bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of caspases‐9, ‐3 and ‐8 in human platelets triggered by BH3‐only mimetic ABT‐737 and calcium ionophore A23187: caspase‐8 is activated via bypass of the death receptors
Authors: Mutlu Asuman , Gyulkhandanyan Armen V. , Freedman John , Leytin Valery 
Published: October 2012

SummaryPlatelet apoptosis and activation have been studied in human platelets treated with BH3‐only mimetic ABT‐737 and calcium ionophore A23187, agents triggering apoptosis through the intrinsic mitochondrial pathway. Platelet apoptosis was determined as activation of crucial apoptosis‐associated caspases, initiator caspase‐9 of intrinsic apoptosis pathway, executioner caspase‐3 and initiator caspase‐8 of extrinsic death receptor pathway, and platelet activation was detected by P‐selectin (CD62) exposure on the platelet surface. We found that ABT‐737 predominantly induced activation of caspases‐9, ‐3 and ‐8 rather than CD62 exposure, whereas A23187 induces both caspases activation and CD62 exposure. Caspase‐8 activation was stimulated independently of the extrinsic apoptosis pathway via mitochondrial membrane permeabilization and depolarization. These data suggest that (i) caspase‐8 activation is triggered in ABT‐737‐ and A23187‐treated anucleate platelets through the mitochondria‐initiated caspase activation cascade bypassing the death receptors, and (ii) ABT‐737‐treated platelets are a useful experimental tool for discerning the role of platelet apoptosis in platelet function and survival.
The genotype of RAET1L (ULBP6), a ligand for human NKG2D (KLRK1), markedly influences the clinical outcome of allogeneic stem cell transplantation
Authors: Antoun Ayman , Vekaria Dhruti , Salama Rafik A. , Pratt Guy , Jobson Shirley , Cook Mark , Briggs David , Moss Paul 
Published: October 2012

SummaryNKG2D (KLRK1) is an activating receptor on natural killer (NK) and T‐cells and binds a diverse panel of polymorphic ligands encoded by the MIC and RAET1 gene families. We studied the clinical importance of retinoic acid early transcript‐1 (RAET1) polymorphism in allogeneic stem cell transplantation (SCT) by determining the frequency of 18 single nucleotide polymorphisms (SNPs) and individual RAET1 alleles in 371 patient‐donor pairs and relating this to clinical outcome. A strong association was observed between the presence of five SNPs within the patient RAET1L (ULBP6) gene and relapse‐free survival and overall survival. Two common alleles of RAET1L were determined and the presence of the protective RAET1L*02 allele in the patient was associated with a relapse‐free survival of 44% at 8 years compared with just 25% in patients who lacked a RAET1L*02 allele (P < 0·001). Overall survival at this time was 55% in those with RAET1L*02 allele compared to 39% in patients who lacked a RAET1L*02 allele (P = 0·003). These novel findings indicate a critical role for NKG2D–RAET1L interactions in determining SCT clinical outcome and show RAET1L may have an important influence on regulating the strength of the alloreactive immune response. The data will be of value in guiding the development of future transplant therapy protocols.
Radiological and micro‐computed tomography analysis of the bone at dental implants inserted 2, 3 and 4 mm apart in a minipig model with platform switching incorporated
Authors: Elian Nicolas , Bloom Mitchell , Dard Michel , Cho Sang‐Choon , Trushkowsky Richard D. , Tarnow Dennis 
Published: October 2012

AbstractBackgroundThe purpose of this study was to assess the effect of inter‐implant distance on interproximal bone utilizing platform switching. Analysis of interproximal bone usually depends on traditional two‐dimensional radiographic assessment. Although there has been increased reliability of current techniques, there has been an inability to track bone level changes over time and in three dimensions. Micro‐CT has provided three‐dimensional imaging that can be used in conjunction with traditional two‐dimensional radiographic techniques.MethodsThis study was performed on 24 female minipigs. Twelve animals received three implants with an inter‐implant distance of 3 mm on one side of the mandible and another three implants on the contra‐lateral side, where the implants were placed 2 mm apart creating a split mouth design. Twelve other animals received three implants with an inter‐implant distance of 3 mm on one side of the mandible and another three implants on the contra‐lateral side, where the implants were placed 4 mm apart creating a split mouth design too. The quantitative evaluation was performed comparatively on radiographs taken at t 0 (immediately after implantation) and at t 8 weeks (after termination). The samples were scanned by micro‐computed tomography (μCT) to quantify the first bone to implant contact (fBIC) and bone volume/total volume (BV/TV). Mixed model regressions using the nonparametric Brunner–Langer method were used to determine the effect of inter‐implant distance on the measured outcomes.ResultsThe change in bone level was determined using radiography and its mean was 0.05 mm for an inter‐implant distance of 3 and 0.00 mm for a 2 mm distance (P = 0.7268). The mean of this outcome was 0.18 mm for the 3 mm and for 4 mm inter‐implant distance (P = 0.9500). Micro‐computed tomography showed that the fBIC was always located above the reference, 0.27 and 0.20 mm for the comparison of 2–3 mm (P = 0.4622) and 0.49 and 0.34 mm for the inter‐implant distance of 3 and 4 mm (P = 0.1699). BV/TV inside the defined parallelepipedic masks reached 82.38% for the 2 mm inter‐implant distance and 85.00% for 3 mm, P = 0.8432. For the comparison of the 3–4 mm inter‐implant distance, the means were 84.69% and 84.38%, respectively, P = 0.8401. Non‐inferiority tests for the smaller inter‐implant distances for both comparisons showed similar differences and similar tolerance ranges.ConclusionThe effect of a smaller interproximal distances between implants on bone level, fBIC and BV/TV assessed by two convergent investigation methods, radiology and μCT, was similar to that of larger distances. Implants can potentially be placed 2 mm apart instead of 3 mm and 3 mm apart instead of 4 mm when platform switching is utilized. Further research with a conventional platform is warranted.
Has Agency Theory Run its Course?: Making the Theory more Flexible to Inform the Management of Reward Systems
Authors: Cuevas‐Rodríguez Gloria , Gomez‐Mejia Luis R. , Wiseman Robert M. 
Published: October 2012

AbstractManuscript TypeConceptualResearch Question/IssueIn this paper we discuss three assumptions of agency theory: (1) conflicts of interest between principal and agent, (2) nature of risk, and (3) the proposed internal mechanisms to reduce agency costs. We review criticisms of agency theory's pessimistic assumptions of human behavior and its simplistic view about individual risk preferences to argue how the context may influence both the interest and mechanisms for aligning interest of principals and agents.Research Findings/InsightsWe draw on alternative theoretical perspectives from behavioral and organizational sciences to describe circumstances under which honesty, loyalty, and trust in agents' behaviors are possible and also the development of cooperative rather than contentious relationships.Theoretical/Academic ImplicationsThis study explores the boundary conditions of traditional agency theory in the hope of extending agency theory outside its current contextual boundaries. In doing so, we provide a more robust and exhaustive view of the economic exchange between principals and agents.Practitioner/Policy ImplicationsThis study offers insights to managers about how intrinsic incentives may provide an alternative mechanism of control over agents' behavior to extrinsic incentives prescribed by traditional agency theory. Indeed, intrinsic incentives of personal satisfaction and identification with organizational objects, combined with implicit social obligations and reciprocity may, under certain circumstances, provide stronger restraints on agent opportunism than the use of traditional extrinsic rewards in the form of incentive alignment.
Diagnostic value of fine needle aspirates processed by ThinPrep® for the assessment of axillary lymph node status in patients with invasive carcinoma of the breast
Authors: Jing X. , Wey E. , Michael C. W. 
Published: October 2012

X. Jing, E. Wey and C. W. Michael
Diagnostic value of fine needle aspirates processed by ThinPrep® for the assessment of axillary lymph node status in patients with invasive carcinoma of the breast
Objective:  To evaluate the utility of ThinPrep® as an optional specimen processing method for the detection of axillary lymph node metastasis of invasive breast carcinoma.Methods:  A computer SNOMED search from the file at our institution between January 2003 and August 2011 retrieved a total of 209 fine needle aspiration (FNA) specimens of axillary lymph nodes prepared by ThinPrep and followed by axillary lymph node biopsy and/or dissection. Original cytological diagnoses and corresponding histological diagnoses were documented. Using the histological diagnoses as the gold standard, the diagnostic parameters including sensitivity, specificity, positive (PPV) and negative predictive values (NPV) and diagnostic accuracy were calculated. Both cytology and histology slides from cyto‐histologically discrepant cases were reviewed.Results:  Out of a total of 209 specimens, 193 (92%) had adequate diagnostic material while the remaining 16 specimens (8%) were inadequate for cytological assessment. The diagnostic specimens included 168 invasive ductal carcinomas (IDC), 15 invasive lobular carcinomas (ILC) and 10 mixed carcinomas (IDC and ILC). Excluding 19 cases with malignant cells on FNA in which no residual tumour was found in fibrotic lymph nodes after neoadjuvant therapy (cytology and histology confirmed on review) ThinPrep detected nodal metastasis with an overall sensitivity of 77.5%, specificity of 100%, PPV of 100% and NPV of 53.7%. Diagnostic accuracy was 82.2%. There was no difference in Bloom–Richardson grade or the number or size of metastases between tumours with true‐positive and false‐negative cytology. Sampling error was the sole factor contributing to cyto‐histological discrepancy.Conclusions:  ThinPrep is a good alternative to the conventional smear for cytological assessment of axillary lymph node status in patients with invasive breast carcinoma, particularly when specimens are collected at remote sites or when cytologists are not available for assistance during FNA.
TEASIng apart alien species risk assessments: a framework for best practices
Authors: Leung Brian , Roura‐Pascual Nuria , Bacher Sven , Heikkilä Jaakko , Brotons Lluis , Burgman Mark A. , Dehnen‐Schmutz Katharina , Essl Franz , Hulme Philip E. , Richardson David M. , Sol Daniel , Vilà Montserrat 
Published: October 2012

AbstractSome alien species cause substantial impacts, yet most are innocuous. Given limited resources, forecasting risks from alien species will help prioritise management. Given that risk assessment (RA) approaches vary widely, a synthesis is timely to highlight best practices. We reviewed quantitative and scoring RAs, integrating > 300 publications into arguably the most rigorous quantitative RA framework currently existing, and mapping each study onto our framework, which combines Transport, Establishment, Abundance, Spread and Impact (TEASI). Quantitative models generally measured single risk components (78% of studies), often focusing on Establishment alone (79%). Although dominant in academia, quantitative RAs are underused in policy, and should be made more accessible. Accommodating heterogeneous limited data, combining across risk components, and developing generalised RAs across species, space and time without requiring new models for each species may increase attractiveness for policy applications. Comparatively, scoring approaches covered more risk components (50% examined > 3 components), with Impact being the most common component (87%), and have been widely applied in policy (> 57%), but primarily employed expert opinion. Our framework provides guidance for questions asked, combining scores and other improvements. Our risk framework need not be completely parameterised to be informative, but instead identifies opportunities for improvement in alien species RA.
Potential for local adaptation in response to an anthropogenic agent of selection: effects of road deicing salts on amphibian embryonic survival and development
Authors: Hopkins Gareth R. , French Susannah S. , Brodie Edmund D. 
Published: October 2012

AbstractThe application of millions of tons of road deicing salts every winter in North America presents significant survival challenges to amphibians inhabiting roadside habitats. While much is known of the effects of NaCl on anuran tadpoles, less is known of effects on amphibian eggs, or any caudate life stage. In addition, little is known of the effects of MgCl2, which is now the 2nd most commonly used road deicer. Most studies have considered amphibians to be helpless victims of deicing salts, and ignore the possibility of the evolution of local adaptation to this stressor. We attempt to address these knowledge gaps and explore this evolutionary potential by examining the effects of NaCl and MgCl2 on the survival and development of eggs from different female rough‐skinned newts (Taricha granulosa) from the same population. We demonstrate that both salts, at environmentally relevant concentrations, severely affect the embryonic survival and development of this amphibian, but that the effects of the salt are dependent on the identity of the mother. This female × treatment interaction results in substantial variation in tolerance to road deicing salts among newt families, providing the raw material necessary for natural selection and the evolution of local adaptation in this amphibian.
The role of AHI1 and CDKN1C in cutaneous T‐cell lymphoma progression
Authors: Litvinov Ivan V. , Kupper Thomas S. , Sasseville Denis 
Published: October 2012

AbstractCutaneous T‐cell lymphoma (CTCL) is the most common lymphoma of the skin. Recent reports suggest that AHI1 is overexpressed in a subset of CTCL‐derived cell lines, where it downregulates the expression of CDKN1C tumor suppressor gene. In the current work, we test the expression of these genes in 60 patients with Mycosis Fungoides and Sezary Syndrome by RT‐PCR and correlate our findings with 6 years of clinical follow‐up. These findings reveal that AHI1 and CDKN1C exhibit opposite expression patterns, where AHI1 is expressed in poor and intermediate prognosis patients, while CDKN1C is expressed in favourable prognosis patients. Kaplan–Meier analysis documents that downregulation of CDKN1C is associated with poor disease outcome in patients with CTCL, while upregulation of AHI1 shows a weak association with aggressive disease course.
A novel missense mutation of the CYLD gene identified in a Hungarian family with Brooke–Spiegler syndrome
Authors: Nagy Nikoletta , Farkas Katalin , Kinyo Ágnes , Nemeth Istvan B. , Kis Erika , Varga János , Bata‐Csorgo Zsuzsanna , Kemeny Lajos , Szell Márta 
Published: October 2012

AbstractBrooke–Spiegler syndrome (BSS; OMIM 605041) is an autosomal dominant disease characterized by skin appendage tumors due to mutations in the cylindromatosis gene (CYLD). We investigated a Hungarian BSS pedigree with two affected members, father and daughter. Direct sequencing demonstrated a novel missense mutation (c.2613C>G; p.His871Gln) in exon 19 within the ubiquitin‐specific protease domain of the encoded protein. We performed preliminary analysis to reveal the functional role of this novel mutation. Our data suggest that this novel CYLD mutation leads to increased ubiquitination of NEMO through influencing deubiquitinating activity of the CYLD protein and thus may result in enhanced NF‐κB signalling.
The response of soil organic carbon of a rich fen peatland in interior Alaska to projected climate change
Authors: Fan Zhaosheng , David McGuire Anthony , Turetsky Merritt R. , Harden Jennifer W. , Michael Waddington James , Kane Evan S. 
Published: October 2012

AbstractIt is important to understand the fate of carbon in boreal peatland soils in response to climate change because a substantial change in release of this carbon as CO2 and CH4 could influence the climate system. The goal of this research was to synthesize the results of a field water table manipulation experiment conducted in a boreal rich fen into a process‐based model to understand how soil organic carbon (SOC) of the rich fen might respond to projected climate change. This model, the peatland version of the dynamic organic soil Terrestrial Ecosystem Model (peatland DOS‐TEM), was calibrated with data collected during 2005–2011 from the control treatment of a boreal rich fen in the Alaska Peatland Experiment (APEX). The performance of the model was validated with the experimental data measured from the raised and lowered water‐table treatments of APEX during the same period. The model was then applied to simulate future SOC dynamics of the rich fen control site under various CO2 emission scenarios. The results across these emissions scenarios suggest that the rate of SOC sequestration in the rich fen will increase between year 2012 and 2061 because the effects of warming increase heterotrophic respiration less than they increase carbon inputs via production. However, after 2061, the rate of SOC sequestration will be weakened and, as a result, the rich fen will likely become a carbon source to the atmosphere between 2062 and 2099. During this period, the effects of projected warming increase respiration so that it is greater than carbon inputs via production. Although changes in precipitation alone had relatively little effect on the dynamics of SOC, changes in precipitation did interact with warming to influence SOC dynamics for some climate scenarios.
Impacts of climate change on paddy rice yield in a temperate climate
Authors: Kim Han‐Yong , Ko Jonghan , Kang Suchel , Tenhunen John 
Published: October 2012

AbstractThe crop simulation model is a suitable tool for evaluating the potential impacts of climate change on crop production and on the environment. This study investigates the effects of climate change on paddy rice production in the temperate climate regions under the East Asian monsoon system using the CERES‐Rice 4.0 crop simulation model. This model was first calibrated and validated for crop production under elevated CO2 and various temperature conditions. Data were obtained from experiments performed using a temperature gradient field chamber (TGFC) with a CO2 enrichment system installed at Chonnam National University in Gwangju, Korea in 2009 and 2010. Based on the empirical calibration and validation, the model was applied to deliver a simulated forecast of paddy rice production for the region, as well as for the other Japonica rice growing regions in East Asia, projecting for years 2050 and 2100. In these climate change projection simulations in Gwangju, Korea, the yield increases (+12.6 and + 22.0%) due to CO2 elevation were adjusted according to temperature increases showing variation dependent upon the cultivars, which resulted in significant yield decreases (−22.1% and −35.0%). The projected yields were determined to increase as latitude increases due to reduced temperature effects, showing the highest increase for any of the study locations (+24%) in Harbin, China. It appears that the potential negative impact on crop production may be mediated by appropriate cultivar selection and cultivation changes such as alteration of the planting date. Results reported in this study using the CERES‐Rice 4.0 model demonstrate the promising potential for its further application in simulating the impacts of climate change on rice production from a local to a regional scale under the monsoon climate system.
Ipilimumab induces simultaneous regression of melanocytic naevi and melanoma metastases
Authors: Libon F. , Arrese J. E. , Rorive A. , Nikkels A. F. 
Published: October 2012

Summary
Ipilimumab blocks cytotoxic T-lymphocyte-associated antigen (CTLA)-4, potentiating the antimelanoma T-cell host response. Ipilimumab has been shown to improve overall survival in patients with previously treated metastatic melanoma. CTLA-4 antibodies generate immune responses to the melanoma-associated antigens Melan-A, NY-ESO-1 and glycoprotein (gp)100 in metastatic melanoma. Digital epiluminescence microscopy (DELM) is a noninvasive method permitting the monitoring of the morphology of melanocytic lesions over time. A 50-year-old man with metastatic melanoma received four ipilimumab injections after failure of dacarbazine chemotherapy. Positron emission tomography revealed regression of pulmonary metastases, and simultaneously, DELM showed regression of several melanocytic naevi. On histological examination of the regressing naevi, prominent CD8+, CD4+ and CD45R0 lichenoid lymphohistiocytic infiltrates were seen, whereas nonregressing naevi were almost free of inflammatory infiltrate. Expression of melanoma-associated antigens in benign melanocytic naevi may explain the induction of naevus regression by ipilimumab. DELM could represent a valuable noninvasive method to monitor ipilimumab efficacy.
Effect of grain tef [Eragrostis tef (Zucc.) Trotter] flour substitution with flaxseed on quality and functionality of injera
Authors: Girma Tewodros , Bultosa Geremew , Bussa Negussie 
Published: October 2012

SummaryInjera from tef substituted with two flaxseed forms at 3%, 6% and 9% and control injera showed substitution had a significant effect on injera proximate, energy, titratable acidity (TA), total phenolics (TP) contents and sensory acceptability. Flaxseed forms had influence on moisture, fibre, total carbohydrate (TC) and TA. With 9% flour and whole flaxseed substitution, percentage energy, moisture, ash, crude protein, fibre and TA increase were 3.5, 27.3, 25.9, 20.4, 114.3 and 10.1, respectively. TC and pH were high for control. In all injera samples, condensed tannins and free fatty acid were insignificant. With an increase in the flaxseed substitution, most sensory acceptance increased, whereas injera eyes and colour decreased and appeared superior for control (100% tef injera). The 9% flaxseed‐substituted injera showed good proximate nutritional and energy contents of functional potential of high in dietary fibre, alpha linolenic acid, lignans, proteins and TP of anti‐oxidant nature.
Controlled and modified atmospheres influence chilling injury, fruit quality and antioxidative system of Japanese plums (Prunus salicina Lindell)
Authors: Singh Sukhvinder Pal , Singh Zora 
Published: October 2012

SummaryOur objective was to compare the effects of controlled atmosphere (CA) and modified atmosphere packaging (MAP) on fruit quality, chilling injury (CI) and pro‐ and antioxidative systems in ‘Blackamber’ Japanese plums. Matured fruit were stored for 5 and 8 weeks at 0–1 °C in normal air, CA‐1 (1% O2 + 3% CO2), CA‐2 (2.5% O2 + 3% CO2) and MAP (~10% O2 and 3.8% CO2). CA was more effective than MAP in retention of flesh firmness and titratable acidity during cold storage. Fruit stored in CA‐1 showed reduced CI and membrane lipid peroxidation after 5 and 8 weeks of cold storage. Low O2 atmospheres appeared to limit the generation of reactive oxygen species (ROS) and their efficient scavenging through the concerted action of superoxide dismutase and peroxidase. The role of ascorbate–glutathione (AsA–GSH) cycle in the regulation of oxidative stress was also studied during and after storage in different atmospheres. In conclusion, optimum CA conditions delayed fruit ripening and CI through augmentation of antioxidative metabolism and suppression of oxidative processes.