bluuebunny/crossref_metadata_2025_split huggingface dataset:
Making global simpler GMRES more stable
Authors: Liu Qiaohua , Shen Dongmei , Jia Ziwei 
Published: July 2018

SummaryThe global GMRES method is well known for the solution of nonsymmetric linear systems with multiple right hands. In this paper, the condition number for evaluating the stability of the global simpler GMRES method is defined. With this condition number, it is shown that Zong et al.'s global simpler method with a simple basis of the Krylov matrix subspace might lead to instability when there is a large decrease in the residual norm. An adaptive global simpler method is then presented to avoid the potential instability. For this adaptive method, theoretical results deliver the lower and upper bounds for the condition number of the basis, and when the linear system is of single right hand, the estimate is proven to be tighter than Jiránek et al.'s upper bound by numerical tests. Numerical results also show that the adaptive strategy leads to a well‐conditioned basis, and in most cases, the global simpler GMRES with normalized residuals as the basis can also be reliable.
A multigrid solver to the Helmholtz equation with a point source based on travel time and amplitude
Authors: Treister Eran , Haber Eldad 
Published: July 2018

SummaryThe Helmholtz equation arises when modeling wave propagation in the frequency domain. The equation is discretized as an indefinite linear system, which is difficult to solve at high wave numbers. In many applications, the solution of the Helmholtz equation is required for a point source. In this case, it is possible to reformulate the equation as two separate equations: one for the travel time of the wave and one for its amplitude. The travel time is obtained by a solution of the factored eikonal equation, and the amplitude is obtained by solving a complex‐valued advection–diffusion–reaction equation. The reformulated equation is equivalent to the original Helmholtz equation, and the differences between the numerical solutions of these equations arise only from discretization errors. We develop an efficient multigrid solver for obtaining the amplitude given the travel time, which can be efficiently computed. This approach is advantageous because the amplitude is typically smooth in this case and, hence, more suitable for multigrid solvers than the standard Helmholtz discretization. We demonstrate that our second‐order advection–diffusion–reaction discretization is more accurate than the standard second‐order discretization at high wave numbers, as long as there are no reflections or caustics. Moreover, we show that using our approach, the problem can be solved more efficiently than using the common shifted Laplacian multigrid approach.
Health‐care providers’ perspectives on traditional and complementary alternative medicine of childhood cancer in Kenya
Authors: Olbara Gilbert , Parigger Josta , Njuguna Festus , Skiles Jodi , Sitaresmi Mei Neni , Gordijn Suzanne , van de Ven Peter , Kaspers Gertjan , Mostert Saskia 
Published: July 2018

AbstractPurposeTraditional and complementary alternative medicine (TCAM) use is rising globally. In many African countries, TCAM has been a way of life as the first and last resort remedy for many ailments, including cancer. Health‐care providers (HCP) should address this need properly. This study explores HCP perspectives on TCAM in Kenya.MethodsThis cross‐sectional study used questionnaires. HCP involved in the care of children with cancer at a Kenyan academic hospital were interviewed.ResultsIn total, 155 HCP (response rate 79%) participated. Only 18% of HCP were positive about TCAM use. However, most HCP (85%) use TCAM themselves. More doctors (90%) than other HCP (56%) think that chemotherapy can cure cancer (P < 0.001).Thirty‐three percent of HCP believe a combination of TCAM and chemotherapy is the best way to cure cancer, while 56% think that usefulness of TCAM is underestimated in conventional medicine. Self‐prayer is regarded as most effective (58%) and safe (76%). Most harmful is witchcraft (80%). Most HCP (71%) think their knowledge about safety and efficacy of TCAM is inadequate. HCP think that their cancer patients use TCAM (97%) and that it is important that parents inform them about this (97%). However, only 5% of HCP always openly discuss TCAM with parents.ConclusionsHCP need to improve their knowledge of TCAM and facilitate open communication about TCAM with families so parents feel safe to discuss their interest in it.
Intermittent or uneven daily administration of low‐dose hydroxyurea is effective in treating children with sickle cell anemia in Angola
Authors: Chambers Tiffany M. , Kahan Silvina , Camanda Joao F. , Scheurer Michael , Airewele Gladstone E. 
Published: July 2018

AbstractBackgroundAlthough hydroxyurea is proven effective in treatment of sickle cell anemia (SCA) and is widely prescribed in high‐income countries, due to questions about feasibility of treating large numbers of patients in resource‐limited health systems, its use is limited in sub‐Saharan Africa (SSA), where most children with SCA live. We assessed hematological response and toxicity of hydroxyurea treatment for SCA in Angola.MethodsRetrospective study of children with SCA (not selected for clinical severity) treated on a fixed dose of hydroxyurea for at least 6 months. Because only the 500 mg capsule was available, dose was averaged weekly. We evaluated toxicity events and magnitude of hydroxyurea‐induced changes in blood counts and compared patients who received a uniform daily dose to those prescribed intermittent or uneven daily doses.ResultsOnly 13% of 303 patients received a uniform dose of hydroxyurea daily. Dose ranged from 16.5 to 22.8 mg/kg/day. Hydroxyurea increased HGB and mean cell volume values by 0.5 g/dL (P < 0.0001) and 8 fL (P < 0.0001), while ANC, PLT, and ARC decreased 1.1 × 109/L (P < 0.0001), 34 × 109/L (P = < 0.0001), and 19 × 109/L (P = 0.0008), respectively. There were no differences in magnitude of hydroxyurea‐induced changes between patients prescribed intermittent or uneven doses and uniform daily doses, or between those treated in the lower and higher dose quartiles. Hematological toxicity events were mild and reversible.ConclusionIntermittent or uneven daily dosing of hydroxyurea is as effective as fixed daily doses in treating SCA. This strategy may enable treatment of additional children with SCA in SSA.
Medication‐related anaphylaxis treated in hospital: Agents implicated, patient outcomes, and management lessons
Authors: Graudins Linda V. , Trubiano Jason A. , Zubrinich Celia M. , Elliott Ainslee S. , Aung Ar Kar 
Published: July 2018

AbstractPurposeOn background of increasing medication‐related anaphylaxis rates in Australia, our aim was to determine epidemiology, outcomes, adverse drug reaction (ADR) reporting rates, and accuracy of coding in patients treated for nonantimicrobial medication‐related anaphylaxis in our hospital network.MethodsFrom January 2010 to December 2015 patients treated in our hospital network for medication‐related anaphylaxis were identified using International Classification of Diseases, 10th Edition diagnosis code T88.6. Cases were also extracted from the hospital ADR database. Medical records were reviewed to ensure consistent diagnosis and to extract clinical, documentation, and outcome data.ResultsOf 1110 patients coded as T88.6, 177 (15.9%) met the medication‐related anaphylaxis definition. Eighty (40.8%) had anaphylaxis due to nonantimicrobial agents. Thirteen of these (16.3%) had a previous reaction to the same medication/group. In 51 (63.8%) patients, anaphylaxis occurred during inpatient stay, with 31 reactions occurring during surgery. Eighty‐five medications were implicated, most commonly neuromuscular blocking agents (31, 36.5%) and nonsteroidal anti‐inflammatory drugs. No trends were noted over the 6‐year period, and there was no anaphylaxis‐related mortality. Fifty‐three (66.3%) patients were assessed in allergy clinics. One in 10 cases did not have the reaction documented in the discharge summary. Adverse drug reaction reports were received for 38 patients (47.5%).ConclusionsAlthough acute patient outcomes were excellent, gaps in practice were noted regarding ADR coding accuracy and reporting rates. One in 6 patients had a prior hypersensitivity reaction to a similar medication, so we recommend accurate documentation, ADR review with allergy follow‐up, and patient held information to decrease re‐exposure risk.
Active surveillance of severe cutaneous adverse reactions: A case‐population approach using a registry and a health care database
Authors: Rodríguez‐Martín Sara , Martín‐Merino Elisa , Lerma Victoria , Rodríguez‐Miguel Antonio , González Olga , González‐Herrada Carlos , Ramírez Elena , Bellón Teresa , de Abajo Francisco J. 
Published: July 2018

AbstractPurposeThe “case‐population” design has been proposed for the surveillance of rare events like Stevens‐Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), wherein a registry of cases is combined with sales data from the source population in order to estimate crude odds ratios (ORs). A major drawback of this method is the inability to distinguish between new and non‐new users of drugs, which for the study of hypersensitivity reactions is of utmost importance.MethodsWe have explored an approach in which the exposure to the drugs of interest in the source population is inferred from a primary health care database (BIFAP), which helped us to identify drug initiators among all users and additionally adjust for potential confounders. A total of 44 SJS/TEN cases from the Registry and 44 000 controls randomly sampled from BIFAP and matched with cases for index date were included. We estimated the adjusted ORs (AORs) and 95% confidence intervals (CI) of SJS/TEN associated with the new use of 13 drugs (for which we had at least two exposed cases) through a conditional logistic regression model.ResultsAORs (95% CI) were estimated for phenytoin, 4618 (434‐49112); cotrimoxazole, 1142 (163‐8015); allopurinol, 160 (36‐709); dexamethasone, 38 (1.33‐1077); ibuprofen, 33 (8.6‐124); lorazepam, 27 (5.8‐124); paracetamol, 13 (2.8‐62); levofloxacine, 12 (1.24‐120); amoxicillin, 6.9 (1.39‐35); pantoprazole, 6.5 (0.10‐420); metamizole, 6.3 (0.69‐57); amoxicillin clavulanic acid, 4.2 (0.53‐34); and omeprazole, 1.34 (0.06‐31). The inclusion of non‐new users dramatically decreased the AORs for all drugs.ConclusionsThe case‐population approach using a registry of cases and a primary health care database proved feasible and efficient for the active surveillance of SJS/TEN.
Synthesis and characterization of versatile amphiphilic dendrimers peripherally decorated with positively charged amino acids
Authors: Alfei Silvana , Catena Silvia 
Published: July 2018

AbstractDendrimers are nanostructured ‘architectural motifs’ with a well‐tailored polymeric structure, symmetric tree‐like shape and the presence of several functional groups and inner cavities, and are of eminent interest in many biomedical applications such as drug delivery, gene transfection and imaging. In the work reported, reliable protocols for the synthesis of polyester‐based, hydrolysable, amphiphilic polycationic dendrimers were developed. A C‐18 hydrocarbon chain provided by a biocompatible fatty acid, stearic acid, and second‐ and third‐generation dendrons based on 2,2‐bis(hydroxymethyl)propionic acid were built on 2,2‐bis(hydroxymethyl)propanol and pentaerythritol as core molecules. αN‐BOC‐ω'N‐(NO2)‐l‐arginine alone, mixed with αN,ϵN‐di‐BOC‐l‐lysine or also with N,N′‐dimethylglycine and αN‐BOC‐methylglycine were successfully bound to the prepared polyester neutral scaffolds and, after the removal of protecting groups, five cationic dendrimers were obtained. Their structure was confirmed using NMR analysis and experimental molecular weight. Their buffer capacity, comparable to that of polyethyleneimines, was optimal, high viability percentage values were obtained from cytotoxicity assays and zeta potential and mean particle size were in the desired ranges. The synthesized nanostructured compounds that harmonize a multifunctional polycationic shell, a biodegradable uncharged polyester matrix and a C‐18 hydrophobic portion helpful for an improved hydrophilic–lipophilic balance in their structure embody all the fundamental features to be suitable for biomedical applications. © 2018 Society of Chemical Industry
Real‐time monitoring and diagnosis of photovoltaic system degradation only using maximum power point—the Suns‐Vmp method
Authors: Sun Xingshu , Chavali Raghu Vamsi Krishna , Alam Muhammad Ashraful 
Published: July 2018

AbstractThe uncertainties associated with technology‐specific and geography‐specific degradation rates make it difficult to calculate the levelized cost of energy, and thus the economic viability of solar energy. In this regard, millions of fielded photovoltaic modules may serve as a global testbed, where we can interpret the routinely collected time series maximum power point (MPP) data to assess the time‐dependent “health” of solar modules. The existing characterization methods, however, cannot effectively mine/decode these datasets to identify various degradation pathways. In this paper, we propose a new methodology called the Suns‐Vmp method, which offers a simple yet powerful approach to monitoring and diagnosing time‐dependent degradation of solar modules by using the MPP data. The algorithm reconstructs “IV” curves by using the natural illumination‐dependent and temperature‐dependent daily MPP characteristics as constraints to fit physics‐based circuit models. These synthetic IV characteristics are then used to determine the time‐dependent evolution of circuit parameters (eg, series resistance), which in turn allows one to deduce the dominant degradation modes (eg, solder bond failure) of solar modules. The proposed method has been applied to a test facility at the National Renewable Energy Laboratory. Our analysis indicates that the solar modules degraded at a rate of ~0.7%/year because of discoloration and weakened solder bonds. These conclusions are validated by independent outdoor IV measurements and on‐site imaging characterization. Integrated with physics‐based degradation models or machine learning algorithms, the method can also serve to predict the lifetime of photovoltaic systems.
Demoralization and death anxiety in advanced cancer
Authors: An Ekaterina , Lo Christopher , Hales Sarah , Zimmermann Camilla , Rodin Gary 
Published: July 2018

AbstractObjectiveThe circumstances of advanced cancer can cause considerable psychological distress, including death anxiety and demoralization. Although these states of existential distress have a negative impact on the quality of life of patients with advanced cancer, they are rarely evaluated as outcomes or targets of interventions in this population. In an effort to improve understanding of existential distress, a structural model of relationships among death anxiety, demoralization, symptom burden, and social relatedness was tested in patients with advanced cancer.MethodsA total of 307 patients with advanced cancer completed baseline measures including the Death and Dying Distress Scale, the Demoralization Scale, the modified Experiences in Close Relationships Scale, the Life Completion subscale of the Quality of Life Evaluation—Cancer scale, the Memorial Symptom Assessment Scale, and Karnofsky Performance Status. A structural equation model of protective and risk factors for demoralization and death anxiety was tested.ResultsThe final model had good fit (SRMR = 0.061; RMSEA = 0.077; CFI = 0.927; NNFI = 0.902) in which death anxiety was positively associated with demoralization (β = 0.71), and demoralization was positively associated with symptom burden (β = 0.31) and negatively associated with social relatedness (β = −0.74).ConclusionsThe findings of this study suggest that demoralization and death anxiety are closely linked in patients with advanced cancer. The contribution of both symptom burden and low social relatedness to demoralization suggests that an integrated intervention addressing both physical and psychosocial disease factors may be most effective at alleviating such states of existential distress.
Multistep mutational transformation of a protein fold through structural intermediates
Authors: Kumirov Vlad K. , Dykstra Emily M. , Hall Branwen M. , Anderson William J. , Szyszka Taylor N. , Cordes Matthew H. J. 
Published: July 2018

AbstractNew protein folds may evolve from existing folds through metamorphic evolution involving a dramatic switch in structure. To mimic pathways by which amino acid sequence changes could induce a change in fold, we designed two folded hybrids of Xfaso 1 and Pfl 6, a pair of homologous Cro protein sequences with ~40% identity but different folds (all‐α vs. α + β, respectively). Each hybrid, XPH1 or XPH2, is 85% identical in sequence to its parent, Xfaso 1 or Pfl 6, respectively; 55% identical to its noncognate parent; and ~70% identical to the other hybrid. XPH1 and XPH2 also feature a designed hybrid chameleon sequence corresponding to the C‐terminal region, which switched from α‐helical to β‐sheet structure during Cro evolution. We report solution nuclear magnetic resonance (NMR) structures of XPH1 and XPH2 at 0.3 Å and 0.5 Å backbone root mean square deviation (RMSD), respectively. XPH1 retains a global fold generally similar to Xfaso 1, and XPH2 retains a fold similar to Pfl 6, as measured by TM‐align scores (~0.7), DALI Z‐scores (7‐9), and backbone RMSD (2–3 Å RMSD for the most ordered regions). However, these scores also indicate significant deviations in structure. Most notably, XPH1 and XPH2 have different, and intermediate, secondary structure content relative to Xfaso 1 and Pfl 6. The multistep progression in sequence, from Xfaso 1 to XPH1 to XPH2 to Pfl 6, thus involves both abrupt and gradual changes in folding pattern. The plasticity of some protein folds may allow for “polymetamorphic” evolution through intermediate structures.
A benchmarking study on virtual ligand screening against homology models of human GPCRs
Authors: Lim Victor Jun Yu , Du Weina , Chen Yu Zong , Fan Hao 
Published: July 2018

AbstractG‐protein‐coupled receptor (GPCR) is an important target class of proteins for drug discovery, with over 27% of FDA‐approved drugs targeting GPCRs. However, being a membrane protein, it is difficult to obtain the 3D crystal structures of GPCRs for virtual screening of ligands by molecular docking. Thus, we evaluated the virtual screening performance of homology models of human GPCRs with respect to the corresponding crystal structures. Among the 19 GPCRs involved in this study, we observed that 10 GPCRs have homology models that have better or comparable performance with respect to the corresponding X‐ray structures, making homology models a viable choice for virtual screening. For a small subset of GPCRs, we also explored how certain methods like consensus enrichment and sidechain perturbation affect the utility of homology models in virtual screening, as well as the selectivity between agonists and antagonists. Most notably, consensus enrichment across multiple homology models often yields results comparable to the best performing model, suggesting that ligand candidates predicted with consensus scores from multiple models can be the optimal option in practical applications where the performance of each model cannot be estimated.
Exploring the conformational landscapes of HIV protease structural ensembles using principal component analysis
Authors: Hassan Sameer , Srikakulam Sanjay Kumar , Chandramohan Yuvaraj , Thangam Manonanthini , Muthukumar Soundharrya , Gayathri Devi P. K. , Hanna Luke Elizabeth 
Published: July 2018

AbstractHIV protease, an essential enzyme for viral particle maturation, is an important drug target of HIV. Its structural conformation is a key determinant of both biological function as well as efficient binding of protease inhibitor molecules. In the present study we analyzed 471 crystal structures of HIV‐1 protease to understand the conformational changes induced by mutations or binding of various ligands and substrates. We performed principal component analysis on the ensembles of the HIV‐1 protease structures to explore the conformational landscapes. The study identified structural differences between drug resistant and drug sensitive protease structures. Conformational changes were identified in the A and B chains of homo‐dimeric HIV protease structures having different combinations of mutations, and also rigidity in the binding conformation of HIV drugs within the active site of the protein.© 2018 Wiley Periodicals, Inc.
A computational model for controlling conformational cooperativity and function in proteins
Authors: Erman Burak 
Published: July 2018

AbstractWe present a computational model that allows for rapid prediction of correlations among a set of residue pairs when the fluctuations of another set of residues are perturbed. The simple theory presented here is based on the knowledge of the fluctuation covariance matrix only. In this sense, the theory is model independent and therefore universal. Perturbation of any set of fluctuations and the resulting response of the remaining set are calculated using conditional probabilities of a multivariate normal distribution. The model is expected to rapidly and accurately map the consequences of mutations in proteins, as well as allosteric activity and ligand binding. Knowledge of triple correlations of fluctuations of residues i, j, and k, emerges as the necessary source of information for controlling residue pairs by perturbing a distant residue. Triple correlations have not received wide attention in literature. Perturbation–response–function relations for ubiquitin (UBQ) are discussed as an example. Covariance matrix for UBQ obtained from the Gaussian Network Model combined with the present computational algorithm is able to reflect the millisecond molecular dynamics correlations and observed NMR results. © 2018 Wiley Periodicals, Inc.
The stereoisomerism of second generation anticoagulant rodenticides: a way to improve this class of molecules to meet the requirements of society?
Authors: Lattard Virginie , Benoit Etienne 
Published: July 2018

ABSTRACTSecond generation anticoagulant rodenticides (SGAR) are generally highly efficient for rodent management even towards warfarin‐resistant rodents. Nevertheless, because of their long tissue‐persistence, they are very associated with non‐target exposure of wildlife and have been identified as ‘Candidates for Substitution’ by the European Union's competent authority. A promising way to reduce ecotoxicity issues associated to SGAR could be the improvement of SGAR based on their stereoisomery, and due to this improvement, positioning about SGAR might be reconsidered. © 2018 Society of Chemical Industry
Adaptive Weight Estimator for Quantum Error Correction in a Time‐Dependent Environment
Authors: Spitz Stephen T. , Tarasinski Brian , Beenakker Carlo W. J. , O'Brien Thomas E. 
Published: July 2018

AbstractQuantum error correction of a surface code or repetition code requires the pairwise matching of error events in a space‐time graph of qubit measurements, such that the total weight of the matching is minimized. The input weights follow from a physical model of the error processes that affect the qubits. This approach becomes problematic if the system has sources of error that change over time. Here, it is shown that the weights can be determined from the measured data in the absence of an error model. The resulting adaptive decoder performs well in a time‐dependent environment, provided that the characteristic timescale τenv of the variations is greater than , with the duration of one error‐correction cycle and the typical error probability per qubit in one cycle.