoter methylation. Amsterdam II criteria, revised Bethesda criteria, and scores from prediction models for gene mutations (the PREMM1,2,6 and PREMM5 prediction models) were ascertained in patients with LS.RESULTSIn total, 1290 patients with CRC and 484 with EC were screened for LS, and genetic testing was recommended for 137 patients (10.6%) and 32 patients (6.6%), respectively (P = .01). LS was identified in 16 patients (1.2%) with CRC and in 8 patients (1.7%) with EC. Among patients for whom genetic testing was recommended, the LS diagnosis rate was higher among those with EC (25.0% vs 11.7%, P = .052). The Amsterdam II criteria, revised Bethesda criteria, and both PREMM calculators would have missed 62.5%, 50.0%, and 12.5% of the identified patients with LS, respectively.CONCLUSIONSExpanding a universal screening program for LS to include patients who had EC identified 50% more patients with LS, and many of these patients would have been missed by risk assessment tools (including PREMM5). Universal screening programs for LS should include both CRC and EC. Cancer 2018. © 2018 American Cancer Society.
Self‐Pressurized Rapid Freezing as Cryo‐Fixation Method for Electron Microscopy and Cryopreservation of Living Cells
Authors: Huebinger Jan , Grabenbauer Markus 
Published: May 2018

AbstractReduction or complete prevention of ice crystal formation during freezing of biological specimens is mandatory for two important biological applications: (1) cryopreservation of living cells or tissues for long‐term storage, and (2) cryo‐fixation for ultrastructural investigations by electron microscopy. Here, a protocol that is fast, easy‐to‐use, and suitable for both cryo‐fixation and cryopreservation is described. Samples are rapidly cooled in tightly sealed metal tubes of high thermal diffusivity and then plunged into a liquid cryogen. Due to the fast cooling speed and high‐pressure buildup internally in the confined volume of the metal tubes, ice crystal formation is reduced or completely prevented, resulting in vitrification of the sample. For cryopreservation, however, a similar principle applies to prevent ice crystal formation during re‐warming. A detailed description of procedures for cooling (and re‐warming) of biological samples using this technique is provided. © 2018 by John Wiley & Sons, Inc.
Bioequivalence Evaluation of Two Oral Formulations of Acetaminophen in Healthy Subjects: Results From a Randomized, Single‐Blind, Crossover Study
Authors: García Aguirre Luis , Bohorquez Nassar Carlos , Ruiz Olmedo Isabel , Dennie Lara , Medina Nolasco Araceli G. 
Published: May 2018

AbstractDespite widespread availability of acetaminophen in Mexico, data on its pharmacokinetic properties in Mexican populations are limited. This single‐center, single‐blind, randomized, 2‐period, 2‐treatment, crossover, single‐dose‐per‐period, 2‐sequence study evaluated the bioequivalence of a test acetaminophen product available in Mexico compared with a reference 500‐mg acetaminophen product in 28 healthy adults under fasting conditions. Blood samples were collected predose and at specified intervals across a 16‐hour period following administration and were analyzed for acetaminophen using a validated reverse‐phase high‐performance liquid chromatography method. Drug products were considered to be bioequivalent if confidence intervals of natural log‐transformed Cmax, AUC0‐t, and AUC0‐∞ data were within the range of 80% to 125%. Results were inconclusive for Cmax due to high levels of intrasubject variability with this parameter. However, criteria for bioequivalence were met for AUC0‐t and AUC0‐∞. All measured acetaminophen concentrations in this study were within a safe therapeutic range, and no adverse events were reported. The level of Cmax intrasubject variability observed in this study does not have any apparent clinical implications that could affect either safety or efficacy.
Enhanced Luminescent Properties of Photo‐Stable Copper Nanoclusters through Formation of “Protein‐Corona”‐Like Assemblies
Authors: Kumar Das Nirmal , Chakraborty Subhajit , Mukherjee Madhumita , Mukherjee Saptarshi 
Published: May 2018

AbstractIn this study, interactions of synthesized copper nanoclusters (CuNCs) with a model transport protein, human serum albumin (HSA), have been systematically investigated by using various spectroscopic approaches. The interactions give rise to the formation of “protein‐corona” like assemblies and the luminescence properties (both steady‐state and time‐resolved) are enhanced due to gradual adsorption of the protein on the surface of the NCs. The associated thermodynamics and binding parameters have been estimated resorting to luminescent experimental techniques as well as isothermal titration calorimetry (ITC) studies, indicating that every NC is surrounded by (4±1) protein molecules. The adsorption of HSA on the surface of the NCs has been characterized by dynamic light scattering (DLS) and time‐resolved anisotropy measurements. Finally, fluorescence correlation spectroscopy (FCS) data substantiate the emergence of new “protein‐corona” like assemblies resulting in slower translational diffusion motions and concomitant rise of the hydrodynamic diameters.
Employee engagement in CSR initiatives and customer‐directed counterproductive work behavior (CWB): The mediating roles of organizational civility norms and job calling
Authors: Hur Won‐Moo , Moon Tae‐Won , Lee Han‐Geun 
Published: May 2018

AbstractThis study aims to examine how service employees' perceptions of corporate social responsibility (CSR) affect their customer‐directed counterproductive work behavior (CWB) and the mediation of this link through their organizational civility norms and job calling. Working with a sample of 252 frontline employees in South Korea hotels, structural equation modeling is employed to test research hypotheses. The results of this study suggest that service employees' perceptions of CSR are negatively related to their customer‐directed CWB. Second, service employees' organizational civility norms mediated the negative relationship between service employees' perceptions of CSR and customer‐directed CWB. Third, service employees' job calling also mediated the negative relationship between their perceptions of CSR and customer‐directed CWB. Finally, the relationship between service employees' perceptions of CSR and customer‐directed CWB is sequentially and fully mediated by organizational civility norms and job calling. The theoretical and managerial implications of the results and limitations of the study are discussed, and future research directions are suggested.
Comparison between preprandial vs. postprandial insulin aspart in patients with type 1 diabetes on insulin pump and real‐time continuous glucose monitoring
Authors: Thuillier Philippe , Sonnet Emmanuel , Alavi Zarrin , Roudaut Nathalie , Nowak Emmanuel , Dion Angélina , Kerlan Véronique 
Published: May 2018

AbstractBackgroundThe objective was to compare glycemic control between preprandial and postprandial bolus administration (15 min before [PRE] or immediately after the meal [POST]) in patients with type 1 diabetes using insulin pump and real‐time continuous glucose monitoring.MethodsBetween September 2015 and February 2016, a single‐centre, open randomized, 2‐way crossover study of patients on bolus insulin aspart administration was conducted during two 14‐day periods and according to 2 administration regimen schedules (PRE/POST or POST/PRE). Inclusion criteria were as follows: patients with type 1 diabetes, ≥18 and ≤ 65 years old, treated with insulin aspart using a Medtronic® insulin pump and trained on functional insulin therapy. Patients were randomly assigned to either regimen schedule. At the beginning of each period, each patient was provided with a standardized high fat meal. Primary outcome was the area under the curve for interstitial glucose above 140 mg/dL per minute (AUC > 140 mg/dL/min) during each period. Secondary outcomes were time spent in hypo/eu/hyperglycemia, glycemic variability indices, and AUC during 4 hours after high fat meal calculated with continuous glucose monitoring data.ResultsTwenty‐two patients were included. Mean AUC > 140 mg/dL/min was statistically higher in patients on POST (43.70 mg/dL/min; 95%CI: 34.08 to 53.31) versus PRE insulin aspart regimen (37.24 mg/dL/min 95%CI: 27.63 to 46.85) (P = 0.03). Mean interstitial glycemia and glycemic variability indices were also increased (P < 0.05) on POST regimen. The mean AUC 4 hours after the high fat meal was higher on POST regimen but not statistically different (P = 0.06).ConclusionsIn our study, postprandial administration of insulin aspart appears to mildly increase glycemic excursion and glycemic variability.
Determining the effects of adulterants on drug detection via enzyme‐linked immunosorbent assay and adulterant tests strips
Authors: Olivieri Bianca , Marić Mark , Bridge Candice 
Published: May 2018

AbstractThe use of immunoassays for drug screening has increased due to their sensitivity towards target analytes, specifically the enzyme‐linked immunosorbent assay (ELISA) technique. Adulterant test strips are commonly used in conjunction with immunoassay tests to ensure the integrity of the specimen has not been altered prior to drug screening. This research focuses on determining which adulterants can produce a false negative result, not only with 1 of the screening tests, but throughout the entire screening process. Seven adulterants were tested for their ability to generate false negative results for the ELISA by decreasing the detectable antigen concentration to below industry‐used cut‐off levels. Each adulterant was added to a urine sample containing 1 of 5 different drugs at 5 different concentrations (0, 5, 10, 25, and 50%). Five different urine samples that contained drugs and drug metabolites of benzoylecgonine, THC‐COOH, α‐PVP, D‐amphetamine, and Diazepam, were treated with each of the 7 adulterants and analyzed on the ELISA and subsequently by 2 different test strips. The results indicated that 4 adulterants (ie, bleach, Drano®, vinegar, and sodium nitrite) generated the most false negatives for both test strips and the ELISA at surprisingly low concentrations, ~5% v/v. Thus indicating that there are still ways that a urine sample that contains drugs could be analyzed and labeled “clean and free of drugs” after going through a common screening process. These results suggest that new drug screening techniques need to be developed to detect adulterants in urine samples for drug screening.
Analyzing big data in social media: Text and network analyses of an eating disorder forum
Authors: Moessner Markus , Feldhege Johannes , Wolf Markus , Bauer Stephanie 
Published: May 2018

AbstractObjectiveSocial media plays an important role in everyday life of young people. Numerous studies claim negative effects of social media and media in general on eating disorder risk factors. Despite the availability of big data, only few studies have exploited the possibilities so far in the field of eating disorders.MethodMethods for data extraction, computerized content analysis, and network analysis will be introduced. Strategies and methods will be exemplified for an ad‐hoc dataset of 4,247 posts and 34,118 comments by 3,029 users of the proed forum on Reddit.ResultsText analysis with latent Dirichlet allocation identified nine topics related to social support and eating disorder specific content. Social network analysis describes the overall communication patterns, and could identify community structures and most influential users. A linear network autocorrelation model was applied to estimate associations in language among network neighbors. The supplement contains R code for data extraction and analyses.DiscussionThis paper provides an introduction to investigating social media data, and will hopefully stimulate big data social media research in eating disorders. When applied in real‐time, the methods presented in this manuscript could contribute to improving the safety of ED‐related online communication.
Symbiotic flagellate protists as cryptic drivers of adaptation and invasiveness of the subterranean termite Reticulitermes grassei Clément
Authors: Duarte Sónia , Nobre Tânia , Borges Paulo A. V. , Nunes Lina 
Published: May 2018

AbstractChanges in flagellate protist communities of subterranean termite Reticulitermes grassei across different locations were evaluated following four predictions: (i) Rural endemic (Portugal mainland) termite populations will exhibit high diversity of symbionts; (ii) invasive urban populations (Horta city, Faial island, Azores), on the contrary, will exhibit lower diversity of symbionts, showing high similarity of symbiont assemblages through environmental filtering; (iii) recent historical colonization of isolated regions—as the case of islands—will imply a loss of symbiont diversity; and (iv) island isolation will trigger a change in colony breeding structure toward a less aggressive behavior. Symbiont flagellate protist communities were morphologically identified, and species richness and relative abundances, as well as biodiversity indices, were used to compare symbiotic communities in colonies from urban and rural environments and between island invasive and mainland endemic populations. To evaluate prediction on the impact of isolation (iv), aggression tests were performed among termites comprising island invasive and mainland endemic populations. A core group of flagellates and secondary facultative symbionts was identified. Termites from rural environments showed, in the majority of observed colonies, more diverse and abundant protist communities, probably confirming prediction (i). Corroborating prediction (ii), the two least diverse communities belong to termites captured inside urban areas. The Azorean invasive termite colonies had more diverse protist communities than expected and prediction (iii) which was not verified within this study. Termites from mainland populations showed a high level of aggressiveness between neighboring colonies, in contrast to the invasive colonies from Horta city, which were not aggressive to neighbors according to prediction (iv). The symbiotic flagellate community of R. grassei showed the ability to change in a way that might be consistent with adaptation to available conditions, possibly contributing to optimization of the colonization of new habitats and spreading of its distribution area, highlighting R. grassei potential as an invasive species.
Development of an electrode for carrots using conductive unvulcanized rubber
Authors: Tada Yasunori , Inoue Masahiro 
Published: May 2018

AbstractElectrical impedance of plants is related to condition of the plant's cell tissue. In existing works, the impedance has been utilized for understanding the condition of the plant. There are three kinds of electrode for measuring the impedance: a needle electrode, a metallic foil electrode, and a conductive gel electrode. However, these electrodes have problems. The needle electrode injures the plants. The metallic foil electrode does not stably contact to the plant because the plants has curve and convexo–concave surface. The conductive gel electrode including NaCl blasts the plants. We proposed a conductive unvulcanized rubber electrode for measuring the electrical impedance of the carrots. Characteristics of the conductive unvulcanized rubber electrode were soft, deformable, and self‐adhesive. Thus, the electrode was noninvasive and did not damage to the carrots. In experiments, we showed that the conductive unvulcanized rubber electrode could be utilized for measuring electrical impedance of a carrot for 912 h. Moreover, we observed that the contact area of the electrode was larger than the contact area of a conductive adhesive tape electrode.
Wave of fire: an anthropogenic signal in historical fire regimes across central Pennsylvania,USA
Authors: Stambaugh Michael C. , Marschall Joseph M. , Abadir Erin R. , Jones Benjamin C. , Brose Patrick H. , Dey Daniel C. , Guyette Richard P. 
Published: May 2018

AbstractIncreasingly detailed records of long‐term fire regime characteristics are needed to test ecological concepts and inform natural resource management and policymaking. We reconstructed and analyzed twelve 350+ yr‐long fire scar records developed from 2612 tree‐ring dated fire scars on 432 living and dead pine (Pinus pungens,Pinus rigida,Pinus resinosa,Pinus echinata) trees from across central Pennsylvania. We used multiple spatial and time series analysis methods to quantify fire regime characteristics (frequency, seasonality, percentages of trees scarred, extent) and fire–climate–human associations. Prior to the 20th‐century fire suppression, fire regimes at the majority of sites consisted of frequent, low‐to‐moderate severity, dormant season fires. Fires were often regionally synchronous when preceded by significantly dry years. Using documentary archives, we provide the first description of a “wave of fire”—an anthropogenic signal in fire frequency that progressively moved across the region. This “wave of fire” reflects a changing progression of anthropogenic fire regimes from Native American occupation and depopulation, to Euro‐American settlement, to industrialization and declining fire use up to the 20th century era of fire suppression. The wave of fire provides a new perspective on historical and modern fire regime dynamics and identifies socio‐ecological impacts since North American colonization. Because the anthropogenic wave of fire exists at sites across North America, we emphasize the need for a broader determination of its geographic prevalence and variability as such determinations could influence historical ecology interpretations and perspectives on past and future roles of humans in managing ecosystems with fire.
Proteomic definition of human mucosal‐associated invariant T cells determines their unique molecular effector phenotype
Authors: Bulitta Björn , Zuschratter Werner , Bernal Isabel , Bruder Dunja , Klawonn Frank , von Bergen Martin , Garritsen Henrikus Stephanus Paulus , Jänsch Lothar 
Published: May 2018

AbstractMucosal‐associated invariant T cells (MAIT) constitute the most abundant anti‐bacterial CD8+ T‐cell population in humans. MR1/TCR‐activated MAIT cells were reported to organize cytotoxic and innate‐like responses but knowledge about their molecular effector phenotype is still fragmentary. Here, we have examined the functional inventory of human MAIT cells (CD3+Vα7.2+CD161+) in comparison with those from conventional non‐MAIT CD8+ T cells (cCD8+) and NK cells. Quantitative mass spectrometry characterized 5500 proteins of primary MAIT cells and identified 160 and 135 proteins that discriminate them from cCD8+ T cells and NK cells donor‐independently. Most notably, MAIT cells showed a unique exocytosis machinery in parallel to a proinflammatory granzyme profile with high levels of the granzymes A, K, and M. Furthermore, 24 proteins were identified with highest abundances in MAIT cells, including CD26, CD98, and L‐amino‐oxidase (LAAO). Among those, expression of granzyme K and CD98 were validated as MAIT‐specific with respect to non‐MAIT CD8+ effector subsets and LAAO was found to be recruited together with granzymes, perforin, and CD107a at the immunological synapse of activated MAIT cells. In conclusion, this study complements knowledge on the molecular effector phenotype of MAIT cells and suggest novel immune regulatory functions as part of their cytotoxic responses.