bluuebunny/crossref_metadata_2025_split huggingface dataset:
Key problems of stratigraphy in the Eastern Crimea Peninsula: some insights from new dating and structural data
Authors: Sheremet Yevgeniya , Sosson Marc , Muller Carla , Gintov Oleg , Murovskaya Anna , Yegorova Tamara 
Published: April 2016

Abstract
The tectonic evolution of the Eastern Black Sea Basin has previously been explained based on offshore and onshore data, some of the latter from the Crimean Mountains (CM). However, changes in the stratigraphy of the CM have recently been proposed: the Late Triassic–Early Jurassic Tauric Group was assigned as younger (Albian). To clarify the stratigraphy and the tectonic evolution of this area, we sampled the eastern CM for micropalaeontological datings (nannoplankton). The results demonstrate an Early Cretaceous age for the Tauric Group in the eastern CM. The samples contained substantial amounts of volcanic ash, indicating a period of magmatic activity along all the eastern CM. Our field observations allowed us to propose a new structural map and cross-sections, using which three main tectonic units were distinguished. We define a phase of extension during the Early Cretaceous and one of shortening during the Paleocene–Early Eocene, before the main Middle Eocene limestone unconformity. These two phases are related to: (1) the opening of the Eastern Black Sea Basin along NNW–SSE-trending normal faults and the associated magmatism; and (2) north–south shortening that could be comparable with the inversion in Dobrogea and/or with north–south shortening linked to the collision of continental blocks in the Pontides and Taurides domains.
Hematopoietic Age at Onset of Triple-Negative Breast Cancer Dictates Disease Aggressiveness and Progression
Authors: Marsh Timothy , Wong Irene , Sceneay Jaclyn , Barakat Amey , Qin Yuanbo , Sjödin Andreas , Alspach Elise , Nilsson Björn , Stewart Sheila A. , McAllister Sandra S. 
Published: April 2016

Abstract
Triple-negative breast cancer (TNBC) is considered an early onset subtype of breast cancer that carries with it a poorer prognosis in young rather than older women for reasons that remain poorly understood. Hematopoiesis in the bone marrow becomes altered with age and may therefore affect the composition of tumor-infiltrating hematopoietic cells and subsequent tumor progression. In this study, we investigated how age- and tumor-dependent changes to bone marrow–derived hematopoietic cells impact TNBC progression. Using multiple mouse models of TNBC tumorigenesis and metastasis, we found that a specific population of bone marrow cells (BMC) upregulated CSF-1R and secreted the growth factor granulin to support stromal activation and robust tumor growth in young mice. However, the same cell population in old mice expressed low levels of CSF1R and granulin and failed to promote tumor outgrowth, suggesting that age influences the tumorigenic capacity of BMCs in response to tumor-associated signals. Importantly, BMCs from young mice were sufficient to activate a tumor-supportive microenvironment and induce tumor progression in old mice. These results indicate that hematopoietic age is an important determinant of TNBC aggressiveness and provide rationale for investigating age-stratified therapies designed to prevent the protumorigenic effects of activated BMCs. Cancer Res; 76(10); 2932–43. ©2016 AACR.
TRX-E-002-1 Induces c-Jun–Dependent Apoptosis in Ovarian Cancer Stem Cells and Prevents Recurrence In Vivo
Authors: Alvero Ayesha B. , Heaton Andrew , Lima Eydis , Pitruzzello Mary , Sumi Natalia , Yang-Hartwich Yang , Cardenas Carlos , Steinmacher Sahra , Silasi Dan-Arin , Brown David , Mor Gil 
Published: April 2016

Abstract
Chemoresistance is a major hurdle in the management of patients with epithelial ovarian cancer and is responsible for its high mortality. Studies have shown that chemoresistance is due to the presence of a subgroup of cancer cells with stemness properties and a high capacity for tumor repair. We have developed a library of super-benzopyran analogues to generate potent compounds that can induce cell death in chemoresistant cancer stem cells. TRX-E-002-1 is identified as the most potent analogue and can induce cell death in all chemoresistant CD44+/MyD88+ ovarian cancer stem cells tested (IC50 = 50 nmol/L). TRX-E-002-1 is also potent against spheroid cultures formed from cancer stem cells, chemosensitive CD44−/MyD88− ovarian cancer cells, and heterogeneous cultures of ovarian cancer cells. Cell death was associated with the phosphorylation and increased levels of c-Jun and induction of caspases. In vivo, TRX-E-002-1 given as daily intraperitoneal monotherapy at 100 mg/kg significantly decreased intraperitoneal tumor burden compared with vehicle control. When given in combination with cisplatin, animals receiving the combination of cisplatin and TRX-E-002-1 showed decreased tumor burden compared with each monotherapy. Finally, TRX-E-002-1 given as maintenance treatment after paclitaxel significantly delayed disease recurrence. Our results suggest that TRX-E-002-1 may fill the current need for better therapeutic options in the control and management of recurrent ovarian cancer and may help improve patient survival. Mol Cancer Ther; 15(6); 1279–90. ©2016 AACR.
T Cells Expressing CD19/CD20 Bispecific Chimeric Antigen Receptors Prevent Antigen Escape by Malignant B Cells
Authors: Zah Eugenia , Lin Meng-Yin , Silva-Benedict Anne , Jensen Michael C. , Chen Yvonne Y. 
Published: April 2016

AbstractThe adoptive transfer of T cells expressing anti-CD19 chimeric antigen receptors (CARs) has shown remarkable curative potential against advanced B-cell malignancies, but multiple trials have also reported patient relapses due to the emergence of CD19-negative leukemic cells. Here, we report the design and optimization of single-chain, bispecific CARs that trigger robust cytotoxicity against target cells expressing either CD19 or CD20, two clinically validated targets for B-cell malignancies. We determined the structural parameters required for efficient dual-antigen recognition, and we demonstrate that optimized bispecific CARs can control both wild-type B-cell lymphoma and CD19– mutants with equal efficiency in vivo. To our knowledge, this is the first bispecific CAR capable of preventing antigen escape by performing true OR-gate signal computation on a clinically relevant pair of tumor-associated antigens. The CD19-OR-CD20 CAR is fully compatible with existing T-cell manufacturing procedures and implementable by current clinical protocols. These results present an effective solution to the challenge of antigen escape in CD19 CAR T-cell therapy, and they highlight the utility of structure-based rational design in the development of receptors with higher-level complexity. Cancer Immunol Res; 4(6); 498–508. ©2016 AACR.See related Spotlight by Sadelain, p. 473.An addendum has been published.
Sphingolipids Contribute to Human Atherosclerotic Plaque Inflammation
Authors: Edsfeldt Andreas , Dunér Pontus , Ståhlman Marcus , Mollet Ines G. , Asciutto Giuseppe , Grufman Helena , Nitulescu Mihaela , Persson Ana Flor , Fisher Rachel M. , Melander Olle , Orho-Melander Marju , Borén Jan , Nilsson Jan , Gonçalves Isabel 
Published: April 2016

Objective—
Lipids are central to the development of atherosclerotic plaques. Specifically, which lipids are culprits remains controversial, and promising targets have failed in clinical studies. Sphingolipids are bioactive lipids present in atherosclerotic plaques, and they have been suggested to have both proatherogenic and antiatherogenic. However, the biological effects of these lipids remain unknown in the human atherosclerotic plaque. The aim of this study was to assess plaque levels of sphingolipids and investigate their potential association with and contribution to plaque vulnerability.

Approach and Results—
Glucosylceramide, lactosylceramide, ceramide, dihydroceramide, sphingomyelin, and sphingosine-1-phosphate were analyzed in homogenates from 200 human carotid plaques using mass spectrometry. Inflammatory activity was determined by analyzing plaque levels of cytokines and plaque histology. Caspase-3 was analyzed by ELISA technique. Expression of regulatory enzymes was analyzed with RNA sequencing. Human coronary artery smooth muscle cells were used to analyze the potential role of the 6 sphingolipids as inducers of plaque inflammation and cellular apoptosis in vitro. All sphingolipids were increased in plaques associated with symptoms and correlated with inflammatory cytokines. All sphingolipids, except sphingosine-1-phosphate, also correlated with histological markers of plaque instability. Lactosylceramide, ceramide, sphingomyelin, and sphingosine-1-phosphate correlated with caspase-3 activity. In vitro experiments revealed that glucosylceramide, lactosylceramide, and ceramide induced cellular apoptosis. All analyzed sphingolipids induced an inflammatory response in human coronary artery smooth muscle cells.

Conclusions—
This study shows for the first time that sphingolipids and particularly glucosylceramide are associated with and are possible inducers of plaque inflammation and instability, pointing to sphingolipid metabolic pathways as possible novel therapeutic targets.
Distinct Endothelial Cell Responses in the Heart and Kidney Microvasculature Characterize the Progression of Heart Failure With Preserved Ejection Fraction in the Obese ZSF1 Rat With Cardiorenal Metabolic Syndrome
Authors: van Dijk Christian G.M. , Oosterhuis Nynke R. , Xu Yan Juan , Brandt Maarten , Paulus Walter J. , van Heerebeek Loek , Duncker Dirk J. , Verhaar Marianne C. , Fontoura Dulce , Lourenço André P. , Leite-Moreira Adelino F. , Falcão-Pires Inês , Joles Jaap A. , Cheng Caroline 
Published: April 2016

Background—
The combination of cardiac and renal disease driven by metabolic risk factors, referred to as cardiorenal metabolic syndrome (CRMS), is increasingly recognized as a critical pathological entity. The contribution of (micro)vascular injury to CRMS is considered to be substantial. However, mechanistic studies are hampered by lack of in vivo models that mimic the natural onset of the disease. Here, we evaluated the coronary and renal microvasculature during CRMS development in obese diabetic Zucker fatty/Spontaneously hypertensive heart failure F1 hybrid (ZSF1) rats.

Methods and Results—
Echocardiographic, urine, and blood evaluations were conducted in 3 groups (Wistar-Kyoto, lean ZSF1, and obese ZSF1) at 20 and 25 weeks of age. Immunohistological evaluation of renal and cardiac tissues was conducted at both time points. At 20 and 25 weeks, obese ZSF1 rats showed higher body weight, significant left ventricular hypertrophy, and impaired diastolic function compared with all other groups. Indices of systolic function did not differ between groups. Obese ZSF1 rats developed hyperproliferative vascular foci in the subendocardium, which lacked microvascular organization and were predilection sites of inflammation and fibrosis. In the kidney, obese ZSF1 animals showed regression of the peritubular and glomerular microvasculature, accompanied by tubulointerstitial damage, glomerulosclerosis, and proteinuria.

Conclusions—
The obese ZSF1 rat strain is a suitable in vivo model for CRMS, sharing characteristics with the human syndrome during the earliest onset of disease. In these rats, CRMS induces microvascular fibrotic responses in heart and kidneys, associated with functional impairment of both organs.
Effectiveness of Arterial Closure Devices for Preventing Complications With Percutaneous Coronary Intervention
Authors: Wimmer Neil J. , Secemsky Eric A. , Mauri Laura , Roe Matthew T. , Saha-Chaudhuri Paramita , Dai David , McCabe James M. , Resnic Frederic S. , Gurm Hitinder S. , Yeh Robert W. 
Published: April 2016

Background—
Bleeding is associated with poor outcomes after percutaneous coronary intervention (PCI). Although arterial closure devices (ACDs) are widely used in clinical practice, whether they are effective in reducing bleeding complications during transfemoral PCI is uncertain. The objective of this study was to evaluate the effectiveness of ACDs for the prevention of vascular access site complications in patients undergoing transfemoral PCI using an instrumental variable approach.

Methods and Results—
We performed a retrospective analysis of the CathPCI Registry from 2009 to 2013 at 1470 sites across the United States. Variation in the proportion of ACDs used by each individual physician operator was used as an instrumental variable to address potential confounding. A 2-stage instrumental variable analysis was used as the primary approach. The main outcome measure was vascular access site complications, and nonaccess site bleeding was used as a falsification end point (negative control) to evaluate for potential confounding. A total of 1 053 155 ACDs were used during 2 056 585 PCIs during the study period. The vascular access site complication rate was 1.5%. In the instrumental variable analysis, the use of ACDs was associated with a 0.40% absolute risk reduction in vascular access site complications (95% confidence interval, 0.31–0.42; number needed to treat=250). Absolute differences in nonaccess site bleeding were negligible (risk difference, 0.04%; 95% confidence interval, 0.01–0.07), suggesting acceptable control of confounding in the comparison.

Conclusions—
ACDs are associated with a modest reduction in major bleeding after PCI. The number needed to treat with ACDs to prevent 1 major bleeding event is high.
Prevalence of Intracranial Atherosclerotic Stenosis Using High-Resolution Magnetic Resonance Angiography in the General Population
Authors: Suri Muhammad Fareed K. , Qiao Ye , Ma Xiaoye , Guallar Eliseo , Zhou Jincheng , Zhang Yiyi , Liu Li , Chu Haitao , Qureshi Adnan I. , Alonso Alvaro , Folsom Aaron R. , Wasserman Bruce A. 
Published: April 2016

Background and Purpose—
Intracranial atherosclerotic stenosis (ICAS) is a common cause of stroke, but little is known about its epidemiology. We studied the prevalence of ICAS and its association with vascular risk factors using high-resolution magnetic resonance angiography in a US cardiovascular cohort.

Methods—
The Atherosclerosis Risk in Communities (ARIC) study recruited participants from 4 US communities from 1987 to 1989. Using stratified sampling, we selected 1980 participants from visit 5 (2011–2013) for high-resolution 3T-magnetic resonance angiography. All images were analyzed in a centralized laboratory, and ICAS was graded as: no stenosis, <50% stenosis, 50% to 69% stenosis, 70% to 99% stenosis, and complete occlusion. We calculated per-vessel and per-person prevalence of ICAS (weighted for n=6538 visit 5 participants) and also estimated the US prevalence. We used multivariable logistic regression to identify variables independently associated with ICAS.

Results—
Subjects who had an adequate magnetic resonance angiography (n=1765) were aged 67 to 90 years, 41% were men, 70% were white, and 29% were black. ICAS was prevalent in 31% of participants and 9% had ICAS ≥50%. Estimated US prevalence of ICAS ≥50% for 65 to 90 years old was 8% for whites and 12% for blacks. Older age, black race, higher systolic blood pressure, and higher low-density lipoprotein cholesterol levels were associated with increased odds of ICAS, whereas higher levels of high-density lipoprotein cholesterol and use of cholesterol-lowering medications were associated with decreased odds of ICAS. Body mass index and smoking were not associated with ICAS.

Conclusions—
The prevalence of ICAS in older adults is high, and it could be a target for primary prevention of stroke and dementia in this population.
Depletion of Cultivatable Gut Microbiota by Broad-Spectrum Antibiotic Pretreatment Worsens Outcome After Murine Stroke
Authors: Winek Katarzyna , Engel Odilo , Koduah Priscilla , Heimesaat Markus M. , Fischer André , Bereswill Stefan , Dames Claudia , Kershaw Olivia , Gruber Achim D. , Curato Caterina , Oyama Naoki , Meisel Christian , Meisel Andreas , Dirnagl Ulrich 
Published: April 2016

Background and Purpose—
Antibiotics disturbing microbiota are often used in treatment of poststroke infections. A bidirectional brain–gut microbiota axis was recently suggested as a modulator of nervous system diseases. We hypothesized that gut microbiota may be an important player in the course of stroke.

Methods—
We investigated the outcome of focal cerebral ischemia in C57BL/6J mice after an 8-week decontamination with quintuple broad-spectrum antibiotic cocktail. These microbiota-depleted animals were subjected to 60 minutes middle cerebral artery occlusion or sham operation. Infarct volume was measured using magnetic resonance imaging, and mice were monitored clinically throughout the whole experiment. At the end point, tissues were preserved for further analysis, comprising histology and immunologic investigations using flow cytometry.

Results—
We found significantly decreased survival in the middle cerebral artery occlusion microbiota-depleted mice when the antibiotic cocktail was stopped 3 days before surgery (compared with middle cerebral artery occlusion specific pathogen-free and sham-operated microbiota-depleted mice). Moreover, all microbiota-depleted animals in which antibiotic treatment was terminated developed severe acute colitis. This phenotype was rescued by continuous antibiotic treatment or colonization with specific pathogen-free microbiota before surgery. Further, infarct volumes on day one did not differ between any of the experimental groups.

Conclusions—
Conventional microbiota ensures intestinal protection in the mouse model of experimental stroke and prevents development of acute and severe colitis in microbiota-depleted mice not given antibiotic protection after cerebral ischemia. Our experiments raise the clinically important question as to whether microbial colonization or specific microbiota are crucial for stroke outcome.
Dzieło sztuki na granicy przeszłości i przyszłości. Historia i patriotyzm w sztuce nieprofesjonalnej
Authors: Jarysz Aleksandra Weronika 
Published: April 2016

A work of art – a link between the present and the past. History and patriotism in non-professional art In her article, the author discusses art of non-professional artists who shape the national identity in an original way. In the former professional art, the works which illustrated and uplifted history were very popular. This phenomenon is still present among folk, naive, intuitive artists, generally speaking – non-professionals. The work of their hands and imagination is a tool serving the purpose of national values and ideas, and is sometimes the basis for broader considerations on the human condition. They balance between historical facts and ahistorical generalities. The martyrdom of the Polish nation with emphasis on the events of WWII has been inspiring artists, stimulating their imagination and artistic creation. Therefore numerous ‘monuments of patriotic art’ can be found in the wood sculpture, ceramics, painting, and glass painting works from the art collection of the Toruń Maria Znamierowska-Prüfferowa Ethnographic Museum. Dzieło sztuki na granicy przeszłości i przyszłości. Historia i patriotyzm w sztuce nieprofesjonalnejW swoim artykule autorka prezentuje sztukę twórców nieprofesjonalnych, którzy w sposób oryginalny kształtują tożsamość narodową. W dawnej sztuce profesjonalnej dzieła, które ilustrowały i uwznioślały historię były bardzo popularne. To zjawisko jest nadal aktualne wśród twórców ludowych, naiwnych, intuicyjnych, ogólnie nazywając – nieprofesjonalnych. Dzieło ich rąk i wyobraźni jest narzędziem w służbie wartości i idei narodowych, a niekiedy stanowi podstawę do szerszych rozważań nad kondycją człowieka. Balansują oni między konkretem historycznym a ahistoryczną ogólnością. Martyrologia narodu polskiego z naciskiem na wydarzenia II wojny światowej inspirowała i inspiruje twórców, pobudza ich wyobraźnię i zmusza do twórczej kreacji. Stąd też zarówno w rzeźbie w drewnie, w ceramice, na obrazach, w malarstwie na szkle, w zbiorach sztuki toruńskiego Muzeum Etnograficznego im. Marii Znamierowskiej-Prűfferowej możemy odnaleźć bogatą reprezentację „pomników sztuki patriotyzmu”.
Branding Grenlandii formą ekspresji tożsamości narodowej?
Authors: Bartnik-Światek Dominika 
Published: April 2016

Branding Greenland as a form of expression of national identity?In the times of globalisation there is a tendency for countries to differentiate from others. More and more governments decide to launch professional nation branding campaigns in order to communicate to a broad public what a particular country has to offer as well as what values and images it wants to be associated with. Greenland is an example of a country that after a long period of colonisation and establishing self-government, in 2009 began to redefine its identity and reveal it to the world. A branding campaign has been implemented to communicate a newly defined image of Greenland. This campaign has been carried out using mainly social media and the tools that the Internet has to offer. The aim of this paper is to explore the concept of nation branding and to define the relation between nation branding and national identity. The purpose is also to analyse what images of Greenland as a brand are presented by “Pioneering nation” campaign. Branding Grenlandii formą ekspresji tożsamości narodowej?W czasach globalizacji poszczególne państwa starają się wyróżnić na tle innych państw. Coraz więcej rządów decyduje się na przeprowadzenie profesjonalnych kampanii brandingowych, po to by podkreślić swoją wyjątkowość oraz to, że mają dużo do zaoferowania. Grenlandia to przykład państwa, które po długim okresie skolonizowania i po uzyskaniu autonomii w 2009 roku, zaczęło na nowo definiować swoją tożsamość i komunikować ją światu. W tym celu wdrożona została kampania, która wykorzystywała głównie media społecznościowe oraz inne narzędzia, które zapewnia internet. Celem niniejszego artykułu jest zbadanie zależności między brandingiem narodowym a tożsamością narodową, jak też analiza obrazu Grenlandii jako marki konstruowanej w kampanii „Pioneering nation”.
Polyurethane one-component foam formulation optimization for low free isocianate monomer content
Authors: Marques Ana C , Dias Helena , Matos Sandro , Sargaço Bruno , Simoes Ricardo , De Schrijver Aster , Bordado João C 
Published: April 2016

Recent changes in legislation have forced one-component foam producers to drop the amount of free monomeric isocyanate in their polyurethane systems. Also, it is required that commercial polyurethane aerosol cans exhibit at least one year of shelf life and polyurethane foams must be classified as B2 on the fire testing following DIN 4102. This paper reports on a systematic optimization study of polyurethane formulations dedicated to address these current industry requirements. A one-component foam system exhibiting simultaneously all of these parameters was achieved by reacting conventional diols, a relatively low-molecular weight monol (2-ethylhexanol), a flame retardant high-molecular weight monol (tris(bromoneopentyl)alcohol), a methylene diphenyl diisocyanate-based prepolymer (GreenAdduct 13), and a small amount of 2,4′-toluene diisocyanate. The use of monols allows producing prepolymers with low free methylene diphenyl diisocyanate by preventing chain extension and, therefore, avoiding extreme viscosity build-up. Toluene diisocyanate also promotes a lower viscosity inside the aerosol can, which enables the use of high enough quantities of high-molecular weight flame retardant monol to achieve a B2 fire test classification.