bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-Priming Smoothened Inhibitor Enhances Deposition and Efficacy of Cytotoxic Nanoparticles in a Pancreatic Cancer Model
Authors: Roy Chaudhuri Tista , Straubinger Ninfa L. , Pitoniak Rosemarie F. , Hylander Bonnie L. , Repasky Elizabeth A. , Ma Wen Wee , Straubinger Robert M. 
Published: October 2015

Abstract
Most pancreatic adenocarcinoma patients present with unresectable disease and benefit little from chemotherapy. Poor tumor perfusion and vascular permeability limit drug deposition. Previous work showed that Smoothened inhibitors of hedgehog signaling (sHHI) promote neovascularization in spontaneous mouse models of pancreatic cancer (PaCA) and enhance tumor permeability to low-molecular weight compounds. Here, we tested the hypothesis that sHHI can enhance tumor deposition and efficacy of drug-containing nanoparticles consisting of 80 to 100 nm sterically-stabilized liposomes (SSL) containing doxorubicin (SSL-DXR). SCID mice bearing low-passage patient-derived PaCA xenografts (PDX) were pretreated p.o. for 10 days with 40 mg/kg/d NVP-LDE225 (erismodegib), followed by i.v. SSL-DXR. Microvessel density, permeability, perfusion, and morphology were compared with untreated controls, as was SSL deposition and therapeutic efficacy. The sHHI alone affected tumor growth minimally, but markedly increased extravasation of nanoparticles into adenocarcinoma cell–enriched regions of the tumor. Immunostaining showed that sHHI treatment decreased pericyte coverage (α-SMA+) of CD31+ vascular endothelium structures, and increased the abundance of endothelium-poor (CD31−) basement membrane structures (collagen IV+), suggesting increased immature microvessels. SSL-DXR (15 mg/kg) administered after sHHI pretreatment arrested tumor volume progression and decreased tumor perfusion/permeability, suggesting an initial vascular pruning response. Compared with controls, one cycle of 10-day sHHI pretreatment followed by 6 mg/kg SSL-DXR doubled median tumor progression time. Three cycles of treatment with sHHI and SSL-DXR, with a 10-day between-cycle drug holiday, nearly tripled median tumor progression time. Based upon these data, short-term sHHI treatment sequenced with nanoparticulate drug carriers constitutes a potential strategy to enhance efficacy of pancreatic cancer therapy. Mol Cancer Ther; 15(1); 84–93. ©2015 AACR.
HMGB1-Driven Inflammation and Intimal Hyperplasia After Arterial Injury Involves Cell-Specific Actions Mediated by TLR4
Authors: Cai Jingjing , Yuan Hong , Wang Qingde , Yang Huan , Al-Abed Yousef , Hua Zhong , Wang Jiemei , Chen Dandan , Wu Jinze , Lu Ben , Pribis John P. , Jiang Weihong , Yang Kan , Hackam David J. , Tracey Kevin J. , Billiar Timothy R. , Chen Alex F. 
Published: October 2015

Objective—
Endoluminal vascular interventions such as angioplasty initiate a sterile inflammatory response resulting from local tissue damage. This response drives the development of intimal hyperplasia (IH) that, in turn, can lead to arterial occlusion. We hypothesized that the ubiquitous nuclear protein and damage-associated molecular pattern molecule, high-mobility group box 1 (HMGB1), is one of the endogenous mediators that activates processes leading to IH after endoluminal injury to the arterial wall. The aim of this study is to investigate whether approaches that reduce the levels of HMGB1 or inhibit its activity suppresses IH after arterial injury.

Approach and Results—
Here, we show that HMGB1 regulates IH in a mouse carotid wire injury model. Induced genetic deletion or neutralization of HMGB1 prevents IH, monocyte recruitment, and smooth muscle cell growth factor production after endoluminal carotid artery injury. A specific inhibitor of HMGB1 myeloid differentiation factor 2–toll-like receptor 4 (TLR4) interaction, P5779, also significantly inhibits IH. HMGB1 deletion is mimicked in this model by global deletion of TLR4 and partially replicated by myeloid-specific deletion of TLR4 but not TLR2 or receptor for advanced glycation endproducts deletion. The specific HMGB1 isoform known to activate TLR4 signaling (disulfide HMGB1) stimulates smooth muscle cell to migrate and produce monocyte chemotactic protein 1/CCL2) via TLR4. Macrophages produce smooth muscle cell mitogens in response to disulfide HMGB1 also in a TLR4/myeloid differentiation primary response gene (88)/Trif-dependent manner.

Conclusions—
These findings place HMGB1 and its receptor, TLR4 as critical regulators of the events that drive the inflammation leading to IH after endoluminal arterial injury and identify this pathway as a possible therapeutic target to limit IH to attenuate damage-associated molecular pattern molecule–mediated vascular inflammatory responses.
Use of Antiplatelet Agents Is Associated With Intraplaque Hemorrhage on Carotid Magnetic Resonance Imaging
Authors: Liem Madieke I. , Schreuder Floris H.B.M. , van Dijk Anouk C. , de Rotte Alexandra A.J. , Truijman Martine T.B. , Daemen Mat J.A.P. , van der Steen Anton F.W. , Hendrikse Jeroen , Nederveen Aart J. , van der Lugt Aad , Kooi M. Eline , Nederkoorn Paul J. ,   Participating centers:, Schreuder A.H.C.M.L. , Koudstaal P.J. , Limburg M. , Weisfelt M. , Korten A.G.G.C. , Saxena R. , van Oostenbrugge R.J. , Mess W.H. , van Orshoven N.P. , Tromp S.C. , Bakker S.L.M. , Kruyt N.D. , de Kruijk J.R. , de Borst G.J. , Meems B.J. , Verhey J.C.B. , Wijnhoud A.D. 
Published: October 2015

Background and Purpose—
Intraplaque hemorrhage (IPH), visualized by magnetic resonance imaging, has shown to be associated with the risk of stroke in patients with carotid artery stenosis. The mechanisms of IPH development are poorly understood. In this study, we investigated the association between clinical patient characteristics and carotid IPH on high-resolution magnetic resonance imaging.

Methods—
Patients participate in the Plaque at Risk (PARISK) study. This prospective, multicenter cohort study included patients with recent amaurosis fugax, hemispheric transient ischemic attack, or nondisabling stroke in the internal carotid artery territory and an ipsilateral carotid stenosis of <70%, who were not scheduled for carotid revascularization procedure. One hundred patients, recruited between 2010 and 2012, underwent a 3-T high-resolution carotid magnetic resonance imaging. We documented clinical patient characteristics and performed multivariable logistic regression analysis to investigate their association with IPH.

Results—
IPH was observed in 45 patients (45%) in 1 or both carotid arteries. Male sex and the use of antiplatelet agents before the index event were associated with IPH in univariable analysis. In a multivariable analysis, only previous use of antiplatelet agents was significantly associated with IPH (odds ratio, 2.71; 95% confidence interval, 1.12–6.61). Risk factors of atherosclerotic arterial disease, including a history of symptomatic arterial diseases, were not associated with IPH.

Conclusions—
In this cohort of 100 patients with recently symptomatic carotid stenosis, the previous use of antiplatelet agents is associated with carotid IPH on magnetic resonance imaging. Antiplatelet therapy may increase the risk of IPH, but our findings need to be confirmed in larger patient cohorts. The implications for risk stratification remain to be determined.
The Naval Research Laboratory Ocean Surface Flux (NFLUX) System: Satellite-Based Turbulent Heat Flux Products
Authors: May Jackie C. , Rowley Clark , Van de Voorde Neil 
Published: October 2015

AbstractThe Naval Research Laboratory ocean surface flux (NFLUX) system provides satellite-based surface state parameter and surface turbulent heat flux fields operationally over the global ocean. These products are presented as an alternative to using numerical weather prediction models—namely, the U.S. Navy Global Environmental Model (NAVGEM)—to provide the surface forcing to operational ocean models. NFLUX utilizes satellite sensor data records from the Special Sensor Microwave Imager/Sounder (SSMIS), the Advanced Microwave Sounding Unit-A (AMSU-A), the Advanced Technology Microwave Sounder (ATMS), and the Advanced Microwave Scanning Radiometer-2 (AMSR-2) sensors as well as satellite environmental data records from WindSat, the Advanced Scatterometers (ASCAT), and the Oceansat scatterometer (OSCAT). The satellite data are processed and translated into estimates of surface specific humidity, surface air temperature, and 10-m scalar wind speed. Two-dimensional variational analyses of quality-controlled satellite data, in combination with an atmospheric-model field, form global gridded surface state parameter fields. Bulk formulas are then applied to produce surface turbulent heat flux fields. Six-hourly analysis fields are created from 1 January 2013 through 31 December 2013. These fields are examined and validated against in situ data and NAVGEM. Overall, the NFLUX fields have a smaller bias, lower or similar root-mean-square error, and increased skill score relative to those of NAVGEM.
Symmetric Instability, Inertial Oscillations, and Turbulence at the Gulf Stream Front
Authors: Thomas Leif N. , Taylor John R. , D’Asaro Eric A. , Lee Craig M. , Klymak Jody M. , Shcherbina Andrey 
Published: October 2015

AbstractThe passage of a winter storm over the Gulf Stream observed with a Lagrangian float and hydrographic and velocity surveys provided a unique opportunity to study how the interaction of inertial oscillations, the front, and symmetric instability (SI) shapes the stratification, shear, and turbulence in the upper ocean under unsteady forcing. During the storm, the rapid rise and rotation of the winds excited inertial motions. Acting on the front, these sheared motions modulate the stratification in the surface boundary layer. At the same time, cooling and downfront winds generated a symmetrically unstable flow. The observed turbulent kinetic energy dissipation exceeded what could be attributed to atmospheric forcing, implying SI drew energy from the front. The peak excess dissipation, which occurred just prior to a minimum in stratification, surpassed that predicted for steady SI turbulence, suggesting the importance of unsteady dynamics. The measurements are interpreted using a large-eddy simulation (LES) and a stability analysis configured with parameters taken from the observations. The stability analysis illustrates how SI more efficiently extracts energy from a front via shear production during periods when inertial motions reduce stratification. Diagnostics of the energetics of SI from the LES highlight the temporal variability in shear production but also demonstrate that the time-averaged energy balance is consistent with a theoretical scaling that has previously been tested only for steady forcing. As the storm passed and the winds and cooling subsided, the boundary layer restratified and the thermal wind balance was reestablished in a manner reminiscent of geostrophic adjustment.
Increased serum IgM, immunodeficiency, and autoimmunity: A clinical series
Authors: Picchianti Diamanti Andrea , Rosado M Manuela , Scarsella Marco , Ceccarelli Sara , Laganà Bruno , D’Amelio Raffaele , Carsetti Rita 
Published: November 2015

Background: Primary immunodeficiencies (PIDs) are generally characterized by recurrent infections; however they may be complicated by other clinical disorders such as allergy, autoimmunity, and lymphoproliferation. In particular, autoimmunity may be the first manifestation of the disease in patients with low serum immunoglobulins (Ig) levels. Here we describe a group of patients that share features of immunodeficiency and autoimmunity. Materials and Methods: All patients went through a complete T and B cell subset characterization and a B cell function analysis in the peripheral blood by flow-cytometry. B cell proliferation and plasma cell differentiation was measured, in vitro, after CpG stimulation for 7 days as previously described. Semi-quantitative PCR analysis for AID and UNG expression as well as serum levels of BAFF were carried out in order to better define the diagnosis. Results: Immunological and molecular analysis did not lead to the identification of known molecular defect typical of Hyper IgM syndrome. A comparative study of the peripheral blood B cell subsets between patients and healthy donors showed that in patients with autoimmune manifestations all circulating B cells expressed high amounts of surface IgM. Conclusions: These results suggest that the increased IgM expression on circulating B cells, reflecting B cell activation, might identify a clinical condition characterized by hyper IgM serum levels of unknown molecular defects, associated with susceptibility to infections and autoimmunity.
Rat bone marrow-derived dendritic cells generated with GM-CSF/IL-4 or FLT3L exhibit distinct phenotypical and functional characteristics
Authors: N’diaye Marie , Warnecke Andreas , Flytzani Sevasti , Abdelmagid Nada , Ruhrmann Sabrina , Olsson Tomas , Jagodic Maja , Harris Robert A , Guerreiro-Cacais Andre Ortlieb 
Published: October 2015

Abstract
Dendritic cells are professional APCs that play a central role in the initiation of immune responses. The limited ex vivo availability of dendritic cells inspires the widespread use of bone marrow-derived dendritic cells as an alternative in research. However, the functional characteristics of bone marrow-derived dendritic cells are incompletely understood. Therefore, we compared functional and phenotypic characteristics of rat bone marrow-derived dendritic cells generated with GM-CSF/IL-4 or FLT3 ligand bone marrow-derived dendritic cells. A comparison of surface markers revealed that FLT3 ligand-bone marrow-derived dendritic cells expressed signal regulatory protein α, CD103, and CD4 and baseline levels of MHC class II, CD40, and CD86, which were highly up-regulated upon stimulation. Conversely, GM-CSF/IL-4-bone marrow-derived dendritic cells constitutively expressed signal regulatory protein α, CD11c, and CD11b but only mildly up-regulated MHC class II, CD40, or CD86 following stimulation. Expression of dendritic cell-associated core transcripts was restricted to FLT3 ligand-bone marrow-derived dendritic cells. GM-CSF/IL-4-bone marrow-derived dendritic cells were superior at phagocytosis but were outperformed by FLT3 ligand-bone marrow-derived dendritic cells at antigen presentation and T cell stimulation in vitro. Stimulated GM-CSF/IL-4-bone marrow-derived dendritic cells secreted more TNF, CCL5, CCL20, and NO, whereas FLT3 ligand-bone marrow-derived dendritic cells secreted more IL-6 and IL-12. Finally, whereas GM-CSF/IL-4-bone marrow-derived dendritic cell culture supernatants added to resting T cell cultures promoted forkhead box p3+ regulatory T cell populations, FLT3 ligand-bone marrow-derived dendritic cell culture supernatants drove Th17 differentiation. We conclude that rat GM-CSF/IL-4-bone marrow-derived dendritic cells and FLT3 ligand-bone marrow-derived dendritic cells are functionally distinct. Our data support the current rationale that FLT3 ligand-bone marrow-derived dendritic cells mostly resemble classic dendritic cells but comprise additional minor subpopulations, whereas GM-CSF/IL-4-bone marrow-derived dendritic cells resemble monocyte-derived inflammatory dendritic cells (iNOS-positive monocyte-derived cells).
The inflammasome NLRP3 plays a protective role against a viral immunopathological lesion
Authors: Gimenez Fernanda , Bhela Siddheshvar , Dogra Pranay , Harvey Lorena , Varanasi Siva Karthik , Jaggi Ujjaldeep , Rouse Barry T 
Published: October 2015

Abstract
Herpes simplex 1 infection of the eye can cause blindness with lesions in the corneal stroma largely attributable to inflammatory events that include components of both adaptive and innate immunity. Several innate immune responses are triggered by herpes simplex 1, but it is unclear how such innate events relate to the subsequent development of stromal keratitis. In this study, we compared the outcome of herpes simplex 1 ocular infection in mice unable to express NLRP3 because of gene knockout (NLRP3−/−) to that of wild-type mice. The NLRP3−/− mice developed more-severe and earlier stromal keratitis lesions and had higher angiogenesis scores than did infected wild-type animals. In addition, NLRP3−/− mice generated an increased early immune response with heightened chemokines and cytokines, including interleukin-1β and interleukin-18, and elevated recruitment of neutrophils. Increased numbers of CD4+ T cells were seen at later stages of the disease in NLRP3−/− animals. Reduction in neutrophils prevented early onset of the disease in NLRP3−/− animals and lowered levels of bioactive interleukin-1β but did not lower bioactive interleukin-18. In conclusion, our results indicate that NLRP3 has a regulatory and beneficial role in herpetic stromal keratitis pathogenesis.
Recruited monocytes modulate malaria-induced lung injury through CD36-mediated clearance of sequestered infected erythrocytes
Authors: Lagassé H A Daniel , Anidi Ifeanyi U , Craig John M , Limjunyawong Nathachit , Poupore Amy K , Mitzner Wayne , Scott Alan L 
Published: October 2015

Abstract
Pulmonary complications occur in a significant percentage of adults and children during the course of severe malaria. The cellular and molecular innate immune mechanisms that limit the extent of pulmonary inflammation and preserve lung function during severe Plasmodium infections remain unclear. In particular, the contributions to pulmonary complications by parasitized erythrocyte sequestration and subsequent clearance from the lung microvasculature by immune cells have not been clearly defined. We used the Plasmodium berghei ANKA-C57BL/6 mouse model of severe malaria to investigate the mechanisms governing the nature and extent of malaria-associated lung injury. We have demonstrated that sequestration of infected erythrocytes on postcapillary endothelial surfaces results in acute lung injury and the rapid recruitment of CCR2+CD11b+Ly6Chi monocytes from the circulation. These recruited cells remain in the lungs as monocyte-derived macrophages and are instrumental in the phagocytic clearance of adherent Plasmodium berghei-infected erythrocytes. In contrast, alveolar macrophages do not play a significant role in the clearance of malaria-infected cells. Furthermore, the results obtained from Ccr2−/−, Cd36−/−, and CD36 bone marrow chimeric mice showed that sequestration in the absence of CD36-mediated phagocytic clearance by monocytes leads to exaggerated lung pathologic features. In summary, our data indicate that the intensity of malaria-induced lung pathologic features is proportional to the steady-state levels of Plasmodium-infected erythrocytes adhering to the pulmonary vasculature. Moreover, the present work has defined a major role of recruited monocytes in clearing infected erythrocytes from the pulmonary interstitium, thus minimizing lung damage.
Kondratieff Cycles in Developed Economies
Authors: Басовский  , Basovskiy Leonid 
Published: October 2015

The objective of this paper is to identify Kondratieff cycles in the developed
economies. Time series spectral analysis of real per capita GDP of the developed
countries and Brazil is performed. Also studied are time series for the period
from the 19th century to 2008. As a result Kondratieff cycles (waves) are found
out in the economic dynamics of all the countries surveyed, except for Finland.
The power of Kondratieff cycles in the economic dynamics is estimated to fall in
the range of 23 to 61% of the total power of all economic cycles with the periods
of 2 to 100 years. The Kondratieff cycles can be found in a number of economies
in the period of 19th — 20th centuries. It allows to distinguish the three moderntime
Kondratieff waves in the said countries and to evaluate productivity of the
fourth, the fifth and the sixth technological modes in their economies. However
in a number of countries the Kondratieff cycles show up only in the 20th century.
So for these countries only one or two modern Kondratieff waves can be clearly
identified, making it possible to evaluate productivity of only the fifth and the
sixth technological modes in their economies.
Cluster Analysis of Human Capital Development in a Selected Region (the Example of the Central Federal District of the RF)
Authors: Комарова  , Komarova Anna 
Published: October 2015

This paper proposes a set of indicators to evaluate the level of the human capital
development in a given region. Provided are the results of cluster analysis of
several regions within the Central Federal District in terms of development of
human capital. Identified are the key areas of human capital development for
clusters of regions composing the Central Federal District of the RF.
Cumulative Growth in User-Generated Content Production: Evidence from Wikipedia
Authors: Aaltonen Aleksi , Seiler Stephan 
Published: October 2015

Open content production platforms typically allow users to gradually create content and react to previous contributions. Using detailed edit-level data across a large number of Wikipedia articles, we investigate how past edits shape current editing activity. We find that cumulative past contributions, embodied by the current article length, lead to significantly more editing activity, while controlling for a host of factors such as popularity of the topic and platform-level growth trends. The magnitude of the effect is large; content growth over an eight-year period would have been 45% lower in its absence. Our findings suggest that other open content production environments are likely to also benefit from similar cumulative growth effects. In the presence of such effects, managerial interventions that increase content are amplified because they trigger further contributions. Data, as supplemental material, are available at http://dx.doi.org/10.1287/mnsc.2015.2253 . This paper was accepted by Pradeep Chintagunta, marketing.
Development formulation of crafts weaving batik ikat East Java: Strategic block and interconnection
Authors: Tranggono Didiek , Dwiridhotjahjono Jojok , Indira Aryani Maria , Rasyidah Resa 
Published: October 2015

Batik tenun ikat has been the traditional legacy in some areas of East Java. This research is based on the findings and analysis on batik tenun ikat in Kediri and Lamongan. The data were collected from observation, in depth-interview, and printed documentations. The SWOT analysis showed that batik tenun ikat in Kediri and Lamongan got the position number two (2). Thus, the priority strategies are 1) extending partnership, 2) diversification of products and 3) e-marketing and integrated one-web destination. In applying those strategies the need of implementation of strategic block and interconnection is inevitable. Strategic blocs and interconnection would deeply increased the connectivity among the actors and hence between the economic elements.
The impact of earnings-announcement timing on technical analysis signal: The case of Indonesia
Authors: Sulistiawan Dedhy 
Published: October 2015

This study discusses technical analysis signal and earnings-announcements timing. Technical analysis signal is used to capture price reaction around earnings announcement dates. Technical analysis is selected because it is potential for competing information as fundamental information in emerging market, especially in Indonesian stock market. The longer reporting lag will result in a tendency of bigger information leakage which makes price reaction before announcements stronger. That reaction produces a reliable technical analysis signal. By using Indonesian stock market data, the results show that (1) technical analysis signal generates bigger (lower) return for late (earlier) reporting, and (2) reporting lag positively affects the performance of technical analysis signal that emerge before annual earnings announcements. These findings indicate a tendency of bigger information leakage for companies that delay earnings announcements. It contributes to building a bridge between technical analysis and earnings-announcement timing studies.