bluuebunny/crossref_metadata_2025_split huggingface dataset:
ELSI
Research Programme of the
NHGRI
Authors: McEwen Jean E , Thomson Elizabeth J , Boyer Joy T 
Published: December 2009

Abstract

The Ethical, Legal and Social Implications (ELSI) research programme of the National Human Genome Research Institute (NHGRI) of the National Institutes of Health (NIH) is a grant programme that supports research designed to anticipate and address the implications of human genetics and genomics research for individuals, families, communities and society. Programme staff and the researchers the programme supports are involved in the bioethics components of major genomics research projects and in many activities that inform genomics‐related research, health and social policies. The programme operates collaboratively with the genomics research community, and in general, the supported research has brought greater depth and strength to the genomics research enterprise. The ELSI programme is a unique experiment in the annals of NIH‐funded biomedical research, and initial results indicate that the experiment has been successful.

Key concepts:

The Ethical, Legal and Social Implications (ELSI) research programme, within the Division of Extramural Research at the National Human Genome Research Institute of the National Institutes of Health, supports research designed to anticipate and address the implications of human genetic and genomic research, technologies and information.

The ELSI programme is currently the largest governmental supporter of bioethics research in the world.

Most ELSI research is investigator‐initiated, but the programme periodically issues requests for applications (RFAs) to solicit research targeted at particular high‐priority areas.

Neither genomics researchers nor administrators responsible for the oversight of genomics research have controlled the content or direction of ELSI research.

The research priorities of the ELSI programme have evolved and span a range of issues relating to the implications of genomics for individuals, families, communities and the broader society.

ELSI research aims to be anticipatory by encouraging researchers to identify issues likely to be raised by advances in genetics and genomics research before they arise.

ELSI research involves researchers from a wide range of disciplines and is often highly transdisciplinary.

The involvement of ELSI programme staff and ELSI researchers in major genomics research projects makes it possible to marshal the findings of relevant ELSI studies directly to inform the design and conduct of genomics research.

ELSI research has had a considerable impact on both health care and broader social policies.
Genetic Counselling Services: Outcomes
Authors: Skirton Heather 
Published: December 2009

Abstract

Outcome studies of genetic services have been undertaken for several decades, but defining outcomes measures that are relevant to this type of service has been challenging. Measures have included client retention of information (including the risk assessment), reproductive behaviour, psychological change and satisfaction. However, some of these outcomes, such as reproductive behaviour are inappropriate for assessment of a genetic service, and others, such as retention of recurrence risk information, appear to be less relevant to the client than to professionals. Resolution of uncertainty and changes in perception of personal control have been highlighted as aspects of the process of genetic counselling that significantly influence the outcome for the client. However, some studies have highlighted a potentially serious mismatch between the client's agenda and that of the service provider. There is a need for further collaborative work with clients to ensure that outcomes that are relevant and measurable are developed.

Key concepts:

Health services should be assessed to enable improvements to be made and to ensure that provision of the service is effective and that they meet the needs of service users.

Clinical genetic services should be assessed using relevant outcome measures.

The service user's retention of recurrence risk information has been used as an outcome measure, but may not be as important to service users as to professionals.

Change in reproductive behaviour is not a viable outcome measure for clinical genetic services.

Patient satisfaction surveys are not sufficient in themselves as outcome measures, but may contribute to the overall assessment of services.

Service users report changes in their psychological state, such as ‘peace of mind’, as a benefit of using genetic services.

Psychological change in the client is relevant as an outcome measure, but finding appropriate psychometric tools to assess these changes is challenging.

There is evidence that there may be a mismatch between what service users require and what professionals provide.

Development of usable outcome measures for genetic services requires input from all relevant stakeholders.

Further work is still required to develop suitable outcome measure tools for genetic services.
Metacommunities: Spatial Community Ecology
Authors: Gonzalez Andrew 
Published: December 2009

AbstractEcology explains the distribution and abundance of species from small to large spatial scales. Explanations based only on processes operating at local scales do not fully account for patterns of diversity at regional scales. Recent decades have seen the unification of local and regional processes as explanations for the maintenance of diversity within the metacommunity concept. A metacommunity is a set of local communities connected by dispersal of multiple potentially interacting species. Metacommunity ecology studies the interactions among species as they occur across a network of patches. The rate and frequency of dispersal mediates the spatial distribution of diversity, abundance and the flux of energy across the metacommunity. The metacommunity concept also provides a deeper understanding of the causes and consequences of species loss, and suggests solutions to mitigate these effects.Key conceptsConcept: SummaryColonization: A spatial process in which a population becomes established in an area where it was previously absent.Open community: A community that experiences immigration and emigration.Metacommunity dynamics: The dynamics of species abundances and distribution within a metacommunity due to the compound effects of species interactions and dispersal.Local versus regional processes: Local processes occur within a community and include density‐dependent growth and interspecific interactions, whereas regional processes occur across communities and include dispersal.Source–sink system: A network of patches of a single species connected by dispersal containing two categories of population types: (1) source populations, in which the birth rate exceeds the death rate and emigration is common and (2) sink populations, in which the death rate exceeds the birth rate and frequent immigration is required to sustain the presence of individuals.Rescue effect: A spatial process in which local extinction is prevented by immigration from other patches in the metacommunity. The rate of immigration per patch increases as the proportion of patches occupied increases.Neutral model: All species are assumed to be identical with respect to their birth and death rates (fitness). Stabilizing mechanisms are absent, and the abundances of all species drift randomly to extinction. Diversity is maintained in the long‐term by speciation.Extinction debt: The delayed loss of species that occurs long after the initial loss of habitat connectivity.Spatial insurance hypothesis: The dispersal‐dependent maintenance of biodiversity and ecosystem processes within a metacommunity.
Dismantling the Apoptotic Cell
Authors: Deming Paula , Kornbluth Sally 
Published: December 2009

Abstract

Apoptosis is a programme of cell death that results in dramatic morphological and biochemical changes in the dying cell due to the systematic dismantling of cellular architecture and functional pathways. The proteins that execute the apoptotic programme are a group of proteases termed caspases (
cysteine‐dependent aspartate‐specific protease
). Caspases proteolytically cleave a host of cellular substrates at aspartate residues, which may render them either functionally inactive or confer novel activities that help to promote cellular demise. Substrates targeted by caspases during the apoptotic programme include proteins involved in maintaining various aspects of cytoskeletal and organelle architecture as well as proteins that function in signalling networks critical for cell function. Following the execution phase of apoptosis, the cellular corpse is packaged in an orderly fashion into membrane‐bound apoptotic bodies that are sensed by phagocytes, which neatly engulf the dead cell without eliciting an immune response.

Key concepts:

Apoptotic caspases are cysteine proteases which become activated in response to diverse extracellular and intracellular stimuli and subsequently carry out the cell death programme by systematically cleaving intracellular proteins.

A hierarchy of caspase activation exists whereby initiator caspases become activated to cleave and activate effector caspases, which then dismantle the cell through proteolytical cleavage of intracellular.

The cellular morphological changes associated with apoptosis encompass three stages: release, membrane blebbing and condensation.

Caspase‐mediated cleavage of target proteins may produce stable functional effector fragments or unstable fragments that are quickly degraded.

Caspases target multiple aspects of the cellular architecture to induce collapse of organelles and the cytoskeleton.

Signalling networks that regulate cellular processes critical for cell survival are inactivated by caspases.

As the dying cell is dismantled during the apoptotic process, it orchestrates its own disposal by displaying ‘eat me’ signals on its cell surface and releasing ‘find me’ signals to recruit phagocytic cells.
Evolution of the Dog Genome
Authors: Webster Matthew T , Karlsson Elinor K 
Published: December 2009

AbstractThe dog genome illuminates several important features of mammalian genome evolution. The dog is a distant relative to the primate and rodent clades, so its genome sequence can be used to identify genetic changes that occurred on these lineages and as an aid in annotating the human genome. The dog also has a complex population history, shaped by ancient domestication events and, recently, strong artificial selection to form distinct breeds. The dog genome sequence enabled studies that shed light on canid phylogeny, revealing that this history created a genomic haplotype structure that is highly amenable to the association mapping. Dogs also exhibit enormous phenotypic variation and suffer from many of the same disorders as humans, making them a powerful model organism for identifying genetic variants responsible for many common traits and diseases including cancer, diabetes, autoimmune disorders and epilepsy.Key concepts:The dog is distantly related to the primate and rodent clades.Dog genome evolution was characterized with a large number of chromosomal fissions and a low activity of transposons.Genetic evidence supports an ancient origin of dogs in East Asia.Dog domestication involved two population bottlenecks, one during dog domestication, over 15 000 years ago, and one during the formation of modern breeds in the past few hundred years.Modern dog breeds exhibit remarkable phenotypic diversity and increased rates of common diseases shared with humans, including cancer, diabetes, autoimmune disorders and epilepsy.Patterns of genetic variation in dogs are highly amenable to trait mapping by association studies.
Death Receptors at the Molecular Level: Therapeutic Implications
Authors: MacFarlane Marion 
Published: December 2009

Abstract

Since the discovery that activation of a subset of cell surface receptors within the tumour necrosis factor (TNF) receptor superfamily could trigger apoptosis, several members of the TNF superfamily including TNF, CD95L and TNF‐related apoptosis‐inducing ligand (
TRAIL
) have been identified as potentially important targets for cancer therapy. Although systemic administration of TNF or CD95L causes severe toxic side effects, thus hampering their potential application in the clinic, the discovery of
TRAIL
and its cognate death receptors,
TRAIL‐R1
and
TRAIL‐R2
, have provided an exciting new opportunity for selective targeting of tumour cells.
TRAIL
receptor activation has emerged as the most promising approach for death receptor‐targeted therapy while inducing minimal toxicity in the majority of normal cells. Intensive research, including detailed analysis of death ligand–death receptor pairs at the structural level have enabled the development of several different approaches aimed at selective targeting of
TRAIL‐R1/TRAIL‐R2
in tumour cells.

Key concepts:

Death receptor ligands, including CD95L and tumour necrosis factor (TNF)‐related apoptosis‐inducing ligand (TRAIL), are potent stimulators of apoptosis.

Unlike TNF and CD95L, which on systemic administration exhibit toxicity, TRAIL is selectively toxic to tumour cells while sparing most normal cells.

Although the molecular basis for the tumour selective activity of TRAIL remains to be fully defined, the TRAIL pathway is an attractive therapeutic target for the treatment of cancer.

Key discoveries at the structural level have revealed several important features of the molecular interaction between TRAIL and its cognate death receptors, TRAIL‐R1/ TRAIL‐R2, that are critical for TRAIL‐receptor triggering of apoptosis.

Based on structural and predicted models of TRAIL in complex with TRAIL‐R1/ TRAIL‐R2, recombinant TRAIL, receptor‐selective TRAIL variants, as well as anti‐TRAIL receptor antibodies have been developed, thus providing the opportunity to target both receptors or selectively target either TRAIL‐R1 or TRAIL‐R2 in tumour cells.

In preclinical trials, recombinant forms of TRAIL and agonistic anti‐TRAIL receptor antibodies can synergise with chemotherapeutic drugs and novel chemotherapeutic agents to effectively kill TRAIL‐resistant primary tumour cells.

Although early phase clinical trials indicate these agents can be delivered safely and are generally well tolerated as monotherapies, the most attractive use of these agents and their greatest promise for further clinical development will be when used in combination with other cancer treatments.
Micrometer‐Sized Specimen Preparation Based on Ion Slicing Technique
Authors: Wurster Stefan , Motz Christian , Jenko Monika , Pippan Reinhard 
Published: December 2009

AbstractThe ion slicing technique has been well known for producing samples for transmission electron microscopy (TEM) investigations. It will be shown that this method can also be used for producing different types of samples for micro‐mechanical experiments. The capability of manufacturing thin freestanding lamellae with a width of some micrometers and subsequently cantilevers and tensile testing specimens on the micrometer‐scale using the focused ion beam (FIB) technique will be demonstrated.
Synthesis of 2‐(N‐arylimino)pyrrolide nickel complexes and polymerization of methyl methacrylate
Authors: Li Jianfeng , Song Haibin , Cui Chunming 
Published: December 2009

AbstractThe synthesis, characterization and methyl methacrylate polymerization behaviors of 2‐(N‐arylimino)pyrrolide nickel complexes are described. The nickel complex [NN]2Ni (1, [NN] = [2‐C(H)NAr‐5‐tBu‐C4H2N]−, Ar = 2,6‐iPr2C6H3) was prepared in good yield by the reaction of [NN]Li with trans‐[Ni(Cl)(Ph)(PPh3)2] in THF. Reaction of [NN]Li with NiBr2(DME) yielded the nickel bromide [NN]Ni(Br)[NNH] (2). Complexes 1 and 2 were characterized by 1H NMR and IR spectroscopy and elemental analysis, and by X‐ray single crystal analysis. Both complexes, upon activation with methylaluminoxane, are highly active for the polymerization of methyl methacrylate to give high molecular weight polymethylmethacrylate with narrow molecular distributions. Copyright © 2009 John Wiley & Sons, Ltd.
Reactivity of organosilicon precursors in remote hydrogen microwave plasma chemical vapor deposition of silicon carbide and silicon carbonitride thin‐film coatings
Authors: Wrobel A. M. , Walkiewicz‐Pietrzykowska A. , Blaszczyk‐Lezak I. 
Published: December 2009

AbstractA number of organosilicon precursors for silicon carbide and silicon carbonitride thin‐film coatings, such as silanes, carbosilanes, aminosilanes, and disilazane, respectively, were characterized in terms of their reactivity in a remote microwave plasma chemical vapor deposition process, which was induced using hydrogen as plasma generating gas. The process displayed high selectivity with respect to the activating species and the chemical bonds in the molecular structure of the precursors. In view of very short life times of excited hydrogen plasma species the activation step takes place with an exclusive contribution of ground‐state hydrogen atoms. The CH, CC, SiC, SiN, CN and NH bonds present in the molecules of the precursors are non‐reactive and only the SiH or SiSi bonds play a key role in the activation step. The reactivity of the precursors was characterized in a quantitative way by the yield of the film growth parameter. The yield parameter expressing the mass of film per unit mass of the precursor fed to the reactor was calculated from the slopes of linear plots of time dependencies of film mass and precursor mass, which were determined for each investigated precursor. The reactivity of the precursors was found to be strongly dependent on the number of the SiH units present in their molecules and those containing two SiH units appeared to be most reactive. Copyright © 2009 John Wiley & Sons, Ltd.
Bis(imino)pyridine palladium(II) complexes as efficient catalysts for the Suzuki–Miyaura reaction in water
Authors: Liu Ping , Yan Mei , He Ren 
Published: December 2009

AbstractBis(imino)pyridine palladium(II) complexes 3 and 4 of type [PdCl(L)PF6] are found to be efficient catalysts for Suzuki–Miyaura reactions of aryl halides and arylboronic acids. The reactions proceed smoothly to generate the corresponding biaryl compounds in moderate to excellent yields. The synthesis of various fluorinated biphenyl derivatives was successfully achieved by the complex 4 catalyzed the Suzuki–Miyaura reaction in the presence of surfactants bearing a long alkyl chain. Copyright © 2009 John Wiley & Sons, Ltd.
New chiral phosphinite ligands with C2‐symmetric axis and their possible applications in Ru‐catalyzed asymmetric transfer hydrogenation
Authors: Aydemir Murat , Meric Nermin , Baysal Akın , Kayan Cezmi , Toǧrul Mahmut , Gümgüm Bahattin 
Published: December 2009

AbstractThe new chiral ligands N,N′‐bis‐[(1R)‐1‐ethyl‐2‐O‐(diphenylphosphinite)ethyl]ethanediamide, 1, and N,N′‐bis‐[(1S)‐1‐isobutyl‐2‐O‐(diphenylphosphinite)ethyl]ethanediamide, 2, and the corresponding ruthenium complexes 3 and 4 were prepared and their structures were elucidated by a combination of multinuclear NMR spectroscopy, IR spectroscopy and elemental analysis. Following activation by NaOH, these chiral ruthenium complexes serve as catalyst precursors for the asymmetric transfer hydrogenation of acetophenone derivatives in iPrOH. The complexes 3 and 4 showed high catalytic activity but low selectivity in asymmetric transfer hydrogenation reactions. Copyright © 2009 John Wiley & Sons, Ltd.
CH bond functionalization of aromatic heterocycles with chelating dicarbene palladium(II) and platinum(II) complexes
Authors: Buscemi Gabriella , Biffis Andrea , Tubaro Cristina , Basato Marino , Graiff Claudia , Tiripicchio Antonio 
Published: December 2009

AbstractChelating dicarbene complexes of palladium(II) and platinum(II) catalyse at room temperature with 1% catalyst loading the reaction of ethyl phenylpropiolate with aromatic heterocycles to yield synthetically useful intermediates for fine chemicals without the need to use prefunctionalized substrates. The reaction outcome was found to be strongly dependent on the nature of the anionic ligands at the metal complex. Addition of silver salts to replace halide ligands with more weakly coordinating anions improves the reaction yield and changes the product distributions: heterocyclealkyne 2:1 adducts are obtained together with the usual hydroarylation products, which potentially broadens the scope of the reaction. The nature of the employed heterocycle, in particular its steric characteristics, is also found to strongly influence the outcome of the reaction. Copyright © 2009 John Wiley & Sons, Ltd.
Reduction of nitroarenes followed by propanol group transfer from tris(3‐hydroxypropyl)‐ amine and cyclization leading to quinolines under heterogeneous PdC catalysis
Authors: Cho Chan Sik , Kim Tae Gyun , Yoon Nam Sik 
Published: December 2009

AbstractNitroarenes having electron‐donating or ‐withdrawing substituents are reduced to anilines and cyclized with tris(3‐hydroxypropyl)amine in the presence of a catalytic amount of PdC along with tin(II) chloride and isopropanol in dioxane‐H2O medium to give the corresponding quinolines in good to excellent yields. Copyright © 2009 John Wiley & Sons, Ltd.
Long‐chain silanes as reducing agents part 1: a facile, efficient and selective route to amine and phosphine‐stabilized active Pd‐nanoparticles
Authors: Chauhan Bhanu P. S. , Thekkathu Ramani , Prasanth K Leon , Mandal Manik , Lewis Kenrick 
Published: December 2009

AbstractRecently, metal nanoparticles have found applications in various fields, which have necessitated exploration of new avenues to obtain such materials. In this publication, a hydrosilane‐based reduction and characterization of resulting palladium nanoparticles is achieved using palladium acetate as nanoparticle precursor and octadecylsilane as a reducing agent. The influence of phosphine and amine ligands in the stabilization of nanoparticles is also investigated. In addition, a brief mechanistic proposal of the reduction process is also discussed. Copyright © 2009 John Wiley & Sons, Ltd.
Viscosity of siloxane gum and silicone rubbers
Authors: Crawford B. , Doherty A. P. , Spedding P. L. , Herron W. , Proctor M. 
Published: December 2009

AbstractOrgano‐silicone compounds are widely used, have many desirable industrial properties and can exist in many different forms. Extrusion is the most commonly used manufacturing process of silicone products, and it is hoped that application of computational fluid dynamics (CFD) will elicit a better understanding of the underlying controlling mechanisms. In this work experimental data on viscoelastic properties obtained from rotational rheometry are presented for siloxane gums and silicone rubbers which, together with previous data on capillary viscometry and wall slip, will enable CFD simulations to be obtained which are more aligned to real behaviour. A general storage, loss moduli, viscosity curve was developed for the gum with an activation energy of 17.36 kJ mol−1. The equivalent could not be made from the room temperature rubber compound data. Wall slip occurred at all stress levels. A critical stress level necessary before slip took place may only be relevant for pressure‐driven flows. The Cox–Merz relation was of limited use. Die swell reduced with increased filler concentration but the extensional viscosity was found to increase. Copyright © 2009 Curtin University of Technology and John Wiley & Sons, Ltd.