gebhart/patrepeval huggingface dataset:
Clinical, Pathologic, and Biologic Features Associated with BRAF Mutations in Non–Small Cell Lung Cancer (2013)

BRAF mutations occur in 4% of NSCLCs and half are non-V600E. Prospective trials are ongoing to validate BRAF as a therapeutic target in NSCLC.
Purification and characterization of particulate endothelium-derived relaxing factor synthase from cultured and native bovine aortic endothelial cells. (1991)

The particulate enzyme responsible for the synthesis of endothelium-derived relaxing factor has been purified from cultured and native (noncultured) bovine aortic endothelial cells. Purification of the solubilized particulate enzyme preparation by affinity chromatography on adenosine 2',5'-bisphosphate coupled to Sepharose followed by Superose 6 gel filtration chromatography resulted in a single protein band after denaturing polyacrylamide gel electrophoresis that corresponded to approximately 135 kDa. The enzyme activity in the various fractions was assayed by its stimulatory effect on soluble guanylyl cyclase of rat fetal lung fibroblasts (RFL-6 cells), by the formation of L-citrulline from L-arginine, by measuring nitrite/nitrate formation, and by bioassay on endothelium-denuded vascular strips. Endothelium-derived relaxing factor synthase was purified 3419-fold from the crude particulate fraction of cultured bovine aortic endothelial cells with a 12% recovery (RFL-6 assay). Purified endothelium-derived relaxing factor synthase required L-arginine, NADPH, Ca2+, calmodulin, and 5,6,7,8-tetrahydrobiopterin for full activity.
Sodium transport in a mouse model of colonic carcinogenesis. (1987)

Following 4 weeks of s.c. injections of 1,2-dimethylhydrazine, a carcinogen that produces colon cancer in CF1 mice, an increase in the unidirectional mucosal to serosal flux and net absorption of sodium was observed in the distal colon. This increase in sodium transport was amiloride sensitive. 1,2-Dimethylhydrazine treatment had no effect on sodium transport in the distal colon of DBA/2 mice, a strain which does not develop colonic malignant transformation. Although stimulation of sodium transport has been observed in cultured cell systems exposed to growth factors, similar changes in sodium transport have not previously been demonstrated in an intact epithelium at an early stage of carcinogenesis. The present study in mouse distal colon demonstrates that sodium transport is altered in 1,2-dimethylhydrazine-induced malignant transformation of the large bowel.
Focal adhesion kinase (FAK) inhibitors VS-6063 and VS-4718 target cancer stem cells. (2013)

e13523 Background: Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that orchestrates cellular signaling through integrins and growth factor receptors and functions in multiple steps of tumorigenesis. Both VS-6063 and VS-4718 are potent, selective, and orally active FAK inhibitors. In a phase I clinical trial, VS-6063 was well tolerated and demonstrated preliminary clinical activity. VS-4718 is in late stage preclinical development and has been shown to inhibit tumor growth and metastasis in tumor models. We report here that the FAK inhibitors VS-6063 and VS-4718 effectively abrogate cancer stem cells (CSCs). Methods: VS-6063 and VS-4718 were evaluated in the ALDEFLUOR and Side Population (SP) CSC assays in vitro and in xenograft tumors in vivo. Results: Treating SUM159 breast cancer cells with FAK inhibitors reduced the percentage of ALDEFLUOR + and SP CSCs. Similar inhibitory effects on CSCs were observed in the ovarian cancer cell lines OVCAR-5 and OVCAR-8 and the mesothelioma cell line H2052. In direct contrast, cytotoxic agents paclitaxel, carboplatin and pemetrexed increased the percentage of CSCs, suggesting that these agents do not effectively target CSCs. Importantly, combination of either VS-6063 or VS-4718 with cytotoxic agents blocked induction of CSCs by these agents. The effect of a FAK inhibitor on CSCs in vivo was evaluated in an MDA-MB-231 human breast cancer orthotopic model. Oral administration of FAK inhibitor substantially reduced the number of ALDH1- positive cells in tumors as assessed by immunofluorescence. Following dissociation of cells from tumors, CSCs were found to be reduced in FAK inhibitor-treated tumors as measured by multiple assays. Furthermore, cells isolated from FAK inhibitor-treated tumors showed reduced tumor-initiating capability upon re-implantation into immunodeficient mice. FAK inhibitor also decreased ALDH1-positive CSCs in an orthotopic MM87 mesothelioma model. Conclusions: Our results provide clear demonstration that FAK inhibitors target cancer stem cells both in vitro and in xenograft tumors in vivo and support the planned clinical development of VS-6063 and VS-4718 to achieve durable clinical responses for cancer patients.
Regioselective ω-hydroxylation of medium-chain n-alkanes and primary alcohols by CYP153 enzymes from Mycobacterium marinum and Polaromonas sp. strain JS666 (2011)

The oxofunctionalization of saturated hydrocarbons is an important goal in basic and applied chemistry. Biocatalysts like cytochrome P450 enzymes can introduce oxygen into a wide variety of molecules in a very selective manner, which can be used for the synthesis of fine and bulk chemicals. Cytochrome P450 enzymes from the CYP153A subfamily have been described as alkane hydroxylases with high terminal regioselectivity. Here we report the product yields resulting from C(5)-C(12) alkane and alcohol oxidation catalyzed by CYP153A enzymes from Mycobacterium marinum (CYP153A16) and Polaromonas sp. (CYP153A P. sp.). For all reactions, byproduct formation is described in detail. Following cloning and expression in Escherichia coli, the activity of the purified monooxygenases was reconstituted with putidaredoxin (CamA) and putidaredoxin reductase (CamB). Although both enzyme systems yielded primary alcohols and α,ω-alkanediols, each one displayed a different oxidation pattern towards alkanes. For CYP153A P. sp. a predominant ω-hydroxylation activity was observed, while CYP153A16 possessed the ability to catalyze both ω-hydroxylation and α,ω-dihydroxylation reactions.
Protein phosphatases come of age (1989)

The level of phosphorylation of any protein depends on the relative activities of protein kinases and protein phosphatases (1), but the latter enzymes have received far less attention, perhaps because of the difficulty in obtaining a well defined substrate before they can be studied. Nevertheless, information about, protein serine/threonine phosphatases has increased enormously over the past few years, and readers are referred to a detailed review (2) for background information and for many of the primary references. This Minireview will concentrate on recent progress that has demonstrated key roles for these enzymes in tumor suppression and in cell division and identified novel phosphatase catalytic subunits. Our current understanding of the structure, substrate specificity, and regulation of protein phosphatases will also be discussed with emphasis on the role of “targeting subunits.” The discovery that certain membrane-bound glycoproteins are protein tyrosine phosphatases is reviewed in Ref. 3.
Nowcasting of the Gross Regional Product (2011)

Business cycles are usually defined at a national level. The implicit assumption being that it affects all regions similarly. This is combined with a lack of timely information on regional economic development as annual values of the gross regional product (GRP) are often published with up to two years lag. The present paper evaluates a method of obtaining values of the GRP as soon as monthly and quarterly business cycle indicators become available. Building on earlier work on using bridge equations to obtaining quarterly values of GDP growth, a method is proposed were annual GRP growth is estimated using a large number of business cycle indicators. The procedure is applied to data for the Northern regions of Sweden. With the present method it is possible to continuously refine GRP growth values throughout the year. By utilizing the information content in available business cycle indicators, a nowcast of the GRP is obtained as opposed to a pure forecast based solely on past information. Nowcasts will then provide valuable information on how current highs or lows are affecting different regions.
Enhanced Performance of Perovskite CH3NH3PbI3Solar Cell by Using CH3NH3I as Additive in Sequential Deposition (2015)

Sequential deposition is a widely adopted method to prepare CH3NH3PbI3 on mesostructured TiO2 electrode for organic lead halide perovskite solar cells. However, this method often suffers from the uncontrollable crystal size, surface morphology, and residual PbI2 in the resulting CH3NH3PbI3, which are all detrimental to the device performance. We herein present an optimized sequential solution deposition method by introducing different amount of CH3NH3I in PbI2 precursor solution in the first step to prepare CH3NH3PbI3 absorber on mesoporous TiO2 substrates. The addition of CH3NH3I in PbI2 precursor solution can affect the crystallization and composition of PbI2 raw films, resulting in the variation of UV-vis absorption and surface morphology. Proper addition of CH3NH3I not only enhances the absorption but also improves the efficiency of CH3NH3PbI3 solar cells from 11.13% to 13.37%. Photoluminescence spectra suggest that the improvement of device performance is attributed to the decrease of recombination rate of carriers in CH3NH3PbI3 absorber. This current method provides a highly repeatable route for enhancing the efficiency of CH3NH3PbI3 solar cell in the sequential solution deposition method.
A second binding site for hydroxytamoxifen within the coactivator-binding groove of estrogen receptor β (2006)

Evidence is presented that the estrogen antagonist 4-hydroxytamoxifen (HT) can occupy not only the core binding pocket within the ligand-binding domain of estrogen receptor (ER) beta but also a second site on its surface. The crystal structure of the ligand-binding domain (LBD) associated with HT was determined to 2.2 A and revealed two molecules of HT bound to the protein. One was located in the consensus ligand-binding pocket, whereas the other bound to a site that overlaps with the hydrophobic groove of the coactivator recognition surface. Relative to the ERalpha-tamoxifen structure, helix 12 has been displaced from the coactivator recognition surface and occupies a unique position. Although it has been demonstrated that association of the antagonist with the core ligand-binding pocket is sufficient to induce an antagonist ligand-binding domain conformation, this structure suggests that small molecules may directly antagonize receptor-coactivator interactions. These results provide a direct demonstration of two binding sites for HT in ERbeta, as has been previously suggested for ERalpha by using biochemical methods, and represent a crystal structure of a small nonpeptide molecule occupying the coactivator recognition site.
Activation of the ERK 1/2 and STAT3 signaling pathways is required for 661W cell survival following oxidant injury. (2012)

We demonstrated that the exposure of 661W cells to H(2)O(2) increased the activation of ERK1/2 and STAT3 signal pathways. Activation of these pathways is required for 661W cell survival following oxidant injury.
Amplified DNA in Y1 mouse adrenal tumor cells: isolation of cDNAs complementary to an amplified c-Ki-rasgene and localization of homologous sequences to mouse chromosome 6 (1984)

We have isolated cDNA clones complementary to a c-Ki-ras cellular oncogene that is amplified in Y1 mouse adrenal tumor cells, with the amplified sequences located on double-minute chromatin bodies (DMs) and homogeneously staining chromosomal regions (HSRs). Characterization of the cDNAs included the isolation of corresponding genomic clones, Northern blot analysis of RNA, and DNA sequence analysis. Our studies demonstrate that the c-Ki-ras gene amplified in the Y1 cells is homologous to the human c-Ki-ras2 gene. We have also obtained evidence that, in addition to c-Ki-ras, at least one other transcription unit has been amplified in the mouse adrenal tumor cells. Moreover, by Southern blot analysis of Chinese hamster-mouse somatic cell hybrids, we have determined that the amplified DNA sequences associated with DMs and HSRs, including the c-Ki-ras gene, are present in normal mouse cells on chromosome 6.
Phase I Study of a Herpes Simplex Virus Type 2 (HSV-2) DNA Vaccine Administered to Healthy, HSV-2-Seronegative Adults by a Needle-Free Injection System (2008)

We conducted a double-blind, vehicle-controlled, dose escalation safety and immunogenicity trial of a candidate herpes simplex virus type 2 (HSV-2) surface glycoprotein D2 (gD2) DNA vaccine administered by use of a needle-free device. Sixty-two healthy adults were randomized using a 4:1 vaccine-to-placebo ratio. Half of the participants were HSV-1 seronegative, and all were HSV-2 seronegative. Vaccine doses included 100 microg, 300 microg, 1,000 microg or 3,000 microg of a plasmid expressing the gD2 protein. Subjects received vaccine at 0, 4, 8, and 24 weeks. Some subjects received an additional 1,000-microg boost at 52 weeks. We found that the vaccine was safe and well tolerated, with most adverse events being local site reactions. No dose-limiting toxicities were observed. gD2-specific cytotoxic T-lymphocyte and lymphoproliferation responses were detected 2 weeks after the third vaccine injection in one of four HSV-1-seronegative, HSV-2-seronegative participants who received 3,000 microg of vaccine. A DNA-based vaccination strategy against HSV-2 appears to be safe and may generate a vaccine-specific cellular immune response, but high vaccine doses are likely needed to elicit an immune response in most vaccinees.
Investment and factor remuneration in small-scale fisheries (1992)

Investment behaviour is a complex process which plays a major role in fisheries dynamics because it determines the size of the fishing fleet. The purpose of this paper is to examine the consequences of the main characteristics of fishing activity on investment. The theoretical dynamic model of a fishery shows us the "bangbang" pallern of investment. Furthermore, fishing activity has a high intrinsic variability. Thus, the system in which income is shared between the crew and the ship owner is also considered as a way of sharing risks and so reducing the variability ofinvestment return. Finally, the type of investment financing (subsidies, loans) can strongly stimulate fisheries dynamics but can also have some undesirable effects. [NOT CONTROLLED OCR]
Validation of the Delirium Rating Scale-Revised-98: Comparison With the Delirium Rating Scale and the Cognitive Test for Delirium (2001)

The DRS-R-98, a 16-item clinician-rated scale with 13 severity items and 3 diagnostic items, was validated against the Cognitive Test for Delirium (CTD), Clinical Global Impression scale (CGI), and Delirium Rating Scale (DRS) among five diagnostic groups (N=68): delirium, dementia, depression, schizophrenia, and other. Mean and median DRS-R-98 scores significantly (P<0.001) distinguished delirium from each other group. DRS-R-98 total scores correlated highly with DRS, CTD, and CGI scores. Interrater reliability and internal consistency were very high. Cutoff scores for delirium are recommended based on ROC analyses (sensitivity and specificity ranges: total, 91%–100% and 85%–100%; severity, 86%–100% and 77%–93%, respectively, depending on the cutoffs or comparison groups chosen). The DRS-R-98 is a valid measure of delirium severity over a broad range of symptoms and is a useful diagnostic and assessment tool. The DRS-R-98 is ideal for longitudinal studies.
Structural Characterization of the Human Androgen Receptor Ligand-binding Domain Complexed with EM5744, a Rationally Designed Steroidal Ligand Bearing a Bulky Chain Directed toward Helix 12 (2007)

Antiandrogens are commonly used to treat androgen-dependent disorders. The currently used drugs unfortunately possess very weak affinity for the human AR (hAR), thus indicating the need to develop new high-affinity steroidal antiandrogens. Our compounds are specially designed to impede repositioning of the mobile carboxyl-terminal helix 12, which blocks the ligand-dependent transactivation function (AF-2) located in the AR ligand-binding domain (ARLBD). Using crystal structures of the hARLBD, we first found that H12 could be directly reached from the ligand-binding pocket (LBP) by a chain positioned on the C18 atom of an androgen steroid nucleus. A set of 5alpha-dihydrotestosterone-derived molecules bearing various C18 chains were thus synthesized and tested for their capacity to bind hAR and act as antagonists. Although most of those having very high affinity for hAR were agonists, several very potent antagonists were obtained, confirming the structural importance of the C18 chain. To understand the role of the C18 chain in their agonistic/antagonistic properties, the structure of the hARLBD complexed with one of these agonists, EM5744, was determined at a 1.65-A resolution. We have identified new interactions involving Gln(738), Met(742), and His(874) that explain both the high affinity of this compound and the inability of its bulky chain to prevent the repositioning of H12. This structural information will be helpful to refine the structure of the chains placed on the C18 atom to obtain efficient H12-directed steroidal antiandrogens.
Ferrous Ion-Dependent l -Serine Dehydratase from Clostridium acidiurici (1972)

l-Serine dehydratase from Clostridium acidiurici was purified 400-fold. The enzyme required activation by catalytic amounts of ferrous ion and a thiol reducing agent before the addition of substrate. Several cations tested were unable to substitute for divalent iron. The reducing agent of choice was dithiothreitol. The activation was presumed to result in the formation of an iron-enzyme complex, because once activated the enzyme retained essentially full activity in a reaction mixture not supplemented with iron or reducing agent. The reaction with substrate was carried out at pH 8.4 in phosphate buffer and was specific for l-serine. The presence of pyridoxal phosphate as coenzyme was indicated by absorption maxima at 330 and 420 nm and fluorescence maxima at 390 and 520 nm.
Germ‐line transmission of a myocardium‐specific GFP transgene reveals critical regulatory elements in the cardiac myosin light chain 2 promoter of zebrafish (2003)

In response to the lack of a transgenic line of zebrafish labeled with heart-specific fluorescence in vivo to serve as a research model, we cloned a 1.6-kb polymerase chain reaction (PCR) -product containing the upstream sequence (-870 bp), exon 1 (39 bp), intron 1 (682 bp), and exon 2 (69 bp) of the zebrafish cardiac myosin light chain 2 gene, (cmlc2). A germ-line transmitted zebrafish possessing a green fluorescent heart was generated by injecting this PCR product fused with the green fluorescent protein (GFP) gene with ends consisting of inverted terminal repeats of an adeno-associated virus. Green fluorescence was intensively and specifically expressed in the myocardial cells located both around the heart chambers and the atrioventricular canal. Neither the epicardium nor the endocardium showed fluorescent signals. The GFP expression in the transgenic line faithfully recapitulated with the spatial and temporal expression of the endogenous cmlc2. Promoter analysis showed that the fragment consisting of nucleotides from -210 to 34 (-210/34) was sufficient to drive heart-specific expression, with a -210/-73 motif as a basal promoter and a -210/-174 motif as an element involved in suppressing ectopic (nonheart) expression. Interestingly, a germ-line of zebrafish whose GFP appeared ectopically in all muscle types (heart, skeletal, and smooth) was generated by injecting the fragment including a single nucleotide mutation from G to A at -119, evidence that A at -119 combined with neighboring nucleotides to create a consensus sequence for binding myocyte-specific enhancer factor-2.
Video2Text: Learning to Annotate Video Content (2009)

This paper discusses a new method for automatic discovery and organization of descriptive concepts (labels) within large real-world corpora of user-uploaded multimedia, such as YouTube. com. Conversely, it also provides validation of existing labels, if any. While training, our method does not assume any explicit manual annotation other than the weak labels already available in the form of video title, description, and tags. Prior work related to such auto-annotation assumed that a vocabulary of labels of interest (e. g., indoor, outdoor, city, landscape) is specified a priori. In contrast, the proposed method begins with an empty vocabulary. It analyzes audiovisual features of 25 million YouTube. com videos - nearly 150 years of video data -- effectively searching for consistent correlation between these features and text metadata. It autonomously extends the label vocabulary as and when it discovers concepts it can reliably identify, eventually leading to a vocabulary with thousands of labels and growing. We believe that this work significantly extends the state of the art in multimedia data mining, discovery, and organization based on the technical merit of the proposed ideas as well as the enormous scale of the mining exercise in a very challenging, unconstrained, noisy domain.
A Standard for the Transmission of IP Datagrams over Ethernet Networks (1984)

Status of this Memo This RFC specifies a standard method of encapsulating Internet Protocol (IP) [1] datagrams on an Ethernet [2]. This RFC specifies a standard protocol for the ARPA-Internet community.
The Fibronectin-binding Domain of Transglutaminase (1995)

Guinea pig liver transglutaminase (EC 2.3.2.13) displays a Ca(2+)-independent binding (Ka = 10(7) M-1) to the same gelatin-binding domain of human plasma fibronectin that is known to form a very tight complex with the human red cell enzyme. The fibronectin-combining site of the liver transglutaminase was investigated by testing fragments obtained from the parent protein by controlled digestion with endoproteinase Lys-C. Overlay assays, probed with anti-fibronectin antibody, revealed that the fibronectin binding ability of the transglutaminase was encoded in a linear sequence in its 28-kDa N-terminal domain. Removal of the first 7 residues by further digestion of the purified 28-kDa material with endoproteinase Glu-C generated a 27-kDa fragment that, however, showed no binding activity. Thus, residues 1-7 in the liver enzyme seem to be of particular importance for influencing its ability to bind to fibronectin.