Miracle-dz/UniFAR-FTUs huggingface dataset:
HIF2 (cid:1) inhibition promotes p53 pathway activity, tumor cell death, and radiation responses

Approximately 50% of cancer patients receive radiation treatment, either alone or in combination with other therapies. Tumor hypoxia has long been associated with resistance to radiation therapy. More-over, the expression of hypoxia inducible factors HIF1 (cid:1) and/or HIF2 (cid:1) correlates with poor prognosis in many tumors. Recent evidence indicates that HIF1 (cid:1) expression can enhance radiation-induced apoptosis in cancer cells. We demonstrate here that HIF2 (cid:1) inhibition promotes tumor cell death and, in contrast to HIF1 (cid:1) , enhances the responsetoradiationtreatment. Speciﬁcally,inhibitingHIF2 (cid:1) expression augments p53 activity, increases apoptosis, and reduces clonogenic survival of irradiated and non-irradiated cells. Moreover, HIF2 (cid:1) inhibition promotes p53-mediated responses by disrupting cellular redoxhomeostasis,therebypermittingreactiveoxygenspecies(ROS) accumulation and DNA damage. These results correlate with altered p53phosphorylationandtargetgeneexpressioninuntreatedhuman tumor samples and show that HIF2 (cid:1) likely contributes to tumor
Water-Intake and Water-Molecule Paths to the Active Site of Secretory Phospholipase A2 Studied Using MD Simulations and the Tracking Tool AQUA-DUCT

: Secretory phospholipases A 2 (sPLA 2 s) are a subclass of enzymes that catalyze the hydrolysis at the sn-2 position of glycerophospholipids, producing free fatty acids and lysophospholi-pids. In this study, di ﬀ erent phospholipids with structural modi ﬁ cations close to the scissile sn-2 ester bond were studied to determine the e ﬀ ect of the structural changes on the formation of the Michaelis − Menten complex and the water entry/exit pathways using molecular dynamics simulations and the computational tracking tool AQUA-DUCT. Structural modi ﬁ cations include methylation, dehy-drogenation, and polarization close to the sn-2 scissile bond. We found that all water molecules reaching the active site of sPLA 2 -IIA pass by the aromatic residues Phe 5 and Tyr 51 and enter the active site through an active-site cleft. The relative amount of water available for the enzymatic reaction of the di ﬀ erent phospholipid − sPLA 2 complexes was determined together with the distance between key atoms in the catalytic machinery. The results showed that ( Z )-unsaturated phospholipid is a good substrate for sPLA 2 -IIA. The computational results are in good agreement with previously reported experimental data on the ability of sPLA 2 -IIA to hydrolyze liposomes made from the di ﬀ erent phospholipids, and the results provide new insights into the necessary active-site solvation of the Michaelis − Menten complex and can pave the road for rational design in engineering applications.
Pn Wave Velocity and Anisotropy in the Northeastern South China Sea and Adjacent Region

Using seismic data from Chinese and ISC stations between 1980~2004, we inverted Pn wave velocity structure and anisotropy of the northeastern South China Sea and adjacent region. The velocity variations at uppermost mantle reflect the features of regional geology and tectonics. Southeastern China has fast velocities, correspondent to the lithospheric mantle in tectonically stable regions. Slow velocities appear near the Binhai fault zone along the coast of southeastern China, which indicates a possible penetration of the fault zone into the uppermost mantle. Similar to southeastern China, fast velocities throughout the northern South China Sea and Taiwan Strait reveal a property of the lithospheric mantle in continental margin, while fast velocities in the Xisha Trough reflect a southward extension of continental shelf and a mantle upwarp produced by Cenozoic rifting. There is no evidence of large-scale mantle heat flows in the northern South China Sea. However, a very slow velocity anomaly is observed in the eastern sub-basin of the South China Sea, where is an extinct mantle upwelling center with high heat flows, indicating a thinning or removal of lithospheric mantle. Along the eastern Taiwan, Luzon and northern Philippine, slow velocities are closely related to seismic and volcanic activity and magmatism in the arc zone, while fast velocities in the eastern South China Sea and western Philippine Sea reflect the character of oceanic lithospheric mantle. Pn velocity anisotropy also reveals the stress state in regional tectonics and the history of deformation of lithospheric mantle. Southeastern China has small anisotropy in response to less deformation there. Anisotropy is observed in the northern South China Sea, with fast directions of anisotropy aligned with shallow structures in crust, which reflect the evidence of the Mesozoic-Cenozoic rifting and shear deformation in lithospheric mantle. Strong anisotropy is also found along the Ryukyu-Taiwan-Luzon arc zone, with fast directions parallel to trenches, which indicates that strong deformation of lithospheric mantle in the leading edge of the Philippine Sea plate and Eurasian continent. The change of the fast directions of anisotropy near the eastern Taiwan is probably caused by a conversion of collision mechanisms between the Eurasian continent and the Philippine Sea plate, and the tear of the lithosphere.
Palaeostress orientation inferred from surface morphology of joints on the southern margin of the Bristol Channel Basin, UK

Abstract A field study of the orientation of surface features on joint planes has been carried out on the north Somerset coast along the southern margin of the Bristol Channel Basin (BCB), with the aim of inferring the palaeostress orientations. Surface features are very delicate structures on joint surfaces and when preserved give important clues regarding the direction of propagation of a joint and the interaction between the remote and local stresses. In this chapter surface features (i.e. plumose structures and twist-hackle fringes) observed on joints in Liassic limestone beds interbedded with shales from the BCB are described and their implications regarding the evolution of the stress field operating during their formation considered. The results are then compared with the generally accepted model for the region of an anticlockwise rotation of the stress field. The incompatibility between N-S-directed remote compression and continually changing local stress caused by the local structures (folds and faults), inhomogeneities and the anisotropy created by rapidly alternating limestone and shale beds resulted in the master joints breaking down into en echelon cracks (twist-hackle fringes). Joints in thicker limestone beds show well-developed plumose structures and twist-hackle fringes, whereas in thinner beds the fringe zones extend from the top to the bottom of the bed. It is found that regardless of the orientation of the parent joint in which the twist-hackle fringes are contained, they generally strike E-W and show both right- and left-stepping arrangements.
Automatic forest inventory parameter determination from terrestrial laser scanner data

Terrestrial laser scanners find rapidly growing interest in photogrammetry as efficient tools for fast and reliable three‐dimensional (3D) point cloud data acquisition. They have opened a wide range of application fields within a short period of time. Beyond interactive measurement in 3D point clouds, techniques for the automatic detection of objects and the determination of geometric parameters form a high priority research issue. With the quality of 3D point clouds generated by laser scanners and the automation potential in data processing, terrestrial laser scanning is also becoming a useful tool for forest inventory. This paper presents a brief review of current laser scanner systems from a technological point of view and discusses different scanner technologies and system parameters regarding their suitability for forestry applications. Methods for the automatic detection of trees in terrestrial laser scanner data as well as the automatic determination of diameter at breast height (DBH), tree height and 3D stem profiles are outlined. Reliability and precision of the techniques are analysed on the basis of several pilot studies. In these pilot studies more than 97% of the trees could be detected correctly, and DBH could be determined with a precision of about 1.8 cm.
Probable tetrapod tracks rediscovered in the Devonian of N Scotland

The discovery of probable tetrapod tracks in the Upper Old Red Sandstone of Easter Ross, N Scotland, lends credibility to 19th century claims of ‘reptilian’ footprints in these rocks. These are the only probable amphibian fossils known in the west European Devonian and are amongst the oldest anywhere.
Development of adenoviral vectors for monitoring telomerase activity in living cells

ABSTRACT Telomerase activity is a potential molecular marker for cancer and primitive cells in regenerative tissues. The most commonly used method to measure telomerase activity in cells is the telomerase reverse amplification protocol (TRAP) assay, where the protein extracts derived from homogenized cells are analysed. In this thesis we focused on developing a method where telomerase activity could be monitored and used to separating cells with high telomerase activity without killing them. We used the promoter sequence of human telomerase reverse transcriptase (hTERT) for transcriptionally controlling a destabilised green fluorescence protein (d2EGFP) reporter gene since there is a strong correlation between hTERT transcriptional activity and telomerase activity in cells. Moreover, we chose to work with adenoviral vectors due to their high level of transient gene expression as a gene transfer system. Unfavourably, adenoviral vector transduction of tumour cells has been hampered by low expression of the coxsackie B and adenovirus receptor (CAR) on the host cells, which is the attachment receptor for the most commonly used adenoviral vector (Ad5). Thus, we used a fibre-modified Ad5 vector with the tropism of Ad35, which uses the ubiquitously expressed CD46 protein as attachment receptor. We transduced a variety of cell lines with the developed hTERT-d2EGFP vector and demonstrated a close correlation between expression levels of the d2EGFP, endogenous telomerase activity, and hTERT mRNA expression. Furthermore, the hTERT-d2EGFP reporter vector was able to monitor the cell cycle and differentiation stage-dependent hTERT transcription activity. Additionally, in order to study the self-renewal process of haematopoietic stem cells (HSCs), we utilised the hTERT-reporter vector for monitoring hTERT transcription activity in human HSCs. Interestingly, increasing hTERT expression was inversely correlated to the self-renewal capacity among primitive HSCs and the hTERT-reporter vector could be used to separate short-term from long-term re-populating human HSCs. In summary, we have developed a versatile adenoviral vector system with Ad35 tropism, which can be used to transiently transduce tumour cells as well as haematopoietic cells. This vector system can be used to study normal regulation of hTERT and has potential in development of novel therapeutic approaches for treatment of tumours and malignancies in the blood system.
Effect of variation of the loading direction on the displacement accumulation of large-diameter piles under cyclic lateral loading in sand

Foundation piles supporting offshore structures experience cyclic lateral loading arising from waves and wind, which are not typically uni-directional over the lifetime of the structure. This paper presents results from centrifuge experiments in sand, representing a large diameter prototype tested at stress levels similar to the field subjected to cyclic lateral loading from varying directions. The results demonstrate increased deformation accumulation due to the changing loading direction, compared to the uni-directional case. Displacement accumulation is not limited to the main loading direction but includes transverse movement as well. Similar trends were observed in small-scale 1g modelling that allowed a larger number of load cycles to be applied. The centrifuge test results provide confidence of the applicability of the findings to the prototype. Current methods that neglect the effect of variation of the loading direction will provide predictions of displacement accumulation of piles that are un-co.
Future changes of wind energy potentials over Europe in a large CMIP5 multi‐model ensemble

A statistical‐dynamical downscaling method is used to estimate future changes of wind energy output (Eout) of a benchmark wind turbine across Europe at the regional scale. With this aim, 22 global climate models (GCMs) of the Coupled Model Intercomparison Project Phase 5 (CMIP5) ensemble are considered. The downscaling method uses circulation weather types and regional climate modelling with the COSMO‐CLM model. Future projections are computed for two time periods (2021–2060 and 2061–2100) following two scenarios (RCP4.5 and RCP8.5). The CMIP5 ensemble mean response reveals a more likely than not increase of mean annual Eout over Northern and Central Europe and a likely decrease over Southern Europe. There is some uncertainty with respect to the magnitude and the sign of the changes. Higher robustness in future changes is observed for specific seasons. Except from the Mediterranean area, an ensemble mean increase of Eout is simulated for winter and a decreasing for the summer season, resulting in a strong increase of the intra‐annual variability for most of Europe. The latter is, in particular, probable during the second half of the 21st century under the RCP8.5 scenario. In general, signals are stronger for 2061–2100 compared to 2021–2060 and for RCP8.5 compared to RCP4.5. Regarding changes of the inter‐annual variability of Eout for Central Europe, the future projections strongly vary between individual models and also between future periods and scenarios within single models. This study showed for an ensemble of 22 CMIP5 models that changes in the wind energy potentials over Europe may take place in future decades. However, due to the uncertainties detected in this research, further investigations with multi‐model ensembles are needed to provide a better quantification and understanding of the future changes.
Some observations on crop profile modelling

Abstract LANDSAT data are typically available for a number of overpasses during a growing season. There is currently considerable interest in modelling the so-called crop profile for such multitemporal data by a non-linear profile function of some (spectral) index for the spectral bands. The derived coefficients are used in a subsequent allocation procedure. This paper outlines some results obtained from an evaluation of the approach for crop data from the wheatbelt of Western Australia. Specifically, the degree of separation of crop classes from pasture classes, as measured by the discriminant root, is compared for analyses based on the original bands, on various spectral indices and on fitted coefficients from a crop profile function describing the temporal change in these indices. For the data considered, a marked loss of discrimination is found for analyses based on various spectral indices, when compared with those based directly on the corresponding discriminant functions (where the linear combinati.
Radar Inaccuracies and Mid-Air Collision Risk: Part 2 En Route Radar Separation Minima

A review of safety targets for en route ATC radar separation suggests that the existing target level of safety (TLS) is over-cautious. If risk budgeting principles are followed consistently, a ‘radar TLS’ of 1·0×10−9 fatal aircraft accidents per flying hour is appropriate. This rate is consistent with Joint Aviation Authorities (JAA) guidance on system failure conditions leading to catastrophic accidents. Dynamic and static calculations using published data are compared. The new methodology shows where there are problems with the traditional static calculations, and how to improve the estimation. A further improvement introduces a simple robust model of the controller's decision processes. The focus is not on describing what controllers would generally do, but on setting criteria based on what they could not reasonably be expected to do. This additional ingredient into the calculation adds realism and ensures that attention is focused on hazardous correlated errors. Focused data collection would be an essential component of new risk estimates. The key information required would be on radar performance and the nature and frequency of use of radar separation, including the relative velocities for proximate events at closest point of approach and the frequency of correlated gross errors (through a conditional probability factor). If this factor is not properly taken into account, then the data collection and analysis could be inefficient.
The use of high energy moisture characteristic to assess soil stability

The laboratory method of determining aggregate stability introduced by Childs in 1940 is reconsidered. A convenient and quick method of interpreting the experimental results is presented and provides the structural index for a given soil treatment. The ratio of the structural indices for two soil treatments provides the stability ratio, which is of relevance to erosion and pedogenetic studies of structure. Illustrative results show that pretreatments such as air drying, grinding and sieving affect the structural index and stability ratio.
Quelques aspects de l'action des termites du sol sur les argiles

Resume La majorité des termites sont en rapport avec le sol et utilisent l'argile de ses horizons, pour édiffer leurs termitières. Pour les termites du sol, dont la plupart sont des maçons, l'argile est avant tout le matériau de base offrant les propriétés de rétention d'eau, de plasticité et d'ahésivité, leur permettant de confectionner les mortiers et les microbétons de leurs unités de constructions. Si les termites humivores absorbent toujours une quantité relativement importante d'éléments argileux avec leurs aliments, les termites lignivores n'ingérent qu'occasionnellement une fraction minime d'argile. Leur action sur l'évolution des silicates se traduit par des néoformations de minéraux argileux au sein de leurs constructions: illite ‘artificielle’, hydrobiotite, vermiculite, halloysite, montmorillonite, et parfoils sépiolite et attapulgite. Ces néoformations résultent de l'action conjugée du travail de broyage et de trituration salivaire de minéraux encore peu altérés de la profondeur du sol, et des conditions physico-chimiques de milieu particulières aux termites.
Characteristic small‐earthquake sequence off Sanriku, northeastern Honshu, Japan

We found eight similar earthquakes of M4.8 regularly occurring from 1957 to 1995 on the plate boundary off Sanriku, northeastern Japan. The mean recurrence interval of the events is 5.35 years and its standard deviation is only 0.53 years. These events have the same focal mechanisms of low‐angle thrust fault type and their source sizes are estimated to be around 1 km. The slip of each event is comparable to the cumulative amount of relative plate motion in the inter‐seismic period. Thus, these events are probably caused by repeating slip at a small but strong asperity surrounded by creeping zone on the plate boundary. The next event was expected to occur by the end of November 2001 with 99% probability and actually M4.7 event occurred on November 13, 2001.
Quantitative analysis of microbial communities in a typical pharmaceutical water system on basis of conventional culture method.

Bacterial contamination of the water supply of newly installed water system unit was investigated. Water samples were collected at different sites from water supply lines to the final utility area. Within hours following connection and continuing for up to several months of the study, water samples were obtained from the air-water syringe of the Unit. The samples were plated on culture media for quantitative analysis. The Total Viable Count procedure involved incubation of sampled water in aerobic conditions and does not allow estimation of anaerobic microbes. Direct pour plate method and subsequently membrane filtration technique was followed to estimate the microbial load. Finally a comparative analysis of microbial load on different steps was made. However the system was found to be useful monitoring the microbial load.
Eradication of metastatic mouse cancers resistant to immune checkpoint blockade by suppression of myeloid-derived cells

Significance Recent clinical trials have shown highly promising responses in a subset of patients treated with immune checkpoint inhibitory anti–programmed cell death-1, anti–programmed cell death ligand-1, and anti–cytotoxic T-lymphocyte-associated antigen-4 antibodies, but the majority of patients in these trials remained unresponsive. Our results show that elevated myeloid-derived suppressor cells(MDSCs) are responsible for the resistance and that elimination of MDSCs can lead to cures of experimental, metastatic tumors. Impressive responses have been observed in patients treated with checkpoint inhibitory anti–programmed cell death-1 (PD-1) or anti–cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibodies. However, immunotherapy against poorly immunogenic cancers remains a challenge. Here we report that treatment with both anti–PD-1 and anti–CTLA-4 antibodies was unable to eradicate large, modestly immunogenic CT26 tumors or metastatic 4T1 tumors. Cotreatment with epigenetic-modulating drugs and checkpoint inhibitors markedly improved treatment outcomes, curing more than 80% of the tumor-bearing mice. Functional studies revealed that the primary targets of the epigenetic modulators were myeloid-derived suppressor cells (MDSCs). A PI3K inhibitor that reduced circulating MDSCs also eradicated 4T1 tumors in 80% of the mice when combined with immune checkpoint inhibitors. Thus, cancers resistant to immune checkpoint blockade can be cured by eliminating MDSCs.
Synchrony matters more than species richness in plant community stability at a 1 global scale 2

93 The stability of ecological communities is critical for the stable provisioning of 94 ecosystem services, such as food and forage production, carbon sequestration and soil 95 fertility. Greater biodiversity is expected to enhance stability across years by decreasing 96 synchrony among species, but the drivers of stability in nature remain poorly resolved. 97 Our analysis of time-series from 79 data sets across the world showed that stability was 98 associated more strongly with the degree of synchrony among dominant species than 99 with species richness. The relatively weak influence of species richness is consistent 100 with theory predicting that the effect of richness on stability weakens when synchrony is 101 higher than expected under random fluctuations, which was the case in most 102 communities. Land management, nutrient addition and climate change treatments, had 103 relatively weak and varying effects on stability, modifying how species richness, 104 synchrony and stability interact. Our results demonstrate the prevalence of biotic drivers 105 on ecosystem stability, with the potential for environmental drivers to alter the intricate 106 relationship among richness, synchrony and stability. 107