bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Note on the Relative Chronology of the English Long Barrows
Authors: Piggott Stuart 
Published: February 2015

The original draft of this paper was read at the First International Congress of Prehistoric Sciences in 1932, and a summary was printed in the ‘Proceedings of the Congress’ (p. 144). It has since been re-written and incorporates new evidence.The English long barrows have not been dealt with as a whole since the classic paper of Dr Thurnam in 1868, but a series of regional studies, mainly the production of the archaeological department of the Ordnance Survey, have made the material available in convenient form. The publication of the Survey's complete map of British megaliths will enable many problems to be approached from the view point of distribution, but the southern English material, which is already published, raises one problem, at least, of first-class importance.
Modeling and friction estimation for wheeled omnidirectional mobile robots
Authors: Conceicao Andre G. S. , Correia Mariane D. , Martinez Luciana 
Published: February 2015

SUMMARYIn this study, a model for wheeled mobile robots that includes a static friction model in the force balance at the robot's center of mass is presented. Additionally, a least-squares method to linearly combine functions is proposed to estimate the friction coefficients. The experimental and simulation results are discussed to demonstrate the effectiveness of this approach in indoor environments for two floor types.
Use of random forest to estimate population attributable fractions from a case-control study of Salmonella enterica serotype Enteritidis infections
Authors: GU W. , VIEIRA A. R. , HOEKSTRA R. M. , GRIFFIN P. M. , COLE D. 
Published: February 2015

SUMMARYTo design effective food safety programmes we need to estimate how many sporadic foodborne illnesses are caused by specific food sources based on case-control studies. Logistic regression has substantive limitations for analysing structured questionnaire data with numerous exposures and missing values. We adapted random forest to analyse data of a case-control study of Salmonella enterica serotype Enteritidis illness for source attribution. For estimation of summary population attributable fractions (PAFs) of exposures grouped into transmission routes, we devised a counterfactual estimator to predict reductions in illness associated with removing grouped exposures. For the purpose of comparison, we fitted the data using logistic regression models with stepwise forward and backward variable selection. Our results show that the forward and backward variable selection of logistic regression models were not consistent for parameter estimation, with different significant exposures identified. By contrast, the random forest model produced estimated PAFs of grouped exposures consistent in rank order with results obtained from outbreak data, with egg-related exposures having the highest estimated PAF (22·1%, 95% confidence interval 8·5–31·8). Random forest might be structurally more coherent and efficient than logistic regression models for attributing Salmonella illnesses to sources involving many causal pathways.
High prevalence of hepatitis C (HCV) in the emergency department (ED) of a London hospital: should we be screening for HCV in ED attendees?
Authors: ORKIN C. , LEACH E. , FLANAGAN S. , WALLIS E. , RUF M. , FOSTER G. R. , TONG C. Y. W. 
Published: February 2015

SUMMARYAn unlinked anonymous study was conducted to estimate the prevalence of hepatitis C virus (HCV) infection in emergency department (ED) attendees at a London Hospital. Nine hundred and ninety-seven samples collected over a 12-day period were tested for HCV antibody (Ab) and reactive samples were further tested for HCV RNA. The HCV seroprevalence was 2·6% (26/997) with 1·2% (12/997) HCV RNA positive. A peak HCV RNA-positive prevalence of 4·8% (3/63) was found in males aged 35–44 years, this was compared to 0% (0/136) in males aged <35 years (P = 0·0614) and 1·4% (4/278) in males aged ⩾45 years (P = 0·2415). Assuming the cost for HCV Ab is £6 and HCV RNA is £40 per test, screening ED attendees aged 25–54 years would cost £360 per viraemic infection and identify 82% of those who were HCV RNA positive, yielding the most favourable cost/benefit ratio. HCV screening of ED attendees aged 25–54 years in this population could be an effective way of identifying patients and limit onward transmission.
The lived experience of volunteering in a palliative care biography service
Authors: Beasley Elizabeth , Brooker Joanne , Warren Narelle , Fletcher Jane , Boyle Christopher , Ventura Adriana , Burney Susan 
Published: February 2015

AbstractObjective:Many patients approaching death experience hopelessness, helplessness, and a depressed mood, and these factors can contribute to a difficult end-of-life (EoL) period. Biography services may assist patients in finding meaning and purpose at this time. The aim of our study was to investigate the lived experience of volunteers involved in a biography service in Melbourne, Australia, using a qualitative methodology.Method:The participants were 10 volunteers who had participated in a biography service within a private palliative care service. Each volunteer was interviewed separately using a study-specific semistructured interview guide. The transcripts of these interviews were then subjected to thematic analysis.Results:Analysis yielded the following themes: motivations for volunteering; dealing with death, dying, and existential issues; psychosocial benefits of volunteering; and benefits and challenges of working with patients and their families. Our results indicated that volunteering gave the volunteers a deeper appreciation of existential issues, and helped them to be more appreciative of their own lives and gain a deeper awareness of the struggles other people experience. They also suggested that volunteers felt that their involvement contributed to their own personal development, and was personally rewarding. Furthermore, the results highlighted that volunteers found that encounters with family members were sometimes challenging. While some were appreciative, others imposed time limits, became overly reliant on the volunteers, and were sometimes offended, hurt, and angered by what was included in the final biography.Significance of Results:It is hoped that the findings of the current study will provide direction for improvements in the biography services that will benefit patients, family members, and volunteers. In particular, our findings highlight the need to provide ongoing support for volunteers to assist them in handling the challenges of volunteering in a palliative care setting.
Development of a brief measure of generativity and ego-integrity for use in palliative care settings
Authors: Vuksanovic Dean , Dyck Murray , Green Heather 
Published: February 2015

AbstractObjective:Our aim was to develop and test a brief measure of generativity and ego-integrity that is suitable for use in palliative care settings.Method:Two measures of generativity and ego-integrity were modified and combined to create a new 11-item questionnaire, which was then administered to 143 adults. A principal-component analysis with oblique rotation was performed in order to identify underlying components that can best account for variation in the 11 questionnaire items.Results:The two-component solution was consistent with the items that, on conceptual grounds, were intended to comprise the two constructs assessed by the questionnaire.Significance of Results:Results suggest that the selected 11 items were good representatives of the larger scales from which they were selected, and they are expected to provide a useful means of measuring these concepts near the end of life.
Miniaturized bent slotted patch antenna over a reactive impedance surface substrate
Authors: Kumar Saurabh , Vishwakarma Dinesh Kumar 
Published: February 2015

A reactive impedance surface (RIS) based miniaturized bent slotted patch antenna is proposed and investigated for S-band applications around 2.39 GHz. Bent slots in the patch reduce the patch antenna size by increasing current path on the patch. Further a RIS substrate with cross-shaped patch elements printed over a grounded dielectric is optimized and investigated for antenna miniaturization. The proposed bent slotted patch antenna over RIS substrate is 38.75% miniaturized with respect to traditional patch antenna at a fixed operating frequency. The proposed antenna reveals an overall volume of 0.280λ0 × 0.280λ0 × 0.036λ0on a low-cost FR4 substrate at 2.39 GHz for S-band applications. The proposed antenna is fabricated and measured for its return loss. The measured results are in good agreement with simulated one.
Brain ischemia downregulates the neuroprotective GDNF-Ret signaling by a calpain-dependent mechanism in cultured hippocampal neurons
Authors: Curcio M , Salazar I L , Inácio A R , Duarte E P , Canzoniero L M T , Duarte C B 
Published: February 2015

AbstractThe glial cell line-derived neurotrophic factor (GDNF) has an important role in neuronal survival through binding to the GFRα1 (GDNF family receptor alpha-1) receptor and activation of the receptor tyrosine kinase Ret. Transient brain ischemia alters the expression of the GDNF signaling machinery but whether the GDNF receptor proteins are also affected, and the functional consequences, have not been investigated. We found that excitotoxic stimulation of cultured hippocampal neurons leads to a calpain-dependent downregulation of the long isoform of Ret (Ret51), but no changes were observed for Ret9 or GFRα1 under the same conditions. Cleavage of Ret51 by calpains was selectively mediated by activation of the extrasynaptic pool of N-methyl-d-aspartate receptors and leads to the formation of a stable cleavage product. Calpain-mediated cleavage of Ret51 was also observed in hippocampal neurons subjected to transient oxygen and glucose deprivation (OGD), a model of global brain ischemia, as well as in the ischemic region in the cerebral cortex of mice exposed to transient middle cerebral artery occlusion. Although the reduction of Ret51 protein levels decreased the total GDNF-induced receptor activity (as determined by assessing total phospho-Ret51 protein levels) and their downstream signaling activity, the remaining receptors still showed an increase in phosphorylation after incubation of hippocampal neurons with GDNF. Furthermore, GDNF protected hippocampal neurons when present before, during or after OGD, and the effects under the latter conditions were more significant in neurons transfected with human Ret51. These results indicate that the loss of Ret51 in brain ischemia partially impairs the neuroprotective effects of GDNF.
The transcriptional repressor HDAC7 promotes apoptosis and c-Myc downregulation in particular types of leukemia and lymphoma
Authors: Barneda-Zahonero B , Collazo O , Azagra A , Fernández-Duran I , Serra-Musach J , Islam A B M M K , Vega-García N , Malatesta R , Camós M , Gómez A , Román-González L , Vidal A , López-Bigas N , Villanueva A , Esteller M , Parra M 
Published: February 2015

AbstractThe generation of B cells is a complex process requiring several cellular transitions, including cell commitment and differentiation. Proper transcriptional control to establish the genetic programs characteristic of each cellular stage is essential for the correct development of B lymphocytes. Deregulation of these particular transcriptional programs may result in a block in B-cell maturation, contributing to the development of hematological malignancies such as leukemia and lymphoma. However, very little is currently known about the role of transcriptional repressors in normal and aberrant B lymphopoiesis. Here we report that histone deacetylase 7 (HDAC7) is underexpressed in pro-B acute lymphoblastic leukemia (pro-B-ALL) and Burkitt lymphoma. Ectopic expression of HDAC7 induces apoptosis, leads to the downregulation of c-Myc and inhibits the oncogenic potential of cells in vivo, in a xenograft model. Most significantly, we have observed low levels of HDAC7 expression in B-ALL patient samples, which is correlated with the increased levels of c-Myc. From a mechanistic angle, we show that ectopically expressed HDAC7 localizes to the nucleus and interacts with the transcription factor myocyte enhancer factor C (MEF2C) and the corepressors HDAC3 and SMRT. Accordingly, both the HDAC7–MEF2C interaction domain as well as its catalytic domain are involved in the reduced cell viability induced by HDAC7. We conclude that HDAC7 has a potent anti-oncogenic effect on specific B-cell malignancies, indicating that its deregulation may contribute to the pathogenesis of the disease.
Albumin-induced apoptosis of tubular cells is modulated by BASP1
Authors: Sanchez-Niño M D , Fernandez-Fernandez B , Perez-Gomez M V , Poveda J , Sanz A B , Cannata-Ortiz P , Ruiz-Ortega M , Egido J , Selgas R , Ortiz A 
Published: February 2015

AbstractAlbuminuria promotes tubular injury and cell death, and is associated with faster progression of chronic kidney disease (CKD) to end-stage renal disease. However, the molecular mechanisms regulating tubular cell death in response to albuminuria are not fully understood. Brain abundant signal protein 1 (BASP1) was recently shown to mediate glucose-induced apoptosis in tubular cells. We have studied the role of BASP1 in albumin-induced tubular cell death. BASP1 expression was studied in experimental puromycin aminonucleoside-induced nephrotic syndrome in rats and in human nephrotic syndrome. The role of BASP1 in albumin-induced apoptosis was studied in cultured human HK2 proximal tubular epithelial cells. Puromycin aminonucleoside induced proteinuria and increased total kidney BASP1 mRNA and protein expression. Immunohistochemistry localized the increased BASP1 to tubular cells. BASP1 expression colocalized with deoxynucleotidyl-transferase-mediated dUTP nick-end labeling staining for apoptotic cells. Increased tubular BASP1 expression was observed in human proteinuric nephropathy by immunohistochemistry, providing evidence for potential clinical relevance. In cultured tubular cells, albumin induced apoptosis and increased BASP1 mRNA and protein expression at 6–48 h. Confocal microscopy localized the increased BASP1 expression in albumin-treated cells mainly to the perinuclear area. A peripheral location near the cell membrane was more conspicuous in albumin-treated apoptotic cells, where it colocalized with actin. Inhibition of BASP1 expression by a BASP1 siRNA protected from albumin-induced apoptosis. In conclusion, albumin-induced apoptosis in tubular cells is BASP1-dependent. This information may be used to design novel therapeutic approaches to slow CKD progression based on protection of tubular cells from the adverse consequences of albuminuria.
Differential roles of RIPK1 and RIPK3 in TNF-induced necroptosis and chemotherapeutic agent-induced cell death
Authors: Moriwaki K , Bertin J , Gough P J , Orlowski G M , Chan F KM 
Published: February 2015

AbstractApoptosis is a key mechanism for metazoans to eliminate unwanted cells. Resistance to apoptosis is a hallmark of many cancer cells and a major roadblock to traditional chemotherapy. Recent evidence indicates that inhibition of caspase-dependent apoptosis sensitizes many cancer cells to a form of non-apoptotic cell death termed necroptosis. This has led to widespread interest in exploring necroptosis as an alternative strategy for anti-cancer therapy. Here we show that in human colon cancer tissues, the expression of the essential necroptosis adaptors receptor interacting protein kinase (RIPK)1 and RIPK3 is significantly decreased compared with adjacent normal colon tissues. The expression of RIPK1 and RIPK3 was suppressed by hypoxia, but not by epigenetic DNA modification. To explore the role of necroptosis in chemotherapy-induced cell death, we used inhibitors of RIPK1 or RIPK3 kinase activity, and modulated their expression in colon cancer cell lines using short hairpin RNAs. We found that RIPK1 and RIPK3 were largely dispensable for classical chemotherapy-induced cell death. Caspase inhibitor and/or second mitochondria-derived activator of caspase mimetic, which sensitize cells to RIPK1- and RIPK3-dependent necroptosis downstream of tumor necrosis factor receptor-like death receptors, also did not alter the response of cancer cells to chemotherapeutic agents. In contrast to the RIPKs, we found that cathepsins are partially responsible for doxorubicin or etoposide-induced cell death. Taken together, these results indicate that traditional chemotherapeutic agents are not efficient inducers of necroptosis and that more potent pathway-specific drugs are required to fully harness the power of necroptosis in anti-cancer therapy.
Mitochondrial Lon regulates apoptosis through the association with Hsp60–mtHsp70 complex
Authors: Kao T-Y , Chiu Y-C , Fang W-C , Cheng C-W , Kuo C-Y , Juan H-F , Wu S-H , Lee A Y-L 
Published: February 2015

AbstractHuman Lon protease is a mitochondrial matrix protein with several functions, including protein degradation, mitochondrial DNA (mtDNA) binding, and chaperone activity. Lon is currently emerging as an important regulator of mitochondria-contributed tumorigenesis due to its overexpression in cancer cells. To understand the mechanism of increased Lon in tumor cells, we studied the interactome to identify the chaperone Lon-associated proteins by proteomics approaches using the cells overexpressing Lon. In the present study, we designed a method connecting co-immunoprecipitation (Co-IP) to in-solution digestion for the shotgun mass spectrometry. We identified 76 proteins that were putative Lon-associated proteins that participated in mitochondrial chaperone system, cellular metabolism and energy, cell death and survival, and mtDNA stability. The association between Lon and NDUFS8 or Hsp60–mtHsp70 complex was confirmed by Co-IP and immunofluorescence co-localization assay. We then found that the protein stability/level of Hsp60–mtHsp70 complex depends on the level of Lon under oxidative stress. Most importantly, the ability of increased Lon-inhibited apoptosis is dependent on Hsp60 that binds p53 to inhibit apoptosis. These results suggest that the mechanism underlying cell survival regulated by Lon is mediated by the maintenance of the protein stability of Hsp60–mtHsp70 complex. This new knowledge of chaperone Lon interactome will allow us to better understand the cellular mechanism of Lon in mitochondrial function and of its overexpression in enhancing cell survival and tumorigenesis.
Selective Sirt2 inhibition by ligand-induced rearrangement of the active site
Authors: Rumpf Tobias , Schiedel Matthias , Karaman Berin , Roessler Claudia , North Brian J. , Lehotzky Attila , Oláh Judit , Ladwein Kathrin I. , Schmidtkunz Karin , Gajer Markus , Pannek Martin , Steegborn Clemens , Sinclair David A. , Gerhardt Stefan , Ovádi Judit , Schutkowski Mike , Sippl Wolfgang , Einsle Oliver , Jung Manfred 
Published: February 2015

AbstractSirtuins are a highly conserved class of NAD+-dependent lysine deacylases. The human isotype Sirt2 has been implicated in the pathogenesis of cancer, inflammation and neurodegeneration, which makes the modulation of Sirt2 activity a promising strategy for pharmaceutical intervention. A rational basis for the development of optimized Sirt2 inhibitors is lacking so far. Here we present high-resolution structures of human Sirt2 in complex with highly selective drug-like inhibitors that show a unique inhibitory mechanism. Potency and the unprecedented Sirt2 selectivity are based on a ligand-induced structural rearrangement of the active site unveiling a yet-unexploited binding pocket. Application of the most potent Sirtuin-rearranging ligand, termed SirReal2, leads to tubulin hyperacetylation in HeLa cells and induces destabilization of the checkpoint protein BubR1, consistent with Sirt2 inhibition in vivo. Our structural insights into this unique mechanism of selective sirtuin inhibition provide the basis for further inhibitor development and selective tools for sirtuin biology.
Climate change as an unexpected co-factor promoting coral eating seastar (Acanthaster planci) outbreaks
Authors: Uthicke S. , Logan M. , Liddy M. , Francis D. , Hardy N. , Lamare M. 
Published: February 2015

AbstractCoral reefs face a crisis due to local and global anthropogenic stressors. A large proportion of the ~50% coral loss on the Great Barrier Reef has been attributed to outbreaks of the crown-of-thorns-seastar (COTS). A widely assumed cause of primary COTS outbreaks is increased larval survivorship due to higher food availability, linked with anthropogenic runoff . Our experiment using a range of algal food concentrations at three temperatures representing present day average and predicted future increases, demonstrated a strong influence of food concentration on development is modulated by temperature. A 2°C increase in temperature led to a 4.2–4.9 times (at Day 10) or 1.2–1.8 times (Day 17) increase in late development larvae. A model indicated that food was the main driver, but that temperature was an important modulator of development. For instance, at 5000 cells ml−1 food, a 2°C increase may shorten developmental time by 30% and may increase the probability of survival by 240%. The main contribution of temperature is to ‘push’ well-fed larvae faster to settlement. We conclude that warmer sea temperature is an important co-factor promoting COTS outbreaks.
Chromatin modifications and genomic contexts linked to dynamic DNA methylation patterns across human cell types
Authors: Yan Haidan , Zhang Dongwei , Liu Hongbo , Wei Yanjun , Lv Jie , Wang Fang , Zhang Chunlong , Wu Qiong , Su Jianzhong , Zhang Yan 
Published: February 2015

AbstractDNA methylation is related closely to sequence contexts and chromatin modifications; however, their potential differences in different genomic regions across cell types remain largely unexplored. We used publicly available genome-scale DNA methylation and histone modification profiles to study their relationships among different genomic regions in human embryonic stem cells (H1), H1-derived neuronal progenitor cultured cells (NPC) and foetal fibroblasts (IMR90) using the Random forests classifier. Histone modifications achieved high accuracy in modelling DNA methylation patterns on a genome scale in the three cell types. The inclusion of sequence features helped improve accuracy only in non-promoter regions of IMR90. Furthermore, the top six feature combinations obtained by mean decrease Gini were important indicators of different DNA methylation patterns, suggesting that H3K4me2 and H3K4me3 are important indicators that are independent of genomic regions and cell types. H3K9me3 was IMR90-specific and exhibited a genomic region-specific correlation with DNA methylation. Variations of essential chromatin modification signals may effectively discriminate changes of DNA methylation between H1 and IMR90. Genes with different co-variations of epigenetic marks exhibited genomic region-specific biological relevance. This study provides an integrated strategy to identify systematically essential epigenetic and genetic elements of genomic region-specific and cell type-specific DNA methylation patterns.