gebhart/patrepeval huggingface dataset:
Azoles, a48 llylamines and drug metabolism (1992)

Four antifungal drugs, the azoles ketoconazole, itraconazole and fluconazole, and the allylamine terbinafine, were studied for their effects on the metabolism of cyclosporin A (CyA) and cortisol by human liver microsomes in vitro (n = 3). Ketoconazole produced marked inhibition of CyA hydroxylase (to metabolites M17 and M1) with IC50 and Ki values of 0.24 +/- 0.01 and 0.022 +/- 0.004 microM, respectively. On the basis of the IC50, itraconazole was 10 times less potent (IC50 of 2.2 +/- 0.2 microM), and fluconazole and terbinafine were each above 100 microM. No kinetic parameters were calculated for terbinafine because of the lack of inhibitory effects. Ketoconazole was the most potent inhibitor of cortisol metabolism (to 6 beta-hydroxycortisol, IC50 = 0.6 microM). Itraconazole produced marked inhibition of cortisol metabolism (IC50 = 2.4 microM), but fluconazole and terbinafine had little effect. These data confirm that ketoconazole is a potent inhibitor of cytochrome P-450-IIIA4, and this has clinical relevance. Although the inhibition with fluconazole was much less than with itraconazole at equimolar concentrations, it should be noted that in-vivo plasma concentrations of fluconazole are much greater than that of itraconazole. Clinical interactions of CyA with both fluconazole and itraconazole have been reported; in contrast to these azoles, terbinafine does not have the same interaction potential.
Breaking the diffraction barrier in fluorescence microscopy at low light intensities by using reversibly photoswitchable proteins (2005)

Fluorescence microscopy is indispensable in many areas of science, but until recently, diffraction has limited the resolution of its lens-based variant. The diffraction barrier has been broken by a saturated depletion of the marker's fluorescent state by stimulated emission, but this approach requires picosecond laser pulses of GW/cm2 intensity. Here, we demonstrate the surpassing of the diffraction barrier in fluorescence microscopy with illumination intensities that are eight orders of magnitude smaller. The subdiffraction resolution results from reversible photoswitching of a marker protein between a fluorescence-activated and a nonactivated state, whereby one of the transitions is accomplished by means of a spatial intensity distribution featuring a zero. After characterizing the switching kinetics of the used marker protein asFP595, we demonstrate the current capability of this RESOLFT (reversible saturable optical fluorescence transitions) type of concept to resolve 50-100 nm in the focal plane. The observed resolution is limited only by the photokinetics of the protein and the perfection of the zero. Our results underscore the potential to finally achieve molecular resolution in fluorescence microscopy by technical optimization.
Unexpected conformational stability of poly(2'azido-2'-deoxyuridylic acid) (1972)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTUnexpected conformational stability of poly(2'azido-2'-deoxyuridylic acid)Paul F. Torrence, James A. Waters, and Bernhard WitkopCite this: J. Am. Chem. Soc. 1972, 94, 10, 3638–3639Publication Date (Print):May 1, 1972Publication History Published online1 May 2002Published inissue 1 May 1972https://pubs.acs.org/doi/10.1021/ja00765a069https://doi.org/10.1021/ja00765a069research-articleACS PublicationsRequest reuse permissionsArticle Views37Altmetric-Citations19LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Lateral exit-zone stenosis and lumbar radiculopathy (1999)

The authors conclude that this lesion presents with characteristic physical findings and on imaging studies that distinguish it from other causes of radiculopathy, and they propose a lesion-specific, facet-sparing surgical technique that has yielded excellent results.
Pathogenesis of Plexiform Neurofibroma: Tumor-Stromal/Hematopoietic Interactions in Tumor Progression (2011)

Neurofibromatosis type 1 (NF1) is a genetic disease that results from either heritable or spontaneous autosomal dominant mutations in the NF1 gene. A second-hit mutation precedes the predominant NF1 neoplasms, which include myeloid leukemia, optic glioma, and plexiform neurofibroma. Despite this requisite NF1 loss of heterozygosity in the tumor cell of origin, nontumorigenic cells contribute to both generalized and specific disease manifestations. In mouse models of plexiform neurofibroma formation, Nf1 haploinsufficient mast cells promote inflammation, accelerating tumor formation and growth. These recruited mast cells, hematopoietic effector cells long known to permeate neurofibroma tissue, mediate key mitogenic signals that contribute to vascular ingrowth, collagen deposition, and tumor growth. Thus, the plexiform neurofibroma microenvironment involves a tumor/stromal interaction with the hematopoietic system that depends, at the molecular level, on a stem cell factor/c-kit-mediated signaling axis. These observations parallel findings in other NF1 disease manifestations and are clearly relevant to medical management of these neurofibromas.
Concentration Variations Within Pipe Cross-Section in a Dilute Phase Pneumatic Conveying System (1997)

Measurements of the distribution of solids over the cross section of a dilute phase pneumatic conveying line were made using attenuation of low energy X-rays. The measurements were taken along a grid of chords across the pipe for mass solids loading ratios up to 3:1 in regions of accelerating flow, fully developed flow in horizontal and vertical orientations, and following 90 degree bends in the horizontal and vertical planes. Image reconstruction methods for visualisation of the data are discussed.
Construction of block-shuffled libraries of DNA for evolutionary protein engineering: Y-ligation-based block shuffling (2002)

Evolutionary protein engineering is now proceeding to a new stage in which novel technologies, besides the conventional point mutations, to generate a library of proteins, are required. In this context, a novel method for shuffling and rearranging DNA blocks (leading to protein libraries) is reported. A cycle of processes for producing combinatorial diversity was devised and designated Y-ligation-based block shuffling (YLBS). Methodological refinement was made by applying it to the shuffling of module-sized and amino acid-sized blocks. Running three cycles of YLBS with module-sized GFP blocks resulted in a high diversity of an eight-block shuffled library. Partial shuffling of the central four blocks of GFP was performed to obtain in-effect shuffled protein, resulting in an intact arrangement. Shuffling of amino acid monomer-sized blocks by YLBS was also performed and a diversity of more than 10(10) shuffled molecules was attained. The deletion problems encountered during these experiments were shown to be solved by additional measures which tame type IIS restriction enzymes. The frequency of appearance of each block was skewed but was within a permissible range. Therefore, YLBS is the first general method for generating a huge diversity of shuffled proteins, recombining domains, exons and modules with ease.
Estimation of Prostate Cancer Probability by Logistic Regression: Free and Total Prostate-specific Antigen, Digital Rectal Examination, and Heredity Are Significant Variables (1999)

The probability calculated by logistic regression provides better diagnostic accuracy for prostate cancer than the presently used multistep algorithms for estimation of the need to perform biopsy.
The Adjunctive Use of Metformin to Treat or Prevent Atypical Antipsychotic-Induced Weight Gain: A Review (2010)

Patients with schizophrenia have a greater incidence of being overweight or obese compared with the general population. Such individuals are often treated with second-generation (atypical) antipsychotics (SGAs), which are associated with weight gain, dyslipidemia, and other metabolic derangements. As a result, frequent monitoring of weight and other metabolic parameters is recommended. In addition, several pharmacologic strategies to help prevent or reduce SGA-induced weight gain have been proposed. Despite this, clinicians often struggle to manage obesity and metabolic issues in such patients. Metformin has attracted attention as a potential treatment option because it is thought to result in weight reduction and improved glycemic control in obese patients with and without type 2 diabetes mellitus. This article focuses on relevant pharmacologic aspects of metformin and reviews currently available evidence on the use of metformin as an augmentation agent for the treatment or prevention of SGA-induced weight gain.
Mutation at either Arg336 or Arg562 in Factor VIII Is Insufficient for Complete Resistance to Activated Protein C (APC)-mediated Inactivation: Implications for the APC Resistance Test (1998)

Activated protein C (APC)-mediated inactivation of factor VIII (FVIII) correlates with cleavage at either Arg336 and/or Arg562. To elucidate the APC cleavage requirements for inactivation of FVIII, APC cleavage site mutants in FVIII (R336I, R562K and R336I/R562K) were made by site-directed mutagenesis. Analysis of these FVIII mutants expressed in COS-1 monkey cells demonstrated the thrombin-cleaved mutant R562K was resistant to APC cleavage at residue 562 but not at Arg336 and the thrombin cleaved mutant R3361 was mostly resistant to APC cleavage at residue 336, but was sensitive to APC cleavage at Arg562. The double mutant R336I/R562K was mostly resistant to cleavage at residue 336 and completely resistant to cleavage at residue 562. Thus, APC cleavage of FVIII does not require a specific order of cleavage at either residue. The functional inactivation by APC was studied using partially purified preparations of FVIII expressed in Chinese hamster ovary cells. Both single mutants were inactivated at similar rates but slower than wild-type FVIII, whereas the double mutant R336I/R562K was resistant to inactivation. The ability of a commercially available APC-resistance assay kit to detect APC resistant FVIII was tested by reconstituting FVIII deficient plasma with the APC resistant mutants. Only the R336I/R562K demonstrated a reduced APC-resistance ratio, indicating that this assay can not detect the single APC cleavage site mutant of FVIII. These results suggest that APC-mediated cleavage at either Arg336 or Arg562 partially inactivate FVIII.
Myelokathexis — A New Form of Chronic Granulocytopenia (1964)

THE quantitative analysis of granulopoiesis requires knowledge not only of the complex relations between cytologic compartments within the bone marrow but also of the distribution and fate of cells capable of leaving the vascular bed after only a brief sojourn in the bloodstream and under conditions not readily accessible to observation. The genesis of many of the granulocytopenic states has thus remained obscure. In certain types increased peripheral destruction by a variety of mechanisms has been invoked. In others it is possible to relate the lack of granulocytes in the blood to a primary disturbance in bone-marrow function leading to . . .
[Polymorphism of regulated upon activation, normal T cell expressed and secreted promoter region -28 position in Chinese allergic asthmatic children]. (2004)

Polymorphism of RANTES C-28G was associated with susceptibility of asthma in children, and may aggravate the disease through increasing the level of RANTES and eosinophils.
Overexpression of Bax enhances antitumor activity of chemotherapeutic agents in human head and neck squamous cell carcinoma. (2000)

Overexpression of the Bax protein in human head and neck squamous cell carcinoma A253 cells was reported to result in an increased sensitivity to various chemotherapeutic agents in vitro (Guo et al., Oncol. Res., 11: 91-99, 1999). In the present study, the relationship between Bax expression and response to chemotherapy was further investigated in vitro and in vivo model systems. For in vitro study, A253, A253/Vec (pcDNA3 vector transfectant), and A253/Bax (pcDNA3/Bax transfectant, expressing 50-fold higher Bax protein than A253 and A253/Vec) cells were exposed to various concentrations of raltitrexed (a specific thymidylate synthase inhibitor) and SN-38 (a topoisomerase I inhibitor) for 2 h, and cell growth inhibition was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide clonogenic assay. Compared to A253/Vec, A253/Bax cells exhibited 9.5- and 13.5-fold increases in sensitivity to raltitrexed and SN-38, respectively. For in vivo study, A253/Vec and A253/Bax tumor xenografts were established by s.c. injection of tumor cells into nude mice. The antitumor activity and toxicity of raltitrexed (i.v. push daily for 5 days) and irinotecan (a prodrug of SN-38; i.v. push daily for 3 days) were evaluated. The maximum tolerated doses of raltitrexed and irinotecan were 30 and 100 mg/kg/day, respectively. At the maximum tolerated doses, minimal antitumor activity was observed with raltitrexed, although irinotecan was more active than raltitrexed against A253 or A253/Vec tumors. In contrast, both raltitrexed and irinotecan were significantly more active against A253/Bax xenografts than against A253/Vec xenografts; the yield for complete tumor regression (cure) was 40% and 100% with raltitrexed and irinotecan, respectively, with no significant toxicity. Furthermore, the observed increase of antitumor activity in A253/Bax tumors was associated with an enhanced induction of apoptosis in vivo. The in vivo results demonstrated a proof of the principal concept that selecting up-regulation of the proapoptosis gene Bax can provide the basis for a greater therapeutic efficacy to a variety of chemotherapeutic agents with different structures and mechanisms of action.
Effects of insulin-like growth factor-I peptides in rats with acute renal failure (1994)

The effect of insulin-like growth factor-I (IGF-I) administration on body weight gain and the rate of recovery of renal function was investigated in rats following an acute episode of renal ischaemia. Since the des(1-3)IGF-I and LR3IGF-I variant forms of IGF-I have been shown to be more potent than IGF-I, their effects were also examined. Acute renal failure was produced in male Sprague-Dawley rats by clamping both renal arteries for 45 min. Treatment was commenced at the time of renal artery occlusion with vehicle (0.1 mol acetic acid/l; control group), IGF-I (2.0 mg/kg per day), des(1-3)IGF-I (2.0 mg/kg per day) or LR3IGF-I (1.5 mg/kg per day) by s.c. osmotic pump, and continued for 7 days, with rats being held in metabolism cages. Glomerular filtration rate (GFR) was estimated by the use of 51Cr-EDTA continuously infused i.p. via osmotic pump. Following the episode of renal ischaemia, body weight gain and nitrogen retention were significantly improved in all three peptide-treated groups, and serum urea concentrations were reduced in the groups treated with IGF-I and des(1-3)IGF-I. However, there was no evidence of the variants having any increased potency over the growth effects of IGF-I itself. GFR was significantly reduced, urine output was increased and urinary concentrating ability was reduced in all groups compared with normal rats, with no significant effect of the IGF peptides being apparent. A closer examination of the acute effects of LR3IGF-I on renal function was undertaken by measuring GFR for 3 days before and 3 days after renal ischaemia in two groups of rats, treated for the latter 3 days with either vehicle (controls) or LR3IGF-I (1.5 mg/kg per day). LR3IGF-I treatment following renal ischaemia resulted in a significantly greater fall in GFR than in controls, urinary osmolality was also significantly reduced, and fractional excretion of sodium was increased. In addition, there was histological evidence of a greater degree of tubular epithelial calcification in the kidneys of the rats treated with LR3IGF-I. This study showed that administration of IGF peptides at doses sufficient to cause significant improvement in anabolic status did not improve renal function in rats following an acute episode of renal ischaemia. Indeed the LR3IGF-I variant of IGF-I had a deleterious effect on renal function in the early stage of the recovery period.
Gain-switched pulsed operation of microchip lasers (1989)

Microchip lasers have produced single-frequency, gain-switched pulses with a FWHM as short as 760 psec for Nd:YAG (Nd(x)Y(3-x)Al(5)O(12)) and 80 psec for LiNdP(4)O(12) (LNP).
Precipitation of calcium carbonate in aqueous solutions (1984)

The precipitation of calcium carbonate from aqueous solutions has been studied at supersaturations sufficient for spontaneous precipitation but low enough to enable highly reproducible experiments to be carried out with respect to induction periods and rates of precipitation. The threshold for the onset of calcium carbonate precipitation at pH 8.60 has been established. The induction periods and rates of precipitation are both strongly dependent on supersaturation. Treatment of the kinetics data according to classical nucleation theory yielded an estimated 68 erg cm–2 value for the surface energy of the solid precipitating. From kinetics plots it is also suggested that the number of precipitating calcium carbonate crystals increases rapidly at the start of nucleation. At a later stage the particles stop increasing in number and subsequently grow. The apparent activation energy of 155 kJ mol–1 calculated from experiments carried out at 25, 35 and 45 °C points to a surface-controlled mechanism for the precipitation of calcium carbonate.
Deep Learning for Pixelwise Classification of Hyperspectral Images: A generalizing model for a fixed scene subject to temporally changing weather, lighting and seasonal conditions (2017)

In hyperspectral (HS) imaging, for every pixel a spectrum of wavelengths is captured. These spectra represent material properties, i.e. the spectral signatures. So, classification of HS imagery is based on material properties. This thesis describes a framework to perform pixelwise classification of HS images of a fixed scene subject to varying ambient conditions. TNO has recorded HS images over the course of one year, every hour between sunrise and sunset. Therefore, this data set is subject to a range of lighting, weather and seasonal conditions, degrading the recorded data. Traditionally, atmospheric models are used to correct for these effects, recovering spectral information. In this work a Fully Convolutional Neural Network (FCN) is trained to perform the segmentation task which also learns to correct for ambient conditions, eliminating the need of implementing an atmospheric model or applying image normalization. A single FCN (U-Net) is implemented to solve a five-class segmentation problem, distinguishing broad leaf trees, grass, sand, asphalt and artificial grass. To start training a neural network, the training data set requires a corresponding ground truth. A sparsely annotated mask is designed which fits images covering the entire recording period. In single-scene segmentation, annotating using a sparse mask is a quick method which allows for moving object borders. Furthermore, it avoids inclusion of mixed pixels. In order to reduce computational load, the training data set is formed by many small patches taken from the original HS images. Consequently, the network is trained with local spectral-spatial information. Training the standard U-Net proves to be limited to training data sets under relatively constant ambient conditions. In order to further enhance generalization over seasons, the network weights are rearranged so that a similar number of weights is maintained. This network is essential for training a complex training data set, as it is able to extract more informative features. The standard U-Net trained with a simple training data set (i.e. relatively constant ambient conditions) achieves an accuracy A &amp;gt; 94% for both sunny and rainy test images irrespective of time of the day. However, this model is valid for a limited period of time. The customized U-Net trained with a complex training data set (i.e. highly varying ambient conditions) yields segmentations with an accuracy ranging between 86 and 93%. This model is valid for a longer period of time, covering multiple seasons. So the experiments show that there is a trade-off between segmentation accuracy and duration of model validity, which is controlled by network weight arrangement.
Making Stories, Making Sense. (1980)

Three characteristics of school writing activities that aay make it difficult for students to learn to write with skill and enthusiasm are identified in this paper. They are: the solitary nature of most writing tasks, a lopsided emphasis on low-level details of text such as grammar and spelling, and the isolation *f writing from reading in the classroom. The paper describes a set of educational devices that attempt to change these aspects of writing instruction: the Story Maker, based on the notion of story trees with which children coapose stories by making choices among story segments: and the Pre-Fab Story Maker and the Story Maker Maker, which allow children more creative input into the stcry-making process. These three tools are described both as suggestions to teachers for innovative classroom language activities and as concrete examples of the implications of tilt theoretical framework developed in the paper. Reaction to the story aaker from a teacher's perspective and the author's response to that reaction are included. (Author/FL) *********************************************************************** * Reproductions supplied by !DPS are the best that can be made * * from the original document. * *********************************************************************** CENTER FOR THE STUDY OF READING Reading Education Report No. 14 MAKING STORIES, MAKING SENSE* Andee Rubin Bolt Beranek and Newman Inc.
Importance of Amplitude Scintillations in Millimetric Radio Links (1974)

Amplitude scintillations in millimetric radio propagation are not usually considered by systems engineers In this paper, the experimental measurements of these scintillations in a 36 GHz radio link have been fitted into a model suitable for the millimetric range. From it, the amplitude scintillations can be regarded as a noise component superimposed on the mean value, with some expected mean rate fading fo. The r.m.s. value of this noise is then used to determine the outages for the scintillation-type fading, as a function of the frequency and link distance. The implications of the results in the power budget are discussed and reference is made to the limiting performance of digital transmission.