bluuebunny/crossref_metadata_2025 huggingface dataset:
Review and comparison of quality standards, guidelines and regulations for laboratories
Authors: Datema Tjeerd A.M. , Oskam Linda , Klatser Paul R.
Published: December 2011

Background: The variety and number of laboratory quality standards, guidelines and regulations (hereafter: quality documents) makes it difficult to choose the most suitable one for establishing and maintaining a laboratory quality management system. Objectives: There is a need to compare the characteristics, suitability and applicability of quality documents in view of the increasing efforts to introduce quality management in laboratories, especially in clinical diagnostic laboratories in low income and middle income countries. This may provide valuable insights for policy makers developing national laboratory policies, and for laboratory managers and quality officers in choosing the most appropriate quality document for upgrading their laboratories. Method: We reviewed the history of quality document development and then selected a subset based on their current use. We analysed these documents following a framework for comparison of quality documents that was adapted from the Clinical Laboratory Standards Institute guideline GP26 Quality management system model for clinical laboratory services. Results: Differences were identified between national and international, and non-clinical and clinical quality documents. The most salient findings were the absence of provisions on occurrence management and customer service in almost all non-clinical quality documents, a low number of safety requirements aimed at protecting laboratory personnel in international quality documents and no requirements regarding ethical behaviour in almost all quality documents. Conclusion: Each laboratory needs to investigate whether national regulatory standards are present. These are preferred as they most closely suit the needs of laboratories in the country. A laboratory should always use both a standard and a guideline: a standard sums up the requirements to a quality management system, a guideline describes how quality management can be integrated in the laboratory processes.
LCGbase: A Comprehensive Database for Lineage-Based Co-regulated Genes
Authors: Wang Dapeng , Zhang Yubin , Fan Zhonghua , Liu Guiming , Yu Jun
Published: December 2011

Animal genes of different lineages, such as vertebrates and arthropods, are well-organized and blended into dynamic chromosomal structures that represent a primary regulatory mechanism for body development and cellular differentiation. The majority of genes in a genome are actually clustered, which are evolutionarily stable to different extents and biologically meaningful when evaluated among genomes within and across lineages. Until now, many questions concerning gene organization, such as what is the minimal number of genes in a cluster and what is the driving force leading to gene co-regulation, remain to be addressed. Here, we provide a user-friendly database—LCGbase (a comprehensive database for lineage-based co-regulated genes)—hosting information on evolutionary dynamics of gene clustering and ordering within animal kingdoms in two different lineages: vertebrates and arthropods. The database is constructed on a web-based Linux-Apache-MySQL-PHP framework and effective interactive user-inquiry service. Compared to other gene annotation databases with similar purposes, our database has three comprehensible advantages. First, our database is inclusive, including all high-quality genome assemblies of vertebrates and representative arthropod species. Second, it is human-centric since we map all gene clusters from other genomes in an order of lineage-ranks (such as primates, mammals, warmblooded, and reptiles) onto human genome and start the database from well-defined gene pairs (a minimal cluster where the two adjacent genes are oriented as co-directional, convergent, and divergent pairs) to large gene clusters. Furthermore, users can search for any adjacent genes and their detailed annotations. Third, the database provides flexible parameter definitions, such as the distance of transcription start sites between two adjacent genes, which is extendable to genes that flanking the cluster across species. We also provide useful tools for sequence alignment, gene ontology (GO) annotation, promoter identification, gene expression (co-expression), and evolutionary analysis. This database not only provides a way to define lineage-specific and species-specific gene clusters but also facilitates future studies on gene co-regulation, epigenetic control of gene expression (DNA methylation and histone marks), and chromosomal structures in a context of gene clusters and species evolution. LCGbase is freely available at http://lcgbase.big.ac.cn/LCGbase .
Sources of carbonaceous aerosols and deposited black carbon in the Arctic in winter-spring: implications for radiative forcing
Authors: Wang Q. , Jacob D. J. , Fisher J. A. , Mao J. , Leibensperger E. M. , Carouge C. C. , Le Sager P. , Kondo Y. , Jimenez J. L. , Cubison M. J. , Doherty S. J.
Published: December 2011

Abstract. We use a global chemical transport model (GEOS-Chem CTM) to interpret observations of black carbon (BC) and organic aerosol (OA) from the NASA ARCTAS aircraft campaign over the North American Arctic in April 2008, as well as longer-term records in surface air and in snow (2007–2009). BC emission inventories for North America, Europe, and Asia in the model are tested by comparison with surface air observations over these source regions. Russian open fires were the dominant source of OA in the Arctic troposphere during ARCTAS but we find that BC was of prevailingly anthropogenic (fossil fuel and biofuel) origin, particularly in surface air. This source attribution is confirmed by correlation of BC and OA with acetonitrile and sulfate in the model and in the observations. Asian emissions are the main anthropogenic source of BC in the free troposphere but European, Russian and North American sources are also important in surface air. Russian anthropogenic emissions appear to dominate the source of BC in Arctic surface air in winter. Model simulations for 2007–2009 (to account for interannual variability of fires) show much higher BC snow content in the Eurasian than the North American Arctic, consistent with the limited observations. We find that anthropogenic sources contribute 90% of BC deposited to Arctic snow in January-March and 60% in April–May 2007–2009. The mean decrease in Arctic snow albedo from BC deposition is estimated to be 0.6% in spring, resulting in a regional surface radiative forcing consistent with previous estimates.
Determination of tropospheric vertical columns of NO2 and aerosol optical properties in a rural setting using MAX-DOAS
Authors: Halla J. D. , Wagner T. , Beirle S. , Brook J. R. , Hayden K. L. , O'Brien J. M. , Ng A. , Majonis D. , Wenig M. O. , McLaren R.
Published: December 2011

Abstract. Multi-AXis Differential Optical Absorption Spectroscopy (MAX-DOAS) measurements were performed in a rural location of southwestern Ontario during the Border Air Quality and Meteorology Study. Slant column densities (SCDs) of NO2 and O4 were determined using the standard DOAS technique. Using a radiative transfer model and the O4 SCDs, aerosol optical depths were determined for clear sky conditions and compared to OMI, MODIS, AERONET, and local PM2.5 measurements. This aerosol information was input to a radiative transfer model to calculate NO2 air mass factors, which were fit to the measured NO2 SCDs to determine tropospheric vertical column densities (VCDs) of NO2. The method of determining NO2 VCDs in this way was validated for the first time by comparison to composite VCDs derived from aircraft and ground-based measurements of NO2. The new VCDs were compared to VCDs of NO2 determined via retrievals from the satellite instruments SCIAMACHY and OMI, for overlapping time periods. The satellite-derived VCDs were higher, with a mean bias of +0.5–0.9×1015 molec cm−2. This last finding is different from previous studies whereby MAX-DOAS geometric VCDs were higher than satellite determinations, albeit for urban areas with higher VCDs. An effective boundary layer height, BLHeff, is defined as the ratio of the tropospheric VCD and the ground level concentration of NO2. Variations of BLHeff can be linked to time of day, source region, stability of the atmosphere, and the presence or absence of elevated NOx sources. In particular, a case study is shown where a high VCD and BLHeff were observed when an elevated industrial plume of NOx and SO2 was fumigated to the surface as a lake breeze impacted the measurement site. High BLHeff values (~1.9 km) were observed during a regional smog event when high winds from the SW and high convection promoted mixing throughout the boundary layer. During this event, the regional line flux of NO2 through the region was estimated to be greater than 112 kg NO2 km−1 h−1.
A Lagrangian view of convective sources for transport of air across the Tropical Tropopause Layer: distribution, times and the radiative influence of clouds
Authors: Tzella A. , Legras B.
Published: December 2011

Abstract. The tropical tropopause layer (TTL) is a key region controlling transport between the troposphere and the stratosphere. The efficiency of transport across the TTL depends on the continuous interaction between the large-scale advection and the small-scale intermittent convection that reaches the Level of Zero radiative Heating (LZH). The wide range of scales involved presents a significant challenge to determine the sources of convection and quantify transport across the TTL. Here, we use a simple Lagrangian model, termed TTL detrainment model, that combines a large ensemble of 200-day back trajectory calculations with high-resolution fields of brightness temperatures (provided by the CLAUS dataset) in order to determine the ensemble of trajectories that are detrained from convective sources. The trajectories are calculated using the ECMWF ERA-Interim winds and radiative heating rates, and in order to establish the radiative influence of clouds, the latter rates are derived both under all-sky and clear-sky conditions. We show that most trajectories are detrained near the mean LZH with the horizontal distributions of convective sources being highly-localized, even within the space defined by deep convection. As well as modifying the degree of source localization, the radiative heating from clouds facilitates the rapid upwelling of air across the TTL. However, large-scale motion near the fluctuating LZH can lead a significant proportion of trajectories to alternating clear-sky and cloudy regions, thus generating a large dispersion in the vertical transport times. The distributions of vertical transport times are wide and skewed and are largely insensitive to a bias of about ±1 km (∓5 K) in the altitude of cloud top heights (the main sensitivity appearing in the times to escape the immediate neighbourhood of the LZH) while some seasonal and regional transport characteristics are apparent for times up to 60 days. The strong horizontal mixing that characterizes the TTL ensures that most air of convective origin is well-mixed within the tropical and eventually within the extra-tropical lower-stratosphere.
Dry deposition fluxes and deposition velocities of seven trace metal species at five sites in Central Taiwan - a summary of surrogate surface measurements and a comparison with model estimation
Authors: Zhang L. , Fang G. C. , Liu C. K. , Huang Y. L. , Huang J. H. , Huang C. S.
Published: December 2011

Abstract. Daily air concentrations and dry deposition fluxes of seven metal species were monitored at five sites in Central Taiwan for five or six days each month from September 2009 to August 2010. Annual average concentrations at the five sites were in the range of 2.8 to 3.6 ng m−3 for As, 25 to 82 ng m−3 for Mn, 1900 to 2800 ng m−3 for Fe, 69 to 109 ng m−3 for Zn, 18 to 33 ng m−3 for Cr, 60 to 110 ng m−3 for Cu, and 25 to 40 ng m−3 for Pb. Annual average dry deposition fluxes were on the order of 3, 20, 400, 50, 25, 50 and 50 μg m−2 day−1 for As, Mn, Fe, Zn, Cr, Cu and Pb, respectively. Annual average dry deposition velocities (Vd) for the seven metal species ranged from 0.18 to 2.22 cm s−1 at these locations. Small seasonal and geographical variations, e.g., from a few percent to a factor of 2 for different species and/or at different locations, were found for measured concentrations, fluxes and Vd. Measured fluxes and air concentrations had moderate to good correlations for several species at several sites, but had weak or no correlations for other species or at other sites, the latter cases were believed to have large uncertainties in flux measurements using surrogate surfaces. Sensitivity tests were conducted for particle Vd using a size-segregated particle dry deposition model, assuming various combinations of three lognormal size distributions representing fine particles (PM2.5), coarse particles (PM2.5-10) and super size particles (PM10+), respectively. It was found that measured dry deposition fluxes can be reproduced reasonably well using the size-segregated particle dry deposition model if the mass fractions of metal species in PM2.5, PM2.5-10 and PM10+ were known. Significant correlations between modeled and measured daily fluxes were found for those cases that were believed to have small uncertainties in flux measurements.
The mathematical principles and design of the NAIS – a spectrometer for the measurement of cluster ion and nanometer aerosol size distributions
Authors: Mirme S. , Mirme A.
Published: December 2011

Abstract. The paper describes the Nanometer aerosol and Air Ion Spectrometer (NAIS) – a multi-channel aerosol instrument capable of measuring the distribution of ions (charged particles and cluster ions) of both polarities in the electric mobility range from 3.2 to 0.0013 cm2 V−1 s−1 and the distribution of aerosol particles in the size range from 2.0 to 40 nm. We introduce the principles of design, data processing and spectrum deconvolution of the instrument.
Calcium carbonate production response to future ocean warming and acidification
Authors: Pinsonneault A. J. , Matthews H. D. , Galbraith E. D. , Schmittner A.
Published: December 2011

Abstract. Anthropogenic carbon dioxide (CO2) emissions are acidifying the ocean, affecting calcification rates in pelagic organisms and thereby modifying the oceanic alkalinity cycle. However, the responses of pelagic calcifying organisms to acidification vary widely between species, contributing uncertainty to predictions of atmospheric CO2 and the resulting climate change. Meanwhile, ocean warming caused by rising CO2 is expected to drive increased growth rates of all pelagic organisms, including calcifiers. It thus remains unclear whether anthropogenic CO2 will ultimately increase or decrease the globally-integrated pelagic calcification rate. Here, we assess the importance of this uncertainty by introducing a variable dependence of calcium carbonate (CaCO3) production on calcite saturation state (ΩCaCO3) in the University of Victoria Earth System Climate Model, an intermediate complexity coupled carbon-climate model. In a series of model simulations, we examine the impact of this parameterization on global ocean carbon cycling under two CO2 emissions scenarios, both integrated to the year 3500. The simulations show a significant sensitivity of the vertical and surface horizontal alkalinity gradients to the parameterization, as well as the removal of alkalinity from the ocean through CaCO3 burial. These sensitivities result in an additional oceanic uptake of carbon when calcification depends on ΩCaCO3 (of up to 13 % of total carbon emissions), compared to the case where calcification is insensitive to acidification. In turn, this response causes a reduction of global surface air temperature of up to 0.4 °C in year 3500, a 13 % reduction in the amplitude of warming. Narrowing these uncertainties will require better understanding of both temperature and acidification effects on pelagic calcifiers. Preliminary examination suggests that alkalinity observations can be used to constrain the range of uncertainties and may exclude large sensitivities of CaCO3 production on ΩCaCO3.
Global patterns of change in discharge regimes for 2100
Authors: Sperna Weiland F. C. , van Beek L. P. H. , Kwadijk J. C. J. , Bierkens M. F. P.
Published: December 2011

Abstract. This study makes a thorough global assessment of the effects of climate change on hydrological regimes and their accompanying uncertainties. Meteorological data from twelve GCMs (SRES scenarios A1B, and control experiment 20C3M) are used to drive the global hydrological model PCR-GLOBWB. We reveal in which regions of the world changes in hydrology can be detected that are significant and consistent amongst the ensemble of GCMs. New compared to existing studies is: (1) the comparison of spatial patterns of regime changes and (2) the quantification of consistent significant change calculatesd relative to both the natural variability and the inter-model spread. The resulting consistency maps indicate in which regions likelihood of hydrological change is large. Projections of different GCMs diverge widely. This underscores the need of using a multi-model ensemble. Despite discrepancies amongst models, consistent results are revealed: by 2100 the GCMs project consistent decreases in discharge for southern Europe, southern Australia, parts of Africa and southwestern South-America. Discharge decreases are large for most African rivers, the Murray and the Danube. While discharge of Monsoon influenced rivers slightly increases. In the Arctic regions river discharge increases and a phase-shift towards earlier peaks is observed. Results are comparable to previous global studies, with a few exceptions. Globally we calculated an ensemble mean discharge increase of more than ten percent. This increase contradicts previously estimated decreases, which is amongst others caused by the use of smaller GCM ensembles and different reference periods.
Homozygous Mutation in MERTK Causes Severe Autosomal Recessive Retinitis Pigmentosa
Authors: Ksantini Mohamed , Lafont Estèle , Bocquet Béatrice , Meunier Isabelle , Hamel Christian P.
Published: December 2011

Purpose

Gene identification in retinitis pigmentosa is a prerequisite to future therapies. Accordingly, autosomal recessive retinitis pigmentosa families were genotyped to search for causative mutations.

Methods

Members of a consanguineous Moroccan family had standard ophthalmologic examination, optical coherence tomography–3 scan, autofluorescence testing, and electroretinogram. Their DNA was genotyped with the 250K SNP microchip (Affymetrix) and homozygosity mapping was done. MERTK exons were polymerase chain reaction amplified and sequenced.

Results

Two sisters and one brother out of 6 siblings had rod cone dystrophy type of retinitis pigmentosa. Salient features were night blindness starting in early infancy, dot-like whitish deposits in fovea and macula with corresponding autofluorescent dots in youngest patients, decreased visual acuity, and cone responses higher than rod responses at electroretinogram. The patients were homozygous in regions from chromosomes 2 and 8, but only that of chromosome 2 was inherited from a common ancestor. Sequencing of the MERTK gene belonging to the chromosome 2 region showed that the 3 affected patients carried a novel homozygous mutation in exon 17, c.2323C>T, leading to p.Arg775X, while their unaffected brothers and sister, parents, and paternal grandfather were heterozygous.

Conclusions

MERTK mutations lead to severe retinitis pigmentosa with discrete dot-like autofluorescent deposits at early stages, which are a hallmark of this MERTK-specific dystrophy.
KIR/HLA Combination Associated with the Risk of Complications in Celiac Disease
Authors: Caggiari Laura , Toffoli Giuseppe , De Re Valli , Orzes Nicoletta , Spina Michele , De Zorzi Mariangela , Maiero Stefania , Cannizzaro Renato , Canzonieri Vincenzo
Published: December 2011

The pathogenesis of celiac disease (CD) is associated with polymorphisms in human leukocyte antigen (HLA) genes; however, compelling evidence suggests that additional non-HLA genes are associated with CD and related complications. The present study investigated whether killer cell immunoglobulin-like receptor (KIR)/HLA gene combinations are associated with CD and its clinical complications in the population of northeast Italy. The study included 61 adults affected by CD: 48 patients were at first diagnosis and 13 patients had CD-related complications (8 with refractory CD and 5 with cancer). Controls were 69 blood donors genotyped for KIR and HLA. Several statistically significant differences emerged between CD patients and blood donors. The results herein presented show that susceptibility to CD with refractory disease or cancer is associated with various genotypes including the 2DS2/2DL2+C1, 2DS3, 3DL1, and 2DL5B genes. In addition, the absence of the Bw4 ligand may be a predisposing factor for cancer. These results suggest that a KIR haplotype and HLA ligands may be involved in the susceptibility to important clinical CD complications such as tumors or refractoriness as a result of a gluten-free diet.
Family-Witnessed Resuscitation: Perceptions of Nurses and Doctors Working in an Australian Emergency Department
Authors: Chapman Rose , Watkins Rochelle , Bushby Angela , Combs Shane
Published: December 2011

Inconsistencies abound in the literature regarding staff attitudes and perceptions toward family-witnessed resuscitation. Our study builds on previous research by using a validated tool to investigate emergency department staff perceptions of family-witnessed resuscitation. A cross-sectional survey was distributed to 221 emergency department doctors' and nurses'. We found few differences between doctors and nurses perceptions toward family-witnessed resuscitation. Both nurses and doctors who held a specialty certification, who were more highly qualified, who had more experience with family presence during resuscitation, and who had a personal preference for having family members present during their own resuscitation perceived more benefits and fewer risks, as well as more confidence in their ability to manage these events. However, nurses more than doctors want patients to provide advanced directives for family presence. The findings will enable clinicians, educators, and hospital management to provide better support to all stakeholders through these events.
A new system for measuring electrical conductivity of water as a function of admittance
Authors: Yacoob Aldosky Haval Y. , Shamdeen Suzan M. H.
Published: December 2011

This paper presents a new system for measuring water conductivity as a function of electrophysical property (admittance). The system is cheap and its manufacturing is easy. In addition, it does not require any sort of electrolysis and calibration. The system consists of four electrodes made of silver (Ag 92.5 g to Cu 7.5 g) fixed in a plastic tube filled by water which allows the use of two and four electrode setups. The admittance (reciprocal of impedance) was measured for different water sources (distilled, rainfall, mineral, river and tap water) using different frequencies between 50 Hz and 100 kHz. These measurements were taken twice, first with four electrodes and then with two electrodes of two modes (inner and outer electrodes). The results showed good correlation between the measured admittance and the conductivity of all the water sources and the best correlation was found at low frequencies between 50 Hz and 20 kHz. The highest efficiency can be achieved by using the four electrode system which allows circumventing the effect of the electrode impedance. This result makes the system efficient compared to traditional conductivity meters which usually require high frequencies for good operation.
Porphyrins and Expanded Porphyrins as Receptors
Authors: Sessler Jonathan L. , Karnas Elizabeth , Sedenberg Elaine
Published: December 2011

This chapter summarizes recent efforts to use porphyrins and expanded porphyrins as receptors. These unique macrocycles bear resemblance to naturally occurring tetrapyrrolic pigments and have been studied extensively as building blocks for a variety of functional molecular receptors. The introduction discusses the inherent characteristics of porphyrins and their analogs from the perspective of receptor design and is designed to highlight key features. These features include ease of synthesis and functionalization, the hydrogen‐bonding ability of the constituent pyrrolic NH protons, and the fact that the systems in question are often highly colored. This latter feature has afforded an extremely useful means of analyzing host–guest interactions.

Because of space limitations, not all of the literature on this topic could be covered in a comprehensive manner. The definition of “receptor” is also limited to species that are thought to be operated via strictly noncovalent‐ or supramolecular‐type interactions. However, this definition is expanded in a few special cases. The goal of this article is not to cite every published article on this topic, but to highlight interesting examples of porphyrin and expanded porphyrins and their utility as receptors. An effort has also been made to describe the analytical techniques used to characterize the resulting host–guest ensembles.

This chapter is organized according to the type of guest. One section covers the relatively new area of supramolecular π–π interactions involving porphyrins and nanomaterials, such as fullerenes and nanotubes. Another section discusses porphyrins as receptors for biological entities, including saccharides, peptides, and proteins, as well as DNA. The next section covers porphyrins and expanded porphyrins as anion receptors. This latter treatment includes a discussion of supramolecular electron‐transfer dyads. The use of porphyrins in sensing applications is also presented in summary form. Finally, a perspective on this rapidly growing field of supramolecular chemistry is included in the final remarks.

It is hoped that the combination of cited references and listed further readings will allow the interested reader to learn more about this fast‐evolving and fascinating topic.
Templated Synthesis of Knots and Ravels
Authors: Sauvage Jean‐Pierre , Amabilino David B.
Published: December 2011

Knots and ravels are complicated molecular forms and topologies that can be made with relative ease using noncovalent interactions. The orthogonal arrangement of molecular fragments, leading to the formation of “entanglements,” can be promoted by their coordination to metal ions as well as by hydrogen bonding between amides in a suitably rigid arrangement, or the perpendicular stacking of aromatic rings. In the area of nanometer‐scale science, the amazing achievements reached in the formation of knotted structures based on DNA provide inspiration and challenging benchmarks for purely synthetic systems. The resolution of the molecular knots into their enantiomers — topological enantiomers — has been achieved, although the full potential of the compounds as materials for any purpose awaits exploitation.
Rational Design of Peptide‐Based Biosupramolecular Systems
Authors: Boyle Aimee L. , Woolfson Derek N.
Published: December 2011

The de novo design of systems comprising peptides and proteins as building blocks presents exciting new challenges in the areas of self‐assembly and supramolecular chemistry and biochemistry. A key issue is that the rules relating protein sequence‐to‐structure are not fully elucidated. However, through the use of rational, “bottom‐up” approaches, systems can be constructed by the careful design and programming of peptidic tectons that use existing sequence‐to‐structure relationships and test new ones. Indeed, there has been considerable success in the design and development of effectively infinite, fibrous systems constructed from α‐helical, β‐structured or collagen‐based tectons. Some designs are now well enough developed that they can be readily functionalized, leading to potential applications in bionanotechnology, synthetic biology, and tissue engineering.

The design of discrete assemblies using similar approaches, however, is proving more challenging, with precise control of assembly being particularly difficult. As a result, there are fewer examples of such systems being reduced to practice.

This chapter describes design rules and approaches exemplified with fibrous and discrete systems, as well as discussing routes to the functionalization of such assemblies and their potential applications.
Supramolecular Nanoparticles for Molecular Diagnostics and Therapeutics
Authors: Chen Kuan‐Ju , Garcia Mitch André , Wang Hao , Tseng Hsian‐Rong
Published: December 2011

The application of nanoparticles toward diagnostics and therapeutics offers many advantages over traditional methods; as a result, this burgeoning field has attracted researchers from the fields of chemistry, engineering, and biology to explore their use in solving clinically relevant problems. Various approaches to generate nanoparticles have been investigated by many researchers, and some promising systems are explored in this chapter. However, many nanoparticle platforms still involve time‐consuming synthetic steps, which limits the ease of generating a diverse library of nanoparticles that have unique surface chemistry and different sizes. This chapter explores nanoparticle‐based diagnostics with examples from the literature involving
in vivo
lymphatic drainage experiments, and protein detection. Some examples of nanoparticle‐based therapeutics will be investigations of laser‐induced photothermal treatment of cancer cells from gold nanoparticles, gene transfection experiments using nanoparticles as a nonviral gene carrier, drug delivery using a drug‐conjugated polymer system, and an example of a clinical trial where nanoparticles are used to deliver siRNA. We anticipate that nanoparticles will establish a new pathway to further facilitate the development of molecular diagnostics and therapeutics. We believe that the inherent advantages that nanoparticle platforms can deliver will pave the way toward personalized medicine and translational clinic.
Orientation Gradients at Boundaries in Micron‐Sized Bicrystals
Authors: Kheradmand Nousha , Vehoff Horst
Published: December 2011

In micron‐sized Ni bicrystals, after compression tests, orientation gradients are measured by electron back scattering diffraction (EBSD). The results clearly show that EBSD can be used to study dislocation pile‐ups at boundaries. Using bicrystals with single and multiple slip orientations our results show that with decreasing the size of the pillars the orientation changes due to cross‐slip decreases and the orientation changes at the boundary increases. This directly indicates a change in the hardening mechanism when the probability of dislocation–dislocation interaction decreases due to source‐limited plasticity in the bicrystals with diameters below approximately two microns.
Photo‐ and pH‐Triggered Release of Anticancer Drugs from Mesoporous Silica‐Coated Pd@Ag Nanoparticles
Authors: Fang Weijun , Yang Jing , Gong Jiawei , Zheng Nanfeng
Published: December 2011

A smart drug delivery system integrating both photothermal therapy and chemotherapy for killing cancer cells is reported. The delivery system is based on a mesoporous silica‐coated Pd@Ag nanoplates composite. The Pd@Ag nanoplate core can effectively absorb and convert near infrared (NIR) light into heat. The mesoporous silica shell is provided as the host for loading anticancer drug, doxorubicin (DOX). The mesoporous shell consists of large pores, ∼10 nm in diameter, and allows the DOX loading as high as 49% in weight. DOX loaded core–shell nanoparticles exhibit a higher efficiency in killing cancer cells than free DOX. More importantly, DOX molecules are loaded in the mesopores shell through coordination bonds that are responsive to pH and heat. The release of DOX from the core‐shell delivery vehicles into cancer cells can be therefore triggered by the pH drop caused by endocytosis and also NIR irradiation. A synergistic effect of combining chemotherapy and photothermal therapy is observed in our core‐shell drug delivery system. The cell‐killing efficacy by DOX‐loaded core–shell particles under NIR irradiation is higher than the sum of chemotherapy by DOX‐loaded particles and photothermal therapy by core–shell particles without DOX.
Silver Nanoparticles Deposited Layered Double Hydroxide Nanoporous Coatings with Excellent Antimicrobial Activities
Authors: Chen Chunping , Gunawan Poernomo , Lou Xiong Wen (David) , Xu Rong
Published: December 2011

Simple and facile processes to produce silver nanoparticles deposited layered double hydroxide (Ag‐LDH) coatings are reported. High quality nanoporous LDH coatings are obtained under hydrothermal conditions via an improved in situ growth method by immersing the substrates in LDH suspensions after removal of free electrolytes. Different types of substrates including metal, ceramics, and glass with planar and non‐planar surfaces can all be coated with the oriented LDH films with strong adhesion. The pore size can be easily tuned by changing the metal:NaOH ratio during the precipiation process of LDH precursors. In the presence of LDH coatings, silver ions can be readily reduced to metallic silver nanoparticles (Ag NPs) in aqueous solutions. The resulting Ag NPs are incorporated evenly on LDH surface. The Ag‐LDH coating exhibits excellent and durable antimicrobial activities against both Gram‐negative (E. Coli and P. Aeruginosa) and Gram‐positive (B. Subtilis and S. Aureus) bacteria. Even at the 4th recycled use, more than 99% of all types of bacteria can be killed. Moreover, the Ag‐LDH coating can also effectively inhibit the bacterial growth and prevent the biofilm formation in the nutrient solutions. These newly designed Ag‐LDH coatings may offer a promising antimicrobial solution for clinical and environmental applications.
Lead‐Free Thermoelectrics: High Figure of Merit in p‐type AgSnmSbTem+2
Authors: Han Mi‐Kyung , Androulakis John , Kim Sung‐Jin , Kanatzidis Mercouri G.
Published: December 2011

Thermoelectric materials based on Pb‐free compositions are of considerable current interest in environmentally friendly power‐generation applications derived from waste‐heat sources. Here, a new study of the thermoelectric properties of the tin‐based compositions with the general formula AgSnmSbTem+2 (m = 2, 4, 5, 7, 10, 14, 18) is presented, where the m value is used as the tuning parameter of the thermoelectric properties. The electrical conductivity, Seebeck coefficient, and thermal conductivity are measured from 300 K to 723 K and the resulting thermoelectric figure of merit is determined as a function of the SnTe/AgSbTe2 ratio. A thermoelectric figure of merit ZT ≈1 is obtained at 710 K for m = 4, indicating that the system AgSnmSbTem+2 holds great promise as an alternative p‐type, lead‐free, thermoelectric material.
Modeling multicomponent adsorption of monoclonal antibody charge variants in cation exchange columns
Authors: Tao Yinying , Chen Nianyun , Carta Giorgio , Ferreira Gisela , Robbins David
Published: December 2011

Transport models are developed for the adsorption of monoclonal antibody charge variants in cation exchange columns for two different matrices: UNOsphere S, which has a macroporous architecture, and Capto S, which contains charged dextran polymers grafted to an agarose matrix. The UNOsphere S protein adsorption kinetics is described by a macropore diffusion model with effective pore diffusivity De = 8.3 × 10−8 cm2/s, which successfully predicts resolution of charge variants by frontal analysis at residence times, L/u, between 0.9 and 5.4 min. The Capto S adsorption kinetics is very fast for individual charge variants and for coadsorption of their mixtures, but is dramatically slower for sequential adsorption, when a more strongly bound variant displaces a more weakly bound one. A Maxwell‐Stefan model assuming single‐file diffusion predicts, in agreement with experiments, poor resolution of charge variants by frontal analysis even at long residence times as a result of highly hindered counterdiffusion. © 2011 American Institute of Chemical Engineers AIChE J, 58: 2503–2511, 2012
The effect of SiO2 porosity on activity profiles and comonomer incorporation in slurry ethylene/butene‐1 polymerization by (SiO2/MgCl2/TEOS/TiCl4) catalyst system
Authors: Vakili Mohammad , Arabi Hassan , Salehi Mobarakeh Hamid
Published: December 2011

To investigate the influence of support porosity parameters e.g., average pore volume (APV), pore diameter (PD), and pore surface area distribution (PSAD) on activity‐profile of catalyst and comonomer incorporation, a series of silica‐supports with different porosity were prepared through sol–gel method and used to synthesize corresponding (SiO2/MgCl2/TEOS/TiCl4) catalysts. Polymerization of ethylene/butene‐1 showed that increasing of APV from 0.75 to 2.2 cm3 g increase initial activity from 120 to 400 (gpoly/gcat.bar.hr) followed by appearance of secondary peaks in activity‐profile which could be attributed to the variation of PSAD. It is found that the effect of support in polymerization is a complicated issue which depends not only on the porosity parameters also on the comonomer concentration. The catalyst with PD of 300 Å gives higher comonomer incorporation and polymers with 15–20% lower crystallinity in contrast to catalyst with PD of 100 Å. Porosity effect was quantitatively studied by modifying of conventional Z‐N catalyst polymerization mechanism through introducing fragmentation term to achieve a new tool in designing and developing of polyolefin catalysts. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011
The Origin of Living Polymerization with an o‐Fluorinated Catalyst: NMR Spectroscopic Characterization of Chain‐Carrying Species
Authors: Möller Heiko M. , Baier Moritz C. , Mecking Stefan , Talsi Evgenii P. , Bryliakov Konstantin P.
Published: December 2011

To characterize the origin of living polymerization with nonmetallocene titanium‐based catalysts containing o‐fluoroaryl substituents, ethene polymerization by an o‐fluorinated bis(enolatoimine) titanium catalyst and its nonfluorinated counterpart has been studied by multinuclear NMR spectroscopy by using methylaluminoxane (MAO) or AlMe3/CPh3B(C6F5)4 as activators. Formation of ion pairs of the type [TiL2Me][MeMAO] and [TiL2Me][B(C6F5)4] has been observed for both catalysts. These ion pairs react with ethene to afford the chain‐propagating species [TiL2P][MeMAO] and [TiL2P][B(C6F5)4], respectively (P=growing polymeryl chain). For the o‐F‐substituted catalyst species of the second type, NMR spectroscopy provides evidence that the o‐F substituents interact with the metal center. This interaction is proposed to keep the polymerization catalysis living by suppressing chain transfer to AlMe3 and β‐hydrogen transfer processes.
Study of the Anticancer Properties of Tin(IV) Carboxylate Complexes on a Panel of Human Tumor Cell Lines
Authors: Rocamora‐Reverte Lourdes , Carrasco‐García Estefanía , Ceballos‐Torres Jesús , Prashar Sanjiv , Kaluđerović Goran N. , Ferragut José A. , Gómez‐Ruiz Santiago
Published: December 2011

A group of organotin(IV) complexes were prepared: [SnCy3(DMNI)] (1), [SnCy3(BZDO)] (2), [SnCy3(DMFU)] (3), and [SnPh2(BZDO)2] (4), for which DMNIH=2,6‐dimethoxynicotinic acid, BZDOH=1,4‐benzodioxane‐6‐carboxylic acid, and DMFUH=2,5‐dimethyl‐3‐furoic acid. The cytotoxic activities of compounds 1–4 were tested against pancreatic carcinoma (PANC‐1), erythroleukemia (K562), and two glioblastoma multiform (U87 and LN‐229) human cell lines; they show very high antiproliferative activity, with IC50 values in the 150–700 nM range after incubation for 72 h. Distribution of cellular DNA upon treatment with 1–4 revealed that whereas compounds 1–3 induce apoptosis in most of the cell lines, compound 4 does not affect cell viability in any cell line tested, indicating a possible difference in cytotoxic mechanism. Studies with the daunomycin‐resistant K562/R cell line expressing P‐glycoprotein (Pgp) showed that compounds 1–4 are not substrates of this protein efflux pump, indicating that these compounds do not induce acquisition of multidrug resistance, which is associated with the overexpression of Pgp.
A Decade of the Human Genome Sequence—How Does the Medicinal Chemist Benefit?
Authors: Brunschweiger Andreas , Hall Jonathan
Published: December 2011

Many have claimed that the sequencing of the human genome has failed to deliver the promised new era of drug discovery and development. Here, we argue that in fact, the availability of the human genome sequence and the genomics technologies that resulted from those research efforts have had a major impact on drug discovery. Medicinal chemists are actively using the data gleaned from structural genomics projects over the past decade to design more selective and more effective drug candidates. For example, large superfamilies of related enzymes, such as the kinome, proteome, proteasome, transportome, identified because of the sequencing of the human genome represent a huge number of potential drug targets. Ten years on, we′re able to design multitarget drugs where the selectivity for a certain subgroup of receptors can lead to increased efficacy rather than the side effects traditionally associated with “off‐targets”. New trends and discoveries in biomedical research are notoriously slow to show their value, and this is also true for genomics technologies. However, the examples we′ve selected show that these are firmly set in the drug‐discovery process, and without the human genome sequence, a number of current clinical candidates and promising drug leads would not have been possible.
Dose‐escalation of whole‐brain radiotherapy for brain metastasis in patients with a favorable survival prognosis
Authors: Rades Dirk , Panzner Annika , Dziggel Liesa , Haatanen Tiina , Lohynska Radka , Schild Steven E.
Published: December 2011

BACKGROUND:

Patients with brain metastases who have a favorable survival prognosis may benefit from intensive treatments, including neurosurgery and radiosurgery. However, many patients cannot receive such treatments, and whole‐brain radiotherapy (WBRT) alone is their only option. The most common WBRT schedule is 30 grays (Gy) in 10 fractions. In this retrospective study, the authors investigated whether these patients benefit from a dose escalation beyond 30 Gy.

METHODS:

Data from 109 patients who received 30 Gy in 10 fractions were compared with 75 patients who received 40 Gy in 20 fractions. All patients had a favorable survival prognosis. Both groups were compared for local control (LC) and overall survival (OS). Subgroup analyses were performed for patients who had less radiosensitive tumors (N = 27) and for other patients (N = 157).

RESULTS:

The LC rate at 1 year was 28% after 30 Gy and 44% after 40 Gy (P = .064). On multivariate analysis, the 40 Gy dose was associated with improved LC (P = .047). The survival rate at 1 year was 50% after 30 Gy and 61% after 40 Gy (P = .007). On multivariate analysis, the 40 Gy dose was associated with improved OS (P = .008). On subgroup analysis of patients who had less radiosensitive tumors, the 1‐year LC rate was 7% after 30 Gy and 38% after 40 Gy (P = .031); and the 1‐year OS rate was 40% and 73%, respectively (P = .008). On subgroup analysis of patients who had other tumor types, the 1‐year LC rate was 31% after 30 Gy and 45% after 40 Gy (P = .26); and the 1‐year OS rate was 52% and 59%, respectively (P = .08).

CONCLUSIONS:

Escalation of the WBRT dose beyond 30 Gy resulted in better outcomes, particularly for patients who had less radiosensitive tumors. Cancer 2012. © 2011 American Cancer Society.
Krüppel‐like factor 4 functions as a tumor suppressor in cervical carcinoma
Authors: Yang Wen‐Ting , Zheng Peng‐Sheng
Published: December 2011

BACKGROUND:

The Krüppel‐like factor 4 (KLF4) protein, a zinc finger transcription factor that is highly expressed in epithelial tissues such as the gut and skin, has been implicated in both tumor suppression and progression. However, the role of KLF4 in human cervical carcinoma is still unclear.

METHODS:

The expression of KLF4 in cervical carcinoma tissues and cervical cancer cell lines was examined with immunohistochemistry and Western blot assay. The effects of KLF4 silencing and overexpression on the cell proliferation, cell viability, and tumor formation of cervical cancer cells were investigated.

RESULT:

KLF4 protein expression showed a pattern of gradual decrease from normal cervix to cervical carcinoma in situ and then to invasive cervical carcinomas (P < .05). Overexpression of KLF4 in SiHa and C33A cells resulted in significantly inhibited cell growth and significantly attenuated tumor formation. Consistently, KLF4 silencing in HeLa cells significantly promoted cell growth and tumor formation. Furthermore, KLF4 overexpression caused cell cycle arrest at the G1/S transition, along with the up‐regulated expression of p27Kip1 protein. Promoter analysis revealed that KLF4 transactivated the expression of p27Kip1 through the specific motif that is between the nucleotides of −435 and −60 in its promoter. The results from chromatin immunoprecipitation assays demonstrated the physical interaction between KLF4 protein and this specific motif in p27Kip1 promoter.

CONCLUSIONS:

KLF4 may function as a tumor suppressor in cervical carcinoma by inhibiting cell growth and tumor formation. Cancer 2012. © 2011 American Cancer Society.
Immunomodulatory medicines for multiple sclerosis: Progress and prospects
Authors: Palmer Alan M.
Published: December 2011

Multiple sclerosis (MS) is a neurodegenerative disease with a major inflammatory component that constitutes the most common progressive and disabling neurological condition in young adults. Current therapies are mainly biological agents (β‐interferons, a 4‐amino acid peptide, and a monoclonal antibody to a cell adhesion molecule on the blood CNS barrier) that either attenuate the inflammatory response or block the movement of immune cells into the CNS. The market landscape for MS drugs is set to change substantially in the near future with the market leaders coming off patent, which gives permission for the emergence of biosimilars. In addition, new small‐molecule immunomodulatory drugs are beginning to enter the market (Gilenya is the first to gain widespread approval), along with a number of immunomodulatory monoclonal antibodies. Both existing and emerging immunomodulatory medicines for MS are reviewed and their impact on the expression and progression of MS (in all its forms) considered, along with the rapidly changing landscape of MS pharmacotherapy. Drug Dev Res 72:664–673, 2011. © 2011 Wiley Periodicals, Inc.
Rheumatoid arthritis and pregnancy: Disease activity, pregnancy outcomes, and treatment options during pregnancy and lactation
Authors: Gogia Maneesh , Furst Daniel E.
Published: December 2011

The present work reviews the available data on rheumatoid arthritis (RA) during pregnancy and the postpartum period. The data generally support some improvement in RA during pregnancy, but these data are not consistent, and a subgroup of patients may have significant disability and flares. The literature supports a tendency toward postpartum flares. Babies born to mothers with RA are found to have lower birth weight, intrauterine growth restriction, and an increased risk of delivery by cesarean section. Limited safety information is available for medications used for treatment during pregnancy and lactation. There are many options for treatment during the first trimester and throughout pregnancy, but each decision must be made on an individual basis. Whereas methotrexate and leflunomide are contraindicated in pregnancy, sulfasalazine is generally considered useful, as is hydroxychloroquine (despite the latter's FDA pregnancy category C rating). Of the biologics, the tumor necrosis factor (TNFi) are classified as category B; the other biologics vary between categories B and C, but more human data are available on TNFi. Drug Dev Res 72:689–702, 2011. © 2011 Wiley Periodicals, Inc.