bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolutionary History of Polar and Brown Bears
Authors: Hailer Frank , Welch Andreanna J
Published: July 2016

Taxonomists have long recognised polar and brown bears as separate species with distinct ecological niches and largely nonoverlapping ranges. Surprisingly, phylogenetic studies of maternally inherited mitochondrial DNA (mtDNA) found polar bears nested within brown bears, with an estimated divergence time of <170 000 years. This indicated an unusually rapid speciation and adaptation of polar bears. However, several recent studies of autosomal and Y‐chromosomal DNA have revisited these findings, giving independent perspectives of bear evolutionary history. Results show that polar bears cluster separately from brown bears, and divergence time estimates are older than those based on mtDNA, ranging from >300 000 to 4–5 million years. These studies confirm uniqueness of the polar bear lineage, provide more time for speciation and adaptation, and have uncovered numerous candidate genes for evolutionary adaptations. Several instances of introgressive hybridisation between polar and brown bears have been inferred, revealing trans‐species transmission of mtDNA and some nuclear loci.

Key Concepts

DNA sequences in conjunction with a calibration of the mutation rate (e.g. inclusion of a previously estimated mutation rate, geological information or inclusion of a radiocarbon‐dated ancient sample) can be used to estimate the timing of speciation between species.

Differentially inherited loci can reveal different aspects of evolutionary history.

The genome of polar bears contains a wealth of alleles that are not found in brown bears, and vice versa.

Polar bears have passed through bottlenecks during their evolutionary history, leaving them much less genetically variable than brown bears.

When analysing DNA sequences that have passed through the species boundary due to introgressive hybridisation, studies will obtain information about the hybridisation event rather than the (earlier) speciation event.

Brown bears have acted as vectors for polar bear alleles, transporting introgressed genetic material far beyond the species' contact zones.

Incomplete lineage sorting (see ‘Glossary’) complicates phylogenetic inferences among rapidly and/or recently diverged taxa. Lineage sorting takes on average four N
e
generations, which for many taxa can span at least several hundred thousand years (N
e
being the effective population size). The time needed for lineages to be reciprocally monophyletic can therefore take very long, even under complete reproductive isolation.

Molecular studies have found signals of positive selection in polar bear genes that are involved in fat metabolism, energy production and cardiovascular function. These genes are exciting candidates that may help us better understand the genetic basis of polar bear adaptations to Arctic conditions.
Aberrant
DNA
Methylation and Histone Modifications in Cancer
Authors: Hudler Petra
Published: July 2016

DNA (deoxyribonucleic acid) methylation of cytosines in CpG dinucleotides and post‐translational modifications of histone amino acids are epigenetic mechanisms that are in normal cells involved in specific cell functions, particularly in regulation of transcription and maintenance of stable chromatin. The epigenetic code is highly dynamic and enables the cells to regulate their responses to the intrinsic or environmental signals. Aberrations of DNA methylation patterns and histone modifications are major features observed in all types of cancer. Integrated research of genomic alterations, erroneous gene expression and modifications of epigenomes in cancer cells has revealed the complexity and heterogeneity of this disease. Some of the novel therapeutic and diagnostic approaches based on aberrant promoter hypermethylation and histone modifications, particularly acetylation, have already been translated into a clinical setting, whereas a number of others are being examined in clinical trials.

Key Concepts

DNA methylation and histone modifications cooperate in regulation of certain cell functions and responses.

Cancer development and progression are characterised by diverse aberrations in epigenetic profiles.

Changes in DNA methylation profiles could be used to define specific subsets of cancers, which harbour characteristic genetic alterations.

Hypermethylation or hypomethylation of gene promoters, resulting in silencing or activating the gene transcription, respectively, are fundamental in the identification of novel tumour suppressors and oncogenes.

Unravelling the functional consequences of methylation signature in nonpromoter regions is complex and will require further research efforts to discern their role in healthy and diseased cells.

Epigenetic profiling of cancers has already identified and is still identifying novel targets for the development of therapeutic and diagnostic approaches.
Biosensors
Authors: Hajek Kathrin , Schmittlein Carina , Oberleitner Maximilian , Shin Ik‐Soo , Wegener Joachim
Published: July 2016

Next to chromatography, spectroscopy or microscopy biosensors complete the available collection of tools to chemically analyse a complex sample. By definition, biosensors are compact analytical devices incorporating a biological or biologically derived sensing element intimately associated with a physicochemical transducer. The latter turns molecular recognition or biological response into a measurable, mostly electronic signal. Typical applications comprise pathogen detection, environmental monitoring, drug or toxicity screening as well as the analysis of clinical samples. This article gives a short overview about (1) general concepts of biosensor design, (2) biological components that are used for sensing, (3) the most important technical transducers and (4) some applications of molecular and cell‐based biosensors.

Key Concepts

A biosensor is a device that consists of (1) a biological element, which is used to specifically capture, convert or sense a target analyte and (2) a physicochemical transducer to convert the interaction with the analyte into a detectable signal.

The group of biological sensing elements comprises biomolecules like antibodies, enzymes, nucleic acids or living bacteria, archaeans or eukaryotic cells. Even cell aggregates, tissues or organs may serve for biorecognition and sensing.

Molecular biosensors detect target analytes either by capturing (antibodies, DNA, aptamers) or converting them (enzymes).

Cell‐based biosensors indicate the presence of the analyte by expression of reporter genes or an integrated, often generic (w)holistic response of cell physiology.

Electrochemical, optical, piezoelectric or calorimetric transducers are applied to quantify the interaction between analyte and sensing element.
Overview of Neuroethics
Authors: Purcell Ryan H , Wolpe Paul R
Published: July 2016

Neuroethics is a subfield of bioethics, and examines the intersection of neuroscience, ethics, philosophy, social science, and law. Neuroethics largely deals with (1) the ethical and social challenges raised by new discoveries and inventions in neuroscience and neurotechnology and (2) the implications of neuroscientific discoveries for our conceptions of topics such as free will, consciousness, religious experience, and morality, among others. As neuroscientists continue to expand our understanding of the human brain, and as neurotechnologies allow us to manipulate or alter cognitive and affective functioning, it is important to continue the neuroethical discussion of whether to allow certain interventions, how to apply our neuroscientific knowledge and technology, and what these new discoveries mean for the human condition and human flourishing.

Key Concepts

Neuroethics is a growing field that examines the ethics of neuroscience and the intersection of neuroscience, philosophy, and society.

Neuroscience is increasingly crossing over into law and society, creating a need to understand the societal implications of neuroscientific progress.

Neuroethicists also study the neuroscience of ethics and morality.

Neuroethicists evaluate both practical, technological issues and more conceptual or philosophical issues.

The study of the brain presents a unique set of issues and challenges compared with other bodily organs.
Social Studies of Autism
Authors: Hollin Gregory JS
Published: July 2016

Autism is a neurodevelopmental disorder characterised by socio‐communicative impairments and restricted interests and repetitive behaviours. While autism is today diagnosed in approximately 1 in 100 children, and retrospectively observed throughout history, it was described for the first time only in the 1940s and seen only rarely until more recently still. Broad social, and specific scientific, developments led to the contemporary form and shape of autism. Social developments include the advent of psychology, the onset of compulsory education and the widespread deinstitutionalisation that occurred in the 1960s. Consideration of scientific change is centred on the move away from psychoanalytic concepts and towards the methods of biology and cognitive psychology. These changes are placed into dialogue with the self‐advocacy movement and consideration of the ethical and conceptual challenges that these movements have ushered in.

Key Concepts

Autism is understood as a neurodevelopmental disorder. This means that autism is a lifelong condition, diagnosable from childhood, which primarily affects the brain.

Autism was first described comparatively recently – in 1943 – and the believed cause, symptoms and prevalence of the condition have altered significantly since this point. This suggests that certain social and scientific developments were required to make autism thinkable.

The emergence of the psy‐disciplines, which claimed expertise over the mind, and compulsory education, which made children visible to society, were of importance to an early recognition of autism.

Widespread deinstitutionalisation in the 1960s – where individuals were moved from hospitals and asylums into the community – made the social impairments associated with autism increasingly visible and significant.

Psychoanalytical methods – which place emphasis upon detailed analysis of individual patients – were largely supplanted by statistical methods in the mid‐twentieth century. This methodological change was associated with significant changes in core autism symptomology.

A further, crucial change has been the importance of self‐advocacy groups. These groups have contested the claim that autism is a form of disability and instead argued that it is a form of difference.
Molecular Genetics of Meningioma
Authors: Smith Miriam J
Published: July 2016

Meningiomas are the most common primary brain tumours in the adult central nervous system. These tumours are not normally malignant, but can cause brain invasion and lead to various motor and sensory deficits, which are dependent on tumour location. Meningiomas are normally single, sporadic tumours, but can occur as multiple meningiomas. Neurofibromatosis type 2 (
NF2
) mutations are the most common genetic cause of meningiomas and multiple meningiomas usually occur within the context of NF2 disease. Recent studies have identified a variety of other, less common, germline and somatic mutations in meningioma disease, showing that alternative mechanisms exist for the initiation and progression of meningioma growth. These discoveries will be useful for determining individual risk and prognosis and to develop individualised therapeutic strategies based on specific meningioma subtypes.

Key Concepts

Meningiomas are the most common tumours in the adult central nervous system.

Most meningiomas are solitary tumours.

The neurofibromatosis type 2 gene is the most common cause of meningiomas.

Rare non‐NF2 meningioma predisposition genes can cause hereditary meningioma disease.

A range of somatic alterations in meningiomas may cause tumour development via differing cellular pathways.
Role of Endogenous Retroviruses in Human Genetic Diseases
Authors: Lin Audrey T , Magiorkinis Gkikas
Published: July 2016

It is now increasingly realised that many repetitive elements such as endogenous retroviruses (ERVs), remnants of ancient retroviral infections, can contribute to the host's genetic and transcriptional identity in complex ways. There is growing evidence that specific ERVs are not genomic ‘junk’, but have biological significance in humans. Some ERVs have been ‘co‐opted’ for human biological processes, and the nucleic acids and proteins of these ERVs are able to modify human gene expression and regulatory networks in a cell and tissue‐specific manner, with implications for healthy development, immune function and susceptibility to diseases. Ongoing research explores the possibility that aberrant expression of HERVs would contribute to the pathogenesis of a number of inflammatory disorders, including cancers, multiple sclerosis, amyotrophic lateral sclerosis and schizophrenia.

Key Concepts

Some HERVs have been ‘co‐opted’ for human biological processes such as placentogenesis, innate immunity pathways, anticancer mechanisms and central nervous system function.

ERVs provide a genetic reservoir for promoters, transcription start sites, enhancers and alternative splice donors and acceptors for regulating host gene expression.

HERV‐K (HML‐2), the youngest HERV in the human genome, is polymorphic in the human population, meaning that not everyone has the same HERV integration at the same chromosomal position.

Np9 and Rec, accessory proteins encoded by HERV‐K (HML‐2), are associated with specific human cancers in several ways: their expression is upregulated, they interact with specific cancer biomarkers and they impact signalling pathways that are implicated with cancer.

Specific HERV LTRs help regulate the innate immune response by acting as a reservoir of interferon‐inducible enhancers.

HERV transcripts play a role in priming and activating B‐cell responses in a T‐cell‐independent pathway against specific pathogens.

Ongoing research explores the possibility that aberrant expression of HERVs would contribute to the pathogenesis of a number of inflammatory disorders, including cancers, multiple sclerosis, amyotrophic lateral sclerosis and schizophrenia.
Adaptive output regulation for offshore managed pressure drilling
Authors: Mahdianfar Hessam , Pavlov Alexey
Published: July 2016

This paper deals with output regulation problem for an offshore managed pressure drilling system subject to sinusoidal disturbances. The disturbance is caused by the heave motion of the floating drilling rig during pipe connections, and the objective is to maintain a constant pressure at the bottom of the well. The controller for the heave disturbance attenuation consists of three cascaded parts. First, a nonlinear inversion element is applied to invert nonlinearity of choke. Second, an adaptive compensator is designed based on internal model, and certainty equivalence principles for asymptotic rejection of time‐varying heave disturbance. Third, an output feedback controller is synthesized for providing stability and improving transient performance of closed‐loop system. Robust stability of closed‐loop system is analyzed using edge theorem. Simulation results of the combined adaptive output regulator are presented, which show satisfactory set‐point tracking and attenuation of the heave disturbance. Copyright © 2016 John Wiley & Sons, Ltd.
Selective Photothermal Tumor Therapy Using Nanodiamond‐Based Nanoclusters with Folic Acid
Authors: Ryu Tae‐Kyung , Baek Seung Woon , Kang Rae Hyung , Choi Sung‐Wook
Published: July 2016

This paper describes the fabrication and evaluation of folic acid (FA)‐conjugated nanodiamond (ND) nanoclusters for selective photothermal tumor therapy. ND nanoclusters with surface carboxyl groups are aminated using ethylenediamine and conjugated with FA via carbodiimide chemistry. The temperature of an aqueous ND dispersion (10 μg mL−1) is increased to 54 °C upon laser exposure for 5 min. FA‐ND nanoclusters are preferentially taken up by KB cells (folate receptor positive) compared to WI‐38 (folate receptor negative) cells, suggesting specificity for tumor cells that overexpress folate receptors. Cell viability tests reveal that FA‐ND nanoclusters effectively and selectively ablate KB cells upon near‐infrared (NIR) laser exposure. In addition, fluorescence microscopy images confirm that only KB cells treated with FA‐ND nanoclusters are ablated in a spot (200 μm in diameter) by NIR laser exposure. In an animal model, a large amount of FA‐ND nanoclusters is accumulated into tumor tissue, resulting in dramatically reduced tumor volume post‐NIR laser exposure as compared to ND nanoclusters.
Acute myeloid leukemia: 2016 Update on risk‐stratification and management
Authors: Estey Elihu
Published: July 2016

Evidence suggest that even patients aged 70 or above benefit from specific AML therapy. The fundamental decision in AML then becomes whether to recommend standard or investigational treatment. This decision must rest on the likely outcome of standard treatment. Hence we review factors that predict treatment related mortality and resistance to therapy, the latter the principal cause of failure even in patients aged 70 or above. We emphasize the limitations of prediction of resistance based only on pre‐ treatment factors and stress the need to incorporate post‐treatment factors, for example indicators of minimal residual disease. We review various newer therapeutic options and considerations that underlie the decision to recommend allogeneic hematopoietic cell transplant. Am. J. Hematol. 91:825–846, 2016. © 2016 Wiley Periodicals, Inc.
Outcomes in patients with multiple myeloma with TP53 deletion after autologous hematopoietic stem cell transplant
Authors: Gaballa Sameh , Saliba Rima M. , Srour Samer , Lu Gary , Brammer Jonathan E. , Shah Nina , Bashir Qaiser , Patel Krina , Bock Fabian , Parmar Simrit , Hosing Chitra , Popat Uday , Delgado Ruby , Rondon Gabriela , Shah Jatin J. , Manasanch Elisabet E. , Orlowski Robert Z. , Champlin Richard , Qazilbash Muzaffar H.
Published: July 2016

TP53 gene deletion is associated with poor outcomes in multiple myeloma (MM). We report the outcomes of patients with MM with and without TP53 deletion who underwent immunomodulatory drug (IMiD) and/or proteasome inhibitor (PI) induction followed by autologous hematopoietic stem cell transplant (auto‐HCT). We identified 34 patients with MM and TP53 deletion who underwent IMiD and/or PI induction followed by auto‐HCT at our institution during 2008–2014. We compared their outcomes with those of control patients (n = 111) with MM without TP53 deletion. Median age at auto‐HCT was 59 years in the TP53‐deletion group and 58 years in the control group (P = 0.4). Twenty‐one patients (62%) with TP53 deletion and 69 controls (62%) achieved at least partial remission before auto‐HCT (P = 0.97). Twenty‐three patients (68%) with TP53 deletion and 47 controls (42%) had relapsed disease at auto‐HCT (P = 0.01). Median progression‐free survival was 8 months for patients with TP53 deletion and 28 months for controls (P < 0.001). Median overall survival was 21 months for patients with TP53 deletion and 56 months for controls (P < 0.001). On multivariate analysis of both groups, TP53 deletion (hazard ratio 3.4, 95% confidence interval 1.9–5.8, P < 0.001) and relapsed disease at auto‐HCT (hazard ratio 2.0, 95% confidence interval 1.2–3.4, P = 0.008) were associated with a higher risk of earlier progression. In MM patients treated with PI and/or IMiD drugs, and auto‐HCT, TP53 deletion and relapsed disease at the time of auto‐HCT are independent predictors of progression. Novel approaches should be evaluated in this high‐risk population. Am. J. Hematol. 91:E442–E447, 2016. © 2016 Wiley Periodicals, Inc.
Androgen receptor CAG repeat polymorphism and hypothalamic‐pituitary‐gonadal function in Filipino young adult males
Authors: Ryan Calen P. , McDade Thomas W. , Gettler Lee T. , Eisenberg Dan T. A. , Rzhetskaya Margarita , Hayes M. Geoffey , Kuzawa Christopher W.
Published: July 2016

Objectives

Testosterone (T), the primary androgenic hormone in males, is stimulated through pulsatile secretion of LH and regulated through negative feedback inhibition at the hypothalamus and pituitary. The hypothalamic‐pituitary‐gonadal (HPG) axis also controls sperm production through the secretion of follicle‐stimulating hormone (FSH). Negative feedback in the HPG axis is achieved in part through the binding of T to the androgen receptor (AR), which contains a highly variable trinucleotide repeat polymorphism (AR‐CAGn). The number of repeats in the AR‐CAGn inversely correlates with transcriptional activity of the AR. Thus, we predicted longer AR‐CAGn to be associated with higher T, LH, and FSH levels.

Methods

We examined the relationship between AR‐CAGn and total plasma T, LH, and FSH, as well as “bioavailable” morning (AM‐T) and evening (PM‐T) testosterone in 722 young (21.5 ± 0.5 years) Filipino males.

Results

There was no relationship between AR‐CAGn and total T, AM‐T, or LH (P > .25 for all). We did observe a marginally non‐significant (P = .066) correlation between AR‐CAGn and PM‐T in the predicted direction, and a negative correlation between AR‐CAGn and FSH (P = .005).

Conclusions

Our results both support and differ from previous findings in this area, and study parameters that differ between our study and others, such as participant age, sample time, and the role of other hormones should be considered when interpreting our findings. While our data point to a modest effect of AR‐CAGn on HPG regulation at best, the AR‐CAGn may still affect somatic traits by regulating androgenic activity at peripheral tissues.
Nine year old boy with chromosome 1q23.3‐q25.1 deletion
Authors: Lam Felicia , Morris Colleen
Published: July 2016

Interstitial deletions of the long arm of chromosome 1 are rare, and recent reports of individuals with molecularly characterized deletions have resulted in advances in genotype–phenotype correlation. The recognizable phenotype associated with 1q23.3‐q25.1 includes pre‐ and post‐natal growth retardation, microcephaly, intellectual disability, delayed language acquisition, small hands and feet with brachydactyly and single palmar crease, and distinctive facial features including short bulbous nose, micrognathia, and ear malformations. We report a patient with an 11.35 Mb deletion from 1q23.3‐q25.1 who has these features in addition to a rarely reported complication—profound sensorineural hearing loss. He has both pre‐ and post‐natal growth deficiency and growth hormone deficiency that was diagnosed at age 2 years. However, unlike other individuals with this deletion and growth hormone deficiency, this boy has responded to treatment with human growth hormone. © 2016 Wiley Periodicals, Inc.
Simultaneous H2 Generation and Biomass Upgrading in Water by an Efficient Noble‐Metal‐Free Bifunctional Electrocatalyst
Authors: You Bo , Jiang Nan , Liu Xuan , Sun Yujie
Published: July 2016

As an environmentally friendly approach to generate H2, electrocatalytic water splitting has attracted worldwide interest. However, its broad employment has been inhibited by costly catalysts and low energy conversion efficiency, mainly due to the sluggish anodic half reaction, the O2 evolution reaction (OER), whose product O2 is not of significant value. Herein, we report an efficient strategy to replace OER with a thermodynamically more favorable reaction, the oxidation of 5‐hydroxymethylfurfural (HMF) to 2,5‐furandicarboxylic acid (FDCA), catalyzed by 3D Ni2P nanoparticle arrays on nickel foam (Ni2P NPA/NF). HMF is one of the primary dehydration intermediates of raw biomass and FDCA is of many industrial applications. As a bifunctional electrocatalyst, Ni2P NPA/NF is not only active for HMF oxidation but also competent for H2 evolution. In fact, a two‐electrode electrolyzer employing Ni2P NPA/NF for simultaneous H2 and FDCA production required a voltage at least 200 mV smaller compared with pure water splitting to achieve the same current density, as well as exhibiting robust stability and nearly unity Faradaic efficiencies.
Metallvermittelte Eintopfsynthese von Isoporphyrin‐Komplexen
Authors: Schweyen Peter , Hoffmann Martin , Krumsieck Jens , Wolfram Benedikt , Xie Xiulan , Bröring Martin
Published: July 2016

Es wurden meso‐Arylisoporphyrine mit exocyclischem Pyrrolyl‐ oder Dipyrrinylsubstituenten am sp3‐Kohlenstoffatom als Zink‐ und Cadmiumkomplexe bei einer Variation der Alder‐Longo‐Porphyrinsynthese isoliert. Entscheidend bei der Bildung und Stabilisierung dieser Isoporphyrine im Eintopf‐Verfahren ist die Gegenwart von Metallacetaten während des Ringschlusses zum Makrocyclus. Die charakteristischen Q‐Banden der neuen Isoporphyrine werden erwartungsgemäß im Nah‐Infrarot‐Bereich zwischen λ=750 und 880 nm gefunden. Alle isolierten Derivate sind stabil an Luft und unter gängigen Laborbedingungen, und erste chemische Transformationen wie BF2‐Koordination, Transmetallierung oder Ligandenaustausch konnten durchgeführt werden.
Rhodium‐Catalyzed Asymmetric Cycloisomerization and Parallel Kinetic Resolution of Racemic Oxabicycles
Authors: Loh Charles C. J. , Schmid Matthias , Webster Robert , Yen Andy , Yazdi Shabnam K. , Franke Patrick T. , Lautens Mark
Published: July 2016

While desymmetrizations by intermolecular asymmetric ring‐opening reactions of oxabicyclic alkenes with various nucleophiles have been reported over the past two decades, the demonstration of an intramolecular variant is unknown. Reported herein is the first rhodium‐catalyzed asymmetric cycloisomerization of meso‐oxabicyclic alkenes tethered to bridgehead nucleophiles, thus providing access to tricyclic scaffolds through a myriad of enantioselective C−O, C−N, and C−C bond formations. Moreover, we also demonstrate a unique parallel kinetic resolution, whereby racemic oxabicycles bearing two different bridgehead nucleophiles can be resolved enantioselectively.
Metal‐Assisted One‐Pot Synthesis of Isoporphyrin Complexes
Authors: Schweyen Peter , Hoffmann Martin , Krumsieck Jens , Wolfram Benedikt , Xie Xiulan , Bröring Martin
Published: July 2016

Zinc and cadmium complexes of meso‐arylisoporphyrins carrying a pyrrolyl or dipyrrinyl substituent at the sp3 carbon atom were obtained through a simple one‐pot variation of the Alder–Longo porphyrin synthesis. Key to the formation and stabilization of isoporphyrins is the presence of metal acetates during the oxidative macrocyclization step. The characteristic Q‐bands of isoporphyrins are found in the NIR region between 750 nm and 880 nm. All of the isolated pyrrolyl‐ and dipyrrinyl‐appended isoporphyrins are stable under typical laboratory conditions and allow chemical transformations like BF2 coordination, transmetalation, and ligand exchange.
Solid‐to‐Liquid Charge Transfer for Generating Droplets with Tunable Charge
Authors: Sun Yajuan , Huang Xu , Soh Siowling
Published: July 2016

Charged liquid droplets are typically generated by a high‐voltage power supply. Herein, a previously unreported method is used for charging liquid droplets: by transferring charge from an insulating solid surface charged by contact electrification to the droplets. Charging the solid surface by contact electrification involves bringing it into contact with another solid surface for generating static charge. Subsequently, water droplets that flow across the surface are found to be charged—thus, the charge is readily transferred from solid to liquid. The charge of the droplets can be tuned continuously from positive to negative by varying the way the solid surface is charged. The amount of charge generated is sufficient for manipulating, coalescing, and sorting the water droplets by solid surfaces charged by contact electrification. This method of generating charged droplets is general, simple, inexpensive, and does not need any additional equipment or power supply.
Topotactic Consolidation of Monocrystalline CoZn Hydroxides for Advanced Oxygen Evolution Electrodes
Authors: Wang Jing , Tan Chuan Fu , Zhu Ting , Ho Ghim Wei
Published: July 2016

We present a room temperature topotactic consolidation of cobalt and zinc constituents into monocrystalline CoZn hydroxide nanosheets, by a localized corrosion of zinc foils with cobalt precursors. By virtue of similar lattice orientation and structure coordination, the hybrid hydroxides amalgamate atomically without phase separation. Importantly, this in situ growth strategy, in combination with configurable percolated nanosheets, renders a high areal density of catalytic sites, immobilized structures, and conductive pathways between the nanosheets and underlying foils—all of which allow monocrystalline CoZn hydroxide nanosheet materials to function as effective electrodes for electrochemical oxygen evolution reactions. This convenient and eco‐friendly topotactical transformation approach facilitates high‐quality single crystal growth with improved multiphase purity and homogeneity, which can be extended to other transition metals for the fabrication of advanced functional nanocomposites.
Triphenylphosphinopalladium(II) complexes with ONO‐donor ligands: syntheses, structures and catalytic applications in CC cross‐coupling reactions
Authors: Prabhu Rupesh Narayana , Babu G. Narendra , Pal Samudranil
Published: July 2016

Reactions of 1‐((2‐hydroxy‐5‐R‐phenylimino)methyl)naphthalen‐2‐ols (H2Ln, n = 1–3 for R = H, Me, Cl, respectively) with [Pd(PPh3)2Cl2] and Et3N in toluene under reflux produced three new mononuclear square‐planar palladium(II) complexes with the general formula [Pd(Ln)(PPh3)] (1, R = H; 2, R = Me; 3, R = Cl). All the complexes were characterized using elemental analysis, solution conductivity and various spectroscopic (infrared, UV–visible and NMR) measurements. Molecular structures of 1, 2, 3 were confirmed using single‐crystal X‐ray diffraction analysis. In each complex, the fused 5,6‐membered chelate rings forming phenolate‐O, azomethine‐N and naphtholate‐O donor (Ln)2− and the PPh3 form a square‐planar ONOP coordination environment around the metal centre. Infrared and NMR spectroscopic features of 1, 2, 3 are consistent with their molecular structures. Electronic spectra of the three complexes display several strong primarily ligand‐centred absorption bands in the range 322–476 nm. All the complexes were found to be effective catalysts for carbon–carbon cross‐coupling reactions of arylboronic acids with aromatic and heteroaromatic aldehydes to form the corresponding diaryl ketones. Copyright © 2016 John Wiley & Sons, Ltd.
Effects of diatomite inorganic fillers on the properties of a melamine–urea–formaldehyde resin
Authors: Li Xiaona , Luo Jing , Li Jianzhang , Gao Qiang
Published: July 2016

In this study, a low‐cost diatomite was used to partly substitute wheat flour as one type of melamine–urea–formaldehyde (MUF) resin filler. Five‐ply plywood was fabricated, and its performance was measured. The crystallinity, fracture surface, and functional groups were tested to determine the effects of diatomite on the performance of the MUF resin. The results show that diatomite was well distributed in the MUF resin system and formed an embedding structure; this improved the wet shear strength of the resulting plywood by 33% to 1.36 MPa. Diatomite captured the free formaldehyde in the resin and the microporous structure formed in the resin accelerate formaldehyde release of the plywood. Consequently, the formaldehyde emission of the plywood was reduced. The diatomite partly replaced wheat flour as an MUF resin filler and could be applied in the plywood industry. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 44095.
Polyamide/polyacrylonitrile thin film composites as forward osmosis membranes
Authors: Hajighahremanzadeh Parisa , Abbaszadeh Mahsa , Mousavi Seyyed Abbas , Soltanieh Mohammad , Bakhshi Hadi
Published: July 2016

Thin film composites (TFCs) as forward osmosis (FO) membranes for seawater desalination application were prepared. For this purpose, polyacrylonitrile (PAN) as a moderately hydrophilic polymer was used to fabricate support membranes via nonsolvent‐induced phase inversion. A selective thin polyamide (PA) film was then formed on the top of PAN membranes via interfacial polymerization reaction of m‐phenylenediamine and trimesoyl chloride (TMC). The effects of PAN solution concentration, solvent mixture, and coagulation bath temperature on the morphology, water permeability, and FO performance of the membranes and composites were studied. Support membranes based on low PAN concentrations (7 wt %), NMP as solvent and low coagulation bath temperature (0 °C) demonstrated lower thickness, thinner skin layer, more porosity, and higher water permeability. Meanwhile, decreasing the PAN solution concentration lead to higher water permeance and flux and lower reverse salt flux, structural parameter, and tortuosity for the final TFCs. Composites made in N,N‐dimethylformamide presented lower permeance and flux for water and salt and higher salt rejection, structural parameter, and tortuosity. FO assay of the composites showed lower water permeance values in saline medium comparing to pure water. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 44130.
Controlled co‐delivery of hydrophilic and hydrophobic drugs from thermosensitive and crystallizable copolymer nanoparticles
Authors: Xu Xianbo , Shan Guorong R. , Pan Pengju
Published: July 2016

Functionalized amphiphilic block copolymers poly(N‐isopropyl acrylamide)‐b‐poly(stearyl methacrylate) (PNIPAM‐PSMA) are synthesized. Their self‐assembled core‐shell nanoparticles have the hydrophilic thermosensitive shell and hydrophobic crystallizable core. Nanoparticles exhibit volume phase transition at temperature of 38  °C and its poly(stearyl methacrylate) (PSMA) moiety could form nano size crystals to retain drugs, making them good carriers for drug co‐delivery system. Thermosensitivity and crystallinity of nanoparticles are characterized with dynamic light scattering (DLS), differential scanning calorimetry (DSC), small‐angle X‐ray scattering (SAXS), and atomic force microscopy (AFM). The interactions and relationship between chemical structures of copolymer nanoparticles and loading drugs are discussed. Different loading techniques and combined loading of hydrophobic/hydrophilic drugs are studied. Nanoparticles show a good and controllable drug loading capacity (DL) of hydrophilic/hydrophobic drugs. The drugs release kinetics is analyzed with Fick's law and Weibull model. A general method for analyzing drug release kinetics from nanoparticles is proposed. Weibull model is well fitted and the parameters with definite physical meaning are analyzed. PNIPAM‐PSMA nanoparticles show a quite different thermal response, temporal regulation, and sustained release effect of hydrophilic and hydrophobic drugs, suggesting a promising application in extended and controlled co‐delivery system of multi‐drug. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 44132.
Synthesis and application of sodium 2‐acrylamido‐2‐methylpropane sulphonate/N‐vinylcaprolactam/divinyl benzene as a high‐performance viscosifier in water‐based drilling fluid
Authors: Xie Binqiang , Liu Xiaodong , Wang Huiqiang , Zheng Lihui
Published: July 2016

Aiming at good thickening ability and temperature resistance in water‐based drilling fluid, a novel copolymer viscosifier (SDKP) of sodium 2‐acrylamido‐2‐methylpropane sulfonate (NaAMPS) with N‐vinylcaprolactam (NVCL) and cross‐linking divinylbenzene (DVB) was prepared by micellar radical polymerization. The composition and molecular structure of optimal SDKP under the optimum reaction conditions was characterized by FT‐IR, 1H‐NMR, and elemental analysis, and the molecular weight was determined by GPC. Thermal gravimetric analysis showed that the SDKP was even stable when the temperature was not higher than 330 °C. The performance of SDKP as viscosifier for aqueous, brines, and saturated brine bentonite drilling fluid was evaluated before and after aging tests at 230 °C for 16 h. The evaluation results indicated that the SDKP had excellent thickening ability, thermal resistant, and salt tolerance. HTHP rheology test showed that the SDKP containing drilling fluids displayed a thermo‐thickening effect in temperature range of 150 to 180 °C, which was beneficial to increase the viscosity and strength of fluids at high temperatures. Shear test showed that the SDKP illustrated a similar shear thinning to xanthan gum. ESEM observations demonstrated that the continuous three‐dimensional network was formed in the SDKP aqueous and brines solution, which was probably the main reason for its excellent thickening properties. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 44140.
Synthesis and In Vitro Pharmacological Evaluation of 5‐(Alkoxymethyl)‐2‐(3‐alkylamino‐2‐hydroxypropoxy)phenylethanones Related to Acebutolol and Celiprolol
Authors: Bruchatá Katarína , Némethy Andrej , Čižmáriková Ružena , Račanská Eva , Habala Ladislav
Published: July 2016

The structure–activity relationships of 13 analogs of aryloxyaminopropanol type derived from 2‐hydroxyphenylethanone as potential β‐blockers are described. The synthesized compounds possess an isopropyl or a tert‐butyl group in the hydrophilic part of the molecule and an alkoxymethyl substitution in the lipophilic moiety. The target compounds were prepared by an established four‐step method and their structures were confirmed by interpretation of their UV, IR, 1H NMR and 13C NMR spectra, and by elemental analysis. The β‐adrenolytic efficacy of the prepared racemic compounds was determined on isolated guinea pig atria (β1) and trachea (β2) and expressed as pA2 values against isoprenaline tachycardia. The assumed cardioselectivity was expressed as β1/β2 ratio and the values of compounds with an alkoxy group (CH3O, iC3H5O, C5H11O, CH2CHCH2O, CH3OCH2CH2O) in the lipophilic part and with tert‐butyl in the hydrophilic part of the molecule were found to be comparable or higher than those of the standards acebutolol and celiprolol. All evaluated substances at a concentration of 10−7 mol/dm3 showed also negative chronotropic effects.
Pricing Asian options of discretely monitored geometric average in the regime‐switching model
Authors: Kim Jerim , Yoo Hyun Joo , Kim Tae‐Wan
Published: July 2016

This paper provides analytic pricing formulas of discretely monitored geometric Asian options under the regime‐switching model. We derive the joint Laplace transform of the discount factor, the log return of the underlying asset price at maturity, and the logarithm of the geometric mean of the asset price. Then using the change of measures and the inversion of the transform, the prices and deltas of a fixed‐strike and a floating‐strike geometric Asian option are obtained. As the numerical results, we calculate the price of a fixed‐strike and a floating‐strike discrete geometric Asian call option using our formulas and compare with the results of the Monte Carlo simulation. Copyright © 2016 John Wiley & Sons, Ltd.
Lack of replication of previous autism spectrum disorder GWAS hits in European populations
Authors: Torrico Bàrbara , Chiocchetti Andreas G. , Bacchelli Elena , Trabetti Elisabetta , Hervás Amaia , Franke Barbara , Buitelaar Jan K. , Rommelse Nanda , Yousaf Afsheen , Duketis Eftichia , Freitag Christine M. , Caballero‐Andaluz Rafaela , Martinez‐Mir Amalia , Scholl Francisco G. , Ribasés Marta ,   ITAN, Battaglia Agatino , Malerba Giovanni , Delorme Richard , Benabou Marion , Maestrini Elena , Bourgeron Thomas , Cormand Bru , Toma Claudio
Published: July 2016

Common variants contribute significantly to the genetics of autism spectrum disorder (ASD), although the identification of individual risk polymorphisms remains still elusive due to their small effect sizes and limited sample sizes available for association studies. During the last decade several genome‐wide association studies (GWAS) have enabled the detection of a few plausible risk variants. The three main studies are family‐based and pointed at SEMA5A (rs10513025), MACROD2 (rs4141463) and MSNP1 (rs4307059). In our study we attempted to replicate these GWAS hits using a case‐control association study in five European populations of ASD patients and gender‐matched controls, all Caucasians. Results showed no association of individual variants with ASD in any of the population groups considered or in the combined European sample. We performed a meta‐analysis study across five European populations for rs10513025 (1,904 ASD cases and 2,674 controls), seven European populations for rs4141463 (2,855 ASD cases and 36,177 controls) and five European populations for rs4307059 (2,347 ASD cases and 2,764 controls). The results showed an odds ratio (OR) of 1.05 (95% CI = 0.84–1.32) for rs10513025, 1.0002 (95% CI = 0.93–1.08) for rs4141463 and 1.01 (95% CI = 0.92–1.1) for rs4307059, with no significant P‐values (rs10513025, P = 0.73; rs4141463, P = 0.95; rs4307059, P = 0.9). No association was found when we considered either only high functioning autism (HFA), genders separately or only multiplex families. Ongoing GWAS projects with larger ASD cohorts will contribute to clarify the role of common variation in the disorder and will likely identify risk variants of modest effect not detected previously. Autism Res 2017, 10: 202–211. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Biogasdoneright™: An innovative new system is commercialized in Italy
Authors: Dale Bruce E. , Sibilla Fabrizio , Fabbri Claudio , Pezzaglia Marco , Pecorino Biagio , Veggia Ezio , Baronchelli Angelo , Gattoni Piero , Bozzetto Stefano
Published: July 2016

A group of over 600 Italian farmers organized as the Italian Biogas Consortium are redesigning their own farming systems to produce food and bioenergy in a nationwide farm‐level movement called Biogasdoneright™. This Feature demonstrates how it is possible to simultaneously increase the economic viability and stability of agriculture by reducing farm input costs and enabling farmers to produce food and fuel more sustainably. © 2016 Society of Chemical Industry and John Wiley & Sons, Ltd
TKI combination therapy: strategy to enhance dasatinib uptake by inhibiting Pgp‐ and BCRP‐mediated efflux
Authors: D'Cunha Ronilda , Bae SoHyun , Murry Daryl J. , An Guohua
Published: July 2016

The overexpression of efflux transporters, especially P‐glycoprotein (Pgp, MDR1, ABCB1) and breast cancer resistance protein (BCRP, ABCG2), represents an important mechanism of multidrug resistance (MDR). Tyrosine kinase inhibitors (TKIs), a novel group of target‐specific anticancer drugs, have recently been found to interact with Pgp and BCRP and to serve as both substrates and inhibitors. Considering their dual role, we anticipate that combination TKI therapy may represent a promising strategy to reverse efflux transporter mediated TKI resistance. Presently, investigations on these interactions are very limited. To fill the literature gap, dasatinib was used as the model drug and the effects of various TKIs on Pgp‐ and BCRP‐ mediated dasatinib efflux were evaluated. Cell uptake studies were performed using LLC‐PK1 and MDCK‐II cells along with their subclones that were transfected with human Pgp and BCRP, respectively. Among the 14 TKIs screened, nine TKIs greatly inhibited Pgp‐mediated dasatinib efflux at 50 μm. Further concentration dependent studies showed that imatinib, nilotinib and pazopanib were potent Pgp inhibitors with IC50 values of 2.42, 6.11 and 8.06 μm, respectively. Additionally, 50 μm of five TKIs greatly increased dasatinib accumulation through BCRP inhibition. Concentration dependent studies revealed that imatinib, erlotinib, nilotinib, axitinib and pazopanib were potent BCRP inhibitors with IC50 values of 0.94, 2.23, 2.50, 6.89 and 10.4 μm, respectively. Our findings point to potential combinations of TKIs that could enhance intracellular concentrations of the targeted TKI, overcome MDR and improve TKI efficacy. Further in vivo studies are warranted to confirm the efflux transporter‐mediated TKI–TKI interaction. Copyright © 2016 John Wiley & Sons, Ltd.
Factor VIII associated with lipidic nanoparticles retains efficacy in the presence of anti‐factor VIII antibodies in hemophilia A mice
Authors: Shetty Krithika A. , Kosloski Matthew P. , Mager Donald E. , Balu‐Iyer Sathy V.
Published: July 2016

The development of inhibitory antibodies against factor VIII (FVIII) is a major challenge in hemophilia A (HA) therapy. Such antibodies develop in nearly 30% of patients receiving replacement FVIII, abrogating therapeutic efficacy. This work evaluated whether B‐domain deleted FVIII encapsulated in phosphatidylinositol containing lipid nanoparticles (PI‐BDD FVIII) could serve as an efficacious FVIII replacement therapy in the presence of inhibitors. The HA mice were given clinically relevant doses of FVIII to develop inhibitors. The efficacy of free and PI‐BDD FVIII was studied in inhibitor‐positive HA mice using a tail clip assay. Mathematical modeling of these data was conducted to evaluate the hypothesis that lipid association sterically shields the protein from inhibitor binding. The immunization protocol resulted in a mean inhibitory titer level of 198 ± 52 BU/ml. Free BDD FVIII was ineffective at controlling blood loss in inhibitor‐positive HA mice as early as 2 h post dose. In contrast, PI‐BDD FVIII treated animals retained partial hemostatic efficacy as long as 18 h post dose. Mathematical modeling supports the hypotheses that a greater fraction of lipid‐associated FVIII remains unbound to inhibitors and that PI‐BDD FVIII has lower binding affinity to inhibitors than does the free protein. In addition, the modeling approaches extend current efforts to model the impact of immunogenicity on PK and the therapeutically meaningful endpoint of efficacy, thereby addressing an important knowledge gap, particularly in the FVIII scientific literature. Clinical translation of these findings could result in a significant improvement in the quality of care of inhibitor‐positive HA patients. Copyright © 2016 John Wiley & Sons, Ltd.
The genome editing revolution: A CRISPR‐Cas TALE off‐target story
Authors: Stella Stefano , Montoya Guillermo
Published: July 2016

In the last 10 years, we have witnessed a blooming of targeted genome editing systems and applications. The area was revolutionized by the discovery and characterization of the transcription activator‐like effector proteins, which are easier to engineer to target new DNA sequences than the previously available DNA binding templates, zinc fingers and meganucleases. Recently, the area experimented a quantum leap because of the introduction of the clustered regularly interspaced short palindromic repeats (CRISPR)‐associated protein (Cas) system (clustered regularly interspaced short palindromic sequence). This ribonucleoprotein complex protects bacteria from invading DNAs, and it was adapted to be used in genome editing. The CRISPR ribonucleic acid (RNA) molecule guides to the specific DNA site the Cas9 nuclease to cleave the DNA target. Two years and more than 1000 publications later, the CRISPR‐Cas system has become the main tool for genome editing in many laboratories. Currently the targeted genome editing technology has been used in many fields and may be a possible approach for human gene therapy. Furthermore, it can also be used to modifying the genomes of model organisms for studying human pathways or to improve key organisms for biotechnological applications, such as plants, livestock genome as well as yeasts and bacterial strains.