bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel nitric oxide‒generating platform using manuka honey as an anti‐biofilm strategy in chronic rhinosinusitis
Authors: Yang Catherina , Mavelli Girish Vallerinteavide , Nacharaju Parimala , Li Kevin , Cleare Levi G. , Nosanchuk Joshua D. , Friedman Joel M. , Abuzeid Waleed M.
Published: December 2019

Background

Bacterial biofilms are implicated in the pathogenesis of chronic rhinosinusitis. Nitric oxide (NO) is a key immune effector with potent antimicrobial effects, but a short half‐life limits achievement of therapeutic concentrations. We hypothesized that manuka honey (MH) could induce sustained reduction of nitrite to NO causing biofilm disruption and that this effect would be enhanced with the addition of a NO‐releasing microparticle.

Methods

Porous organosilica microparticles containing nitrosylated thiol groups were formulated (SNO‐MP). MH was combined with serial dilutions of nitrite. NO release was evaluated using a NO analyzer. The susceptibility of 2 strains of Pseudomonas aeruginosa biofilms to these NO‐releasing platforms was evaluated using confocal microscopy. Cell viability and biofilm volume were quantified. Statistical analysis was performed using the Mann‐Whitney U test with SPSS software.

Results

MH with nitrite generated a linear increase in NO formation. SNO‐MP induced a bolus release of NO within 5 minutes, followed by a sustained plateau phase. MH with nitrite combined with SNO‐MP enhanced NO release during the plateau phase. MH with nitrite reduced biofilm live cells and volume by 88.5% to 96.9% and 95.1% to 95.6%, respectively, vs control (p < 0.0001). SNO‐MP reduced live cells and volume by 61.0% to 98.5% and 74.7% to 85.7%, respectively, vs control (p < 0.0001). MH with nitrite combined with SNO‐MP nearly eradicated biofilm, with a 98.3% to 99.8% (log 1.8‐2.6) reduction in viability and a 91.4% to 97.7% decrease in volume (p < 0.0001 vs control).

Conclusion

A novel platform that generates NO using MH and nitrite produces a potent anti‐biofilm effect, which can be further enhanced with the addition of SNO‐MP.
Synthesis of Arylidene – Isoquinolinones bearing Combretastatin Skeleton by Cyclocarbopalladation/cross coupling Tandem Heck‐Suzuki Miaura Reactions using nano catalyst Pd@Py‐IL‐SPION
Authors: Asgari Mohammad Sadegh , Rashidi Ranjbar Parviz , Rahimi Rahmatollah , Mahdavi Mohammad
Published: December 2019

Cyclocarbopalladation/cross‐coupling cascade intramolecular Heck–Suzuki–Miyaura reactions is applied for the first time by palladium immobilized on pyridine‐imidazolium ionic liquid supported magnetic iron oxide nanoparticle catalyst (denoted Pd@Py‐IL‐SPION) for the last step to synthesize trisubstituted arylidene–isoquinolinones derivatives having Combretastatin skeleton. The reaction is performedviapropargylamide intermediates prepared by Ugi 4‐CR reactions, which undergoes intramolecular Heck–Suzuki–Miyaura domino reaction to produce the desired trisubstituted arylidene‐isoquinolinones. The method shows full regio‐ and stereoselectivity derives from the particular Pd‐catalyzedsyn‐insertion of triple bond.
Application of new Ru (II) pyridine‐based complexes in the partial oxidation of n‐octane
Authors: Chanerika Revana , Friedrich Holger B. , Shozi Mzamo L.
Published: December 2019

Tridentate and bidentate Ru (II) complexes were prepared through reaction of four pyridine‐based ligands: pyCH2N(R)CH2py {R = propyl, tert‐butyl, cyclohexyl and phenyl; py = pyridine} with the [(η6‐C6H6)Ru(μ‐Cl)Cl]2 dimer. Crystal structures of the new terdentate Ru (II) complexes [Ru{pyCH2N(R)CH2py}C6H6](PF6)2 (R = C3H7 (1), C (CH3)3 (2), C6H11 (3) and the bidentate Ru (II) complex [Ru{pyCH2N(R)}C6H6]PF6 (R = C6H5 (4)) are reported. It was found that complexes 1, 2, 3 and 4 crystallised as mono‐metallic species, with a piano stool geometry around each Ru centre. All complexes were active in the selective oxidation of n‐octane using t‐BuOOH and H2O2 as oxidants. Complexes 2 and 4 reached a product yield of 12% with t‐BuOOH as oxidant, however, superior yields (23–32%) were achieved using H2O2 over all systems. The selectivity was predominantly towards alcohols (particularly 2‐octanol) over all complexes using t‐BuOOH and H2O2 after reduction of the formed alkylhydroperoxides in solution by PPh3. High TONs of up to 2400 were achieved over the Ru/H2O2 systems.
Nuclear Magnetic Resonance Spectroscopy: A Versatile Tool for Qualitative and Quantitative Analysis of an Emulsifier Mixture of Soybean Oil
Authors: Vafaei Nazanin , Marat Kirk , Eskin Michael N. A. , Rempel Curtis B. , Jones Peter J. H. , Scanlon Martin G.
Published: December 2019

Finding a fast, reliable, and reproducible approach for an accurate analysis of complex lipid mixtures of emulsifiers is crucial for the food and beverages, pharmaceuticals, personal care products, cosmetics, and agrochemicals industries. In the current study, a comprehensive qualitative and quantitative nuclear magnetic resonance (NMR) spectroscopy analysis of a high monoester mixture of soybean oil (HMMS) was conducted using1H,13C, and31P NMR of 2‐chloro‐4,4,5,5‐tetramethyl‐1,3,2‐dioxaphospholane (CTDP) derivatives. The HMMS was produced by enzymatic alcoholysis of soybean oil and 1.2‐propanediol in a supercritical CO2system. Compositional distribution analysis, quantified by aliphatic carbons with13C NMR, showed that HMMS is composed of more unsaturated fatty acids, comprised of polyunsaturated fatty acids (PUFA) (60 ± 1.1%) and monounsaturated fatty acids (MUFA) (22 ± 0.8%), than saturated fatty acids (18 ± 0.9%). The31P NMR quantification of HMMS demonstrated that, out of the total amount of monoacylglycerols (MAG), they are composed of 21 ± 2.9% of 2‐MAG and 4 ± 0.3% of 1‐MAG. Among the three techniques,31P NMR spectroscopy proved to be a practical methodology with high reproducibility for the precise detection and quantification of partially esterified glycerols and free fatty acids in complex lipid mixtures.
Comparison of computational fluid dynamics–discrete element method and discrete element method simulations for a screw conveyor
Authors: Wang Shuyan , Ji Yu , Wang Shuqing , Chen Yujia , Tian Ruichao , Ma Yimei , Sun Qiji
Published: December 2019

Flow behavior of particles is simulated by means of discrete element method (DEM) in a screw conveyor. The gas flow is considered by the Euler model. The subgrid scale model turbulence model is applied to solve gas turbulence. A detailed description of the model equations applied has been presented. The comparison between computational fluid dynamics (CFD)‐DEM (i.e., considering gas flow) and DEM (i.e., not considering gas flow) simulation results is performed. Predicted mass flow rate with CFD‐DEM model is in better agreement with experiments by Roberts and Wills comparing with DEM results. The effects of incline angle and filling rate on the flow behavior of particles are predicted. The simulation results show that the gas flow has a major impact on particle flow behavior at a high rotation speed, whereas the velocity of particles increases with an increase of rotation speed. As the filling rate rises, both the translational granular temperature and the rotational granular particle temperature decline, which means that the particles fluctuation turns weak. While with an increase of incline angle, from the horizontal to vertical, the translational granular temperature is increased, but the rotational granular temperature reduces and then goes up. In brief, translational motion is a main mode of motion in a screw conveyor.
RhIII‐Catalyzed Synthesis of Highly Substituted 2‐Pyridones using Fluorinated Diazomalonate
Authors: Das Debapratim , Sahoo Gopal , Biswas Aniruddha , Samanta Rajarshi
Published: December 2019

A RhIII‐catalyzed strategy was developed for the rapid construction of highly substituted 2‐pyridone scaffolds using α,β‐unsaturated oximes and fluorinated diazomalonate. The reaction proceeds through direct, site‐selective alkylation based on migratory insertion and subsequent cyclocondensation. A wide substrate scope with different functional groups was explored. The requirement of fluorinated diazomalonate was explored for this transformation. The developed methodology was further extended with the synthesis of the bioactive compound.
Observer‐based adaptive DSC with nonlinear gain and recursive sliding mode for non‐affine nonlinear systems
Authors: Yang Yang , Meng Qing , Yue Dong , Ge Hui , Hou Xiaolei
Published: December 2019

The output feedback control issue is addressed for a class of non‐affine nonlinear systems in this paper. In the situation that the internal states of the system are not available, we design a neural network (NN) observer and employ NNs to compensate unknown dynamics in real time. Considering the error and dynamic performance of each subsystem, we introduce the recursive sliding‐mode dynamic surface method and nonlinear gain function into the output feedback control strategy. The proposed strategy not only enhances the range of control parameters but also makes a compromise between the control accuracy and dynamic performance. The boundedness of the closed‐loop signals is proven by the Lyapunov theory. Finally, the simulation results verify the validity of the control strategy.
An evaluation of estimation data collection to trial‐by trial data collection during discrete trial teaching
Authors: Ferguson Julia L. , Milne Christine M. , Cihon Joseph H. , Dotson Anna , Leaf Justin B. , McEachin John , Leaf Ronald
Published: December 2019

There are many data collection procedures used during discrete trial teaching including first‐trial data collection, probe data, trial‐by‐trial data collection, and estimation data. Continuous, or trial‐by‐trial data collection, consists of the interventionist collecting data on learner behavior on each trial. Estimation data consists of the interventionist estimating learner performance after a teaching session using a rating scale. The purpose of the present study was to compare trial‐by‐trial data collection to estimation data collection during discrete trial teaching to teach children expressive labels. The data collection procedures were examined in terms of accuracy of data collection, efficiency of teaching (i.e., number of trials delivered per session), and rate of child acquisition of targets. Results of the adapted alternating treatment design replicated across three participants and multiple targets found estimation data collection to be as accurate as trial‐by‐trial data collection in determining mastery of targets. Estimation data collected by the interventionist was also found to be accurate when compared to the actual trial‐by‐trial data collected after the study concluded.
Involvement of Yes‐associated protein 1 (YAP1) in doxorubicin‐induced cytotoxicity in H9c2 cardiac cells
Authors: Takaguri Akira , Akihiro Ohmiya , Sasano Jun , Satoh Kumi
Published: December 2019

Cardiac cell death is one of the major events implicated in doxorubicin‐induced cardiotoxicity, which leads to heart failure. We recently reported that Yes‐associated protein 1 (YAP1) regulates cell survival and apoptosis. However, it is unclear whether YAP1 regulates doxorubicin‐induced cell death in cardiomyocytes. We investigated whether YAP1 is involved in doxorubicin‐induced cell death using H9c2 cardiac cells and mouse heart. In an in vivo study, YAP1 protein expression was significantly decreased in hearts of doxorubicin‐treated mice with increased caspase‐3 activation. Doxorubicin also caused cell death by increasing caspase‐3 activation in H9c2 cells. Doxorubicin reduced YAP1 protein expression and messenger RNA expression accompanied by increased phosphorylation of YAP1 at Ser127. Doxorubicin further increased cell death with increased caspase‐3/7 activation in the absence of YAP1 when compared with doxorubicin or siYAP1 treatment alone. Overexpression of constitutively active YAP1 (YAP1–5SA) using an adenovirus gene transfer technique significantly reversed doxorubicin‐induced cell death by decreasing caspase‐3/7 activation in H9c2 cells. Akt, a potential prosurvival factor, decreased in doxorubicin‐ and YAP1 short interfering RNA (siRNA)‐treated cells. Doxorubicin further significantly decreased Akt protein expression when YAP1 was silenced. Overexpression of YAP1 canceled decreased Akt protein expression induced by doxorubicin treatment in H9c2 cells. In conclusion, these results suggest that doxorubicin‐induced cardiac cell death is mediated in part by down‐regulation of YAP1 and YAP1‐targeted gene, Akt. Modulating YAP1 and its related Hippo pathway on local cardiomyocytes may be a promising therapeutic approach for doxorubicin‐induced cardiotoxicity.
Hierarchical Porous Carbon Anode Materials Derived from Rice Husks with High Capacity and Long Cycling Stability for Sodium‐Ion Batteries
Authors: Nie Wei , Liu Xiaolin , Xiao Qingmei , Li Liuxin , Chen Guoxin , Li Dong , Zeng Min , Zhong Shengwen
Published: December 2019

Compared with the cathode materials, the research on the anode materials of the sodium‐ion batteries has lagged behind. Therefore, development of the anode materials with high capacity, long life, and excellent rate properties is the key to unlocking the practical application for sodium‐ion batteries. This study presents the preparation of hierarchical porous hard carbon as an active anode material from rice husks. The as‐synthesized materials are characterized by X‐ray diffraction, N2 adsorption, Raman spectra, scanning electron microscopy and transmission electron microscopy. These porous hard carbon materials exhibit a high specific surface area and are promising for reversible sodium storage. Galvanostatic studies show that the specific initial capacities of all samples were in the range of 130–300 mA h g−1 at a current density of 100 mA g−1 between 0.01 V and 2.3 V. Compared to the other samples, the hard carbon materials prepared at 800 °C from rice husk (RHPC‐800) can deliver a high reversible capacity of 274 mA h g−1 at a current density of 25 mA g−1, maintain a capacity of approximately 260 mA h g−1, and retain 92.7 % of its capacity after 500 cycles. This excellent electrochemical performance of the as‐prepared RHPC‐800 material is attributed to the high specific surface area and low charge transfer resistance.
Electrolyte Engineering as a Key Strategy Towards a Sustainable Energy Scenario?
Authors: Exner Kai S.
Published: December 2019

Major challenges still need to be resolved on the way towards a sustainable energy scenario. A future vision comprises the development of electrocatalysts, refraining from using scarce noble metals, for electrocatalytic key processes, such as hydrogen and oxygen evolution and reduction reactions or CO2 reduction. Hitherto, the focus was set on the investigation of electrode materials, whereas only little emphasis was put on the electrolyte solution. Recently, it was reported that, under non‐acidic pH conditions, the composition of the electrolyte solution has a non‐negligible effect on the activity of electrocatalytic processes: this outcome puts forth the idea of electrolyte engineering, a promising strategy that, besides the study of enhanced electrode materials, should be put in the focus of future research investigations in electrocatalysis.
Transapical mitral valve repair with neochordae implantation: FSI analysis of neochordae number and complexity of leaflet prolapse
Authors: Caballero Andrés , Mao Wenbin , McKay Raymond , Sun Wei
Published: December 2019

Transapical mitral valve repair with neochordae implantation is a relatively new minimally invasive technique to treat primary mitral regurgitation. Quantifying the complex biomechanical interaction and interdependence between the left heart structures and the neochordae during this procedure is technically challenging. The aim of this parametric computational study is to investigate the immediate effects of neochordae number and complexity of leaflet prolapse on restoring physiologic left heart dynamics after optimal transapical neochordae repair procedures. Neochordae implantation using three and four sutures was modeled under three clinically relevant prolapse conditions: isolated P2, multi‐scallop P2/P3, and multi‐scallop P2/P1. A fluid‐structure interaction (FSI) modeling framework was used to evaluate the left heart dynamics under baseline, prerepair, and postrepair states. Despite immediate restoration of leaflet coaptation and no residual mitral regurgitation in all postrepair models, the average and peak stresses in the repaired scallop(s) increased >40% and >100%, respectively, compared with the baseline state. Additionally, anterior mitral leaflet marginal chordae tension increased >30%, while posterior mitral leaflet chordae tension decreased at least 30%. No marked differences in hemodynamic performance, in native and neochordae forces, and in leaflet stress were found when implanting three or four sutures. We report, to our knowledge, the first set of time‐dependent in silico FSI human neochordae tension measurements during transapical neochordae repair. This work represents a further step towards an improved understanding of the biomechanical outcomes of minimally invasive mitral valve repair procedures.
Pharmacokinetics and Safety of a Single Oral Dose of Peficitinib (ASP015K) in Japanese Subjects With Normal and Impaired Hepatic Function
Authors: Miyatake Daisuke , Shibata Tomohisa , Toyoshima Junko , Kaneko Yuichiro , Oda Kazuo , Nishimura Tetsuya , Katashima Masataka , Sakaki Masashi , Inoue Kazuaki , Ito Takayoshi , Uchida Naoki , Furihata Kenichi , Urae Akinori
Published: December 2019

Peficitinib (ASP015K) is a novel Janus kinase inhibitor developed for the treatment of rheumatoid arthritis (RA). The impact of hepatic impairment on the peficitinib pharmacokinetic (PK) and safety profile was investigated in non‐RA subjects (n = 24) in an open‐label, parallel‐group, multicenter comparative study in Japan. Subjects received a single, clinically relevant, oral dose of a peficitinib 150 mg tablet under fasting conditions. Plasma PK parameters were measured for peficitinib and its metabolites H1 (sulfate and methylated metabolite), H2 (sulfate metabolite), and H4 (methylated metabolite) in subjects with normal hepatic function, mild hepatic impairment, or moderate hepatic impairment. The peficitinib area under the plasma‐concentration–time curve from time 0 to infinity (AUCinf) and maximum observed concentration (Cmax) were not markedly different in subjects with mild hepatic impairment versus normal hepatic function. In subjects with moderate hepatic impairment versus normal hepatic function, the geometric mean ratios for peficitinib AUCinf and Cmax, were 1.92 (90% CI: 1.39, 2.66) and 1.82 (90% CI: 1.24, 2.69), respectively. Five treatment‐emergent adverse events (TEAEs) were experienced by 3 subjects, 1 in each group. There were no deaths, no serious TEAEs, and no TEAEs leading to withdrawal. In summary, the PK profile was unaltered in subjects with mild hepatic impairment after a single clinically relevant dose of peficitinib, but exposure almost doubled in subjects with moderate hepatic impairment. Peficitinib dose reduction may be considered in RA patients with moderate hepatic impairment.
Altered peripheral nerve structure and function in latent autoimmune diabetes in adults
Authors: Issar Tushar , Yan Aimy , Kwai Natalie C. G. , Poynten Ann M. , Borire Adeniyi A. , Arnold Ria , Krishnan Arun V.
Published: December 2019

Aim

The present study was undertaken to investigate mechanisms of peripheral nerve dysfunction in latent autoimmune diabetes in adults (LADA).

Materials and methods

Participants with LADA (n = 15) underwent median nerve ultrasonography and nerve excitability to examine axonal structure and function, in comparison to cohorts of type 1 diabetes (n = 15), type 2 diabetes (n = 23) and healthy controls (n = 26). The LADA group was matched for diabetes duration, glycaemic control, and neuropathy severity with the type 1 and type 2 diabetes groups. A validated mathematical model of the human axon was utilized to investigate the pathophysiological basis of nerve dysfunction.

Results

The most severe changes in nerve structure and function were noted in the LADA group. The LADA cohort demonstrated a significant increase in nerve cross‐sectional area compared to type 1 participants and controls. Compared to type 1 and 2 diabetes, measures of threshold electrotonus, which assesses nodal and internodal conductances, were significantly worse in LADA in response to both depolarising currents and hyperpolarising currents. In the recovery cycle, participants with LADA had a significant increase in the relative refractory period. Mathematical modelling of excitability recordings indicated the basis of nerve dysfunction in LADA was different to type 1 and 2 diabetes.

Conclusions

Participants with LADA exhibited more severe changes in nerve function and different underlying pathophysiological mechanisms compared to participants with type 1 or 2 diabetes. Intensive management of risk factors to delay the progression of neuropathy in LADA may be required.
The evolution of crocodilian nesting ecology and behavior
Authors: Murray Christopher M. , Crother Brian I. , Doody J. Sean
Published: December 2019

Crocodilians comprise an ancient and successful lineage of archosaurs that repeatedly raises questions on how they survived a mass extinction and remained relatively unchanged for ~100 million years. Was their success due to the change‐resistant retention of a specific set of traits over time (phylogenetic conservatism) or due to flexible, generalist capabilities (e.g., catholic diets, phenotypic plasticity in behavior), or some combination of these? We examined the evolution of reproductive ecology and behavior of crocodilians within a phylogenetic perspective, using 14 traits for all 24 species to determine whether these traits were phylogenetically constrained versus (ecologically) convergent. Our analysis revealed that the ancestral crocodilian was a mound nester that exhibited both nest attendance and defense. Nesting mode exhibited 4–5 transformations from mound to hole nesting, a convergence of which habitat may have been a driving factor. Hole nesters were more likely to nest communally, but this association may be biased by scale. Although there were exceptions, mound nesters typically nested during the wet season and hole nesters during the dry season; this trait was relatively conserved, however. About two‐thirds of species timed their nesting with the wet season, while the other third timed their hatching with the onset of the wet season. Nest attendance and defense were nearly ubiquitous and thus exhibited phylogenetic conservatism, but attendance lodging was diverse among species, showing multiple reversals between water and burrows. Collectively, our analysis reveals that reproductive trait evolution in crocodilians reflects phylogenetic constraint (nest attendance, nest defense), ecological convergence (seasonal timing of nesting, nest attendance lodging), or both (mode of nesting). Some traits (e.g., communal nesting and mode of nesting) were autocorrelated. Our analysis provides a framework for addressing hypotheses raised for why there has been trait convergence in reproductive ecology and behavior in crocodilians and why some traits remained phylogenetically conserved.
Prey density affects predator foraging strategy in an Antarctic ecosystem
Authors: Busdieker Karl M. , Patrick Samantha C. , Trevail Alice M. , Descamps Sébastien
Published: December 2019

Studying the effects of prey distribution on predator behavior is complex in systems where there are multiple prey species. The role of prey density in predator behavior is rarely studied in closed ecosystems of one predator species and one prey species, despite these being an ideal opportunity to test these hypotheses. In this study, we investigate the effect of prey density on the foraging behavior of a predatory species in an isolated Antarctic ecosystem of effectively a single predatory species and a single prey species. We use resource selection models to compare prey density in areas utilized by predators (obtained from fine‐scale GPS telemetry data) to prey density at randomly generated points (pseudoabsences) throughout the available area. We demonstrate that prey density of breeding Antarctic petrels (Thalassoica antarctica) is negatively associated with the probability of habitat use in its only predator, the south polar skua (Catharacta maccormicki). Skuas are less likely to utilize habitats with higher petrel densities, reducing predation in these areas, but these effects are present during chick rearing only and not during incubation. We suggest that this might be caused by successful group defense strategies employed by petrel chicks, primarily spitting oil at predators.
Difficulties in benchmarking ecological null models: an assessment of current methods
Authors: Molina Chai , Stone Lewi
Published: December 2019

Identifying species interactions and detecting when ecological communities are structured by them is an important problem in ecology and biogeography. Ecologists have developed specialized statistical hypothesis tests to detect patterns indicative of community‐wide processes in their field data. In this respect, null model approaches have proved particularly popular. The freedom allowed in choosing the null model and statistic to construct a hypothesis test leads to a proliferation of possible hypothesis tests from which ecologists can choose to detect these processes. Here, we point out some serious shortcomings of a popular approach to choosing the best hypothesis for the ecological problem at hand that involves benchmarking different hypothesis tests by assessing their performance on artificially constructed data sets. Terminological errors concerning the use of Type I and Type II errors that underlie these approaches are discussed. We argue that the key benchmarking methods proposed in the literature are not a sound guide for selecting null hypothesis tests, and further, that there is no simple way to benchmark null hypothesis tests. Surprisingly, the basic problems identified here do not appear to have been addressed previously, and these methods are still being used to develop and test new null models and summary statistics, from quantifying community structure (e.g., nestedness and modularity) to analyzing ecological networks.
Chlorotropylium Promoted Conversions of Oximes to Amides and Nitriles
Authors: Xu Jiaxi , Gao Yu , Li Zhenjiang , Liu Jingjing , Guo Tianfo , Zhang Lei , Wang Haixin , Zhang Zhihao , Guo Kai
Published: December 2019

Chlorotropylium chloride as a catalyst for the transformations of oximes, ketones, and aldehydes to their corresponding amides and nitriles in excellent yields (up to 99 %) and in short reaction times (mostly 10–15 min). Oximes were electrophilically attacked on the hydroxyl oxygen by chlorotropylium. The produced tropylium oxime ethers were the key intermediates, of which the ketoxime ether led to amide through Beckmann rearrangement, and the aldoxime ether led to nitrile by nitrogen base DBU assisted formal dehydration. This chlorotropylium activation protocol offered general, mild, and efficient avenues bifurcately from oximes to both amides and nitriles by one organocatalyst.
Pactamycin and Its Derivatives: Improved Synthesis Route
Authors: Ohmi Kohki , Miura Yusuke , Nakao Yuta , Goto Atsumi , Yoshimura Satoshi , Ouchi Hitoshi , Inai Makoto , Asakawa Tomohiro , Yoshimura Fumihiko , Kondo Mitsuru , Kan Toshiyuki
Published: December 2019

Stereoselective construction of the cyclopentane core 21 of pactamycin (1) was achieved from symmetric cyclohexadiene 7. Our synthetic strategy features catalytic Rh‐mediated desymmetric aziridination of the cyclohexadiene derivative, selective ring‐opening reaction at the C2 position of sulfonylaziridine with NaN3, ring‐contraction of cyclohexene 9 by ozonolysis followed by intramolecular aldol reaction via enamine intermediate 11, and construction of the two consecutive tetra‐substituted carbon centers by stereoselective epoxidation of the exo‐methylene moiety of 14c with DMDO, followed by methylation reaction. Introduction of the urea unit on tetra‐substituted carbon of 16 was achieved by amidation and subsequent Hofmann rearrangement.
A parsimonious approach to delineating groundwater potential zones using geospatial modeling and multicriteria decision analysis techniques under limited data availability condition
Authors: Kumar Sanjay , Machiwal Deepesh , Parmar Babu S
Published: December 2019

This study delineates groundwater potential zones by following an “equifinality” approach and adopting a standard methodology using remote sensing, geospatial modeling, geographic information system (GIS) and multicriteria decision analysis (MCDA) techniques. A total of 11 thematic layers (ie, rainfall, topographic elevation, slope, slope length, slope steepness, soil, geomorphology, geology, drainage density, and pre‐ and post‐monsoon groundwater levels) which have an influence on the occurrence of the groundwater are developed. The suitable weights to themes and their features are assigned and then normalized by using an analytic hierarchy process (AHP)—MCDA technique. All themes are integrated in GIS for generating a groundwater potential index (GPI) map, which classifies the study area into three zones of “good” (588.5 km2, 34.1%), “moderate” (933.4 km2, 54.1%), and “poor” (203.3 km2, 11.8%) groundwater potential. Furthermore, the accuracy of the developed GPI map is verified from the coherent estimates of rainfall‐recharge. Unlike earlier studies, this study further evaluates relative sensitivity of the themes, and develops a novel “parsimonious” groundwater potential index (PGPI). The PGPI is a cost‐effective and time‐efficient method that excludes redundant parameters from the analysis and employs only the most sensitive themes in assessing groundwater potential. The results of both GPI and PGPI are found in good harmony over 86.7% area, which confirms the efficacy of the developed PGPI. The results of this study may be of interest to planners and policymakers as a guideline for locating appropriate groundwater development sites and managing sustainable water supplies, especially under data scarcity conditions and/or in developing countries.
Development of a Triton X‐100 replacement for effective virus inactivation in biotechnology processes
Authors: Farcet Jean‐Baptiste , Kindermann Johanna , Karbiener Michael , Kreil Thomas R.
Published: December 2019

After the transmission of human viruses through plasma derivatives had been recognized in the early 1980s, virus inactivation and then removal steps have been implemented into their manufacturing processes. These measures have kept plasma derivatives safe ever since and have also served as a barrier against more recently emerging viruses. Given the success of these interventions, they have also been embedded into the manufacturing processes for cell‐derived biological medicinal products. The most effective inactivation process for lipid‐enveloped viruses is treatment by detergents or combinations of solvents and detergents, and thus, these processes have been almost universally adopted. One of the most widely used detergents, Triton X‐100, has recently raised environmental concerns because one of its degradation products possesses hormone‐like (estrogen‐mimetic) activity that may act on wildlife. Consequently, use of the chemical in the European Union will ultimately be prohibited. The current study was conducted to establish an environmentally friendly detergent alternative to Triton X‐100 with fully equivalent efficacy in biotechnological use. A newly synthesized compound, named Nereid, as well as Triton X‐100 reduced, seem to satisfy these requirements, and thus may be suitable replacements for Triton X‐100.
Development of collapse‐consistent loading protocols for experimental testing of steel columns
Authors: Suzuki Yusuke , Lignos Dimitrios G.
Published: December 2019

In order to effectively utilize results from quasi‐static cyclic testing on structural components for the earthquake‐induced collapse risk quantification of structures, the need exists to establish collapse‐consistent loading protocols representing the asymmetric lateral drift demands of structures under low‐probability of occurrence earthquakes. This paper summarizes the development of such protocols for experimental testing of steel columns prone to inelastic local buckling. The protocols are fully defined with a deformation‐ and a force‐controlled parameter. They are generally applicable to quantify the capacity and demands of steel columns experiencing constant and variable axial load coupled with lateral drift demands. Through rigorous nonlinear earthquake collapse simulations, it is found that the building height, the column's local slenderness ratio, and ground motion type have the largest influence on the dual‐parameter loading protocol indexes. Comprehensive comparisons with measured data from full‐scale shake table collapse tests suggest that unlike routinely used symmetric cyclic loading histories, the proposed loading protocol provides sufficient information for modeling strength and stiffness deterioration in steel columns at large inelastic deformations.
Ambient vibration tools to validate the rigid diaphragm assumption in the seismic assessment of buildings
Authors: Sivori Daniele , Lepidi Marco , Cattari Serena
Published: December 2019

Vibration tests are encountering a growing success in earthquake engineering as a valuable tool for the seismic assessment of buildings. Ambient vibration measurements, in particular, offer reliable support for the updating of mechanical models, as well as the enhancement of seismic mitigation strategies for existing buildings. In this respect, the common description of the floor diaphragms as planar rigid bodies tends to oversimplify the actual mechanical behaviour of some traditional structural solutions, especially in masonry buildings. This assumption can be violated even in modern concrete and steel buildings due to inadequate design, poor manufacturing, or damage. The paper addresses the mathematical validation of the rigid diaphragm simplification using vibration measurements. To this purpose, a model‐based inverse kinematic problem is stated and solved to discriminate the in‐plane rigid motion and the angular deformation time histories from vibration data. Simple formulas, leveraging the approximate solution in the case of problem under‐determinacy, exploit the spectral content of vibration data to discuss the diaphragm deformability. Natural modes exhibiting different (rigid, quasi‐rigid, or nonrigid) diaphragm behaviour are distinguishable by comparing the power spectral densities of the rigid motion and angular deformation. Modes of pure floor deformability can also be identified. The influence of adverse testing conditions is discussed through pseudo‐experimental data simulating the dynamic response of a simple frame structure. As a complementary contribution, the procedure effectiveness is experimentally verified by analysing vibration data related to, first, laboratory tests on a scaled concrete‐steel frame and, finally, full‐scale tests on a masonry building.
Characteristics and clinical trajectories of patients meeting criteria for avoidant/restrictive food intake disorder that are subsequently reclassified as anorexia nervosa
Authors: Norris Mark L. , Santos Alexandre , Obeid Nicole , Hammond Nicole G. , Valois Darcie D. , Isserlin Leanna , Spettigue Wendy
Published: December 2019

Objective

To examine the initial assessment profiles and early treatment trajectories of youth meeting the criteria for avoidant/restrictive food intake disorder (ARFID) that were subsequently reclassified as anorexia nervosa (AN).

Method

A retrospective cohort study of patients assessed and treated in a tertiary care eating disorders (ED) program was completed.

Results

Of the 77 included patients initially meeting criteria for ARFID, six were reclassified as having AN (7.8%) at a median rate of 71 days after the first assessment. Patients in this cohort presented at very low % treatment goal weight (median 71.6%), self‐reported abbreviated length of illness (median 6 months), and exhibited low resting heart rates (median 46 beats per minute). Nutrition and feeding focused worries related more to general health as opposed to specific weight and shape concerns or fears at assessment in half of those reclassified with AN. Treatment at the 6‐month mark varied among patients, but comprised family and individual therapy, as well as prescription of psychotropic medication.

Conclusion

Prospective longitudinal research that utilizes ARFID‐specific as well as traditional eating disorder diagnostic measures is required to better understand how patients with restrictive eating disorders that deny fear of weight gain can be differentiated and best treated.
State‐space models for predicting IBNR reserve in row‐wise ordered runoff triangles: Calendar year IBNR reserves & tail effects
Authors: Costa Leonardo , Pizzinga Adrian
Published: December 2019

The issue of modeling and forecasting IBNR (incurred but not reported) actuarial reserve under Kalman filter techniques and extensions, using data arranged in a runoff triangle, is a frequent theme in the literature. One quite recent approach is to order the runoff triangle under a row‐wise fashion and use linear state‐space models for the resulting data set. To allow new possibilities for short‐term IBNR reserves as well as to mitigate insolvency risk, in this paper we extend such a state‐space method by: (i) a calendar year IBNR reserve prediction; and (ii) a tail effect for the row‐wise ordered triangle. The extension is implemented with a real runoff triangle and compared with some traditional IBNR predictors. Empirical results indicate that the approach of this paper outperforms the competing methods in terms of out‐of‐sample comparisons and gives more conservative IBNR reserves than the original state‐space method.
Forecasting of dependence, market, and investment risks of a global index portfolio
Authors: Arreola Hernandez Jose , Al Janabi Mazin A.M.
Published: December 2019

This paper undertakes an in‐sample and rolling‐window comparative analysis of dependence, market, and portfolio investment risks on a 10‐year global index portfolio of developed, emerging, and commodity markets. We draw our empirical results by fitting vine copulas (e.g., r‐vines, c‐vines, d‐vines), IGARCH(1,1) RiskMetrics value‐at‐risk (VaR), and portfolio optimization methods based on risk measures such as the variance, conditional value‐at‐risk, conditional drawdown‐at‐risk, minimizing regret (Minimax), and mean absolute deviation. The empirical results indicate that all international indices tend to correlate strongly in the negative tail of the return distribution; however, emerging markets, relative to developed and commodity markets, exhibit greater dependence, market, and portfolio investment risks. The portfolio optimization shows a clear preference towards the gold commodity for investment, while Japan and Canada are found to have the highest and lowest market risk, respectively. The vine copula analysis identifies symmetry in the dependence dynamics of the global index portfolio modeled. Large VaR diversification benefits are produced at the 95% and 99% confidence levels by the modeled international index portfolio. The empirical results may appeal to international portfolio investors and risk managers for advanced portfolio management, hedging, and risk forecasting.
Quaternary landform study in Kosi and Dabka river valleys in Kumaun sub‐Himalaya: Implication of reactivation of thrusts
Authors: Luirei Khayingshing , Bhakuni Surendra S. , Longkumer Limasanen , Joshi Lalit Mohan , Kothyari Girish C.
Published: December 2019

Landforms developed along the Main Boundary Thrust (MBT) and Himalayan Frontal Thrust (HFT) zones in Ramnagar area of Kumaun sub‐Himalaya are studied. The geomorphic analyses suggest their spatial and temporal relationship with the reactivation of the boundary thrusts, faults, and associated later developed transverse faults. Mapping of geomorphic features and structural analysis of the MBT and HFT established an intimate relationship between thrusting of rocks along these major thrusts and evolution of landforms. The reactivations of the MBT and HFT have resulted in recent rejuvenation of landscapes formed in the thrust zones. In the MBT zone, the swerving of the channels, linear development of elongated depressions, sudden topographic breaks, and presence of relatively fresh‐looking escarpments, uplifted present ground surfaces, V‐shaped valleys, and occurrence of linear series of dormant and active landslides are observed. Along the Kosi River section, the vertical‐dipping Neoproterozoic Lesser Himalayan rocks have overridden the recent landslide debris along the subsidiary steep reverse faults associated with the MBT. The HFT is topographically represented by an escarpment trending ESE‐WNW along the Himalayan mountain front. In the HFT zone particularly at Ramnagar area, four levels of terraces are noted, the highest being a strath terrace. The surface trace of the HFT is offset by a transverse N‐S trending Ramnagar Fault, which coincides with the course along which Kosi Rver flows. Uplift of the hanging wall block near the HFT has resulted in subsidence of the present ground surface towards the northeast away from the HFT trace. During this process, the transverse streams have vigorously incised the uplifted surfaces. Rivers and streams realigning with the bedrock structure suggest tectonic control on morphology of drainage patterns. Neotectonic activity along the intra‐Siwalik thrust has offset a terrace surface into two surfaces that are separated by a fault scarp of about 50 m high. The bedrocks in the HFT region are gentle to steep dipping towards NW/NE/ESE. Both normal and reverse faults are recognized in the bedrocks. The general trend of the lineaments, which are concentrated in the thrust zones, is E‐W. Two transverse faults trending nearly N‐S cut and offset the HFT. Tectonic activity during the deposition of the Upper Siwalik rocks is evident from the occurrence of liquefaction features. Soft‐sediment deformation structures are observed in fine‐ to medium‐grained friable sandstones. These include up‐welled structures (with vertical to inclined bedding planes), sand dykes, faults (reverse and normal), folds, pseudo‐nodules, and deformed laminations.
Alterations in genetic pathways following radiotherapy for head and neck cancer
Authors: Naghavi Arash O. , Kim Youngchul , Yang George Q. , Ahmed Kamran A. , Caudell Jimmy J.
Published: December 2019

Background

Radiotherapy (RT) is an integral component in the treatment of head and neck cancer (HNC).We hypothesized there would be alterations in gene‐expression and pathway activity in HNC samples obtained in recurrent HNC that were previously treated with RT, when compared to RT‐naïve disease.

Methods

Patient data was abstracted from a prospectively maintained database. Linear‐microarray analysis and supervised gene‐set enrichment‐analysis were employed to compare RT‐naive and recurrent disease after prior‐RT.

Results

A total of 157 patients were analyzed, 96 (61%) were RT‐naive and 61 (39%) had RT.After radiation, there was upregulation of genes associated with angiogenesis, protein‐translation‐machinery, cell‐cycle regulation, and growth factors, and downregulation associated with Myc activity, and hypoxic response (all P < .001).Previously irradiated HNC was associated with downregulation in 19/42 genes in the Wnt/B‐catenin‐pathway (P = .045)and 119/199 genes involved in the MYC target pathway (P = .024).

Conclusion

Patients with recurrences salvaged surgically post‐RT had significant alterations in gene‐expression and in Wnt/B‐catenin and MYC‐target pathways. These pathways may represent potential targets to prevent development of resistance to RT.
Variations in concerns reported on the patient concerns inventory in patients with head and neck cancer from different health settings across the world
Authors: Rogers Simon N. , Alvear Alvaro , Anesi Alexandre , Babin Emmanuel , Balik Ali , Batstone Martin , Brockmeyer Phillipp , Carrasco Claudia Celedon , Chien Chih‐Yen , Chirila Magdalena , Dholam Kanchan P. , Doss Jennifer G. , Finizia Caterina , Ghani Wan M. Nabilah , Gurav Sandeep V. , Kadir Kathreena , Kolator Mateusz , Lima Roberto , Lin Yu‐Tsai , Nhongo Simon , Ozdemir‐Karatas Meltem , Peker Kadriye , Pesic Zoran , Ransy Pierre , Santos Izabella , Schliephake Henning , Shah Ketan , Souza Fernanda , Sunil Geethu , Thankappan Krishnakumar , Ehrsson Ylva Tiblom , Tiple Cristina , Tuomi Lisa , Valerini Sara , Lara Pablo Vasquez , Zatoński Tomasz , Lowe Derek
Published: December 2019

Background

The aim was to collate and contrast patient concerns from a range of different head and neck cancer follow‐up clinics around the world. Also, we sought to explore the relationship, if any, between responses to the patient concerns inventory (PCI) and overall quality of life (QOL).

Methods

Nineteen units participated with intention of including 100 patients per site as close to a consecutive series as possible in order to minimize selection bias.

Results

There were 2136 patients with a median total number of PCI items selected of 5 (2‐10). “Fear of the cancer returning” (39%) and “dry mouth” (37%) were most common. Twenty‐five percent (524) reported less than good QOL.

Conclusion

There was considerable variation between units in the number of items selected and in overall QOL, even after allowing for case‐mix variables. There was a strong progressive association between the number of PCI items and QOL.
Onset of hypothyroidism after total laryngectomy: Effects of thyroid gland surgery and preoperative and postoperative radiotherapy
Authors: Plaat Robert E. , van Dijk Boukje A. C. , Muller Kobold Anneke C. , Steenbakkers Roel J. H. M. , Links Thera P. , van der Laan Bernard F. A. M. , Plaat Boudewijn E. C.
Published: December 2019

Background

To determine time of onset and risk of hypothyroidism after total laryngectomy (TL) with and without (hemi)thyroidectomy in relation to treatment regimen, that is, preoperative radiotherapy (RT‐TL), postoperative radiotherapy (TL‐RT), and postoperative re‐irradiation (RT‐TL‐RT).

Methods

Retrospective review of 128 patients treated by RT‐TL (51 patients), TL‐RT (55 patients), and RT‐TL‐RT (22 patients). Risk of hypothyroidism was determined by multivariable Cox regression analysis and euthyroid survival was calculated using Kaplan‐Meier method.

Results

Hypothyroidism developed in 69 (54%) patients. The median onset of hypothyroidism was later (P < .01) and the risk of hypothyroidism was lower (hazard ratio 0.49; P = .014) in the TL‐RT group compared to both other treatment regimens. Euthyroid survival did not differ between the treatment regimens. Two years euthyroid survival was 24% with and 61% without (hemi)thyroidectomy (P < .001).

Conclusions

Patients treated with TL‐RT have later onset of hypothyroidism. Higher risk for hypothyroidism is associated with salvage TL after radiotherapy and (hemi)thyroidectomy.
The Spectrum of Reactive Cholangiocytes in Primary Sclerosing Cholangitis
Authors: Guicciardi Maria Eugenia , Trussoni Christy E. , LaRusso Nicholas F. , Gores Gregory J.
Published: December 2019

Cholangiocytes are the target of a group of chronic liver diseases termed the “cholangiopathies,” in which cholangiocytes react to exogenous and endogenous insults, leading to disease initiation and progression. In primary sclerosing cholangitis (PSC), the focus of this review, the cholangiocyte response to genetic or environmental insults can lead to a heterogeneous response; that is, a subpopulation acquires a ductular reactive and proliferative phenotype, while another subpopulation undergoes senescence and growth arrest. Both ductular reactive cholangiocytes and senescent cholangiocytes can modify the periductal microenvironment through their ability to secrete various cytokines, chemokines, and growth factors, initiating and perpetuating inflammatory and profibrotic responses. This review discusses the similarities and differences, the interrelationships, and the potential pathogenic roles of these reactive proliferative and senescent cholangiocyte subpopulations in PSC.