bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Genome Project as a Social Enterprise
Authors: Lowe James WE 
Published: November 2016

AbstractAs a social enterprise, the Human Genome Project (HGP) can be understood in a number of different ways, including the social organisation of science, the influence of society and culture on scientific work and the influence of scientific findings and endeavours on society. The HGP introduced new forms of organisation to the biological and biomedical sciences; these include the entrance of ‘Big Science’ modes of organisation, automation and routinisation. Disagreements between the public HGP and private projects were based on different aims, organisation and guiding norms. In particular, there is a tension between the norm of collaboration in science and the role of competition. Despite concerns that the HGP would promote genetic determinism and even eugenics, these fears have not been realised.Key ConceptsThe founding and funding of the Human Genome Project required advocacy from government departments and agencies, prominent scientists and support in the US Congress; there was opposition within and without the scientific community.The Human Genome Project was an international collaboration that required models of organisation appropriate to ensure coordination between the centres that conducted the sequencing.The project has been conceived as an example of ‘Big Science’ and also ‘Fast Science’; it brought new ways of organising research into the biological sciences.The opposition of the public Human Genome Project and private sector initiative centred on organisation, the values of collaboration and/or competition and the dissemination and prospective use of the data generated by sequencing.Fears that the Human Genome Project would provide support for eugenics and genetic determinism have not been realised.
‘Race’,
IQ
and Genes
Authors: Carson Michael , Beckwith Jon 
Published: November 2016

Abstract

Dominant social classes have often used scientific arguments to explain their privileged status. With the development of intelligence quotient (IQ) tests and the founding of the field of genetics, some researchers explained racial differences in behaviours such as IQ test performance as due to genetic differences. Recent discoveries in molecular genetics have provided evidence that human variation at the deoxyribonucleic acid (DNA) level is slight; much more variation exists within the members of any single group than between two different population groups. However, as the DNA of populations worldwide has been further characterised, some have assumed that racial differences in intelligence or other social behaviours can be ascribed to those slight interracial genetic differences. Scientists must remain vigilant and expose misrepresentations of scientific data that overemphasise the genetics of group differences and that support genetically deterministic explanations for complex behaviours, such as intelligence.

Key Concepts

Science, through measurements of brain size and IQ test scores, has been misused to support the idea of presumed racial hierarchies in intelligence.

Identical twin studies yield heritability numbers for various traits such as intelligence. However these heritability numbers do not give any information on the strength of genetic contributions to the trait under study. Furthermore, questionable assumptions that are made in carrying out these studies raise issues about the validity of the numbers themselves.

The search for gene variants with strong influences on complex behavioural traits, including intelligence, has been largely unsuccessful.

Environment plays a major role in the manifestation of most genetic traits.

Recent discoveries in molecular genetics have shown that most of the genetic variation that is found among human beings around the world is found in all racial and ethnic groups, and only a small amount is found in specific groups.

Using large numbers of genetic variants that differ only slightly in proportion between population groups, researchers can assort individuals into major continental geographic clusters with a high degree of accuracy.

Aside from a small fraction of genes influencing apparent, visible physical features distinguishing people, the distribution of genetic variation does not support a biological basis for the concept of human races.

Preliminary and faulty scientific studies on issues relating to race and intelligence are often rapidly and unjustifiably translated into calls for changes in social policy.

Scientists have a responsibility to help ensure that studies on the genetics of group differences are not misused and misrepresented to support racist theories regarding human behaviours.
Genome‐Wide Association Studies in Asthma
Authors: Portelli Michael , Sayers Ian 
Published: November 2016

AbstractAsthma is a complex respiratory disease, with both genetic and environmental factors contributing to disease susceptibility. Genome‐wide association studies (GWAS) have now identified novel risk alleles and loci associated with asthma diagnosis and more recently with clinical subgroups of disease. However, while providing insight into potential disease mechanisms these risk alleles have modest effect sizes and account for a small proportion of the anticipated heritability of asthma. In this article we provide an overview of GWAS in asthma to date including reproducible associations and advances in our understanding of the biology of asthma. In addition we discuss ancestry‐specific findings and how genetics may contribute to the development of multiple allergic conditions known as the ‘atopic march’. Finally, we outline the strengths and weaknesses of GWAS and look to future approaches including a greater focus to functional variation and assessment of gene–gene and gene–environment interactions.Key ConceptsAsthma is a common respiratory disease that is heterogeneous with respect to its underlying pathology and clinical presentation.Susceptibility to develop asthma involves both genetic and environmental risk factors.Genome‐wide association is the current method of choice to identify genetic factors underlying complex, multifactorial diseases such as asthma.GWAS of asthma have identified several genetic risk factors and genes with confidence, for exampleIL33, IL1RL1, ORMDL3loci. Replication of findings remains the gold standard.GWAS of subgroups of asthma, for example, childhood‐onset disease have identified specific genetic risk factors.The effect sizes identified in GWAS are typically modest for single variants.GWAS have provided a unique insight into the altered biology of asthma including changes in innate and adaptive immune responses, altered airway smooth muscle function and epithelial barrier/function abnormalities.While GWAS of asthma have been successful there remains a large missing heritability.Future approaches include better clinical definition of asthma and greater interrogation of genetic factors not currently addressed, for example, regulatory variants, rare variants, copy number variants and greater attention to gene–environment interactions, gene–gene interactions and epigenetic mechanisms.
Molecular Genetics of Dystonia
Authors: Lohmann Katja 
Published: November 2016

Abstract

Dystonia is a clinically and genetically highly heterogeneous, rare movement disorder that is characterised by sustained or intermittent muscle contractions causing abnormal movements and/or postures. Dystonic syndromes can manifest from early infancy to late adulthood and display diverse anatomical expressivity. Phenotypically, dystonias are classified as isolated, combined (in combination with another movement disorder) or complex dystonia (usually as one of several disease manifestations in a complex syndrome). Over 100 dystonia genes have been identified including pathogenic genomic variants (mutations) in
TOR1A
,
THAP1
,
GNAL
,
GCH1
,
ATP1A3
,
PRKRA
,
SGCE
,
TUBB4A
,
ADCY5
and
GNB1
. The encoded proteins do not seem to belong to a common pathway but rather affect diverse cellular functions including, for instance, dopamine biosynthesis, signal transduction as ion channels or G proteins as well as transcriptional regulation.

Key Concepts

Dystonias represent a heterogeneous group of movement disorders.

Over 100 genes have been linked to dystonic features.

Owing to the advent of next‐generation sequencing many novel dystonia genes have been reported but their role needs to be confirmed.

Dystonia can affect all age groups.

In some cases, it starts in early childhood and then often generalises.

The most common form of dystonia is late‐onset, focal dystonia.

Diverse pathways are affected by dystonia‐causing mutations.
Sex Differences in Disease Genetics
Authors: Gilks William P 
Published: November 2016

Abstract

There is long‐standing evidence for the gene‐by‐sex interactions in disease risk, which can now be tested in genome‐wide association studies with participant numbers in the hundreds of thousands. The current methods start with a separate test for each sex, but a more powerful approach is to use sex as an interaction term in a combined sample. The most compelling evidence is for adiposity (predictive of cardiac disease) as well as type
II
diabetes, asthma and inflammatory bowel disease. Autism exhibits a different kind of sex difference, with hypermasculinisation of the brain, and the intriguing enrichment of structural variants in females. Sexually dimorphic gene expression varies exquisitely and unexpectedly, by tissue, age and chromosome, so sex‐dependent genetic effects are expected for a wide range of diseases. Because natural selection against sex‐dependent risk alleles is in one sex only, their effect size is expected to be greater than conventional risk loci.

Key Concepts

Compelling findings of sex‐dependent genetic effects on disease have been made in adiposity‐related anthropometric traits, type II diabetes and inflammatory bowel disease, and other disorders remain to be more fully investigated, regardless of what sexual dimorphism they exhibit in prevalence and presentation.

Initial evidence indicates that sex difference in gene expression is not required for a sex‐dependent genetic effect on gene expression. However, sex differences in expression levels vary dynamically by tissue type and age, so such generalisations may be inaccurate, without more comprehensive data.

Sex‐dependent risk alleles are predicted to be of greater effect size than conventional ones, because natural selection acts only against the sex which has the disease. There is evidence for this from a high‐powered GWAS of adiposity‐related traits.

Sexual dimorphism in gene expression seems likely to fall into different categories, and thus categorisation of sex‐dependent genetic effects is expected to follow the same patterns.

Many of the large GWAS meta‐analyses look for sex‐dependent genetic effects by testing male and female groups separately. However, this may be underpowered compared to a whole‐sample, gene‐by‐sex interaction test.
Concise Synthesis of Dithiophene Derivatives by a Palladium‐ Catalyzed Multiple C–S Cross Coupling/Cyclization Sequence
Authors: Oechsle Peter , Hou Peng , Flörke Ulrich , Paradies Jan 
Published: November 2016

AbstractThe facile synthesis of new sulfur‐containing fused heterocycles was achieved by a two‐fold domino reaction consisting of a carbon‐sulfur cross‐coupling, followed by a 5‐endo‐dig cyclization. Using this strategy a series of benzo‐, thiopheno‐, pyridine‐ and pyrazino‐dithienoacenes with electron‐neutral (‐C6H4‐n‐Hex), electron‐rich (‐C6H4‐NPh2) and electron‐deficient (‐C4H3N2) substituents was synthesized in high yields. The developed method was applied in the efficient synthesis of a complex donor‐acceptor molecule. The photophysical and electrochemical properties of the products were analyzed by UV‐VIS/luminescence spectroscopy and cyclic voltammetry.magnified image
Far field photoluminescence imaging of single AlGaN nanowire in the sub‐wavelength scale using confinement of polarized light
Authors: Sivadasan A. K. , Sardar Manas , Dhara Sandip 
Published: November 2016

Till now the nanoscale focusing and imaging in the sub‐diffraction limit is achieved mainly with the help of plasmonic field enhancement by confining the light assisted with noble metal nanostructures. Using far field imaging technique, we have recorded polarized spectroscopic photoluminescence (PL) imaging of a single AlGaN nanowire (NW) of diameter ∼100 nm using confinement of polarized light. It is found that the PL from a single NW is influenced by the proximity to other NWs. The PL intensity is proportional to 1/(l×d), where l and d are the average NW length and separation between the NWs, respectively. We suggest that the proximity induced PL intensity enhancement can be understood by assuming the existence of reasonably long lived photons in the intervening space between the NWs. A nonzero non‐equilibrium population of such photons may cause stimulated emission leading to the enhancement of PL emission with the intensity proportional to 1/(l×d). The enhancement of PL emission facilitates far field spectroscopic imaging of a single semiconductor AlGaN NW of sub‐wavelength dimension.
image
Solvent‐assisted formation of ruthenium(II)/copper(I) complexes containing thiourea derivatives: Synthesis, crystal structure, density functional theory, enzyme mimetics and in vitro biological perspectives
Authors: Vijayan Paranthaman , Viswanathamurthi Periasamy , Sugumar Paramasivam , Ponnuswamy Mondikalipudur Nanjappagounder , Malecki Jan Grzegorz , Velmurugan Krishnaswamy , Nandhakumar Raju , Balakumaran Manickam Dakshinamoorthi , Kalaichelvan Pudupalayam Thangavelu 
Published: November 2016

N,N‐[(diethylamino)(thiocarbonyl)]‐substituted benzamidine ligands have been synthesized from the reaction of N,N‐[(diethylamino)(thiocarbonyl)]benzimidoyl chloride with functionalized amines such as 2‐aminophenol and 2‐picolylamine. The reaction of N,N‐[(diethylamino)(thiocarbonyl)]‐2‐hydroxyphenylbenzamidine (H2L1) with ruthenium(II) precursor [RuHCl(CO)(PPh3)3] afforded complex 1 of the type [Ru(L1)(CO)(PPh3)2] in which the ligand coordinated in tridentate ONS mode. The reaction of H2L1 with copper precursor [Cu(CH3COO)(PPh3)2] induced C═N bond cleavage of the ligand and afforded complex 3 of the type [Cu(1,1‐DT)(Cl)(PPh3)2] (1,1‐DT = 1,1‐diethylthiourea) in which the ligand coordinated in a monodentate fashion. The ligand N,N‐[(diethylamino)(thiocarbonyl)]‐2‐picolylbenzamidine (HL2) reacted with ruthenium(II) and copper(I) precursors to form complex 2 of the type [Ru(1,1‐DT)(Cl2)(CO)(PPh3)2] and complex 3, respectively, in which the ligand underwent C═N cleavage and coordinated in a monodentate fashion via C═S group. In complexes 1 and 2, the two triphenylphosphine co‐ligands coordinated in trans position whereas, in complex 3, the two triphenylphosphine co‐ligands coordinated in cis position. All the compounds were characterized using infrared, UV–visible, (1H, 13C, 31P) NMR, ESI‐MS and elemental analyses. The molecular structures of ligand H2L1 and complexes 1–3 were determined using X‐ray crystallography, which confirmed the coordination mode of the ligands with metals. The crystal structure of complexes 1 and 2 revealed a distorted octahedral geometry around the ruthenium ion and the structure of complex 3 indicated a tetrahedral geometry around the copper ion. With the X‐ray structures, density functional theory computations were carried out to determine the electronic structure of the compounds. The interactions of complexes 1–3 with calf thymus DNA and bovine serum albumin protein were investigated using UV–visible and fluorescence spectroscopic and viscometric methods. Catecholase‐ and phosphatase‐like activities promoted by complexes 1–3 under physiological conditions have been studied. In vitro anticancer activities have been demonstrated by MTT assay, acridine orange/ethidium bromide and diamidino‐2‐phenylindole staining against various cancerous cell lines.
Layer‐by‐layer self‐assembly of a lignin–poly(vinyl alcohol) based polyelectrolyte with a conductivity method
Authors: Su Ling , Zhang Shengming , Jiang Guiquan , Pang Jiuyin , Wang Di , Shi Junyou , Fang Guizhen 
Published: November 2016

ABSTRACTIn this study, we made a new attempt to examine the relationship between the conductivity and the concentration of a polyelectrolyte solution and to prepare multilayer films with cationic lignin and polyanions through layer‐by‐layer self‐assembly. The nitrogen content of trimethyl lignin quaternary amine salt (TLQA) was 3.56%, and the carboxyl content of carboxymethylated poly (vinyl alcohol) (CMPVA) was 0.62 mmol/g. Attenuated total reflectance spectra confirmed that TLQA and CMPVA were fabricated and assembled successfully. The concentration of TLQA had a polynomial correlation with the conductivity [correlation coefficient (R2) = 0.9953], and the concentration of CMPVA was linear with the conductivity (R2 = 0.9819). The electrostatic sequential adsorption process was monitored with a UV–visible spectrophotometer, and the morphology of the (TLQA/CMPVA)n(wherenis the number of double membranes) multilayer film was observed by atomic force microscopy and scanning electron microscopy. When the absorbance of the (TLQA/CMPVA)nmultilayer film increased linearly, the linear equation wasy = 0.0267x + 0.07453 andR2was 0.9735. When five layers of TLQA and CMPVA were assembled, the surface root mean square roughness of TLQA and CMPVA were 21.07 and 65.28 nm, respectively. When the number of layers increased, the film surface roughness increased. The stability of the multilayer films in aqueous solution was determined by a conductivity meter. The (TLQA/CMPVA)nmultilayer film was stable in water. The results of the research demonstrate for the first time that TLQA and CMPVA could be assembled and successfully driven by electrostatic forces. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2017,134, 44416.
Chemicals from biomass: technological versus environmental feasibility. A review
Authors: Fiorentino Gabriella , Ripa Maddalena , Ulgiati Sergio 
Published: November 2016

AbstractThe production of chemicals from renewable feedstocks is becoming an attractive area of investment for industries in the framework of a more sustainable economy. From a technical point of view, a large fraction of industrial chemicals and materials from fossil resources can be replaced by their bio‐based counterparts. Nevertheless, fossil‐based chemistry is still dominant because of optimized production processes and lower costs. The best approach to maximize the valorization of biomass is the processing of biological feedstocks in integrated biorefineries where both bio‐based chemicals and energy carriers can be produced, similar to a traditional petroleum refinery. The challenge is to prove, together with the technical and economic feasibility, an environmental feasibility, in terms of lower impact over the entire production chain. In this review, potential renewable substrates, conversion pathways, and target molecules are carefully investigated with reference to the most recent technological advancements. Potential environmental impacts and benefits over the life cycle of products are also reviewed. While an economic and technical feasibility can be, and sometimes has been already, reached, the same is not true yet for environmental feasibility, where several issues still need to be explored and the risk for burden shift is not negligible. The aim of this review is to provide an overview of the opportunities and constraints related to the transition from petroleum to biomass chemistry and to draw a roadmap of the most sustainable technologies and promising biomass value chains, screening in parallel their environmental implications, toward a market implementation of bio‐based chemistry. © 2016 Society of Chemical Industry and John Wiley & Sons, Ltd
Circumferential suction-assisted lipectomy in the treatment of primary and secondary end-stage lymphoedema of the leg
Authors: Lamprou D-A A , Voesten H G J , Damstra R J , Wikkeling O R M 
Published: November 2016

Abstract

Background
The treatment of end-stage lymphoedema of the leg is challenging, especially when conservative treatment fails and there is a large volume difference between the affected and unaffected legs. Circumferential suction-assisted lipectomy (CSAL) has been described as a treatment option for end-stage lymphoedema of the leg. Here, the long-term results of CSAL in end-stage primary and secondary lymphoedema of the leg were analysed.

Methods
This was a descriptive study of patients treated with CSAL for unilateral chronic irreversible lymphoedema of the leg. Compression therapy was resumed after surgery. Leg volumes were measured before surgery, and at 1, 6, 12 and 24 months after the procedure.

Results
A total of 47 patients with primary lymphoedema had a median preoperative volume difference between affected and unaffected legs of 3686 (i.q.r. 2851–5121) ml. Two years after surgery, this volume difference was reduced to 761 ml, a 79 per cent reduction. In the 41 patients treated for secondary lymphoedema, the median preoperative volume difference was 3320 (i.q.r. 2533–4783) ml, decreasing after 2 years to −38 ml (101 per cent reduction). The preoperative volume difference and the sex of the patient significantly influenced the final outcome after 2 years. The outcome was not related to BMI or other patient characteristics.

Conclusion
CSAL is an effective method for treating both primary and secondary lymphoedema of the leg.
Validated high‐performance liquid chromatography method for the determination of the inhibitor of cancer cell invasion (E)‐N‐benzyl‐6‐[2‐(3, 4‐dihydroxy benzylidene)hydrazinyl]‐N‐methylpyridine‐3‐sulfonamide in rat plasma and its application to pharmacokinetic study
Authors: Kim Tae Kon , Choi Hyun Kyung 
Published: November 2016

AbstractIn this study, a reliable method for the quantitation of (E)‐N‐benzyl‐6‐[2‐(3, 4‐dihydroxy benzylidene)hydrazinyl]‐N‐methylpyridine‐3‐sulfonamide (JW‐55) in rat plasma was developed and validated using high‐performance liquid chromatography. Plasma samples were deproteinized; sildenafil was used as an internal standard. Chromatographic separation was achieved using a reversed‐phase C18 column. The mobile phase, 0.02 m ammonium acetate buffer:acetonitrile (48:52, v/v), was run at a flow rate of 1.0 mL/min at room temperature, and the column eluent was monitored using an ultraviolet detector at 280 nm. The retention times of JW‐55 and sildenafil were ~5.9 and 7.7 min, respectively. The detection limit of JW‐55 in rat plasma was 0.03 μg/mL. Pharmacokinetic parameters of JW‐55 were evaluated after intravenous and oral administration of JW‐55 (10 mg/kg) in rats. After oral administration, the F value was approximately 73.7%.