Miracle-dz/UniFAR-FTUs huggingface dataset:
Short Communication Differential Impact of P-Glycoprotein (ABCB1) and Breast Cancer Resistance Protein (ABCG2) on Axitinib Brain Accumulation and Oral Plasma Pharmacokinetics

The second-generation tyrosine kinase inhibitor and anticancer drug axitinib is a potent, orally active inhibitor of the vascular endothelial growth factor receptors 1, 2, and 3. Axitinib has clinical activity against solid tumors such as metastatic renal cell carcinoma and advanced pancreatic cancer. We studied axitinib transport using Madin-Darby canine kidney II cells overexpressing human ABCB1 or ABCG2 or murine Abcg2. Axitinib was a good substrate of ABCB1 and Abcg2, whereas transport activity by ABCG2 was moderate. These transporters may therefore contribute to axitinib resistance in tumor cells. Upon oral administration of axitinib, Abcg2( / ) and Abcb1a/1b;Abcg2( / ) mice displayed 1.7and 1.8-fold increased axitinib areas under the plasma concentration-time curve from 0 to 4 compared with those of wild-type mice. Plasma concentrations in Abcb1a/1b( / ) mice were not significantly increased. In contrast, relative brain accumulation of axitinib in Abcb1a/1b( / ) and Abcb1a/1b;Abcg2( / ) mice was, respectively, 6.8and 13.9-fold higher than that in wild-type mice at 1 h and 4.9and 20.7-fold at 4 h after axitinib administration. In Abcg2( / ) mice, we found no significant differences in brain accumulation compared with those in wild-type mice. Thus, Abcb1 strongly restricts axitinib brain accumulation and completely compensates for the loss of Abcg2 at the blood-brain barrier, whereas Abcg2 can only partially take over Abcb1-mediated axitinib efflux. Hence, Abcg2 has a stronger impact on axitinib oral plasma pharmacokinetics, whereas Abcb1 is the more important transporter at the blood-brain barrier. These findings illustrate that in vitro transport data for ABCB1 and ABCG2 cannot always be simply extrapolated to the prediction of the relative impact of these transporters on oral availability versus brain penetration.
Melia azedarach based agroforestry system in transitional tract of Karnataka

A field trial on Melia azedarach based Agroforestry system was initiated at Main Agricultural Research Station, University of Agricultural Sciences, Dharwad on medium black clay soil under rainfed conditions during 2002. The experiment consisted four spacing viz, 5m x 1m, 5m x 2m, 5m x 3m and 5m x 4m. Soybean (JS - 335) crop was grown in the interspace of Melia azedarach rows during Kharif every year. Recommended package of practices were followed for soybean. Fertilizer dose of 100:50:100 NPK kg/ha was applied to Melia azedarach in the initial four years. All the silvicultural practices were followed for better development of Melia azedarach. At the end of 10th year the soybean yield were significantly decreased in 5m x 1m and 5m x 2 m spacing of Melia azedarach as compared to 5 x 4m spacing. The diameter at breast height was significantly higher in wider row spacing viz., 5m x 4m as compared to 5m x 1m spacing. The net returns and B:C ratio were significantly higher in Melia azedarach at 5m x 4m soybean followed by at 5m x 3m + soybean as compared to the other treatments. Hence, it can be recommended that 5m x 4 m is suitable under rainfed conditions. It can be recommended for planting on bunds / canal / nala etc.
Principles of human pre-60S biogenesis

During early stages of human large ribosomal subunit (60S) biogenesis, an ensemble of assembly factors establishes and fine-tunes the essential RNA functional centers of pre-60S particles by an unknown mechanism. Here, we report a series of cryo-electron microscopy structures of human nucleolar and nuclear pre-60S assembly intermediates at resolutions of 2.5-3.2 Å. These structures show how protein interaction hubs tether assembly factor complexes to nucleolar particles and how GTPases and ATPases couple irreversible nucleotide hydrolysis steps to the installation of functional centers. Nuclear stages highlight how a conserved RNA processing complex, the rixosome, couples large-scale RNA conformational changes to pre-rRNA processing by the RNA degradation machinery. Our ensemble of human pre-60S particles provides a rich foundation to elucidate the molecular principles of ribosome formation. One-Sentence Summary High-resolution cryo-EM structures of human pre-60S particles reveal new principles of eukaryotic ribosome assembly.
Performance and applications of an automated c-axis ice-fabric analyzer

Abstract A completely automated instrument for ice-fabric analysis has been built, tested and applied. The analysis of a thin section is performed in two steps. First, the section is loaded into the machine and is automatically imaged in about 16 min. Then, at a later time and convenient location, the grains in the section are identified from a stored image (either automatically or by the user), and the c-axis orientation of each grain is calculated at a rate of 1200 grains h−1. Comparison of automated results with manual Rigsby stage results shows excellent agreement. Diagnostics indicate that the accuracy of the new technique is 0.5° in the c-axis orientation. Two specific applications are demonstrated: (1) the ability to measure internal grain orientations that may reveal internal stress, and (2) the ability to measure very thin thin sections. The latter, combined with the ability to zoom in on small regions of a section, will be useful for examining the fabric of fine-grained (< 1 mm size grains) ice.
Novel synergies and isolate specificities in the drug interactions landscape of Mycobacterium abscessus

Mycobacterium abscessus infections are difficult to treat and are often considered untreatable without tissue resection. Due to the intrinsic drug-resistant nature of the bacteria, combination therapy of three or more antibiotics is recommended. A major challenge in treating M. abscessus infections is the absence of a universal combination therapy with satisfying clinical success rates, leaving clinicians to treat infections using antibiotic lacking efficacy data. We systematically measured drug combinations in M. abscessus to establish a resource of drug interaction data and identify patterns of synergy to help design optimized combination therapies. We measured approximately 230 pairwise drug interactions among 22 antibiotics and identified 71 synergistic pairs, 54 antagonistic pairs, and four potentiator-antibiotics not previously reported. We found that commonly used drug combinations in the clinic, such as azithromycin and amikacin, are antagonistic in lab reference strain ATCC19977, whereas novel combinations, such as azithromycin and rifampicin, are synergistic. Another challenge in developing universally effective multidrug therapies for M. abscessus is the significant variation in drug response between isolates. We measured drug interactions in a focused set of 36 drug pairs across a small panel of clinical isolates with rough and smooth morphotypes. We observed highly strain-dependent drug interactions that cannot be predicted from single-drug susceptibility profiles or known drug mechanisms of action. Our study demonstrates the immense potential to identify synergistic drug combinations in the vast drug combination space and emphasizes the importance of strain-specific combination measurements for designing improved therapeutic interventions.
Antibiotic Resistance of Isolated Bacteria from Urban and Hospital Wastewaters in Hamadan City

Background and Objectives: widely use of antibiotics as therapy and uncontrolled discharge of them to receiving waters increased the percentages of antibiotic resistant bacteria in various environments which may cause problems in therapy. The aim of this study was to investigate the antibiotic resistance of E. coli, K. pneumoniae and P. aeruginosa bacteria isolated from urban and hospital wastewaters. Nine antibiotics namely Chloramphenicol, Ciprofloxacin, Trimethoprim Sulfamethoxazol, Gentamycin, Ceftizoxime, Nalidixic Acid, Ceftazidime, Ceftriaxon and Cefalexin were investigated in this study. Materials and Methods: through a cross-sectional descriptive study the isolation of bacteria from hospital and urban wastewater samples was performed by microbiological identification techniques. The resistance to nine antibiotics was tested by application of the standard disc diffusion technique and zone-size interpretation chart of Kirby-Baeur. Non-parametric Mann-Whitney test was used to assessing two environments differences. Results: The resistance percentage of E. coli to studied antibiotics was significantly less (ranged from 1.81 to 51.02%) than the resistance percentage of P. aeroginosa (ranged from 3.57 to 61.76) and K. pneumoniae (ranged from 6.45 to 91.83%). the highest resistance to antibiotics studied was for K. pneumonia in comparison with others. E. coli, K. pneumonia and P. aeroginosa bacteria showed the highest resistance to CAZ, SXT and CN, respectively. The study showed the resistance rate in hospital wastewater is more than urban wastewater. Conclusion: Easy access and uncontrolled usage of antibiotics cause discharge of antibiotics to wastewaters and consequently diminish the drugs’ effectiveness. High concentration of antibiotic and diversity in wastewater of hospital in comparison with urban wastewater causes to transfer resistant agents between bacteria and increased the multiple resistances.
Study on spatial pattern of land-use change in China during 1995–2000

It is more and more acknowledged that land-use/cover dynamic change has become a key subject urgently to be dealt with in the study of global environmental change. Supported by the Landsat TM digital images, spatial patterns and temporal variation of land-use change during 1995 –2000 are studied in the paper. According to the land-use dynamic degree model, supported by the 1km GRID data of land-use change and the comprehensive characters of physical, economic and social features, a dynamic regionalization of land-use change is designed to disclose the spatial pattern of land-use change processes. Generally speaking, in the traditional agricultural zones, e.g., Huang-Huai-Hai Plains, Yangtze River Delta and Sichuan Basin, the built-up and residential areas occupy a great proportion of arable land, and in the interlock area of farming and pasturing of northern China and the oases agricultural zones, the reclamation of arable land is conspicuously driven by changes of production conditions, economic benefits and climatic conditions. The implementation of “returning arable land into woodland or grassland” policies has won initial success in some areas, but it is too early to say that the trend of deforestation has been effectively reversed across China. In this paper, the division of dynamic regionalization of land-use change is designed, for the sake of revealing the temporal and spatial features of land-use change and laying the foundation for the study of regional scale land-use changes. Moreover, an integrated study, including studies of spatial pattern and temporal process of land-use change, is carried out in this paper, which is an interesting try on the comparative studies of spatial pattern on change process and the change process of spatial pattern of land-use change.
Temporoparietal hypometabolism in frontotemporal lobar degeneration and associated imaging diagnostic errors.

OBJECTIVE To evaluate the cause of diagnostic errors in the visual interpretation of positron emission tomographic scans with fludeoxyglucose F 18 (FDG-PET) in patients with frontotemporal lobar degeneration (FTLD) and patients with Alzheimer disease (AD). DESIGN Twelve trained raters unaware of clinical and autopsy information independently reviewed FDG-PET scans and provided their diagnostic impression and confidence of either FTLD or AD. Six of these raters also recorded whether metabolism appeared normal or abnormal in 5 predefined brain regions in each hemisphere-frontal cortex, anterior cingulate cortex, anterior temporal cortex, temporoparietal cortex, and posterior cingulate cortex. Results were compared with neuropathological diagnoses. SETTING Academic medical centers. PATIENTS Forty-five patients with pathologically confirmed FTLD (n=14) or AD (n=31). RESULTS Raters had a high degree of diagnostic accuracy in the interpretation of FDG-PET scans; however, raters consistently found some scans more difficult to interpret than others. Unanimity of diagnosis among the raters was more frequent in patients with AD (27 of 31 patients [87%]) than in patients with FTLD (7 of 14 patients [50%]) (P=.02). Disagreements in interpretation of scans in patients with FTLD largely occurred when there was temporoparietal hypometabolism, which was present in 7 of the 14 FTLD scans and 6 of the 7 scans lacking unanimity. Hypometabolism of anterior cingulate and anterior temporal regions had higher specificities and positive likelihood ratios for FTLD than temporoparietal hypometabolism had for AD. CONCLUSIONS Temporoparietal hypometabolism in FTLD is common and may cause inaccurate interpretation of FDG-PET scans. An interpretation paradigm that focuses on the absence of hypometabolism in regions typically affected in AD before considering FTLD is likely to misclassify a significant portion of FTLD scans. Anterior cingulate and/or anterior temporal hypometabolism indicates a high likelihood of FTLD, even when temporoparietal hypometabolism is present. Ultimately, the accurate interpretation of FDG-PET scans in patients with dementia cannot rest on the presence or absence of a single region of hypometabolism but rather must take into account the relative hypometabolism of all brain regions.
A Simple Method for Precise Determination of 23 Trace Elements in Granitic Rocks by ICP‐MS after Lithium Tetraborate Fusion

Abstract. An improved alkali fusion method followed by HF‐HNO3‐HC1O4 treatment is performed for simultaneous determination of 23 trace elements (Sr, Y, Zr, Nb, Ba, Hf, Ta, Th, U, and REE) by ICP‐MS in rock reference materials: basaltic rocks (JB‐2, JB‐3) and granitic rocks (JG‐la, JG‐2, JG‐3). Our improved method offers several advantages including: (1) suppression of whitish precipitates probably composed of insoluble fluorides by addition of HCIO4, (2) simple and reliable preparation procedure, (3) instrument calibration which enables straightforward simultaneous multi‐elemental analysis, and (4) the very low background levels by using pure lithium tetraborate flux. We obtained the analytical results with a reproducibility of mostly <2 % (1s̀) for the basaltic rocks and <7 % for the granitic rocks. The higher relative standard deviation (RSD) values for granitic rocks may be attributed to sample heterogeneity of coarse‐grained granitic rocks. The analytical results of the granitic rocks demonstrate that Zr and Hf abundances are consistent with the compiled values and that REE concentrations agree well with recently published data, suggesting that the Li2B4O7 fusion method applied in the present study is suitable for the analysis of the granitic rocks.
Title: Low peripheral levels of insulin growth factor-1 are associated with high incidence of delirium among elderly patients: A systematic review and meta-analysis

Introduction: Delirium, a serious condition observed in critically ill patients, clinically presents with impaired cognition and consciousness. The relationship between delirium and peripheral levels of insulin growth factor-1 (IGF-1) is unclear. Thus we conducted a metaanalysis to address this issue. AC CE PT ED M AN US CR IP T
A SPATIAL PERSPECTIVE ON THE NEW YORK DRUMLIN FIELD

This study spatially evaluates the applicability of a deformation approach to drumlin genesis for the New York drumlin field. It also assesses whether the Onondaga Escarpment, Appalachian Plateau, and Glacial Lake Iroquois influenced the spatial characteristics of drumlins. Spatial and morphometric analyses generally show a random drumlin distribution, down-ice increases in drumlin density, and down-ice decreases in drumlin elongation. These patterns are consistent with the deformation model. The Onondaga Escarpment, located transverse to ice flow, superimposed additional patterns. Compressive ice flow conditions near the escarpment: (1) nucleated drumlins through variable rates of clast deformation, drumlin densities thus increase and become clustered; and (2) reduced ice velocity so that drumlin streamlining was retarded. As the glacier advanced onto the Appalachian Plateau, drumlin-forming conditions declined because ice was nearly immobile on interfluves. Active ice was instead funneled into valleys n.
POTENTIAL EFFECTS OF CLIMATE CHANGE ON AGRICULTURAL WATER USE IN THE SOUTHEAST U.S. 1

ABSTRACT: Climate change has the potential to have dramatic effects on the agricultural sector nationally and internationally as documented in many research papers. This paper reports on research that was focused on a specific crop growing area to demonstrate how farm managers might respond to climate‐induced yield changes and the implications of these responses for agricultural water use. The Hadley model was used to generate climate scenarios for important agricultural areas of Georgia in 2030 and 2090. Linked crop response models indicated generally positive yield changes, as increased temperatures were associated with increased precipitation and CO2. Using a farm management model, differences in climate‐induced yield impacts among crops led to changes in crop mix and associated water use; non‐irrigated cropland received greater benefit since irrigated land was already receiving adequate moisture. Model results suggest that farm managers will increase cropping intensity by decreasing fallowing and increasing double cropping; corn acreage decreased dramatically, peanuts decreased moderately and cotton and winter wheat increased. Water use on currently irrigated cropland fell. The potential for increased water use through conversion of agriculturally important, but currently non‐irrigated, growing areas is substantial.
First Permian–Early Triassic zircon ages for tin‐bearing granites from the Gemeric unit (Western Carpathians, Slovakia): connection to the post‐collisional extension of the Variscan orogen and S‐type granite magmatism

This study presents the first preliminary U–Pb zircon data on tin‐bearing S‐type granites from the Gemeric unit of the Western Carpathians (Slovakia). U–Pb single zircon dating controlled by cathodoluminescence suggests crystallization of the Gemeric granites during Permian to Early Triassic (303–241 Ma) time. Post‐crystallization, low‐temperature metamorphic overprint is reflected by partial Pb loss in zircons. These Gemeric granites are younger than the highly fractionated, S‐type, tin‐ and rare‐element‐bearing leucogranites in the European Variscides. They may have resulted from partial melting, triggered by increased heat flow from the mantle below the continental crust, and most probably intruded during the post‐collisional extension and initial rifting of the Variscan orogenic belt. During Alpine orogeny, the Gemeric granites were affected by a low‐temperature deformation and metamorphism.
A Classification of Alluvial Channel Systems

Abstract A new classification of alluvial channel systems is proposed, based on the braiding parameter: the number of braids per mean meander wavelength, braids being defined by the mid-line of the channels surrounding each braid bar. Single-channel and multi-channel systems are defined as having braiding parameters less than and more than one, respectively. Channel systems are further divided into low-and high-sinuosity categories at the boundary 1.5, giving four types, of which single-channel high-sinuosity (meandering) and multi-channel low-sinuosity (braided) are by far the most common. The other two types are much less abundant: single-channel low-sinuosity (straight), and multi-channel high-sinuosity (anastomosing). The classification can be applied to ancient alluvial deposits through an understanding of the processes that relate channel morphologies to their resulting sedimentary suites. As the processes are imperfectly understood, so the application to paleochannels is imprecise. However, it can be made satisfactorily in most cases, provided maximum use is made of the channel-process information in alluvial sedimentary models.
Growth Patterns of Subaqueous Depositional Channel Lobe Systems Developed Over A Basement With A Downdip Break In Slope: Laboratory Experiments

Abstract A series of large-scale experiments on nonchannelized, depositional turbidity currents show the evolution and complex stratigraphy of channel–lobe systems developed updip and downdip of a break in slope. Two different sets of experimental turbidity currents with different sediment concentrations were run. The results provided a comparative picture of the gross structure of the fans, with information on their surfaces, growth sequences, and times of activity of the incised channels and lobed features. In particular, data analysis focused on: (a) velocity and suspended-sediment concentration of the flows themselves; (b) time and spatial sequences of channel and lobe construction and modification, and (c) spatial trends in grain-size distribution along the deposit. Significantly, the floor geometry employed in this study allowed investigation of adjustments in deep-sea fan deposition associated with natural changes in bed slope. We show here that the break in slope played a very important role in governing channel aggradation and lobe architecture over the deposit. More specifically, the slope break tended to break up the formation of long channels and enhance the formation of lobate features. A comparison with field submarine lobe analogs demonstrates that the morphodynamics and stratigraphy associated with lobed fans can indeed be modeled, within limits, at laboratory scale.