bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis of 4′‐Selenoribonucleosides, the Building Blocks of 4′‐SelenoRNA, Using a Hypervalent Iodine
Authors: Saito‐Tarashima Noriko , Ota Masashi , Minakawa Noriaki 
Published: September 2017

AbstractHerein is described a detailed protocol for the synthesis of 4′‐selenoribonucleoside derivatives that involves the use of a hypervalent iodine species. These derivatives are versatile units for the preparation of 4′‐selenoRNA. Large‐scale synthesis of a 4‐selenosugar starting from D‐ribose is achieved in eight steps, including a final chromatographic purification. The resulting 4‐selenosugar is then subjected to the one‐pot Pummerer‐like reaction using hypervalent iodine in the presence of silylated nucleobases. The reaction with silylated uracil affords the desired 4′‐selenouridine derivatives with excellent β‐selectivity and in good yield. Conversely, when purine nucleobases are used in the Pummerer‐like reaction, N7 4′‐selenoribonucleoside isomers are obtained alongside the desired N9 isomers. However, the undesired N7 isomers can be converted to the desired N9 ones under acidic conditions. © 2017 by John Wiley & Sons, Inc.
Quantitative Analysis of Nucleic Acid Stability with Ligands Under High Pressure to Design Novel Drugs Targeting G‐Quadruplexes
Authors: Takahashi Shuntaro , Sugimoto Naoki 
Published: September 2017

AbstractNucleic acids (DNA and RNA) can form various non‐canonical structures. Because some serious diseases are caused by the conformational change of G‐quadruplex DNA structures, the development of ligands that bind and stabilize G‐quadruplex DNA is of interest to the field of nucleic acid chemistry. Volumetric changes (ΔV) in the biomolecular reaction include the structural change of biomolecules and hydration behaviors, which provide information about the tertiary interaction between G‐quadruplex DNA and ligands. Thus, it is valuable to investigate ΔV values to understand the mechanism of interaction between non‐canonical structures and their ligands. This unit describes methods that can be used to quantitatively analyze the interaction between G‐quadruplex DNA and ligands by using high‐pressure UV melting. The combination of thermodynamic parameters (ΔG, ΔH, ΔS, and ΔV) is a powerful tool to elucidate the mechanism of ligand binding to G‐quadruplex without real structural analysis by NMR and X‐ray spectroscopy, and gives useful information to design novel drugs. © 2017 by John Wiley & Sons, Inc.
Role of Co‐Sensitizers in Dye‐Sensitized Solar Cells
Authors: Krishna Narra Vamsi , Krishna Jonnadula Venkata Suman , Mrinalini Madoori , Prasanthkumar Seelam , Giribabu Lingamallu 
Published: September 2017

AbstractCo‐sensitization is a popular route towards improved efficiency and stability of dye‐sensitized solar cells (DSSCs). In this context, the power conversion efficiency (PCE) values of DSSCs incorporating Ru‐ and porphyrin‐based dyes can be improved from 8–11 % to 11–14 % after the addition of additives, co‐adsorbents, and co‐sensitizers that reduce aggregation and charge recombination in the device. Among the three supporting material types, co‐sensitizers play a major role to enhance the performance and stability of DSSCs, which is requried for commercialization. In this Minireview, we highlight the role co‐sensitizers play in improving photovoltaic performance of devices containing Ru‐ and porphyrin‐based sensitizers.
Polaronic Charge Carrier–Lattice Interactions in Lead Halide Perovskites
Authors: Wolf Christoph , Cho Himchan , Kim Young‐Hoon , Lee Tae‐Woo 
Published: September 2017

AbstractAlmost ten years after the renaissance of the popular perovskite‐type semiconductors based on lead salts with the general formula AMX3 (A=organic or inorganic cation; M=divalent metal; X=halide), many facets of photophysics continue to puzzle researchers. In this Minireview, light is shed on the low mobilities of charge carriers in lead halide perovskites with special focus on the lattice properties at non‐zero temperature. The polar and soft lattice leads to pronounced electron‐phonon coupling, limiting carrier mobility and retarding recombination. We propose that the proper picture of excited charge carriers at temperature ranges that are relevant for device operations is that of a polaron, with Fröhlich coupling constants between 1<α<3. Under the aspect of light‐emitting diode application, APbX3 perovskite show moderate second order (bimolecular) recombination rates and high third‐order (Auger) rate constants. It has become apparent that this is a direct consequence of the anisotropic polar A‐site cation in organic–inorganic hybrid perovskites and might be alleviated by replacing the organic moiety with an isotropic cation.
Mechanistic Parameters of Electrocatalytic Water Oxidation on LiMn2O4 in Comparison to Natural Photosynthesis
Authors: Köhler Lennart , Ebrahimizadeh Abrishami Majid , Roddatis Vladimir , Geppert Janis , Risch Marcel 
Published: September 2017

AbstractTargeted improvement of the low efficiency of water oxidation during the oxygen evolution reaction (OER) is severely hindered by insufficient knowledge of the electrocatalytic mechanism on heterogeneous surfaces. We chose LiMn2O4 as a model system for mechanistic investigations as it shares the cubane structure with the active site of photosystem II and the valence of Mn3.5+ with the dark‐stable S1 state in the mechanism of natural photosynthesis. The investigated LiMn2O4 nanoparticles are electrochemically stable in NaOH electrolytes and show respectable activity in any of the main metrics. At low overpotential, the key mechanistic parameters of Tafel slope, Nernst slope, and reaction order have constant values on the RHE scale of 62(1) mV dec−1, 1(1) mV pH−1, −0.04(2), respectively. These values are interpreted in the context of the well‐studied mechanism of natural photosynthesis. The uncovered difference in the reaction sequence is important for the design of efficient bio‐inspired electrocatalysts.
Climatic and anthropogenic drivers of northern Amazon fires during the 2015–2016 El Niño event
Authors: Fonseca Marisa G. , Anderson Liana O. , Arai Egidio , Shimabukuro Yosio E. , Xaud Haron A. M. , Xaud Maristela R. , Madani Nima , Wagner Fabien H. , Aragão Luiz E. O. C. 
Published: September 2017

AbstractThe strong El Niño Southern Oscillation (ENSO) event that occurred in 2015–2016 caused extreme drought in the northern Brazilian Amazon, especially in the state of Roraima, increasing fire occurrence. Here we map the extent of precipitation and fire anomalies and quantify the effects of climatic and anthropogenic drivers on fire occurrence during the 2015–2016 dry season (from December 2015 to March 2016) in the state of Roraima. To achieve these objectives we first estimated the spatial pattern of precipitation anomalies, based on long‐term data from the TRMM (Tropical Rainfall Measuring Mission), and the fire anomaly, based on MODIS (Moderate Resolution Imaging Spectroradiometer) active fire detections during the referred period. Then, we integrated climatic and anthropogenic drivers in a Maximum Entropy (MaxEnt) model to quantify fire probability, assessing (1) the model accuracy during the 2015–2016 and the 2016–2017 dry seasons; (2) the relative importance of each predictor variable on the model predictive performance; and (3) the response curves, showing how each environmental variable affects the fire probability. Approximately 59% (132,900 km2) of the study area was exposed to precipitation anomalies ≤−1 standard deviation (SD) in January and ~48% (~106,800 km2) in March. About 38% (86,200 km2) of the study area experienced fire anomalies ≥1 SD in at least one month between December 2015 and March 2016. The distance to roads and the direct ENSO effect on fire occurrence were the two most influential variables on model predictive performance. Despite the improvement of governmental actions of fire prevention and firefighting in Roraima since the last intense ENSO event (1997–1998), we show that fire still gets out of control in the state during extreme drought events. Our results indicate that if no prevention actions are undertaken, future road network expansion and a climate‐induced increase in water stress will amplify fire occurrence in the northern Amazon, even in its humid dense forests. As an additional outcome of our analysis, we conclude that the model and the data we used may help to guide on‐the‐ground fire‐prevention actions and firefighting planning and therefore minimize fire‐related ecosystems degradation, economic losses and carbon emissions in Roraima.
A Novel Chemical Sensor Based on Sb2S3 Film for Highly Sensitive Detection of Hydrazine
Authors: Guo Huiyun , Hou Wenlong , Yang Jingkai , Yu Lan , Liang Bo , Zhang Haiquan 
Published: September 2017

AbstractThe Sb2S3 film on indium‐tin oxide (ITO) substrate has been used as an efficient electron transfer mediator for the fabrication of novel chemical sensor towards hydrazine, which is a diamine known as neurotoxin and carcinogen. Sb2S3 film is deposited on ITO substrate by drop‐casting process using Sb2S3 solution as precursor and possesses reticular structure with the morphology of uniform hollow hemispheres. The fabricated chemical sensor for selective detection of hydrazine displays a high sensitivity of 106.25 μA/(mM cm2) with a low detection limit of 0.5 μM and it also exhibits excellent reproducibility and stability in hydrazine detection.
Gender differences in brain networks during verbal Sternberg tasks: A simultaneous near‐infrared spectroscopy and electro‐encephalography study
Authors: Gao Chenyang , Sun Jinyan , Yang Xiaoquan , Gong Hui 
Published: September 2017

Gender differences in psychological processes have been of great interest in a variety of fields including verbal fluency, emotion processing and working memory. Previous studies suggested that women outperform men in verbal working memory (VWM). However, the inherent mechanisms are still unclear. To obtain a deeper insight into the gender differences in brain networks in VWM, this study used near‐infrared spectroscopy (NIRS) and electro‐encephalography (EEG) simultaneously to investigate gender‐related brain networks during verbal Sternberg tasks. NIRS results confirmed that women surpass men in VWM from the perspective of both brain activation and connectivity. Results of EEG (effective connectivity and event‐related spectral power) showed that men tend to use a more visuospatial strategy to encode memory. In addition, novel analysis methods of brain networks can provide useful information about the gender specifics of brain functions.Gender‐related pseudo‐color maps constructed from all channels of average HbO2 activity during low‐ and high‐load tasks (from 0 to 6 seconds after beginning).
Single‐dose local administration of teriparatide with a octacalcium phosphate collagen composite enhances bone regeneration in a rodent critical‐sized calvarial defect
Authors: Kajii Fumihiko , Iwai Atsushi , Tanaka Hidenori , Matsui Keiko , Kawai Tadashi , Kamakura Shinji 
Published: September 2017

AbstractOctacalcium phosphate and collagen composite (OCP/Col) achieves stable bone regeneration without cell transplantation in preclinical studies. Recently, a sponsor‐initiated clinical trial was conducted to commercialize the material. The present study investigated bone regeneration by OCP/Col with the single local administration of teriparatide (parathyroid hormone 1‐34; TPTD). OCP/Col was prepared by mixing sieved granules of OCP and atelocollagen for medical use and a disk was molded. After the creation of a rodent critical‐sized calvarial defect, OCP/Col or OCP/Col with dripped TPTD solution (1.0 or 0.1 µg; OCP/Col/TPTDd1.0 or OCP/Col/TPTDd0.1) was implanted into the defect. Six defects in each group were fixed 12 weeks after implantation. Radiographic examinations indicated that radiopaque figures in defects treated with OCP/Col with TPTD (OCP/Col/TPTDd) occupied a wider range than those treated with OCP/Col. Histological results demonstrated that most of the defect in OCP/Col/TPTDd was filled with newly formed bone. A histomorphometrical examination indicated that the percentage of newly formed bone was significantly higher in the defects of OCP/Col/TPTDd 1.0 (53.6 ± 4.3%) and OCP/Col/TPTDd 0.1 (52.2 ± 7.4%) than in those of OCP/Col (40.1 ± 8.4%), whereas no significant differences were observed between OCP/Col/TPTDd1.0 and OCP/Col/TPTDd0.1. These results suggest that OCP/Col with the single local administration of TPTD enhances bone regeneration in a rodent calvarial critical‐sized bone defect. © 2017 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1851–1857, 2018.
Laser micro‐ablation of fibrocartilage tissue: Effects of tissue processing on porosity modification and mechanics
Authors: Matuska A. M. , McFetridge P. S. 
Published: September 2017

ABSTRACTThe temporomandibular joint disk (TMJd) is an extremely dense and avascular fibrocartilaginous extracellular matrix (ECM) resulting in a limited regenerative capacity. The use of decellularized TMJd as a biocompatible scaffold to guide tissue regeneration is restricted by innate subcellular porosity of the ECM that hinders cellular infiltration and regenerative events. Incorporation of an artificial microporosity through laser micro‐ablation (LMA) can alleviate these cell and diffusion based limitations. In this study, LMA was performed either before or after decellularization to assess to effect of surfactant treatment on porosity modification as well as the resultant mechanical and physical scaffold properties. Under convective flow or agitation schemes, pristine and laser ablated disks were decellularized using either low (0.1% w/v) or high (1% w/v) concentrations of sodium dodecyl sulfate (SDS). Results show that lower concentrations of SDS minimized collagen degradation and tissue swelling while retaining its capacity to solubilize cellular content. Regardless of processing scheme, laser ablated channels incorporated after SDS treatment were relatively smaller and more uniform than those incorporated before SDS treatment, indicating an altered laser interaction with surfactant treated tissues. Smaller channels correlated with less disruption of native biomechanical properties indicating surfactant pre‐treatment is an important consideration when using LMA to produce artificial porosity in ex vivo derived tissues. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1858–1868, 2018.
Clinical Pharmacology Tools and Evaluations to Facilitate Comprehensive Dose Finding in Oncology: A Continuous Risk‐Benefit Approach
Authors: Bullock Julie M. , Lin Tiffany , Bilic Sanela 
Published: September 2017

AbstractTargeted therapies are now considered an integral component in the treatment armamentarium for many malignancies, and the approach to developing these drugs needs to be refined from the previous cytotoxic paradigm of toxicity‐guided dose finding and identification of maximum tolerated dose to a paradigm driven by target activity. Moving away from the toxicity‐driven dose finding and justification model requires an integrated approach in order to adequately characterize the risk‐benefit of a drug. This approach starts with understanding the importance of collecting samples for pharmacokinetic and pharmacodynamic assessments in all phases of clinical development to fully characterize the pharmacokinetics and identify covariates and then correlating exposure to key markers of safety and efficacy in pharmacometric analyses to perform a robust risk‐benefit assessment and establish the right dose. In addition, for oral agents, decisions on administering the drug with respect to food can impact dose among other clinical trial outcomes such as tolerability and patient compliance. Understanding the importance of model‐based drug development as a decision‐making tool to support drug development through incorporation of all relevant data allows for a robust risk‐benefit assessment at key decision points. Utilization of clinical pharmacology tools and assessments throughout development will provide the key components of a successful oncology development program.
Pharmacokinetic‐Guided Dosing of New Oral Cancer Agents
Authors: Lucas Catherine J. , Martin Jennifer H. 
Published: September 2017

AbstractGenerally, licensed drug‐dosing recommendations for chemotherapy are based on results from clinical trials in which subjects are usually of relatively normal body size, middle‐aged, and are relatively racially homogeneous, with minimal comorbidity and specific tumor characteristics. Very few nontrial patients meet these characteristics, resulting in clinical practice having to extrapolate dosing recommendations to the specific patient. There is insufficient research on the impact of obesity‐associated physiological changes prevalent in patients with common cancers on standard pharmacokinetic and pharmacodynamic parameters. Yet quantifying the influence of obesity on the pharmacology of chemotherapy is vital, as dosing inappropriate for body composition (ie, flat dosing or mg/kg based on total body weight) may increase the risk of adverse events and reduce clinical effectiveness. Unfortunately, there are few cancer guidelines to aid clinicians in selecting the optimal dose in the obese—even recent guidelines are based predominantly on clinical opinion/current practice in treating obese patients, rather than evidence. Data in many other vulnerable groups, for example, those with significant comorbidity and older patients, are also scarce. Because of the known limitations of body surface area–guided dosing, therapeutic drug monitoring or pharmacokinetic‐guided dosing, which predicts an individual's exposure, has increasingly been shown to be a powerful tool in cancer therapy. Used appropriately, it can adjust for differences in pharmacokinetic parameters not considered when body size–based dosing or “one dose fits all” is used. This review will focus predominantly on the rationale for pharmacokinetic‐guided dosing of the newer oral molecularly targeted antineoplastics in people whose drug exposure is not predicted by their physiology or body composition.
How Often Are Drugs Made Available Under the Food and Drug Administration's Expanded Access Process Approved?
Authors: McKee Amy E. , Markon André O. , Chan‐Tack Kirk M. , Lurie Peter 
Published: September 2017

AbstractIn this review of individual patient expanded‐access requests to the Center for Drug Evaluation and Research for the period Fiscal Year 2010 to Fiscal Year 2014, we evaluated the number of applications received and the number allowed to proceed. We also evaluated whether drugs and certain biologics obtained under expanded access went on to be approved by the Food and Drug Administration. Finally, we considered concerns that adverse events occurring during expanded access might place sponsors at risk for legal liability. Overall, 98% of individual patient expanded‐access requests were allowed to proceed. During the study period, among drugs without a previous approval for any indication or dosage form, 24% of unique drugs (ie, multiple applications for access to the same drug were considered to relate to 1 unique drug), and 20% of expanded‐access applications received marketing approval by 1 year after initial submission; 43% and 33%, respectively, were approved by 5 years after initial submission. A search of 3 legal databases and a database of news articles did not appear to identify any product liability cases arising from the use of a product in expanded access. Our analyses seek to give physicians and patients a realistic perspective on the likelihood of a drug's approval as well as certain information regarding the product liability risks for commercial sponsors when providing expanded access to investigational drugs. The US Food and Drug Administration (FDA)’s expanded‐access program maintains a careful balance between authorizing patient access to potentially beneficial drugs and protecting them from drugs that may have unknown risks. At the same time, the agency wishes to maintain the integrity of the clinical trials process, ultimately the best way to get safe and effective drugs to patients.
Antibody–Drug Conjugates as Cancer Therapeutics: Past, Present, and Future
Authors: Vezina Heather E. , Cotreau Monette , Han Tae H. , Gupta Manish 
Published: September 2017

AbstractAntibody–drug conjugates (ADCs) represent an innovative therapeutic approach that provides novel treatment options and hope for patients with cancer. By coupling monoclonal antibodies (mAbs) to cytotoxic small‐molecule payloads with a plasma‐stable linker, ADCs offer the potential for increased drug specificity and fewer off‐target effects than systemic chemotherapy. As evidence for the potential of these therapies, many new ADCs are in various stages of clinical development. Because their structure poses unique challenges to pharmacokinetic and pharmacodynamic characterization, it is critical to recognize the differences between ADCs and conventional chemotherapy in the design of ADC clinical development strategies. Although some properties may be determined mainly by either the mAb or the small‐molecule portion, the behavior of these agents is not always predictable. Furthermore, because the absorption, distribution, metabolism, and excretion (ADME) of ADCs are influenced by all 3 of its components (mAb, linker, and payload), it is important to characterize the intact molecule, any target‐mediated catabolic clearance of the mAb, and the ADME properties of the small‐molecule payload. Here we describe key issues in the clinical development of ADCs, including considerations for designing first‐in‐human studies for ADCs. We discuss some difficulties of ADC pharmacokinetic characterization and current approaches to overcoming these challenges. Finally, we consider all aspects of clinical pharmacology assessment required during drug development, using examples from the literature to illustrate the discussion.
Pharmacogenomics Implementation at the National Institutes of Health Clinical Center
Authors: Sissung Tristan M. , McKeeby Jon W. , Patel Jharana , Lertora Juan J. , Kumar Parag , Flegel Willy A. , Adams Sharon D. , Eckes Ellen J. , Mickey Frank , Plona Teri M. , Mellott Stephanie D. , Baugher Ryan N. , Wu Xiaolin , Soppet Daniel R. , Barcus Mary E. , Datta Vivekananda , Pike Kristen M. , DiPatrizio Gary , Figg William D. , Goldspiel Barry R. 
Published: September 2017

AbstractThe National Institutes of Health Clinical Center (NIH CC) is the largest hospital in the United States devoted entirely to clinical research, with a highly diverse spectrum of patients. Patient safety and clinical quality are major goals of the hospital, and therapy is often complicated by multiple cotherapies and comorbidities. To this end, we implemented a pharmacogenomics program in 2 phases. In the first phase, we implemented genotyping for HLA‐A and HLA‐B gene variations with clinical decision support (CDS) for abacavir, carbamazepine, and allopurinol. In the second phase, we implemented genotyping for drug‐metabolizing enzymes and transporters: SLCO1B1 for CDS of simvastatin and TPMT for CDS of mercaptopurine, azathioprine, and thioguanine. The purpose of this review is to describe the implementation process, which involves clinical, laboratory, informatics, and policy decisions pertinent to the NIH CC.