Miracle-dz/UniFAR-FTUs huggingface dataset:
Demethylating drugs as novel analgesics for cancer pain.

e13531 Background: Cancer pain is a major public health problem for which little progress has been made. Effective treatment could result from targeting undiscovered mechanisms of cancer pain. DNA methylation is common in carcinogenesis, but has no known role in pain. We recently showed that methylation is a novel mechanism mediating pain in cancer patients. Reversal of methylation by demethylating drugs could therefore serve as novel therapy for cancer pain. OBJECTIVE To determine the analgesic potential of demethylating drugs zebularine and decitabine on cancer pain in a mouse model. METHODS A mouse cancer model was created by inoculating HSC-3, an oral squamous cell carcinoma cell line, into the right hindpaw of BALB/c mice. Mice were divided into the 4 groups: 1) zebularine-only treatment, 2) decitabine-only treatment, 3) combination treatment of both drugs, and 4) control sham treatment. Zebularine was administered in drinking water, given ad libitum starting post-inoculation day (PID) 4. Decitabine was given as a single dose of 2mg/kg weight by an osmotic pump. Mechanical allodynia (pain), assessed by paw withdrawal, was measured at baseline and at intervals up to PID 21. ANOVA and Holm Sidak statistical tests were used. Molecular analysis of tumors was performed. RESULTS Mice developed visible tumors by PID 4. Mechanical allodynia increased significantly from baseline, indicating increased pain. Zebularine-only treatment decreased cancer pain to baseline levels (p<0.05) by PID 15. Combination treatment of decitabine and zebularine resulted in an even more profound decrease in pain by PID 7 (p<0.05). Methylation quantification of tumors showed that treated mice had demethylation of the OPRM1 gene, which codes for the mu-opioid receptor that binds opiates, compared to control mice. The resultant increase in mu-opioid receptor expression also stimulated secretion of beta-endorphin, an endogenous opioid, in the cancer microenvironment. CONCLUSIONS In this study we demonstrate a novel mechanism of cancer pain and the use of demethylating drugs to treat cancer pain. Demethylating drugs act through an endogenous analgesic mechanism, which is potentially more effective than the exogenous analgesics currently used.
Late Paleozoic to Triassic evolution of the Gondwana margin: Evidence from Chilean Frontal Cordilleran batholiths (28°S to 31°S)

Upper Paleozoic to Triassic Chilean granitoids in the Andean Frontal Cordillera between 28°S and 31°S record crustal and mantle conditions at the Gondwana margin during the final assembly and initial breakup of the Pangea supercontinent. This period overlaps the end of Paleozoic terrane accretion and precedes Andean subduction. Integration of new trace-element and isotopic data with other information on the granitoids and the regional geology leads to a tectonic model that has implications for other parts of the Gondwana margin. In the model, the Carboniferous to Early Permian is a period of oblique convergence. Associated Elqui complex granitoids are diverse. Those in the Guanta and Montosa units are predominantly related to subduction processes, whereas those in the Cochiguas and El Volcan units are dominated by melting of the subduction complex and older crust. Progressive oblique collision of the last pre-Pangea terrane (Equis) along the margin resulted in crustal thickening associated with shortening deformation of foreland basinal sedimentary rocks and uplift of the Elqui complex. Subsequent gravitational collapse of the inactive slab and lithospheric delamination resulted in the production of large amounts of basalt, which intruded and melted the crust, producing the post-collisional Ingaguas complex. The Los Carricitos granitoids formed in thickened crust, whereas the Chollay, El Colorado, and El Leon units formed in thinner crust. The Ingaguas complex is part of the Choiyoi granite-rhyolite province, whose formation, similar to that of other Gondwana silicic provinces, was probably accentuated by anomalously hot upper mantle associated with the Pangea supercontinent.
Relationships between mineralogical, chemical, and isotopic properties of some North American kimberlites

Late Precambrian to Cretaceous kimberlites from North America have initial Sr and Nd isotopic compositions (eSr0 = −4 to 37, eNd0 = −4 to 6) which form a trend falling roughly within the mantle array. Two groups can be defined on the basis of mineralogical and geochemical characteristics: group A encompasses most of the northeast American kimberlites whose rare earth element (REE) concentrations are moderately fractionated, relative to chondrites. Nd isotopic ratios (eNd0 = 3 to 6) fall within the field of common ocean island basalts. They are also distinctive by the presence of phlogopite phenocrysts and high-temperature garnet peridotite xenocrysts. Group B includes kimberlites from the Colorado-Wyoming, Kansas and British Columbia areas and one sample from Pennsylvania. They lack the above quoted peridotite suite and abundant phlogopite. Their light REE concentrations show a strong enrichment, relative to chondrites, correlated with relatively unradiogenic Nd (eNd0 = −4 to 2). Kimberlites of both groups have radiogenic Pb (206Pb/204Pb = 18.17–19.41) and a wide range in 207Pb/204Pb. In both cases, melts were probably generated in the sublithospheric mantle, but group B melts interacted with an enriched component, resulting mainly from magmatic processes, and probably located within the deep lithosphere. By contrast, the Prairie Creek lamproite (Arkansas), as other ultrapotassic rocks, received its distinctive geochemical properties from a crustal component present in the mantle source.
Discussion of a paper by D. M. Hershfield, ‘An empirical comparison of predictive values of three extreme value procedures’

Hershfield [1962] states his problem in the opening paragraph thus: ‘The selection of the proper extreme value procedure which includes both distribution and curve fitting methods is one of the major problems encountered in the analysis of extreme value rainfall’ and ends this paragraph by saying, ‘The solution of this problem can be resolved only in terms of empirical extremes involving many observations. ’ After examining the data from some 339 rainfall stations he finally draws the conclusion that ‘If the assumptions upon which this study is based are valid, all three procedures have some deficiencies. A basic difficulty in the analysis of extreme values, namely, the effect of outliers on the return period estimates, might be overcome by creating a test statistic which can be used to adjust the outlier. ’ The writer wishes to comment on the suitability of the technique employed in the examination of the problem and on the conclusions drawn concerning outliers.
RED-NET: A Recursive Encoder-Decoder Network for Edge Detection

In this paper, we introduce RED-NET: A Recursive Encoder-Decoder Network with Skip-Connections for edge detection in natural images. The proposed network is a novel integration of a Recursive Neural Network with an Encoder-Decoder architecture. The recursive network enables us to increase the network depth without increasing the number of parameters. Adding skip-connections between encoder and decoder helps the gradients reach all the layers of a network more easily and allows information related to finer details in the early stage of the encoder to be fully utilized in the decoder. Based on our extensive experiments on popular boundary detection datasets including BSDS500 \cite{Arbelaez2011}, NYUD \cite{Silberman2012} and Pascal Context \cite{Mottaghi2014}, RED-NET significantly advances the state-of-the-art on edge detection regarding standard evaluation metrics such as Optimal Dataset Scale (ODS) F-measure, Optimal Image Scale (OIS) F-measure, and Average Precision (AP).
Starting over. Why remarriages are more unstable.

Previously divorced and remarried couples have a higher probability of divorce and decline in marital quality. Models which have explained this behavior focus on: willingness to leave marriage; selection; socioeconomic status; the remarriage market; and incomplete marriages. Each model is examined among a population of marrieds and remarrieds to distinguish attributes and the extent to which these attributes increase the probability of decline in marital quality or divorce. Data were obtained from a sample of 2033 marrieds 55 years old who were interviewed over the telephone in 1980, 1983, and 1988 in the Marital Instability Over the Life Course Study. Incomplete marriage was measured by whether and to what extent parents or parents-in-law made contact and the number of relatives that party was close to. Willingness to leave was based on attitudes to divorce and the ability to handle emotion and financial affairs if the marriage ended. Selection referred to poor marriage material (drugs or alcohol, criminal conduct, mismanagement of money, immature behavior. Socioeconomic status was reflected in occupational status, educational levels, and income. The marriage market was a measure of age, education, and religious differences. Marital quality was examined in terms of happiness, interaction, disagreement, and divorce proneness. Multiple classification analysis was used to compare attributes by marital history. The methods of Kessler and Greenberg were used to examine changes in marital quality over time in first time marriages and remarriages. The results indicate that individuals in remarriages have relationships with attributes which potentially lower marital quality and increase the probability of divorce. When both individuals have prior marriage and divorce experience, there is even lower social integration, greater willingness to leave marriage, higher probability of marrying as a teen, lower socioeconomic status, and greater likelihood of age differences. Remarriage variables and marital quality variables both showed linear relationships. Remarriage variables and marital quality variables both showed linear relationships. In the cross sectional analysis of the 1980 data there is a statistically significant relationship with attributes which potentially lower marital quality in 1980 indicates remarried persons are more prone to lower marital quality than people in first marriages.
Methotrexate induces intestinal mucositis and alters gut protein metabolism independently of reduced food intake

One of the main secondary toxic side effects of antimitotic agents used to treat cancer patients is intestinal mucositis. This one is characterized by compromised digestive and absorptive functions, barrier integrity and immune competence. In the same time, food intake is decreased and may induce intestinal damages per se. The aim of the study was to characterize which alterations are specific to methotrexate, independently of the anorexic effect of the drug. Male Sprague-Dawley rats received subcutaneously saline solution as control group or 2.5 mg/kg of methotrexate during three days (D0-D2). Methotrexate-treated rats were compared to ad libitum and pair-fed controls. Histological examinations and specific markers of the immune and non-immune gut barrier function were assessed at D4 or D7. As compared to ad libitum and pair fed controls, methotrexate induced at D4 villus atrophy associated with epithelial necrosis. Mucosal protein synthesis rate and mucin contents of methotrexate treated rats were reduced. In the same time, cathepsin D proteolytic activity was increased compared with ad libitum and pair fed controls whereas calpain activity was increased when compared with the only pair fed controls. These intestinal lesions were associated with various metabolic disturbances such as increased TNF-α level and inflammation score in the jejunum but also disturbances of amino acid concentrations in duodenum and plasma. At D7, these alterations were partially or completely normalised. In addition to consequences of a low food intake, methotrexate further impairs different biological processes leading to a dramatic loss of gut homeostasis. Targeted nutritional management of chemotherapy receiving patients should be set up to prevent or limit such alterations.
Sedimentary structures exposed in bar tops in the Brahmaputra River, Bangladesh

Abstract The Brahmaputra River is one of the world’s largest sand-bed braided rivers with a channel belt up to 15 km wide, a mean channel depth of 5 m and maximum scour depths of up to 40 m. The recorded discharge varies by around 60 000 cumecs every year following the annual monsoon, producing dramatic stage fluctuations with the water level falling between 7 and 8 m from bankfull to low flow stage. In the dry season large areas of bar top and channel bed are exposed and low flow channels cut natural sections through bar tops exposing the internal stratification. Elements of upstream, downstream and lateral accretion are identified, although the high width/depth ratio of channels (up to 500:1) results in extremely low depositional dips on bed bounding surfaces. Within the accretionary elements vertical and lateral changes in sedimentary structures are ubiquitous and varied but some patterns can be discerned. Channel deposits are dominated by sinuous-crested dunes and trough cross-stratification. Upper stage plane bed lamination, often with a very low angle depositional dip, has been observed in beds up to 4 m thick and is generally found at the base of the exposed bar top sections. Trough cross-stratification in bar tops occurs in sets from 0.1 m to 3 m thick with rapid vertical and lateral changes in set thickness. Very large sets of trough cross-stratification, >3 m thick, do not occur in the bar top sections. Current ripple lamination is most abundant on the tops of bars with very high rates of climb associated with high rates of sediment deposition. From these observations a generalised vertical sequence of bar top origin might include trough cross-stratification overlain by upper stage plane bed lamination, isolated sets of trough cross-stratification truncated and capped by current ripple lamination. This sequence, which is considered to represent the deposits of a single flood, may occur within the upstream, downstream or lateral accretion elements. However, it should be noted that vertical and lateral changes in facies are extremely abundant with many changes in sedimentary structures and reactivation surfaces within each depositional episode.
Elastic constants of single‐crystal forsterite as a function of temperature and pressure

The nine adiabatic elastic stiffness constants of single-crystal forsterite (Mg2SiO4) have been measured as a function of hydrostatic pressure and temperature using a pulse super-position technique. The pressure dependence was linear, within experimental error, for all nine coefficients up to 10 kb. Temperature measurements were made in the range from 300° to 700°K. At lower temperatures some curvature was present, but above 500°K the data were linear. The nine adiabatic stiffnesses and their isothermal pressure derivatives at 25°C are presented, and the isobaric temperature derivatives are given at zero pressure in the high temperature limit above 500°K. The elastic constants and their pressure derivatives agree approximately with theoretical data for a hexagonal close-packed structure of oxygen anions assuming only nearest neighbor interactions and central forces. This agreement indicates that the elastic properties of forsterite are predominantly determined by the oxygen anion framework. In addition, the results were used to calculate the isothermal pressure dependence of the volume and of the lattice parameters of forsterite at high pressure from the Murnaghan and Birch equations of state.
Implication of spatiotemporal distribution of black shales deposited during the Cretaceous Oceanic Anoxic Event-2

ABSTRACT Oceanic Anoxic Events (OAEs) mark the contemporaneous deposition of organic-rich marine sediments termed “black shales” in the wide areas of the oceans. An anoxic event that occurred at the Cenomanian-Turonian boundary, OAE-2, has been recognized as one of the largest events in the Cretaceous. Carbon isotopic compositions (δ13C) of sedimentary carbonate and organic matter exhibit a positive excursion across the OAE-2, reflecting an enhanced burial rate of 13C-depleted organic carbon during the event. Here we compile a spatiotemporal distribution of black shales on the basis of their onset timings relative to the δ13C excursion as a time-control reference, and discuss the “spreading patterns” of black shale deposition. The patterns suggest that the deposition of black shales started from marginal regions of the southern North Atlantic and the Western Interior Seaway in North America, and spread to the northern North Atlantic and Tethys Sea. Strangely, the black shales whose onset corresponds to that of the δ13C excursion have not been found in many locations. Furthermore, extensive deposition of black shales in the Tethys and some sites in the North Atlantic occurred significantly after the major shift of the δ13C excursion. Sediments in the largely unexplored Pacific basin may be the missing link in the temporal relationship between the black shale deposition and the isotopic excursion.
Phosphate mining and the relocation of the Banabans to northern Fiji in 1945: Lessons for climate change-forced displacement

At the end of the xixth Century, Banaba was an unknown, and then ‘unclaimed’, island in the central Pacific; however, all was soon to change for its 450 residents. In 1900, a rock propping open a Sydney-office door of the Pacific Islands Phosphate Company was found to consist almost entirely of high-grade phosphate. It was soon traced back to the island; mining activity commenced shortly after and the operation quickly grew. The tiny island was transformed into a major phosphate-mining settlement. With continued mineral extraction it became apparent that Banaba would, in time, become uninhabitable and plans were devised by colonial authorities to relocate the island community to an alternative home. This article examines the decisions, events and processes that led to the relocation of the Banabans to Rabi Island, Fiji in 1945. Original colonial documents and correspondence are examined and key members of the elderly Banaban community, based in Suva and Rabi, consulted. Parallels with contemporary relocations, associated with climate change, are given and learnings presented that will aid future climate-induced community relocations. Lessons to take forward are the need for long-term, post-relocation planning, including the creation of livelihoods, and on-going support by external agencies for those displaced.
Evaluating Ginkgo Leaf Necrosis and Asymmetric Crown Discoloration Induced by Typhoon 0613 with RGB Image Analysis

As one kind of disaster, typhoons can cause serious damage to landscape trees both mechanically and physiologically. The Typhoon 0613 was characterized by strong wind associated with less rainfall when it passed through Yamaguchi City, Japan. After hit by it, the symptoms of leaf necrosis appeared on many ginkgo trees from coast to inland and the crowns of them became asymmetrically discolored. Due to the big body of ginkgo trees, this kind of phenomenon was often described by visual scale method characterized by significant deviation and observer specific. In order to quantitatively estimate the symptoms of damage, the leaf necrotic area percentage (LNAP), crown discoloration area percentage (CDAP) and inflection point (IP) of the threshold response function for asymmetric discolored crowns were determined by image pixel method. The green/luminance (G/L) value was measured by using the RGB images respectively scanned by a flat bed scanner from individual leaves and taken with a CCD digital camera from crowns. Significant relationship between G/Lleaf and LNAP, and between G/Lcrown and CDAP were obtained with the correlation coefficient of R2=0.941 and R2=0.826 separately. This suggested that both leaf necrosis and asymmetric crown discoloration of ginkgo trees induced by Typhoon 0613 can be quantitatively estimated by measuring the G/L value from both leaves and crowns. The significant relation between CDAP and IP (R2=0.811) reveals that both statistically calculated IP value and visually divided CDAP value can be used in estimating the asymmetric crown characters. The estimation of sampled leaves showed that it was the difference of necrotic leaves between windward and leeward made the crown of damaged ginkgo trees appear asymmetrical discoloration. Image threshold responsive analysis of ginkgo crowns hit by Typhoon 0613 indicated that the injury of ginkgo crowns was more serious on windward than leeward. The relationship between the distance from coastline (DC) and G/Lcrown value presented that the farther from the coastline, the bigger the G/Lcrown value of ginkgo crowns. Comparing to the sampling method, image analysis can be more effective being applied in field measurement of damaged status of ginkgo trees hit by severe typhoons for the reason of less labor and less time requirement. It may be an alternative tool to be used in estimating the degree of damage to ginkgo trees by typhoons like Typhoon 0613.
Earthquake nucleation on model faults with rate‐ and state‐dependent friction: Effects of inertia

Laboratory studies suggest that earthquake nucleation involves a transition from quasi-static slip when inertial effects are negligible to inertia-driven, dynamic motion. This transition occurs via quasi-dynamic motion, during which the effects of inertia become increasingly important. The characteristics of this transition, which depend on frictional properties of the fault, determine the observability of earthquake nucleation by seismic, geodetic, or other means. By investigating the role of inertia during nucleation, we obtain a quantitative definition of the limiting velocity Vin, which marks the end of quasi-dynamic motion and the onset of instability. For reasonable friction parameters and fault widths, we obtain estimates of Vin for crustal faults. To study the roles of inertia, stiffness, and friction parameters on preseismic motion, we simulate triggered instabilities in a one-dimensional model of a homogeneous fault, with rate and state variable friction. In most of our simulations, triggering is achieved by applying a stress perturbation to an initially creeping fault under steady state friction. We also investigate triggering on faults which are initially locked and overstressed compared to their nominal frictional strength, due to time-dependent healing. We study the amount, Up, and duration, Tp, of preseismic slip as a function of system mass m and other model parameters. For crustal faults, we interpret the relevant mass as a product of density and fault width and find that wider fault zones result in smaller Up and larger Tp. Both Up and Tp are proportional to the system stiffness K, the characteristic slip distance Dc, and the friction constitutive parameter a and inversely proportional to the size of the triggering event. We find greater Up and Tp for constitutive laws which allow strengthening at zero velocity, compared to laws that require slip or a combination of slip and aging for state evolution. In contrast to quasi-static modeling, our simulations suggest a minimum stress perturbation criterion for instability, which may be interpreted in terms of a strain threshold for triggered seismicity.