bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of iso-CF2I2 in frequency and ultrafast time domains
Authors: El-Khoury Patrick Z. , George Lisa , Kalume Aimable , Reid Scott A. , Ault Bruce S. , Tarnovsky Alexander N.
Published: March 2010

The photolysis of diiododifluoromethane (CF2I2) in condensed phases was studied by a combination of matrix isolation and ultrafast time-resolved spectroscopy, in concert with ab initio calculations. Photolysis at wavelengths of 355 or 266 nm of CF2I2:Ar samples (1:5000) held at ∼8 K yielded iso-CF2I2 (F2C–I–I), a metastable isomer of CF2I2, characterized here for the first time. The infrared (IR) spectra of this isomer were recorded in matrix experiments, and the derived positions of the C–F stretching modes are in very good agreement with the predictions of high level ab initio calculations, which show that the iso-form is a minimum on the CF2I2 ground state potential energy surface. The formation of this isomer following 350 nm excitation of CF2I2 in room temperature CCl4 solutions was monitored through its intense C–F stretching mode by means of ultrafast time-resolved IR absorption. Together, matrix isolation and ultrafast IR absorption experiments suggest that the formation of iso-CF2I2 occurs via recombination of CF2I radical and I atom. Ultrafast IR experiments detect a delayed rise of iso-CF2I–I absorption, placing an upper limit of 400 fs for the C–I bond dissociation and primary geminate recombination processes. The product absorption spectrum recorded 1 ns after 350 nm excitation of CF2I2 in solution is virtually identical to the visible absorption spectrum of iso-CF2I2 trapped in matrix isolation experiments [with subtracted I2(X) absorption]. The formation of this isomer in solution at room temperature has direct dynamic implications for the ultrafast production of molecular iodine from electronically excited CF2I2.
Globular structure of a human immunodeficiency virus-1 protease (1DIFA dimer) in an effective solvent medium by a Monte Carlo simulation
Authors: Pandey R. B. , Farmer B. L.
Published: March 2010

A coarse-grained model is used to study the structure and dynamics of a human immunodeficiency virus-1 protease (1DIFA dimer) consisting of 198 residues in an effective solvent medium on a cubic lattice by Monte Carlo simulations for a range of interaction strengths. Energy and mobility profiles of residues are found to depend on the interaction strength and exhibit remarkable segmental symmetries in two monomers. Lowest energy residues such as Arg41 and Arg140 (most electrostatic and polar) are not the least mobile; despite the higher energy, the hydrophobic residues (Ile, Leu, and Val) are least mobile and form the core by pinning down the local segments for the globular structure. Variations in the gyration radius (Rg) and energy (Ec) of the protein show nonmonotonic dependence on the interaction strength with the smallest Rg around the largest value of Ec. Pinning of the conformations by the hydrophobic residues at high interaction strength seems to provide seed for the protein chain to collapse.
AlGaAs/GaAs single electron transistor fabricated without modulation doping
Authors: See A. M. , Klochan O. , Hamilton A. R. , Micolich A. P. , Aagesen M. , Lindelof P. E.
Published: March 2010

We have fabricated a quantum dot single electron transistor, based on AlGaAs/GaAs heterojunction without modulation doping, which exhibits clear and stable Coulomb blockade oscillations. The temperature dependence of the Coulomb blockade peak line shape is well described by standard Coulomb blockade theory in the quantum regime. Bias spectroscopy measurements have allowed us to directly extract the charging energy, and showed clear evidence of excited state transport, confirming that individual quantum states in the dot can be resolved.
Thermal averaging of the indirect nuclear spin-spin coupling constants of ammonia: The importance of the large amplitude inversion mode
Authors: Yachmenev Andrey , Yurchenko Sergei N. , Paidarová Ivana , Jensen Per , Thiel Walter , Sauer Stephan P. A.
Published: March 2010

Analytic internal-coordinate representations are reported for two accurate ab initio spin-spin coupling surfaces of the ammonia molecule, J1 (N15,H) and J2(H,H). Calculations were carried out at the level of the second-order polarization propagator approximation involving coupled-cluster singles and doubles amplitudes (CCSD) and using a large specialized basis set, for a total of 841 different geometries corresponding to 2523 distinct points on the J1 (N15,H) and J2(H,H) surfaces. The results were fitted to power series expansions truncated after the fourth-order terms. While the one-bond nitrogen-hydrogen coupling depends more on the internuclear distance, the geminal hydrogen-hydrogen coupling exhibits a pronounced dependence on the bond angle. The spin-spin parameters are first vibrationally averaged, using vibrational wave functions obtained variationally from the TROVE computer program with a CCSD(T) based potential energy surface, for ammonia and its various deuterated isotopologues. The vibrationally averaged quantities are then thermally averaged to give values of the couplings at absolute temperatures of 300 and 600 K. We find that the nuclear-motion corrections are rather small. The computed one-bond couplings and their minute isotope effects are in excellent agreement with the experimental values.
Flexible picene thin film field-effect transistors with parylene gate dielectric and their physical properties
Authors: Kawasaki Naoko , Kalb Wolfgang L. , Mathis Thomas , Kaji Yumiko , Mitsuhashi Ryoji , Okamoto Hideki , Sugawara Yasuyuki , Fujiwara Akihiko , Kubozono Yoshihiro , Batlogg Bertram
Published: March 2010

Flexible picene thin film field-effect transistors (FETs) have been fabricated with parylene gate dielectric on polyethylene terephthalate substrates. The picene thin film FETs show p-channel output/transfer characteristics and the field-effect mobility μ reaches ∼1 cm2 V−1 s−1 in vacuum. The FET shows a clear O2 gas sensing effect and negligible hysteresis in the transfer curves, indicating a possible application of the transistor as O2 selective gas sensor. Furthermore, it has been found that the parylene gate dielectric can eliminate a reduction in on-state drain current caused by continuous bias-voltage application which is observed if a SiO2 gate dielectric is used.
An electrochemical cell for the efficient turn around of wafer working electrodes
Authors: Wozniak Nicholas R. , Frey Alyssa A. , Osterbur Lucas W. , Boman Timothy S. , Hampton Jennifer R.
Published: March 2010

We present a new design for an electrochemical cell for use with wafer working electrodes. The key feature of the design is the use of half turn thumb screws to form a liquid-tight seal between an o-ring and the sample surface. The assembly or disassembly of the cell requires a half turn of each thumb screw, which facilitates the quick turn around of wafer samples. The electrochemical performance of the cell is demonstrated by cyclic voltammetry and double step chronoamperometry measurements of the ferricyanide/ferrocyanide couple.
Tunneling of holes observed at work function measurements of metal/HfO2/SiO2/n-Si gate stacks
Authors: Rothschild J. A. , Avraham H. , Lipp E. , Eizenberg M.
Published: March 2010

The voltage bias that causes a transition from direct tunneling to Fowler–Nordheim tunneling in the current-voltage characteristic of a metal/HfO2/SiO2/n-Si capacitor was measured. The transition occurs in the negative gate voltage regime and can be attributed to conduction of electrons from the metal through a defect level in the HfO2 or to conduction of holes from the Si through the valence band of the HfO2. The dependence of the determined barrier height on the gate-metal work function indicates the validity of the latter model.
Origin of definite Hall voltage and positive slope in mobility-donor density relation in disordered oxide semiconductors
Authors: Kamiya Toshio , Nomura Kenji , Hosono Hideo
Published: March 2010

Amorphous oxide semiconductors (AOSs) are expected for alternative channel materials in thin-film transistors owing to their large electron mobilities. While, it is known that AOSs exhibit peculiar electron transport properties. Definite Hall voltages are observed even for mobilities <0.2 cm2/V s, which correspond to a very short mean free path (MFP) of 0.008 nm. Furthermore, Hall mobility increases with increasing the donor density. This paper reports that a percolation conduction model explains them; quantitative analyses based on the Boltzmann’s transport theory prove that carriers within the potential barriers have large MFPs of 0.5–1 nm. The percolation model also explains variable-range-hoppinglike and weak-localizationlike behaviors.
Compact and low crosstalk waveguide crossing using impedance matched metamaterial
Authors: Ding Weiqiang , Tang Donghua , Liu Yan , Chen Lixue , Sun Xiudong
Published: March 2010

A waveguide crossing mechanism based on metamaterial is proposed and numerically investigated using finite difference in time domain method. The waveguide cross is filled with impedance matched metamaterial, which has a large absolute value of refractive index, and effectively suppresses the diffraction of the guiding mode in the crossing region. The waveguide cross is ultra compact, and valid for a wide range of crossing angle with negligible crosstalk and insertion loss. The compactness and high efficiency make this crossing mechanism valuable in micro and nano photonics.
Noncontact brain activity measurement system based on near-infrared spectroscopy
Authors: Funane Tsukasa , Atsumori Hirokazu , Suzuki Atsushi , Kiguchi Masashi
Published: March 2010

We have developed a noncontact brain activity measurement system based on near-infrared spectroscopy. With this system, phosphor is placed on the scalp of the forehead and irradiated only by excitation light that has propagated in tissue. Only fluorescence emitted by the phosphor is detected, while the excitation and disturbance lights are cut using optical filters. This configuration resolved the problem of the signal-to-noise ratio loss induced by the disturbance light. The changes in hemoglobin of the human brain were measured during a working memory task, and typical time course data were obtained.
High temperature sensitivity of manganese-assisted excitonic photoluminescence from inverted core/shell ZnSe:Mn/CdSe nanocrystals
Authors: Yu Xue-Feng , Peng Xiao-Niu , Chen Zhen-Qian , Lian Chao , Su Xiong-Rui , Li Jian-Bo , Li Min , Liu Bao-Li , Wang Qu-Quan
Published: March 2010

We report efficient and long-lived exciton photoluminescence (PL) from inverted core/shell ZnSe:Mn/CdSe nanocrystals (NCs) at room temperature. Contrary to low temperature-sensitivity of Mn2+ PL from ZnSe:Mn/ZnSe NCs, the Mn2+-assisted excitonic PL from the ZnSe:4%Mn/CdSe NCs exhibits unusually high temperature-sensitivity (−2.4% per K) in the temperature range 298–334 K, which is even higher than that of the pure excitonic PL from the undoped ZnSe/CdSe NCs. Such unexpected temperature-dependence of the Mn2+-assisted excitonic PL is well explained by the deduced exciton rate equation involving the exciton-Mn2+ resonant energy transfer in the ZnSe:Mn/CdSe NCs.
Dialogical mindfulness in supervision role‐play
Authors: Andersson Lars , King Robert , Lalande Lloyd
Published: March 2010

Aims: This exploratory pilot study investigated Mindfulness‐based Role‐play (MBRP) supervision to find out how therapists would experience the approach, and to what extent they would find it useful, particularly in relation to empathy toward clients. Method: Thirteen therapists participated in a workshop, introducing mindfulness and MBRP supervision, and subsequently had one individual MBRP supervision session. Data collection and analysis: Qualitative data were collected by means of semi‐structured interviews and analysed with regard to participants' supervision experiences by means of a modified version of the Consensual Qualitative Research method. Findings: Participants predominantly had positive emotional and cognitive responses to their supervision experiences. The main supervision outcomes were empathy with the client's emotional experience, enhanced awareness of functioning as a therapist, and thoughts about how to proceed in therapy. A subset of participants also reported observed effects in therapy with clients. Conclusions: Even taking into account the methodological limitations of the study, these findings are promising and suggest that further research into the MBRP supervision approach is warranted.
Myosin II activity regulates vinculin recruitment to focal adhesions through FAK-mediated paxillin phosphorylation
Authors: Pasapera Ana M. , Schneider Ian C. , Rericha Erin , Schlaepfer David D. , Waterman Clare M.
Published: March 2010

Focal adhesions (FAs) are mechanosensitive adhesion and signaling complexes that grow and change composition in response to myosin II–mediated cytoskeletal tension in a process known as FA maturation. To understand tension-mediated FA maturation, we sought to identify proteins that are recruited to FAs in a myosin II–dependent manner and to examine the mechanism for their myosin II–sensitive FA association. We find that FA recruitment of both the cytoskeletal adapter protein vinculin and the tyrosine kinase FA kinase (FAK) are myosin II and extracellular matrix (ECM) stiffness dependent. Myosin II activity promotes FAK/Src-mediated phosphorylation of paxillin on tyrosines 31 and 118 and vinculin association with paxillin. We show that phosphomimic mutations of paxillin can specifically induce the recruitment of vinculin to adhesions independent of myosin II activity. These results reveal an important role for paxillin in adhesion mechanosensing via myosin II–mediated FAK phosphorylation of paxillin that promotes vinculin FA recruitment to reinforce the cytoskeletal ECM linkage and drive FA maturation.
The PI3K p110α isoform regulates endothelial adherens junctions via Pyk2 and Rac1
Authors: Cain Robert J. , Vanhaesebroeck Bart , Ridley Anne J.
Published: March 2010

Endothelial cell–cell junctions control efflux of small molecules and leukocyte transendothelial migration (TEM) between blood and tissues. Inhibitors of phosphoinositide 3-kinases (PI3Ks) increase endothelial barrier function, but the roles of different PI3K isoforms have not been addressed. In this study, we determine the contribution of each of the four class I PI3K isoforms (p110α, -β, -γ, and -δ) to endothelial permeability and leukocyte TEM. We find that depletion of p110α but not other p110 isoforms decreases TNF-induced endothelial permeability, Tyr phosphorylation of the adherens junction protein vascular endothelial cadherin (VE-cadherin), and leukocyte TEM. p110α selectively mediates activation of the Tyr kinase Pyk2 and GTPase Rac1 to regulate barrier function. Additionally, p110α mediates the association of VE-cadherin with Pyk2, the Rac guanine nucleotide exchange factor Tiam-1 and the p85 regulatory subunit of PI3K. We propose that p110α regulates endothelial barrier function by inducing the formation of a VE-cadherin–associated protein complex that coordinates changes to adherens junctions with the actin cytoskeleton.
Socioeconomic Disparities in Cancer Incidence and Mortality
Authors: KAWACHI ICHIRO , KROENKE CANDYCE
Published: March 2010

The association between socioeconomic status (SES) and health status is so robust and consistent that epidemiologists routinely adjust for it as a potential confounding variable when evaluating the etiologic role of other risk factors for disease. This chapter turns this logic on its head, focusing on SES as a fundamental determinant of disease, specifically cancer incidence, and mortality. The chapter is organized into four sections. The first section defines the concept of SES and describes the various approaches to its measurement. The second section summarizes observations on the general nature of the association between SES and cancer morbidity, mortality, and survival. The third section outlines the general categories of explanations, both causal and noncausal, that have been put forward to account for the association between SES and cancer. The fourth and final section provides a survey of the specific causal mechanisms underlying the relation between SES and cancer.
Solar Radiation
Authors: GREEN ADELE C. , WHITEMAN DAVID C.
Published: March 2010

This chapter discusses link between solar radiation and cancer. Topics covered include methods of measurement, determinants of solar irradiance and solar dose, measuring personal exposure to solar radiation, artificial sources of ultraviolet radiation exposure, biologic mechanisms for ultraviolet radiation carcinogenesis, cancers associated with ultraviolet radiation exposure, and opportunities for prevention.
Occupation
Authors: SIEMIATYCKI JACK , RICHARDSON LESLEY , BOFFETTA PAOLO
Published: March 2010

This chapter discusses the link between occupational carcinogens and cancer. Topics covered include sources of evidence on risk to humans due to chemicals, published literature in the field of occupational cancer, percentage of cancer attributable to occupation, occupational cancer epidemiology, molecular epidemiology and gene environment interactions, cancer prevention, and structural challenges and obstacles to conduct epidemiological research on occupational cancer.
Physical Activity
Authors: LEE I-MIN , OGUMA YUKO
Published: March 2010

This chapter discusses epidemiologic studies of physical activity and cancer prevention. There is a large body of epidemiologic data on the relation between physical activity and the risk of developing cancer. Although the direct evidence on this relation comes only from observational studies, randomized clinical trials have provided indirect evidence by examining the association of physical activity with markers of cancer risk, such as body weight and hormone levels. Moreover, several plausible biological mechanisms support the hypothesis that higher levels of physical activity decrease the incidence of various cancers. The data are clearest for colon and breast cancer, with case-control and cohort studies supporting a moderate, inverse relation between physical activity and the development of these cancers.
Infectious Agents
Authors: MUELLER NANCY E. , BIRMANN BRENDA M. , PARSONNET JULIE , SCHIFFMAN MARK H. , STUVER SHERRI O.
Published: March 2010

There is substantial evidence that infectious agents play a causal role in a variety of human malignancies. These cancers include the liver, cervix, stomach, nasopharynx, bladder, and bile duct as well as Kaposi sarcoma (KS) and several lymphomas. This chapter summarizes the biological and epidemiologic features of each of the major oncogenic infections, beginning with the viruses, followed by H. pylori, and with a brief summary of the relevant parasites.
Immunologic Factors
Authors: MORGAN GARETH J. , LINET MARTHA S. , RABKIN CHARLES S.
Published: March 2010

This chapter discusses the immunologic factors in cancer. Topics covered include structure and function of the immune system, immune variation and cancer risk, and age-related changes in immune function. Experience with a wide range of immune deficient conditions indicates that loss of immune competence does not globally increase cancer incidence. Limited sets of malignancies are increased that are specific to the underlying immune abnormalities. A common feature is the prominent excess of non-Hodgkin lymphoma (NHL) in many of these disorders.
Hereditary Neoplastic Syndromes
Authors: LINDOR NORALANE M. , LINDOR CARL J. , GREENE MARK H.
Published: March 2010

The recent clinical availability of germ-line mutation testing for susceptibility genes related to the hereditary forms of common tumors such as breast, ovary, colorectum, and melanoma has served as a powerful catalyst for diverse research activities. Laboratory research, which has been propelled forward by access to carefully annotated biological samples obtained from cancer-prone families, is now challenged by an increasingly complex regulatory environment related to the ethical use of such specimens. Practitioners are being confronted by a host of new clinical issues, including those related to predictive risk assessment, genetic counseling, and germ-line mutation testing for clinical decision-making; the duty to warn at-risk relatives versus their high-risk patient's right to privacy and confidentiality; and, most importantly, the need for evidence-based, safe, and effective management recommendations for high-risk individuals. This chapter touches briefly upon some of these issues then provides a thumbnail description of selected hereditary cancer syndromes. It considers only some disorders for which a Mendelian mode of inheritance has been established and for which at least one germ-line susceptibility gene has been identified.
Cancer of the Larynx
Authors: OLSHAN ANDREW F.
Published: March 2010

This chapter discusses the most common and best-studied histologic type of laryngeal cancer: squamous cell carcinoma of the larynx. Topics covered include classification, demographic patterns, environmental factors, host factors, and preventive measures.
Cancers of the Vulva and Vagina
Authors: MADELEINE MARGARET M. , DALING JANET R.
Published: March 2010

Vulvar and vaginal cancers are rare throughout the world. In Africa and Asia the age-adjusted incidence rates of vulvar and vaginal cancer vary from 0.1 to 1.4 per 100,000 women. Higher rates for invasive vulvar cancer were reported in Europe and the Americas. This chapter reviews the epidemiology of vulvar and vaginal cancers. Topics covered include classification, molecular genetic characteristics, demographic patterns, environmental factors, host factors, pathogenesis, and preventive measures.
Renal Cancer
Authors: MCLAUGHLIN JOSEPH K. , LIPWORTH LOREN , TARONE ROBERT E. , BLOT WILLIAM J.
Published: March 2010

Malignant tumors of the kidney account for about 2% of all new cancer cases in the United States and worldwide, with 38,890 cases and 12,840 deaths estimated for 2006 in the United States. This chapter reviews the epidemiology of renal cancer. Demographic patterns and risk factors are discussed.
Bladder Cancer
Authors: SILVERMAN DEBRA T. , DEVESA SUSAN S. , MOORE LEE E. , ROTHMAN NATHANIEL
Published: March 2010

In the United States, an estimated 57,400 cases of cancer of the urinary bladder are diagnosed and 12,500 deaths from the disease occur each year. These account for 6% of all new cases of cancer among men and 2% of cases among women, as well as 3% of cancer deaths among men and 1% among women. This chapter reviews the epidemiology of bladder cancer. Topics covered include demographic patterns, risk factors, biological markers of exposure, tumor markers, and preventive measures.
Prostate Cancer
Authors: PLATZ ELIZABETH A. , GIOVANNUCCI EDWARD
Published: March 2010

Prostate cancer is the most commonly diagnosed cancer in American men and its incidence is rising internationally. Although intensively studied, little is known conclusively about its causes, with the exception of older age, African-American racial group, and family history of prostate cancer. This chapter reviews the epidemiology of prostate cancer. Topics covered include classification, demographic patterns, environmental and host risk factors, pathogenesis, and preventive measures.
Cutaneous and Ocular Melanoma
Authors: GRUBER STEPHEN B. , ARMSTRONG BRUCE K.
Published: March 2010

This chapter reviews the epidemiology of cutaneous and ocular melanomas. Cutaneous melanoma is the most lethal form of skin cancer. There were an estimated 160,000 new cases diagnosed worldwide in 2002, more than 80% in developed countries, and 41,000 deaths, 66% in developing countries. Sun exposure is its major cause, although a variety of phenotypic and genotypic characteristics contribute substantially to the risk of this complex disease. Ocular melanoma is globally much less significant than cutaneous melanoma and shows little current evidence of uptrend in incidence, in contrast to the continuing uptrend in melanoma. Melanocytes that give risk to ocular melanomas lie principally in pigmentary epithelia that extend continuously from the choroid, a vascular membrane that separates the neural elements of the retina from the fibrous outer covering of the eye (the sclera), anteriorly to the ciliary body and iris.
Multiple Primary Cancers
Authors: SCHOTTENFELD DAVID , BEEBE-DIMMER JENNIFER L.
Published: March 2010

This chapter focuses on multiple primary cancers. Approximately 200,000 new cancers each year in the United States are multiple primary cancers, or about 16% of the annual incidence of invasive cancers. Epidemiological research on multiple primary cancers, and the risk mechanisms and patterns of multiple primary cancers are discussed.
Regulating Carcinogens
Authors: SAMET JONATHAN M. , BURKE THOMAS A. , GOLDMAN LYNN
Published: March 2010

This chapter provides a broad overview of governmental regulatory approaches to controlling exposures to carcinogens. It focuses specifically on statutes related to the United States, while giving lesser coverage to approaches in Europe. The focus is at the federal level, even though states may also promulgate regulations. Topics discussed include the identification of carcinogens, principles underlying regulations for carcinogens, and carcinogen regulation outside the United States.
Useful Biomarkers in Pediatric Eosinophilic Duodenitis and Their Existence: A Case‐control, Single‐blind, Observational Pilot Study
Authors: Neilan Nancy A , Dowling Paul J , Taylor Debra L , Ryan Pam , Schurman Jennifer V , Friesen Craig A
Published: March 2010

Objectives:

The aim of this study was to determine whether screening for food hypersensitivity could be a clinically useful biomarker for eosinophilic duodenitis in the pediatric population.

Patients and Methods:

Twenty‐two patients with functional dyspepsia and 19 controls with no significant history of gastrointestinal or allergic disorders were enrolled. Participants underwent skin prick, atopy patch, and serum‐specific (S)‐IgE, ‐IgG, and ‐IgG4 testing to corn, wheat, soy, peanut, milk, and egg. Participants in the patient group also underwent endoscopy with biopsies as part of standard care.

Results:

Three participants in the patient group did not exhibit duodenal eosinophilia on biopsy and were excluded from data analyses. The patient group consisted of 13 females and 6 males, 8 to 17 years of age. The control group consisted of 10 females and 9 males, 8 to 17 years of age. Seven patients had at least 1 positive reaction to food by skin prick, atopy patch, or SIgE testing compared with 7 controls; odds ratio 1; 95% confidence interval 0.3 to 3.7. Receiver operating characteristics curves showed SIgG and SIgG4 performed poorly or no better than chance for predicting group assignment.

Conclusions:

Allergy screening for the foods tested was not useful as a biomarker for eosinophilic duodenitis in this small study. A higher rate of positive reactions to patch testing was observed in the control group than previous studies have reported. The incidence of a positive food patch test in nonselected subjects needs further investigation. Method standardization and establishment of reference intervals are needed for atopy patch tests, SIgG, and SIgG4 to better evaluate the clinical value of these measures.
Wetting behaviour of laser synthetic surface microtextures on Ti–6Al–4V for bioapplication
Authors: Dahotre Narendra B. , Paital Sameer R. , Samant Anoop N. , Daniel Claus
Published: March 2010

Wettability at the surface of an implant material plays a key role in its success as it modulates the protein adsorption and thereby influences cell attachment and tissue integration at the interface. Hence, surface engineering of implantable materials to enhance wettability to physiological fluid under
in vivo
conditions is an area of active research. In light of this, in the present work, laser-based optical interference and direct melting techniques were used to develop synthetic microtextures on Ti–6Al–4V alloys, and their effects on wettability were studied systematically. Improved wettability to simulated body fluid and distilled water was observed for Ca–P coatings obtained by direct melting technique. This superior wettability was attributed to both the appropriate surface chemistry and the three-dimensional surface features obtained using this technique. To assert a better control on surface texture and wettability, a three-dimensional thermal model based on COMSOL’s multiphysics was employed to predict the features obtained by laser melting technique. The effect of physical texture and wetting on biocompatibility of laser-processed Ca–P coatings was evaluated in the preliminary efforts on culturing of mouse MC3T3-E1 osteoblast cells.
The role of disc-type crystal shape for micromechanical predictions of elasticity and strength of hydroxyapatite biomaterials
Authors: Fritsch Andreas , Hellmich Christian , Dormieux Luc
Published: March 2010

The successful design of ceramic bone biomaterials is challenged by two competing requirements: on the one hand, such materials need to be stiff and strong, which would suggest a low porosity (of pore sizes in the 10–100 μm range) to be targeted; on the other hand, bone biomaterials need to be bioactive (in particular vascularized), which suggests a high porosity of such materials. Conclusively, reliable information on how porosity drives the stiffness and strength properties of ceramic bone biomaterials (tissue engineering scaffolds) is of great interest. In this context, mathematical models are increasingly being introduced into the field. Recently, self-consistent continuum micromechanics formulations have turned out as expressedly efficient and reliable tools to predict hydroxyapatite biomaterials’ stiffness and strength, as a function of the biomaterial-specific porosity, and of the ‘universal’ properties of the individual hydroxyapatite crystals: their stiffness, strength and shape. However, the precise crystal shape can be suitably approximated by specific ellipsoidal shapes: while it was shown earlier that spherical shapes do not lead to satisfactory results, and that acicular shapes are an appropriate choice, we here concentrate on disc-type crystal shape as, besides needles, plates are often reported in micrographs of hydroxyapatite biomaterials. Disc-based model predictions of a substantial set of experimental data on stiffness and strength of hydroxyapatite biomaterials almost attain the quality of the very satisfactory needle-based models. This suggests that, as long as the crystal shape is clearly non-spherical, its precise shape is of secondary importance if stiffness and strength of hydroxyapatite biomaterials are predicted on the basis of continuum micromechanics, from their micromorphology and porosity.
Next-generation biomedical implants using additive manufacturing of complex, cellular and functional mesh arrays
Authors: Murr L. E. , Gaytan S. M. , Medina F. , Lopez H. , Martinez E. , Machado B. I. , Hernandez D. H. , Martinez L. , Lopez M. I. , Wicker R. B. , Bracke J.
Published: March 2010

In this paper, we examine prospects for the manufacture of patient-specific biomedical implants replacing hard tissues (bone), particularly knee and hip stems and large bone (femoral) intramedullary rods, using additive manufacturing (AM) by electron beam melting (EBM). Of particular interest is the fabrication of complex functional (biocompatible) mesh arrays. Mesh elements or unit cells can be divided into different regions in order to use different cell designs in different areas of the component to produce various or continually varying (functionally graded) mesh densities. Numerous design elements have been used to fabricate prototypes by AM using EBM of Ti-6Al-4V powders, where the densities have been compared with the elastic (Young) moduli determined by resonant frequency and damping analysis. Density optimization at the bone–implant interface can allow for bone ingrowth and cementless implant components. Computerized tomography (CT) scans of metal (aluminium alloy) foam have also allowed for the building of Ti-6Al-4V foams by embedding the digital-layered scans in computer-aided design or software models for EBM. Variations in mesh complexity and especially strut (or truss) dimensions alter the cooling and solidification rate, which alters the
α
-phase (hexagonal close-packed) microstructure by creating mixtures of
α
/
α
′ (martensite) observed by optical and electron metallography. Microindentation hardness measurements are characteristic of these microstructures and microstructure mixtures (
α
/
α
′) and sizes.
What can we learn about the distribution of fitness effects of new mutations from DNA sequence data?
Authors: Keightley Peter D. , Eyre-Walker Adam
Published: March 2010

We investigate several questions concerning the inference of the distribution of fitness effects (DFE) of new mutations from the distribution of nucleotide frequencies in a population sample. If a fixed sequencing effort is available, we find that the optimum strategy is to sequence a modest number of alleles (approx. 10). If full genome information is available, the accuracy of parameter estimates increases as the number of alleles sequenced increases, but with diminishing returns. It is unlikely that the DFE for single genes can be reliably estimated in organisms such as humans and
Drosophila
, unless genes are very large and we sequence hundreds or perhaps thousands of alleles. We consider models involving several discrete classes of mutations in which the selection strength and density apportioned to each class can vary. Models with three classes fit almost as well as four class models unless many hundreds of alleles are sequenced. Large numbers of alleles need to be sequenced to accurately estimate the distribution's mean and variance. Estimating complex DFEs may therefore be difficult. Finally, we examine models involving slightly advantageous mutations. We show that the distribution of the absolute strength of selection is well estimated if mutations are assumed to be unconditionally deleterious.
Genetic hitchhiking versus background selection: the controversy and its implications
Authors: Stephan Wolfgang
Published: March 2010

The controversy on the relative importance of background selection (BGS; against deleterious mutations) and genetic hitchhiking (associated with positive directional selection) in explaining patterns of nucleotide variation in natural populations stimulated research activities for almost a decade. Despite efforts from many theorists and empiricists, fundamental questions are still open, in particular, for the population genetics of regions of reduced recombination. On the other hand, the development of the BGS and hitchhiking models and the long struggle to distinguish them, all of which seem to be a purely academic exercise, led to quite practical advances that are useful for the identification of genes involved in adaptation and domestication.
Beneficial mutations and the dynamics of adaptation in asexual populations
Authors: Sniegowski Paul D. , Gerrish Philip J.
Published: March 2010

We discuss the dynamics of adaptive evolution in asexual (clonal) populations. The classical ‘periodic selection’ model of clonal evolution assumed that beneficial mutations are very rare and therefore substitute unfettered into populations as occasional, isolated events. Newer models allow for the possibility that beneficial mutations are sufficiently common to coexist and compete for fixation within populations. Experimental evolution studies in microbes provide empirical support for stochastic models in which both selection and mutation are strong effects and clones compete for fixation; however, the relative importance of competition among clones bearing mutations of different selective effects versus competition among clones bearing multiple mutations remains unresolved. We provide some new theoretical results, moreover, suggesting that population dynamics consistent with the periodic selection model can arise even in a deterministic model that can accommodate a very high beneficial mutation rate.
Forces that influence the evolution of codon bias
Authors: Sharp Paul M. , Emery Laura R. , Zeng Kai
Published: March 2010

The frequencies of alternative synonymous codons vary both among species and among genes from the same genome. These patterns have been inferred to reflect the action of natural selection. Here we evaluate this in bacteria. While intragenomic variation in many species is consistent with selection favouring translationally optimal codons, much of the variation among species appears to be due to biased patterns of mutation. The strength of selection on codon usage can be estimated by two different approaches. First, the extent of bias in favour of translationally optimal codons in highly expressed genes, compared to that in genes where selection is weak, reveals the long-term effectiveness of selection. Here we show that the strength of selected codon usage bias is highly correlated with bacterial growth rate, suggesting that selection has favoured translational efficiency. Second, the pattern of bias towards optimal codons at polymorphic sites reveals the ongoing action of selection. Using this approach we obtained results that were completely consistent with the first method; importantly, the frequency spectra of optimal codons at polymorphic sites were similar to those predicted under an equilibrium model. Highly expressed genes inEscherichia coliappear to be under continuing strong selection, whereas selection is very weak in genes expressed at low levels.
Multilocus variable-number tandem repeat analysis of Vibrio cholerae O1 El Tor strains harbouring classical toxin B
Authors: Choi Seon Young , Lee Je Hee , Jeon Yoon-Seong , Lee Hye Ri , Kim Eun Jin , Ansaruzzaman M. , Bhuiyan Nurul A. , Endtz Hubert P. , Niyogi S. K. , Sarkar B. L. , Nair G. Balakrish , Nguyen Binh Minh , Hien Nguyen Tran , Czerkinsky Cecil , Clemens John D. , Chun Jongsik , Kim Dong Wook
Published: March 2010

AtypicalVibrio choleraeO1 strains – hybrid strains (strains that cannot be classified either as El Tor or classical biotype) and altered strains (El Tor biotype strains that produce classical cholera toxin) – are currently prevalent in Asia and Africa. A total of 74 hybrid and altered strains that harboured classical cholera toxin were investigated by multilocus variable-number tandem repeat analysis (MLVA). The results showed that the hybrid/altered strains could be categorized into three groups and that they were distant from the El Tor strain responsible for the seventh cholera pandemic. Hybrid/altered strains with a tandem repeat of the classical CTX prophage on the small chromosome were divided into two MLVA groups (group I: Mozambique/Bangladesh group; group III: Vietnam group), and altered strains with the RS1–CTX prophage containing the El Tor typerstRand classicalctxBon the large chromosome were placed in two MLVA groups (group II: India/Bangladesh group; group III: India/Vietnam group).
Can finger‐prick sampling replace venous sampling to determine the pharmacokinetic profile of oral paracetamol?
Authors: Mohammed Baba S. , Cameron Garry A. , Cameron Lindsay , Hawksworth Gabrielle H. , Helms Peter J. , McLay James S.
Published: March 2010

WHAT IS ALREADY KNOWN ABOUT THE SUBJECT

• Finger‐prick blood samples are increasingly used for the clinical and biomedical measurement of drugs and endogenous substance concentration.

• The use of different sampling sites can give rise to different drug concentration measurements.

WHAT THIS STUDY ADDS

• During the absorption phase, the paracetamol concentration in finger‐prick blood samples is significantly greater than that in venous blood samples, following oral administration.

• Finger‐prick and venous blood samples will result in equivalent pharmacokinetic parameters of oral paracetamol only after distribution equilibrium is attained.

The drive to increase the availability of paediatric pharmacokinetic data with minimum blood loss has led to the development of micro‐sampling techniques. However studies have suggested that pharmacokinetic data from venous or capillary blood samples may not be directly comparable.

AIM

The aim of this study was to determine whether paracetamol demonstrates concentration differences between finger‐prick and venous blood samples.

METHODS

Paired finger‐prick and venous blood samples were taken at 0, 15, 30 and 60 min following 1 g oral paracetamol, from 12 male adult subjects. Paracetamol concentration was determined using HPLC and UV detection with a LLOQ of 2200 pg on column. Intra‐assay coefficient of variation for paracetamol at the LLOQ was 3%.

RESULTS

At 15, 30, and 60 min post dose the median finger‐prick paracetamol concentration was 349%, 72%, and 9.3% greater than the equivalent venous concentrations, respectively. Regression analysis confirmed a significant relationship between finger‐prick and venous paracetamol concentrations at 15 min (r2 = 0.81, P = 0.006), at 30 min (r2 = 0.82, P < 0.0001) and at 60 min (r2 = 0.87, P < 0.0001) post dose. The regression equation for venous and finger‐prick blood concentrations at 15, 30 and 60 min post dose were Venous15 = Finger15 − 3.4, Venous30 = Finger30 − 3.4 and Venous60 = 0.68Finger60 + 3.06, respectively.

CONCLUSIONS

Paracetamol demonstrates an arteriovenous difference in concentration, and the use of finger‐prick samples may give rise to results which differ from those obtained with traditional venous sampling especially during the first 1 h following drug ingestion.
Warfarin and vitamin K intake in the era of pharmacogenetics
Authors: Lurie Yael , Loebstein Ronen , Kurnik Daniel , Almog Shlomo , Halkin Hillel
Published: March 2010

The considerable variability in the warfarin dose–response relationship between individuals, is explained mainly by genetic variation in its major metabolic (CYP2C9) and target (VKORC1) enzymes. Despite the predominance of pharmacogenetics, environmental factors also affect the pharmacokinetics and pharmacodynamics of warfarin, and are often overlooked. Among these factors, dietary and supplemental vitamin K consumption is a controllable contributor to within‐, and between‐patient variability of warfarin sensitivity. In this commentary we review the current role of vitamin K in warfarin anticoagulation therapy, with emphasis on the following:

1 The effect of dietary and supplemental vitamin K on warfarin anticoagulation, beyond the impact of genetic variability in CYP2C9 and VKORC1. We deal separately with the effects of vitamin K on warfarin dose requirements during the induction of therapy, as opposed to its effect on stability of anticoagulation control during maintenance therapy.

2 The role of vitamin K supplementation in warfarin treated patients with vitamin K deficiency as well as in patients with unstable warfarin anticoagulation, and

3 The role of therapeutic vitamin K in cases of warfarin over‐anticoagulation.
The ‘apparent clearance’ of free phenytoin in elderlyvs.younger adults
Authors: Wright Daniel F. B. , Begg Evan J.
Published: March 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• The clearance of many drugs is reduced in the elderly, but the data regarding phenytoin are conflicting. Most studies have estimated phenytoin metabolic clearance using total drug concentrations (bound plus unbound), which may be confounded by protein binding effects. Free phenytoin concentrations are independent of protein binding and should more accurately reflect true metabolic clearance changes in elderly patients.

WHAT THIS STUDY ADDS

• The two studies reported in this paper suggest a trend towards reduced free phenytoin ‘apparent clearance’ in the elderly, although statistically significant results were not found. Other published studies have largely found similar trends, suggesting an age effect.

AIMS

To test the hypothesis that the ‘apparent clearance’ of free phenytoin is reduced in elderly patients.

METHODS

Two separate studies were conducted comparing free phenytoin ‘apparent clearance’ in elderlyvs.younger adults. The first study was a retrospective analysis of free phenytoin concentrations measured at Christchurch Hospital from 1997 to 2006. In the second study free phenytoin concentrations were measured prospectively in ambulatory subjects who were taking phenytoin regularly.

RESULTS

In the retrospective study (n= 29), free phenytoin ‘apparent clearance’ was 0.27 ± 0.04 l kg−1day−1(95% CI 0.19, 0.34) in the elderly cohortvs.0.37 ± 0.06 l kg−1day−1(95% CI 0.22, 0.52) in younger adults, but the difference was not statistically significant. In the prospective study, free phenytoin ‘apparent clearance’ showed a non‐significant trend to being reduced in the elderly patients (0.12 ± 0.02 l kg−1day−1, 95% CI 0.07, 0.17) compared with the younger cohort (0.18 ± 0.07 l kg−1day−1, 95% CI 0.09, 0.26) in those not taking interacting drugs (n= 21).

CONCLUSIONS

This research does not prove the hypothesis that the ‘apparent clearance’ of free phenytoin is reduced in the elderly. However, the trends found in these two studies are supported by trends in the same direction in other published studies, suggesting an age effect.
Dosing and monitoring of enoxaparin (Low molecular weight heparin) therapy in children
Authors: Ignjatovic Vera , Najid Siti , Newall Fiona , Summerhayes Robyn , Monagle Paul
Published: March 2010

Low molecular weight heparins (LMWHs) are commonly used in paediatric tertiary institutions for primary prophylaxis and treatment of thromboembolic events. Despite this widespread use, the therapeutic and prophylactic guidelines for LMWH therapy in children are extrapolated from adult guidelines. In fact, there is very little information regarding the pharmacokinetics, clinical effectiveness, adverse event profile and optimal dose schedule for LMWH therapy in children. This study was designed to determine whether paediatric‐specific dosage requirements for LMWH are justified, by investigating the doses required to achieve target therapeutic ranges. Patients who were treated with enoxaparin between October 2003 and July 2007 were identified for inclusion in this study. One hundred forty patients had an anti‐activated factor X assay result with a total of 55 (39%) patients achieving therapeutic levels 4–6 h post dose. Children younger than 1 year required the highest dose of enoxaparin/kg and highest number of dose changes to achieve the target therapeutic range. Major bleeding occurred in one patient, equating to 0·7%, with complete clot resolution recorded in 16 (11%) patients. This study demonstrated a 2–3‐fold variation in individual dose requirements for LMWH in children ≤5 years of age, and further mandates the need for age‐specific dosage requirements in children receiving enoxaparin.