bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detecting climate signals in precipitation extremes from TRMM (1998–2013)—Increasing contrast between wet and dry extremes during the “global warming hiatus”
Authors: Wu Huey‐Tzu Jenny , Lau William K.‐M. 
Published: December 2015

AbstractWe investigate changes in daily precipitation extremes using Tropical Rainfall Measuring Mission (TRMM) data (1998–2013), which coincides with the “global warming hiatus.” Results show a change in probability distribution functions of local precipitation events (LPEs) during this period consistent with previous global warming studies, indicating increasing contrast between wet and dry extremes, with more intense LPE, less moderate LPE, and more dry (no rain) days globally. Analyses for land and ocean separately reveal more complex and nuanced changes over land, characterized by a strong positive trend (+12.0% per decade, 99% confidence level (c.l.)) in frequency of extreme LPEs over the Northern Hemisphere extratropics during the wet season but a negative global trend (−6.6% per decade, 95% c.l.) during the dry season. A significant global drying trend (3.2% per decade, 99% c.l.) over land is also found during the dry season. Regions of pronounced increased dry events include western and central U.S., northeastern Asia, and Southern Europe/Mediterranean.
Strengthening relationship between ENSO and western Russian summer surface temperature
Authors: Sun Cheng , Li Jianping , Ding Ruiqiang 
Published: December 2015

AbstractWestern Russia (WR) experienced an extremely hot summer in 2010 that caused tremendous social and economic losses. The WR summer surface temperature (WRST) in the observational record is characterized by substantial interannual variability superimposed on the secular warming trend. Analysis of the 130 year observational record reveals that a strong and significant inverse relationship between WRST interannual variability and the tropical El Niño–Southern Oscillation (ENSO) has emerged during the past three decades. The ENSO influence on the summer extratropical atmospheric circulation was weak before 1980 but became strong and significant afterward, showing a structure similar to the East Atlantic/WR teleconnection pattern. This pattern is associated with rising/falling upper level geopotential height over WR, which leads to the warming/cooling of surface and tropospheric air temperatures. Numerical simulations from a theoretical linear baroclinic model and Atmospheric Model Intercomparison Project models further suggest that the enhancement of the ENSO teleconnection to WR may be attributable to a change in the ENSO‐related tropical thermal forcing. A tripole‐type rainfall anomaly pattern over tropical Pacific and Atlantic is found to be associated with ENSO in the past three decades. The tripole heating pattern can excite a Rossby wave that extends northwestward reaching WR and is necessary for the strong influence of ENSO on WR summer climate.
Interaction of magnetospheric Alfvén waves with the ionosphere in the Pc1 frequency band
Authors: Fedorov E. , Mazur N. , Pilipenko V. , Engebretson M. 
Published: December 2015

AbstractA characteristic feature of the upper ionosphere is the occurrence of the ionospheric Alfvén resonator (IAR) and MHD waveguide, which can trap electromagnetic wave energy in the range from fractions of a Hz to a few Hz. This wave trapping ensures the strong dependence of the ionospheric transmission/reflective properties on frequency. We have developed a numerical model of the magnetospheric Alfvén wave interaction with the ionosphere and transmission to the ground based on the solution of multifluid magnetohydrodynamic (MHD) full wave equations in a realistic ionosphere, whose parameters were reconstructed from the International Reference Ionosphere model. The MHD modes are coupled owing to the frequency‐dependent Hall conductivity and geomagnetic field line inclination. This model can be applied to the interpretation of the spectral structure of electromagnetic emissions of the magnetospheric origin in the band 0.1–10 Hz observed at various latitudes. The model predicts that the upper part of the ULF spectrum (f > 1 Hz) will be severely absorbed upon wave transmission through the daytime ionosphere to the ground. At nighttime the transmission coefficient of Alfvén waves has an oscillatory dependence on frequency, with “transmission windows” at the lowest IAR eigenfrequencies (<3 Hz). At higher frequencies (3–10 Hz) the reflection/transmission coefficients are dominated by periodic scale‐dependent modulation owing to the waveguide modes. Broad maxima/minima of the transmission coefficient are determined by the phasing between Alfvén and fast magnetosonic waves at the bottom of the ionosphere.
The impacts of precipitating hydrometeors radiative effects on land surface temperature in contemporary GCMs using satellite observations
Authors: Li J.‐L. F. , Lee Wei‐Liang , Yu Jia‐Yuh , Hulley Glynn , Fetzer Eric , Chen Yi‐Chun , Wang Yi‐Hui 
Published: December 2015

AbstractAn accurate representation of the land surface temperature (LST) climatology of the coupled land‐atmosphere system has strong implications for the reliability of projected land surface processes and their variability inferred by the global climate models (GCMs) contributed to the Intergovernmental Panel on Climate Change CMIP5. We have identified a substantial underestimation of the total ice water path and biases of surface radiation budget commonly seen in the CMIP models which are highly correlated to the biases of LST over land. One of the potential causes of the CMIP model biases is the missing representation of large frozen precipitating hydrometeors and their radiative effects (i.e., snow) in all CMIP3 and most CMIP5 models. We examine the impacts of snow on the radiation, all‐sky and clear‐sky LST, and air‐land heat fluxes to explore the implications to the common biases in CMIP models by performing sensitivity experiments with and without snow radiation effects using the National Center for Atmospheric Research Community Earth System Model version 1. It is found that an exclusion of the snow radiative effects the CESM1 generates the LST biases (up to 2–3 K) in the midlatitude and high latitude, in particular, in December, January, and February (DJF). All‐sky and clear‐sky LST in model simulations are found to be too cold and are mainly due to underestimated downward surface (longwave) LW radiation in DJF, which is consistent with those in CMIP models. The correlation between the changes of the LST and downward surface LW radiation is very high both in summer and winter seasons.
Effects of amines on particle growth observed in new particle formation events
Authors: Tao Ye , Ye Xingnan , Jiang Shuqing , Yang Xin , Chen Jianmin , Xie Yuanyuan , Wang Ruyu 
Published: December 2015

AbstractParticle size distributions in the range of 0.01–10 µm were measured in urban Shanghai in the summer of 2013 using a Wide‐range Particle Spectrometer (WPS). Size‐segregated aerosol samples were collected concurrently using a Micro‐Orifice Uniform Deposit Impactor (MOUDI), which aided our in‐depth understanding of the new particle formation (NPF) mechanism in the polluted Yangtze River Delta area. During the observations, 16 NPF events occurred at high temperatures (~34.7°C) on clear and sunny days. In the ammonium‐poor PM1.0 (particulate matter less than 1.0 µm), sulfate and ammonium accounted for 92% of the total water‐soluble inorganic species. Six aminiums were detected in these MOUDI samples, among which the group of diethylaminium and trimethylaminium (DEAH+ + TMAH+) was the most abundant. The very high level of aminiums (average concentration up to 86.4 ng m−3 in PM1.8), together with highly acidic aerosols, provided insight into the frequent NPF events. The high mass ratio of total aminiums to NH4+ (>0.2 for PM0.056) further highlighted the important role of amines in promoting NPF. The concentration of DEAH+ + TMAH+ in new particles below 180 nm was strongly correlated with aerosol phase acidity, indicating that acid‐base reactions dominated the aminium formation in NPF events. The unexpected enhancement of DEAH+ + TMAH+ on a nonevent day was attributed to the transportation of an SO2 plume. Our results reveal that the heterogeneous uptake of amines is dominated by the acid‐base reaction mechanism, which can effectively contribute to particle growth in NPF events.
ADME
for Therapeutic Biologics: What Can We Leverage from Great Wealth of
ADME
Knowledge and Research for Small Molecules
Authors: Wang Weirong , Prueksaritanont Thomayant 
Published: December 2015

Abstract
This chapter presents a brief historical perspective on how the roles of drug metabolism and pharmacokinetics (DMPK) and the key enablers for studying the absorption, distribution, metabolism, and excretion (ADME) processes of small molecule (SM) drugs and their underlying mechanisms have evolved over time in order to influence internal de‐risking strategy and decisions. It reviews external factors, such as changing regulatory environments and evolving large molecule (LM) discovery and development landscape. The chapter also provides an overview of a DMPK concept analogy between SMs and LMs, as well as case examples to demonstrate the applicability of SM DMPK knowledge and experiences to LM drug discovery and development. The commonly used bioanalytical methods for the determination of LMs in biological fluids are ligand‐binding assays that are immunological in nature. These assays usually have an associated degree of nonspecificity.
ADMEfor Therapeutic Biologics: Antibody‐Derived Proteins and Proteins with Novel Scaffolds
Authors: Rathi Chetan , Meibohm Bernd 
Published: December 2015

AbstractTherapeutic monoclonal antibodies (mAbs) are the largest and most rapidly growing class of therapeutic proteins. Recent advances in protein engineering have opened up new avenues of modulating the desired properties of therapeutic proteins. This includes not only the optimization of existing protein therapeutics by approaches such as glycoengineering, but also the creation of new scaffolds such as antibody‐ drug conjugates (ADCs), antibody fragments, antibody‐based fusion proteins, nanobodies, and bispecifics. ADCs and bipecifics are among the most promising classes of antibody‐based therapeutics with a large number of candidates in various stages of preclinical and clinical development. Pharmacokinetic (PK) characterization is one of the most important determinants toward rational development of these novel scaffolds. This chapter discusses the ADME properties of ADCs, and bispecifics and its role in guiding the development of next‐generation therapeutic biologics.
Overview of
ADME
and
PK/PD
of
ADCs
Authors: Zhao Baiteng , Han Tae H. 
Published: December 2015

Abstract
This chapter primarily discusses the absorption, distribution, metabolism/catabolism, and elimination (ADME) properties for antibody‐drug conjugates (ADCs) in oncology therapy and associated pharmacokinetic (PK) and pharmacokinetic/pharmacodynamics (PK/PD) modeling of ADCs. Drug‐linker stability is a key attribute required for the development of a successful ADC and has been a primary focus in ADC technology. Premature release of the conjugated drug prior to reaching its intended target may cause unwanted systemic toxicity and reduce the amount of drug delivered to the target tissues. An exposure‐response relationship exists for all therapeutic proteins and small molecule drugs. Multiple modeling efforts have been attempted to incorporate the deconjugation process and/or nonlinear clearance in ADC PK models. A full mechanistic PK model encompassing all major processes of ADC distribution, binding, and elimination of different drug‐to‐antibody ratio (DAR) species was proposed and multiple approximations were applied to simplify the model based on different assumptions.
Fixed Dosing versus Body‐Size‐Based Dosing for Therapeutic Biologics—A Clinical Pharmacology Strategy
Authors: Wang Diane D. , Hoffman Justin T. , Parivar Kourosh 
Published: December 2015

Abstract
This chapter focuses on the dosing strategies for therapeutic biologics in human adult populations, and it is acknowledged that the strategies for the dosing of pediatric populations may be different. The aim of any dosing strategy for a therapeutic agent is to optimize the overall clinical performance within an intended indication by maximizing the efficacious effect while minimizing the adverse events within the target patient population. The performance of body‐size‐based dosing and fixed‐dosing approaches have been evaluated for monoclonal antibodies (mAbs) and therapeutic peptides/proteins, in terms of their population and individual performances in reducing intersubject pharmacokinetic (PK) and/or pharmacodynamic (PD) variability in adult patients. The results of these simulation studies have demonstrated that in contrast to conventional assumption, body‐size‐based dosing did not always result in less intersubject variability in drug exposure and PD measurements when compared to fixed‐dosing approaches.
Impact of Diseases, Comorbidity, and Target Physiology onADME, PK, andPK/PDof Therapeutic Biologics
Authors: Zheng Songmao , Wang Weirong , Zhou Honghui 
Published: December 2015

AbstractConceptually, any disease or comorbidity that can regulate or impact the ADME and subsequently the pharmacokinetics/pharmacodynamics (PK/PD) of a biologic would have an impact on the treatment response that may sometimes necessitate a dose alteration in different patient populations, different disease states, patients with varying disease burdens, or in patients with different comorbidities. The PD of a biologic is not the only aspect driven by target engagement, the PK is also often impacted via target‐mediated drug disposition (TMDD) interactions. This chapter provides an overview of our current knowledge on how diseases, comorbidity, target physiology, and other treatment interventions (e.g., surgery) impact the ADME, PK, and PK/PD of therapeutic biologics. The chapter discusses the underlying mechanisms associated with these processes. Additionally, a few case examples demonstrate, in detail, the interplay between disease, target physiology, and PK/PD of therapeutic biologics.
Integrated Quantitation of Biotherapeutic Drug–Target Binding, Biomarkers, and Clinical Response to Support Rational Dose Regimen Selection
Authors: Lowe Philip J. , Kümmel Anne , Vasalou Christina , Matsushima Soichiro , Skerjanec Andrej 
Published: December 2015

Abstract
In the development of new medicines, the posology can be critical to get the intended clinical benefit whilst minimizing dose‐related unintended or adverse effects. The use of direct drug‐target‐binding models has increased over the years, forming, in effect, a new class to be added to the original effect site and indirect response models. This chapter focuses on the capture of soluble targets. However, it is also possible to quantitate the nonlinear target‐mediated disposition in the phamacokinetics (PK) to provide an estimate of whole‐body target engagement. If related to downstream biomarkers or, preferably, to clinical outcomes, this is just as valuable to the posologist as soluble target capture. The chapter shows that the PK/phamacodynamics process enables an integrated quantitation of biotherapeutic drug‐target binding, biomarkers, and clinical response to support rational dose regimen selection.
Target‐Driven Pharmacokinetics of Biotherapeutics
Authors: Meno‐Tetang Guy M.L. 
Published: December 2015

AbstractBiotherapeutics are a class of molecules that are produced by living organisms. They comprise monoclonal antibodies (mAbs), antibody‐drug conjugates (ADCs), antibody fragments, fusion proteins, peptides, recombinant cytokines, vaccines, growth factors, oligonucleotides, and deoxyribonucleic acid (DNA) preparations. This chapter reviews published data on the contribution of target biology including expression, turnover, and binding on the PK of fusion proteins, mAbs, ADCs, cytokines, and recombinant proteins. Peptide‐Fc fusion proteins (or peptibodies) are construct proteins generated by fusing a biologically active peptide with the Fc domain of an immunoglobulin G (IgG). This construct combines the biologic activity of peptides with the stability of mAbs. Biotherapeutics display both linear and nonlinear kinetics. The PK of biotherapeutics that exhibit target‐mediated drug disposition (TMDD) are controlled by the level of target expression, turn over, and affinity. Interspecies scaling is used to predict human PK for first‐in‐ human clinical trials.
Regioselective Direct Difunctionalization of Glycals: Convenient Access to 2‐Deoxyglycoconjugates Mediated by Tetra‐n‐butylammonium Iodide/Sodium Periodate
Authors: Kundoor Govindareddy , Rao Dodla Sivanageswara , Kashyap Sudhir 
Published: December 2015

AbstractA combination of nBu4NI and NaIO4 promoted the intermolecular stereo and regioselective bisfunctionalization of glycals in a metal‐free, one‐pot process. The oxidative iodocaboxylation, iodoamination, and iodoazidation of enol ether moieties by employing carboxylic or aromatic acids, and N‐nucleophiles such as 1‐H‐benzotriazole or NaN3 led to glycosyl carboxylates, glycosyl amines, and glycosyl azides, respectively. The protocol is operationally simple, employs readily available and environmental benign reagents, and was applicable for a diverse range of substrates to obtain stereodivergent glycoconjugates in yields up to 99 % with diastereomeric ratios up to 100 %.
Multicomponent Reactions of Aldo‐X Bifunctional Reagent α‐Oxoketene Dithioacetals and Indoles or Amines: Divergent Synthesis of Dihydrocoumarins, Quinolines, Furans, and Pyrroles
Authors: Liu Changhui , Zhou Li , Jiang Dan , Gu Yanlong 
Published: December 2015

AbstractSix multicomponent reactions were developed by using aldo‐X reagents and α‐oxoketene dithioacetals with indoles or amines as substrates, which can be used to prepare many heterocycles, such as dihydrocoumarins, quinolines, furans and pyrroles, in a straightforward way. A combination of two bifunctional aldo‐X reagents and α‐oxoketene dithioacetals is the key to make the discovery of these multicomponent reactions possible because these reagents have a minimum of two reactive sites, which enable different substrates to be assembled together in various manners.
The reality of virtual anthropology: Comparing digitizer and laser scan data collection methods for the quantitative assessment of the cranium
Authors: Algee‐Hewitt Bridget F.B. , Wheat Amber D. 
Published: December 2015

ABSTRACTObjectivesThe use of geometric morphometry to study cranial variation has steadily grown in appeal over the past decade in biological anthropology. Publication trends suggest that the most popular methods for three‐dimensional data acquisition involve landmark‐based coordinate data collection using a digitizer. Newer laser scan approaches are seeing increasing use, owing to the benefits that densely sampled data offer. While both of these methods have their utility, research that investigates their compatibility is lacking. The purpose of this project is to compare, quantitatively, craniometrics collected with a digitizer against data extracted from laser scans using the same individuals and laboratory conditions.Materials and MethodsThree‐dimensional (x,y,z) coordinates and traditional inter‐landmark distances (ILDs) were obtained with a Microscribe digitizer and 360° color models produced from NextEngine laser scans for 38 adult crania representing five cemeteries from the ADBOU skeletal collection in Denmark. Variance‐based tests were performed to evaluate the disagreement between data collected with a digitizer and from laser scan models. Consideration was given to differences among landmarks by type, between ILDs calculated from landmark coordinates, and in morphology for the cemetery populations. Further, the reliability of laser scan data collection was assessed by intra‐observer error tests.ResultsResearchers should be aware of the potential error associated with the use of Types II and III landmarks and the limitations on reliability imposed by object‐to‐scanner placement.DiscussionThis project reveals how laser scans can provide a valuable digital archive of cranial material that can be reasonably exploited for the “virtual” collection of coordinates and the calculation of ILDs. Am J Phys Anthropol 160:148–155, 2016. © 2015 Wiley Periodicals, Inc.
New Prospects in Regional Health Governance: Migrant Workers' Health in the Association of Southeast Asian Nations
Authors: Nodzenski Marie , Phua Kai Hong , Bacolod Nicole 
Published: December 2015

AbstractThe Association of South East Asian Nations (ASEAN) has potential in creating regional health governance frameworks. Yet in light of the ASEAN Economic Community 2015, pressing challenges remain. Further integration will likely lead to increased movements of migrants. Protecting the health of migrant workers is thus key to ensure that regional integration's objectives of economic growth and political stability are met.With the potentially negative repercussions of unhealthy migration on ASEAN's economic and political integration, much effort should be directed towards further social integration. Why and how should a regional framework to protect migrant workers' health be negotiated through ASEAN? A key to the successful ASEAN regional framework for migrant workers' health, which is also a key challenge for the region, is the effective inclusion of various stakeholders involved in the protection of migrant workers' health. ASEAN will play a crucial role in coordinating initiatives and in creating common standards regarding treatment of migrant workers.
Pi‐Extended Diindole‐Fused Azapentacenone: Synthesis, Characterization, and Photophysical and Lithium‐Storage Properties
Authors: Zhao Jianfeng , Li Renping , Ai Wei , Dong Dai , Li Jiewei , Chen Lin , Xie Linghai , Yu Ting , Huang Wei 
Published: December 2015

AbstractPi‐extended polyaromatics tend to exhibit improved electronic properties with respect to the intrinsic structures. Herein, the rational design of a π‐extended diindole‐fused diazapentacenone (IP), with a nine‐ring‐fused core, obtained by applying an intramolecular Friedel–Crafts diacylation synthetic routine, is reported. The chemical structure, physical properties, and morphology of IP were fully characterized. Serving as an organic cathode material for a lithium‐ion battery, the as‐prepared nanorods of π‐extended IP display higher conductivity and superior electrochemical performance than those of the naked diazapentacenone without diindole fusion.