gebhart/patrepeval huggingface dataset:
Repurposing itraconazole for the treatment of cancer (2017)

The repurposing of drugs is becoming increasingly attractive as it avoids the lengthy process and cost implications associated with bringing a novel drug to market. Itraconazole is a broad‑spectrum anti‑fungal agent. An emerging body of in vivo, in vitro and clinical evidence have confirmed that it also possesses antineoplastic activities and has a synergistic action when combined with other chemotherapeutic agents. It acts via several mechanisms to prevent tumour growth, including inhibition of the Hedgehog pathway, prevention of angiogenesis, decreased endothelial cell proliferation, cell cycle arrest and induction of auto‑phagocytosis. These allow itraconazole, either alone or in combination with other cytotoxic agents, to increase drug efficacy and overcome drug resistance. This study reviews the reported literature on the use of itraconazole in a variety of malignancies and highlights the recent insights into the critical pathways acted upon to prevent tumour growth.
Accelerated Clearance of Polyethylene Glycol-Modified Proteins by Anti-Polyethylene Glycol IgM (1999)

Tumor therapy by the preferential activation of a prodrug at tumor cells targeted with an antibody-enzyme conjugate may allow improved treatment efficacy with reduced side effects. We examined antibody-mediated clearance of poly(ethylene glycol)-modified beta-glucuronidase (betaG-sPEG) as a method to reduce serum concentrations of enzyme and minimize systemic prodrug activation. Enzyme-linked immunosorbent assay and immunoblot analysis of two monoclonal antibodies generated by immunization of BALB/c mice with an antibody-betaG-sPEG conjugate showed that mAb 1E8 (IgG1) bound betaG and betaG-sPEG whereas mAb AGP3 (IgM) bound poly(ethylene glycol). Neither antibody affected the betaG activity. mAb 1E8 and AGP3 were modified with 36 and 208 galactose residues (1E8-36G and AGP3-208G) with retention of 72 and 48% antigen-binding activity, respectively, to target immune complexes to the asialoglycoprotein receptor on liver cells. mAb 1E8 and AGP3 cleared betaG-PEG from the circulation of mice as effectively as 1E8-36G and AGP3-208G, respectively. mAb AGP3, however, cleared betaG-sPEG more completely and rapidly than 1E8, reducing the serum concentration of betaG-sPEG by 38-fold in 8 h. AGP3 also reduced the concentration of an antibody-betaG-sPEG conjugate in blood by 280-fold in 2 h and 940-fold in 24 h. AGP3-mediated clearance did not produce obvious damage to liver, spleen, or kidney tissues. In addition, AGP3 clearance of betaG-sPEG before administration of BHAMG, a glucuronide prodrug of p-hydroxyaniline mustard, prevented toxicity associated with systemic activation of the prodrug based on mouse weight and blood cell numbers. AGP3 should be generally useful for accelerating the clearance of PEG-modified proteins as well as for improving the tumor/blood ratios of antibody-betaG-PEG conjugates for glucuronide prodrug therapy of cancer.
Evaporation of picoliter droplets on surfaces with a range of wettabilities and thermal conductivities (2012)

The evaporation of picoliter water and ethanol droplets generated by drop-on-demand inkjet printing was investigated on substrates with apparent contact angles between 10^{∘} and 135^{∘} and thermal conductivities between 0.25 and 149 Wm^{-1}K^{-1}. Drying times were calculated from a diffusion-limited model for droplets with both pinned and moving contact lines as a function of droplet diameter and apparent contact angle. Droplets with a moving contact line take longer to dry on hydrophilic substrates than pinned droplets. The difference in drying times between evaporative modes vanishes at large apparent contact angles. Hence similar drying times are obtained for both modes on hydrophobic substrates. The predicted drying times for glass and silicon substrates were in good quantitative agreement with experimental data, suggesting that thermal effects are negligible for substrates of these base materials. However, on a PTFE substrate which has a lower thermal conductivity more relevant to inkjet printing, evaporative cooling reduces the evaporation rate causing drying times to be underpredicted by isothermal models.
β‐Mannosidase deficiency: Heterogeneous manifestation in the first female patient and her brother (1990)

beta-Mannosidase deficiency was demonstrated in fibroblasts of a girl who showed severe psychomotor retardation, bone deformities and gargoylism and recurrent skin and respiratory infections and who died at 20 years of age from bronchopneumonia. This first demonstration of a female patient confirms the autosomal recessive inheritance of beta-mannosidosis. Further investigation of this gypsy family revealed beta-mannosidosis in an older brother with a milder manifestation of gargoyl facial dysmorphology, mental retardation, hearing impairment and recurrent infections. beta-Mannosidase activity was completely deficient in his cultured skin fibroblasts, leukocytes and plasma. In urine a characteristic disaccharide was present. Heterozygote levels of beta-mannosidase were found in fibroblasts and/or plasma of the parents and one sister.
Nanostructured TiO2-based gas sensors with enhanced sensitivity to reducing gases (2016)

2D TiO<sub>2</sub> thin films and 3D flower-like TiO<sub>2</sub>-based nanostructures, also decorated with SnO<sub>2</sub>, were prepared by chemical and thermal oxidation of Ti substrates, respectively. The crystal structure, morphology and gas sensing properties of the TiO<sub>2</sub>-based sensing materials were investigated. 2D TiO<sub>2</sub> thin films crystallized mainly in the form of rutile, while the flower-like 3D nanostructures as anatase. The sensor based on the 2D TiO<sub>2</sub> showed the best performance for H<sub>2</sub> detection, while the flower-like 3D nanostructures exhibited enhanced selectivity to CO(CH<sub>3</sub>)<sub>2</sub> after sensitization by SnO<sub>2</sub> nanoparticles. The sensor response time was of the order of several seconds. Their fast response, high sensitivity to selected gas species, improved selectivity and stability suggest that the SnO<sub>2</sub>-decorated flower-like 3D nanostructures are a promising material for application as an acetone sensor.
Design Considerations for a Minimally Invasive High-Throughput Automation System for Radiation Biodosimetry (2007)

Design aspects of a minimally invasive high-throughput automation system for radiation biodosimetry are reported. The system, currently under development, relies on robotic devices and advanced high-speed automated image acquisition to perform mass triage following a radiological event. A design concept of the automation system is proposed based on the use of an input stage, a centrifuge module, a cell harvesting system, a liquid handling module, an imaging system and a service robot. The biological assays are described along with an analysis of the throughput requirements. The special requirements imposed by bioassay automation, system throughput and minimal invasiveness lead to the design of a custom-made multipurpose gripper and a cell harvesting module. Results on the embodiment design of these modules are provided. A prototype of the automation system is described.
Measles Virus Vaccine Attenuation: Suboptimal Infection of Lymphatic Tissue and Tropism Alteration (2007)

The mechanisms of measles virus (MV) vaccine attenuation are insufficiently characterized. Because the Edmonston vaccine strain can enter cells through CD46 in addition to the primary MV receptor signaling lymphocyte activation molecule (SLAM or CD150), we asked whether and how its tropism is altered. In human tonsillar tissue, this vaccine strain infects naive (CD45RA(+)CD62L(+)) T lymphocytes, which express SLAM very infrequently, with much higher efficiency than do wild-type strains. By contrast, it infects B lymphocytes, macrophages, and NK cells with significantly lower efficiencies than those of wild-type strains. Infection levels by wild-type strains correlate with the frequency of SLAM expression and are highest in B cells, which are 40%-55% infected. SLAM-expressing T cells are more readily infected by all MV strains than are SLAM-expressing B cells. Thus, vaccine attenuation may be caused by tropism alteration in combination with suboptimal replication.
<title>Fractal dimension estimation for optical image segmentation</title> (1993)

This research investigated the use of fractal dimension measure to segment regions of interest from simulated terrain imagery. The underlying assumption is: a given region of interest in a real-world image has a different fractal dimension than its surrounding terrain. Virtually illuminated, digitally simulated fractal surfaces with known fractal dimensions were investigated. The terrain types that were considered varied from bumpy to flat surfaces. An optically based image segmentation system was constructed to perform the otherwise computationally intensive Fourier transform of the image to be segmented.
The active site of galactose oxidase. (1988)

The copper enzyme galactose oxidase has been prepared in three distinct redox modifications; two of these represent nearly homogeneous preparations of active and inactive species which have been described previously, while the third has never before been reported. Preparation of these redox modifications as homogeneous species has permitted detailed spectroscopic and catalytic studies of each for the first time. We find that the form which has been extensively probed by EPR spectroscopy is devoid of catalytic activity and does not interact with substrate. The detailed characterization of oxidatively activated galactose oxidase and its anion interactions has led to a spectroscopic assignment of the copper oxidation state in this complex which indicates that the one-electron redox process which converts the inactive form to catalytically active enzyme is associated with oxidation of the protein rather than the metal center as has been proposed previously. This oxidation step is required for catalytic activity and is the basis of the two-electron redox reactivity for the enzyme active site: anaerobic addition of hydroxylic substrates results in reduction of the two-electron redox unit, and the spectral features associated with both the copper ion and the non-metal redox center are eliminated, apparently forming a cuprous site. The two-electron reactivity resulting from protein participation in redox catalysis has important implications in this and other mechanisms where oxygen reduction occurs at a mononuclear metal ion active site.
Layered vanadium and molybdenum oxides: batteries and electrochromics (2009)

The layered oxides of vanadium and molybdenum have been studied for close to 40 years as possible cathode materials for lithium batteries or electrochromic systems. The highly distorted metal octahedra naturally lead to the formation of a wide range of layer structures, which can intercalate lithium levels exceeding 300 Ah/kg. They have found continuing success in medical devices, such as pacemakers, but many challenges remain in their application in long-lived rechargeable devices. Their high-energy storage capability remains an encouragement to researchers to resolve the stability concerns of vanadium dissolution and the tendency of lithium and vanadium to mix changing the crystal structure on cycling the lithium in and out. Nanomorphologies have enabled higher reactivities to be obtained for both vanadium and molybdenum oxides, and with the latter show promise for electrochromic displays.
Total hip arthroplasty in patients younger than 21 years: a minimum, 10-year follow-up. (2003)

INTRODUCTION: To evaluate the function, radiographic results and implant survival in patients younger than 21 years at the time of operation and with at least a 10-year follow-up, we reviewed the course of young adults who underwent total hip arthroplasty at McGill University Health Centre. PATIENTS AND METHODS: Twelve patients (16 hips) met the criteria for inclusion in this study. They ranged in age from 10–20 years (median 16.5 yr). One patient (1 hip) died 5 years after the index surgery and was excluded from the study. Functional results were measured by the Harris hip score, and radiographs of surviving implants were assessed for radiolucencies, osteolysis and eccentric polyethylene wear. RESULTS: Eleven arthroplasties were cementless, 2 were hybrid and 2 were cemented. At follow-up ranging from 10 to 25 years (mean 13.6 yr), the Harris hip score ranged from 34.2–97.2 (mean 64.5). Four (26%) acetabular components were revised and (at the time of writing) 1 required revision. Only 1 (7%) femoral stem was revised. Radiographically, there was a high prevalence of eccentric polyethylene wear, but none of the surviving implants were found to be loose. Overall, 67% (10 of 15) of the total hip arthroplasties continued to function well at a mean of 13.6 years postoperatively. CONCLUSIONS: Total hip arthroplasty remains a reasonable option in adolescence and early adulthood in selected patients with severe debility from multiple joint disease. Polyethylene wear is a particularly significant problem in this group of active young people.
Targeted PCR for Detection of Vaginal Bacteria Associated with Bacterial Vaginosis (2007)

Several novel bacterial species have been detected in subjects with bacterial vaginosis (BV) by using broad-range PCR assays, but this approach is insensitive for detecting minority species. We developed a series of taxon-directed 16S rRNA gene PCR assays for more sensitive detection of key vaginal bacteria. We sought to determine the prevalence of each species in the vagina, its association with BV, and the utility of PCR for the microbiological diagnosis of BV. Targeted PCR assays were developed for 17 vaginal bacterial species and applied to 264 vaginal-fluid samples from 81 subjects with and 183 subjects without BV. The results were compared to those of two widely accepted methods for diagnosing BV, the use of clinical findings (Amsel criteria) and the interpretation of vaginal-fluid Gram stains (Nugent criteria). Leptotrichia/Sneathia, Atopobium vaginae, an Eggerthella-like bacterium, Megasphaera species, and three novel bacteria in the order Clostridiales are among the bacterial species significantly associated with BV. PCR detection of either a Megasphaera species or one of the Clostridiales bacteria yielded a sensitivity of 99% and a specificity of 89% for diagnosis of BV compared to the Amsel clinical criteria and a sensitivity of 95.9% and a specificity of 93.7% compared to the Nugent criteria (Gram stain). PCR detection of one or more fastidious bacterial species is a more reliable indicator of BV than detection of bacteria, such as Gardnerella vaginalis, previously linked to BV, highlighting the potential of PCR for the diagnosis of BV.
Understanding the difficulty of training deep feedforward neural networks (2010)

Whereas before 2006 it appears that deep multilayer neural networks were not successfully trained, since then several algorithms have been shown to successfully train them, with experimental results showing the superiority of deeper vs less deep architectures. All these experimental results were obtained with new initialization or training mechanisms. Our objective here is to understand better why standard gradient descent from random initialization is doing so poorly with deep neural networks, to better understand these recent relative successes and help design better algorithms in the future. We first observe the influence of the non-linear activations functions. We find that the logistic sigmoid activation is unsuited for deep networks with random initialization because of its mean value, which can drive especially the top hidden layer into saturation. Surprisingly, we find that saturated units can move out of saturation by themselves, albeit slowly, and explaining the plateaus sometimes seen when training neural networks. We find that a new non-linearity that saturates less can often be beneficial. Finally, we study how activations and gradients vary across layers and during training, with the idea that training may be more difficult when the singular values of the Jacobian associated with each layer are far from 1. Based on these considerations, we propose a new initialization scheme that brings substantially faster convergence. 1 Deep Neural Networks Deep learning methods aim at learning feature hierarchies with features from higher levels of the hierarchy formed by the composition of lower level features. They include
The fermentation of L‐sorbose by Gluconobacter melanogenus. I. General characteristics of the fermentation (1972)

Abstract Growing cultures, washed cells, and cell‐free preparations of Gluconobacter melanogecnus IFO 3293 converted L ‐sorbose to 2‐keto‐ L ‐gulonic acid, to D ‐sorbitol (which was metabolized further) and to 5‐keto‐ D ‐fructose.
Role of Stat3 in Lipopolysaccharide-Induced IL-10 Gene Expression (2000)

IL-10 is a unique cytokine because it is anti-inflammatory and immunosuppressive. IL-10 is regulated at the level of transcription, but the critical motifs and the relevant transcription factors controlling this gene have remained elusive to date. We now report that a sequence at -120 bp in the human IL-10 promoter binds Stat3 but no other Stat proteins. Mutation of this motif abrogates LPS-induced trans-activation. Overexpression of dominant negative Stat3 suppresses promoter activity, while wild-type Stat3 leads to an enhancement of this activity. Our results show that Stat3, by binding to a single motif in the IL-10 promoter, is controlling expression of the human IL-10 gene.
Major Histocompatibility Complex Class II-dependent Unfolding, Transport, and Degradation of Endogenous Proteins (1997)

We have analyzed the ability of major histocompatibility (MHC) class II molecules to capture proteins in the biosynthetic pathway and whether this may be associated with MHC class II-dependent antigen processing. When coexpressed with HLA-DR 4 molecules in HeLa cells, influenza hemagglutinin was inhibited from folding and trimerization in the biosynthetic pathway, targeted to endosomal compartments, and rapidly degraded. Due to the interaction with MHC class II molecules, therefore, unfolded forms of hemagglutinin were bypassing the quality control mechanism of the secretory pathway. More important, however, the transport, endocytosis, and rapid degradation of unfolded hemagglutinin in the presence of MHC class II molecules suggest that proteins captured in the endoplasmic reticulum by class II molecules may become substrates for antigen processing and presentation to CD4-positive T cells. In insect cells we show that this phenomenon is not restricted to a few proteins such as hemagglutinin. A highly heterogeneous mixture of proteins from the endoplasmic reticulum including coexpressed hemagglutinin can form stable complexes with soluble HLA-DR alpha and beta chains that were transported into the supernatant. This mechanism may gain biological significance in abnormal situations associated with accumulation of unfolded or malfolded proteins in the endoplasmic reticulum, for example during viral infections.
The Integrin Cytoplasmic-tail Motif EKQKVDLSTDC Is Sufficient to Promote Tumor Cell Invasion Mediated by Matrix Metalloproteinase (MMP)-2 or MMP-9 (2004)

Integrins promote cellular invasion through a combination of activities, including adhesion to an extracellular matrix ligand, which result in the generation of intracellular signals that lead to changes in cell behavior. Until now, there have been no data that identify a particular region of the cytoplasmic tail of integrin subunits as being responsible specifically for promoting the invasive activity of tumor cells. In this report, we show that amino acids with the sequence EKQKVDLSTDC, which are the C-terminal residues of the integrin beta6 subunit, promote alphavbeta6-dependent invasion in a matrix metalloproteinase (MMP)-9-dependent fashion. This same peptide sequence, when expressed at the cytoplasmic end of the beta3 integrin subunit, was able to enhance alphavbeta3-mediated invasive and enzymatic activity of tumor cells in an MMP-2-dependent fashion. Our results show that these 11 amino acids, when expressed at the C terminus of the beta subunit, are responsible for regulating the activity of invasion-promoting degradative enzymes, whereas the specific MMP involved in this cellular behavior is dependent on the context of the remainder of the beta integrin subunit.
The role of prostaglandin E2 receptors in the pathogenesis of rheumatoid arthritis (2002)

rheumatoid arthritis (RA); nonsteroidal anti-inflammatory drug (NSAID); cyclooxygenase (COX); prostaglandin E2 (PGE2); collagen
Surface Acoustic Waves in Materials Science (2002)

Laser-generated surface waves provide new tools for studying material properties, from linear elastic behavior to fracture.
Laser optoacoustic imaging system for detection of breast cancer (2009)

We designed, fabricated and tested the laser optoacoustic imaging system for breast cancer detection (LOIS-64), which fuses optical and acoustic imaging techniques in one modality by utilizing pulsed optical illumination and ultrawide-band ultrasonic detection of resulting optoacoustic (OA) signals. The system was designed to image a single breast slice in craniocaudal or mediolateral projection with an arc-shaped array of 64 ultrawide-band acoustic transducers. The system resolution on breast phantoms was at least 0.5 mm. The single-channel sensitivity of 1.66 mVPa was estimated to be sufficient for single-pulse imaging of 6 to 11 mm tumors through the whole imaging slice of the breast. The implemented signal processing using the wavelet transform allowed significant reduction of the low-frequency (LF) acoustic noise, allowed localization of the optoacoustic signals from tumors, and enhanced the contrast and sharpened the boundaries of the optoacoustic images of the tumors. During the preliminary clinical studies on 27 patients, the LOIS-64 was able to visualize 18 out of 20 malignant lesions suspected from mammography and ultrasound images and confirmed by the biopsy performed after the optoacoustic tomography (OAT) procedure.
Role of tumor necrosis factor-alpha in E1A oncogene-induced susceptibility of neoplastic cells to lysis by natural killer cells and activated macrophages. (1989)

NIH-3T3 cells transfected with adenovirus E1A oncogene cDNA were found to exhibit cytolytic susceptibility to murine NK cells and activated macrophages associated with a threshold level of oncogene product expression exceeding that required for morphological transformation. A similar correlation was observed between threshold levels of E1A gene product expression and target cell susceptibility to direct cytotoxicity by rTNF. Inhibition of splenic NK cell and peritoneal macrophage cytolysis by antisera specific for murine rTNF confirmed the importance of E1A-induced TNF susceptibility as one determinant of target cell cytolytic susceptibility. Anti-TNF antibody was, however, unable to block killing of E1A-expressing targets by the NK cell line, NKB61A2. These results suggest a direct link between the functions of E1A oncogene products and cellular mechanisms of action of TNF elaborated by host effector cells and indicate that E1A expression also affects target cell susceptibility to TNF-independent cytolytic mechanisms.
Total Synthesis of Eleutherobin (1997)

Taxol-like activity is exhibited by eleutherobin (1), one of the most promising antitumor agents isolated from nature in recent years. The first total synthesis of this compound also provided a route to two biologically active analogues, thus enabling the first structure–activity relationships within the eleutherobin family to be established.
[Expression and Clinical Significance of ABCC10 in the Patients with Non-small Cell Lung Cancer.]. (2009)

ABCC10 is overexpressed in NSCLC. The expression of ABCC10 in adenocarcinoma is higher than that in squamous cell carcinoma. The expression in adenocarcinoma is correlated to pathological grades and TNM stages. The results of this study would be benefit for further study of ABCC10 in tumor and its chemoresistance.