bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Genetic Services in the United Kingdom
Authors: Fryer Alan 
Published: September 2014

Abstract

The aim of clinical genetic services is to help individuals or families with, or at risk of, conditions which may have a genetic basis to live and reproduce as normally as possible. In the UK, such specialist genetic services have, in general, developed as a network of regional genetics centres of which there are 23 (17 in England, 1 in Wales, 1 in Northern Ireland and 4 in Scotland) that serve populations of between 650 000 and 5 million people. Clinical geneticists work within these centres in multidisciplinary teams together with genetic counsellors and laboratory scientists. The clinical services are delivered through a network of central and district clinics and, in some cases, joint clinics with other specialists. Each centre also has a vital role in education as the relevance of genetics and genomics to all branches of medicine increases. Each centre also plays a key role in research, sometime initiating studies and sometimes recruiting their patients to multi‐centre surveillance studies and clinical trials.

Key Concepts:

Clinical genetic services are organised on a regional geographical basis.

Each centre has multidisciplinary working.

There are regional differences in practice and some differences between the four UK countries.

Mainstreaming genetic knowledge and skills to other clinicians is an important and increasing activity.

National standards have been developed and are developing to provide a high quality service.
Protein Structure Prediction and Databases
Authors: Kalinina Olga V , Lengauer Thomas 
Published: September 2014

Abstract

Three‐dimensional structures of proteins are the key to understanding their molecular function. Most reliably protein structures are determined by experiment. Recent advances in experimental techniques have lead to a large increase in numbers of both protein sequences and 3D structures. Yet, the number of experimentally resolved proteins 3D structures is three orders of magnitude lower than that of sequences. This calls for computer support of protein structure prediction. Today several databases complement the comparatively small set of experimentally resolved protein structures with much larger sets of protein models generated by computer.

Key Concepts:

Protein structure prediction relies heavily on the experimental data on protein structures; the volume of such data is the prime determinant for the quality of protein structure predictions.

The three major types of methods for protein structure prediction are homology, or template‐based modelling; fold recognition, or threading;
de novo
, or
ab initio
prediction.

Homology modelling is the most reliable class of methods, but require experimental knowledge of a structure of a homologous – and thus structurally similar – protein, called the template.

Sensitive sequence similarity search tools are used for detection of potential templates.

The protein structure is modelled step‐wise: (1) aligning the target protein to the template, (2) placing the aligned target residues onto their respective template residues, (3) placing the side chains of nonconserved residues, healing backbone breaks and modelling loops that form gaps in the alignment, and (4) refining the model.

The two most popular computational tools for homology modelling are MODELLER and SWISS‐MODEL; the two protein model databases based on them are ModBase and the SWISS‐MODEL Repository, respectively.

The Protein Modelling Portal unites data from these and other databases, and provides an independent system for model evaluation called CAMEO.
Direct‐to‐Consumer Genetic Testing
Authors: Kalokairinou Louiza , Howard Heidi C , Borry Pascal 
Published: September 2014

Abstract

Currently, a wide variety of genetic tests are offered direct‐to‐consumer (DTC), often without involving a healthcare professional. The potential benefits and harms of such tests have caused controversy; proponents stress the right to genetic information and consumer empowerment, while concerns include the questionable scientific quality and utility of tests and potential harmful health decisions taken in the absence of medical supervision and genetic counselling. Studies indicate that despite the relatively low public awareness regarding such services, consumers value genetic information and their motivation for buying such tests ranges from acquiring health‐related information to satisfying curiosity. Furthermore, healthcare professionals seem to be sceptical regarding this provision model and the utility of some tests. The ongoing revision of European legislation regarding, among others, genetic testing, and recent regulatory action taken against a genetic testing company in the US indicate that DTC genetic testing landscape may change significantly in the future.

Key Concepts:

Over the last decade, commercial companies have been offering health‐related and non‐health‐related tests direct‐to‐consumer (DTC), often without the involvement of healthcare providers.

Various aspects of DTC genetic testing have caused concerns among numerous healthcare professionals, policy makers and consumers, however, this provision model has also gained supporters.

Consumers’ motivations for using such services may vary widely.

Healthcare providers seem, to some degree, sceptical regarding DTC genetic testing.

The Food and Drug Administration recently adopted a stricter position regarding the regulation of DTC genetic testing, by requiring the company 23andMe to provide evidence of safety and efficacy of its personal genome service.

The ongoing revision of the EU Directive on
in vitro
diagnostic medical devices is expected to have, among others, an important impact on the European DTC genetic testing landscape.
Tubulin and FtsZ Superfamily of Protein Assembly Machines
Authors: Oliva María A , Andreu José M 
Published: September 2014

Abstract

Eukaryotic αβ‐tubulin and bacterial FtsZ self‐assemble into dynamic cytoskeletal polymers, microtubules or filaments, which are essential for chromosome segregation or bacterial cell division, respectively. Both share homologous core structures with
guanosine‐5'‐triphosphate (GTP)
‐binding and GTPase‐activating domains joined by a central helix, and form similar protofilaments with 4 nm spaced subunits along them. During assembly, the GTPase‐activating domain of one subunit associates with the GTP binding domain of the preceding subunit, completing the active site. GTP hydrolysis triggers disassembly, which is coupled to free subunits switching into inactive conformation. Microtubule dynamics is inhibited by anticancer drugs binding near tubulin assembly interfaces. FtsZ is a target for new antibiotics discovery; several bacterial division inhibitors bind between FtsZ domains or at its GTP site. Other proteins in this superfamily include: gamma‐tubulin that is essential for microtubule organisation; bacterial tubulin, a primitive structural homologue; and recently discovered TubZ, distant homologue employed by plasmids and phages for
deoxyribonucleic acid
positioning.

Key Concepts:

Tubulin superfamily proteins share a common fold within two domains that is different from other GTPases.

They assemble into microtubules and other different types of dynamic cytoskeletal filaments.

GTP hydrolysis is activated upon assembly and triggers disassembly.

Tubulin homologues spread among most organisms, where they are central to essential functions including DNA segregation or cell division.

They have important biomedical implications. Several effective antitumor drugs work by impairing microtubule dynamics. FtsZ is a target for new antibiotics.
On Eliciting Intelligence from Human Sources: Contextualizing the Scharff‐Technique
Authors: Oleszkiewicz Simon , Granhag Pär Anders , Kleinman Steven M. 
Published: September 2014

SummaryThree techniques for eliciting intelligence from human sources were examined. Two versions of the Scharff‐technique (conceptualized as four tactics) were compared against the Direct Approach (open and direct questions). The Scharff confirmation technique used correct claims to elicit information, and the Scharff disconfirmation/confirmation technique used a mix of correct and incorrect claims. The participants (N = 119) took the role of ‘sources’ holding information about a terrorist attack and tried not to reveal too much or too little information during an interview. The Scharff confirmation resulted in more new information than the Scharff disconfirmation/confirmation and the Direct Approach. The sources in the Scharff conditions had a more difficult time reading the interviewer's information objectives. The sources in the Scharff conditions underestimated, whereas sources in the Direct Approach overestimated, how much new information they revealed. The study advances previous work and shows that the Scharff‐technique is a promising intelligence gathering technique. Copyright © 2014 John Wiley & Sons, Ltd.
The Effects of Experience and Disuse on Crossword Solving
Authors: Moxley Jerad H. , Ericsson K. Anders , Scheiner Aaron , Tuffiash Michael 
Published: September 2014

AbstractAt the annual American Crossword Puzzle Tournament, participants filled out a questionnaire about their experience with crossword solving and related activities for every year since they began solving crossword puzzles. This study focused on the role of crossword‐solving disruptions in influencing objective performance at the tournament. The number of breaks (a period of at least a year without crossword solving) predicted decreases in current performance, and the more time since the last break predicted increased performance. The effects of different types of experience on crossword performance are discussed with respect to their influence on performance, such as regular leisure engagement in crossword solving and more focused efforts to improve particular aspects of performance. Copyright © 2014 John Wiley & Sons, Ltd.
To swaddle, or not to swaddle? paleoepidemiology of developmental dysplasia of the hip and the swaddling dilemma among the indigenous populations of North America
Authors: Blatt Samantha H. 
Published: September 2014

ObjectivesClinical prevalence of developmental dysplasia of the hip (DDH) is high among modern indigenous populations of North America, yet no systematic study of the paleoepidemiology of this group exists. This study discusses the skeletal criteria, epidemiology, pathophysiology, and risk factors of DDH. A range of cases of DDH from an archaeological Native American population are described and the clinical and prehistoric prevalence of DDH among indigenous populations of North America are calculated and discussed within a biocultural perspective.MethodsPelves of 390 adults from the Late Prehistoric (1490 B.P. ± 70) Buffalo site, West Virginia, were examined for DDH. Morphology of true and false acetabula was classified and other changes of the pelvis, lower limb, and spine were noted along with cranial deformation, providing evidence of infant restriction. Prevalence of DDH among living and archaeological indigenous peoples of North America were calculated and compared. Cranial deformation was assessed as evidence for swaddling.ResultsDDH was identified in 18 adults from Buffalo, resulting in a minimum prevalence of 46.15 per 1,000, within the range reported in modern indigenous groups in North America. Most, but not all, of the DDH cases were associated with cranial deformation, but not all cases of cranial deformation were associated with DDH.ConclusionsThe etiology of DDH suggests that components of both genetic predisposition and swaddling practices have combined to create a high‐risk environment for the development of DDH, contributing to high prevalence within archaeological populations, like Buffalo, and modern Indigenous groups of North America. Am. J. Hum. Biol. 27:116–128, 2015. © 2014 Wiley Periodicals, Inc.
State Selectivity and Dynamics in Dissociative Electron Attachment to CF3I Revealed through Velocity Slice Imaging
Authors: Ómarsson Frímann H. , Mason Nigel J. , Krishnakumar E. , Ingólfsson Oddur 
Published: September 2014

AbstractIn light of its substantially more environmentally friendly nature, CF3I is currently being considered as a replacement for the highly potent global‐warming gas CF4, which is used extensively in plasma processing. In this context, we have studied the electron‐driven dissociation of CF3I to form CF3− and I, and we compare this process to the corresponding photolysis channel. By using the velocity slice imaging (VSI) technique we can visualize the complete dynamics of this process and show that electron‐driven dissociation proceeds from the same initial parent state as the corresponding photolysis process. However, in contrast to photolysis, which leads nearly exclusively to the 2P1/2 excited state of iodine, electron‐induced dissociation leads predominantly to the 2P3/2 ground state. We believe that the changed spin state of the negative ion allows an adiabatic dissociation through a conical intersection, whereas this path is efficiently repressed by a required spin flip in the photolysis process.
Iridium‐Catalyzed Regio‐ and Enantioselective Allylic Substitution of Silyl Dienolates Derived from Dioxinones
Authors: Chen Ming , Hartwig John F. 
Published: September 2014

AbstractReported herein is the iridium‐catalyzed regio‐ and enantioselective allylic substitution reactions of unstabilized silyl dienolates derived from dioxinones. Asymmetric allylic substitution of a variety of allylic trichloroethyl carbonates with these silyl dienolates gave γ‐allylated products selectively in 60–84 % yield and 90–98 % ee.
Mechanistic Studies on the Rearrangement of 1‐Alkenyl‐2‐alkynylcyclopropanes: From Allylic Gold(I) Cations to Stable Carbocations
Authors: Tudela Eva , González Jairo , Vicente Rubén , Santamaría Javier , Rodríguez Miguel A. , Ballesteros Alfredo 
Published: September 2014

AbstractAn allylic gold(I) cation, proposed as key intermediate in the gold‐promoted rearrangement of 1,5‐enynes bearing a fixed conformation, has been detected and characterized by NMR spectroscopy. Moreover, its participation in the overall transformation was confirmed. Computational studies indicate that the gold‐catalyzed transformation occurs through an uncommon rearrangement. Additionally, this study led us to isolate and characterize a stable homoantiaromatic carbocation.
π Aromaticity and Three‐Dimensional Aromaticity: Two sides of the Same Coin?
Authors: Poater Jordi , Solà Miquel , Viñas Clara , Teixidor Francesc 
Published: September 2014

AbstractA bridge between classical organic polycyclic aromatic hydrocarbons (PAH) and closo borohydride clusters is established by showing that they share a common origin regulated by the number of valence electrons in an electronic confined space. Application of the proposed electronic confined space analogy (ECSA) method to archetypal PAHs leads to the conclusion that the 4n+2 Wade–Mingos rule for three‐dimensional closo boranes is equivalent to the (4n+2)π Hückel rule for two‐dimensional PAHs. More importantly, use of ECSA allows design of new interesting fused closo boranes which can be a source of inspiration for synthetic chemists.
Nickel‐Catalyzed Asymmetric Transfer Hydrogenation of Olefins for the Synthesis of α‐ and β‐Amino Acids
Authors: Yang Peng , Xu Haiyan , Zhou Jianrong (Steve) 
Published: September 2014

AbstractThe field of asymmetric (transfer) hydrogenation of prochiral olefins has been dominated by noble metal catalysts based on rhodium, ruthenium, and iridium. Herein we report that a simple nickel catalyst is highly active in the transfer hydrogenation using formic acid. Chiral α‐ and β‐amino acid derivatives were obtained in good to excellent enantioselectivity. The key toward success was the use of the strongly donating and sterically demanding bisphosphine Binapine.
De Novo 3D Structure Determination from Sub‐milligram Protein Samples by Solid‐State 100 kHz MAS NMR Spectroscopy
Authors: Agarwal Vipin , Penzel Susanne , Szekely Kathrin , Cadalbert Riccardo , Testori Emilie , Oss Andres , Past Jaan , Samoson Ago , Ernst Matthias , Böckmann Anja , Meier Beat H. 
Published: September 2014

AbstractSolid‐state NMR spectroscopy is an emerging tool for structural studies of crystalline, membrane‐associated, sedimented, and fibrillar proteins. A major limitation for many studies is still the large amount of sample needed for the experiments, typically several isotopically labeled samples of 10–20 mg each. Here we show that a new NMR probe, pushing magic‐angle sample rotation to frequencies around 100 kHz, makes it possible to narrow the proton resonance lines sufficiently to provide the necessary sensitivity and spectral resolution for efficient and sensitive proton detection. Using restraints from such spectra, a well‐defined de novo structure of the model protein ubiquitin was obtained from two samples of roughly 500 μg protein each. This proof of principle opens new avenues for structural studies of proteins available in microgram, or tens of nanomoles, quantities that are, for example, typically achieved for eukaryotic membrane proteins by in‐cell or cell‐free expression.
Remarkable Enhancement of Enantioselectivity in the Asymmetric Conjugate Addition of Dimethylzinc to (Z)‐Nitroalkenes with a Catalytic [(MeCN)4Cu]PF6–Hoveyda Ligand Complex
Authors: Zeng Xingzhong , Gao Joe J. , Song Jinhua J. , Ma Shengli , Desrosiers Jean‐Nicolas , Mulder Jason A. , Rodriguez Sonia , Herbage Melissa A. , Haddad Nizar , Qu Bo , Fandrick Keith R. , Grinberg Nelu , Lee Heewon , Wei Xudong , Yee Nathan K. , Senanayake Chris H. 
Published: September 2014

AbstractAn enantioselective copper‐catalyzed asymmetric conjugate addition of Me2Zn to (Z)‐nitroalkenes led to the formation of all‐carbon quaternary stereogenic centers with high stereoselectivity. The key features of the new method are the unprecedented use of [(MeCN)4Cu]PF6 in conjunction with the Hoveyda ligand L1 and the use of (Z)‐nitroalkene substrates so that undesired nitroalkene isomerization is minimized and enantioselectivity is enhanced dramatically. We also describe a novel, practical, and highly (Z)‐selective nitroalkene synthesis.
Probing the Anticancer Mechanism of (−)‐Ainsliatrimer A through Diverted Total Synthesis and Bioorthogonal Ligation
Authors: Li Chao , Dong Ting , Li Qiang , Lei Xiaoguang 
Published: September 2014

AbstractHerein, we report an efficient approach for exploring the novel anticancer mechanism of (−)‐ainsliatrimer A, a structurally complex and unique trimeric sesquiterpenoid, through a combined strategy of diverted total synthesis (DTS) and bioorthogonal ligation (TQ ligation), which allowed us to visualize the subcellular localization of this natural product in live cells. Further biochemical studies facilitated by pretarget imaging revealed that PPARγ, a nucleus receptor, was a functional cellular target of ainsliatrimer A. We also confirmed that the anticancer activity of ainsliatrimer A was caused by the activation of PPARγ.
Reactions in Nitroimidazole Triggered by Low‐Energy (0–2 eV) Electrons: Methylation at N1‐H Completely Blocks Reactivity
Authors: Tanzer Katrin , Feketeová Linda , Puschnigg Benjamin , Scheier Paul , Illenberger Eugen , Denifl Stephan 
Published: September 2014

AbstractLow‐energy electrons (LEEs) at energies of less than 2 eV effectively decompose 4‐nitroimidazole (4NI) by dissociative electron attachment (DEA). The reactions include simple bond cleavages but also complex reactions involving multiple bond cleavages and formation of new molecules. Both simple and complex reactions are associated with pronounced sharp features in the anionic yields, which are interpreted as vibrational Feshbach resonances acting as effective doorways for DEA. The remarkably rich chemistry of 4NI is completely blocked in 1‐methyl‐4‐nitroimidazole (Me4NI), that is, upon methylation of 4NI at the N1 site. These remarkable results have also implications for the development of nitroimidazole based radiosensitizers in tumor radiation therapy.
Influence of the Auxiliary Acceptor on the Absorption Response and Photovoltaic Performance of Dye‐Sensitized Solar Cells
Authors: Wu ZhiFang , Li Xin , Li Jing , Hua JianLi , Ågren Hans , Tian He 
Published: September 2014

AbstractThree new dyes with a 2‐(1,1‐dicyanomethylene)rhodanine (IDR‐I, ‐II, ‐III) electron acceptor as anchor were synthesized and applied to dye‐sensitized solar cells. We varied the bridging molecule to fine tune the electronic and optical properties of the dyes. It was demonstrated that incorporation of auxiliary acceptors effectively increased the molar extinction coefficient and extended the absorption spectra to the near‐infrared (NIR) region. Introduction of 2,1,3‐benzothiadiazole (BTD) improved the performance by nearly 50 %. The best performance of the dye‐sensitized solar cells (DSSCs) based on IDR‐II reached 8.53 % (short‐circuit current density (Jsc)=16.73 mA cm−2, open‐circuit voltage (Voc)=0.71 V, fill factor (FF)=71.26 %) at AM 1.5 simulated sunlight. However, substitution of BTD with a group that featured the more strongly electron‐withdrawing thiadiazolo[3,4‐c]pyridine (PT) had a negative effect on the photovoltaic performance, in which IDR‐III‐based DSSCs showed the lowest efficiency of 4.02 %. We speculate that the stronger auxiliary acceptor acts as an electron trap, which might result in fast combination or hamper the electron transfer from donor to acceptor. This inference was confirmed by electrical impedance analysis and theoretical computations. Theoretical analysis indicates that the LUMO of IDR‐III is mainly localized at the central acceptor group owing to its strong electron‐withdrawing character, which might in turn trap the electron or hamper the electron transfer from donor to acceptor, thereby finally decreasing the efficiency of electron injection into a TiO2 semiconductor. This result inspired us to select moderated auxiliary acceptors to improve the performance in our further study.
Melamine as an Effective Supramolecular Modifier and Stabilizer in a Nanotube‐Constituted Supergel
Authors: Xing Pengyao , Chu Xiaoxiao , Ma Mingfang , Li Shangyang , Hao Aiyou 
Published: September 2014

AbstractSelf‐assembly of N‐fluorenyl‐9‐methoxycarbonyl glutamic acid (Fmoc‐Glu) in water generates metastable single‐wall nanotubes. These nanotubes entangle and bundle together to form unstable gels that shrink with time and finally result in lamellar crystalline precipitates. Melamine (Mm) was employed as a supramolecular modifier and stabilizer to improve the stability of the nanotubes. Mm interacts with the carboxyl‐rich surfaces of the nanotubes via H‐bonds and static electronic forces to diminish the high affinity of individual nanotubes and facilitate Fmoc‐Glu supergelation (critical gelation concentration <0.1 wt %). Although the basic process of nanotube formation is not disturbed, Mm inverts the supramolecular helicity of nanotubes from P to M.