bluuebunny/crossref_metadata_2025_split huggingface dataset:
A multidisciplinary study of the final episode of the Manda Hararo dyke sequence, Ethiopia, and implications for trends in volcanism during the rifting cycle
Authors: Barnie T. D. , Keir D. , Hamling I. , Hofmann B. , Belachew M. , Carn S. , Eastwell D. , Hammond J. O. S. , Ayele A. , Oppenheimer C. , Wright T. 
Published: May 2015

Abstract

The sequence of dyke intrusions between 2005 and 2010 in the Manda Hararo rift segment, Ethiopia, provided an opportunity to test conceptual models of continental rifting. Based on trends up to dyke 13 in the sequence, it was anticipated that, should magma supply continue, dykes would shorten in length and eruptions would increase in size and decrease in distance from the segment centre as extensional stress was progressively released. In this paper we revisit these predictions by presenting a comprehensive overview of the May 2010 dyke and fissure eruption, the 14th and last in the sequence, from InSAR, seismicity, satellite thermal data, ultraviolet SO
2
retrievals and multiple LiDAR surveys. We find the dyke is longer than other eruptive dykes in the sequence, propagating in two directions from the segment centre, but otherwise fairly typical in terms of opening, propagation speed and geodetic and seismic moment. However, though the eruption is located closer to the segment centre, it is much smaller than previous events. We interpret this as indicating that either the Manda Hararo rifting event was magma limited, or that extensional stress varies north and south of the segment centre.
A major dyke swarm in the Ogaden region south of Afar and the early evolution of the Afar triple junction
Authors: Mège D. , Purcell P. , Bézos A. , Jourdan F. , La C. 
Published: May 2015

Abstract

Geological mapping in the Ogaden region of SE Ethiopia, integrated with aeromagnetic data, has revealed a large dyke swarm extending SSE more than 600 km from the southern Afar margin across the Somali Plate to the Ethiopia–Somalia border.
40
Ar/
39
Ar age dating shows that emplacement occurred at 24–27 Ma, contemporaneous with early rifting and dyking in the Red Sea. Slab-pull forces generated at the Zagros subduction zone strained the lithosphere in the Afro-Arabian plate, and dyking began to extend south from the Red Sea at
c.
27 Ma, extending across Afar, fed by a plume-related magma source, rather than the rift-related source prevailing along the Red Sea. Immediately south of the Afar margin, the dyke system was emplaced along the Precambrian Marda Fault Zone, and the continuation across the Ogaden may have been controlled by lithospheric weakness associated with a splay of the Marda Fault. We suggest that the Ogaden Dyke Swarm is a zone of crustal dilation continuing the Red Sea trend across the Horn of Africa and constituting the original third ‘arm’ of the Afar triple junction. Geochemical and geochronological analyses indicate that basaltic outpourings from the Ogaden Dyke Swarm flowed at least as far east as the Ethiopia–Somalia border and emanated from the same magma source as the Ethiopian flood basalts, which had erupted earlier at
c.
30 Ma. Dykes are emergent only occasionally and are marked at the surface by linear sand-filled troughs varying from 2 to 20 m deep caused by tensional collapse above the dyke tip. Magnetic anomalies associated with the dykes vary in width up to 1 km and likely identify dyke zones.

Supplementary material:

Geological map of the Marda Fault Zone and surroundings; argon dating analytical protocol and isotopic data corrected from baseline; petrographic description of representative samples of the Ogaden Dyke Swarm and analytical protocol used for geochemistry are available at
http://www.geolsoc.org.uk/SUP18829
.
KRAS Genomic Status Predicts the Sensitivity of Ovarian Cancer Cells to Decitabine
Authors: Stewart Michelle L. , Tamayo Pablo , Wilson Andrew J. , Wang Stephanie , Chang Yun Min , Kim Jong W. , Khabele Dineo , Shamji Alykhan F. , Schreiber Stuart L. 
Published: May 2015

Abstract
Decitabine, a cancer therapeutic that inhibits DNA methylation, produces variable antitumor response rates in patients with solid tumors that might be leveraged clinically with identification of a predictive biomarker. In this study, we profiled the response of human ovarian, melanoma, and breast cancer cells treated with decitabine, finding that RAS/MEK/ERK pathway activation and DNMT1 expression correlated with cytotoxic activity. Further, we showed that KRAS genomic status predicted decitabine sensitivity in low-grade and high-grade serous ovarian cancer cells. Pretreatment with decitabine decreased the cytotoxic activity of MEK inhibitors in KRAS-mutant ovarian cancer cells, with reciprocal downregulation of DNMT1 and MEK/ERK phosphorylation. In parallel with these responses, decitabine also upregulated the proapoptotic BCL-2 family member BNIP3, which is known to be regulated by MEK and ERK, and heightened the activity of proapoptotic small-molecule navitoclax, a BCL-2 family inhibitor. In a xenograft model of KRAS-mutant ovarian cancer, combining decitabine and navitoclax heightened antitumor activity beyond administration of either compound alone. Our results define the RAS/MEK/DNMT1 pathway as a determinant of sensitivity to DNA methyltransferase inhibition, specifically implicating KRAS status as a biomarker of drug response in ovarian cancer. Cancer Res; 75(14); 2897–906. ©2015 AACR.
Molecular Pathways: Targeting Tumor-Infiltrating Myeloid-Derived Suppressor Cells for Cancer Therapy
Authors: Di Mitri Diletta , Toso Alberto , Alimonti Andrea 
Published: May 2015

Abstract
Tumor-infiltrating myeloid-derived suppressor cells (MDSC) are a heterogeneous and immunosuppressive cell subset that blocks the proliferation and the activity of both T and natural killer (NK) cells and promotes tumor vasculogenesis and progression. Recent evidences demonstrate that the recruitment of MDSCs in tumors also blocks senescence induced by chemotherapy promoting chemoresistance. Hence, the need of novel therapeutic approaches that can efficiently target MDSC recruitment and function in cancer. Among them, novel combinatorial treatments of chemotherapy and immunotherapy or treatments that induce depletion of MDSCs in peripheral sites should be taken in consideration. Clin Cancer Res; 21(14); 3108–12. ©2015 AACR.
Effect of Sulforaphane in Men with Biochemical Recurrence after Radical Prostatectomy
Authors: Cipolla Bernard G. , Mandron Eric , Lefort Jean Marc , Coadou Yves , Della Negra Emmanuel , Corbel Luc , Le Scodan Ronan , Azzouzi Abdel Rahmene , Mottet Nicolas 
Published: May 2015

Abstract
Increases in serum levels of prostate-specific antigen (PSA) occur commonly in prostate cancer after radical prostatectomy and are designated “biochemical recurrence.” Because the phytochemical sulforaphane has been studied extensively as an anticancer agent, we performed a double-blinded, randomized, placebo-controlled multicenter trial with sulforaphane in 78 patients (mean age, 69 ± 6 years) with increasing PSA levels after radical prostatectomy. Treatment comprised daily oral administration of 60 mg of a stabilized free sulforaphane for 6 months (M0–M6) followed by 2 months without treatment (M6–M8). The study was designed to detect a 0.012 log (ng/mL)/month decrease in the log PSA slope in the sulforaphane group from M0 to M6. The primary endpoint was not reached. For secondary endpoints, median log PSA slopes were consistently lower in sulforaphane-treated men. Mean changes in PSA levels between M6 and M0 were significantly lower in the sulforaphane group (+0.099 ± 0.341 ng/mL) than in placebo (+0.620 ± 1.417 ng/mL; P = 0.0433). PSA doubling time was 86% longer in the sulforaphane than in the placebo group (28.9 and 15.5 months, respectively). PSA increases &gt;20% at M6 were significantly greater in the placebo group (71.8%) than in the sulforaphane group (44.4%); P = 0.0163. Compliance and tolerance were very good. Sulforaphane effects were prominent after 3 months of intervention (M3–M6). After treatment, PSA slopes from M6 to M8 remained the same in the 2 arms. Daily administration of free sulforaphane shows promise in managing biochemical recurrences in prostate cancer after radical prostatectomy. Cancer Prev Res; 8(8); 712–9. ©2015 AACR.
Interleukin-6/STAT3 Pathway Signaling Drives an Inflammatory Phenotype in Group A Ependymoma
Authors: Griesinger Andrea M. , Josephson Rebecca J. , Donson Andrew M. , Mulcahy Levy Jean M. , Amani Vladimir , Birks Diane K. , Hoffman Lindsey M. , Furtek Steffanie L. , Reigan Phillip , Handler Michael H. , Vibhakar Rajeev , Foreman Nicholas K. 
Published: May 2015

Abstract
Ependymoma (EPN) in childhood is a brain tumor with substantial mortality. Inflammatory response has been identified as a molecular signature of high-risk Group A EPN. To better understand the biology of this phenotype and aid therapeutic development, transcriptomic data from Group A and B EPN patient tumor samples, and additional malignant and normal brain data, were analyzed to identify the mechanism underlying EPN Group A inflammation. Enrichment of IL6 and STAT3 pathway genes were found to distinguish Group A EPN from Group B EPN and other brain tumors, implicating an IL6 activation of STAT3 mechanism. EPN tumor cell growth was shown to be dependent on STAT3 activity, as demonstrated using shRNA knockdown and pharmacologic inhibition of STAT3 that blocked proliferation and induced apoptosis. The inflammatory factors secreted by EPN tumor cells were shown to reprogram myeloid cells, and this paracrine effect was characterized by a significant increase in pSTAT3 and IL8 secretion. Myeloid polarization was shown to be dependent on tumor secretion of IL6, and these effects could be reversed using IL6-neutralizing antibody or IL6 receptor–targeted therapeutic antibody tocilizumab. Polarized myeloid cell production of IL8 drove unpolarized myeloid cells to upregulate CD163 and to produce a number of proinflammatory cytokines. Collectively, these findings indicate that constitutive IL6/STAT3 pathway activation is important in driving tumor growth and inflammatory cross-talk with myeloid cells within the Group A EPN microenvironment. Effective design of Group A–targeted therapy for children with EPN may require reversal of this potentially immunosuppressive and protumor pathway. Cancer Immunol Res; 3(10); 1165–74. ©2015 AACR.
Perivascular Adipose Adiponectin Correlates With Symptom Status of Patients Undergoing Carotid Endarterectomy
Authors: Sharma Gaurav , Tao Ming , Ding Kui , Yu David , King William , Deyneko Galina , Wang Xiaosong , Longchamp Alban , Schoen Frederick J. , Ozaki C. Keith , Semel Marcus E. 
Published: May 2015

Background and Purpose—
Recent symptoms stand as a major determinant of stroke risk in patients with carotid stenosis, likely reflective of atherosclerotic plaque destabilization. In view of emerging links between vascular and adipose biology, we hypothesized that human perivascular adipose characteristics associate with carotid disease symptom status.

Methods—

Clinical history, carotid plaques, blood, and subcutaneous and perivascular adipose tissues were prospectively collected from patients undergoing carotid endarterectomy. Nine adipose-associated biological mediators were assayed and compared in patients with symptomatic (n=15) versus asymptomatic (n=19) disease. Bonferroni correction was performed for multiple testing (
α
/9=0.006).

Results—

Symptomatic patients had 1.9-fold higher perivascular adiponectin levels (
P
=0.005). Other circulating, subcutaneous, and perivascular biomarkers, as well as microscopic plaque characteristics, did not differ between symptomatic and asymptomatic patients.

Conclusions—
Symptomatic and asymptomatic carotid endarterectomy patients display a tissue-specific difference in perivascular adipose adiponectin. This difference, which was not seen in plasma or subcutaneous compartments, supports a potential local paracrine relationship with vascular disease processes that may be related to stroke mechanisms.
White Matter Damage Relates to Oxygen Saturation in Children With Sickle Cell Anemia Without Silent Cerebral Infarcts
Authors: Kawadler Jamie M. , Kirkham Fenella J. , Clayden Jonathan D. , Hollocks Matthew J. , Seymour Emma L. , Edey Rosanna , Telfer Paul , Robins Andrew , Wilkey Olu , Barker Simon , Cox Tim C.S. , Clark Chris A. 
Published: May 2015

Background and Purpose—
Sickle cell anemia is associated with compromised oxygen-carrying capability of hemoglobin and a high incidence of overt and silent stroke. However, in children with no evidence of cerebral infarction, there are changes in brain morphometry relative to healthy controls, which may be related to chronic anemia and oxygen desaturation.

Methods—
A whole-brain tract-based spatial statistics analysis was carried out in 25 children with sickle cell anemia with no evidence of abnormality on T2-weighted magnetic resonance imaging (13 male, age range: 8–18 years) and 14 age- and race-matched controls (7 male, age range: 10–19 years) to determine the extent of white matter injury. The hypotheses that white matter damage is related to daytime peripheral oxygen saturation and steady-state hemoglobin were tested.

Results—

Fractional anisotropy was found to be significantly lower in patients in the subcortical white matter (corticospinal tract and cerebellum), whereas mean diffusivity and radial diffusivity were higher in patients in widespread areas. There was a significant negative relationship between radial diffusivity and oxygen saturation (
P
<0.05) in the anterior corpus callosum and a trend-level negative relationship between radial diffusivity and hemoglobin (
P
<0.1) in the midbody of the corpus callosum.

Conclusions—
These data show widespread white matter abnormalities in a sample of asymptomatic children with sickle cell anemia, and provides for the first time direct evidence of a relationship between brain microstructure and markers of disease severity (eg, peripheral oxygen saturation and steady-state hemoglobin). This study suggests that diffusion tensor imaging metrics may serve as a biomarker for future trials of reducing hypoxic exposure.
Stroke Induces Nuclear Shuttling of Histone Deacetylase 4
Authors: Kassis Haifa , Shehadah Amjad , Chopp Michael , Roberts Cynthia , Zhang Zheng Gang 
Published: May 2015

Background and Purpose—
Histone deacetylases (HDACs) 4 and 5 are abundantly expressed in the brain and have been implicated in the regulation of neurodegeneration. Under physiological conditions, HDACs 4 and 5 are expressed in the cytoplasm of brain cells where they cannot directly access chromatin. In response to external stimuli, they can shuttle to the nucleus and regulate gene expression. However, the effect of stroke on nuclear shuttling of HDACs 4 and 5 remains unknown.

Methods—
Using a rat model of middle cerebral artery occlusion, we examined the subcellular localization of HDACs 4 and 5 in the peri-infarct cortex during brain repair after stroke.

Results—
Stroke significantly increased nuclear HDAC4 immunoreactivity in neurons, but not in astrocytes or in oligodendrocytes, of the peri-infarct cortex at 2, 7, and 14 days after middle cerebral artery occlusion. Neurons with nuclear HDAC4 immunoreactivity distributed across all layers of the peri-infarct cortex and were Ctip2+ excitatory and parvalbumin+ inhibitory neurons. These neurons were not TUNEL or BrdU positive. Furthermore, nuclear HDAC4 immunoreactivity was positively and significantly correlated with increased dendritic, axonal, and myelin densities as determined by microtubule-associated protein 2, phosphorylated neurofilament heavy chain, and myelin basic protein, respectively. Unlike HDAC4, stroke did not alter nuclear localization of HDAC5.

Conclusions—
Our data show that stroke induces nuclear shuttling of HDAC4 in neurons in the peri-infarct cortex, and that increased nuclear HDAC4 is strongly associated with neuronal remodeling but not with neuronal cell death, suggesting a role for nuclear HDAC4 in promoting neuronal recovery after ischemic injury.
The Atmospheric Response to Weak Sea Surface Temperature Fronts*
Authors: Schneider Niklas , Qiu Bo 
Published: May 2015

Abstract
The response of the atmospheric boundary layer to fronts of sea surface temperature (SST) is characterized by correlations between wind stress divergence and the downwind component of the SST gradient and between the wind stress curl and the crosswind component of the SST gradient. The associated regression (or coupling) coefficients for the wind stress divergence are consistently larger than those for the wind stress curl. To explore the underlying physics, the authors introduce a linearized model of the atmospheric boundary layer response to SST-induced modulations of boundary layer hydrostatic pressure and vertical mixing in the presence of advection by a background Ekman spiral. Model solutions are a strong function of the SST scale and background advection and recover observed characteristics. The coupling coefficients for wind stress divergence and curl are governed by distinct physics. Wind stress divergence results from either large-scale winds crossing the front or from a thermally direct, cross-frontal circulation. Wind stress curl, expected to be largest when winds are parallel to SST fronts, is reduced through geostrophic spindown and thereby yields weaker coupling coefficients.
Filament Frontogenesis by Boundary Layer Turbulence
Authors: McWilliams James C. , Gula Jonathan , Molemaker M. Jeroen , Renault Lionel , Shchepetkin Alexander F. 
Published: May 2015

AbstractA submesoscale filament of dense water in the oceanic surface layer can undergo frontogenesis with a secondary circulation that has a surface horizontal convergence and downwelling in its center. This occurs either because of the mesoscale straining deformation or because of the surface boundary layer turbulence that causes vertical eddy momentum flux divergence or, more briefly, vertical momentum mixing. In the latter case the circulation approximately has a linear horizontal momentum balance among the baroclinic pressure gradient, Coriolis force, and vertical momentum mixing, that is, a turbulent thermal wind. The frontogenetic evolution induced by the turbulent mixing sharpens the transverse gradient of the longitudinal velocity (i.e., it increases the vertical vorticity) through convergent advection by the secondary circulation. In an approximate model based on the turbulent thermal wind, the central vorticity approaches a finite-time singularity, and in a more general hydrostatic model, the central vorticity and horizontal convergence are amplified by shrinking the transverse scale to near the model’s resolution limit within a short advective period on the order of a day.
Subcutaneous immunoglobulin in treating inflammatory neuromuscular disorders
Authors: Yoon Min-Suk , Gold Ralf , Kerasnoudis Antonios 
Published: May 2015

Objective: Intravenous immunoglobulin administration has long been used in the treatment of autoimmune neuromuscular disorders. Immunoglobulins may be administered by intramuscular, intravenous or subcutaneous routes. Methods: This is a report on the long-term clinical follow up of six patients with inflammatory neuromuscular disorders, that is, three chronic inflammatory demyelinating polyneuropathy (CIDP), one multifocal motor neuropathy (MMN), one inclusion body myositis (IBM) and one myasthenia gravis (MG), treated with subcutaneous immunoglobulins for a mean of 3.25 years. Results: One MMN and two CIDP patients received a weekly dose of subcutaneous immunoglobulins equivalent to intravenous immunoglobulin. One CIDP patient received a 50% dose reduction, the IBM patient received a 30% reduction and the MG patient a 20% reduction. The lower dose chosen in the majority of patients was based not only on clinical effects, but also on studies of primary immunodeficiency syndromes. One patient with CIDP showed clinical fluctuation, which was successfully treated with an adaptation of the dose of subcutaneous immunoglobulins, while the remaining patients with neuromuscular disorders had a stable clinical course for 2 years. No serious side effects were observed. Conclusions: Our results suggest that subcutaneous immunoglobulins can be an attractive alternative therapy in autoimmune neuromuscular disorders.
Safety, tolerability and pharmacodynamics of a novel immunomodulator, MIS416, in patients with chronic progressive multiple sclerosis
Authors: Luckey Alison M , Anderson Tim , Silverman Michael H , Webster Gill 
Published: May 2015

Background Preclinical studies have demonstrated that MIS416, a bacterially derived immune modulator, targets myeloid cells following systemic delivery. MIS416 stimulated myeloid cells have the capacity to regulate innate inflammation, a potential therapeutic target for progressive multiple sclerosis. Objectives To determine the safety, tolerability, pharmacodynamics and maximum tolerated dose and/or recommended Phase 2 dose of MIS416. Methods An open-label, non-randomized, phase II, dose-escalation study, in patients with progressive multiple sclerosis: dose-escalation phase, with MIS416 administered once weekly for four weeks to determine maximum tolerated dose; and dose-confirmation phase, administered once weekly for up to 12 weeks. Results The safety profile indicates the majority of adverse events were mild or moderate, tolerable, self-limiting and consistent with the known bioactivity of MIS416 (acute flu-like symptoms). Maximum tolerated dose was not reached. A dose of 500 µg/week was recommended for the Phase 2 dose. Conclusion MIS416 is well tolerated at a dose of 500 µg/week. The adverse event profile is consistent with the mechanism of action of MIS416, indicating bioactivity within the signal transduction pathways and supported by induction of a known MIS416 pharmacodynamic marker. It is recommended that safety and efficacy of MIS416 is investigated further in a larger randomized controlled trial. http://clinicaltrials.gov reference NCT01191996
Hypermorphic mutation of phospholipase C, γ2 acquired in ibrutinib-resistant CLL confers BTK independency upon B-cell receptor activation
Authors: Liu Ta-Ming , Woyach Jennifer A. , Zhong Yiming , Lozanski Arletta , Lozanski Gerard , Dong Shuai , Strattan Ethan , Lehman Amy , Zhang Xiaoli , Jones Jeffrey A. , Flynn Joseph , Andritsos Leslie A. , Maddocks Kami , Jaglowski Samantha M. , Blum Kristie A. , Byrd John C. , Dubovsky Jason A. , Johnson Amy J. 
Published: May 2015

Key Points
Hypermorphic PLCγ2 is independent of BTK activation. SYK or LYN inhibition antagonizes mutant PLCγ2-mediated signaling events.
A novel triple therapy for ITP using high-dose dexamethasone, low-dose rituximab, and cyclosporine (TT4)
Authors: Choi Philip Young-Ill , Roncolato Fernando , Badoux Xavier , Ramanathan Sundra , Ho Shir-Jing , Chong Beng H. 
Published: May 2015

Key Points
Triple therapy is well tolerated and effective in patients with chronic ITP. Relapse free survival was 92% for responders after 12 months and 76% after 24 months.