gebhart/patrepeval huggingface dataset:
Protein farnesyltransferase inhibitors block the growth of ras-dependent tumors in nude mice. (1994)

The posttranslational addition of a farnesyl moiety to the Ras oncoprotein is essential for its transforming activity. Cell-active inhibitors of the enzyme that catalyzes this reaction, protein farnesyltransferase, have been shown to selectively block ras-dependent transformation of cells in culture. Here we describe the protein farnesyltransferase inhibitor 2(S)-[2(S)-[2(R)-amino-3-mercapto]propylamino-3(S)-methyl] pentyloxy-3-phenylpropionylmethioninesulfone methyl ester (L-739,749), which suppressed the anchorage-independent growth of Rat1 cells transformed with viral H-ras and the human pancreatic adenocarcinoma cell line PSN-1, which harbors altered K-ras, myc, and p53 genes. This compound also suppressed the growth of tumors arising from ras-transformed Rat1 cells in nude mice by 66%. Under the same conditions, doxorubicin inhibited tumor growth by 33%. Control tumors formed by v-raf- or v-mos-transformed Rat1 cells were unaffected by L-739,749. Furthermore, mice treated with L-739,749 exhibited no evidence of systemic toxicity. This is a demonstration of antitumor activity in vivo using a synthetic small molecule inhibitor of protein farnesyltransferase.
The Pro-angiogenic Cytokine Pleiotrophin Potentiates Cardiomyocyte Apoptosis through Inhibition of Endogenous AKT/PKB Activity (2007)

Pleiotrophin is a development-regulated cytokine and growth factor that can promote angiogenesis, cell proliferation, or differentiation, and it has been reported to have neovasculogenic effects in damaged heart. Developmentally, it is prominently expressed in fetal and neonatal hearts, but it is minimally expressed in normal adult heart. Conversely, we show in a rat model of myocardial infarction and in human dilated cardiomyopathy that pleiotrophin is markedly up-regulated. To elucidate the effects of pleiotrophin on cardiac contractile cells, we employed primary cultures of rat neonatal and adult cardiomyocytes. We show that pleiotrophin is released from cardiomyocytes in vitro in response to hypoxia and that the addition of recombinant pleiotrophin promotes caspase-mediated genomic DNA fragmentation in a dose- and time-dependent manner. Functionally, it potentiates the apoptotic response of neonatal cardiomyocytes to hypoxic stress and to ultraviolet irradiation and of adult cardiomyocytes to hypoxia-reoxygenation. Moreover, UV-induced apoptosis in neonatal cardiomyocytes can be partially inhibited by small interfering RNA-mediated knockdown of endogenous pleiotrophin. Mechanistically, pleiotrophin antagonizes IGF-1 associated Ser-473 phosphorylation of AKT/PKB, and it concomitantly decreases both BAD and GSK3beta phosphorylation. Adenoviral expression of constitutively active AKT and lithium chloride-mediated inhibition of GSK3beta reduce the potentiated programmed cell death elicited by pleiotrophin. These latter data indicate that pleiotrophin potentiates cardiomyocyte cell death, at least partially, through inhibition of AKT signaling. In conclusion, we have uncovered a novel function for pleiotrophin on heart cells following injury. It fosters cardiomyocyte programmed cell death in response to pro-apoptotic stress, which may be critical to myocardial injury repair.
Environmental effects on vibronic band intensities in pyrene monomer fluorescence and their application in studies of micellar systems (1977)

LPI
A Potent Human Immunodeficiency Virus Type 1 Protease Inhibitor, UIC-94003 (TMC-126), and Selection of a Novel (A28S) Mutation in the Protease Active Site (2002)

We identified UIC-94003, a nonpeptidic human immunodeficiency virus (HIV) protease inhibitor (PI), containing 3(R),3a(S),6a(R)-bis-tetrahydrofuranyl urethane (bis-THF) and a sulfonamide isostere, which is extremely potent against a wide spectrum of HIV (50% inhibitory concentration, 0.0003 to 0.0005 microM). UIC-94003 was also potent against multi-PI-resistant HIV-1 strains isolated from patients who had no response to any existing antiviral regimens after having received a variety of antiviral agents (50% inhibitory concentration, 0.0005 to 0.0055 microM). Upon selection of HIV-1 in the presence of UIC-94003, mutants carrying a novel active-site mutation, A28S, in the presence of L10F, M46I, I50V, A71V, and N88D appeared. Modeling analysis revealed that the close contact of UIC-94003 with the main chains of the protease active-site amino acids (Asp29 and Asp30) differed from that of other PIs and may be important for its potency and wide-spectrum activity against a variety of drug-resistant HIV-1 variants. Thus, introduction of inhibitor interactions with the main chains of key amino acids and seeking a unique inhibitor-enzyme contact profile should provide a framework for developing novel PIs for treating patients harboring multi-PI-resistant HIV-1.
Natural Killer T Cells Infiltrate Neuroblastomas Expressing the Chemokine CCL2 (2004)

CD1d-restricted Valpha24-Jalpha18-invariant natural killer T cells (iNKTs) are potentially important in tumor immunity. However, little is known about their localization to tumors. We analyzed 98 untreated primary neuroblastomas from patients with metastatic disease (stage 4) for tumor-infiltrating iNKTs using TaqMan((R)) reverse transcription polymerase chain reaction and immunofluorescent microscopy. 52 tumors (53%) contained iNKTs, and oligonucleotide microarray analysis of the iNKT(+) and iNKT(-) tumors revealed that the former expressed higher levels of CCL2/MCP-1, CXCL12/SDF-1, CCL5/RANTES, and CCL21/SLC. Eight tested neuroblastoma cell lines secreted a range of CCL2 (0-21.6 ng/ml), little CXCL12 (</=0.1 ng/ml), and no detectable CCL5 or CCL21. CCR2, the receptor for CCL2, was more frequently expressed by iNKT compared with natural killer and T cells from blood (P < 0.001). Supernatants of neuroblastoma cell lines that produced CCL2 induced in vitro migration of iNKTs from blood of patients and normal adults; this was abrogated by an anti-CCL2 monoclonal antibody. CCL2 expression by tumors was found to inversely correlate with MYCN proto-oncogene amplification and expression (r = 0.5, P < 0.001), and MYCN-high/CCL2-low expression accurately predicted the absence of iNKTs (P < 0.001). In summary, iNKTs migrate toward neuroblastoma cells in a CCL2-dependent manner, preferentially infiltrating MYCN nonamplified tumors that express CCL2.
The Algorithmic Foundations of Differential Privacy (2014)

The problem of privacy-preserving data analysis has a long history spanning multiple disciplines. As electronic data about individuals becomes increasingly detailed, and as technology enables ever more powerful collection and curation of these data, the need increases for a robust, meaningful, and mathematically rigorous definition of privacy, together with a computationally rich class of algorithms that satisfy this definition. Differential Privacy is such a definition. After motivating and discussing the meaning of differential privacy, the preponderance of this monograph is devoted to fundamental techniques for achieving differential privacy, and application of these techniques in creative combinations, using the query-release problem as an ongoing example. A key point is that, by rethinking the computational goal, one can often obtain far better results than would be achieved by methodically replacing each step of a non-private computation with a differentially private implementation. Despite some astonishingly powerful computational results, there are still fundamental limitations — not just on what can be achieved with differential privacy but on what can be achieved with any method that protects against a complete breakdown in privacy. Virtually all the algorithms discussed herein maintain differential privacy against adversaries of arbitrary computational power. Certain algorithms are computationally intensive, others are efficient. Computational complexity for the adversary and the algorithm are both discussed. We then turn from fundamentals to applications other than queryrelease, discussing differentially private methods for mechanism design and machine learning. The vast majority of the literature on differentially private algorithms considers a single, static, database that is subject to many analyses. Differential privacy in other models, including distributed databases and computations on data streams is discussed. Finally, we note that this work is meant as a thorough introduction to the problems and techniques of differential privacy, but is not intended to be an exhaustive survey — there is by now a vast amount of work in differential privacy, and we can cover only a small portion of it.
Management of Thyroid Nodules Detected at US: Society of Radiologists in Ultrasound Consensus Conference Statement (2005)

The Society of Radiologists in Ultrasound convened a panel of specialists from a variety of medical disciplines to come to a consensus on the management of thyroid nodules identified with thyroid ultrasonography (US), with particular focus on which nodules should be subjected to US-guided fine needle aspiration and which thyroid nodules need not be subjected to fine-needle aspiration. The panel met in Washington, DC, October 26-27, 2004, and created this consensus statement. The recommendations in this consensus statement, which are based on analysis of the current literature and common practice strategies, are thought to represent a reasonable approach to thyroid nodular disease.
Pronuclear injection-based mouse targeted transgenesis for reproducible and highly efficient transgene expression (2010)

Mouse transgenesis has proven invaluable for analysis of gene function and generation of human disease models. We describe here the development of a pronuclear injection-based targeted transgenesis (PITT) system, involving site-specific integration in fertilized eggs. The system was applied to two different genomic target loci to generate a series of transgenic lines including fluorescent mice, which reproducibly displayed strong, ubiquitous and stable transgene expression. We also demonstrated that knockdown mice could be readily generated by PITT by taking advantage of the reproducible and highly efficient expression system. The PITT system, which circumvents the problem of unpredictable and unstable transgene expression of conventional random-integration transgenic mice, reduces the time, cost and effort needed to generate transgenic mice, and is potentially applicable to both in vivo 'gain-of-function' and 'loss-of-function' studies.
The TetR Family of Transcriptional Repressors (2005)

We have developed a general profile for the proteins of the TetR family of repressors. The stretch that best defines the profile of this family is made up of 47 amino acid residues that correspond to the helix-turn-helix DNA binding motif and adjacent regions in the three-dimensional structures of TetR, QacR, CprB, and EthR, four family members for which the function and three-dimensional structure are known. We have detected a set of 2,353 nonredundant proteins belonging to this family by screening genome and protein databases with the TetR profile. Proteins of the TetR family have been found in 115 genera of gram-positive, alpha-, beta-, and gamma-proteobacteria, cyanobacteria, and archaea. The set of genes they regulate is known for 85 out of the 2,353 members of the family. These proteins are involved in the transcriptional control of multidrug efflux pumps, pathways for the biosynthesis of antibiotics, response to osmotic stress and toxic chemicals, control of catabolic pathways, differentiation processes, and pathogenicity. The regulatory network in which the family member is involved can be simple, as in TetR (i.e., TetR bound to the target operator represses tetA transcription and is released in the presence of tetracycline), or more complex, involving a series of regulatory cascades in which either the expression of the TetR family member is modulated by another regulator or the TetR family member triggers a cell response to react to environmental insults. Based on what has been learned from the cocrystals of TetR and QacR with their target operators and from their three-dimensional structures in the absence and in the presence of ligands, and based on multialignment analyses of the conserved stretch of 47 amino acids in the 2,353 TetR family members, two groups of residues have been identified. One group includes highly conserved positions involved in the proper orientation of the helix-turn-helix motif and hence seems to play a structural role. The other set of less conserved residues are involved in establishing contacts with the phosphate backbone and target bases in the operator. Information related to the TetR family of regulators has been updated in a database that can be accessed at www.bactregulators.org.
Pessimal print: a reverse Turing test (2002)

We exploit the gap in ability between human and machine vision systems to craft a family of automatic challenges that tell human and machine users apart via graphical interfaces including Internet browsers. Turing proposed (1950) a method whereby human judges might validate "artificial intelligence" by failing to distinguish between human and machine interlocutors. Stimulated by the "chat room problem", and influenced by the CAPTCHA project of Blum et al. (2000), we propose a variant of the Turing test using pessimal print: that is, low-quality images of machine-printed text synthesized pseudo-randomly over certain ranges of words, typefaces, and image degradations. We show experimentally that judicious choice of these ranges can ensure that the images are legible to human readers but illegible to several of the best present-day optical character recognition (OCR) machines. Our approach is motivated by a decade of research on performance evaluation of OCR machines and on quantitative stochastic models of document image quality. The slow pace of evolution of OCR and other species of machine vision over many decades suggests that pessimal print will defy automated attack for many years. Applications include 'bot' barriers and database rationing.
Modular microchannel cooled heatsinks for high average power laser diode arrays (1992)

Detailed performance results for an efficient and low thermal impedance laser diode array heatsink are presented. High duty factor or CW operation of fully filled laser diode arrays is made possible at high average power. Low thermal impedance is achieved using a liquid coolant and laminar flow through microchannels. The microchannels are fabricated in silicon using an anisotropic chemical etching process. A modular rack-and-stack architecture is adopted for the heatsink design, allowing arbitrarily large two-dimensional arrays to be fabricated and easily maintained. The excellent thermal control of the microchannel cooled heatsinks is ideally suited to pump array requirements for high average power crystalline lasers.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The lux gene of the luminous bacterial symbiont, Photobacterium leiognathi, of the ponyfish (1991)

The lux genes required for light expression in the luminescent bacterium Photobacterium leiognathi (ATCC 25521) have been cloned and expressed in Escherichia coli and their organization and nucleotide sequence determined. Transformation of a recombinant 9.5-kbp chromosomal DNA fragment of P. leiognathi into an E. coli mutant (43R) gave luminescent colonies that were as bright as those of the parental strain. Moreover, expression of the lux genes in the mutant E. coli was strong enough so that not only were high levels of luciferase detected in crude extracts, but the fatty-acid reductase activity responsible for synthesis of the aldehyde substrate for the luminescent reaction could readily be measured. Determination of the 7.3-kbp nucleotide sequence of P. leiognathi DNA, including the genes for luciferase (luxAB) and fatty-acid reductase (luxCDE) as well as a new lux gene (luxG) found recently in luminescent Vibrio species, showed that the order of the lux genes was luxCDABEG. Moreover, luxF, a gene homologous to luxB and located between luxB and luxE in Photobacterium but not Vibrio strains, was absent. In spite of this different lux gene organization, an intergenic stem-loop structure between luxB and luxE was discovered to be highly conserved in other Photobacterium species after luxF.
Transmission of 8 × 480-Gb/s super-Nyquist-filtering 9-QAM-like signal at 100 GHz-grid over 5000-km SMF-28 and twenty-five 100 GHz-grid ROADMs (2013)

We experimentally demonstrate a highly filtering-tolerant multi-modulus equalization (MMEQ) process for very aggressively spectrum-shaped 9-ary quadrature-amplitude-modulation (9-QAM)-like polarization division multiplexing quadrature phase shift keying (PDM-QPSK) signal to achieve 400-Gb/s wavelength-division-multiplexing (WDM) channels on the 100-GHz grid for ultra-long-haul reach and high tolerance of the filter narrowing effect caused by reconfigurable optical add-drop multiplexers (ROADMs). We successfully transmitted 8 channels 480-Gb/s super-Nyquist (channel occupancy much less than signal baud rate) WDM signals at 100-GHz grid over 25 × 200 km conventional single-mode fiber-28 (SMF-28) with post Raman amplification and 25 ROADMs at a net spectral efficiency (SE) of 4b/s/Hz, after excluding the 20% soft-decision forward-error-correction (FEC) overhead. The system performance is significantly enhanced by the MMEQ based on 9-QAM-like constellations compared to the conventional 4 point QPSK constellation. A record transmission distance over conventional SMF-28 with a large number of ROADMs is firstly reported on the 400-Gb/s channels at 100-GHz grid.
Next Generation Sequencing to Characterize Mitochondrial Genomic DNA Heteroplasmy (2011)

This protocol describes the methodology to characterize mitochondrial DNA (mtDNA) heteroplasmy by parallel sequencing. Mitochondria play an important role in essential cellular functions. Each eukaryotic cell contains hundreds of mitochondria with hundreds of mitochondria genomes. Mutant and wild-type mtDNA may co-exist as heteroplasmy, and cause human disease. The purpose of this protocol is to simultaneously determine mtDNA sequence and quantify the heteroplasmic level. This protocol includes a two-fragment mitochondrial genome DNA PCR amplification. The PCR product is then mixed at an equimolar ratio. The samples are then barcoded and sequenced with high-throughput, next-generation sequencing technology. This technology is highly sensitive, specific, and accurate in determining mtDNA mutations and the level of heteroplasmy.
Isolation of natural products by droplet counter-current chromatography and related methods (1984)

K. Hostettmann, M. Hostettmann and A. Marston, Nat. Prod. Rep., 1984, 1, 471 DOI: 10.1039/NP9840100471
A model of atomicity for multilevel transactions (2002)

Data management applications that use multilevel database management system (DBMS) capabilities have the requirement to read and write objects at multiple levels within the bounds of a multilevel transaction. The authors define a new notion of atomicity that is meaningful within the constraints of the multilevel environment. They offer a model of multilevel atomicity that defines varying degrees of atomicity and recognizes that lower security level operations within a transaction must be able to commit or abort independently of higher security level operations. Execution graphs are provided as a tool for analyzing atomicity requirements in conjunction with internal semantic interdependencies among the operations of a transaction and rules for determining the greatest degree of atomicity are proved that can be attained for a given multilevel transaction. Several alternative transaction management algorithms that can be used to preserve multilevel atomicity are presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Vascular Endothelial Growth Factor And Soluble Adhesion Molecules As A Diagnostic Markers For Spontaneous Bacterial Peritonitis In Cirrhotic Liver Disease (2006)

Spontaneous bacterial peritonitis (SBP) is a frequent and severe complication in cirrhotic patients with ascites that usually results in renal failure and death despite the efficacy of the current antibiotic therapy. The aim of this study was determine serum and ascitic fluid of soluble-L selectin (s-L Selectin), intracellular adhesion molecule-1 (ICAM-1), Vascular cell adhesion molecule-1 (VCAM-1) and vascular endothelial growth factor (VEGF) in cirrhotic patients, and to search for a relationship between them and SBP. This study was performed on 30 cirrhotic patients with SBP. Their ages ranged (from 38- 55 years) with mean of (32 + 5.5), 30 cirrhotic patients with non-infected ascites; their ages ranged (from 30-52 years) with mean of (35 + 6.5). This group considered as cirrhotic control group and 20 healthy control subjects their ages ranged (from 28-55 years) with mean of (30 + 7.5). Serum and ascitic fluid of adhesion molecules as well as VEGF levels were significantly higher in cirrhotic patients with SBP as well as cirrhotic patients with non-infected ascites as compared to healthy control group. There were significant increase in serum and ascitic fluid level of leukocyte, PMN and ICAM-1 in SBP as compared to cirrhotic with non-infected ascites. There was non-significant decrease in serum and AF level of VEGF in cirrhotic control group as compared to SBP group. The ascitic fluid PMN and s-L Selectin were higher in culture positive SBP patients particularly in those with gram positive isolates, where these are non-significant increase in serum and ascitic fluid level of VEGF in culture positive SBP than culture negative cases. Positive correlation was found between serum and ascitic fluid level of ICAM-1 in SBP and non-infected cirrhotic group. Also, positive correlation was found between VEGF levels in serum ascetic fluid levels in both cirrhotic groups (SBP and non-infected cirrhotic group). These data suggest that: Significant elevated level of VEGF in both SBP and non infected cirrhotic patient may have pathophsiological consequences of local regulation of vascular tone and endothelial permeability, significant elevated level of adhesion molecules in both SBP and non-infected cirrhotic patients are due to inflammatory response and endothelial cell activation. Serum and ascetic fluid of ICAM-1 can be used as useful marker for diagnosis of SBP and for monitoring the treatment of cirrhotic patients.
Diastereotropic Phenomena for the Appearance of SmCA* Phase in α-Trifluoromethyl-β-methyl-substituted Liquid Crystalline Molecules (1996)

Abstract Anti-ferroelectric (SmCA*) and ferroelectric (SmC*) phases of α-trifluoromethyl-β-methyl-substituted liquid crystalline (LC) molecules, synthesized highly diastereo- and enantioselectively through our chiral titanium complex-catalyzed fluoral-ene reaction, were determined by thermal analysis and electro-optic measurements. Phase transitions were thus found to be critically dependent on the diastereomeric excess (diastereotropic) for ul (Rα, Sβ)-diastereomers of the LC molecules.