Miracle-dz/UniFAR-FTUs huggingface dataset:
N-Demethylation Is a Major Route of 2-Amino-3-Methylimidazo[4,5-f]quinoline Metabolism in Mouse

2-Amino-3-methylimidazo[4,5-f]quinoline (IQ) metabolism was evaluated in mouse to better understand its tumorigenicity. Urinary metabolites from mice orally administered 40 mg/kg [14C]IQ were compared with those from similarly treated rats. The recovery of radioactivity was significantly greater in mouse urine. The relative proportion of metabolites was significantly different, and a new rodent metabolite was detected. For rat, the proportion of previously identified metabolites excreted was 5-O-glucuronide > sulfamate > 5-sulfate > N-glucuronide. In mouse urine, a new metabolite, demethyl-IQ, represented approximately 26% of IQ metabolism with the proportion of metabolites as follows: 5-O-glucuronide > demethyl-IQ > sulfamate > N-glucuronide > 5-sulfate. Mouse metabolites were identified by electrospray ionization mass spectrometry. Demethyl-IQ was shown to be 2-aminoimidazo[4,5-f]quinoline. N-Acetyl-2-amino-3-methylimidazo[4,5-f]quinoline was not detected with mice. Mouse liver slices produced 5-O-glucuronide, demethyl-IQ, and sulfamate with the former two being significantly reduced by ellipticine. Liver microsomes only produced demethyl-IQ. Ellipticine, a cytochrome P450 1A inhibitor, but not furafylline, an 1A2 selective inhibitor, prevented microsomal N-demethylation. Inhibitors had similar effects on 7-ethoxyresorufin O-deethylation activity. Demethyl-IQ was not further metabolized by an intact mouse or liver microsomes. Thus, mouse IQ metabolism is significantly different from that in rat, and these differences may affect IQ tumorigenicity. N-Demethylation of IQ-like heterocyclic amines occurs in mouse, monkey, and human but not in rat.
House Prices, Heterogeneous Banks and Unconventional Monetary Policy Options

This paper develops a nancial mechanism which integrates housing and the real econ- omy through housing-secured debt. In this environment, movements in home prices are ampli ed through both borrowers and banks' balance sheets, leading to a self-reinforcing credit/liquidity crunch. When placed within a traditional business cycle model, this - financial structure quantitatively captures empirical relationships the traditional nancial accelerator mechanism struggles to explain and the qualitative predictions of the model are consistent with dynamic responses from a VAR. The model provides a framework to examine the ability of QE policies and equity injections into big banks to mitigate a housing bust. Although both are e ective, the nuances of the policies are important. A prolonged asset purchase program is preferable to a short-term equity injection; however, the model suggests the equity injections may have been necessary to prevent an economic collapse at the acute stage of the 2008 Financial Crisis.
Q2237+0305 source structure and dimensions from light‐curve simulation

Assuming a two-component quasar structure model consisting of a central compact source and an extended outer feature, we produce microlensing simulations for a population of star-like objects in the lens galaxy. Such a model is a simplified version of that adopted to explain the brightness variations observed in Q0957 (Schild & Vakulik 2003). The microlensing light curves generated for a range of source parameters were compared to the light curves obtained in the framework of the OGLE program. With a large number of trials we built, in the domain of the source structure parameters, probability distributions to find ”good” realizations of light curves. The values of the source parameters which provide the maximum of the joint probability distribution calculated for all the i mage components, have been accepted as estimates for the source structure parameters. The resul ts favour the two-component model of the quasar brightness structure over a single compact central source model, and in general the simulations confirm the Schild-Vakulik model that previ ously described successfully the microlensing and other properties of Q0957. Adopting 3300 km/s for the transverse velocity of the source, the effective size of the central source was determined to be about 2� 10 15 cm, ande≈ 2 was obtained for the ratio of the integral luminosity of the outer feature to that of the central source.
Impacted-Region Optimization for Distributed Model Predictive Control Systems With Constraints

For a large-scale distributed system, distributed model predictive control (DMPC) is a method of choice because of its ability to explicitly accommodate constraints and to achieve good dynamic performance. In the design of a DMPC, guaranteeing stability with a strong global performance is known to be a challenge. In this paper, we consider a large-scale distributed system whose input is constrained to given sets in their respective spaces and propose a stabilizing DMPC design, where each subsystem-based model predictive control (MPC) optimizes the cost function of the entire system over the region it directly impacts on. Consistency constraints and stability constraints, which bound the estimation errors of the interaction sequences among subsystems, are designed to guarantee that, if an initially feasible solution can be found, subsequent feasibility of the algorithm is guaranteed at every update, and that the closed-loop system is asymptotically stable. A key feature of the proposed DMPC is that it coordinates the MPCs of the subsystems by redefining the impact region of a subsystem according to the coordination strategy. Simulation results show that the performance of the proposed DMPC is very close to that of a centralized MPC.
Social Context–Induced Song Variation Affects Female Behavior and Gene Expression

Social cues modulate the performance of communicative behaviors in a range of species, including humans, and such changes can make the communication signal more salient. In songbirds, males use song to attract females, and song organization can differ depending on the audience to which a male sings. For example, male zebra finches (Taeniopygia guttata) change their songs in subtle ways when singing to a female (directed song) compared with when they sing in isolation (undirected song), and some of these changes depend on altered neural activity from a specialized forebrain-basal ganglia circuit, the anterior forebrain pathway (AFP). In particular, variable activity in the AFP during undirected song is thought to actively enable syllable variability, whereas the lower and less-variable AFP firing during directed singing is associated with more stereotyped song. Consequently, directed song has been suggested to reflect a “performance” state, and undirected song a form of vocal motor “exploration. ” However, this hypothesis predicts that directed–undirected song differences, despite their subtlety, should matter to female zebra finches, which is a question that has not been investigated. We tested female preferences for this natural variation in song in a behavioral approach assay, and we found that both mated and socially naive females could discriminate between directed and undirected song—and strongly preferred directed song. These preferences, which appeared to reflect attention especially to aspects of song variability controlled by the AFP, were enhanced by experience, as they were strongest for mated females responding to their mate's directed songs. We then measured neural activity using expression of the immediate early gene product ZENK, and found that social context and song familiarity differentially modulated the number of ZENK-expressing cells in telencephalic auditory areas. Specifically, the number of ZENK-expressing cells in the caudomedial mesopallium (CMM) was most affected by whether a song was directed or undirected, whereas the caudomedial nidopallium (NCM) was most affected by whether a song was familiar or unfamiliar. Together these data demonstrate that females detect and prefer the features of directed song and suggest that high-level auditory areas including the CMM are involved in this social perception.
Advanced Therapeutic Options for Treatment of Metastatic Castration Resistant Prostatic Adenocarcinoma

The initial stage of prostatic adenocarcinoma (PaC) has been treated with surgery and radiation therapy, but the advanced stages need systemic novel treatment. Since 2010, several advanced therapeutic innovations have been introduced in various randomized clinical trials to improve survival and reduce morbidity and mortality. Several of these therapeutics have shown substantial survival assistance globally, even in the advanced stages of metastatic castration-resistant prostatic adenocarcinoma (mCRPC). This article describes advanced PaC therapy regimens including chemotherapeutic options, hormonal therapies (abiraterone, enzalutamide), immunotherapeutic agents, and bone-modifying agents. We discussed various pros and cons of gene therapy approaches including Crispr/Cas9 mediation, oncolytic viruses, suicidal genes, and micro-RNA based antitumor therapy. The mCRPC microenvironment is characterized by elevated prostate-specific antigen (PSA) levels, which ultimately trigger the androgen receptor (AR) and its dependent signaling pathways. The advanced therapeutics target these receptors and inhibit the steroidogenic enzymes that play an important role in increasing testosterone (T) and dihydrotestosterone (DHT) levels in the body. These advanced therapeutic novelties also target AR-independent oncogenic signaling pathways by focusing on DNA damage repair (DDR) pathways and their mechanisms. Some of these options appear to be very attractive strategies for acute and chronic stages of PaC and mCRPC treatment by overcoming the mechanisms of resistance.
Developmental Considerations of Sperm Protein 17 Gene Expression in Rheumatoid Arthritis Synoviocytes

Rheumatoid arthritis (RA) is an autoimmune disease characterized by proliferative synovial tissue. We used mRNA differential display and library subtraction to compare mRNA expression in RA and osteoarthritis (OA) synoviocytes. We initially compared the mRNA expression patterns in 1 female RA and 1 OA synovia and found a differentially expressed 350 bp transcript in the RA synoviocytes which was, by sequence analysis, 100% homologous to sperm protein 17 (Sp17). Moreover, the Sp17 transcript was found differentially expressed in a RA synovial library that was subtracted with an OA synovial library. Using specific primers for full length Sp17, a 1.1 kb transcript was amplified from the synoviocytes of 7 additional female RA patients, sequenced and found to 100% homologous to Sp17. Thus, we found the unexpected expression of Sp17, a thought to be gamete-specific protein, in the synoviocytes of 8/8 female RA patients in contrast to control OA synoviocytes. Interestingly, Sp17's structural relationship with cell-binding and recognition proteins, suggests that Sp17 may function in cell-cell recognition and signaling in the RA synoviocyte. Further, Sp17 could have a significant regulatory role in RA synoviocyte gene transcription and/or signal transduction. Thus, Sp17 could have an important role in RA synoviocyte proliferation or defective apoptosis. Finally, the presence of Sp17 in synoviocytes has interesting developmental considerations.
MR Elastography Can Be Used to Measure Brain Stiffness Changes as a Result of Altered Cranial Venous Drainage During Jugular Compression

The authors evaluated the effect of jugular compression on brain tissue stiffness and CSF flow by evaluating 9 volunteers, with and without jugular compression, with MR elastography and phase-contrast CSF flow imaging. The shear moduli of the brain tissue increased with the percentage of blood draining through the internal jugular veins during venous compression. Subjects who maintain venous drainage through the internal jugular veins during jugular compression have stiffer brains than those who divert venous blood through alternative pathways. BACKGROUND AND PURPOSE: Compressing the internal jugular veins can reverse ventriculomegaly in the syndrome of inappropriately low pressure acute hydrocephalus, and it has been suggested that this works by “stiffening” the brain tissue. Jugular compression may also alter blood and CSF flow in other conditions. We aimed to understand the effect of jugular compression on brain tissue stiffness and CSF flow. MATERIALS AND METHODS: The head and neck of 9 healthy volunteers were studied with and without jugular compression. Brain stiffness (shear modulus) was measured by using MR elastography. Phase-contrast MR imaging was used to measure CSF flow in the cerebral aqueduct and blood flow in the neck. RESULTS: The shear moduli of the brain tissue increased with the percentage of blood draining through the internal jugular veins during venous compression. Peak velocity of caudally directed CSF in the aqueduct increased significantly with jugular compression (P < .001). The mean jugular venous flow rate, amplitude, and vessel area were significantly reduced with jugular compression, while cranial arterial flow parameters were unaffected. CONCLUSIONS: Jugular compression influences cerebral CSF hydrodynamics in healthy subjects and can increase brain tissue stiffness, but the magnitude of the stiffening depends on the percentage of cranial blood draining through the internal jugular veins during compression—that is, subjects who maintain venous drainage through the internal jugular veins during jugular compression have stiffer brains than those who divert venous blood through alternative pathways. These methods may be useful for studying this phenomenon in patients with the syndrome of inappropriately low-pressure acute hydrocephalus and other conditions.
Transducin Translocation in Rods Is Triggered by Saturation of the GTPase-Activating Complex

Light causes massive translocation of G-protein transducin from the light-sensitive outer segment compartment of the rod photoreceptor cell. Remarkably, significant translocation is observed only when the light intensity exceeds a critical threshold level. We addressed the nature of this threshold using a series of mutant mice and found that the threshold can be shifted to either a lower or higher light intensity, dependent on whether the ability of the GTPase-activating complex to inactivate GTP-bound transducin is decreased or increased. We also demonstrated that the threshold is not dependent on cellular signaling downstream from transducin. Finally, we showed that the extent of transducin α subunit translocation is affected by the hydrophobicity of its acyl modification. This implies that interactions with membranes impose a limitation on transducin translocation. Our data suggest that transducin translocation is triggered when the cell exhausts its capacity to activate transducin GTPase, and a portion of transducin remains active for a sufficient time to dissociate from membranes and to escape from the outer segment. Overall, the threshold marks the switch of the rod from the highly light-sensitive mode of operation required under limited lighting conditions to the less-sensitive energy-saving mode beneficial in bright light, when vision is dominated by cones.
Mapping Stacked Decision Forests to Deep and Sparse Convolutional Neural Networks for Semantic Segmentation

We consider the task of pixel-wise semantic segmentation given a small set of labeled training images. Among two of the most popular techniques to address this task are Random Forests (RF) and Neural Networks (NN). The main contribution of this work is to explore the relationship between two special forms of these techniques: stacked RFs and deep Convolutional Neural Networks (CNN). We show that there exists a mapping from stacked RF to deep CNN, and an approximate mapping back. This insight gives two major practical benefits: Firstly, deep CNNs can be intelligently constructed and initialized, which is crucial when dealing with a limited amount of training data. Secondly, it can be utilized to create a new stacked RF with improved performance. Furthermore, this mapping yields a new CNN architecture, that is well suited for pixel-wise semantic labeling. We experimentally verify these practical benefits for two different application scenarios in computer vision and biology, where the layout of parts is important: Kinect-based body part labeling from depth images, and somite segmentation in microscopy images of developing zebrafish.
A Traceable Data Fusion Based on Data Provenance

Data fusion is a hot topic in data integration which at least includes the two stages: entity resolution and data conflict resolution. However, the existing fusion process is transparent and the fusion stages are isolated. So in this paper, we proposed a traceable data fusion mechanism based on data provenance which can trace the data sources of fusion re- sults and the evolutionary process. The mechanism mainly targets forwards entity resolution and data conflict resolution stage. We represented the provenance of data origin using PI-CS which is more accurate because PI-CS can record the in- termediate process of data evolution. In order to record the evolution process of data fusion, we proposed two transforma- tion provenances: entity resolution provenance and data conflict resolution provenance which record respectively the evo- lution process of entity resolution and data conflict resolution. Finally, we give an example to validate the availability of the traceable mechanism for data fusion.
Slow Recovery of Lichen on Burned Caribou Winter Range in Alaska Tundra: Potential Influences of Climate Warming and Other Disturbance Factors

ABSTRACT Lichen regeneration timelines are needed to establish sound fire management guidelines for caribou (Rangifer tarandus) winter range. Paired burned and unburned permanent vegetative cover transects were established after 1981, 1977, and 1972 tundra fires in northwestern Alaska to document regrowth of tundra vegetation including caribou forage lichens in the wintering range of Alaska's largest caribou herd. Following fire, lichen had recovered very little compared to unburned transects (1% cover vs.15% cover) after 14 years. After 24 or 25 years, lichen cover in the burns remained low (3–4%), whether or not caribou were present during the recovery period. In addition, lichen cover on unburned transects at one study site had decreased from 14% to 6%. Shrub cover was higher on the burned plots than the unburned plots. Cover of cottongrass (Eriophorum vaginatum) initially increased following the fire and tussocks quickly became more vigorous than on paired unburned transects, remaining so for more than 14 years. Persistent changes in vegetation following fire likely reflect the cumulative impacts of seasonal caribou use and favorable growing conditions (warmer soils, longer growing season) for rooted vascular species during the recovery period. The actual recovery of forage lichens after fire on our study sites is slower than predictions based on ideal growth potential.
Trends in diagnostic biochip development

Technological advancements in biochips for diagnosis and prevention lead to improved healthcare cost containment with a decreasing birth rate and an aging population. Biochips have been attracting attention as a tool for improving healthcare costs. There are technological, standardization-related, ethical and societal problems in biochip development. For biochip market expansion, in addition to technological problems, it is necessary to overcome social, institutional, marketing and economic problems all together. It is expected that the application of biochip technologies will facilitate not only ‘super’ early diagnosis of diseases and disease prevention based on the diagnosis, but also early treatment.
Biomarkers of Methylmercury Exposure Immunotoxicity among Fish Consumers in Amazonian Brazil

Background: Mercury (Hg) is a ubiquitous environmental contaminant with neurodevelopmental and immune system effects. An informative biomarker of Hg-induced immunotoxicity could aid studies on the potential contribution to immune-related health effects. Objectives: Our objectives were to test the hypothesis that methylmercury (MeHg) exposures affect levels of serum biomarkers and to examine interactions between Hg and selenium (Se) in terms of these responses. Methods: This cross-sectional epidemiological study assessed adults living along the Tapajós River, a system long affected by MeHg. We measured antinuclear (ANA) and antinucleolar (ANoA) autoantibody levels and eight cytokines in serum samples (n = 232). Total Hg (including MeHg) and Se were measured in blood, plasma, hair, and urine. Results: The median (range) total Hg concentrations were 14.1 μg/g (1.1–62.4), 53.5 μg/L (4.3–288.9), 8.8 μg/L (0.2–40), and 3.0 μg/L (0.2–16.1) for hair, blood, plasma, and urine, respectively. Elevated titers of ANA (but not ANoA) were positively associated with MeHg exposure (log-transformed, for blood and plasma), unadjusted [odds ratio (OR) = 2.6; 95% confidence interval (CI): 1.1, 6.2] and adjusted for sex and age (OR = 2.9; 95% CI: 1.1, 7.5). Proinflammatory [interleukin (IL)-6 and interferon (IFN)-©], anti-inflammatory (IL-4), and IL-17 cytokine levels were increased with MeHg exposure; however, in the subset of the population with elevated ANA, proinflammatory IL-1®, IL-6, IFN-©, and tumor necrosis factor (TNF)-〈 and anti-inflammatory (IL-4) cytokine levels were decreased with MeHg exposure. Although Se status was associated with MeHg level (correlation coefficient = 0.86; 95% CI: 0.29, 1.43), Se status was not associated with any changes in ANA and did not modify associations between Hg and ANA titers. Conclusions: MeHg exposure was associated with an increased ANA and changes in serum cytokine profile. Moreover, alterations in serum cytokine profiles differed based on ANA response, suggesting a specific phenotype of MeHg susceptibility. Further research on the potential health implications of these observed immunological changes is warranted.
Structure of the Rotor Ring of F-Type Na+-ATPase from Ilyobacter tartaricus

In the crystal structure of the membrane-embedded rotor ring of the sodium ion–translocating adenosine 5′-triphosphate (ATP) synthase of Ilyobacter tartaricus at 2.4 angstrom resolution, 11 c subunits are assembled into an hourglass-shaped cylinder with 11-fold symmetry. Sodium ions are bound in a locked conformation close to the outer surface of the cylinder near the middle of the membrane. The structure supports an ion-translocation mechanism in the intact ATP synthase in which the binding site converts from the locked conformation into one that opens toward subunit a as the rotor ring moves through the subunit a/c interface.