bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure–property relationship study of the HPLC enantioselective retention of neuroprotective 7‐[(1‐alkylpiperidin‐3‐yl)methoxy]coumarin derivatives on an amylose‐based chiral stationary phase
Authors: Pisani Leonardo , Rullo Mariagrazia , Catto Marco , de Candia Modesto , Carrieri Antonio , Cellamare Saverio , Altomare Cosimo Damiano 
Published: February 2018

AbstractThe enantiomer separation of a number of racemic 7‐[(1‐alkylpiperidin‐3‐yl)methoxy]coumarin derivatives, some of which show outstanding in vitro multitarget neuroprotective activities, was successfully achieved on a polysaccharide‐based chiral stationary phase, bearing amylose tris(3,5‐dimethylphenylcarbamate) as a chiral selector, in normal polar mode (methanol and acetonitrile as the mobile phases). The majority of the screened selectands, especially those bearing 1‐(3‐X‐benzyl)piperidin‐3‐yl moieties, showed baseline enantiomer separations, and compound 8 (X = NO2) was the best resolved (α = 2.01; RS = 4.27). Linear free energy relationships, usefully complemented by molecular docking calculations, have the key role in enantioselective retention of aromatic interactions between π‐donor moieties in the chiral selector and π‐acceptor moieties in selectand, strengthened by hydrogen bond interaction between a hydrogen bond donor in the chiral selector and the hydrogen bond acceptor group(s) in the selectand. Statistically, reliable equations highlighted the importance of the substituent's size and substitution pattern (meta better than para) to affect the enantiorecognition of the title compounds. The chromatographic data support the scalability of the optimized experimental conditions for preparative purposes.
An Extended Group Additivity Method for Polycyclic Thermochemistry Estimation
Authors: Han Kehang , Jamal Adeel , Grambow Colin A. , Buras Zachary J. , Green William H. 
Published: February 2018

ABSTRACTAutomatic kinetic mechanism generation, virtual high‐throughput screening, and automatic transition state search are currently trending applications requiring exploration of a large molecule space. Large‐scale search requires fast and accurate estimation of molecules' properties of interest, such as thermochemistry. Existing approaches are not satisfactory for large polycyclic molecules: considering the number of molecules being screened, quantum chemistry (even cheap density functional theory methods) can be computationally expensive, and group additivity, though fast, is not sufficiently accurate. This paper provides a fast and moderately accurate alternative by proposing a polycyclic thermochemistry estimation method that extends the group additivity method with two additional algorithms: similarity match and bicyclic decomposition. It significantly reduces Hf(298 K) estimation error from over 60 kcal/mol (group additivity method) to around 5 kcal/mol, Cp(298 K) error from 9 to 1 cal/mol/K, and S(298 K) error from 70 to 7 cal/mol/K. This method also works well for heteroatomic polycyclics. A web application for estimating thermochemistry by this method is made available at http://rmg.mit.edu/molecule_search.
Solvophobic Acceleration of a Diels–Alder Reaction in True Solutions in Organic Solvents
Authors: Sedov Igor A. , Kornilov Dmitry A. , Kiselev Vladimir D. 
Published: February 2018

ABSTRACTThe rate of Diels–Alder reaction of diene 9,10‐bis(hydroxymethyl)anthracene with dienophile N‐ethylmaleimide was studied in a series of solvents with different polarity and hydrogen‐bonding ability. Enthalpies and entropies of activation were determined from the temperature dependences of the rate constants. Rate acceleration in nonaqueous protic solvents such as glycerol, propylene, and ethylene glycols was observed. In addition, enthalpy versus entropy of activation plots show a compensation pattern different from the other considered solvents, which can be linked with the solvophobic effects observed in polyhydric alcohols. However, the solvophobic acceleration was not as strong as the hydrophobic acceleration in water. Hydrogen bonding of the reactants and transition state with solvent also influences the reaction rate. The studied reaction is slightly promoted in hydrocarbon solvents in comparison with aprotic polar solvents. This was explained by hydrogen bonding of the hydroxyl groups of diene with dienophile in transition state, which requires prior breaking of the hydrogen bonds of these groups with polar solvent molecules.
Insights from Ion Binding Site Network Analysis into Evolution and Functions of Proteins
Authors: Škrlj Blaž , Kunej Tanja , Konc Janez 
Published: February 2018

AbstractMany biological phenomena can be represented as complex networks. Using a protein binding site comparison approach, we generated a network of ion binding sites on the scale of all known protein structures from the Protein Data Bank. We found that this ion binding site similarity network is scale‐free, indicating a network in which a few ion binding site scaffolds are the network hubs, and these are connected to hundreds of nodes, whereas the vast majority of nodes have only a few neighbors. Enrichment and statistical analysis of the network components and communities yielded insights into underlying processes from the functional and the structural perspective. Largest components and communities were observed to be closely related to basic metabolic processes and some of the most common structural folds, which, from the evolutionary point of view, indicates that they may be the oldest ones. Further, we derived the first comprehensive map of ion interchangeability, based on binding site similarity. Several highly interchangeable protein‐ion binding site pairs emerged (e.g., Ca2+ and Mg2+), as well as structurally distinct ones. The constructed network of ion binding site similarities will aid in understanding the general principles of protein‐ion binding sites structure, function and evolution. We demonstrate potential uses of the network on proteins involved in cancer development and immune response, where individual ions play prominent roles in disease development.
Technical Note: Kinect V2 surface filtering during gantry motion for radiotherapy applications
Authors: Nazir Souha , Rihana Sandy , Visvikis Dimitris , Fayad Hadi 
Published: February 2018

PurposeIn radiotherapy, the Kinect V2 camera, has recently received a lot of attention concerning many clinical applications including patient positioning, respiratory motion tracking, and collision detection during the radiotherapy delivery phase. However, issues associated with such applications are related to some materials and surfaces reflections generating an offset in depth measurements especially during gantry motion. This phenomenon appears in particular when the collimator surface is observed by the camera; resulting in erroneous depth measurements, not only in Kinect surfaces itself, but also as a large peak when extracting a 1D respiratory signal from these data.MethodsIn this paper, we proposed filtering techniques to reduce the noise effect in the Kinect‐based 1D respiratory signal, using a trend removal filter, and in associated 2D surfaces, using a temporal median filter. Filtering process was validated using a phantom, in order to simulate a patient undergoing radiotherapy treatment while having the ground truth.ResultsOur results indicate a better correlation between the reference respiratory signal and its corresponding filtered signal (Correlation coefficient of 0.76) than that of the nonfiltered signal (Correlation coefficient of 0.13). Furthermore, surface filtering results show a decrease in the mean square distance error (85%) between the reference and the measured point clouds.ConclusionThis work shows a significant noise compensation and surface restitution after surface filtering and therefore a potential use of the Kinect V2 camera for different radiotherapy‐based applications, such as respiratory tracking and collision detection.
Topology optimization of finite strain viscoplastic systems under transient loads
Authors: Ivarsson Niklas , Wallin Mathias , Tortorelli Daniel 
Published: February 2018

SummaryA transient finite strain viscoplastic model is implemented in a gradient‐based topology optimization framework to design impact mitigating structures. The model's kinematics relies on the multiplicative split of the deformation gradient, and the constitutive response is based on isotropic hardening viscoplasticity. To solve the mechanical balance laws, the implicit Newmark‐beta method is used together with a total Lagrangian finite element formulation. The optimization problem is regularized using a partial differential equation filter and solved using the method of moving asymptotes. Sensitivities required to solve the optimization problem are derived using the adjoint method. To demonstrate the capability of the algorithm, several protective systems are designed, in which the absorbed viscoplastic energy is maximized. The numerical examples demonstrate that transient finite strain viscoplastic effects can successfully be combined with topology optimization.
Acute lymphoblastic leukemia and lymphoblastic lymphoma in adolescents and young adults
Authors: McNeer Jennifer L. , Bleyer Archie 
Published: February 2018

AbstractCompared to younger and older age groups, the incidence of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) has increased more in the adolescent and young adult (AYA) population, the cause of which is unknown. As of the last decade, only half of the AYA patients with these diseases were surviving 10 years. Strong evidence exists that favors “pediatric” treatment regimens for AYAs compared to “adult” treatment regimens in terms of survival rates, hospitalization time, toxicities, late effects, and quality of life both during and after treatment. Targeted agents are clinically accessible for certain subsets of patients with Philadelphia‐like ALL, the incidence of which peaks in AYAs. Treatment teams must appreciate the complex psychosocial underpinnings in these patients in order to maximize compliance with the prolonged and complex treatment plans during the AYA years.
The extraordinary challenge of treating patients with congenital rhabdoid tumors—a collaborative European effort
Authors: Nemes Karolina , Clément Nathalie , Kachanov Denis , Bens Susanne , Hasselblatt Martin , Timmermann Beate , Schneppenheim Reinhard , Gerss Joachim , Siebert Reiner , Furtwängler Rhoikos , Bourdeaut Franck , Frühwald Michael Christoph ,   EU‐RHAB consortium
Published: February 2018

AbstractBackgroundCongenital rhabdoid tumors are rare and highly aggressive malignancies. In general, patients are considered to be incurable and are often treated using an exclusive, primarily palliative approach.MethodsA prospective and retrospective collection of 42 patients from the European Rhabdoid Registry (EU‐RHAB), France and Moscow (2006–2016) diagnosed within the first 28 days of life was evaluated. Genetic and clinical reference evaluation included SMARCB1 and/or SMARCA4 (fluorescence‐in‐situ‐hybridization, multiplex ligation‐dependent probe amplification, and sequencing) mutation analysis and immunohistochemistry. Forty‐eight percent (20/42) of patients were treated according to the EU‐RHAB therapy, 7% (3/42) according to the pilot approach Rhabdoid 2007, 33% (14/42) with individual schedules, and 12% (5/42) received no chemotherapy at all.ResultsForty point five percent (17/42) of patients presented with extracranial rhabdoid tumors, 33.5% (14/42) with rhabdoid tumors of the central nervous system (atypical teratoid/rhabdoid tumor), and the remainder 26% (11/42) demonstrated synchronous tumors. Metastases at diagnosis were present in 52% (22/42) of patients. A germline mutation was detected in 66% (25/38) and was associated with a poor prognosis (4.2 ± 4.1% vs. 48 ± 16.4%, P < 0.00005). A gross total resection (GTR) was realized in 17%. A GTR (42.9 ± 18.7% vs. 4.9 ± 4.3%, P = 0.04), therapy according to a standardized approach (20.9 ± 8.7% vs. 7.1 ± 6.9 %, P = 0.0018), and a complete remission (CR) (23.6 ± 9.8% vs. 1.3 ± 3.6%, P = 0.04) were significant prognostic factors.ConclusionsThe management of patients with congenital rhabdoid tumors requires a major multidisciplinary effort. In many instances, cure is not possible and a palliative approach is warranted. Our data indicate a positive impact of standardized therapeutic approaches on survival, making a tailored approach toward affected patients and their families mandatory.
Fetal pulmonary valve stenosis or atresia with intact ventricular septum: Predictors of need for neonatal intervention
Authors: Wang Qing , Wu Yu Rong , Jiao Xian Ting , Wu Peng Fei , Zhao Li Qing , Chen Sun , Sun Kun 
Published: February 2018

AbstractObjectivesTo compare the fetal echocardiographic measurements and neonatal outcome of fetuses with diagnosis of critical pulmonary stenosis (CPS/IVS) and pulmonary atresia with intact ventricular septum (PA/IVS) to identify the predictors of neonatal ductus dependence and the need for neonatal intervention.MethodsForty‐four fetuses with a diagnosis of membranous PA/IVS or CPS/IVS referred to Shanghai Xinhua Hospital Affiliated to Shanghai Jiaotong University between June 2009 and November 2014 were respectively analyzed. We analyzed their fetal and pediatric echocardiographic features and clinical features after birth.ResultsAmong the 29 infants in the final analysis, 19 were ductal dependent and were diagnosed as CPS/IVS or PA/IVS after birth. Ten patients with fetal CSP/IVS were ductal independent and were diagnosed as pulmonary stenosis after birth. In midtrimester, significance was only detected in pulmonary valve (PV) regurgitation between 2 groups (P = .009). The fetuses with PV regurgitation in midtrimester were more likely to be ductal independent (odds ratio = 6.67; P = .010) than those with absence of PV regurgitation in the midtrimester scan. In late trimester, the infants in ductus‐independent group had better fetal right ventricular development than those in ductus dependent group. The right ventricle over left ventricle length ratio in last scan over 0.86 had the best capability in predicting ductus independence during neonatal period with help of receiver‐operating characteristic curve and the logistic regression analysis.ConclusionAmong fetuses with pulmonary valve stenosis and right ventricle dysplasia at the time of first fetal echo in midtrimester, use of pulmonary valve regurgitation can identify who will be ductal dependent at births. In late trimester, right ventricle over left ventricle length ratio less than 0.86 had the best capability of predicting neonatal ductal dependence. Fetuses with reversed ductus arteriosus flow direction in late trimester were more likely to be ductus dependent after birth.
Obstetricians' views on the ethics of cardiac surgery for newborns with common aneuploidies
Authors: Fruhman Gary , Miller Collin , Amon Erol , Raible Darbey , Bradshaw Rachael , Martin Kimberly 
Published: February 2018

AbstractObjectiveTo examine whether obstetricians think that cardiac surgery is ethical in babies with common aneuploidies and whether insurance companies should be required to pay for these surgeries.Study DesignA survey was e‐mailed to 2897 OB‐GYNs, and 898 (31%) actively practicing obstetricians responded to the survey. Respondents were asked whether it is ethical to offer cardiac surgery for babies with heart defects diagnosed with trisomies 21, 18, and 13 and Turner syndrome and whether insurance companies should be required to pay for such surgeries in cases of trisomy 18 or 13. Chi‐square tests were utilized to compare responses by using an alpha level of .05.ResultsMost obstetricians thought that offering cardiac surgery was ethical if the baby had trisomy 21 or Turner syndrome (94%), but not trisomy 18 or 13 (75%). Most obstetricians (69%) thought that insurance companies should not be legally required to pay for cardiac surgery for the latter group.ConclusionObstetricians were more likely to think cardiac surgery was ethical if the prognosis or the outcome was good. Most respondents did not think that insurance companies should be required to subsidize the cost of cardiac surgeries for all babies with trisomy 18 or 13.
Real‐world evaluation of the DESMOND type 2 diabetes education and self‐management programme
Authors: Chatterjee Sudesna , Davies Melanie J , Stribling Bernie , Farooqi Azhar , Khunti Kamlesh 
Published: February 2018

AbstractDiabetes education and self‐management programmes are associated with improved biomedical, psychosocial and behavioural outcomes according to a number of randomised controlled trials (RCT) and systematic reviews. Observational studies are necessary to determine whether delivery of this education translates to improved outcomes in the real world. In 2008, the results of an RCT evaluating Diabetes Education and Self‐Management for Ongoing and Newly Diagnosed (DESMOND) in a multi‐ethnic population were published confirming the benefits of participating in this programme with sustained improvements at three years along with confirmed cost‐effectiveness. DESMOND has therefore been recommended by NICE as a robust and validated national diabetes structured education programme.DESMOND courses have been offered by the Leicester City, Leicestershire and Rutland (LLR) clinical commissioning groups for people newly diagnosed or with pre‐existing type 2 diabetes since 2008, and we reviewed the outcomes of participants who attended a course between January 2014 and March 2015. During this period, 1678 (53%) participants attended one of 244 courses in LLR compared with 5.3% attending any validated structured education programme nationally. Notably, there was a statistically significant reduction in HbA1c of 0.96% at six months and 0.70% at 12 months (both p < 0.005). Qualitative evaluation from surveys completed by 302/1678 (18%) respondents immediately after attending DESMOND found that the programme was well received by participants who noted improvements in their ability to self‐manage diabetes.This 15‐month evaluation of DESMOND confirms the benefits of attending the programme in the real world. Copyright © 2018 John Wiley & Sons.
Depletion of amyloid‐β peptides from solution by sequestration within fibril‐seeded hydrogels
Authors: Yau Wai‐Ming , Tycko Robert 
Published: February 2018

AbstractAggregation of amyloid‐β (Aβ) peptides in brain tissue leads to neurodegeneration in Alzheimer's disease (AD). Regardless of the kinetics or detailed mechanisms of Aβ aggregation, aggregation can only occur if Aβ concentrations exceed their local equilibrium solubility values. We propose that excess Aβ peptides can be removed from supersaturated solutions, including solutions in biological fluids, by the addition of hydrogels that are seeded with Aβ fibril fragments. Fibril growth within the hydrogels then sequesters excess peptides until equilibrium concentrations are reached. Experiments with 40‐ and 42‐residue Aβ peptides (Aβ40 and Aβ42) in phosphate buffer at 24°C and in filtered fetal bovine serum at 37°C, using crosslinked polyacrylamide hydrogels, demonstrate the validity of this concept. Aβ sequestration in fibril‐seeded hydrogels (or other porous media) may prove to be a useful technique in experiments with animal models of AD and may represent a possible approach to preventing or slowing the progression of AD in humans.
A laser desorption ionization/matrix‐assisted laser desorption ionization target system applicable for three distinct types of instruments (LinTOF/curved field RTOF, LinTOF/RTOF and QqRTOF) with different performance characteristics from three vendors
Authors: Rados Edita , Pittenauer Ernst , Frank Johannes , Varmuza Kurt , Allmaier Günter 
Published: February 2018

RationaleWe have developed a target system which enables the use of only one target (i.e. target preparation set) for three different laser desorption ionization (LDI)/matrix‐assisted laser desorption ionization (MALDI) mass spectrometric instruments. The focus was on analysing small biomolecules with LDI for future use of the system for the study of meteorite samples (carbonaceous chondrites) using devices with different mass spectrometric performance characteristics.MethodsThree compounds were selected due to their potential presence in meteoritic chondrites: tryptophan, 2‐deoxy‐d‐ribose and triphenylene. They were prepared (with and without MALDI matrix, i.e. MALDI and LDI) and analysed with three different mass spectrometers (LinTOF/curved field RTOF, LinTOF/RTOF and QqRTOF). The ion sources of two of the instruments were run at high vacuum, and one at intermediate pressure. Two devices used a laser wavelength of 355 nm and one a wavelength of 337 nm.ResultsThe developed target system operated smoothly with all devices. Tryptophan, 2‐deoxy‐d‐ribose and triphenylene showed similar desorption/ionization behaviour for all instruments using the LDI mode. Interestingly, protonated tryptophan could be observed only with the LinTOF/curved field RTOF device in LDI and MALDI mode, while sodiated molecules were observed with all three instruments (in both ion modes). Deprotonated tryptophan was almost completely obscured by matrix ions in the MALDI mode whereas LDI yielded abundant deprotonated molecules.ConclusionsThe presented target system allowed successful analyses of the three compounds using instruments from different vendors with only one preparation showing different analyser performance characteristics. The elemental composition with the QqRTOF analyser and the high‐energy 20 keV collision‐induced dissociation fragmentation will be important in identifying unknown compounds in chondrites.
Anwendungsgrenzen für eine teilweise Verdübelung von Verbundträgern mit oberflanschlosen Stahlprofilen und Verbunddübelleisten
Authors: Classen Martin , Stiller Leoni Katharina 
Published: February 2018

AbstractFür Verbundträger mit oberflanschlosen Stahlträgern und Verbunddübelleisten sind die Anwendungsgrenzen für eine teilweise Verdübelung bisher nicht geklärt. Im vorliegenden Beitrag (Fortsetzung von [1]) wird das Trag‐ und Verformungsverhalten dieser Verbundträger anhand experimentell verifizierter FE‐Modelle analysiert. Hierzu wird eine umfassende Parameterstudie durchgeführt. Neben dem Verdübelungsgrad und den Querschnittsabmessungen werden hierin Eigenschaften, die vom statischen System abhängen, wie die Belastungssituation (Einzellast oder Linienlast) und die Spannweite ebenso variiert, wie das Verbundmittelverformungsverhalten, indem unterschiedliche Duktilitäten bzw. Dübelkennlinien für das Ausstanz‐ und das Stahlversagen angesetzt werden. Anhand der Simulationsergebnisse werden Ingenieurmodelle für den Mindestverdübelungsgrad von Verbundträgern mit oberflanschlosen Stahlprofilen und Verbunddübelleisten einschließlich aller erforderlichen Anwendungsgrenzen für die plastische Biegebemessung hergeleitet. Diese werden den Regelungen einer allgemeinen bauaufsichtlichen Zulassung für Verbunddübelleisten gegenübergestellt. Die Modelle lassen sich auf Verbundträger mit Stahl‐T‐Querschnitt und liegenden Kopfbolzendübeln übertragen.