Miracle-dz/UniFAR-FTUs huggingface dataset:
Control of glioma cell migration and invasiveness by GDF-15

Growth and differentiation factor (GDF)-15 is a member of the transforming growth factor (TGF)-β family of proteins. GDF-15 levels are increased in the blood and cerebrospinal fluid of glioblastoma patients. Using a TCGA database interrogation, we demonstrate that high GDF-15 expression levels are associated with poor survival of glioblastoma patients. To elucidate the role of GDF-15 in glioblastoma in detail, we confirmed that glioma cells express GDF-15 mRNA and protein in vitro. To allow for a detailed functional characterization, GDF-15 expression was silenced using RNA interference in LNT-229 and LN-308 glioma cells. Depletion of GDF-15 had no effect on cell viability. In contrast, GDF-15-deficient cells displayed reduced migration and invasion, in the absence of changes in Smad2 or Smad1/5/8 phosphorylation. Conversely, exogenous GDF-15 stimulated migration and invasiveness. Large-scale expression profiling revealed that GDF-15 gene silencing resulted in minor changes in the miRNA profile whereas several genes, including members of the plasminogen activator/inhibitor complex, were deregulated at the mRNA level. One of the newly identified genes induced by GDF-15 gene silencing was the serpin peptidase inhibitor, clade E nexin group 1 (serpine1) which is induced by TGF-β and known to inhibit migration and invasiveness. However, serpine1 down-regulation alone did not mediate GDF-15-induced promotion of migration and invasiveness. Our findings highlight the complex contributions of GDF-15 to the invasive phenotype of glioma cells and suggest anti-GDF-15 approaches as a promising therapeutic strategy.
Late Weichselian environmental change in southern Sweden and Denmark.

A synthesis is presented of the envronmental and climatic variations that are inferred to have occurred in southern Sweden (up to latitude 59°N) and Denmark during the Weichselian Late-glacial (14-9 ka BP). The chronology and characteristics of the main phases of deglaciation, sea-level change, periglacial activity, soil development, vegetation cover and climate change are summarised. A curve representing the main changes in temperature, including quantitative estimates based upon beetle data and using the ‘mutual climatic range’ method, is presented.
RIPK3 expression in cervical cancer cells is required for PolyIC-induced necroptosis, IL-1α release, and efficient paracrine dendritic cell activation

Previous studies have shown that cervical cancer cells only release low levels of pro-inflammatory cytokines owing to infection with human papillomaviruses. This results in low immunogenicity of the cancer cells. The viral dsRNA analog PolyIC has been suggested as a promising adjuvant for cervical cancer immunotherapy. However, little is known about the molecular requirements resulting in successful immune activation. Here, we demonstrate that stimulation of cervical cancer cells with PolyIC induced necroptotic cell death, which was strictly dependent on the expression of the receptor-interacting protein kinase RIPK3. Necroptotic cancer cells released interleukin-1α (IL-1α), which was required for powerful activation of dendritic cells (DC) to produce IL-12, a cytokine critical for anti-tumor responses. Again both, IL-1α release and DC activation, were strictly dependent on RIPK3 expression in the tumor cells. Of note, our in situ analyses revealed heterogeneous RIPK3 expression patterns in cervical squamous cell carcinomas and adenocarcinomas. In summary, our study identified a novel RIPK3-dependent mechanism that explains how PolyIC-treatment of cervical cancer cells leads to potent DC activation. Our findings suggest that the RIPK3 expression status in cervical cancer cells might critically influence the outcome of PolyIC-based immunotherapeutic approaches and should therefore be assessed prior to immunotherapy.
Associations of potentially functional variants in IL-6, JAKs and STAT3 with gastric cancer risk in an eastern Chinese population

The interleukin-6 (IL-6)/JAK/STAT3 signaling pathway plays a central role in inflammation-mediated cancers, including gastric cancer (GCa). We evaluated associations between 10 potentially functional single nucleotide polymorphisms (SNPs) of four essential genes in the pathway and GCa risk in a study of 1,125 GCa cases and 1,221 cancer-free controls. We found that a significant higher GCa risk was associated with IL-6 rs2069837G variant genotypes [adjusted odds ratios (OR) = 1.33; 95% confidence interval (CI) = 1.12-1.59 for AG + GG vs. AA)] and JAK1 rs2230587A variant genotypes (adjusted OR = 1.20; 95% CI = 1.02-1.43 for GA + AA vs. GG). We also found that a significant decreased GCa risk was associated with STAT3 rs1053004G variant genotypes (adjusted OR = 0.84; 95% CI = 0.71-0.99 for AG + GG vs. AA). The combined analysis of IL-6 rs2069837G and JAK1 rs2230587A variant risk genotypes revealed that individuals with one-or-two risk genotypes exhibited an increased risk for GCa (adjusted OR = 1.34; 95% CI = 1.13-1.59). Genotypes and mRNA expression correlation analysis using the data from the HapMap 3 database provided further support for the observed risk associations. Larger studies are warranted to validate these findings.
Mutation analysis of hepcidin and ferroportin genes in Italian prospective blood donors with iron overload

Maintenance of iron balance is essential for humans and requires the coordinate regulation of iron transport into plasma from dietary sources in the duodenum, from recycled senescent red cells in macrophages, and from storage in hepatocytes. Hepcidin, a recently identified antimicrobial peptide produced in the liver, has been shown to play a central role in the homeostatic regulation of iron absorption and distribution [1]. It is a negative regulator of iron absorption in the small intestine and of iron release from macrophages engaged in the recycling of iron senescent erythrocytes [2]. The human hepcidin gene contains three exons that encode a 72-aa precursor (pro-hepcidin) with a characteristic furin cleavage site immediately N-terminal to the 25-aa major hepcidin species found in plasma and urine [3]. Recently, hepcidin has been shown to regulate iron homeostasis by interaction with ferroportin, an iron cellular exporter highly expressed in absorptive enterocytes, macrophages, hepatocytes, and placental cells [4].
P-wave seismic velocity structure derived from sonic logs and industry reflection data in the Los An

[1] We present a new three-dimensional seismic P wave velocity model of the Los Angeles basin that is based on more than 150 sonic logs and 7000 stacking velocities from industry reflection profiles. The model was developed using kriging techniques implemented in GoCAD (a commercial application specializing in the construction of surfaces, the analysis of spatially distributed data, and the modeling or simulation of properties) and is characterized by a heterogeneous, spatial varying velocity gradient with maximum velocities of ∼5000 m/s in the sedimentary section. Variability of the observed P wave velocities increases with depth, reflecting complex structural and sedimentological controls. The model contains a new representation of the basin shape as defined by the sediment-basement interface, which was mapped using well control and seismic reflection profiles. Our model differs substantially in approach and outcome from previous representations of crustal velocity structure in southern California.
High‐pressure granulites in the Sanggan area, North China craton: metamorphic evolution, P–T paths and geotectonic significance

High‐pressure basic granulites are widely distributed as enclaves and sheet‐like blocks in the Huaian TTG gneiss terrane in the Sanggan area of the Central Zone of the North China craton. Four stages of the metamorphic history have been recognised in mineral assemblages based on inclusion, exsolution and reaction textures integrated with garnet zonation patterns as revealed by compositional maps and compositional profiles. The P–T conditions for each metamorphic stage were obtained using thermodynamically and experimentally calibrated geothermobarometers. The low‐Ca core of growth‐zoned garnet, along with inclusion minerals, defines a prograde assemblage (M1) of garnet + clinopyroxene + plagioclase + quartz, yielding 700 °C and 10 kbar. The peak of metamorphism at about 750–870 °C and 11–14.5 kbar (M2) is defined by high‐Ca domains in garnet interiors and inclusion minerals of clinopyroxene, plagioclase and quartz. Kelyphites or coronas of orthopyroxene + plagioclase ± magnetite around garnet porphyroblasts indicate garnet breakdown reactions (M3) at conditions around 770–830 °C and 8.5–10.5 kbar. Garnet exsolution lamellae in clinopyroxene and kelyphites of amphibole + plagioclase around garnet formed during the cooling process at about 500–650 °C and 5.5–8 kbar (M4). These results help define a sequential P–T path containing prograde, near‐isothermal decompression (ITD) and near‐isobaric cooling (IBC) stages.
Receiver functions and crustal structure of the northwestern Andean region, Colombia

We used the receiver function technique to deduce crustal thickness beneath the northwestern Andean system, using data from the permanent seismic network of Colombia, combined with some of the IRIS and CTBTO stations in Colombia and Ecuador. The estimation of crustal thickness was made using the primary P to s conversion and crustal reverberations. The bulk crustal VP/VS ratio was constrained using a crustal thickness versus VP/VS stacking method, in addition to estimations using a time to depth conversion technique based on results of a modified Wadati diagram analysis. We observed a wide range of crustal thicknesses, including values around 17 km beneath the Malpelo Island on the Pacific Ocean, 20 to 30 km at the coastal Pacific and Caribbean plains of Colombia, 25 to 40 km beneath the eastern plains and foothills, 35 km beneath the Western Cordillera, 45 km at the Magdalena River intermountain valley, 52 to 58 km under the northern Central Cordillera, and reaching almost 60 km beneath some of the volcanoes of the Southern Cordilleran system of Colombia; crustal thickness can be slightly greater than 60 km beneath the plateau of the Eastern Cordillera. The values of VP/VS are particularly high for some of the stations on the volcanic centers, reaching values above 1.79, probably related to the addition of mafic materials to the lower crust, and in the plateau of the Eastern Cordillera near Bogota, where we speculate about the possibility of crustal seismic anisotropy associated with shear zones.
Recent BRCAPRO upgrades significantly improve calibration

The recent release of version 2.0-8 of the BayesMendel package contains an updated BRCAPRO risk prediction model, which includes revised modeling of Contralateral Breast Cancer (CBC) penetrance, provisions for pedigrees of mixed ethnicity and an adjustment for mastectomies among family members. We estimated penetrance functions for contralateral breast cancer by a combination of parametric survival modeling of literature data and deconvolution of SEER9 data. We then validated the resulting updated model of CBC in BRCAPRO by comparing it with the previous release (BayesMendel 2.0-7), using pedigrees from the Cancer Genetics Network (CGN) Model Validation Study. Version 2.0-8 of BRCAPRO discriminates BRCA1/BRCA2 carriers from noncarriers with similar accuracy compared to the previous version (increase in AUC: 0.0043), is slightly more precise in terms of RMSE (decrease in RMSE: 0.0108), and it significantly improves calibration (ratio of observed to expected events of 0.9765 in version 2.0-8, compared to 0.8910 in version 2.0-7). We recommend that the new version be used in clinical counseling, particularly in settings where families with CBC are common.
Improving Surgical Outcome: Combine Evidence from Unimodal Interventions

To the Editor Recently, Banz et al. reviewed different pathophysiological factors to be considered to improve outcome after major surgery. Obviously, this topic is of considerable interest because of a need for improved quality as well as reduced costs in the present health care system. Although the different individual risk factors and pathogenic factors for postoperative morbidity were well covered, it was rather disappointing that the conclusions were that “further studies are needed to evaluate the value of ‘bundles’ of interventions and whether they can improve outcome after major surgery. ” Thus, none of the 123 quoted references included a discussion of the well-established, well-documented, and evidence-based “fast-track surgery” approach leading to enhanced recovery and decreased morbidity and hospital stay across procedures. Especially in colorectal surgery, clinical benefits have been demonstrated with a decreased length of stay from about 6 to 10 days to about 3 to 4 days and with about 50% reduction of morbidity and enhanced recovery of paralytic ileus. However, similar achievements, although less well documented, have been made during many other procedures. These efforts have been well reviewed in metaanalyses and Cochrane Reviews, and the future is now to implement the evidence by combining unimodal evidencebased perioperative interventions into a multimodal enhanced recovery program. In their review, it might therefore have been appropriate to actually refer to the documented improvements in postoperative outcome on the basis of their pathophysiological considerations.
A systematic analysis of the Mid‐Atlantic Ridge morphology and gravity between 15°N and 40°N: Constraints of the thermal structure

Multibeam bathymetry data obtained along a 2400 km long section of the Mid-Atlantic Ridge (MAR) from 15°N to the Azores platform (40°N) and satellite-derived gravity data were used to calculate the mantle Bouguer anomaly (MBA) along this portion of the MAR. Both data sets were used to determine the relations between gravity anomalies and topographic variations and discuss these in terms of thermal difference. A long-wavelength influence of the Azores hot spot is characterized by a gentle, continuous slope of the average ridge axial depth and a general gradient in the along-axis MBA profile. This thermal influence of the Azores hot spot controls a systematic southward propagation of the spreading segments at least to 26°30′N. South of 26°30′N, the direction of the segment propagation is controlled by the local difference in thermal state between adjacent segments. Except on the Azores platform, the systematic along-axis 11–90 km long wavelength segmentation is independent of the long-wavelength influence of the Azores. At the segment center, the axial morphology is linked to the thermal state of the segments between: (1) “Hotter segments” characterized by a smooth axial morphology, a well-defined shallow ”inner valley”, high ΔMBA and a long length;(2) “colder segments” which present a rough axial morphology with a deep, wide and well-defined rift valley, a low ΔMBA and a small length. For ”hotter segments” the formation of the abyssal hills is mainly due to a magmato-tectonic cycle over periods of 0.3 to 1 Myr, whereas on “colder segments” the axial morphology is mainly controlled by a tectonic rift valley formation. We propose that these different segment types correspond to a temporal evolution of the rift valley morphology over periods of several million years.
New insights from seismic tomography on the complex geodynamic evolution of two adjacent domains: Gulf of Cadiz and Alboran Sea

In this study, we present a three‐dimensional P wave upper‐mantle tomography model of the southwest Iberian margin and Alboran Sea based on teleseismic arrival times recorded by Iberian and Moroccan land stations and by a seafloor network deployed for 1 year in the Gulf of Cadiz area during the European Commission Integrated observations from NEAR shore sourcES of Tsunamis: towards an early warning system (EC NEAREST) project. The three‐dimensional model was computed down to 600 km depth. The tomographic images exhibit significant velocity contrasts, as large as 3%, confirming the complex evolution of this plate boundary region. Prominent high‐velocity anomalies are found beneath Betics‐Alboran Sea, off‐shore southwest Portugal, and north Portugal, at sublithospheric depths. The transition zones between high‐ and low‐velocity anomalies in southwest and south Iberia are associated to the contact of oceanic and continental lithosphere. The fast structure below the Alboran Sea‐Granada area depicts an L‐shaped body steeply dipping from the uppermost mantle to the transition zone where it becomes less curved. This anomaly is consistent with the results of previous tomographic investigations and recent geophysical data such as stress distribution, GPS measurements of plate motion, and anisotropy patterns. In the Atlantic domain, under the Horseshoe Abyssal Plain, the main feature is a high‐velocity zone found at uppermost mantle depths. This feature appears laterally separated from the positive anomaly recovered in the Alboran domain by the interposition of low‐velocity zones which characterize the lithosphere beneath the southwest Iberian peninsula margin, suggesting that there is no continuity between the high‐velocity anomalies of the two domains west and east of the Gibraltar Strait.
Afterbody Heating Predictions for a Mars Science Laboratory Entry Vehicle

*The Mars Science Laboratory mission intends to deliver a large rover to the Martian surface within 10 km of its target site. One candidate entry vehicle aeroshell consists of a 3.75-m diameter, 70-deg sphere-cone forebody and a biconic afterbody similar to that of Viking. This paper presents computational fluid dynamics predictions of laminar afterbody heating rates for this configuration and a 2010 arrival at Mars. Computational solutions at flight conditions used an 8-species Mars gas model in chemical and thermal non-equilibrium. A grid resolution study examined the effects of mesh spacing on afterbody heating rates and resulted in grids used for heating predictions on a reference entry trajectory. Afterbody heating rate reaches its maximum value near 0.6 W/cm 2 on the first windward afterbody cone at the time of peak freestream dynamic pressure. Predicted afterbody heating rates generally are below 3% of the forebody laminar nose cap heating rate throughout the design trajectory. The heating rates integrated over time provide total heat load during entry, which drives thermal protection material thickness. Nomenclature
Who are the Net Food Importing Countries?

The purpose of this paper is to update the information on net food importing countries, using different definitions of food, separating countries by their level of income, whether they are in conflict and whether they are significant oil exporters. The study also estimates the changes in net food importing status of these countries over the last two and a half decades, and, most important, the study measures the relative importance of these net food imports in the import basket of the countries. Our results show that while many low-income countries are net food importers, the importance and potential impact of the net food importing status has been highly exaggerated. Many low-income countries that have larger food deficits are either oil exporters or countries in conflict. Food deficits of most low-income countries are not that significant as a percentage of their imports. Our results also show that only 6 low-income countries have food deficits that are more than 10 percent of their imports. Last two decades have seen a significant improvement in the food trade balances of low-income developing countries. SSA low-income countries are an exception to this trend. On the other hand, there are a group of countries which are experiencing civil conflicts which are large importers of food, and these countries can not meet their basic needs. They also need special assistance in the distribution of food within their boundaries. Therefore, one should modify the WTO Ministerial Declaration, and focus on these conflict countries rather than the broad net food importers.
Near-surface eddy dynamics in the Southern Ocean

The Antarctic Circumpolar Current (ACC) is a crucial component of the global ocean conveyor belt, acting as a zonal link among the major ocean basins but, to some extent, limiting meridional exchange and tending to isolate the ocean south of it from momentum and heat income. In this work we investigate one of the most important mechanisms contributing to the poleward transfer of properties in the Southern Ocean, that is the eddy component of the dynamics. For this particular purpose, observations obtained from near-surface drifters have been used: they represent a very useful data set to analyse the eddy field because of their ability to catch a large number of scales of motion while providing a quasi-synoptic coverage of the investigated area. Estimates of the eddy heat and momentum fluxes are carried out using data taken from the Global Drifter Program databank; they refer to Surface Velocity Program drifter trajectories collected in the area south of 35°S between 1995 and 2006. Eddy kinetic energies, variance ellipses, momentum and heat fluxes have been calculated using the pseudo-Eulerian method, showing patterns in good agreement with those present in the literature based on observational and model data, although there are some quantitative differences. The eddy fluxes have been separated into their rotational and divergent portions, the latter being responsible for the meridional transports. The associated zonal and depth-exponentially integrated meridional heat transport exhibits values spanning over a range between -0.4 PW and –1.1 PW in the ACC region, consistent with previous estimates.
Thermal Performance of the Mars Science Laboratory Rover During Mars Surface Operations

On November 26, 2011, NASA launched a large (900 kg) rover as part of the Mars Science Laboratory (MSL) mission to Mars. Eight months later, on August 5, 2012, the MSL rover (Curiosity) successfully touched down on the surface of Mars. As of the writing of this paper, the rover had completed over 200 Sols of Mars surface operations in the Gale Crater landing site (4.5 deg S latitude). This paper describes the thermal performance of the MSL Rover during the early part of its two Earth-0.year (670 Sols) prime surface mission. Curiosity landed in Gale Crater during early Spring (Ls=151) in the Southern Hemisphere of Mars. This paper discusses the thermal performance of the rover from landing day (Sol 0) through Summer Solstice (Sol 197) and out to Sol 204. The rover surface thermal design performance was very close to pre-landing predictions. The very successful thermal design allowed a high level of operational power dissipation immediately after landing without overheating and required a minimal amount of survival heating. Early morning operations of cameras and actuators were aided by successful heating activities. MSL rover surface operations thermal experiences are discussed in this paper. Conclusions about the rover surface operations thermal performance are also presented.