bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNA methylation patterns in naïve CD4+ T cells identify epigenetic susceptibility loci for malar rash and discoid rash in systemic lupus erythematosus
Authors: Renauer Paul , Coit Patrick , Jeffries Matlock A , Merrill Joan T , McCune W Joseph , Maksimowicz-McKinnon Kathleen , Sawalha Amr H 
Published: September 2015

ObjectiveSystemic lupus erythematosus (SLE) is a complex autoimmune disease characterised by heterogeneous clinical manifestations, autoantibody production and epigenetic dysregulation in T cells. We sought to investigate the epigenetic contribution to the development of cutaneous manifestations in SLE.MethodsWe performed genome-wide DNA methylation analyses in patients with SLE stratified by a history of malar rash, discoid rash or neither cutaneous manifestation, and age, sex and ethnicity matched healthy controls. We characterised differentially methylated regions (DMRs) in naïve CD4+ T cells unique to each disease subset, and assessed functional relationships between DMRs using bioinformatic approaches.ResultsWe identified 36 and 37 unique DMRs that contribute to the epigenetic susceptibility to malar rash and discoid rash, respectively. These DMRs were primarily localised to genes mediating cell proliferation and apoptosis. Hypomethylation ofMIR886andTRIM69,and hypermethylation ofRNF39were specific to patients with SLE with a history of malar rash. Hypomethylation of the cytoskeleton-related geneRHOJwas specific to patients with SLE with a history of discoid rash. In addition, discoid rash-specific hypomethylated DMRs were found in genes involved in antigen-processing and presentation such asTAP1andPSMB8. Network analyses showed that DMRs in patients with SLE with but not without a history of cutaneous manifestations are associated with TAP-dependent processing and major histocompatibility-class I antigen cross-presentation (p=3.66×10−18in malar rash, and 3.67×10−13in discoid rash).ConclusionsWe characterised DNA methylation changes in naïve CD4+ T cells specific to malar rash and discoid rash in patients with SLE. These data suggest unique epigenetic susceptibility loci that predispose to or are associated with the development of cutaneous manifestations in SLE.
System design and new applications for atomic force microscope based on tunneling
Authors: Wang X. , Liu A. P. , Yang X. H. 
Published: September 2015

The design of atomic force microscopy (AFM) with high resolution is introduced in this paper. Mainly, we have developed the system design of the apparatus based on tunneling. AFM.IPC-208B, this kind of apparatus combines scanning tunnel microscopy (STM) and AFM availability, and its lens body with original frame enhances the capability of the machine. In order to analyze the performance of AFM.IPC-208B, as a new tool in the field of Life Science, we make use of the system to study natural mica and molecular protein structures of Cattle-insulin and human antibody immunoglobulin G (IgG) coupled with staphylococcus protein A (SPA). As the results of new applications, the resolution of AFM.IPC-208B is proved to be 0.1 nm, and these nanometer measurement results provide much valuable information for the study of small molecular proteins and HIV experiments.
Chapter 12 Eruptive frequency and volcanic hazards zonation in São Miguel Island, Azores
Authors: Gaspar J. L. , Guest J. E. , Queiroz G. , Pacheco J. , Pimentel A. , Gomes A. , Marques R. , Felpeto A. , Ferreira T. , Wallenstein N. 
Published: September 2015

Abstract

São Miguel Island comprises five active volcanic systems, including three central volcanoes with calderas and two basaltic fissure systems. Volcanic eruptions in São Miguel are of basaltic and trachytic nature (
s.l.
), including Hawaiian, Strombolian, sub-Plinian, Plinian and Vulcanian events, the more explosive ones frequently including hydromagmatic phases. Large Plinian eruptions are related to caldera-forming events that occurred in the past. With reference to the Fogo A stratigraphic marker, a total of 73 individual volcanic eruptions have been identified in the last 5 ka, giving a recurrence interval of 68.5 years. Taking into account that only six events have occurred in historical times, the recurrence interval increases to 95 years and, clearly, a future event is overdue because the most recent eruption occurred in 1652. It should be noted, however, that some volcanic eruptions in the past have occurred in clusters.

The eruptive frequencies of the last 5 ka of activity have been determined for all types of eruptions and related hazards, including lava flows, pyroclastic falls, pyroclastic density currents (PDCs) and lahars. The areas susceptible to volcanic products have been mapped and modelled under different eruptive conditions.
Chapter 13 Landslides on São Miguel Island (Azores): susceptibility analysis and validation of rupture zones using a bivariate GIS-based statistical approach
Authors: Marques R. , Amaral P. , Araújo I. , Gaspar J. L. , Zêzere J. L. 
Published: September 2015

Abstract
Since settlement of São Miguel Island in the middle of the fifteenth century, several destructive landslides have occurred. These have been triggered by various factors, of which rainfall is the most common. Between 1900 and 2008, based on extensive documentary evidence, 193 landslide events with socio-economic impact have been identified. These events have been responsible for 67 deaths, about 20 people have been seriously injured, and dozens of houses destroyed and people rendered homeless. In this chapter, the Information Value Method is used to produce a landslide rupture susceptibility map for São Miguel. Success and prediction rate curves (SRC and PRC) are computed and areas under the curve (AUC) calculated in order to not only support the results of modelling, but also assess the robustness of the suggested susceptibility algorithm. Twelve predisposing factors are used as independent variables and a total of 9890 landslide depletion areas are used as the dependent variable. The AUC for both the SRC and the PRC was 0.90. The methodology used for the construction of the susceptibility map was shown to be both accurate and reliable. The map is an important tool for land-use/emergency planning and for landslide risk mitigation.
Chapter 15 Diffuse soil emanations of radon and hazard implications at Furnas Volcano, São Miguel Island (Azores)
Authors: Silva C. , Viveiros F. , Ferreira T. , Gaspar J. L. , Allard P. 
Published: September 2015

Abstract

Furnas Caldera Volcanic Complex, São Miguel Island (Azores), last erupted in 1630 and is famous for its intense hydrothermal activity (i.e. fumarolic fields, thermal springs, cold CO
2
-rich mineral waters and diffuse CO
2
soil emanations), which directly affect the villages of Furnas and Ribeira Quente. Here we report the first systematic investigations and mapping of soil radon (
222
Rn) emanations in the Furnas Volcanic Complex, and we examine their potential health risks for local inhabitants.
222
Rn in volcanic soils (60 cm depth) was repeatedly measured between 2005 and 2010 using a portable solid-state alpha detector (RAD7, Durridge Company Inc.). Results reveal a local background of 8000 Bq m
−3
and several areas with anomalously high
222
Rn activity (up to
c.
400 000 Bq m
−3
), which coincide with advective or convective gas transport through volcanic structures and active fault zones. High
222
Rn radioactivity in Furnas and Ribeira Quente villages represents a risk to the population. Continuous monitoring performed during November and December 2005 in a house in Furnas shows indoor
222
Rn reaching 13 273 Bq m
−3
, two orders of magnitude greater than the reference level (150 Bq m
−3
), when the ventilation efficiency is reduced.
Chapter 18 Tectonic and volcanic deformation at São Miguel Island, Azores, observed by continuous GPS analysis 2008–13
Authors: Okada Jun , Sigmundsson Freysteinn , Ófeigsson Benedikt G. , Ferreira Teresa J. L. , Rodrigues Rita M. M. T. C. 
Published: September 2015

Abstract

We use a Global Positioning System (GPS) to unravel the complex geodynamics of the Azores Triple Junction where tectonic and volcanic activities coexist. The temporal analysis of densely distributed continuous GPS data on São Miguel for the period 2008–13 provides an improved understanding of interactions between present-day plate boundary kinematics and volcanic deformation. We find a high-strain-rate (0.28 ppm a
–1
) zone between Congro and Furnas, which accommodates about 50% of the Eurasian–Nubian plate spreading as predicted by the MORVEL plate angular velocity model. The seismic unrest of Fogo–Congro (2011–12) shows a strong similarity with the Matsushiro (Japan) earthquake swarm (1965–66) and the Campi Flegrei (Italy) volcanic unrest (1969–72 and 1982–85), in that an edifice-scale inflation associated with intense high-frequency earthquakes and inflation–deflation reversals coincided with a sharp drop in seismicity. We propose the following hypothesis for the Fogo unrest: (1) the primary inflation source beneath Fogo promotes lateral diffusion of fluids that is selectively guided by existing cracks/fissures formed from regional extension; (2) an influx of fluids increases pressure in cracks/fissures and generates lower-frequency earthquakes; and (3) discharge of fluids causes pressure decrease and dilatancy recovery (i.e. seismic quiescence).
Chapter 19 Hydrogeochemical characterization of mineral waters in São Miguel Island, Azores
Authors: Cruz J. V. , Freire P. , Costa A. , Fontiela J. , Cabral L. , Coutinho R. M. 
Published: September 2015

Abstract

A dataset on the chemical composition of mineral water discharges from São Miguel, 76 samples, depicts a large variability of chemical types and dissolved solids content. The distribution of the discharges shows an association with the three active Quaternary central volcanoes that dominate the geology of São Miguel, namely Furnas, Fogo and Sete Cidades, 74% of which are springs, 13% fumaroles, 12% wells and 1% hand-dug wells. Total dissolved solids (TDS) values are in the range of 159–20 957 mg l
−1
, discharge temperature varies from 15 to 99.5°C and waters are mainly strongly acid to slightly alkaline (pH ranging between 2.2 and 7.71). Springs discharge mainly from perched-water bodies, corresponding to Na-HCO
3
and Na-HCO
3
-Cl-type waters, with a composition influenced by absorption of CO
2
and mixing between meteoric water and boiling waters with a hydrothermal component. Instead the majority of the wells are distributed along the coast and depict chloride enrichment owing to mixture with seawater. The lower pH values are associated with boiling pools at Fogo Volcano with a SO
4
-dominated chemistry, resulting from steam-heating of shallow perched-water bodies.
Chapter 2 The structure of the Azores Triple Junction: implications for São Miguel Island
Authors: Miranda J. M. , Luis J. F. , Lourenço N. , Fernandes R. M. S. 
Published: September 2015

Abstract

To date, a lack of reliable morphological and geophysical data has been a major limitation to understanding the tectonic and magmatic processes that shape the Azores Triple Junction and the Terceira Rift. This situation has changed recently: for the first time both areas are covered by high-quality swath bathymetry surveys and marine magnetic data with GPS quality positioning. This provides a good description of the surface morphology, and also of magnetic chrons that give fundamental information for the timing of spreading processes in a geological time frame. There is also a large amount of data from GPS stations that provide accurate estimations of present-day velocities for most of the islands. It is shown that only two main rift systems can be found on the plateau, the older one matching the Princess Alice Basin, and the newer one matching Terceira Rift; the shift between the two probably occurs close to
c.
3 Ma. It is shown that extension is currently concentrated on the Terceira Rift, progressively attaching Graciosa and Terceira islands to Eurasia, while São Miguel is being strained by rifting. It is also shown that no right lateral strike-slip fault connects the Terceira Rift to the Mid-Atlantic Ridge.
Chapter 20 Permanent monitoring of soil CO
2
degassing at Furnas and Fogo volcanoes (São Miguel Island, Azores)
Authors: Viveiros F. , Ferreira T. , Silva C. , Vieira J. C. , Gaspar J. L. , Virgili G. , Amaral P. 
Published: September 2015

Abstract

Eight years of permanent soil CO
2
diffuse degassing monitoring at Furnas and Fogo volcanoes shows that several environmental variables may influence soil CO
2
flux to a different extent depending on the location. Stepwise multivariate regression analysis applied to the data acquired by the permanent flux stations installed on São Miguel showed that the monitored environmental variables may influence the gas flux in a proportion between 18 and 51%. The external variables that most significantly correlate with the soil CO
2
flux values for Fogo and Furnas volcanoes monitoring sites are the rainfall/soil water content with its effect on permeability; the barometric pressure pumping effect; the wind speed owing to the atmospheric air intrusion and the air temperature through the action of atmospheric tides. These variables are responsible not only for spike-like oscillations in CO
2
emission, but also for the long-term oscillations with higher and lower values registered usually during winter and summer months, respectively. Residual time-series, calculated using regression models, are compared with other geophysical and geochemical monitoring data in order to recognize changes that may be correlated with the volcanic/hydrothermal systems.
Chapter 21 Hydrogeology of São Miguel Island, Azores: a review
Authors: Coutinho R. , Fontiela J. , Freire P. , Cruz J. V. 
Published: September 2015

Abstract

Groundwater is the main source of water supply on São Miguel. Groundwater abstraction (25 hm
3
a
−1
) relies almost exclusively on springs discharging from perched aquifers. A total of 1100 springs (1.5 springs/km
2
) are located on São Miguel, mainly in the Água de Pau and the Furnas–Povoação groundwater bodies. Only 26 wells have been drilled, distributed principally in the west-central zone. Specific capacity ranges between 0.49 and 100 l (s m)
−1
(median=1.11 l (s m)
−1
), while transmissivity ranges between 5.98×10
−4
and 1.22×10
−1
m
2
s
−1
(median=1.35×10
−3
m
2
s
−1
). Groundwater is predominantly of the Na-Cl and Na-HCO
3
types and electrical conductivity in springs ranges from 36 to 440 μS cm
−1
(median=152 μS cm
−1
), which is lower than in wells (211–9670 μS cm
−1
; median=515 μS cm
−1
). These values result from seawater spray, a CO
2
soil contribution and limited dissolution of primary silicate minerals from volcanic rocks. In the case of wells, seawater intrusion may also influence electrical conductivity. One of the main problems in groundwater quality is total and faecal coliform microbial contamination. A pollution risk map constructed for São Miguel as a whole showed that risk in the majority of the groundwater bodies is only very low to moderate.
Chapter 3 Active tectonics in the central and eastern Azores islands along the Eurasia–Nubia boundary: a review
Authors: Madeira J. , Brum da Silveira A. , Hipólito A. , Carmo R. 
Published: September 2015

Abstract

The geodynamic setting of the Azores archipelago, straddling the triple junction between the North America, Eurasia and Nubia plates, is reflected in frequent volcanic and tectonic activity. A review of neotectonics is presented for the islands forming the central and eastern groups of the Azores (Faial, Pico, São Jorge, Graciosa, Terceira, São Miguel and Santa Maria). The geometry and kinematics of active faults displacing stratigraphic and geomorphological markers of Pleistocene and Holocene age are presented. Slip-rates were determined using the available ages for the displaced markers. Maximum expected moment magnitudes were estimated using empirical correlations between magnitude and fault length, fault area and maximum observed surface displacement during surface-rupturing palaeoearthquakes. Neotectonic parameters show that the faults are in most cases very to moderately active, with slip-rates usually ranging from a few tenths of millimetres to a few millimetres per year, while maximum expected magnitudes vary from M
w
6 to 7. These magnitudes are in agreement with the instrumental and historical seismic record in the region. Neotectonic data define a dextral transtensive stress regime acting on the region and contribute to characterizing the complexity of the geodynamic processes that dominate the western-most segment of the Eurasia–Nubia plate boundary.
Chapter 6 Volcano-tectonic structures of São Miguel Island, Azores
Authors: Carmo R. , Madeira J. , Ferreira T. , Queiroz G. , Hipólito A. 
Published: September 2015

Abstract
The Azores archipelago is located at the triple junction between the Eurasia, Nubia and North America lithospheric plates. São Miguel Island, situated at the southeastern part of the western segment of the Azores–Gibraltar Fracture Zone, presents an east–west elongated shape, comprising three quiescent central volcanoes with summit calderas linked by zones of fissure volcanism. The eastern part of the island is older and inactive. Active faulting is represented by prominent fault scarps that constitute important extensional structures, or by linear volcanic structures in fissural volcanic zones, with a dominant NW–SE to WNW–ESE trend. Although less frequent, there are also NNW–SSE to north–south, NE–SW and east–west faults, reflected by some volcanic alignments and linear segments of the drainage system and sea cliffs. The geometric and kinematic data are in agreement with that observed in the rest of the archipelago. However, at eastern São Miguel Island data indicate two distinct groups of conjugated faults characterized by three-dimensional strain: NW–SE to WNW–ESE normal dextral structures are conjugated with NNW–SSE normal left-lateral faults and NW–SE to WNW–ESE normal left-lateral faults are conjugated with NE–SW normal dextral structures, showing the presence of two different stress fields separated in time.
Chapter 7 Eruptive history and evolution of Sete Cidades Volcano, São Miguel Island, Azores
Authors: Queiroz G. , Gaspar J. L. , Guest J. E. , Gomes A. , Almeida M. H. 
Published: September 2015

Abstract
Sete Cidades is an active central volcano on the western part of São Miguel. The geological record reveals that subaerial activity started more than 250 ka ago. Stratigraphic units defined for Sete Cidades deposits reflect major events in the history of the volcano and are organized into two main groups: the Inferior Group and the Superior Group. Caldera formation resulted from three major paroxysmal events that occurred at about 36, 29 and 16 ka ago. Analysis of the eruptive history of Sete Cidades shows that effusive or moderately explosive eruptions, of Hawaiian and/or Strombolian styles, were located on the slopes of the central volcano. Conversely, trachytic explosive activity is mostly centred inside the caldera involving, in a first stage, predominantly Plinian and sub-Plinian phenomena, changing about 5 ka ago to a dominant hydromagmatic style. Trachytic effusive eruptions are represented by domes and associated lava flows that crop out in the inner caldera walls and on the western slopes of the volcano. Offshore submarine activity is represented by the historic Surtseyan eruptions of 1638 and 1811. In the last 5 ka Sete Cidades was the most active central volcano in the Azores with 17 explosive eruptions predominantly with hydromagmatic character.
Chapter 9 The volcanic history of Furnas Volcano, São Miguel, Azores
Authors: Guest J. E. , Pacheco J. M. , Cole P. D. , Duncan A. M. , Wallenstein N. , Queiroz G. , Gaspar J. L. , Ferreira T. 
Published: September 2015

Abstract

Furnas is the easternmost of the trachytic active central volcanoes of São Miguel. Unlike the other central volcanoes, Sete Cidades and Fogo, Furnas does not have a substantial edifice built up above sea-level. Although not as dominant as the other two volcanoes, Furnas does, however, have an edifice rising from the basal basaltic lavas exposed on the north coast to around 600 m asl on the northern rim of the main caldera. In common with Sete Cidades and Fogo, Furnas had major trachytic explosive eruptions in its volcanic history that emplaced welded ignimbrites. In the last 5 ka Furnas has had 10 moderately explosive trachytic eruptions of sub-Plinian character; two of these have taken place since the island was settled in the mid-fifteenth century. A future eruption of sub-Plinian magnitude is a major hazard posed by Furnas Volcano. Even when not in eruption, Furnas is a hazardous environment. Its fumarolic fields discharge high levels of CO
2
and concentrations in some area of Furnas village present a risk to health; the steep slopes and poorly consolidated volcanic materials are prone to landslides, in particular when triggered by earthquakes or following heavy rain, as was the case in 1997, when landslides caused severe damage and casualties in Ribeira Quente.
Molecular Pathways: Targeting the Stimulator of Interferon Genes (STING) in the Immunotherapy of Cancer
Authors: Corrales Leticia , Gajewski Thomas F. 
Published: September 2015

Abstract
Novel immunotherapy approaches are transforming the treatment of cancer, yet many patients remain refractory to these agents. One hypothesis is that immunotherapy fails because of a tumor microenvironment that fails to support recruitment of immune cells, including CD8+ T cells. Therefore, new approaches designed to initiate a de novo antitumor immune response from within the tumor microenvironment are being pursued. Recent evidence has indicated that spontaneous activation of the Stimulator of Interferon Genes (STING) pathway within tumor-resident dendritic cells leads to type I IFN production and adaptive immune responses against tumors. This pathway is activated in the presence of cytosolic DNA that is detected by the sensor cyclic GMP-AMP synthase (cGAS) and generates cyclic GMP-AMP (cGAMP), which binds and activates STING. As a therapeutic approach, intratumoral injection of STING agonists has demonstrated profound therapeutic effects in multiple mouse tumor models, including melanoma, colon, breast, prostate, and fibrosarcoma. Better characterization of the STING pathway in human tumor recognition, and the development of new pharmacologic approaches to engage this pathway within the tumor microenvironment in patients, are important areas for clinical translation. Clin Cancer Res; 21(21); 4774–9. ©2015 AACR.
Differential IKK/NF-κB Activity Is Mediated by TSC2 through mTORC1 in PTEN-Null Prostate Cancer and Tuberous Sclerosis Complex Tumor Cells
Authors: Gao Yu , Gartenhaus Ronald B. , Lapidus Rena G. , Hussain Arif , Zhang Yanting , Wang Xinghuan , Dan Han C. 
Published: September 2015

Abstract
The serine/threonine protein kinase Akt plays a critical role in regulating proliferation, growth, and survival through phosphorylation of different downstream substrates. The mTOR is a key target for Akt to promote tumorigenesis. It has been reported that Akt activates mTOR through phosphorylation and inhibition of the tuberous sclerosis complex (TSC) protein TSC2. Previously, it was demonstrated that mTOR activates IKK/NF-κB signaling by promoting IκB kinase (IKK) activity downstream of Akt in conditions deficient of PTEN. In this study, the mechanistic role of the tumor-suppressor TSC2 was investigated in the regulation of IKK/NF-κB activity in PTEN-null prostate cancer and in TSC2-mutated tumor cells. The results demonstrate that TSC2 inhibits IKK/NF-κB activity downstream of Akt and upstream of mTORC1 in a PTEN-deficient environment. However, TSC2 promotes IKK/NF-κB activity upstream of Akt and mTORC1 in TSC2 mutated tumor cells. These data indicate that TSC2 negatively or positively regulates IKK/NF-κB activity in a context-dependent manner depending on the genetic background.
Implications: This study provides fundamental insight for understanding the molecular details by which TSC2/mTOR regulates NF-κB signaling in different tumors. Mol Cancer Res; 13(12); 1602–14. ©2015 AACR.