gebhart/patrepeval huggingface dataset:
A locally adaptive data compression scheme (1986)

A data compression scheme that exploits locality of reference, such as occurs when words are used frequently over short intervals and then fall into long periods of disuse, is described. The scheme is based on a simple heuristic for self-organizing sequential search and on variable-length encodings of integers. We prove that it never performs much worse than Huffman coding and can perform substantially better; experiments on real files show that its performance is usually quite close to that of Huffman coding. Our scheme has many implementation advantages: it is simple, allows fast encoding and decoding, and requires only one pass over the data to be compressed (static Huffman coding takes two passes).
Sch-66336 (Sarasar&#174;) and Other Benzocycloheptapyridyl Farnesyl Protein Transferase Inhibitors: Discovery, Biology and Clinical Observations (2003)

Farnesyl Protein Transferase as a target for therapeutic intervention is currently under investigation in human clinical trials. Sch-66336 (sarasar), a benzocycloheptapyridyl Farnesyl Transferase Inhibitor (FTI), has been found to be effective in cellular proliferation assays and in in vivo oncology models both as a single agent and in combination with other anti-cancer agents. Clinically, early evidence is being generated that suggests efficacy in humans, particularly in patients with leukemia. Herein, we review the biology of FPT, the discovery of Sch-66336 and other benzocycloheptapyridyl FTIs, and the clinical evaluation of Sch-66336 for the treatment of leukemia and solid tumors.
Hydroxypropylation (1972)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHydroxypropylationPhilip E. Eaton, Gary F. Cooper, Richard C. Johnson, and Richard H. MuellerCite this: J. Org. Chem. 1972, 37, 12, 1947–1950Publication Date (Print):June 1, 1972Publication History Published online1 May 2002Published inissue 1 June 1972https://pubs.acs.org/doi/10.1021/jo00977a019https://doi.org/10.1021/jo00977a019research-articleACS PublicationsRequest reuse permissionsArticle Views535Altmetric-Citations77LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Comparison of the Pharmacological Effects of a Novel Selective Androgen Receptor Modulator, the 5α-Reductase Inhibitor Finasteride, and the Antiandrogen Hydroxyflutamide in Intact Rats: New Approach for Benign Prostate Hyperplasia (2004)

Tissue-selective androgen receptor modulators (SARMs) demonstrate tissue selectivity in both castrated and intact male rats, behaving as partial agonists in androgenic tissues (i.e. prostate and seminal vesicle), but full agonists in anabolic tissues (i.e. levator ani muscle). The partial agonist activity of SARMs (compounds S-1 and S-4) in the prostate of intact rats suggested that SARM could be used for androgen suppression in the treatment of benign prostate hyperplasia (BPH). This study was designed to explore the mechanisms of action of SARM and to characterize the tissue selectivity of S-1 in intact male rats compared with that of hydroxyflutamide (antiandrogen) and finasteride (5alpha-reductase inhibitor), two major drugs used for androgen suppression treatment of BPH. In intact male rats, S-1 (5, 10, and 25 mg/kg) selectively decreased the prostate weight with similar efficacy to finasteride (5 mg/kg), without affecting the levator ani muscle or increasing the plasma levels of testosterone, LH, and FSH. Hydroxyflutamide (0.5, 1, 5, 10, and 25 mg/kg), however, decreased both the prostate and levator ani muscle weights without any selectivity and increased plasma hormone levels in a dose-dependent manner. Furthermore, S-1 and S-4 showed very weak inhibitory effects toward transiently expressed type I and II human 5alpha-reductase (Ki, >20 microm) during in vitro assays. Therefore, although S-1 and finasteride showed very similar suppressive effects in the prostate of intact male rats, they decreased prostate size via different mechanisms of action. S-1 simply worked as androgen receptor partial agonist, whereas finasteride inhibited prostatic 5alpha-reductase. These studies indicate that SARMs may demonstrate clinical utility as single agent or combination therapy for BPH.
High-resolution genome-wide in vivo footprinting of diverse transcription factors in human cells (2010)

Regulation of gene transcription in diverse cell types is determined largely by varied sets of cis-elements where transcription factors bind. Here we demonstrate that data from a single high-throughput DNase I hypersensitivity assay can delineate hundreds of thousands of base-pair resolution in vivo footprints in human cells that precisely mark individual transcription factor-DNA interactions. These annotations provide a unique resource for the investigation of cis-regulatory elements. We find that footprints for specific transcription factors correlate with ChIP-seq enrichment and can accurately identify functional versus nonfunctional transcription factor motifs. We also find that footprints reveal a unique evolutionary conservation pattern that differentiates functional footprinted bases from surrounding DNA. Finally, detailed analysis of CTCF footprints suggests multiple modes of binding and a novel DNA binding motif upstream of the primary binding site.
Thermal conductivity and electromechanical property of single-crystal lead magnesium niobate titanate (1999)

Thermal conductivity of a single-crystal lead magnesium niobate titanate-(1-x)Pb(Mg1/3Nb2/3)O3-xPbTiO3 with x=0.34 has been studied at temperatures from 20 to 320 K and in an applied electric field. The thermal conductivity of the crystal is similar to that of a typical amorphous solid both in the temperature dependence and in magnitude. The electric field dependence of the thermal conductivity and strain show an abrupt change at about 15 kV/cm, which is interpreted as due to a field-induced phase transformation in the crystal.
Cis/trans isomerization in HIV‐1 capsid protein catalyzed by cyclophilin A: Insights from computational and theoretical studies (2004)

A network of protein vibrations has recently been identified in the enzyme cyclophilin A (CypA) that is associated with its peptidyl-prolyl cis/trans isomerization activity of small peptide substrates. It has been suggested that this network may have a role in promoting the catalytic step during the isomerization reaction. This work presents the results from the characterization of this network during the isomerization of the Gly89-Pro90 peptide bond in the N-terminal domain of the capsid protein (CA(N)) from human immunodeficiency virus type 1 (HIV-1), which is a naturally occurring, biologically relevant protein substrate for CypA. A variety of computational and theoretical studies are utilized to investigate the protein dynamics of the CypA-CA(N) complex, at multiple time scales, during the isomerization step. The results provide insights into the detailed mechanism of isomerization and confirm the presence of previously reported network of protein vibrations coupled to the reaction. Conserved CypA residues at the complex interface and at positions distal to the interface form parts of this network. There is HIV-1 related medical interest in CypA; incorporation of CypA, complexed with the capsid protein, into the virion is required for the infectious activity of HIV-1. Interaction energy and dynamical cross-correlation calculations are used for a detailed investigation of the protein-protein interactions in the CypA-CA(N) complex. The results show that CA(N) residues His87-Ala-Gly-Pro-Ile-Ala92 form the majority of the interactions with CypA residues. New protein-protein interactions distal to the active site (CypA Arg148-CA(N) Gln95 and CypA Arg148-CA(N) Asn121) are also identified.
&alpha;-Methylprednisolone conjugated cyclodextrin polymer-based nanoparticles for rheumatoid arthritis therapy (2008)

A glycinate derivative of alpha-methylprednisolone (MP) was prepared and conjugated to a linear cyclodextrin polymer (CDP) with a loading of 12.4% w/w. The polymer conjugate (CDP-MP) self-assembled into nanoparticles with a size of 27 nm. Release kinetics of MP from the polymer conjugate showed a half-life (t1/2) of 50 h in phosphate buffer solution (PBS) and 19 h in human plasma. In vitro, the proliferation of human lymphocytes was suppressed to a similar extent but with a delayed effect when CDP-MP was compared with free MP. In vivo, CDP-MP was administered intravenously to mice with collagen-induced arthritis and compared with free MP. CDP-MP was administered weekly for six weeks (0.07, 0.7, and 7 mg/kg/week) and MP was administered daily for six weeks (0.01, 0.1, and 1 mg/kg/day). Body weight changes were minimal in all animals. After 28 days, a significant decrease in arthritis score was observed in animals treated weekly with an intermediate or high dose of CDP-MP. Additionally, dorsoplantar swelling was reduced to baseline in animals treated with CDP-MP at the intermediate and high dose level. Histological evaluation showed a reduction in synovitis, pannus formation and disruption of architecture at the highest dose level of CDP-MP. MP administered daily at equivalent cumulative doses showed minimal efficacy in this model. This study demonstrates that conjugation of MP to a cyclodextrin-polymer may improve its efficacy, leading to lower doses and less frequent administration for a safer and more convenient management of rheumatoid arthritis.
A prototype beam delivery system for the proton medical accelerator at Loma Linda (1991)

A variable energy proton accelerator was commissioned at Fermi National Accelerator Laboratory for use in cancer treatment at the Loma Linda University Medical Center. The advantages of precise dose localization by proton therapy, while sparing nearby healthy tissue, are well documented [R. R. Wilson, Radiology 47, 487 (1946); M. Wagner, Med. Phys. 9, 749 (1982); M. Goitein and F. Chen, Med. Phys. 10, 831 (1983)]. One of the components of the proton therapy facility is a beam delivery system capable of delivering precise dose distributions to the target volume in the patient. To this end, a prototype beam delivery system was tested during the accelerator's commissioning period. The beam delivery system consisted of a beam spreading device to produce a large, uniform field, a range modulator to generate a spread out Bragg peak (SOBP), and various beam detectors to measure intensity, beam centering, and dose distributions. The beam delivery system provided a uniform proton dose distribution in a cylindrical volume of 20-cm-diam area and 9-cm depth. The dose variations throughout the target volume were found to be less than +/- 5%. Modifications in the range modulator should reduce this considerably. The central axis dose rate in the region of the SOBP was found to be 0.4 cGy/spill with an incident beam intensity of 6.7 x 10(9) protons/spill. With an accelerator repetition rate of 30 spills/min and expected intensity of 2.5 x 10(10) protons/spill for patient treatment, this system can provide 50 cGy/min for a 20-cm-diam field and 9-cm range modulation.(ABSTRACT TRUNCATED AT 250 WORDS)
The Proto-oncogene Product c-Cbl Becomes Tyrosine Phosphorylated by Stimulation with GM-CSF or Epo and Constitutively Binds to the SH3 Domain of Grb2/Ash in Human Hematopoietic Cells (1995)

Granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (Epo) are hematopoietic growth factors that regulate proliferation and differentiation of hematopoietic cells. They elicit and control a cascade of biochemical events, the earliest of which is tyrosine phosphorylation of several cellular proteins. Grb2/Ash is composed of SH2 and SH3 domains. The SH2 domain binds to tyrosine-phosphorylated proteins, and the SH3 domains bind to proteins containing proline-rich regions. It is considered that Grb2/Ash functions as an adapter protein linking tyrosine kinases and Ras in downstream of receptors for growth factors in fibroblasts. However, the mechanisms of signal transduction through Grb2/Ash and the roles of proteins associated with Grb2/Ash remain to be determined in hematopoietic cells. By means of the binding experiments using the glutathione S-transferase fusion protein including the full-length Grb2/Ash, we have found that Shc and unidentified 130- and 135-kDa proteins are associated with Grb2/Ash and that they are tyrosine phosphorylated by treatment with GM-CSF or Epo in a human leukemia cell line, UT-7. We have purified the 130-kDa protein (pp130) using the glutathione S-transferase-Grb2/Ash affinity column. The amino acid sequence analysis of the three peptides derived from the in situ protease digestion of the purified pp130 showed that the pp130 was identical to the human c-cbl proto-oncogene product (c-Cbl). c-Cbl constitutively binds to the SH3 domain of Grb2/Ash both in vitro and in vivo but not to the SH2 domain of Grb2/Ash, and the binding of Grb2/Ash to c-Cbl or Sos was not altered by GM-CSF stimulation. Moreover, c-Cbl (pp130) becomes tyrosine phosphorylated rapidly and transiently depending on GM-CSF or Epo stimulation. These findings strongly suggest that c-Cbl is implicated in the signal transduction of GM-CSF or Epo in hematopoietic cells and that c-Cbl is involved in another signaling pathway different from the Ras signaling pathway.
An investigation of the Bosch process. (1976)

Thesis: Sc. D., Massachusetts Institute of Technology, Department of Chemical Engineering, 1976
Soluble MIC is elevated in the serum of patients with pancreatic carcinoma diminishing γδ T cell cytotoxicity (2006)

Intestinal cells express MHC related molecules termed MICA/MICB, which are up-regulated under stress and in many gastrointestinal tumors. These molecules can be recognized by the immunoreceptor NKG2D, which is present on NK and gammadelta T cells. Release of MIC molecules from the cell surface is thought to constitute an immune escape mechanism of tumor cells. The immediate effect of soluble MIC (sMIC) on cellular cytotoxicity of gammadelta T cells is yet not investigated. We determined sMIC levels in sera of patients with pancreatic carcinoma and the expression of MIC on the surface of tumor cells by FACS. The effect of sMIC content in patient serum on cellular cytotoxicity of gammadelta T and NK cells was investigated by cytotoxicity assays. Subsequently, the effect of IFN-alpha treatment on MIC expression, release and cellular cytotoxicity was investigated. Pancreatic carcinoma cells express MIC, and patient sera contain elevated sMIC levels that correlate with tumor stage and differentiation. Furthermore, cellular cytotoxicity of gammadelta T cells and NK cells against pancreatic carcinoma is impaired by sMIC in patient sera which is prevented by sMIC neutralization. Incubation of pancreatic cancer cells with IFN-alpha increases MIC expression without induction of sMIC resulting in enhanced lysis of tumor cells. Our results demonstrate that sMIC impairs NKG2D-mediated immunity against pancreatic carcinoma by directly diminishing cytotoxicity of gammadelta T cells and NK cells. IFN-alpha, which is used in adjuvant treatment of pancreatic carcinoma, might partly act via up-regulation of MIC without induction of sMIC release.
Integrin α4β1-Dependent Adhesion to ADAM 28 (MDC-L) Requires an Extended Surface of the Disintegrin Domain (2003)

ADAMs (a disintegrin and metalloprotease) are a family of proteins that possess functional adhesive and proteolytic domains. ADAM 28 (MDC-L) is expressed by human lymphocytes and contains a disintegrin-like domain that serves as a ligand for the leukocyte integrin, alpha4beta1. To elucidate which residues comprise the alpha4beta1 binding site in the ADAM 28 disintegrin domain, a charge-to-alanine mutagenesis strategy was utilized. Each alanine substitution mutant was evaluated and compared to the native sequence for its ability to support cell adhesion of the T-lymphoma cell line, Jurkat. This approach identified ADAM 28 residues Lys(437), Lys(442), Lys(455), Lys(459), Lys(460), Lys(469), and Glu(476) as being essential for alpha4beta1-dependent cell adhesion. The epitope for a function-blocking monoclonal antibody, Dis 1-1, was localized to the N-terminal end of the ADAM 28 disintegrin domain using these same charge-to-alanine mutants. Three distinct molecular models based upon the known structures of snake venom disintegrins suggested that residues contributing to alpha4beta1 recognition are aligned on one face of the domain. This study demonstrates that residues located outside of the disintegrin loop participate in integrin recognition of mammalian disintegrins.
CONSIDERING EXCHANGE RATE MOVEMENTS IN ECONOMIC EVALUATION OF FOREIGN DIRECT INVESTMENTS (1995)

ABSTRACT One of the major risks encountered in economic evaluation of foreign direct investment is the changes in future exchange rates that may affect the accuracy of the estimated economic worm of the investment. The objective of this article is to present a model for reducing the uncertainty associated with changes in foreign exchange rates when conducting economic evaluations of foreign direct investments. The model uses the Purchasing Power Parity Theorem and weighted averages for creating a procedural approach in which future changes in exchange rates are considered and included in the calculation of an overall profitability measure.
Theory of the backpropagation neural network (1989)

The author presents a survey of the basic theory of the backpropagation neural network architecture covering architectural design, performance measurement, function approximation capability, and learning. The survey includes previously known material, as well as some new results, namely, a formulation of the backpropagation neural network architecture to make it a valid neural network (past formulations violated the locality of processing restriction) and a proof that the backpropagation mean-squared-error function exists and is differentiable. Also included is a theorem showing that any L/sub 2/ function from (0, 1)/sup n/ to R/sup m/ can be implemented to any desired degree of accuracy with a three-layer backpropagation neural network. The author presents a speculative neurophysiological model illustrating how the backpropagation neural network architecture might plausibly be implemented in the mammalian brain for corticocortical learning between nearby regions of the cerebral cortex.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A Versatile Scheme for Routing Highly Variable Traffic in Service Overlays and IP Backbones (2006)

The emergence of new applications on the Internet like voice-over-IP, peer-to-peer, and video-on-demand has created highly dynamic and changing traffic patterns. In order to route such traffic with Quality-of-Service (QoS) guarantees without requiring detection of traffic changes in real-time or reconfiguring the network in response to it, we consider a routing and bandwidth allocation scheme that allows preconfiguration of the network such that all traffic patterns permissible within the network’s natural ingress-egress capacity constraints can be handled in a capacity efficient manner. The scheme routes traffic in two phases. In the first phase, incoming traffic is sent from the source to a set of intermediate nodes and then, in the second phase, from the intermediate nodes to the final destination. The traffic in the first phase is distributed to the intermediate nodes in predetermined proportions that depend on the intermediate nodes. In this paper, we develop linear programming formulations and a fast combinatorial algorithm for routing under the scheme so as to maximize throughput (or, minimize maximum link utilization). We compare the throughput performance of the scheme with that of the optimal scheme among the class of all schemes that are allowed to even make the routing dependent on the traffic matrix. For our evaluations, we use actual Internet Service Provider topologies collected for the Rocketfuel project. We also bring out the versatility of the scheme in not only handling widely fluctuating traffic but also accommodating applicability to several widely differing networking scenarios, including (i) economical Virtual Private Networks (VPNs), (ii) supporting indirection in specialized service overlay models like Internet Indirection Infrastructure (i3), (iii) adding QoS guarantees to services that require routing through a network-based middlebox, and (iv) reducing IP layer transit traffic and handling extreme traffic variability in IP-over-Optical networks without dynamic reconfiguration of the optical layer. The two desirable properties of supporting indirection in specialized service overlay models and static optical layer provisioning in IP-over-Optical networks are not present in other approaches for routing variable traffic, such as direct source-destination routing along fixed paths.
Control of Bacteria Adhesion by Cell-Wall Engineering (2004)

UDP-MurNAc-pentapeptide derivative bacterial cell-wall precursors were synthesized as effective tools for surface display on living bacteria. Lactobacilli were incubated in the ketone-modified precursor-containing medium, and the ketone moiety was displayed on the bacterial surface through cell-wall biosynthesis. Oligomannose was coupled with the ketone moiety on the bacterial surface via a aminooxyl linker, thereby displaying this oligosaccharide on the surface of the bacteria. The increase in the adhesion of the sugar-displaying bacteria onto a concanavalin A-attached film compared to that of native bacteria was confirmed by microscopic observation and surface plasmon resonance measurement. The incorporation of the artificial cell-wall precursors was enhanced when incubated with fosfomycin, an inhibitor of cell-wall precursor biosynthesis.
Regulation of NF-κB by Cyclin-Dependent Kinases Associated with the p300 Coactivator (1997)

The nuclear factor kappaB (NF-kappaB) transcription factor is responsive to specific cytokines and stress and is often activated in association with cell damage and growth arrest in eukaryotes. NF-kappaB is a heterodimeric protein, typically composed of 50- and 65-kilodalton subunits of the Rel family, of which RelA(p65) stimulates transcription of diverse genes. Specific cyclin-dependent kinases (CDKs) were found to regulate transcriptional activation by NF-kappaB through interactions with the coactivator p300. The transcriptional activation domain of RelA(p65) interacted with an amino-terminal region of p300 distinct from a carboxyl-terminal region of p300 required for binding to the cyclin E-Cdk2 complex. The CDK inhibitor p21 or a dominant negative Cdk2, which inhibited p300-associated cyclin E-Cdk2 activity, stimulated kappaB-dependent gene expression, which was also enhanced by expression of p300 in the presence of p21. The interaction of NF-kappaB and CDKs through the p300 and CBP coactivators provides a mechanism for the coordination of transcriptional activation with cell cycle progression.