bluuebunny/crossref_metadata_2025 huggingface dataset:
MicroRNA‐127‐5p Regulates Matrix Metalloproteinase 13 Expression and Interleukin‐1β–Induced Catabolic Effects in Human Chondrocytes
Authors: Park Su Jin , Cheon Eun Jeong , Lee Mi Hyun , Kim Hyun Ah
Published: September 2013

Objective

MicroRNAs (miRNAs), small noncoding RNA molecules, are involved in the pathogenesis of various diseases such as cancer and arthritis. The aim of this study was to determine whether miR‐127‐5p regulates interleukin‐1β (IL‐1β)–induced expression of matrix metalloproteinase 13 (MMP‐13) and other catabolic factors in human chondrocytes.

Methods

Expression of miR‐127‐5p and MMP‐13 by normal and osteoarthritic (OA) human cartilage was determined using real‐time polymerase chain reaction. The effect of miR‐127‐5p on MMP‐13 expression was evaluated using transient transfection of human chondrocytes or chondrogenic SW‐1353 cells with miR‐127‐5p or its antisense inhibitor (anti–miR‐127‐5p). MMP‐13 protein production was quantified by enzyme‐linked immunosorbent assay, and the involvement of miR‐127‐5p in IL‐1β–mediated catabolic effects was examined by immunoblotting. MicroRNA‐127‐5p binding with the putative site in the 3′‐untranslated region (3′‐UTR) of MMP‐13 messenger RNA (mRNA) was validated by luciferase reporter assay.

Results

There was a significant reduction in miR‐127‐5p expression in OA cartilage compared with normal cartilage. Up‐regulation of MMP‐13 expression by IL‐1β was correlated with down‐regulation of miR‐127‐5p expression in human chondrocytes. MicroRNA‐127‐5p suppressed IL‐1β–induced MMP‐13 production as well as the activity of a reporter construct containing the 3′‐UTR of human MMP‐13 mRNA. In addition, mutation of the miR‐127‐5p binding site in the 3′‐UTR of MMP‐13 mRNA abolished miR‐127‐5p–mediated repression of reporter activity. Conversely, treatment with anti–miR‐127‐5p remarkably increased reporter activity and MMP‐13 production. Interestingly, the IL‐1β–induced activation of JNK, p38, and NF‐κB and expression of MMP‐1 and cyclooxygenase 2 were significantly inhibited by miR‐127‐5p.

Conclusion

MicroRNA‐127‐5p is an important regulator of MMP‐13 in human chondrocytes and may contribute to the development of OA.
Andrographolide: Solving Chemical Instability and Poor Solubility by Means of Cocrystals
Authors: Suresh Kuthuru , Goud N. Rajesh , Nangia Ashwini
Published: September 2013

The bioactive agent andrographolide was screened with pharmaceutically acceptable coformers to discover a novel solid form that will solve the chemical instability and poor solubility problems of this herbal medicine. Liquid‐assisted grinding of andrographolide with GRAS (generally regarded as safe) coformers in a fixed stoichiometry resulted in cocrystals with vanillin (1:1), vanillic acid (1:1), salicylic acid (1:1), resorcinol (1:1), and guaiacol (1:1). All the crystalline products were characterized by thermal, spectroscopic, and diffraction methods. Interestingly, even though the cocrystals are isostructural, their physicochemical properties are quite different. The andrographolide–salicylic acid cocrystal completely inhibited the chemical transformation of andrographolide to its inactive sulfate metabolite, and moreover, the cocrystal exhibited a dissolution rate that was three times faster and a drug release that was two times higher than pure andrographolide.
Sensor‐Based Long Baseline Navigation: Observability Analysis and Filter Design
Authors: Batista Pedro , Silvestre Carlos , Oliveira Paulo
Published: September 2013

This paper presents a novel long baseline (LBL) position and velocity navigation filter for underwater vehicles based directly on the sensor measurements. The solution departs from previous approaches as the range measurements are explicitly embedded in the filter design, therefore avoiding inversion algorithms and allowing also the consideration of the cases of reduced numbers of readings, in particular when there are only two or three distance measurements. The nonlinear system dynamics are considered to their full extent and no linearizations are carried out whatsoever. The filter error dynamics are globally exponentially stable (GES) and it is shown, in a realistic simulation environment, that the filter achieves similar performance to the extended Kalman filter (EKF) and outperforms linear position and velocity filters based on algebraic estimates of the position obtained from the range measurements.
Autonomic Responses to Social and Nonsocial Pictures in Adolescents With Autism Spectrum Disorder
Authors: Louwerse Anneke , Tulen Joke H. M. , van der Geest Jos N. , van der Ende Jan , Verhulst Frank C. , Greaves‐Lord Kirstin
Published: September 2013

It remains unclear why individuals with autism spectrum disorder (ASD) tend to respond in an atypical manner in social situations. Investigating autonomic and subjective responses to social vs. nonsocial stimuli may help to reveal underlying mechanisms of these atypical responses. This study examined autonomic responses (skin conductance level and heart rate) and subjective responses to social vs. nonsocial pictures in 37 adolescents with an ASD and 36 typically developing (TD) adolescents. Thirty‐six pictures from the International Affective Picture System were presented, divided into six categories based on social content (social vs. nonsocial) and pleasantness (pleasant, neutral, and unpleasant). Both in adolescents with ASD as well as TD adolescents, pictures with a social content resulted in higher skin conductance responses (SCRs) for pleasant and unpleasant pictures than for neutral pictures. No differences in SCRs were found for the three nonsocial picture categories. Unpleasant pictures, both with and without a social content, showed more heart rate deceleration than neutral pictures. Self‐reported arousal ratings were influenced by the social and affective content of a picture. No differences were found between individuals with ASD and TD individuals in their autonomic and subjective responses to the picture categories. These results suggest that adolescents with ASD do not show atypical autonomic or subjective responses to pictures with and without a social content. These findings make it less likely that impairments in social information processing in individuals with ASD can be explained by atypical autonomic responses to social stimuli. Autism Res 2014, 7: 17–27. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.
Design‐based treatment of unit nonresponse in environmental surveys using calibration weighting
Authors: Fattorini Lorenzo , Franceschi Sara , Maffei Daniela
Published: September 2013

Unit nonresponse is often a problem in sample surveys. It arises when the values of the survey variable cannot be recorded for some sampled units. In this paper, the use of nonresponse calibration weighting to treat nonresponse is considered in a complete design‐based framework. Nonresponse is viewed as a fixed characteristic of the units. The approach is suitable in environmental and forest surveys when sampled sites cannot be reached by field crews. Approximate expressions of design‐based bias and variance of the calibration estimator are derived and design‐based consistency is investigated. Choice of auxiliary variables to perform calibration is discussed. Sen–Yates–Grundy, Horvitz–Thompson, and jackknife estimators of the sampling variance are proposed. Analytical and Monte Carlo results demonstrate the validity of the procedure when the relationship between survey and auxiliary variables is similar in respondent and nonrespondent strata. An application to a forest survey performed in Northeastern Italy is considered.
Reflections on the aerobic fermentation stoichiometry of crabtree positive yeasts
Authors: Villadsen John , Jørgensen Sten Bay
Published: September 2013

In this communication a stoichiometric steady state model for Crabtree positive yeasts is proposed. The model is sufficiently simple to be corroborated by experimental data on the key metabolic events around Dcrit. The key feature of the model is that the bottleneck aperture for biomass production in the model of Sonnleitner and Käppeli, 1986 shrinks abruptly at Dcrit and continues to decrease with increasing dilution rate. A black box stoichiometric analysis of experiments reported in literature indicates that production of acetaldehyde might account for the abrupt shrinkage through a severe poisoning effect on the respiratory system. Biotechnol. Bioeng. 2014;111: 632–637. © 2013 Wiley Periodicals, Inc.
Adult Eyewitness Memory and Compliance: Effects of Post‐event Misinformation on Memory for a Negative Event
Authors: Paz‐Alonso Pedro M. , Goodman Gail S. , Ibabe Izaskun
Published: September 2013

This study investigated effects of misleading post‐event information, delay, and centrality definition on eyewitness memory and suggestibility for a negative event (a vividly filmed murder). Either immediately or 2 weeks after viewing the film, 93 adults read a (misleading or control) narrative about the event and then completed a recognition memory test. Misinformation acceptance was operative, but strong evidence for memory malleability was lacking. Compliance predicted misinformation effects, especially on the delayed test. Although accuracy was generally higher for central than peripheral information, centrality criteria influenced the pattern of results. Self‐report of greater distress was associated with better recognition accuracy. The results suggest that use of different centrality definitions may partly explain inconsistencies across studies of memory and suggestibility for central and peripheral information. Moreover, social factors appeared, at least in part, to influence misinformation effects for the highly negative event, especially as memory faded. Implications for eyewitness memory and suggestibility are discussed. Copyright © 2013 John Wiley & Sons, Ltd.
CO2 Activation and Catalysis Driven by Iridium Complexes
Authors: Fernández‐Alvarez Francisco J. , Iglesias Manuel , Oro Luis A. , Polo Víctor
Published: September 2013

Recent reports on homogeneous catalytic transformation of carbon dioxide by iridium complexes have prompted us to review the area. Progress on new iridium catalysts for carbon dioxide transformations should take into account the interaction of carbon dioxide with the iridium center, which seems to be governed by the oxidation state of iridium and the nature of the carbon dioxide molecule. Most examples of iridium catalyzed carbon dioxide reductions are based on IrIII centers. These reactions take place through outer‐sphere mechanisms, by means of nucleophilic attack on the carbon atom. In all the reported systems, the nucleophile is always a hydrido ligand coordinated to a IrIII center. Future challenges on iridium catalyzed functionalization of carbon dioxide include the development of efficient electrophiles, compatible with the inclusion of appropriate nucleophiles, which would allow the preparation of value‐added organic molecules using CO2 as C1 feedstock.
Application of orthogonal space regression to calibration transfer without standards
Authors: Lin Zhaozhou , Xu Bing , Li Yang , Shi Xinyuan , Qiao Yanjiang
Published: September 2013

To transfer a calibration model in cases where the standardization samples are rare or unstable, a method based on orthogonal space regression (OSR) is proposed. It uses virtual standardization spectra to account for response changes between instruments or batches. A comparative study of the proposed OSR, piecewise direct standardization, finite impulse response, orthogonal signal correction, and model updating (MU) was conducted on both pharmaceutical tablet data and chlorogenic acid data. The results of these studies suggest that both the OSR and the MU are superior to the other transfer techniques in terms of root‐mean‐squared error of prediction and ratio of performance to interquartile distance. Moreover, OSR requires no identical standard samples, and it avoids re‐optimizing the transfer models. In conclusion, both the differences among spectra measured on different spectrometers and the differences between different batches can be corrected successfully using the OSR method. Copyright © 2013 John Wiley & Sons, Ltd.
Controllable Syntheses of Porous Metal–Organic Frameworks: Encapsulation of LnIII Cations for Tunable Luminescence and Small Drug Molecules for Efficient Delivery
Authors: Wang Yun , Yang Jin , Liu Ying‐Ying , Ma Jian‐Fang
Published: September 2013

Two porous metal–organic frameworks (MOFs), [Zn3(L)(H2O)2]⋅3 DMF⋅7 H2O (MOF‐1) and [(CH3)2NH2]6[Ni3(L)2(H2O)6]⋅3 DMF⋅15 H2O (MOF‐2), were synthesized solvothermally (H6L=1,2,3,4,5,6‐hexakis(3‐carboxyphenyloxymethylene)benzene). In MOF‐1, neighboring ZnII trimers are linked by the backbones of L ligands to form a fascinating 3D six‐connected framework with the point symbol (412.63) (412.63). In MOF‐2, eight L ligands bridge six NiII atoms to generate a rhombic‐dodecahedral [Ni6L8] cage. Each cage is surrounded by eight adjacent ones through sharing of carboxylate groups to yield an unusual 3D porous framework. Encapsulation of LnIII cations for tunable luminescence and small drug molecules for efficient delivery were investigated in detail for MOF‐1.
The Redox‐Neutral Approach to CH Functionalization
Authors: Peng Bo , Maulide Nuno
Published: September 2013

The direct functionalization of CH bonds is an attractive strategy in organic synthesis. Although several advances have been made in this area, the selective activation of inert sp3 CH bonds remains a daunting challenge. Recently, a new type of sp3 CH activation mode through internal hydride transfer has demonstrated the potential to activate remote sp3 CH linkages in an atom‐economic manner. This Minireview attempts to classify recent advances in this area including the transition to non‐activated sp3 CH bonds and asymmetric hydride transfers.
Multifunctional Nanoprobe for MRI/Optical Dual‐Modality Imaging and Radical Scavenging
Authors: Zhen Mingming , Zheng Junpeng , Wang Yifan , Shu Chunying , Gao Fabao , Zou Jing , Pyykkö Ilmari , Wang Chunru
Published: September 2013

The development of novel nanomaterials for the diagnosis and/or treatment of human diseases has become an important issue. In this work, a multifunctional theranostic agent was designed by covalently binding hydroxyl‐ and amino‐bearing C60 derivatives (C60O∼10(OH)∼16(NH2)∼6(NO2)∼6⋅24 H2O) with gadolinium diethylenetriaminepentaacetic acid (Gd‐DTPA) to yield C60O∼10(OH)∼16(NH2)∼6(NO2)∼6⋅24 H2O/(Gd‐DTPA)3 (DF1Gd3). The obtained DF1Gd3 shows more than fourfold contrast improvement over commercial Gd‐DTPA along with multiwavelength fluorescent emission for dual‐modality diagnosis. An inner‐ear magnetic resonance imaging (MRI) study was designed as a model of biological barriers, including the blood/brain barrier (BBB) for DF1Gd3 to investigate its in vivo behavior. This revealed that the fabricated contrast agent dramatically increases the local contrast but can not cross the middle ear/inner ear barrier and endolymph/perilymph barrier in the inner ear, and thus it is also BBB‐prohibited in normal individuals. In vivo biodistribution studies suggested that 1) DF1Gd3 could circulate in vessels for a relatively long time and is mainly eliminated through liver and kidney, 2) DF1Gd3 may potentially function as a liver‐specific MRI contrast agent. Interestingly, DF1Gd3 also shows an excellent quenching effect on hydroxyl radicals, as revealed by the DMPO spin trap/ESR method. The combination of enhanced MRI/FL imaging and local treatment of lesions is unique to DF1Gd3 and potentiates the medical paradigm of “detect and treat/prevent” in combating human diseases related to reactive oxygen.
Multimodal Use of New Coumarin‐Based Fluorescent Chemosensors: Towards Highly Selective Optical Sensors for Hg2+ Probing
Authors: Bazzicalupi Carla , Caltagirone Claudia , Cao Zenfeng , Chen Qibin , Di Natale Corrado , Garau Alessandra , Lippolis Vito , Lvova Larisa , Liu Honglai , Lundström Ingemar , Mostallino M. Cristina , Nieddu Mattia , Paolesse Roberto , Prodi Luca , Sgarzi Massimo , Zaccheroni Nelsi
Published: September 2013

Despite several types of fluorescent sensing molecules have been proposed and examined to signal Hg2+ ion binding, the development of fluorescence‐based devices for in‐field Hg2+ detection and screening in environmental and industrial samples is still a challenging task. Herein, we report the synthesis and characterization of three new coumarin‐based fluorescent chemosensors featuring mixed thia/aza macrocyclic framework as receptors units, that is, ligands L1–L3. These probes revealed an OFF–ON selective response to the presence of Hg2+ ions in MeCN/H2O 4:1 (v/v), which allowed imaging of this metal ion in Cos‐7 cells in vitro. Once included in silica core–polyethylene glycol (PEG) shell nanoparticles or supported on polyvinyl chloride (PVC)‐based polymeric membranes, ligands L1–L3 can also selectively sense Hg2+ ions in pure water. In particular we have developed an optical sensing array tacking advantage of the fluorescent properties of ligand L3 and based on the computer screen photo assisted technique (CSPT). In the device ligand L3 is dispersed into PVC membranes and it quantitatively responds to Hg2+ ions in natural water samples.
Electronic Tuning of Iron–Oxo‐Mediated CH Activation: Effect of Electron‐Donating Ligand on Selectivity
Authors: Hitomi Yutaka , Arakawa Kengo , Kodera Masahito
Published: September 2013

We have reported previously that an iron(III) complex supported by an anionic pentadentate monoamido ligand, dpaqH (dpaqH=2‐[bis(pyridin‐2‐ylmethyl)]amino‐N‐quinolin‐8‐yl‐acetamido), promotes selective CH hydroxylation with H2O2 with high regioselectivity. Herein, we report on the preparation of FeIII–dpaq derivatives that have a series of substituent groups at the 5‐position of a quinoline moiety in the parent ligand dpaqH (dpaqR, R: OMe, H, Cl, and NO2), and examine them with respect to their catalytic activity in CH hydroxylation with H2O2. As the substituent group becomes more electron‐withdrawing, both the selectivity and the turnover number increase, but the selectivity of epoxidation shows the opposite trend.
Stability of slot‐rectangular spouted beds with multiple slots
Authors: Chen Zhiwei , Lim C. Jim , Grace John R.
Published: September 2013

Stability of the spouting in slot‐rectangular spouted beds with multiple compartments and slots is investigated and compared with a single‐chamber, single‐slot spouted bed. Several different configurations of multiple slots were tested, including parallel and aligned, with gas drawn from a common plenum chamber. The stability of the spouting was observed visually and identified by the evolution of pressure drop and its fluctuation. The stability of multiple spouting was found to be mainly affected by the interaction between adjacent fountains and spouts. Stable steady state spouting could be achieved when the chambers were separated by a suspended partition, providing a scale‐up method for slot‐rectangular spouted beds.
Synthesis and Anti‐Plasmodium Activity of Benzimidazole Analogues Structurally Related to Astemizole
Authors: Roman Gheorghe , Crandall Ian E. , Szarek Walter A.
Published: September 2013

A series of compounds structurally related to astemizole were designed and synthesized with the goal of determining their anti‐Plasmodium activity. Several modifications of the astemizole structure, namely the removal of the 4‐fluorobenzyl and/or 4‐methoxyphenethyl moieties, substitution of the benzene ring of the benzimidazole scaffold, replacement of the fluorine atom in the 4‐fluorobenzyl group, and variation of the 4‐aminopiperidine moiety, were explored. In vitro evaluation of the anti‐Plasmodium activity of these compounds using the ItG strain showed that astemizole and some of its structurally similar derivatives have IC50 values in the nanomolar range and exhibit toxicity towards the parasite over Chinese ovarian hamster (CHO) cells with a selectivity as high as 200. The presence of a secondary cyclic amine at position 2 and substitution with chlorine at positions 4 and 5 in the benzimidazole moiety are two modifications that resulted in potent and selective antimalarials based on astemizole.
Which of these things is not like the others?
Authors: Kaufman Jay S. , MacLehose Richard F.
Published: September 2013

Many published reports in cancer epidemiology assert subgroup‐specific effects without adequate justification. Heterogeneity tests play an important role in justifying claims that an exposure has an effect only on one or another subgroup.
New Anthracene Derivatives as Triplet Acceptors for Efficient Green‐to‐Blue Low‐Power Upconversion
Authors: Liang Zuo‐Qin , Sun Bin , Ye Chang‐Qing , Wang Xiao‐Mei , Tao Xu‐Tang , Wang Qin‐Hua , Ding Ping , Wang Bao , Wang Jing‐Jing
Published: September 2013

Three new anthracene derivatives [2‐chloro‐9,10‐dip‐tolylanthracene (DTACl), 9,10‐dip‐tolylanthracene‐2‐carbonitrile (DTACN), and 9,10‐di(naphthalen‐1‐yl)anthracene‐2‐carbonitrile (DNACN)] were synthesized as triplet acceptors for low‐power upconversion. Their linear absorption, single‐photon‐excited fluorescence, and upconversion fluorescence properties were studied. The acceptors exhibit high fluorescence yields in DMF. Selective excitation of the sensitizer PdIIoctaethylporphyrin (PdOEP) in solution containing DTACl, DTACN, or DNA‐CN at 532 nm with an ultralow excitation power density of 0.5 W cm−2 results in anti‐Stokes blue emission. The maximum upconversion quantum yield (ΦUC=17.4 %) was obtained for the couple PdOEP/DTACl. In addition, the efficiency of the triplet–triplet energy transfer process was quantitatively studied by quenching experiments. Experimental results revealed that a highly effective acceptor for upconversion should combine high fluorescence quantum yields with efficient quenching of the sensitizer triplet.
Integrating Sustainability into Corporate Governance: An Empirical Study on Board Diversity
Authors: Ferrero‐Ferrero Idoya , Fernández‐Izquierdo María Ángeles , Muñoz‐Torres María Jesús
Published: September 2013

This study explores the mediating role of corporate social responsibility (CSR) management quality in the relationship between board diversity and CSR performance. It states that generational diversity is a consistent construct of age diversity as variety, and uses three different proxies to measure CSR management quality and performance. The sample consists of 146 companies listed in FTSE 100, DAX 30, and CAC 40 for the year 2009. The results reveal that generational diversity enables a more effective design of vision and strategies to address financial and extra‐financial aspects, and consequently, it encourages companies to adopt a sustainable approach to their businesses. This study concludes that generational diversity is a key component for improving good corporate governance codes. The findings of this research recommend enhancing generational diversity in board structures to encourage sustainability in firms that aspire to be in tune with the needs of the times. Copyright © 2013 John Wiley & Sons, Ltd and ERP Environment
The Antecedents of Corporate Social and Environmental Irresponsibility
Authors: Wu Jie
Published: September 2013

This study combines internal and external perspectives to examine the antecedents of corporate social and environmental irresponsibility. In terms of internal factors, we focus on the extent to which a firm incorporates corporate social responsibility (CSR) into its business strategy and the level of firm‐specific R&D investment. With respect to external factors, we focus on market cost pressure and local government corruption. We developed hypotheses and tested them using original survey data of 295 Chinese firms covering four years. The results show that incorporating corporate social responsibility into business strategy and investing in R&D both predict less socially or environmentally irresponsible behavior by a firm. In contrast, cost pressures and government corruption correlate with an increased likelihood of irresponsible social and environmental behavior by firms. Copyright © 2013 John Wiley & Sons, Ltd and ERP Environment
Validation of cell‐based fluorescence assays: practice guidelines from the ICSH and ICCS – part II – preanalytical issues
Authors: Davis Bruce H. , Dasgupta Amar , Kussick Steven , Han Jin‐Yeong , Estrellado Annalee ,   ; on behalf of ICSH/ICCS Working Group
Published: September 2013

Flow cytometry and other technologies of cell‐based fluorescence assays are as a matter of good laboratory practice required to validate all assays, which when in clinical practice may pass through regulatory review processes using criteria often defined with a soluble analyte in plasma or serum samples in mind. Recently the U.S. Food and Drug Administration (FDA) has entered into a public dialogue in the U.S. regarding their regulatory interest in laboratory developed tests (LDTs) or so‐called “home brew” assays performed in clinical laboratories. The absence of well‐defined guidelines for validation of cell‐based assays using fluorescence detection has thus become a subject of concern for the International Council for Standardization of Haematology (ICSH) and International Clinical Cytometry Society (ICCS). Accordingly, a group of over 40 international experts in the areas of test development, test validation, and clinical practice of a variety of assay types using flow cytometry and/or morphologic image analysis were invited to develop a set of practical guidelines useful to in vitro diagnostic (IVD) innovators, clinical laboratories, regulatory scientists, and laboratory inspectors. The focus of the group was restricted to fluorescence reporter reagents, although some common principles are shared by immunohistochemistry or immunocytochemistry techniques and noted where appropriate. The work product of this two year effort is the content of this special issue of this journal, which is published as 5 separate articles, this being Validation of Cell‐based Fluorescence Assays: Practice Guidelines from the ICSH and ICCS ‐ Part II ‐ Preanalytical issues. © 2013 International Clinical Cytometry Society
Validation of cell‐based fluorescence assays: Practice guidelines from the ICSH and ICCS – part III – analytical issues
Authors: Tangri Shabnam , Vall Horacio , Kaplan David , Hoffman Bob , Purvis Norman , Porwit Anna , Hunsberger Ben , Shankey T. Vincent ,   ; on behalf of ICSH/ICCS Working Group
Published: September 2013

Clinical diagnostic assays, may be classified as quantitative, quasi‐quantitative or qualitative. The assay's description should state what the assay needs to accomplish (intended use or purpose) and what it is not intended to achieve. The type(s) of samples (whole blood, peripheral blood mononuclear cells (PBMC), bone marrow, bone marrow mononuclear cells (BMMC), tissue, fine needle aspirate, fluid, etc.), instrument platform for use and anticoagulant restrictions should be fully validated for stability requirements and specified. When applicable, assay sensitivity and specificity should be fully validated and reported; these performance criteria will dictate the number and complexity of specimen samples required for validation. Assay processing and staining conditions (lyse/wash/fix/perm, stain pre or post, time and temperature, sample stability, etc.) should be described in detail and fully validated. © 2013 International Clinical Cytometry Society
Validation of cell‐based fluorescence assays: Practice guidelines from the ICSH and ICCS – part IV – postanalytic considerations
Authors: Barnett David , Louzao Raaul , Gambell Peter , De Jitakshi , Oldaker Teri , Hanson Curtis A. ,   ; on behalf of ICSH/ICCS Working Group
Published: September 2013

Flow cytometry and other technologies of cell‐based fluorescence assays are as a matter of good laboratory practice required to validate all assays, which when in clinical practice may pass through regulatory review processes using criteria often defined with a soluble analyte in plasma or serum samples in mind. Recently the U.S. Food and Drug Administration (FDA) has entered into a public dialogue in the U.S. regarding their regulatory interest in laboratory developed tests (LDTs) or so‐called home brew assays performed in clinical laboratories. The absence of well‐defined guidelines for validation of cell‐based assays using fluorescence detection has thus become a subject of concern for the International Council for Standardization of Haematology (ICSH) and International Clinical Cytometry Society (ICCS). Accordingly, a group of over 40 international experts in the areas of test development, test validation, and clinical practice of a variety of assay types using flow cytometry and/or morphologic image analysis were invited to develop a set of practical guidelines useful to in vitro diagnostic (IVD) innovators, clinical laboratories, regulatory scientists, and laboratory inspectors. The focus of the group was restricted to fluorescence reporter reagents, although some common principles are shared by immunohistochemistry or immunocytochemistry techniques and noted where appropriate. The work product of this two year effort is the content of this special issue of this journal, which is published as 5 separate articles, this being Validation of Cell‐based Fluorescence Assays: Practice Guidelines from the ICSH and ICCS ‐ Part IV ‐ Postanalytic considerations. © 2013 International Clinical Cytometry Society
Validation of cell‐based fluorescence assays: Practice guidelines from the ICSH and ICCS – part V – assay performance criteria
Authors: Wood Brent , Jevremovic Dragan , Béné Marie C. , Yan Ming , Jacobs Patrick , Litwin Virginia ,   ; on behalf of ICSH/ICCS Working Group
Published: September 2013

Multi‐color flow cytometry is a unique technology, which enables the analysis of heterogeneous cellular systems and provides multiparametric information on a cell‐by‐cell basis. A variety of factors contribute to the complexity of validating cell‐based flow cytometric methods, including the lack of fully characterized cellular reference materials and the difficulty in obtaining, or creating, samples with varying levels of a given cell type or varying levels of expression of a given antigen. This document summarizes validation requirements and describes validation strategies for quasi‐quantitative and qualitative cell‐based flow cytometric assays. © 2013 International Clinical Cytometry Society
The Gut Microbiome: Insights for Personalized Medicine
Authors: Gurwitz David
Published: September 2013

The large scope of the human microbiome and its interactions with host tissues is currently unfolding. The complex interactions of the human microbiome with the human metabolome and epigenome may affect the susceptibility to and severity of complex diseases that include metabolic disorder, cancer and CNS disease states. In addition, the individual microbiome may modulate drug pharmacokinetics (PK) and pharmacodynamics (PD), contributing to drug response variations between individual patients. Current knowledge of such interactions represents only the tip of a very large iceberg. In the context of drug discovery and development, a notable aspect that deserves special attention is the study of microbiome‐host interactions that impact the individual response to therapeutics.
TLR7 signaling exacerbates CNS autoimmunity through downregulation of Foxp3+Treg cells
Authors: Lalive Patrice H. , Benkhoucha Mahdia , Tran Ngoc Lan , Kreutzfeldt Mario , Merkler Doron , Santiago‐Raber Marie‐Laure
Published: September 2013

The innate Toll‐like receptor 7 (TLR7) detects infections by recognizing viral and bacterial single‐stranded RNA. In addition to pathogen‐derived RNA, immune cells expressing high levels of TLR7, such as B cells and dendritic cells (DCs), can be activated by self‐RNA. During myelin‐induced experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, TLR7 expression is increased within the central nervous system (CNS). To define the contribution of TLR7 to the development of EAE, we evaluated the course of the disease in C57BL/6‐Tlr7‐deficient mice compared with that in WT mice and found that TLR7‐deficient mice had decreased disease severity. This protection was associated with decreased myelin oligodendrocyte glycoprotein‐specific T‐cell activation by primed DCs, decreased circulating autoantibodies, attenuated inflammation within the CNS, and increased Foxp3+ regulatory T cells in the periphery and in the CNS. In conclusion, we show that TLR7 is involved in the maintenance of autoimmunity in the pathogenesis of EAE.
CD161++CD8+T cells, including the MAIT cell subset, are specifically activated by IL‐12+IL‐18 in a TCR‐independent manner
Authors: Ussher James E. , Bilton Matthew , Attwod Emma , Shadwell Jonathan , Richardson Rachel , de Lara Catherine , Mettke Elisabeth , Kurioka Ayako , Hansen Ted H. , Klenerman Paul , Willberg Christian B.
Published: September 2013

CD161++CD8+ T cells represent a novel subset that is dominated in adult peripheral blood by mucosal‐associated invariant T (MAIT) cells, as defined by the expression of a variable‐α chain 7.2 (Vα7.2)‐Jα33 TCR, and IL‐18Rα. Stimulation with IL‐18+IL‐12 is known to induce IFN‐γ by both NK cells and, to a more limited extent, T cells. Here, we show the CD161++ CD8+ T‐cell population is the primary T‐cell population triggered by this mechanism. Both CD161++Vα7.2+ and CD161++Vα7.2− T‐cell subsets responded to IL‐12+IL‐18 stimulation, demonstrating this response was not restricted to the MAIT cells, but to the CD161++ phenotype. Bacteria and TLR agonists also indirectly triggered IFN‐γ expression via IL‐12 and IL‐18. These data show that CD161++ T cells are the predominant T‐cell population that responds directly to IL‐12+IL‐18 stimulation. Furthermore, our findings broaden the potential role of MAIT cells beyond bacterial responsiveness to potentially include viral infections and other inflammatory stimuli.
Platinum(II) Complexes Bearing 2‐(9,9‐Dihexadecyl‐7‐R‐fluoren‐2‐yl)‐1,10‐phenanthroline Ligands: Synthesis, Photophysics and Reverse Saturable Absorption
Authors: Liu Xu‐Guang , Sun Wenfang
Published: September 2013

Invited for the cover of this issue is the group of Wenfang Sun at North Dakota State University (NDSU), USA. The cover image illustrates the reverse saturable absorption (RSA) mechanism.
Synthesis and Tautomerism of Substituted Pyrazolo[4,3‐c]pyrazoles
Authors: Kadam Shivaji S. , Maier Lukáš , Kostakis Ioannis , Pouli Nicole , Toušek Jaromír , Nečas Marek , Marakos Panagiotis , Marek Radek
Published: September 2013

Fused five‐membered nitrogen heterocycles comprise a very important group of compounds frequently utilized in pharmaceutical applications. In this study, we report the first systematic synthesis of substituted pyrazolo[4,3‐c]pyrazoles and three regioisomers of their N‐methyl derivatives. All compounds were fully characterized by NMR spectroscopy in solution and selected compounds also were studied by X‐ray diffraction in the solid state. 1H, 13C, and 15N NMR spectroscopic data for all isomers were interpreted by DFT calculations of nuclear shielding constants and indirect spin–spin coupling constants. The N‐methyl isomers were used in the following steps as model compounds to investigate a potential N1‐H/N4‐H, N2‐H/N4‐H, and N1‐H/N5‐H tautomerism of 3,6‐substituted pyrazolo[4,3‐c]pyrazoles by using low‐temperature NMR spectroscopy. All bases were shown to occur predominantly in the N1‐H/N4‐H tautomeric form and the structure of minor form was governed by the substituents at positions 3 and 6. Stabilities of individual tautomeric forms are calculated by DFT methods and discussed. A relationship between the tautomeric populations and the ratios among N‐methyl isomers obtained upon methylation of selected bases in solution are investigated.
Synthesis of cycloSal‐(Glycopyranosyl‐6)‐phosphates as Activated Sugar Phosphates
Authors: Huchting Johanna , Ruthenbeck Alexandra , Meier Chris
Published: September 2013

The synthesis of cycloSal‐masked glycopyranosyl phosphates demands suitably protected precursors. A highly regioselective strategy for the preparation of cycloSal‐(1,2,3,4‐tetra‐O‐acetylglycopyranosyl‐6)‐phosphates was developed. Intermediate introduction of the Fmoc‐group allowed the isolation of the 1,2,3,4‐tetra‐O‐acetyl glycopyranoses to be skipped, thus, no isomerization occurred. Glycopyranoses were first converted into the 6‐O‐TBDMS‐1,2,3,4‐tetra‐O‐acetyl derivatives then, in a one‐pot reaction, the silyl ether was cleaved and the resulting 1,2,3,4‐tetra‐O‐acetyl glycopyranoses were trapped with Fmoc‐chloride. In this exchange of protecting groups no acetyl group migration occurred. The 6‐O‐Fmoc‐protected intermediates were selectively converted into the cycloSal‐masked glycopyranosyl phosphates in a one‐pot reaction. Finally, the reactivity of these activated glycopyranosyl‐6‐phosphates was demonstrated in the synthesis of 1,6‐diglycopyranosyl‐phosphates.
Total Synthesis of Transtaganolide E and F: Insight in the Biosynthesis of the Transtaganolides
Authors: Larsson Rikard , Scheeren Hans W. , Aben Rene W. M. , Johansson Martin , Sterner Olov
Published: September 2013

A total synthesis of transtaganolide E and F, proposed intermediates in the biosynthesis of the potent transtaganolides, including an Ireland–Claisen rearrangement and a high‐pressure intramolecular Diels–Alder cycloaddition reaction of an unactivated 2‐pyrone derivative, is reported. The implication of the results to the proposed transtaganolides biosynthesis is discussed.
CO2 capture in a chemical looping combustion power plant evaluated with an advanced exergetic analysis
Authors: Petrakopoulou Fontina , Tsatsaronis George , Morosuk Tatiana
Published: September 2013

CO2 capture and storage (CCS) is a way to minimize harmful emissions generated from the combustion of fossil fuels in power plants. Measures to increase the thermodynamic efficiency of power plants incorporating CCS can improve their economic viability, as well as reduce the environmental impact of such applications. Exergy‐based analyses are tools that aid the evaluation of energy conversion systems and reveal paths to improve them. In this article, an advanced exergetic analysis is applied to a near‐zero‐emission power plant that incorporates chemical looping combustion. The final goal is to reveal ways toward a more efficient and less polluting operation of the power plant. The objectives of the article further include the quantification of the different parts of the exergy destruction and the demonstration of the advantages of using such an advanced method. It has been found that most of the exergy destruction of the plant is endogenous and, for the majority of the components, unavoidable. When calculating the total avoidable exergy destruction caused by each component, it is found that the most important plant component is the reactor unit, followed by the expander and the compressor of the gas turbine. Lastly, the potential for improvement is found to lie mainly with the internal operation of the components, while the interactions among the plant components are less significant. © 2013 American Institute of Chemical Engineers Environ Prog, 33: 1017–1025, 2014
Effects of drying and storage on year‐round production of butanol and biodiesel from algal carbohydrates and lipids using algae from water remediation
Authors: Jernigan Alice , May Michael , Potts Thomas , Rodgers Brigitte , Hestekin Jamie , May Peter I. , McLaughlin John , Beitle Robert R. , Hestekin Christa
Published: September 2013

Algae harvested from a pilot water quality improvement technology at the Rockaway Wastewater Treatment Facility in New York were examined as a source of carbohydrates and lipids for the production of biofuels. Dried stocks of algae harvested during a 6‐month period were used to feed the bioreactors, and the process to extract sugar from the natural wastewater grown algae was optimized. The length of storage time, storage conditions, sugar extraction process, and fuel production were studied. The results show that if the algae is stored dry (<25% moisture) the algae stock can be used for up to a year with good conversion of carbohydrates to sugars using a 10% w/v of dried algae. These optimized conditions extracted the maximum amount of sugar, which yielded an average of 0.11 (g butanol/g sugar) from the bioreactors year‐round from a wide range of diatoms and other microalgae used to treat wastewater. Similarly, lipids could be obtained from the stored algal with value of >0.015 g/g algae even after a year in storage. These results demonstrate the potential for year round production of fuel from algae harvested as part of a water reclamation process. © 2013 American Institute of Chemical Engineers Environ Prog, 32: 1013–1022, 2013
Genesis of Hurricane Sandy (2012) simulated with a global mesoscale model
Authors: Shen B.‐W. , DeMaria M. , Li J.‐L. F. , Cheung S.
Published: September 2013

In this study, we investigate the formation predictability of Hurricane Sandy (2012) with a global mesoscale model. We first present five track and intensity forecasts of Sandy initialized at 00Z 22–26 October 2012, realistically producing its movement with a northwestward turn prior to its landfall. We then show that three experiments initialized at 00Z 16–18 October captured the genesis of Sandy with a lead time of up to 6 days and simulated reasonable evolution of Sandy's track and intensity in the next 2 day period of 18Z 21–23 October. Results suggest that the extended lead time of formation prediction is achieved by realistic simulations of multiscale processes, including (1) the interaction between an easterly wave and a low‐level westerly wind belt (WWB) and (2) the appearance of the upper‐level trough at 200 hPa to Sandy's northwest. The low‐level WWB and upper‐level trough are likely associated with a Madden‐Julian Oscillation.
Decomposition of Fe3S above 250 GPa
Authors: Ozawa Haruka , Hirose Kei , Suzuki Toshihiro , Ohishi Yasuo , Hirao Naohisa
Published: September 2013

We have determined subsolidus phase relations in the Fe–FeS system up to 271 GPa using laser‐heated diamond‐anvil cell techniques. In situ synchrotron X‐ray diffraction (XRD) measurements performed at high pressure and high temperature demonstrate the coexistence of hexagonal close‐packed (hcp) Fe and tetragonal Fe3S up to 241 GPa and 2510 K. In contrast, the XRD data obtained above 250 GPa show that the hcp phase coexists with the CsCl (B2)‐type phase for three different Fe–S bulk compositions (10, 16, and 20 atm% S). Furthermore, chemical analyses using a scanning transmission electron microscope on a retrieved sample indicate that Fe3S sample decomposes into two phases at 271 GPa and 2530 K, consistent with the XRD data. Theory predicts the presence of extensive solid solution between Fe and FeS at inner core conditions, whereas our results suggest that the Fe–FeS system remains eutectic at least to 271 GPa.
Advanced Technologies for Engineering Tissue Mimetics
Authors: Cohen‐Karni Tzahi , Dvir Tal
Published: September 2013

Micro‐ and nanotechnologies have become central to fields ranging from tissue and cellular biophysics to regenerative medicine toward the creation of more complex and progressive tissues. In this article, we overview some of the new technological concepts in this field for recapitulating the native extracellular matrix, designing dynamic microenvironments, and the incorporation of small‐scale devices for actuating and monitoring engineered tissue performances.
EFFECTS OF FLOW PATH DEPTH ON EMITTER CLOGGING AND SURFACE TOPOGRAPHICAL CHARACTERISTICS OF BIOFILMS
Authors: Zhou Bo , Li Yunkai , Liu Yaoze , Pei Yiting , Jiang Yinguang , Liu Honglu
Published: September 2013

The depth of the flow path of a drip irrigation emitter can affect the anti‐clogging ability of a drip irrigation system by changing the flow velocity distribution and material transportation process. In order to evaluate these effects, in this paper a drip irrigation experiment using reclaimed water was performed, and four types of emitters with four flow path depths were chosen for the experiment. The dynamic outflow changes of the emitters were tested with constant intervals and the surface topographical characteristics of biofilms at the inlets and outlets of emitters and the inner lateral walls were tested with the 3D‐WLSI (3D white‐light scanning interferometer). Thus, the effect of flow path depth on emitter clogging was analysed. The results showed that emitter clogging with different degrees in the 204 hrs was observed. The discharge ratio variation (Dra) and coefficient of uniformity (CU) of emitters all slightly decreased with fluctuant changes. Moreover, clogged emitters were more likely to occur at the end part of the lateral, which revealed obvious difference among emitters with different flow path depths. The average thickness (Sd) and relative average thickness (RSd) of biofilms increased with deeper flow path, while surface topographical characteristics of biofilms varied from smooth to rough. On the other hand, the average thickness and relative thickness of the biofilms at different positions of the lateral represented the order as: Sd head < Sd middle < Sd end and RSd head < RSd middle < RSd end. This was because the flow velocity decreased from the head to the end part of the lateral. Higher flow velocity resulted in limited nutrient supply and slower microbial metabolism, as well as higher turbulence intensity and hydraulic shear stress, which led to the easier detachment of biofilms. In contrast, the lower flow velocity and turbulence could result in the accumulation of biofilms and more serious clogging in the end part. Moreover, the average biofilm thickness at the emitter inlet closest to the end part of the lateral could be selected as a suitable site for monitoring emitter clogging and biofilm growth characteristics. On the other hand, the appropriate range of flow path depths for drip irrigation emitters using reclaimed water was 0.70–0.75 mm, which will provide the reference for exploring the emitter clogging mechanism of reclaimed water drip irrigation and developing efficient clogging control strategies. Copyright © 2013 John Wiley & Sons, Ltd.
Engagement: A Critical Aspect of Family Therapy Practice*
Authors: Jackson Sue , Chable Daniel G.
Published: September 2013

Engagement must be appreciated as an integral ongoing aspect of therapy. It can provide therapists with a wealth of information about the structure and functioning of the family. Engagement/counter‐engagement, assessment and interventions are essential, interdependent processes which occur throughout treatment. Ways of enhancing the engagement process are discussed.
Blackmail is Against the Law Part Five: I Have a Waiting List!
Authors: McCallum Peter , Lang Moshe
Published: September 2013

This paper reports in detail on the fifth and final session of family therapy which began after both mother and 14‐year‐old daughter attempted suicide. The work of the previous sessions is reviewed and an attempt is made to delineate the changes which have occurred within the family and the means by which they have been achieved.
The Last Time: A Metaphor For Leaving*
Authors: Relph Andrew
Published: September 2013

Much has been written about the beginning phase of family therapy, little about the end. Joining may be said to set the tone for later therapy, ending establishes directions for the future. As such, this last and crucial phase of therapy warrants careful study. This paper examines the importance of the last session of therapy for both family and therapist, and illustrates techniques which may facilitate future change.
Family Therapy's Coming of Age: Less Haste, More Speed
Authors: Crawley Jim
Published: September 2013

Responding to the question implicit in the title of the 1985 National Family Therapy Conference ‘Coming of Age’, the author argues that Australian family therapy still has a number of issues to face before it can be said to be a mature and independent adult. The paper focuses on three issues — ideology in family therapy, theory for practice, and practice itself— and raises questions about the adequacy of Australian family therapy's theoretical maturity, suggesting that there is still too much reliance on the ‘new’ and on the ‘guru’ rather than on a solid building on therapeutic experience.