bluuebunny/crossref_metadata_2025_split huggingface dataset:
Secondary Ion Mass Spectrometry
Authors: Watts John F. , Wolstenholme John , Webb Roger P. 
Published: October 2012

Abstract
An overview of secondary ion mass spectrometry (SIMS) is given. It is placed in context of other surface analytical techniques. The SIMS technique is divided into static, dynamic, and imaging SIMS. The basic operations, assumptions, and variations are explained with examples from the scientific literature. Problems associated with interpreting the collected data and the ways in which the data is interpreted are given. The recommendations from ASTM and ISO in the use of SIMS and interpretation of the data are referenced.
Ultrasonic Atomic Force Microscopy
Authors: Yamanaka Kazushi , Tsuji Toshihiro 
Published: October 2012

Abstract
For the development of advanced electronic and mechanical devices on the micro‐ and nanoscale, there is an increasing need for the characterization of elasticity and subsurface defects. As a useful method, principle, implementation, and applications of ultrasonic atomic force microscopy (UAFM) and related methods for elastic materials characterization are described. It measures the contact stiffness from the resonance frequency of cantilever with the tip in contact with the sample surface. We focus on the concept of effective enhancement of the cantilever stiffness caused by the inertia of a soft cantilever at or above the contact resonance frequency. By virtue of this effect, new findings on elasticity of materials were achieved by many groups so far. Relation between UAFM and ordinary atomic force microscopy (AFM) is explained in detail. Also, lateral modulation atomic force microscopy (LM‐AFM) with application to nanotribology is explained.
Magneto‐Optical Characterization of Magnetic Thin Films, Surfaces, and Interfaces at Small Length and Short Timescales
Authors: Kirilyuk Andrei , Kimel Alexey V. , Savoini Matteo , Rasing Theo 
Published: October 2012

AbstractThe understanding of magnetism at its fundamental length and timescales related to the exchange interaction, that is, at nanometer (nm) length and femtosecond (fs) timescales, is becoming essential as future magnetic recording aims at Tbit densities switched at THz rates, which is exactly this regime. Magnetization‐sensitive second harmonic generation (MSHG) is a nonlinear optical technique that, due to the dipole selection rules, is specifically sensitive to surfaces and interfaces of centrosymmetric media. This surface/interface sensitivity of MSHG in combination with very large magneto‐optical effects has lead to a fast development of this technique over the past decade, demonstrating atomic scale resolution in the direction perpendicular to the interfaces. To increase the lateral resolution of magneto‐optics beyond the diffraction limit, scanning near‐field optical microscopy techniques are more appropriate. The development of novel probes that preserve the polarization has led to the possibility of magneto‐optical characterization of magnetic nanostructures with spatial resolution beyond 100 nm. The combination of these and other magneto‐optical techniques with pump–probe approaches finally allows one to include time resolution down to the femtosecond range in the magneto‐optical characterization of magnetic structures. The main attention of the present chapter is on the application of the MSHG, SNOM, and pump–probe techniques to magnetic thin films and surfaces, with a focus on the achieved progress in understanding of magnetic phenomena at the smallest length and shortest timescales. On the one hand, an extreme sensitivity of MSHG to the electronic and magnetic structure of clean surfaces has been successfully demonstrated. On the other hand, the penetration depth of light has allowed to use this sensitivity to study buried interfaces in multilayer systems. Various phenomena, such as surface states on magnetic metals, enhanced magnetic moments of low‐coordinated atoms, and quantum well states, have been studied. Complimentary to these developments, we show how SNOM gives in‐plane information about submicron magnetic domain structures. Finally, we demonstrate how magneto‐optical pump–probe techniques can be used to study the dynamics of magnetic phenomena with a time resolution down to femtoseconds.
Review of Drug Metabolism in Drug Discovery and Development
Authors: White Ronald E. 
Published: October 2012

AbstractDrug metabolism is the process of chemical conversion of a drug to a metabolite preparatory to its elimination from the body. Four general categories of drug metabolic reactions occur: oxidations, reductions, conjugations, and hydrolyses. Metabolism is an important aspect of the clinical profile of a drug, since it is often a determinant of half‐life, a source of drug–drug interactions, a reason for interindividual variability of drug response, and a source of toxicities.
Extrahepatic Drug‐Metabolizing Enzymes and Their Significance
Authors: Jhajra Shalu , Ramesh Varkhede Ninad , Suresh Ahire Deepak , Vidyasagar Naik Bukke , Prasad Bhagwat , Paliwal Jyoti , Singh Saranjit 
Published: October 2012

AbstractDrug‐metabolizing enzymes (DMEs) are primarily expressed in the liver but their role in the extrahepatic tissues such as gastrointestinal tract (GIT), pulmonary, excretory, nervous, cardiovascular system, and skin cannot be neglected. Generally, the expression of DMEs in extrahepatic tissues is quantitatively lower than that in the liver, but there are a few enzymes such as CYP1A1, CYP1B1, CYP2F1, and CYP2U1 that are more abundant in extrahepatic organs. As many extrahepatic organs are portals for administered drugs, DMEs expressed in these organs can be responsible for significant metabolism, leading to first‐pass effects and lower bioavailability. Extrahepatic DMEs are also involved in bioactivation of prodrugs and formation of reactive metabolites that may interact with cellular components, resulting in organ‐specific toxicity. Activity and expression of extrahepatic DMEs is often altered by coadministered drugs, leading to drug–drug interactions. Expression of DMEs in living beings affected by a host of environmental and genetic factors such as genetic polymorphism, age, gender, pathophysiological conditions, inborn errors in metabolism, food habits, and environmental pollutants, contributing to varied drug effects and idiosyncratic toxicities.
The Significance and Determination of Plasma Protein Binding
Authors: Damre Anagha A. , Iyer Krishna R. 
Published: October 2012

Abstract
Drug protein binding can impact both the pharmacokinetics (absorption, distribution and clearance) and pharmacodynamics (receptor/enzyme interaction) of a drug. Among all the proteins that drugs can potentially bind to, binding to plasma proteins and more specifically to human serum albumin, is of significance. Thus, estimation of plasma protein binding is an important part of characterization of a new chemical entity during its development into a drug. Methods to determine plasma protein binding can be broadly divided into methods that either involve or obviate the need for prior separation of protein‐bound and unbound drug. Methods requiring no separation of bound and unbound drug include surface plasmon resonance, capillary electrophoresis, NMR, fluorescence spectroscopy, etc., while equilibrium dialysis, ultracentrifugation, ultrafiltration, microdialysis, involve pre‐separation of bound and free drug for the determination of free fraction of the drug. Some of the methods are amenable to automation and high throughput requirements of drug discovery, but equilibrium dialysis is still considered the ‘gold standard’ for estimation of drug protein binding.
Influence of Changes in Physiology, Transporters, and Enzyme Expression on Disposition and Metabolism of Drugs during Pregnancy and Clinical Implications
Authors: Jhajra Shalu , Singh Saranjit , Holm Karsten A. , Faqi Ali Said , Sahi Jasminder 
Published: October 2012

AbstractSafe and effective administration of drugs during pregnancy is a challenge due to physiological changes in the mother and limited development of the mechanisms of metabolism of xenobiotics in the fetus. In particular, concentrations of transporters such as PgP, BCRP, MRP3, OCT3, and OCTN1 change in the mother's placenta and fetal tissues with advancing gestation, confounding standard therapies. Drug‐metabolizing enzymes in the placenta and developing fetus differ from those in the liver of the mother. For example, CYP3A7 is the predominant CYP3A isoform in the fetus, while CYP3A4 is predominant in adults. These isoforms have different substrates and kinetics, and thus, challenges to the fetus can be very different. Hence, there is a need for selectivity in administration of drugs and for titrating the dose to maintain efficacy and/or minimize side effects during pregnancy. This is particularly important for drugs with a narrow therapeutic window or those with marked pharmacologic or toxicological outcomes, and also for drugs that are metabolized predominantly by a single enzyme or transporter. Before initiating any new drug regimen during pregnancy, there is the need for systemic monitoring of plasma concentrations for exposure, especially during the initial days of therapy. It is anticipated that with the advancement of understanding of drug metabolism and transport in the placenta and fetus, the potential for making early predictions with respect to effect and tolerance of drugs may be possible, resulting in safer drug therapies for both pregnant mothers and fetus.
When and How to Apply
ADMET
Principles to Drug Discovery and Development
Authors: Smith Dennis A. 
Published: October 2012

Abstract

Absorption, Distribution, Metabolism and Toxicity screening data is now a routine part of drug discovery. Although similar screening systems are providing structure activity relationships (SAR) to projects throughout the world both in industry and academica, the use of the data is not constant. This chapter reviews the various screens and puts the output of the screens into context. Examples of misused screening data are exemplified by protein binding. Many projects try to optimise molecules to provide a higher free fraction based on static
in vitro
experiments. This is scientifically wrong sine unbound plasma concentrations for oral drugs are controlled by intrinsic clearance, data which is provided by completely different screens. The data from screens for intrinsic clearance may themselves be compromised by lack of correction for reagent binding. The chapter provides a framework for designing screening strategies which include ADMET and list important criteria to be considered in defining probabilities of project success.
Applications Using C
aco
‐2 and
TC
7 Cells for Drug Metabolism Studies
Authors: Ferrec Eric Le , Fardel Olivier 
Published: October 2012

Abstract
The purpose of this chapter is the description of cell culture model most used for the study of intestinal passage. After a brief description of intestinal metabolism, the advantages and disadvantages of the caco‐2 model and an example of protocol are discussed. The use of this cellular the model requires precision. These pages are therefore intended to assist a new user in the development of this model in the laboratory.
Triple Quadrupole and Quadrupole Ion Trap Mass Spectrometers
Authors: Ridgeway Mark E. , Glish Gary L. 
Published: October 2012

AbstractMass spectrometers based on ion separation using electrodynamic quadrupolar fields have been dominant in the evolution of the field of mass spectrometry. This chapter discusses triple quadrupole mass spectrometers and quadrupole ion trap mass spectrometers, two of the most important and commercially successful instruments in the history of mass spectrometry. An overview of the principles of operation is discussed in terms of the Mathieu stability diagram, a well‐known graphical representation to determine whether ions will have stable or unstable trajectories in a radio frequency (RF) electric field. A brief introduction of tandem mass spectrometry (MS/MS) is also presented. After the general introduction, each type of instrument is discussed individually. A brief historical background is provided for each type of instrument. Finally, there is an overview of the wide array of methods to perform MS/MS experiments.
Current and Future Tools for Predicting Clinical Drug–Drug Interactions
Authors: Bullock Peter L. , Trubetskoy Olga V. 
Published: October 2012

AbstractIn this chapter we describe mechanisms of DDIs in different segments of clinical populations focusing on PK‐based, clinically significant DDIs, and provide information and discuss availablein vitroanalytical tools, assays and platforms to assess and predict possible DDIs in humans at the different stages of drug development process. We analyze and discuss successes and limitation of current approaches including future developments and modern technological advances of the field.
Mechanical Alloying of β‐Type Ti–Nb for Biomedical Applications
Authors: Zhuravleva Ksenia , Scudino Sergio , Khoshkhoo Mohsen Samadi , Gebert Annett , Calin Mariana , Schultz Ludwig , Eckert Jürgen 
Published: October 2012

Abstractβ‐Type Ti–Nb powders which are needed as precursors for porous implant materials were produced by mechanical alloying of elemental powders. The effect of different fractions of the inorganic milling agent NaCl on the phase reactions during the milling process was investigated by means of X‐ray diffraction and scanning and transmission electron microscopy. It was demonstrated, that addition of ≥2 wt% NaCl during continuous ball milling is efficient for establishing a nanostructured β‐phase alloy and for the achievement of high powder yield.
Cytokine responses in relation to age, gender, body mass index, Mycobacterium tuberculosis infection, and otitis media among inuit in greenland
Authors: Nielsen Nina O. , Soborg Bolette , Børresen Malene , Andersson Mikael , Koch Anders 
Published: October 2012

AbstractObjectives:To evaluate the cytokine response pattern in Inuit in Greenland in relation to age, gender, body mass index (BMI), Mycobacterium tuberculosis infection (MTI), and otitis media (OM) to assess whether Inuit may have signs of impaired immune responsiveness to infection.Methods:A cross‐sectional health assessment was conducted among inhabitants of Maniitsoq, West Greenland, in 2009, and several health outcomes were measured. The prevalence of MTI, overweight, and obesity was assessed among 263 school children and 137 adults, and OM was assessed among the children. Cytokine responses were measured in whole blood cultures after stimulation with phytohemagglutinin or purified protein derivative (PPD). Associations between cytokine concentrations, age, gender, BMI, MTI, and OM were estimated by linear regression.Results:Adults had generally higher cytokine concentrations than children. Children with MTI had 2.7 times higher interleukin (IL)‐10 concentrations than those without (P = 0.01), and girls had 80% higher IL‐10 than boys (P < 0.01) after phytohemagglutinin stimulation. Interferon (IFN)γ and tumor necrosis factor (TNF) concentrations were strongly elevated among children (PIFNγ < 0.001 and PTNF < 0.001) and adults (PIFNγ < 0.001 and PTNF <0.01) with MTI compared to those without after PPD stimulation. Adult women had significantly lower IFNγ (P = 0.03) and TNF (P = 0.04) concentrations than men. TNF was positively correlated with BMI in children (P = 0.01), and IL‐10 was positively correlated with BMI in adults (P = 0.0004) after PPD stimulation.Conclusion:We found cytokine patterns similar to those reported from other immune competent study populations. Therefore, the study does not support the suggestion that Inuit may have impaired immune reactivity to infection. Am. J. Hum. Biol., 2013. © 2012Wiley Periodicals, Inc.
Paternal age at birth and the risk of obesity in young adulthood: A register‐based birth cohort study of norwegian males
Authors: Eriksen Willy , Sundet Jon M. , Tambs Kristian 
Published: October 2012

AbstractObjectives:The aim of this study was to determine the relationship between paternal age at birth and the risk of obesity in young adulthood.Methods:Data from the medical birth register of Norway were linked with register data from the Norwegian National Conscript Service and the national statistics agency, Statistics Norway. This study used the data on 346,609 registered males who were born at term in single birth without physical anomalies during 1967–1984 and who were examined at the time of the mandatory military conscription (age 18–20 years). The relationship between paternal age at birth and the occurrence of obesity (body mass index (BMI) ≥ 30.0 kg/m2) at conscription was examined using a multinomial logistic regression analysis with BMI < 25.0 kg/m2 as the reference outcome category.Results:The relative risk of obesity at conscription increased linearly with increasing paternal age at birth but did not increase (P = 0.52) with maternal age at birth. Men born when their fathers were 50 years or older had a 55% (95% confidence interval (CI): 14%, 110%) higher relative risk of obesity than men born when their fathers were younger than 20 years of age, after adjustment for age at conscription, birth order, birth year, maternal age at birth, the mother's total number of children, and maternal and paternal education levels.Conclusions:The risk of obesity in young Norwegian men increases with advancing paternal age at birth but does not increase with advancing maternal age at birth. Am. J. Hum. Biol., 2013. © 2012Wiley Periodicals, Inc.
A three‐dimensional analysis of bilateral directional asymmetry in the human clavicle
Authors: Abdel Fatah Emam ElHak , Shirley Natalie R. , Mahfouz Mohamed R. , Auerbach Benjamin M. 
Published: October 2012

AbstractThis study presents a novel three‐dimensional analysis using statistical atlases and automated measurements to assess diaphyseal morphology of the clavicle and its relationship to muscle asymmetry. A sample of 505 individuals (285 males, 220 females) from the William McCormick Clavicle Collection was CT scanned, segmented, and added to a statistical bone atlas that captures correspondence between homologous points on the bone surfaces. Muscle attachment sites were localized on the atlas and then propagated across the entire population. Cross‐sectional contours were extracted at 5% increments along the entire bone, as well as at muscle attachment sites and the clavicle waist; maximum and minimum dimensions of each cross‐sectional contour were calculated. In addition, the entire three‐dimensional surface was examined for asymmetry by analyzing the magnitude and directional differences between homologous points across all bone surfaces in the dataset. The results confirm the existing studies on clavicle asymmetry, namely that the left clavicle is longer than the right, but the right is more robust than the left. However, the patterns of asymmetry are sexually dimorphic. Males are significantly asymmetric in all dimensions and at muscle and ligament attachment sites (P < 0.05), whereas female asymmetry is more variable. We hypothesize that this is related to absolute and relative differences in male muscle strength compared to females. However, an area with no muscle attachments on the posterior midshaft was significantly asymmetric in both sexes. We suggest that this is a curvature difference caused by opposing muscle actions at the medial and lateral ends of the bone. Am J Phys Anthropol 2012. © 2012 Wiley Periodicals, Inc.
Measurement of concentration profiles using confocal Raman spectroscopy in multicomponent polymeric coatings—model validation
Authors: Arya Raj Kumar , Vinjamur Madhu 
Published: October 2012

AbstractConcentrations of the solvents were measured using confocal laser Raman Spectroscopy for two ternary systems, poly(styrene)—tetrahydrofuran—p‐xylene and poly(methyl methacrylate)—ethylbenzene—tetrahydrofuran, during drying at room temperature. The concentrations were compared with predictions of drying models, which utilize several existing theories for mutual diffusion coefficients for polymer solvent systems. Of the nine free volume parameters required to predict diffusion coefficients of binary systems, four for each of the four pairs studied here were estimated as suggested by the literature. Estimation was done by minimizing the difference between predictions of the model and experimental weight loss data for each binary pair. It is found that the predictions of the models which include cross term diffusion coefficients are in better agreement with measured concentrations than those which ignore the cross terms. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013
Heterologous Expression and Structural Characterisation of a Pyrazinone Natural Product Assembly Line
Authors: Wyatt Morgan A. , Mok M. C. Y. , Junop Murray , Magarvey Nathan A. 
Published: October 2012

AbstractThrough a number of strategies nonribosomal peptide assembly lines give rise to a metabolic diversity not possible by ribosomal synthesis. One distinction within nonribosomal assembly is that products are elaborated on an enzyme‐tethered substrate, and their release is enzyme catalysed. Reductive release by NAD(P)H‐dependent catalysts is one observed nonribosomal termination and release strategy. Here we probed the selectivity of a terminal reductase domain by using a full‐length heterologously expressed nonribosomal peptide synthetase for the dipeptide aureusimine and were able to generate 17 new analogues. Further, we generated an X‐ray structure of aureusimine terminal reductase to gain insight into the structural details associated with this enzymatic domain.
Referenced Dual Pressure‐ and Temperature‐Sensitive Paint for Digital Color Camera Read Out
Authors: Fischer Lorenz H. , Karakus Cüneyt , Meier Robert J. , Risch Nikolaus , Wolfbeis Otto S. , Holder Elisabeth , Schäferling Michael 
Published: October 2012

AbstractThe first fluorescent material for the referenced simultaneous RGB (red green blue) imaging of barometric pressure (oxygen partial pressure) and temperature is presented. This sensitive coating consists of two platinum(II) complexes as indicators and a reference dye, each of which is incorporated in appropriate polymer nanoparticles. These particles are dispersed in a polyurethane hydrogel and spread onto a solid support. The emission of the (oxygen) pressure indicator, PtTFPP, matches the red channel of a RGB color camera, whilst the emission of the temperature indicator [PtII(Br‐thq)(acac)] matches the green channel. The reference dye, 9,10‐diphenylanthracene, emits in the blue channel. In contrast to other dual‐sensitive materials, this new coating allows for the simultaneous imaging of both indicator signals, as well as the reference signal, in one RGB color picture without having to separate the signals with additional optical filters. All of these dyes are excitable with a 405 nm light‐emitting diode (LED). With this new composite material, barometric pressure can be determined with a resolution of 22 mbar; the temperature can be determined with a resolution of 4.3 °C.
Jahn–Teller Effect in Circulenes: X‐ray Diffraction Study of Coronene and Corannulene Radical Anions
Authors: Filatov Alexander S. , Sumner Natalie J. , Spisak Sarah N. , Zabula Alexander V. , Rogachev Andrey Yu. , Petrukhina Marina A. 
Published: October 2012

AbstractSingle‐crystal X‐ray diffraction studies of two polyaromatic radical anions crystallized as sodium salts, namely [Na(DME)3]+[C20H10−] (1) and [Na(DME)3]+[C24H12−] (2) are reported. This allowed the first structural evaluation of Jahn–Teller (JT) effects for monoreduced circulenes and a comparison between bowl‐shaped corannulene and planar coronene. The Cs and D2h symmetrical distortions are found to fit the experimental data for C20H10.− and C24H12.−, respectively. The continuous symmetry measure (CSM) analysis was carried out to provide a quantitative measure of the JT distortions in 1 and 2. In addition, the X‐ray crystallographic results were fully supported by DFT calculations.