bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanism of E-cadherin dimerization probed by NMR relaxation dispersion
Authors: Li Ying , Altorelli Nicole L. , Bahna Fabiana , Honig Barry , Shapiro Lawrence , Palmer Arthur G. 
Published: September 2013

Significance
Dimerization of transmembrane protein epithelial cadherin (E-cadherin) molecules extending from apposing cells is a critical event in calcium-dependent cell adhesion, a process essential for the formation and maintenance of tissues and organs. This study elucidates the molecular mechanism of E-cadherin dimerization by utilizing nuclear magnetic resonance spectroscopy to detect and characterize sparsely populated molecular species. In this mechanism, E-cadherin monomers first interact at an auxiliary interface to form a dimeric intermediate, which is followed by the conformational changes required to form the mature dimer. Besides contributing to the understanding of E-cadherin binding and recognition, the mechanism described in this work may illustrate a more general mechanism by which proteins with occluded binding sites interact with each other.
Adaptor complex AP2/PICALM, through interaction with LC3, targets Alzheimer's APP-CTF for terminal degradation via autophagy
Authors: Tian Yuan , Chang Jerry C. , Fan Emily Y. , Flajolet Marc , Greengard Paul 
Published: September 2013

Significance
β-Amyloid aggregates are often found in the brains of Alzheimer’s patients. We have previously reported that β-amyloid levels can be down-regulated through activation of autophagy, a process involving the degradation of unnecessary or harmful proteins. However, the underlying mechanism of β-amyloid autophagy-mediated degradation is unknown. Here we demonstrate that the complex adaptor protein 2/phosphatidylinositol clathrin assembly lymphoid-myeloid leukemia (AP2/PICALM), via an interaction with a β-amyloid precursor, bridges β-amyloid degradation and autophagy. This work reveals mechanistic steps for the targeting of the β-amyloid precursor for degradation via autophagy and supports a genome-wide association study identifying PICALM as a risk factor for Alzheimer’s disease (AD). Altogether, these findings support the notion that activating autophagy is a valid approach for the AD field, which urgently needs novel therapeutic strategies.
Conversion from CUL4-based COP1–SPA E3 apparatus to UVR8–COP1–SPA complexes underlies a distinct biochemical function of COP1 under UV-B
Authors: Huang Xi , Ouyang Xinhao , Yang Panyu , Lau On Sun , Chen Liangbi , Wei Ning , Deng Xing Wang 
Published: September 2013

Significance
CONSTITUTIVE PHOTOMORPHOGENESIS 1 (COP1) is a well-conserved multifunctional protein in both plants and animals. Depending on the context, COP1 can have distinct roles, such as an oncogene or a tumor suppressor in mammalian cells. In light regulation of plant development, COP1 is a central repressor under far-red and visible light whereas it is a positive regulator under UV-B. However, how COP1 positively regulates UV-B signaling remains largely unknown. In this study, we demonstrate that the UV-B–induced reorganization of COP1 complexes achieves a functional switch of COP1 from repressing to promoting photomorphogenesis.
Far-infrared spectroscopy of a lensed starburst: a blind redshift from Herschel
Authors: George R. D. , Ivison R. J. , Hopwood R. , Riechers D. A. , Bussmann R. S. , Cox P. , Dye S. , Krips M. , Negrello M. , Neri R. , Serjeant S. , Valtchanov I. , Baes M. , Bourne N. , Clements D. L. , De Zotti G. , Dunne L. , Eales S. A. , Ibar E. , Maddox S. , Smith M. W. L. , Valiante E. , van der Werf P. 
Published: September 2013

Abstract
We report the redshift of HATLAS J132427.0+284452 (hereafter HATLAS J132427), a gravitationally lensed starburst galaxy, the first determined ‘blind’ by the Herschel Space Observatory. This is achieved via the detection of [C ii] consistent with z = 1.68 in a far-infrared spectrum taken with the SPIRE Fourier Transform Spectrometer (FTS). We demonstrate that the [C ii] redshift is secure via detections of CO J = 2 → 1 and 3 → 2 using the Combined Array for Research in Millimeter-wave Astronomy and the Institut de Radioastronomie Millimétrique's Plateau de Bure Interferometer. The intrinsic properties appear typical of high-redshift starbursts despite the high lensing-amplified fluxes, proving the ability of the FTS to probe this population with the aid of lensing. The blind detection of [C ii] demonstrates the potential of the SPICA Far-infrared Instrument imaging spectrometer, proposed for the much more sensitive Space Infrared Telescope for Cosmology and Astrophysics mission, to determine redshifts of multiple dusty galaxies simultaneously without the benefit of lensing.
Method of spiral bevel gear tooth contact analysis performed in CAD environment
Authors: Sobolewski Bartłomiej , Marciniec Adam 
Published: September 2013

Purpose
– The purpose of this paper is to present the use of a CAD system for the analysis of meshing of spiral bevel gears.

Design/methodology/approach
– The TCA computer programs are based on a purely mathematical model and require to get the numerical solution of a set of nonlinear equations. There are situations that the programs fail to obtain the proper solution. In such cases, geometrical gear models defined in CAD environment prove to be a good choice. This paper describes a tool for analyzing tooth contact and transmission errors of spiral bevel gear sets with tooth flanks represented as CAD free-form surfaces.

Findings
– A new method has been proposed to keep those surfaces in continuous contact in the whole range of meshing of a mating tooth pair. During meshing, the points of contact as well as the corresponding angles of rotation of both the pinion and the ring gear are recorded. Thus, the tooth contact path as well as the motion transmission error graph is determined. Then, the contact pattern that is formed by a set of instantaneous contact ellipses is designated.

Practical implications
– The TCA results are essential for the assessment of the gear set quality in the early stages of the process of its development.

Originality/value
– All the results presented in graphical form are very illustrative and easy to interpret.
Benefiting from your buddy
Authors: K. Dutta Dev 
Published: September 2013

Purpose
– The purpose of this paper is to offer a conceptual understanding of the role played by social capital when firms engage in collaborative partnerships to develop their innovative capability, especially under environmental turbulence.

Design/methodology/approach
– The paper is theoretical in nature, drawing conceptual insights from two complementary theories: the resource-based view of the firm and institutional theory.

Findings
– Social capital plays a beneficial role by enhancing the innovative capability of firms, but only up to a point. The paper argues social capital has both positive and negative effects and follows a non-linear relationship with innovative capability. Further, this relationship is also affected by the level of environmental turbulence faced by the firm.

Originality/value
– By conceptualizing social capital as a double-edged sword in terms of its impact on firm innovative capability, the paper offers insights for managerial action and practice.
Commercialization of innovations: an overarching framework and research agenda
Authors: Datta Avimanyu , Reed Richard , Jessup Len 
Published: September 2013

Purpose
– The commercialization of innovation, which is key to entrepreneurial success, is a combination of several entrepreneurial activities. Building on research from fields of management, strategy, entrepreneurship, economics, and marketing, the paper summarized the extant literature to develop a framework of commercialization and an agenda for future research. The paper aims to discuss these issues.

Design/methodology/approach
– Extensive review of literature, which was comprised of 194 articles across 62 journals in the fields of management, strategy, entrepreneurship, economics, and marketing.

Findings
– The literature was categorized into six broad themes of entrepreneurial activities: sources of innovations, types of innovation, market entry (capabilities and feasibility), protection, development, and deployment. Most of the research papers that were reviewed were concentrated on single theme.

Practical implications
– Given the identification of six key themes of entrepreneurial activity leading to the commercialization of innovations, research questions were posed as a means to move the research forward by integrating the themes.

Originality/value
– This is the first paper in its kind to integrate 194 papers from 62 journals to provide a comprehensive framework of commercialization of innovations.
The role of relational social capital in examining exporter-intermediary relationships
Authors: Carlos M.R. Pinho José 
Published: September 2013

Purpose– This paper aims to rely on a conceptual model that builds on, and synthesizes, the theoretical foundations of social capital (relational and cognitive) and cooperation. It assumes that the network of relationships and the set of resources embedded within it strongly influence the extent to which exporter-intermediary cooperation occurs.Design/methodology/approach– Following a quantitative methodological approach, a survey was applied to a sample of exporters to empirically test the proposed model.Findings– The findings reveal that among the six relationships, five are positively supported. Specifically, this study finds a positive and a significant impact of the two dimensions of social capital: cognitive (shared values) and relational (trust) on both commitment and cooperation. However, it did not support the impact of cognitive social capital on relational social capital.Research limitations/implications– One possible shortfall of this research relates to the characteristics of different cultural environments that small and medium sized enterprises (SMEs) face which may have influenced the results.Practical implications– Empirical findings are relevant as they may assist SME managers to invest in business relationships which enable the firms to achieve important competitive advantages.Originality/value– This article presents the original approach of looking at the link between relational social capital and export-intermediary relationships, which challenges the way this topic is generally examined.
An analysis of safety advisor roles and site safety performance
Authors: Cameron Iain , Hare Billy , Duff Roy 
Published: September 2013

Purpose
– Present findings from a UK study, funded by the Institution of Occupational Safety and Health (IOSH), on the relationship between safety advisor roles and safety performance.

Design/methodology/approach
– Roles and organisational factors for contractors’ safety advisors (independent variables) were derived from existing literature. The dependent variable was “safety performance”, measured by accident incidence rate (AIR). Data were provided by 101 contractors and variance of means analysis was conducted.

Findings
– Contractors using only external safety consultants had an average AIR approximately three times those with internal safety staff. However, simply increasing internal safety personnel did not lead to increased safety performance. Contractors, where at least one safety advisor had authority to give orders had a lower mean AIR than those who did not. Other significant variables were: delivering safety training to employees; vetting sub-contractors; and the inclusion of an environmental management role.

Practical implications
– Employing at least one full-time internal safety person is better than relying solely on a safety consultant. If these safety advisers report to senior management then they have a greater chance of influencing others to act safely or commit resources to manage safety. Delivery of training, vetting sub-contractors and including environmental duties should feature in safety advisor roles.

Originality/value
– The assumption that merely increasing safety personnel improves safety has been challenged. It is apparent from these findings that what the safety personnel actually do is more important than how many are employed. This is a major finding in relation to theory and practice which challenges previous research.
Addressing patients’ colorectal cancer needs in preoperative education
Authors: Jane Spalding Nicola , McCulloch Jane , Mary Poland Fiona , Gregory Sheila , Sargen Kevin , Vicary Penny 
Published: September 2013

Purpose
– The purpose of this paper is to understand and develop ways to enhance patients’ experiences of preoperative education received prior to surgery for colorectal cancer.

Design/methodology/approach
– Based in the UK, three-action research cycles were undertaken to evaluate preoperative education, identify changes seen by patients and staff as likely to improve the service and to re-evaluate such changes following implementation. Data in each cycle were collected from: observations of clinic interactions; patient questionnaires; individual semi-structured interviews with multidisciplinary colorectal unit staff; longitudinal semi-structured interviews with patients and carers pre-surgery, two weeks post-surgery and 12 weeks post-surgery; patient and carer focus groups post-surgery; and existing educational material.

Findings
– In total, 138 participants shared their experiences of either giving or receiving preoperative education. Findings were themed into why patients want preoperative education, and patients’ views of the educational processes.

Practical implications
– Patients emphasised the need for educational provision to be fully understandable, comprehensive and client-centred using a range of communication processes. Patients emphasised the need for educational provision to be more fully understandable, comprehensive and client-centred and that important messages should be reinforced using a range of media. At a time of many uncertainties for patients’ lives, such education needed to encompass the experiences patients could expect, delivered by confident healthcare professionals.

Originality/value
– Contextualising understanding and facilitating their own actions, enabled patients to regain control in circumstances particularly disruptive of bodily and other life routines. Establishing a sense of control is confirmed as important for patient's wellbeing in preparing for surgery and postoperative rehabilitation.
Genetic Marker Suitable for Identification and Genotyping of Plasmodium ovale curtisi and Plasmodium ovale wallikeri
Authors: Tanomsing Naowarat , Imwong Mallika , Sutherland Colin J. , Dolecek Christiane , Hien Tran Tinh , Nosten Francois , Day Nicholas P. J. , White Nicholas J. , Snounou Georges 
Published: September 2013

ABSTRACT

We present a seminested PCR method that specifically discriminates between
Plasmodium ovale curtisi
and
P. ovale wallikeri
with high sensitivity. The test is based on species-specific amplification of a size-polymorphic fragment of the tryptophan-rich antigen gene,
potra
, which also permits discrimination of intraspecific sequence variants at this locus.
Comparative Cost-Effectiveness of Two-Tiered Testing Strategies for Serodiagnosis of Lyme Disease with Noncutaneous Manifestations
Authors: Wormser Gary P. , Levin Andrew , Soman Sandeep , Adenikinju Omosalewa , Longo Michael V. , Branda John A. 
Published: September 2013

ABSTRACT
The mainstay of laboratory diagnosis for Lyme disease is two-tiered serological testing, in which a reactive first-tier enzyme-linked immunosorbent assay (ELISA) or an immunofluorescence assay is supplemented by separate IgM and IgG immunoblots. Recent data suggest that the C6 ELISA can be substituted for immunoblots without a reduction in either sensitivity or specificity. In this study, the costs of 4 different two-tiered testing strategies for Lyme disease were compared using the median charges for these tests at 6 commercial diagnostic laboratories in 2012. The study found that a whole-cell sonicate ELISA followed by the C6 ELISA was the most cost-effective two-tiered testing strategy for Lyme disease with acute-phase serum samples. We conclude that the C6 ELISA can substitute for immunoblots in the two-tiered testing protocol for Lyme disease without a loss of sensitivity or specificity and is less expensive.
High-Throughput Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry as an Alternative Approach to Monitoring Drug Resistance of Hepatitis B Virus
Authors: Rybicka Magda , Stalke Piotr , Dreczewski Marcin , Smiatacz Tomasz , Bielawski Krzysztof Piotr 
Published: September 2013

ABSTRACTLong-term antiviral therapy of chronic hepatitis B virus (HBV) infection can lead to the selection of drug-resistant HBV variants and treatment failure. Moreover, these HBV strains are possibly present in treatment-naive patients. Currently available assays for the detection of HBV drug resistance can identify mutants that constitute ≥5% of the viral population. Furthermore, drug-resistant HBV variants can be detected when a viral load is >104copies/ml (1,718 IU/ml). The aim of this study was to compare matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) and multitemperature single-strand conformation polymorphism (MSSCP) with commercially available assays for the detection of drug-resistant HBV strains. HBV DNA was extracted from 87 serum samples acquired from 45 chronic hepatitis B (CHB) patients. The 37 selected HBV variants were analyzed in 4 separate primer extension reactions on the MALDI-TOF MS. Moreover, MSSCP for identifying drug-resistant HBV YMDD variants was developed and turned out to be more sensitive than INNOLiPA HBV DR and direct sequencing. MALDI-TOF MS had the capability to detect mutant strains within a mixed viral population occurring with an allelic frequency of approximately 1% (with a specific value of ≥102copies/ml, also expressed as ≥17.18 IU/ml). In our study, MSSCP detected 98% of the HBV YMDD variants among strains detected by the MALDI-TOF MS assay. The routine tests revealed results of 40% and 11%, respectively, for INNOLiPA and direct sequencing. The commonly available HBV tests are less sensitive than MALDI-TOF MS in the detection of HBV-resistant variants, including quasispecies.
Mycobacterium tuberculosis Outbreak Strain of Danish Origin Spreading at Worrying Rates among Greenland-Born Persons in Denmark and Greenland
Authors: Lillebaek T. , Andersen A. B. , Rasmussen E. M. , Kamper-Jørgensen Z. , Pedersen M. K. , Bjorn-Mortensen K. , Ladefoged K. , Thomsen V. O. 
Published: September 2013

ABSTRACT

Transmission of
Mycobacterium tuberculosis
continues at high rates among Greenland-born persons in Greenland and Denmark, with 203 and 450 notified cases per 10
5
population, respectively, in the year 2010. Here, we document that the predominant
M. tuberculosis
outbreak strain C2/1112-15 of Danish origin has been transmitted to Greenland-born persons in Denmark and subsequently to Greenland, where it is spreading at worrying rates and adding to the already heavy tuberculosis burden in this population group. It is now clear that the C2/1112-15 strain is able to gain new territories using a new population group as the “vehicle.” Thus, it might have the ability to spread even further, considering the potential clinical consequences of strain diversity such as that seen in the widely spread Beijing genotype. The introduction of the predominant
M. tuberculosis
outbreak strain C2/1112-15 into the Arctic circumpolar region is a worrying tendency which deserves attention. We need to monitor whether this strain already has, or will, spread to other countries.
Stewardship Approach for Optimizing Antimicrobial Therapy through Use of a Rapid Microarray Assay on Blood Cultures Positive for Enterococcus Species
Authors: Sango Aaron , McCarter Yvette S. , Johnson Donald , Ferreira Jason , Guzman Nilmarie , Jankowski Christopher A. 
Published: September 2013

ABSTRACT

Enterococci are a major cause of bloodstream infections in hospitalized patients and have limited antimicrobial treatment options due to their many resistance mechanisms. Molecular technologies have significantly shortened the time to enterococcal isolate identification compared with conventional methods. We evaluated the impact of rapid organism identification and resistance detection with the Verigene Gram-positive blood culture microarray assay on clinical and economic outcomes for patients with enterococcal bacteremia. A single-center preintervention/postintervention quasiexperimental study compared inpatients with enterococcal bacteremia from 1 February 2012 to 9 September 2012 (preintervention period) and 10 September 2012 to 28 February 2013 (postintervention period). An infectious disease and/or critical care pharmacist was contacted with the microarray assay results, and effective antibiotics were recommended. The clinical and economic outcomes for 74 patients were assessed. The mean time to appropriate antimicrobial therapy was 23.4 h longer in the preintervention group than in the postintervention group (
P
= 0.0054). A nonsignificant decrease in the mean time to appropriate antimicrobial therapy was seen for patients infected with vancomycin-susceptible
Enterococcus
isolates (
P
= 0.1145). For patients with vancomycin-resistant
Enterococcus
bacteremia, the mean time to appropriate antimicrobial therapy was 31.1 h longer in the preintervention group than in the postintervention group (
P
< 0.0001). In the postintervention group, the hospital length of stay was significantly 21.7 days shorter (
P
= 0.0484) and mean hospital costs were $60,729 lower (
P
= 0.02) than in the preintervention group. The rates of attributed deaths in the two groups were not statistically different. Microarray technology, supported by pharmacy and microbiology departments, can decrease the time to appropriate antimicrobial therapy, the hospital length of stay, and health care costs.
Comparison of Heat Inactivation and Cell Disruption Protocols for Identification of Mycobacteria from Solid Culture Media by Use of Vitek Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry
Authors: Machen Alexandra , Kobayashi Miwako , Connelly Mary Robin , Wang Yun F. (Wayne) 
Published: September 2013

ABSTRACT

Two novel protocols for inactivation and extraction were developed and used to identify 107
Mycobacterium
clinical isolates, including
Mycobacterium tuberculosis
complex, from solid cultures using Vitek matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry. The protocol using heat inactivation with sonication and cell disruption with glass beads resulted in 82.2% and 88.8% species and genus level identifications, respectively.