bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pulmonary Alveolar Macrophages Contribute to the Premetastatic Niche by Suppressing Antitumor T Cell Responses in the Lungs
Authors: Sharma Sharad K. , Chintala Navin K. , Vadrevu Surya Kumari , Patel Jalpa , Karbowniczek Magdalena , Markiewski Maciej M. 
Published: April 2015

Abstract
In contrast to tumor-associated macrophages, myeloid-derived suppressor cells, or inflammatory monocytes, functions of tissue resident macrophages, including alveolar macrophages (AM), in cancer were not well studied. Using a mouse model of breast cancer, we show that AM promote cancer metastasis to the lungs by suppressing antitumor T cells in this organ. AM accumulated in the premetastatic lungs through complement C5a receptor–mediated proliferation but not through recruitment from the circulation. AM preconditioned by breast tumors inhibited Th1 and favored generation of Th2 cells that had lower tumoricidal activity than Th1 cells. In addition, AM reduced the number and maturation of lung dendritic cells by regulating TGF-β in the lung environment. Depletion of AM reversed immunosuppression imposed by these cells and strengthened local Th1 responses, which significantly reduced lung metastatic burden. C5a receptor deficiency, which also lessens myeloid-derived suppressor cells in the premetastatic niche, synergized with the depletion of AM in preventing metastasis, leading to protection of mice from lung metastases. This study identifies AM as a new component of the premetastatic niche, which is harnessed by tumors to impose immunosuppression, and as a new target for cancer immunotherapies to eliminate or reduce metastasis. Because the lungs are the most common target for hematogenous metastasis, this research offers a plausible explanation for susceptibility of the lungs to cancer metastasis.
Early Effector Cells Survive the Contraction Phase in Malaria Infection and Generate Both Central and Effector Memory T Cells
Authors: Opata Michael M. , Carpio Victor H. , Ibitokou Samad A. , Dillon Brian E. , Obiero Joshua M. , Stephens Robin 
Published: April 2015

Abstract
CD4 T cells orchestrate immunity against blood-stage malaria. However, a major challenge in designing vaccines to the disease is poor understanding of the requirements for the generation of protective memory T cells (Tmem) from responding effector T cells (Teff) in chronic parasite infection. In this study, we use a transgenic mouse model with T cells specific for the merozoite surface protein (MSP)-1 of Plasmodium chabaudi to show that activated T cells generate three distinct Teff subsets with progressive activation phenotypes. The earliest observed Teff subsets (CD127−CD62LhiCD27+) are less divided than CD62Llo Teff and express memory genes. Intermediate (CD62LloCD27+) effector subsets include the most multicytokine-producing T cells, whereas fully activated (CD62LloCD27−) late effector cells have a terminal Teff phenotype (PD-1+, Fashi, AnnexinV+). We show that although IL-2 promotes expansion, it actually slows terminal effector differentiation. Using adoptive transfer, we show that only early Teff survive the contraction phase and generate the terminal late Teff subsets, whereas in uninfected recipients, they become both central and effector Tmem. Furthermore, we show that progression toward full Teff activation is promoted by increased duration of infection, which in the long-term promotes Tem differentiation. Therefore, we have defined markers of progressive activation of CD4 Teff at the peak of malaria infection, including a subset that survives the contraction phase to make Tmem, and show that Ag and cytokine levels during CD4 T cell expansion influence the proportion of activated cells that can survive contraction and generate memory in malaria infection.
MijnBorne2030: evaluatie van een democratisch experiment
Authors: Denters Bas , Klok Pieter-Jan 
Published: April 2015

MyBorne2030: evaluation of a democratic experiment
This article is about one of the experiments in local democratic renewal: MyBorne2030 (in Dutch ‘MijnBorne2030’). The aim of the project was to develop a communal vision for Borne (a relatively small suburban municipality of 20.000 inhabitants in the East of the Netherlands) for the year 2030. A steering committee of 20 local organizations has worked out four scenarios on the basis of three building stones: an identity study, a research of societal trends and the formulation of ambitions. These four scenarios have been submitted to the citizens of Borne in a referendum. The scenario that has received the most votes (‘Dynamic villages’) is further elaborated in a new vison for the future called MyBorne2030. Institutionally the decision-making process in Borne can be described as a mixture of participative (deliberative), associative and direct (plebiscitary) democracy. The authors conclude that it was a successful experiment, that has produced broad support for the vision of Borne for the future and a solid basis for the implementation of this vision. Participants (as well as non-participants) think this approach can be repeated not only in Borne, but also in other municipalities. The authors add that this could also be the case for the level above of cooperating municipalities.
Dichotoom in dialoog? Lokale referenda in Nederland
Authors: van der Krieken Koen , de Graaf Laurens 
Published: April 2015

Dichotomous in dialogue? Local referenda in the Netherlands
This article is about local referenda in the Netherlands. Based on extensive empirical research the authors make clear how the local referendum in the Dutch democracy has developed not only in time and practice, but also how we can interpret the referendum theoretically. They show how in scientific literature, but also in practice, they are still looking for the meaning of the local referendum for Dutch local democracy. The authors also show that the practice of Dutch local referenda is searching, varied and in continuous development. Since 1906 193 local referenda are organized in the Netherlands. By far most referenda took place after the nineties of the last century. Local referenda are a local democratic ‘domain’, that will be explored in the Netherlands in the coming years. Last year a lot of attention has been given to the (local) referendum in the domain of legislation. The process of legislation has not been finished yet. The authors believe this offers an unique opportunity to share the available knowledge and experience about referenda and debate the adequate filling in and anchoring of the (local) referendum. This is a task for scientists, administrators and politicians alike.
Placental Mesenchymal Stromal Cells Rescue Ambulation in Ovine Myelomeningocele
Authors: Wang Aijun , Brown Erin G. , Lankford Lee , Keller Benjamin A. , Pivetti Christopher D. , Sitkin Nicole A. , Beattie Michael S. , Bresnahan Jacqueline C. , Farmer Diana L. 
Published: April 2015

Abstract

Myelomeningocele (MMC)—commonly known as spina bifida—is a congenital birth defect that causes lifelong paralysis, incontinence, musculoskeletal deformities, and severe cognitive disabilities. The recent landmark Management of Myelomeningocele Study (MOMS) demonstrated for the first time in humans that in utero surgical repair of the MMC defect improves lower limb motor function, suggesting a capacity for improved neurologic outcomes in this disorder. However, functional recovery was incomplete, and 58% of the treated children were unable to walk independently at 30 months of age. In the present study, we demonstrate that using early gestation human placenta-derived mesenchymal stromal cells (PMSCs) to augment in utero repair of MMC results in significant and consistent improvement in neurologic function at birth in the rigorous fetal ovine model of MMC. In vitro, human PMSCs express characteristic MSC markers and trilineage differentiation potential. Protein array assays and enzyme-linked immunosorbent assay show that PMSCs secrete a variety of immunomodulatory and angiogenic cytokines. Compared with adult bone marrow MSCs, PMSCs secrete significantly higher levels of brain-derived neurotrophic factor and hepatocyte growth factor, both of which have known neuroprotective capabilities. In vivo, functional and histopathologic analysis demonstrated that human PMSCs mediate a significant, clinically relevant improvement in motor function in MMC lambs and increase the preservation of large neurons within the spinal cord. These preclinical results in the well-established fetal ovine model of MMC provide promising early support for translating in utero stem cell therapy for MMC into clinical application for patients.

Significance
This study presents placenta-derived mesenchymal stromal cell (PMSC) treatment as a potential therapy for myelomeningocele (MMC). Application of PMSCs can augment current in utero surgical repair in the well-established and rigorously applied fetal lamb model of MMC. Treatment with human PMSCs significantly and dramatically improved neurologic function and preserved spinal cord neuron density in experimental animals. Sixty-seven percent of the PMSC-treated lambs were able to ambulate independently, with two exhibiting no motor deficits whatsoever. In contrast, none of the lambs treated with the vehicle alone were capable of ambulation. The locomotor rescue demonstrated in PMSC-treated lambs indicates great promise for future clinical trials to improve paralysis in children afflicted with MMC.
Stress and mass changes at a “wet” volcano: Example during the 2011–2012 volcanic unrest at Kawah Ijen volcano (Indonesia)
Authors: Caudron Corentin , Lecocq Thomas , Syahbana Devy K. , McCausland Wendy , Watlet Arnaud , Camelbeeck Thierry , Bernard Alain , Surono  
Published: April 2015

AbstractSince 2010, Kawah Ijen volcano has been equipped with seismometers, and its extremely acid volcanic lake has been monitored using temperature and leveling sensors, providing unprecedented time resolution of multiparametric data for an acidic volcanic lake. The nature of stress and mass changes of the volcano is studied by combining seismic analyses and volcanic lake measurements that were made during the strongest unrest ever recorded by the seismic network at Kawah Ijen. The distal VT earthquake swarm that occurred in May 2011 was the precursor of volcanic unrest in October 2011 that caused an increase in shallow earthquakes. The proximal VT earthquakes opened pathways for fluids to ascend by increasing the permeability of the rock matrix. The following months were characterized by two periods of strong heat and mass discharge into the lake and by the initiation of monochromatic tremor (MT) activity when steam/gases interacted with shallow portions of the aquifer. Significant seismic velocity variations, concurrent with water level rises in which water contained a large amount of steam/gas, were associated with the crises, that caused an although the unrest did not affect the shallow hydrothermal system at a large scale. Whereas shallow VT earthquakes likely reflect a magmatic intrusion, MT and relative seismic velocity changes are clearly associated with shallow hydrothermal processes. These results will facilitate the forecast of future crises.
Can we define an asymptotic value for the ice active surface site density for heterogeneous ice nucleation?
Authors: Niedermeier Dennis , Augustin‐Bauditz Stefanie , Hartmann Susan , Wex Heike , Ignatius Karoliina , Stratmann Frank 
Published: April 2015

AbstractThe immersion freezing behavior of droplets containing size‐segregated, monodisperse feldspar particles was investigated. For all particle sizes investigated, a leveling off of the frozen droplet fraction was observed reaching a plateau within the heterogeneous freezing temperature regime (T >− 38°C). The frozen fraction in the plateau region was proportional to the particle surface area. Based on these findings, an asymptotic value for ice active surface site density ns, which we named , could be determined for the investigated feldspar sample. The comparison of these results with those of other studies not only elucidates the general feasibility of determining such an asymptotic value but also shows that the value of strongly depends on the method of the particle surface area determination. However, such an asymptotic value might be an important input parameter for atmospheric modeling applications. At least it shows that care should be taken when ns is extrapolated to lower or higher temperature.
Fate of the Amazon River dissolved organic matter in the tropical Atlantic Ocean
Authors: Medeiros Patricia M. , Seidel Michael , Ward Nicholas D. , Carpenter Edward J. , Gomes Helga R. , Niggemann Jutta , Krusche Alex V. , Richey Jeffrey E. , Yager Patricia L. , Dittmar Thorsten 
Published: April 2015

AbstractConstraining the fate of dissolved organic matter (DOM) delivered by rivers is a key to understand the global carbon cycle, since DOM mineralization directly influences air‐sea CO2 exchange and multiple biogeochemical processes. The Amazon River exports large amounts of DOM, and yet the fate of this material in the ocean remains unclear. Here we investigate the molecular composition and transformations of DOM in the Amazon River‐ocean continuum using ultrahigh resolution mass spectrometry and geochemical and biological tracers. We show that there is a strong gradient in source and composition of DOM along the continuum, and that dilution of riverine DOM in the ocean is the dominant pattern of variability in the system. Alterations in DOM composition are observed in the plume associated with the addition of new organic compounds by phytoplankton and with bacterial and photochemical transformations. The relative importance of each of these drivers varies spatially and is modulated by seasonal variations in river discharge and ocean circulation. We further show that a large fraction (50–76%) of the Amazon River DOM is surprisingly stable in the coastal ocean. This results in a globally significant river plume with a strong terrigenous signature and in substantial export of terrestrially derived organic carbon from the continental margin, where it can be entrained in the large‐scale circulation and potentially contribute to the long‐term storage of terrigenous production and to the recalcitrant carbon pool found in the deep ocean.
Fractal particle size distribution of pulverized fault rocks as a function of distance from the fault core
Authors: Muto Jun , Nakatani Tsurugi , Nishikawa Osamu , Nagahama Hiroyuki 
Published: April 2015

AbstractThe size distributions of particle in pulverized rocks from the San Andreas fault and the Arima‐Takatsuki Tectonic Line were measured. The rocks are characterized by the development of opening mode fractures with an apparent lack of shear. Fragments in the rocks in both fault zones show a fractal size distribution down to the micron scale. Fractal dimensions, dependent on mineral type, decrease from 2.92 to 1.97 with increasing distance normal to the fault core. The fractal dimensions of the rocks are higher than those of both natural and experimentally created fault gouges measured in previous studies. Moreover, the dimensions are higher than the theoretically estimated upper fractal limit under confined comminution. Dimensions close to 3.0 have been reported in impact loading experiments. The observed characteristics indicate that pulverization is likely to have occurred by a dynamic stress pulse with instantaneous volumetric expansion, possibly during seismic rupture propagation similar to impact loading.
Role of dust direct radiative effect on the tropical rain belt over Middle East and North Africa: A high‐resolution AGCM study
Authors: Bangalath Hamza Kunhu , Stenchikov Georgiy 
Published: April 2015

AbstractTo investigate the influence of direct radiative effect of dust on the tropical summer rain belt across the Middle East and North Africa (MENA), the present study utilizes the high‐resolution capability of an Atmospheric General Circulation Model, the High‐Resolution Atmospheric Model. Ensembles of Atmospheric Model Intercomparison Project style simulations have been conducted with and without dust radiative impacts, to differentiate the influence of dust on the tropical rain belt. The analysis focuses on summer season. The results highlight the role of dust‐induced responses in global‐ and regional‐scale circulations in determining the strength and the latitudinal extent of the tropical rain belt. A significant response in the strength and position of the local Hadley circulation is predicted in response to meridionally asymmetric distribution of dust and the corresponding radiative effects. Significant responses are also found in regional circulation features such as African Easterly Jet and West African Monsoon circulation. Consistent with these dynamic responses at various scales, the tropical rain belt across MENA strengthens and shifts northward. Importantly, the summer precipitation over the semiarid strip south of Sahara, including Sahel, increases up to 20%. As this region is characterized by the “Sahel drought,” the predicted precipitation sensitivity to the dust loading over this region has a wide range of socioeconomic implications. Overall, the study demonstrates the extreme importance of incorporating dust radiative effects and the corresponding circulation responses at various scales, in the simulations and future projections of this region's climate.
Groundwater in the Earth's critical zone: Relevance to large‐scale patterns and processes
Authors: Fan Ying 
Published: April 2015

AbstractAlthough we have an intuitive understanding of the behavior and functions of groundwater in the Earth's critical zone at the scales of a column (atmosphere‐plant‐soil‐bedrock), along a toposequence (ridge to valley), and across a small catchment (up to third‐order streams), this paper attempts to assess the relevance of groundwater to understanding large‐scale patterns and processes such as represented in global climate and Earth system models. Through observation syntheses and conceptual models, evidence are presented that groundwater influence is globally prevalent, it forms an environmental gradient not fully captured by the climate, and it can profoundly shape critical zone evolution at continental to global scales. Four examples are used to illustrate these ideas: (1) groundwater as a water source for plants in rainless periods, (2) water table depth as a driver of plant rooting depth, (3) the accessibility of groundwater as an ecological niche separator, and (4) groundwater as the lower boundary of land drainage and a global driver of wetlands. The implications to understanding past and future global environmental change are briefly discussed, as well as critical discipline, scale, and data gaps that must be bridged in order for us to translate what we learn in the field at column, hillslope and catchment scales, to what we must predict at regional, continental, and global scales.
What does Medicare pay rhinologists? An analysis of Medicare payment data
Authors: Clair Brandon , Goyal Parul 
Published: April 2015

BackgroundInformation about charges and payments for physician services continues to be scrutinized. Recently, the Centers for Medicare and Medicaid Services (CMS) released data regarding Medicare charges and payments to all physicians for calendar year 2012. The purpose of this study was to investigate the variability and patterns in Medicare charges and payments among a large sample of rhinologists.MethodsCharge and payment data were obtained from publicly available CMS datasets (http://www.cms.gov). Data for all otolaryngologists and rhinology subsets were extracted. Charges, payments, fee multipliers, and total submitted claims were compared. Unequal variance 2‐tailed t tests were used for analysis.ResultsMean submitted charges for rhinologists were $291,464 compared to $211,209 for all otolaryngologists (p = 0.0014). Mean payments to rhinologists were $70,172 compared to $77,275 for all otolaryngologists (p = 0.24). Fees for services ranged from 1.33 to 14.29 times Medicare reimbursement rates (mean = 4.47). The fee multiplier was significantly higher for operating room–based codes compared to office‐based codes (9.43 vs 3.44, p < 0.001). Academic rhinologists submitted fewer claims and had a higher fee multiplier than private rhinologists (p < 0.001). Academic and private rhinologists had no difference in submitted charges (p = 0.28).ConclusionThe wide availability of Medicare payment information makes it important for physicians to understand how their individual data compares to that of their colleagues. Medicare payments to rhinologists were comparable to otolaryngologists as a whole. Charges for services commonly performed by rhinologists vary widely. Academic rhinologists submitted fewer claims than their private colleagues, but overall charges and payments were comparable between the 2 groups.
A pharmacogenetic study implicates SLC9a9 in multiple sclerosis disease activity
Authors: Esposito Federica , Sorosina Melissa , Ottoboni Linda , Lim Elaine T. , Replogle Joseph M. , Raj Towfique , Brambilla Paola , Liberatore Giuseppe , Guaschino Clara , Romeo Marzia , Pertel Thomas , Stankiewicz James M. , Martinelli Vittorio , Rodegher Mariaemma , Weiner Howard L. , Brassat David , Benoist Christophe , Patsopoulos Nikolaos A. , Comi Giancarlo , Elyaman Wassim , Martinelli Boneschi Filippo , De Jager Philip L. 
Published: April 2015

ObjectiveA proportion of multiple sclerosis (MS) patients experience disease activity despite treatment. The early identification of the most effective drug is critical to impact long‐term outcome and to move toward a personalized approach. The aim of the present study is to identify biomarkers for further clinical development and to yield insights into the pathophysiology of disease activity.MethodsWe performed a genome‐wide association study in interferon‐β (IFNβ)‐treated MS patients followed by validation in 3 independent cohorts. The role of the validated variant was examined in several RNA data sets, and the function of the presumed target gene was explored using an RNA interference approach in primary T cells in vitro.ResultsWe found an association between rs9828519G and nonresponse to IFNβ (pdiscovery = 4.43 × 10−8) and confirmed it in a meta‐analysis across 3 replication data sets (preplication = 7.78 × 10−4). Only 1 gene is found in the linkage disequilibrium block containing rs9828519: SLC9A9. Exploring the function of this gene, we see that SLC9A9 mRNA expression is diminished in MS subjects who are more likely to have relapses. Moreover, SLC9A9 knockdown in T cells in vitro leads an increase in expression of IFNγ, which is a proinflammatory molecule.InterpretationThis study identifies and validates the role of rs9828519, an intronic variant in SLC9A9, in IFNβ‐treated subjects, demonstrating a successful pharmacogenetic screen in MS. Functional characterization suggests that SLC9A9, an Na+‐H+ exchanger found in endosomes, appears to influence the differentiation of T cells to a proinflammatory fate and may have a broader role in MS disease activity, outside of IFNβ treatment. Ann Neurol 2015;78:115–127