gebhart/patrepeval huggingface dataset:
Phenotyping of cytochromes P -450 in human tissues with monoclonal antibodies (1982)

Cytochrome P-450 (P-450)-dependent aryl hydrocarbon hydroxylase (AHHase) and 7-ethoxycoumarin deethylase (ECDEtase) in human tissues were differentially inhibited by monoclonal antibodies (MAbs) that were prepared to inhibit and completely inhibited the activity of 3-methylcholanthrene-induced rat liver P-450. The AHHase and ECDEtase of placentas from individual women who smoked were inhibited by the MAbs by 83-90% and by 34-74%, respectively. Benz[a]anthracene (BaA)-induced AHHase and ECDEtase in lymphocytes were inhibited 18-65% and 30-78%, respectively. The enzymes in both control and BaA-induced human cells in culture were inhibited to different extents. Both the AHHase and ECDEtase in control and BaA-induced monocytes and in normal liver were largely unaffected by the MAb. Thus, we have with the MAbs: (i) identified P-450s with a common antigenic site in placenta, lymphocytes, and human cells in culture; (ii) identified two forms of hydrocarbon-induced P-450s in lymphocytes, at least one of which is common with the induced P-450s of placenta and with a P-450 form present in uninduced lymphocytes; (iii) identified two forms of P-450 responsible for smoking-induced ECDEtase activity in placenta, one of which is also responsible for AHHase activity; (iv) shown that the P-450s of liver, basal, and BaA-induced monocytes are different from the MAb-sensitive P-450s of placenta and lymphocytes; (v) quantitated in several human tissues the percentages of control and inducible AHHase and ECDEtase that are dependent on the MAb-sensitive P-450; and (vi) defined by HPLC the contribution of the MAb-sensitive P-450 to the formation of specific benzo[a]-pyrene metabolites. The results demonstrate the value of MAbs for defining antigenic site relatedness for different enzymatic functions of P-450s and for identifying and quantifying the amount of a specific enzyme activity in a tissue dependent on specific P-450s. This study may be a prototype for the use of MAbs for phenotyping and mapping of P-450s responsible for specific metabolic reactions and, thus, may be useful in determining the relationship of P-450 phenotype to individual differences in drug metabolism and carcinogen susceptibility.
Characterization of a cDNA coding for human factor X. (1984)

A lambda gt11 cDNA library containing DNA inserts prepared from human liver mRNA has been screened with an antibody to human factor X, a plasma protein participating in the middle phase of the blood coagulation cascade. Ten positive clones were isolated from 2 X 10(6) phage and plaque purified. The cDNA in the phage containing the largest insert has been sequenced and shown to code for human factor X. This cDNA insert contained 1137 base pairs coding for a portion of the light chain of the molecule, a connecting region, the heavy chain, a stop codon, a short 3' noncoding region, and a poly(A) tail. The sequence of A-T-T-A-A-A, which functions as a potential recognition site for polyadenylylation or processing, was present in the 3' end of the coding sequence and preceded the stop codon of TGA by 1 base pair and the poly(A) tail by 14 base pairs. The amino acid sequence deduced from the cDNA indicated that factor X is synthesized as a single-chain polypeptide containing the light and heavy chains connected by an Arg-Lys-Arg tripeptide. The single-chain molecule is then converted to the light and heavy chains by cleavage of two (or more) internal peptide bonds. In plasma, these two chains are linked together by a disulfide bond. The DNA sequence coding for the active site of human factor X showed a high degree of identity with prothrombin and factor IX, two other vitamin K-dependent serine proteases that participate in blood coagulation. These data along with the protein sequence data previously published for the light chain of human factor X establish the complete amino acid sequence for the mature protein present in plasma.
A Large-Scale Screen for Artificial Selection in Maize Identifies Candidate Agronomic Loci for Domestication and Crop Improvement (2005)

Maize (Zea mays subsp mays) was domesticated from teosinte (Z. mays subsp parviglumis) through a single domestication event in southern Mexico between 6000 and 9000 years ago. This domestication event resulted in the original maize landrace varieties, which were spread throughout the Americas by Native Americans and adapted to a wide range of environmental conditions. Starting with landraces, 20th century plant breeders selected inbred lines of maize for use in hybrid maize production. Both domestication and crop improvement involved selection of specific alleles at genes controlling key morphological and agronomic traits, resulting in reduced genetic diversity relative to unselected genes. Here, we sequenced 1095 maize genes from a sample of 14 inbred lines and chose 35 genes with zero sequence diversity as potential targets of selection. These 35 genes were then sequenced in a sample of diverse maize landraces and teosintes and tested for selection. Using two statistical tests, we identified eight candidate genes. Extended gene sequencing of these eight candidate loci confirmed that six were selected throughout the gene, and the remaining two exhibited evidence of selection in the 3' portion of each gene. The selected genes have functions consistent with agronomic selection for nutritional quality, maturity, and productivity. Our large-scale screen for artificial selection allows identification of genes of potential agronomic importance even when gene function and the phenotype of interest are unknown.
Prospective Assessment of Discontinuation and Reinitiation of Erlotinib or Gefitinib in Patients with Acquired Resistance to Erlotinib or Gefitinib Followed by the Addition of Everolimus (2007)

In patients who develop acquired resistance, stopping erlotinib or gefitinib results in symptomatic progression, increase in SUV(max), and increase in tumor size. Symptoms improve and SUV(max) decreases after restarting erlotinib or gefitinib, suggesting that some tumor cells remain sensitive to epidermal growth factor receptor blockade. No responses were observed with combined everolimus and erlotinib or gefitinib. We recommend a randomized trial to assess the value of continuing erlotinib or gefitinib after development of acquired resistance.
Cancer precursors and their control by stimulation of the immune system. (1984)

BCG vaccination at birth according to our studies and those from Montreal, Austria, and Israel, lowers the mortality from leukemia and, in my studies, to all forms of cancer followed over a period of 20 years. It has been proposed by several studies that the lymphoreticulo-endothelial system detects and destroys neoantigens such as would be the case in remnant embryonic antigens. It follows that stimulation of the immune system would be desirable at birth to augment the removal of such neoantigens. There are numerous vaccines which stimulate the immune system, and BCG is among the foremost. I propose, therefore, that the mechanism of cancer mortality reduction in those BCG vaccinated at birth was at least in part due to the detection and destruction of embryonic cells or components thereof. To prove this theory, I recommend: Retrospective studies be done in those BCG vaccinated at birth and those not vaccinated for the incidence of cancer and leukemia over the years. Test cells, sera, and urine of those BCG vaccinated and non-vaccinated for the presence of embryonic antigens or antibodies. BCG vaccinated individuals should have lower titers of fetal antigens or antibodies than the non-vaccinated. Examine the organs on post mortem of BCG vaccinated and non-vaccinated individuals who died from trauma for the presence of fetal antigens or antibodies.
Tumor Necrosis Factor-α Increases Airway Smooth Muscle Oxidants Production through a NADPH Oxidase-like System to Enhance Myosin Light Chain Phosphorylation and Contractility (2002)

Tumor necrosis factor plays a critical role in airway smooth muscle hyperresponsiveness observed in asthma. However, the mechanisms underlying this phenomenon are poorly understood. We investigated if tumor necrosis factor-stimulated airway smooth muscle produced reactive oxygen species, leading to muscular hyperresponsiveness. Tumor necrosis factor increased intracellular and extracellular oxidants production in guinea pig airway smooth muscle cells and tissue homogenates. This production was abolished by inhibitors of NADPH oxidase (diphenylene iodinium or apocynin) and was enhanced by NADPH, whereas inhibitors of mitochondrial respiratory chain, nitric-oxide synthase, cyclooxygenase, and xanthine oxidase had no effect. NADPH oxidase subunits p22(phox) and p47(phox) were detected in smooth muscle cells and tissue homogenates by Western blot, immunohistochemistry, and spectral analysis. Furthermore, oxidants production was significantly reduced by transient transfection of smooth muscle cells with p22(phox) antisense oligonucleotides. Intracellular antioxidants and diphenylene iodinium abolished tumor necrosis factor-induced muscular hyperresponsiveness and increased in phosphorylation of the myosin light chain. Finally, NADPH oxidase subunits p22(phox) and p47(phox) were also detected in human airway smooth muscle. Collectively, these results demonstrate that tumor necrosis factor-stimulated airway smooth muscle produces oxidants through a NADPH oxidase-like system, which plays a pivotal role in muscle hyperresponsiveness and myosin light chain phosphorylation.
PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENT (1951)

Since 1922 when Wu proposed the use of the Folin phenol reagent for the measurement of proteins (l), a number of modified analytical procedures ut.ilizing this reagent have been reported for the determination of proteins in serum (2-G), in antigen-antibody precipitates (7-9), and in insulin (10).
Vertical Handoff Decision Algorithms for Providing Optimized Performance in Heterogeneous Wireless Networks (2009)

There are currently a large variety of wireless access networks, including the emerging vehicular ad hoc networks (VANETs). A large variety of applications utilizing these networks will demand features such as real-time, high-availability, and even instantaneous high-bandwidth in some cases. Therefore, it is imperative for network service providers to make the best possible use of the combined resources of available heterogeneous networks (wireless area networks (WLANs), Universal Mobile Telecommunications Systems, VANETs, Worldwide Interoperability for Microwave Access (WiMAX), etc.) for connection support. When connections need to migrate between heterogeneous networks for performance and high-availability reasons, seamless vertical handoff (VHO) is a necessary first step. In the near future, vehicular and other mobile applications will be expected to have seamless VHO between heterogeneous access networks. With regard to VHO performance, there is a critical need to develop algorithms for connection management and optimal resource allocation for seamless mobility. In this paper, we develop a VHO decision algorithm that enables a wireless access network to not only balance the overall load among all attachment points (e.g., base stations and access points) but also maximize the collective battery lifetime of mobile nodes (MNs). In addition, when ad hoc mode is applied to 3/4G wireless data networks, VANETs, and IEEE 802.11 WLANs for a more seamless integration of heterogeneous wireless networks, we devise a route-selection algorithm for forwarding data packets to the most appropriate attachment point to maximize collective battery lifetime and maintain load balancing. Results based on a detailed performance evaluation study are also presented here to demonstrate the efficacy of the proposed algorithms.
Fabrication techniques to realize CMOS-compatible microfluidic microchannels (2001)

With microfluidic systems becoming more prominent, fabrication techniques for microfluidic systems are increasingly more important. An interesting alternative to existing fabrication techniques is to embed fluidic systems within an integrated circuit by micromachining materials in the integrated circuit itself. This paper describes novel methods for fabricating one component in the complementary metal-oxide-semiconductor (CMOS) microfluidic system, the microchannel. These techniques allow direct integration of sensors, actuators, or other electronics with the microchannel. This method expands the functional applications for microfluidic systems beyond their current abilities. By utilizing the methods described within this paper, a complete "smart" microfluidic system could be batch fabricated on a single integrated circuit (IC) chip.
Integrin α3β1, a Novel Receptor for α3(IV) Noncollagenous Domain and a Trans-dominant Inhibitor for Integrin αvβ3 (2006)

Exogenous soluble human alpha3 noncollagenous (NC1) domain of collagen IV inhibits angiogenesis and tumor growth. These biological functions are attributed to the binding of alpha3NC1 to integrin alphavbeta3. However, in some tumor cells that express integrin alphavbeta3, the alpha3NC1 domain does not inhibit proliferation, suggesting that integrin alphavbeta3 expression is not sufficient to mediate the anti-tumorigenic activity of this domain. Therefore, in the present study, we searched for novel binding receptors for the soluble alpha3NC1 domain in cells lacking alphavbeta3 integrin. In these cells, soluble alpha3NC1 bound integrin alpha3beta1; however, unlike alphavbeta3, alpha3beta1 integrin did not mediate cell adhesion to immobilized alpha3NC1 domain. Interestingly, in cells lacking integrin alpha3beta1, adhesion to the alpha3NC1 domain was enhanced due to activation of integrin alphavbeta3. These findings indicate that integrin alpha3beta1 is a receptor for the alpha3NC1 domain and transdominantly inhibits integrin alphavbeta3 activation. Thus integrin alpha3beta1, in conjunction with integrin alphavbeta3, modulates cellular responses to the alpha3NC1 domain, which may be pivotal in the mechanism underpinning its anti-angiogenic and anti-tumorigenic activities.
Estimating cardiac transmembrane activation and recovery times from unipolar and bipolar extracellular electrograms: a simulation study. (1989)

A model of one-dimensional action potential propagation was used to compare activation times and recovery times measured from simulated unipolar and bipolar electrograms with the activation and recovery times measured from simulated transmembrane action potentials. Theory predicts that the intrinsic deflection--the time of the maximum negative slope of the unipolar electrogram QRS complex--corresponds to the time of maximum positive slope of action potential depolarization. Similarly, the time of the maximum positive slope of the unipolar electrogram T wave corresponds to the time of maximum negative slope of action potential repolarization. This study showed that the difference between the unipolar electrogram activation time and the action potential activation time and the difference between the unipolar electrogram recovery time and the action potential recovery time were small during ideal conditions of uniform propagation in a long cable. Nonideal conditions, however, were associated with activation time differences in excess of 1.8 msec and recovery time differences in excess of 30 msec (243 msec in certain conditions). Nonideal conditions that had a major influence were changes in activation sequence, propagation in a short cable, and propagation through regions of nonuniform coupling resistance and/or nonuniform membrane properties. Nonideal conditions that had a smaller influence were variations in distance from the measurement site to the simulated tissue surface, nonzero reference potentials, and the addition of distant events. Recovery time differences were more sensitive to the nonideal conditions than were activation time differences, and both depended on the action potential shape. When distant events significantly contributed to the unipolar electrogram waveform, the time differences when bipolar electrograms were used were less than those when unipolar electrograms were used; however, under other conditions, the time differences were comparable. Results showed that activation times and especially recovery times measured from electrograms can be greatly affected by conditions independent of changes in the underlying action potential waveforms.
PRC17, a novel oncogene encoding a Rab GTPase-activating protein, is amplified in prostate cancer. (2002)

We used cDNA-based genomic microarrays to examine DNA copy number changes in a panel of prostate tumors and found a previously undescribed amplicon on chromosome 17 containing a novel overexpressed gene that we termed prostate cancer gene 17 (PRC17). When overexpressed in 3T3 mouse fibroblast cells, PRC17 induced growth in low serum, loss of contact inhibition, and tumor formation in nude mice. The PRC17 gene product contains a GTPase-activating protein (GAP) catalytic core motif found in various Rab/Ypt GAPs, including RN-Tre. Similar to RN-Tre, we found that PRC17 protein interacts directly with Rab5 and stimulates its GTP hydrolysis. Point mutations that alter conserved amino acid residues within the PRC17 GAP domain abolished its transforming abilities, suggesting that GAP activity is essential for its oncogenic function. Whereas PRC17 is amplified in 15% of prostate cancers, it is highly overexpressed in approximately one-half of metastatic prostate tumors. The potent oncogenic activity of PRC17 is likely to influence the tumorigenic phenotype of these prostate cancers.
Highly general stereo-, regio-, and chemo-selective synthesis of terminal and internal conjugated enynes by the Pd-catalysed reaction of alkynylzinc reagents with alkenyl halides (1977)

The reaction of an alkynylzinc chloride, readily obtainable from the corresponding alkynyl-lithium and anhydrous zinc chloride, with an alkenyl iodide or bromide in the presence of a catalytic amount of a Pd–phosphine complex provides the corresponding terminal or internal enyne in high yield, the stereospecificity of the reaction being 97%.
Development and Characterization of PCR Markers in Cucumber (2002)

Highly polymorphic microsatellites or simple sequence repeat (SSR), along with sequence characterized amplified region (SCAR) and single nucleotide polymorphisms (SNP), markers are reliable, cost-effective, and amenable for large scale analyses. Molecular polymorhisms are relatively rare in cucumber ( Cucumis sativus L.) (3% to 8%). Therefore, experiments were designed to develop SSR, SCAR and SNP markers, and optimize reaction conditions for PCR. A set of 110 SSR markers was constructed using a unique, strategically applied methodology that included the GeneTrapper (Life Technologies, Gaithersburg, Md.) kit to select plasmids harboring microsatellites. Of these markers, 58 (52%) contained dinucleotide repeats (CT, CA, TA), 21 (19%) possessed trinucleotide repeats (CTT, ATT, ACC, GCA), 3 (2.7%) contained tetranucleotide repeats (TGCG, TTAA, TAAA), 4 (3.6%) enclosed pentanucleotide repeat (ATTTT, GTTTT, GGGTC, AGCCC), 3 (2.7%) contained hexanucleotide repeats (CCCAAA, TAAAAA, GCTGGC) and 21 possessed composite repeats. Four SCARs (L18-3 SCAR, AT1-2 SCAR, N6-A SCAR, and N6-B SCAR) and two PCR markers based on SNPs (L18-2H19 A and B) that are tightly linked to multiple lateral branching (i.e., a yield component) were also developed. The SNP markers were developed from otherwise monomorphic SCAR markers, producing genetically variable amplicons. The markers L18-3 SCAR and AT1-2 SCAR were codominant. A three-primer strategy was devised to develop a codominant SCAR from a sequence containing a transposable element, and a new codominant SCAR product was detected by annealing temperature gradient (ATG) PCR. The use of a marker among laboratories can be enhanced by methodological optimization of the PCR. The utility of the primers developed was optimized by ATG-PCR to increase reliability and facilitate technology transfer. This array of markers substantially increases the pool of genetic markers available for genetic investigation in Cucumis .
Targeting and therapy of human glioma xenografts in vivo utilizing radiolabeled antibodies. (1990)

Radiolabeled antibodies provide a potential basis for selective radiotherapy of human gliomas. We have measured tumor targeting by radiolabeled monoclonal antibodies directed against neuroectodermal and tumor-associated antigens in nude mice bearing human glioma xenografts. Monoclonal P96.5, a mouse IgG2a immunoglobulin, defines an epitope of a human melanoma cell surface protein and specifically binds the U-251 human glioma as measured by immunoperoxidase histochemistry. IIIIn-radiolabeled P96.5 specifically targets the U-251 human glioma xenograft and yields 87.0 microCi of tumor activity/g/100 microCi injected activity compared to 4.5 microCi following administration of 100 microCi radiolabeled irrelevant monoclonal antibody. Calculations of targeting ratios demonstrate the deposited dose to be 11.6 times greater with radiolabeled P96.5 administration compared to irrelevant monoclonal antibody. The dose found in normal organs is less than 20% of that in the tumor, further supporting specific targeting of the human glioma xenograft by this antibody. Monoclonal antibody ZME018, which defines a second melanoma-associated antigen, demonstrates positive immunoperoxidase staining of the tumor, but comparatively decreased targeting. To test the therapeutic potential of 90Y-radiolabeled P96.5 and ZME018, tumors and normal sites were implanted with miniature thermoluminescent dosimeters. Average absorbed doses of 3770 +/- 445 (SEM) and 645 +/- 48 cGy in tumor, 353 +/- 41 and 222 +/- 13 cGy in a contralateral control i.m. site, 980 +/- 127 and 651 +/- 63 cGy in liver, and 275 +/- 14 and 256 +/- 18 cGy in total body were observed 7 days following administration of 100 microCi 90Y-radiolabeled P96.5 and ZME018, respectively. Calculations of absorbed dose by the medical internal radiation dose method confirmed thermoluminescent dosimeter absorbed dose measurements. To test the therapeutic potential, tumor-bearing nude mice were given intracardiac injections of either buffer or 90Y-radiolabeled P96.5 or ZME018. Tumor regression was measured in 1 of 12, 9 of 10, and 12 of 12 compared to 0 of 10, 1 of 10, and 2 of 10 animals following administration of 50, 100, or 200 microCi 90Y-labeled P96.5 and ZME018, respectively. Average maximal decreases in tumor volume were 42.7 +/- 11.9 and 94.2 +/- 3.3% 28 and 58 days following 100 and 200 microCi 90Y-radiolabeled P96.5 administration, respectively. In contrast, no average decrease in tumor volume was noted following 50, 100, or 200 microCi 90Y-labeled ZME018.(ABSTRACT TRUNCATED AT 400 WORDS)