bluuebunny/crossref_metadata_2025_split huggingface dataset:
The experimental survey of protein-folding energy landscapes
Authors: Oliveberg Mikael , Wolynes Peter G. 
Published: June 2006

1. Introduction 22. The macroscopic and microscopic views of protein folding 22.1 The macroscopic view: the experimental folding free-energy profile 22.2 The microscopic view: an underlying energy landscape 33. The micro to macro projection: from an energy landscape to a free-energy profile 64. Global features of the protein folding transition-state ensemble 124.1 Overall transition state location β[Dagger]: a measure of compactness 124.2 What makes folding so robust ? 135. Structural characterization of the transition-state ensemble 165.1 Insights from ϕ-value analysis 166. Deviations from ideality 206.1 β[Dagger] shifts along seemingly robust trajectories 216.2 Anomalous ϕ values, frustration and inhomogeneities 257. Intermediates 288. Detours, traps and frustration 298.1 Premature collapse and non-native trapping 299. Diffusion on the energy landscape and the elementary events of protein folding 3010. Malleability of folding routes: changes of the dominant collective coordinates for folding 3311. The evolution of the shape of the energy landscape 3511.1 Negative design: the hidden dimension of the folding code 3512. Mechanistic multiplicity and evolutionary choice 3613. Acknowledgements 3714. References 38We review what has been learned about the protein-folding problem from experimental kinetic studies. These studies reveal patterns of both great richness and surprising simplicity. The patterns can be interpreted in terms of proteins possessing an energy landscape which is largely, but not completely, funnel-like. Issues such as speed limitations of folding, the robustness of folding, the origin of barriers and cooperativity and the ensemble nature of transition states, intermediate and traps are assessed using the results from several experimental groups highlighting energy-landscape ideas as an interpretive framework.
Psychometric evaluation of the Chinese version of the Fagerstrom Tolerance Questionnaire as a measure of cigarette dependence
Authors: Huang Chih‐Ling , Lin Hsi‐Hui , Wang Hsiu‐Hung 
Published: June 2006

Aim.  The aim of this study is to estimate the psychometric properties of the Chinese version of the Fagerstrom Tolerance Questionnaire as a measure of nicotine dependence.Background.  The Chinese Fagerstrom Tolerance Questionnaire has been used in smoking cessation programmes in Taiwan. However, the psychometric properties of the Chinese version have not been tested.Methods.  A cross‐sectional, descriptive study was conducted from June 2004 to July 2005 with 247 adult smokers. The criterion validity of the Chinese Fagerstrom Tolerance Questionnaire was determined using two biomarkers (exhaled CO and saliva cotinine levels). Because the responses to the items are dichotomous or nominal, the validity and factorial structures were examined using tetrachoric techniques. Construct reliability was evaluated to accommodate the lack of tau‐equivalence assumed in computing Cronbach's alpha.Findings.  The item ‘smoke more in the morning’ was not statistically significantly correlated with either biomarker because many participants expressed the desire to smoke after meals instead of in the morning. The items ‘nicotine yield’ and ‘inhalation’ performed poorly in terms of criterion validity and construct validity. This evidence supports modification of the Chinese version of the Fagerstrom Tolerance Questionnaire to the six‐item Fagerstrom Test for Nicotine Dependence. In addition, the item ‘difficulty refraining from smoking in forbidden places’ had relatively poor psychometric performance. The reason may be culturally specific, having to do with the relative lack of forbidden places and restrictions on tobacco use in Taiwan. The predictive ability of the Chinese version of the Fagerstrom Tolerance Questionnaire for biomarkers is higher than the English version. The reliability coefficient (0·65) was higher than Cronbach's alpha, but did not meet the satisfactory standard of 0·70.Conclusion.  The Chinese version of the Fagerstrom Tolerance Questionnaire is a fairly reliable and valid scale, but needs to be revised to accommodate cross‐cultural differences.
Scoping workplace aggression in nursing: findings from an Australian study
Authors: Farrell Gerald A. , Bobrowski Christina , Bobrowski Peter 
Published: June 2006

Aim.  This paper reports a study of workplace aggression among nurses in Tasmania, Australia.Background.  There is international concern about a perceived rise in occupational violence as a major worldwide public health problem, with associated financial costs. There is reason to suspect that aggression towards nurses is increasing. For example, increased illicit drug use puts nurses at the sharp end in managing patients admitted with drug‐related problems. Such people are often resistant to healthcare intervention, and often have associated disorders, including mental illness. Despite this increased awareness, comprehensive data on occupational violence in nursing are not available.Method.  A specially designed questionnaire was sent to all nurses registered with the Nursing Board of Tasmania (n = 6326) in November/December 2002, with 2407 usable questionnaires returned. The response rate was 38%.Findings.  A majority of respondents (63·5%) had experienced some form of aggression (verbal or physical abuse) in the four working weeks immediately prior to the survey. Patients/clients or their visitors were identified as the main perpetrators, followed by medical and nursing colleagues. Abuse influenced nurses’ distress, their desire to stay in nursing, their productivity and the potential to make errors, yet they were reluctant to make their complaints ‘official’. As well as reporting high levels of verbal and physical abuse, nurses were distressed because they could not provide the appropriate care to meet patients’ needs. Few working environments were free of aggression.Conclusion.  Future research should try to determine the specific factors, including staff characteristics and environment, associated with the high levels of aggression reported in ‘hot spots’ where, on the basis of the present results, many staff experience high levels of verbal and physical abuse. Unless managers take steps to improve the situation, attrition from the profession for this reason will continue.
Three‐dimensional finite element simulations of microstructurally small fatigue crack growth in 7075 aluminium alloy
Authors: JOHNSTON S. R. , POTIRNICHE G. P. , DANIEWICZ S. R. , HORSTEMEYER M. F. 
Published: June 2006

ABSTRACTThree‐dimensional finite element simulations were performed to study the growth of microstructurally small fatigue cracks in aluminium alloy 7075‐T651. Fatigue crack propagation through five different crystallographic orientations was simulated using crystal plasticity theory, and plasticity‐induced crack opening stresses were calculated. The computed crack opening stresses were used to construct small crack da/dN‐ΔKdiagrams. The generated da/dN‐ΔKcurves compared well with experimental small crack data from the literature. The variance observed among the da/dN‐ΔKresults, which occurred as a consequence of the different crystallographic orientations employed, was found to be of the same order of magnitude as commonly observed variability in small fatigue crack growth data. This suggests that grain orientation is a major contributor to observed small fatigue crack data scatter.
Inhibition of 26S proteasome activity by huntingtin filaments but not inclusion bodies isolated from mouse and human brain
Authors: Díaz‐Hernández Miguel , Valera Adriana G. , Morán María A. , Gómez‐Ramos Pilar , Alvarez‐Castelao Beatriz , Castaño José G. , Hernández Félix , Lucas José J. 
Published: June 2006

AbstractIn Huntington's disease (HD), as in the rest of CAG triplet‐repeat disorders, the expanded polyglutamine (polyQ)‐containing proteins form intraneuronal fibrillar aggregates that are gathered into inclusion bodies (IBs). Since IBs contain ubiquitin and proteasome subunits, it was proposed that inhibition of proteasome activity might underlie pathogenesis of polyQ disorders. Recent in vitro enzymatic studies revealed the inability of eukaryotic proteasomes to digest expanded polyQ, thus suggesting that occasional failure of polyQ to exit the proteasome may interfere with its proteolytic function. However, it has also recently been found that in vitro assembled aggregates made of synthetic polyQ fail to inhibit proteasome activity. Because synthetic polyQ aggregates lack the post‐translational modifications found inside affected neurons, such as poly ubiquitylation, we decided to study the effect of mutant huntingtin (htt) aggregates isolated from the Tet/HD94 mouse model and from human HD brain tissue. Here, we show that isolated ubiquitylated filamentous htt aggregates, extracted from IBs by a previously reported method, selectively inhibited the in vitro peptidase activity of the 26S but not of the 20S proteasome in a non‐competitive manner. In good agreement, immuno‐electron microscopy revealed a direct interaction of htt filaments with the 19S ubiquitin‐interacting regulatory caps of the 26S proteasome. Here, we also report a new method for isolation of IBs based on magnetic sorting. Interestingly, isolated IBs did not modify proteasome activity. Our results therefore show that mutant htt filamentous aggregates can inhibit proteasome activity, but only when not recruited into IBs, thus strengthening the notion that IB formation is protective by neutralizing toxicity of dispersed filamentous htt aggregates.
The genetics of neurodegenerative diseases
Authors: Hardy John , Orr Harry 
Published: June 2006

AbstractIn the last 50 years, an enormous amount of progress has been made in dissecting the etiology of hereditary neurodegenerative diseases, including the dementias, the parkinsonisms, the ataxias and the motor‐neuron diseases. In addition, these genetic findings are beginning to provide insights into the pathogeneses of the sporadic forms of the diseases. Through animal and cellular modeling studies we are beginning to gain insights into the pathogenic pathways to disease. This mechanistic understanding is now leading to therapeutic strategies based on this new understanding. As yet, however, no mechanistic therapies are in use in the clinic.
Inositol 1,4,5‐trisphosphate (IP3) receptors and their role in neuronal cell function
Authors: Mikoshiba Katsuhiko 
Published: June 2006

AbstractInositol 1,4,5‐trisphosphate (IP3) receptor is a Ca2+ release channel localized on the endoplasmic reticulum (ER) and plays an important role in neuronal function. IP3 receptor was discovered as a developmentally regulated protein missing in the cerebellar mutant mice. Recent studies indicate that IP3Rs are involved in early development and neuronal plasticity. IP3 works to release IRBIT from the IP3 binding core in addition to release Ca2+. IRBIT binds to and activates Na, Bicarbonate cotransporter. Electron microscopic study show the IP3 receptor has allosteric property to change its form from square to windmill in the presence of Ca2+. IP3R associates with ERp44, a redox sensor, Homer, other proteins and is transported as vesicular ER on microtubules. All these data suggests IP3 receptor/CA2+ channel works as a signaling center inside cells.
Postoperative pulmonary complications in dogs undergoing laparotomy: anesthetic and perioperative factors
Authors: Brainard Benjamin M. , Alwood Amy J. , Kushner Lynne I. , Drobatz Kenneth J. , King Lesley G. 
Published: June 2006

AbstractObjective:To define the peri‐anesthetic risk factors that are associated with the development of postoperative pulmonary complications (PPCs) in dogs following laparotomy.Study design:Retrospective study.Animals:One hundred and sixty‐two dogs that underwent laparotomy at a veterinary teaching hospital.Methods:Cases were evaluated for factors including signalment, American Society of Anesthesiologists (ASA) physical status (PS) score, duration of fast, duration of anesthesia, anesthetic and analgesic protocols, fluid and blood product therapy, animal positioning, and postoperative temperature.Results:Statistically significant differences between dogs that developed PPCs and those that did not (nPPCs) were identified in the following categories: ASA PS score≥III (P=0.041), emergent surgery (P=0.038), longer duration of anesthesia (P=0.0462), and use of butorphanol or oxymorphone instead of hydromorphone for postoperative medication (P=0.04 and 0.015, respectively). Dogs that received transfusions of stored blood products (fresh frozen plasma or packed red blood cells) during their hospital stay were also more likely to develop PPCs (P=0.035 and 0.005, respectively). Dogs that developed PPCs were also more likely to have received antagonists for potent opiates or benzodiazepines postoperatively and to have recovered in the intensive care unit (ICU) (P=0.03 and 0.009, respectively).Conclusions:Dogs with ASA PS scores≥III, or those requiring longer or emergency anesthesia are at a higher risk of developing PPCs. Additionally, dogs receiving stored blood products in the perioperative period may be at risk for pulmonary complications. Dogs fitting criteria for the above risk factors should be monitored closely postoperatively for development of pulmonary complications.
A common origin of the 4143insA ADAMTS13 mutation
Authors: Hovinga Johanna A. , Becker Tim , Budde Ulrich , Karpman Diana , Brockhaus Wolfgang , Hrachovinová Ingrid , Korczowski Bartosz , Oyen Florian , Rittich Šimon , von Rosen Johannes , Tjønnfjord Geir , Pimanda John , Wienker Thomas , Lämmle Bernhard , Schneppenheim Reinhard 
Published: June 2006

SummarySeverely deficient activity of the von Willebrand Factor (VWF) cleaving metalloprotease,ADAMTS13, is associated with thrombotic thrombocytopenic purpura (TTP).The mutation spectrum of ADAMTS13 is rather heterogeneous,and numerous mutations spread across the gene have been described in association with congenital TTP. The 4143insA mutation is unusual with respect to its geographic concentration. Following the initial report from Germany in which the 4143insA mutation was detected in four apparently unrelated families, we have now identified this mutation in a further eleven patients from Norway, Sweden, Poland, Germany, the Czech Republic and Australia. Confirmation that the Australian patient is of German ancestry, together with the Northern and Central European origin of most of the other patients, suggests that the 4143insA mutation has a common genetic background. We established ADAMTS13 haplotypes by analyzing 17 polymorphic intragenic markers. The haplotypes linked to 4143insA were identical in all informative families. Three novel candidate mutations, C347S, P671L and R1060W, as well as the known mutation R507Q, were also identified during the course of the study. We conclude that 4143insA has a common genetic background and is frequent among patients with hereditary ADAMTS13 deficiency in Northern and Central European countries.
Interleukin-10 promoter polymorphism and venous thrombosis
Authors: Cochery-Nouvellon Eva , Vitry Fabien , Cornillet-Lefebvre Pascale , Hezard Nathalie , Gillot Lucile , Nguyen Philippe 
Published: June 2006

SummaryThe human interleukin-10 promoter gene is highly polymorphic. IL-10 polymorphisms have been associated with various autoimmune and lymphoproliferative disorders. Although IL-10 has been shown to modulate thrombin generation in several experimental models, it is not known whether IL-10 polymorphisms could be a risk factor for venous thrombosis. We therefore conducted a case-control study comparing 74 consecutive patients who experienced at least one episode of documented venous thromboembolic event and 100 healthy controls. All subjects were Caucasians. Five polymorphisms of the IL-10 promoter gene were studied: two highly polymorphic dinucleotide repeats, IL-10 R and IL-10G, and three single nucleotide polymorphisms at position −1082, −819 and −592. Factor VG1691C Leiden mutation was systematically determined. Multivariate logistic regression analysis showed that IL-10 G13 and G10 alleles are independent risk factors for venous thrombosis (Odds ratio:OR = 3.33, p = 0.003 and OR = 2.83, p = 0.03, respectively). Furthermore, IL-10 G10 allele is more frequent in recurrent disease.
Flow cytometry-sorted non-viable endotoxin-treated human monocytes are strongly procoagulant
Authors: Klingenberg Olav , Joø Gun-Britt , Kierulf Peter , Henriksson Carola , Hellum Marit , Landsverk Kirsti 
Published: June 2006

SummaryMonocytes/macrophages are important in disease states such as gram-negative sepsis and coronary artery disease. Following exposure to lipopolysaccharide (LPS), monocytes express tissue factor (TF), the main initiator of blood coagulation. We previously demonstrated that human monocytes treated with high concentrations of LPS, or with LPS and calcium ionophore, displayed higher TF activity than monocytes treated with only low concentrations of LPS, even though the monocytes under all conditions expressed similar amounts of cell surface TF antigen. Such restrained TF activity is often referred to as encryption and its release as de-encryption. We also observed that the increase in TF activity, de-encryption, coincided with an increase in cell surface phosphatidylserine (PS) representing apoptosis and necrosis. In the present work, we separated LPS and LPS and calcium ionophore-treated human monocytes into two populations, one of mainly viable, PS negative cells, and one of mainly non-viable, PS positive cells, by sorting flow-cytometry. We observed that non-viable cells expressed considerably less TF antigen than viable cells. Despite this, non-viable cells were clearly more procoagulant than viable cells in two different coagulation assays. Procoagulant activity was dependent on both TF and PS. We consider the higher content of externalized PS in non-viable monocytes as the major reason for the stronger procoagulant activity of these cells. Thus, TF de-encryption appears largely to occur on PS positive, non-viable cells under these conditions. This supports the important role of PS in coagulation, and it suggests that PS expression signifying cell death, may be clinically relevant.
Synthesis of Diphenyl Carbonate from CO2, Phenoxide, and CCl4 with ZnCl2 as Catalyst
Authors: Li Zhenhuan , Qin Zhangfeng , Zhu Huaqing , Wang Jianguo 
Published: June 2006

Abstract
Direct synthesis of diphenyl carbonate (DPC) from phenoxide, CO2 and CCl4 in one pot was realized with ZnCl2 as catalyst. Trichloromethyl cation may act on potassium phenyl carbonate, which brings the carbonyl more easily attached on by the phenoxide. Onium salts promote the reaction greatly, especially with phenol and potassium carbonate instead of phenoxide as reactants. Moreover, the substituent on the aromatic ring has significant effects on the selectivity and yield of carbonate.
A Novel Poly(Dl-lactic acid) Nanoparticle of Nitroxide Derivative, 4-Ferrocenecarboxyl-2,2,6,6-tetramethyl Piperidine-1-oxyl
Authors: Wu Ying , Miao Lede , Yuan Huihui , Zuo Shaohua , Ding Changming , Lan Minbo 
Published: June 2006

Abstract
A newly synthesized nitroxide radical, 4-ferrocenecarboxyl-2,2,6,6-tetramethyl piperidine-1-oxyl (FC-TEMPO), was firstly encapsulated in the poly(Dl-lactic acid) (PLA) nanoparticles by the modified spontaneous emulsification solvent diffusion method. The formation of the nanoparticles with diameters of 120 ± 15 nm has been confirmed by a laser particle size analyzer. The morphology of the nanoparticles exhibited a fine spherical shape without aggregation or adhesion by the scanning electron microscopy (SEM). The electron paramagnetic resonance (EPR) spectra indicated that FC-TEMPO was mainly encapsulated into PLA nanoparticle core.
A Precursor Route for the Preparation of Metal–Dielectric Composite in Large Scale
Authors: Tian Chungui , Wang Enbo , Gao Lei , Kang Zhenhui , Zhang Chao , Wang Chunlei , Lan Yang 
Published: June 2006

Abstract
In this paper, a novel method based on formation of a precursor was developed to fabricate metal–dielectric colloids in large scale. Metal nanoparticles formed in situ on the surface of the polyethyleneimine (PEI)-modified dielectric colloids.
The Paradox Facing DNA Patenting in Europe
Authors: Hsu Shun-liang 
Published: June 2006

AbstractNowadays there are increasing biological innovations standing in the filing queue to be passed by the authority so that the patentee can claim the trophy of exclusive right awarded by State. On the one hand, this may be seen as a sign that the heavily invested bio-industry is beginning to bear fruits, which according to some famous management school, serves as an important indication to demonstrate how competitive a State is as a whole. Whereas, on the other hand, because the controversy centering biotechnology has long time been the materialDNA, deoxyribonucleic acid consists of four building blocks, termed nucleotides – Adenine (A), Guanine (G), Cytosine (C) and Thymine (T). Usually in the cell nucleus, genes are contained in long DNA molecules and can be represented as letters in a four- letter alphabet used to write out the biological messages. Each cell of the human body maintains information-containing hereditary units, the genes that control identifiable traits of an organism. There are approximately 26,000 to 31,000 protein-encoding genes in the human genome.In the knowledge-based era, patent provides an excellent vehicle to drive technology further into exploration of the unknown world. Despite any potential risk from upstream scientific R&D to downstream business strategy, government's policy often plays a pivotal role in the whole picture. As a result, political interpretation of a newly developed technology seems to always surpass the appealing benefits envisaged by different interested groups, being academia or industry. The reason why biotech craze can boom within the industry is likely to be attributed to the incentive a rather rigid patent system can provide. In addition to other pre-requisites, to determine whether a biological invention constitutes patentable subject matter, two notions have been raised to argue in practical evaluation. The first one is the substantial difference between discovery and invention and the second, the ethical judgment-whether or not an invention is contrary to ‘‘Despite any potential drawbacks imposed by ethical deliberation, what seems fast growing nowadays is the piled up applications for gene patent and a still ambiguous principle tangled by vigorous ethical debate.
Gesteuerter und ungesteuerter Grammatikerwerb, Bericht über die AG 4 auf der Jahrestagung der „Deutschen Gesellschaft für Sprachwissenschaft“ (DGfS) in Mainz, 25.–27. Februar 2004
Authors: Becker Tabea , Peschel Corinna 
Published: June 2006

AbstractDer traditionelle Grammatikunterricht hat sich immer wieder vorwerfen lassen müssen, die Verstehens- und Handlungsmöglichkeiten der Schülerinnen und Schüler nicht ausreichend zur berücksichtigen. Dieser Vorwurf liegt vor allem darin begründet, dass Kenntnisse über das Sprachwissen der Schüler und damit über die Integrierbarkeit und Verwendbarkeit des unterrichtlich zu Vermittelnden bei Lehrkräften in der Regel nur in sehr eingeschränktem Maße vorhanden sind. Fragen wie die folgenden sind aber für einen schülergerechten wie auch sachangemessenen Grammatikunterricht unerlässlich: Was wissen Schüler schon über sprachliche Formen und ihre Funktionen, was müssen sie neu lernen? Was sollte lediglich aus dem Status impliziten Wissens in explizites Wissen umgewandelt werden. Hier kommt der Kategorie der „Sprachbewusstheit” entscheidende Bedeutung zu.