Miracle-dz/UniFAR-FTUs huggingface dataset:
The Inhibitory Effects of Herbal Components on CYP2C9 and CYP3A4 Catalytic Activities in Human Liver Microsomes

Herbal medicines are widely consumed by patients in different clinical settings in the United States and all over the world. In this study, 7 herbal components ginsenosides Rb1, Rb2, Rc, and Rd (from ginseng quercetin) ginkgolides A and B (from ginkgo biloba) were investigated for their inhibitory effects on hepatic CYP2C9 and CYP3A4 catalytic activities in human liver microsomes. Tolbutamide 4-methylhydroxylation and testosterone 6β-hydroxylation were used as index reactions of CYP2C9 or CYP3A4 catalytic activities, respectively. The metabolites of both reactions were measured by high-performance liquid chromatography and used as indicators of whether enzymes were inhibited or unaffected by these agents. Herbal components were studied at various concentrations (0.1, 1, 10, 100, 200 μmol/L). The herbal compounds investigated were capable of inhibiting CYP2C9 and CYP3A4 catalytic activities, but the potencies differed. Quercetin showed marked inhibitory effects on both tolbutamide 4-methylhydroxylation and testosterone 6β-hydroxylation with IC50 values of 35 and 38 μmol/L, respectively. Ginsenoside Rd also had significant inhibitory potency on both CYP2C9- and CYP3A4-mediated index reactions with IC50 values of 105 and 62 μmol/L, respectively. Ginsenosides Rb1, Rb2, and Rc had limited inhibitory activities on both enzyme reaction systems, whereas the effects of ginkgolides A and B appeared negligible. It is concluded that the components of ginseng and ginkgo biloba screened are capable of inhibiting CYP2C9- and CYP3A4-mediated metabolic reactions. Our findings suggest that quercetin and ginsenoside Rd have the potential to interact with conventional medicines that are metabolized by CYP2C9 and CYP3A4 in vivo.
Global relaxed non-stationary multisplitting multi-parameter methods

Abstract Based on the local relaxed method and the system relaxed method of parallel multisplitting described by Frommer and Mayer, the paper presents a global relaxed non-stationary multisplitting multi-parameter method by introducing some relaxed parameters. Convergence of these methods when coefficient matrices are H-matrices is investigated. Efficiency of the global relaxed non-stationary multisplitting multi-parameter method is shown by numerical experiments. These indicate that, when choosing the approximately optimal relaxed parameters, the methods have a faster convergent rate than previous methods.
Ocean Acidification Leads to Counterproductive Intestinal Base Loss in the Gulf Toadfish (Opsanus beta)

Oceanic CO2 has increased from 280 to 380 μatm since preindustrial times and is expected to reach 1,900 μatm by 2300. In addition, regional upwelling zones exhibit levels up to 2,300 μatm, making exploration at future global projected CO2 levels ecologically relevant today. Recent work has demonstrated that CO2 exposure as low as 1,000 μatm induces acidosis in toadfish (Opansus beta), leading to metabolic compensation by retention of blood in an effort to defend pH. Since increased serosal translates to increased secretion rates in isolated intestinal tissue, we predicted that blood elevation of and Pco2 during exposure to 1,900 μatm CO2 would increase in vivo base secretion rates. Rectal fluid and CaCO3 excretions were collected from toadfish exposed to 380 (control) and 1,900 μatm CO2 for 72 h. Fluids were analyzed for pH, osmolality, ionic composition, and total CO2. Precipitated CaCO3 was analyzed for titratable alkalinity, Mg2+, and Ca2+ content. Fish exposed to 1,900 μatm CO2 exhibited higher rectal base excretion rates, higher rectal fluid (mmol L−1), and lower fluid Cl− (mmol L−1) than controls, suggesting increased intestinal anion exchange as a result of the compensated respiratory acidosis. This study verifies that imminent projected CO2 levels expected by the year 2300 lead to greater intestinal loss, a process that acts against compensation for a CO2-induced acidosis.
Learning Dimensional Descent for Optimal Motion Planning in High-dimensional Spaces

We present a novel learning-based method for generating optimal motion plans for high-dimensional motion planning problems. In order to cope with the curse of dimensional- ity, our method proceeds in a fashion similar to block co- ordinate descent in finite-dimensional optimization: at each iteration, the motion is optimized over a lower dimensional subspace while leaving the path fixed along the other dimen- sions. Naive implementations of such an idea can produce vastly suboptimal results. In this work, we show how a prof- itable set of directions in which to perform this dimensional descent procedure can be learned efficiently. We provide suf- ficient conditions for global optimality of dimensional de- scent in this learned basis, based upon the low-dimensional structure of the planning cost function. We also show how this dimensional descent procedure can easily be used for problems that do not exhibit such structure with monotonic convergence. We illustrate the application of our method to high dimensional shape planning and arm trajectory planning problems.
Development and Field Validation of a Multimedia Exposure Assessment Model for Waste Load Allocation in Aquatic Ecosystems: Application to 2,3,7,8-Tetrachlorodibenzo-p-dioxin and 2,3,7,8-Tetrachlorodibenzofuran in the Fraser River Watershed

Knowledge of the relationship between contaminant emissions and ambient concentrations is crucial in achieving environmental quality objectives. This paper reports the development and field validation of EcoFate, a time dependent multimedia mass balance simulation model of the environmental distribution food-chain accumulation of organic contaminants in aquatic ecosystems. The purpose of the model is to present a methodology for deriving maximum daily-loading estimates in accordance with environmental quality objectives for a variety of aquatic ecosystems impacted by emissions from one or several point or nonpoint sources. The application of the model to multiple, time-varying pulp and paper mill discharges of 2,3,7,8-tetrachlorodibenzo-p-dioxin and 2,3,7,8-tetrachlorodibenzofuran in the Fraser-Thompson River system from 1988 to 1995 is demonstrated. The ability of the model to predict chemical concentrations in various environmental media and organisms resulting from chemical emissions is tested against field data collected over a 7 year period. The results include (1) a comparison of observed and predicted concentrations, (2) an assessment of uncertainty, and (3) a test of the model`s temporal response to changes in contaminant loadings. The application of the model for the derivation of maximum daily loadings for multiple point sources in watersheds is illustrated.
An Examination of Experimental Methodology for Classifiers of Relational Data

Experimental methodology for evaluating classification algorithms in relational (i.e., networked) data is complicated by dependencies between related data instances. We survey the literature on relational classifiers and examine the various experimental methodologies reported therein. Our survey reveals that methodologies fall into two main groups, based on distinct formulations of the classification problem: (1) between-network classification and (2) within-network classification. While the methodology for the between- network setting is relatively straightforward, methodologies for within-network classification are more complex and varied. We explore a number of these variations and present experimental results to illustrate important similarities and differences among different methodologies for within-network classification.
Trends in Treatment Patterns and Outcomes for Ductal Carcinoma In Situ.

BACKGROUND Impact of contemporary treatment of pre-invasive breast cancer (ductal carcinoma in situ [DCIS]) on long-term outcomes remains poorly defined. We aimed to evaluate national treatment trends for DCIS and to determine their impact on disease-specific (DSS) and overall survival (OS). METHODS The Surveillance, Epidemiology, and End Results (SEER) registry was queried for patients diagnosed with DCIS from 1991 to 2010. Treatment pattern trends were analyzed using Cochran-Armitage trend test. Survival analyses were performed using inverse probability weights (IPW)-adjusted competing risk analyses for DSS and Cox proportional hazard regression for OS. All tests performed were two-sided. RESULTS One hundred twenty-one thousand and eighty DCIS patients were identified. The greatest proportion of patients was treated with lumpectomy and radiation therapy (43.0%), followed by lumpectomy alone (26.5%) and unilateral (23.8%) or bilateral mastectomy (4.5%) with significant shifts over time. The rate of sentinel lymph node biopsy increased from 9.7% to 67.1% for mastectomy and from 1.4% to 17.8% for lumpectomy. Compared with mastectomy, OS was higher for lumpectomy with radiation (hazard ratio [HR] = 0.79, 95% confidence interval [CI] = 0.76 to 0.83, P < .001) and lower for lumpectomy alone (HR = 1.17, 95% CI = 1.13 to 1.23, P < .001). IPW-adjusted ten-year DSS was highest in lumpectomy with XRT (98.9%), followed by mastectomy (98.5%), and lumpectomy alone (98.4%). CONCLUSIONS We identified substantial shifts in treatment patterns for DCIS from 1991 to 2010. When outcomes between locoregional treatment options were compared, we observed greater differences in OS than DSS, likely reflecting both a prevailing patient selection bias as well as clinically negligible differences in breast cancer outcomes between groups.
Presence of Alternaria in Scalp of Patients with Alopecia Areata: Triggering Factor or Coexistence?

AA (Alopecia areata) is the most frequent cause of inflammation-induced hair loss, affecting 0.1 to 0.2% of population worldwide. The development of organ-specific autoimmune reactions directed against anagen hair follicles seems to play a key role in the pathogenesis of alopecia areata. However, the triggering antigen(s) responsible for inducing autoimmune phenomena in these individuals remain unknown. Viral, bacterial or fungal pathogens have been implied as possible triggering factors of autoimmune reactions. The present study aims to identify the role of dematiaceous fungi in the pathogenesis of alopecia areata. 30 patients diagnosed clinically as alopecia areata and 30 normal age matched persons have undergone mycological examination. Mycology examination of the epidermal scrapings was done by DME (direct microscopic examination), culture on SDA (sabouraud's dextrose agar) and imaging. There is significantly higher percentage of positive results for Alternaria species by culture on sabouraud's agar in patients group (20%) compared to controls (13.3%) P-value < 0.05. The possible role of Alternaria antigens (e.g. antigens involved in melanin synthesis) in triggering autoimmunity in alopecia areata still needs further research on a wider scale of cases.
Glacial Processes and Morphologies in the Southern Hemisphere of Mars

Understanding the history of ice on Mars provides important insight into Martian geologic and climatic history. A model capable of ice reconstruction that requires few input parameters, and a detailed analyses of landforms in an area with hypothesized glacial modification, Argyre Planitia, provide further understanding of Martian ice. A threshold-sliding model was developed to model perfectly-plastic deformation of ice that is applicable to ice bodies that deform when a threshold basal shear stress is exceeded. The model requires three inputs describing bed topography, ice margins, and a function defining the threshold basal shear stress. The model was tested by reconstructing the Greenland ice sheet and then used to reconstruct ice draping impact craters on the margins of the Martian South Polar Layered Deposits using an average constant basal shear stress of ~0.6 bars for the majority of Martian examples. This inferred basal shear stress value is almost 1/3 of the average basal shear stress calculated for the Greenland ice sheet. Reasons for the lower Martian basal shear stress are unclear but could involve the strain-weakening behavior of ice. The threshold-sliding model can be used for ice reconstruction and forward modeling of erosion and deposition to provide further insight into the history of ice on Mars. To test the glacial hypothesis in the Argyre region, landforms are examined using images from the High Resolution Imaging Science Experiment (HiRISE) and other Martian datasets. Linear grooves and streamlined hills are consistent with glacial erosion. Deep semi-circular embayments in mountains resemble cirques. U-shaped valleys have stepped longitudinal profiles and tributary valleys have hanging valley morphology similar to terrestrial glacial valleys. Boulders blanketing a valley floor resemble ground
The Polarity Protein Scribble Regulates Myelination and Remyelination in the Central Nervous System

The development and regeneration of myelin by oligodendrocytes, the myelin-forming cells of the central nervous system (CNS), requires profound changes in cell shape that lead to myelin sheath initiation and formation. Here, we demonstrate a requirement for the basal polarity complex protein Scribble in CNS myelination and remyelination. Scribble is expressed throughout oligodendroglial development and is up-regulated in mature oligodendrocytes where it is localised to both developing and mature CNS myelin sheaths. Knockdown of Scribble expression in cultured oligodendroglia results in disrupted morphology and myelination initiation. When Scribble expression is conditionally eliminated in the myelinating glia of transgenic mice, myelin initiation in CNS is disrupted, both during development and following focal demyelination, and longitudinal extension of the myelin sheath is disrupted. At later stages of myelination, Scribble acts to negatively regulate myelin thickness whilst suppressing the extracellular signal-related kinase (ERK)/mitogen-activated protein kinase (MAP) kinase pathway, and localises to non-compact myelin flanking the node of Ranvier where it is required for paranodal axo-glial adhesion. These findings demonstrate an essential role for the evolutionarily-conserved regulators of intracellular polarity in myelination and remyelination.
Sequential Pattern Mining: A Survey

Data mining [Chen et al. 1996] is the process of extracting interesting (non-trivial, implicit, previously unknown and potentially useful) information or patterns from large information repositories such as: relational database, data warehouses, XML repository, etc. Also data mining is known as one of the core processes of Knowledge Discovery in Database (KDD). Many people take data mining as a synonym for another popular term, Knowledge Discovery in Database (KDD). Alternatively other people treat Data Mining as the core process of KDD. The KDD processes are shown in Figure 1 [Han and Kamber 2000]. Usually there are three processes. One is called preprocessing, which is executed before data mining techniques are applied to the right data. The preprocessing includes data cleaning, integration, selection and transformation. The main process of KDD is the data mining process, in this process different algorithms are applied to produce hidden knowledge. After that comes another process called postprocessing, which evaluates the mining result according to users’ requirements and domain knowledge. Regarding the evaluation results, the knowledge can be presented if the result is satisfactory, otherwise we have to run some or all of those processes again until we get the satisfactory result. The actually processes work as follows. First we need to clean and integrate the databases. Since the data source may come from different databases, which may have some inconsistences and duplications, we must clean the data source by removing those noises or make some compromises. Suppose we have two different databases, different words are used to refer the same thing in their schema. When we try to integrate the two sources we can only choose one of them, if we know that they denote the same thing. And also real world data tend to be incomplete and noisy due to the manual input mistakes. The integrated data sources can be stored in a database, data warehouse or other repositories. As not all the data in the database are related to our mining task, the second process is to select task related data from the integrated resources and transform them into a format that is ready to be mined. Suppose we want to find which items are often purchased together in a supermarket, while the database that records the purchase history may contains customer ID, items bought, transaction time, prices, number of each items and so on, but for this specific task we only need items bought. After selection of relevant data, the database that we are going to apply our data mining techniques to will be much smaller, consequently the whole process will be
Cyathin, a new antibiotic complex produced by Cyathus helenae.

The fungus Cyathus helenae Brodie (Gasteromycetes) produces a complex of antibiotic substances collectively called cyathin. Highest yields were obtained when the fungus was grown at room temperature for 25 days on a chemically defined liquid medium in static culture. The action spectrum of cyathin (and its components) was determined by placing cyathin-bearing paper discs on agar plates seeded with the microorganisms being tested. The cyathin complex is active against actinomycetes, bacteria (gram-positive as well as gram-negative), and some fungi, including dermatophytes. Weaker antimicrobial activity is also shown by C. striatus (Huds.) Willd. ex Pers. , C. poeppigii L. , and C. limbatus L. Seven different compounds have been isolated from the cyathin complex: 2,4,5-trihydroxybenzaldehyde (C7H6O4),cyathin A3(C20H30O3), cyathin A4(C20H30O4),allocyathinA4(C20H30O4),cyathin B3(C20H28O3), cyathin B4(C20H28O4), and cyathin C5(C20H26O5). Aside from 2,4,5-trihydroxybenzaldehyde, these compounds appear not to have.
History of burial diagenesis determined from isotopic geochemistry, Frio Formation, Brazoria County, Texas

Progressive burial diagenesis of the Oligocene Frio Formation in Brazoria County, Texas, has resulted in extensive reaction between pore fluids and sediment in a major shift toward water/rock equilibrium. Carbon and oxygen isotopic data, combined with fluid isotopic data from the literature, indicate that quartz cement formed at 75 to 80°C and kaolinite at approximately 100°C. The zone of most rapid albitization is near 150°C. Authigenic carbonates formed over a wide range of temperatures, and those within the peak zone of hydrocarbon generation are depleted in 13C. At depths shallower than approximately 2,600 m, quartz and carbonate cementation in primary intergranular pore spaces (passive diagenesis) dominated. Below 2,600 m, within the geopres ured zone, reaction of detrital components (active diagenesis) is the major process. Organic maturation, albitization, and the transition of smectite to illite are the processes that contribute most of the components required for precipitation of cements. Quartz cementation occurred quite early in the burial history of the Frio (beginning at approximately 1,500 m of burial), when rates of fluid expulsion were at a maximum and when little of the Frio sandstone section had reached the zone of albitization.
Functional Impact of the Ryanodine Receptor on the Skeletal Muscle L-Type Ca2+ Channel

L-type Ca2+ channel (L-channel) activity of the skeletal muscle dihydropyridine receptor is markedly enhanced by the skeletal muscle isoform of the ryanodine receptor (RyR1) (Nakai, J., R.T. Dirksen, H.T. Nguyen, I.N. Pessah, K.G. Beam, and P.D. Allen. 1996. Nature. 380:72–75.). However, the dependence of the biophysical and pharmacological properties of skeletal L-current on RyR1 has yet to be fully elucidated. Thus, we have evaluated the influence of RyR1 on the properties of macroscopic L-currents and intracellular charge movements in cultured skeletal myotubes derived from normal and “RyR1-knockout” (dyspedic) mice. Compared with normal myotubes, dyspedic myotubes exhibited a 40% reduction in the amount of maximal immobilization-resistant charge movement (Qmax, 7.5 ± 0.8 and 4.5 ± 0.4 nC/μF for normal and dyspedic myotubes, respectively) and an approximately fivefold reduction in the ratio of maximal L-channel conductance to charge movement (Gmax/Qmax). Thus, RyR1 enhances both the expression level and Ca2+ conducting activity of the skeletal L-channel. For both normal and dyspedic myotubes, the sum of two exponentials was required to fit L-current activation and resulted in extraction of the amplitudes (Afast and Aslow) and time constants (τslow and τfast) for each component of the macroscopic current. In spite of a >10-fold in difference current density, L-currents in normal and dyspedic myotubes exhibited similar relative contributions of fast and slow components (at +40 mV; Afast/[Afast + Aslow] ∼ 0.25). However, both τfast and τslow were significantly (P < 0.02) faster for myotubes lacking the RyR1 protein (τfast, 8.5 ± 1.2 and 4.4 ± 0.5 ms; τslow, 79.5 ± 10.5 and 34.6 ± 3.7 ms at +40 mV for normal and dyspedic myotubes, respectively). In both normal and dyspedic myotubes, (−) Bay K 8644 (5 μM) caused a hyperpolarizing shift (∼10 mV) in the voltage dependence of channel activation and an 80% increase in peak L-current. However, the increase in peak L-current correlated with moderate increases in both Aslow and Afast in normal myotubes, but a large increase in only Afast in dyspedic myotubes. Equimolar substitution of Ba2+ for extracellular Ca2+ increased both Afast and Aslow in normal myotubes. The identical substitution in dyspedic myotubes failed to significantly alter the magnitude of either Afast or Aslow. These results demonstrate that RyR1 influences essential properties of skeletal L-channels (expression level, activation kinetics, modulation by dihydropyridine agonist, and divalent conductance) and supports the notion that RyR1 acts as an important allosteric modulator of the skeletal L-channel, analogous to that of a Ca2+ channel accessory subunit.
Controlled trial on nutrition supplementation in outpatients with symptomatic alcoholic cirrhosis.

A controlled trial on nutrition supplementation in ambulatory patients with decompensated alcoholic liver disease was carried out during 1 year. Fifty-one patients were studied; 26 were assigned to an experimental group receiving a daily supplement of 1000 kcal and 34 g of proteins given as a casein-based enteral nutrition product and 25 to a control group receiving one placebo capsule. Patients were examined in a special clinic once a month or more if required. Sixty-eight percent of patients admitted to alcohol ingestion or had alcohol in urine samples on at least one occasion. Dietary recalls showed a significantly higher protein and caloric intake in case patients subjects (p < .0001). Nine patients died during the study, three case patients and six control patients (p = NS). The frequency of hospitalizations was significantly less in the experimental group. This difference was attributed to a reduction in severe infections. Mid-arm circumference, serum albumin concentration, and hand grip strength improved earlier in case patients, although both groups had a significant improvement in these parameters. Bilirubin and aspartate aminotransferase decreased and prothrombin time increased significantly in both groups during the study period, without differences between groups. It is concluded that nutrition support decreases nutrition-associated complications in patients with alcoholic liver disease.