gebhart/patrepeval huggingface dataset:
A Bicistronic CYCLIN D1-TROP2 mRNA Chimera Demonstrates a Novel Oncogenic Mechanism in Human Cancer (2008)

A chimeric CYCLIN D1-TROP2 mRNA was isolated from human ovarian and mammary cancer cells. The CYCLIN D1-TROP2 mRNA was shown to be a potent oncogene as it transforms naïve, primary cells in vitro and induces aggressive tumor growth in vivo in cooperation with activated RAS. Silencing of the chimeric mRNA inhibits the growth of breast cancer cells. The CYCLIN D1-TROP2 mRNA was expressed by a large fraction of the human gastrointestinal, ovarian, and endometrial tumors analyzed. It is most frequently detected in intestinal cell aneuploid cancers and it is coexpressed with activated RAS oncogenes, consistent with a cooperative transforming activity in human cancers. The chimeric mRNA is a bicistronic transcript of post transcriptional origin that independently translates the Cyclin D1 and Trop-2 proteins. This is a novel mechanism of CYCLIN D1 activation that achieves the truncation of the CYCLIN D1 mRNA in the absence of chromosomal rearrangements. This leads to a higher CYCLIN D1 mRNA stability, with inappropriate expression during the cell cycle. The stabilized CYCLIN D1 mRNA cooperates with TROP2 in stimulating the growth of the expressing cells. These findings show a novel epigenetic, oncogenic mechanism, which seems to be widespread in human cancers.
The Peptidome of Behçet's Disease–Associated HLA–B*51:01 Includes Two Subpeptidomes Differentially Shaped by Endoplasmic Reticulum Aminopeptidase 1 (2015)

ERAP-1 has a significant influence on the B*51:01 peptidome and its affinity. This influence is based on very distinct effects on the 2 subpeptidomes, whereby only peptides in the subpeptidome with Ala at position 2 are extensively destroyed, except when their position 1 residues are ERAP-1 resistant. This pattern provides a mechanism for the epistatic association of ERAP-1 and B*51:01 in Behçet's disease.
The binding of reduced nicotinamide adenine dinucleotide to citrate synthase of Escherichia coli K12 (1976)

Citrate synthase from Escherichia coli enhances the fluorescence of its allosteric inhibitor, NADH, and shifts the peak of emission of the coenzyme from 457 to 428 nm. These effects have been used to measure the binding of NADH to this enzyme under various conditions. The dissociation constant for the NADH-citrate synthase complex is about 0.28 muM at pH 6.2, but increases toward alkaline pH as if binding depends on protonation of a group with a pKa of about 7.05. Over the pH range 6.2-8.7, the number of binding sites decreases from about 0.65 to about 0.25 per citrate synthase subunit. The midpoint of this transition is at about pH 7.7, and it may be one reflection of the partial depolymerization of the enzyme which is known to occur in this pH range. A gel filtration method has been used to verify that the fluorescence enhancement technique accurately reveals all of the NADH molecules bound to the enzyme in the concentration range of interest. NAD+ and NADP+ were weak competitive inhibitors of NADH binding at pH 7.8 (Ki values greater than 1 mM), but stronger inhibition was shown by 5'-AMP and 3'-AMP, with Ki values of 83 +/- 5 and 65 +/- 4 muM, respectively. Acetyl-CoA, one of the substrates, and KCl, an activator, also inhibit the binding in a weakly cooperative manner. All of these effects are consistent with kinetic observations on this system. We interpret our results in terms of two types of binding site for nucleotides on citrate synthase: an active site which binds acetyl-CoA, the substrate, or its analogue 3'-AMP; and an allosteric site which binds NADH or its analogue 5'-AMP and has a lesser affinity for other nicotinamide adenine dinucloetides. When the active site is occupied, we propose that NADH cannot bind to the allosteric site, but 5'-AMP can; conversely, when NADH is the in the allosteric site, the active site cannot be occupied. In addition to these two classes of sites, there must be points for interaction with KCl and other salts. Oxaloacetate, the second substrate, and alpha-ketoglutarate, an inhibitor whose mode of action is believed to be allosteric, have no effect on NADH binding to citrate synthase at pH 7.8. When NADH is bound to citrate synthase, it quenches the intrinsic tryptophan fluorescence of the enzyme. The amount of quenching is proportional to the amount of NADH bound, at least up to a binding ratio of 0.50 NADH per enzyme subunit. This amount of binding leads to the quenching of 53 +/- 5% of the enzyme fluorescence, which means that one NADH molecule can quench all the intrinsic fluorescence of the subunit to which it binds.
Heparin-binding peptides from thrombospondins 1 and 2 contain focal adhesion-labilizing activity. (1993)

The cell adhesion regulating extracellular matrix glycoprotein, thrombospondin (TSP), causes a loss of focal adhesion plaques from spread endothelial cells and fibroblasts. To localize the site on TSP that has focal adhesion-labilizing activity, we initially tested proteolytic fragments of TSP for activity. The heparin-binding fragment has significant focal adhesion-labilizing activity, whereas the nonheparin-binding 140-kDa fragment had no significant activity. These results were consistent with previous data that showed that both a monoclonal antibody to the heparin-binding domain of TSP (A2.5) and heparin neutralized TSP activity. Peptides from putative heparin binding sequences of the amino-terminal heparin-binding domain of TSP were synthesized and tested for their ability to cause loss of focal adhesions. The hep I peptide (amino acids 17-35) caused maximal loss of focal adhesions and was active at 0.1 microM, whereas peptide hep II (74-95) and peptide hep III (170-189) were inactive. The activity of the hep I peptide was neutralized by the addition of heparin and heparan sulfate but not by chondroitin sulfate. The basic amino acids in the hep I sequence appear to be required for focal adhesion-labilizing activity, because modification of the lysine residues at amino acids 24 and 32 rendered the peptide completely inactive. In addition, a peptide from the analogous sequence of mouse TSP 2, in which basic residues are conserved, was nearly as active as hep I from TSP1. These data show that the anti-adhesive activity of TSP is conserved in both TSP1 and TSP2 and that the active site is located in a 19-amino acid sequence in the heparin-binding domain of TSPs.
Purification from Bovine Serum of a Survival-Promoting Factor for Cultured Central Neurons and Its Identification as Selenoprotein-P (1998)

We purified from bovine serum a glycoprotein that promotes the survival of rat embryonic neurons cultured from septum and other brain regions. A 40,000-fold purification was achieved by using a combination of ammonium sulfate precipitation, Zn2+ affinity chromatography, Cibacron blue 3-GA dye affinity chromatography, ABx ion exchange chromatography, and preparative PAGE. The active protein had an apparent molecular weight of 50-60 kDa. The concentration required for half-maximal survival (EC50) was 12 ng/ml ( approximately 200 pM) for the final fraction. Amino acid sequencing after cyanogen bromide cleavage yielded two sequences that are homologous to regions of deduced sequence of the selenoprotein-P (SPP) family in bovine, rat, and human. Antibodies against a synthetic peptide within the bovine SPP sequence immunoprecipitated and inhibited the survival-promoting activity of a partially purified serum fraction. The purified protein supported neuronal survival more effectively than inorganic selenium. These results suggest that SPP or an SPP-like protein contributes to the neuronal survival-promoting activity of serum.
T-lymphocyte interleukin 2-dependent tyrosine protein kinase signal transduction involves the activation of p56lck. (1991)

Addition of interleukin 2 (IL-2) to IL-2-dependent T cells results in tyrosine protein kinase signal transduction events even though the IL-2 receptor alpha and beta chains lack intrinsic enzymatic activity. Here we report that addition of IL-2 to IL-2-dependent human T cells transiently stimulates the specific activity of p56lck, a member of the src family of nonreceptor tyrosine protein kinases expressed at high levels in T lymphocytes. The ability of IL-2 to induce p56lck activation was found to be independent of the capacity of p56lck to associate with either CD4 or CD8. Following IL-2 treatment, p56lck was found to undergo serine/threonine phosphorylation modifications that resulted in altered mobility of the lck gene product on polyacrylamide gels. These observations raise the possibility that p56lck participates in IL-2-mediated signal transduction events in T cells.
Efficient TALEN-mediated gene knockout in livestock (2012)

Transcription activator-like effector nucleases (TALENs) are programmable nucleases that join FokI endonuclease with the modular DNA-binding domain of TALEs. Although zinc-finger nucleases enable a variety of genome modifications, their application to genetic engineering of livestock has been slowed by technical limitations of embryo-injection, culture of primary cells, and difficulty in producing reliable reagents with a limited budget. In contrast, we found that TALENs could easily be manufactured and that over half (23/36, 64%) demonstrate high activity in primary cells. Cytoplasmic injections of TALEN mRNAs into livestock zygotes were capable of inducing gene KO in up to 75% of embryos analyzed, a portion of which harbored biallelic modification. We also developed a simple transposon coselection strategy for TALEN-mediated gene modification in primary fibroblasts that enabled both enrichment for modified cells and efficient isolation of modified colonies. Coselection after treatment with a single TALEN-pair enabled isolation of colonies with mono- and biallelic modification in up to 54% and 17% of colonies, respectively. Coselection after treatment with two TALEN-pairs directed against the same chromosome enabled the isolation of colonies harboring large chromosomal deletions and inversions (10% and 4% of colonies, respectively). TALEN-modified Ossabaw swine fetal fibroblasts were effective nuclear donors for cloning, resulting in the creation of miniature swine containing mono- and biallelic mutations of the LDL receptor gene as models of familial hypercholesterolemia. TALENs thus appear to represent a highly facile platform for the modification of livestock genomes for both biomedical and agricultural applications.
Bitcoin and Beyond: A Technical Survey on Decentralized Digital Currencies. (2015)

Besides attracting a billion dollar economy, Bitcoin revolutionized the field of digital currencies and influenced many adjacent areas. This also induced significant scientific interest. In this survey, we unroll and structure the manyfold results and research directions. We start by introducing the Bitcoin protocol and its building blocks. From there we continue to explore the design space by discussing existing contributions and results. In the process, we deduce the fundamental structures and insights at the core of the Bitcoin protocol and its applications. As we show and discuss, many key ideas are likewise applicable in various other fields, so that their impact reaches far beyond Bitcoin itself.
Parallelization in co-compilation for configurable accelerators-a host/accelerator partitioning compilation method (2002)

The paper introduces a novel co-compiler and its "vertical" parallelization method, including a general model for co-operating host/accelerator platforms and a new parallelizing compilation technique derived from it. Small examples are used for illustration. It explains the exploitation of different levels of parallelism to achieve optimized speed ups and hardware resource utilization. Section II introduces novel vertical parallelization techniques involving parallelism exploitation at four different levels (task, loop, statement, and operation level) is explained, achieved by for configurable accelerators. Finally the results are illustrated by a simple application example. But first the paper summarizes the fundamentally new dynamically reconfigurable hardware platform underlying the co-compilation method.
Validation of DEMs derived from radar interferometry, airborne laser scanning and photogrammetry by using GPS-RTK (2004)

A high resolution digital elevation model (DEM) enables easy derivation of subsequent information for various applications. This work uses real-time kinematic (RTK) GPS to examine the quality of some DEMs generated by such means as radar interferometry (InSAR), airborne laser scanning (ALS) and photogrammetry. The preliminary results show that a DEM generated from ALS has the highest accuracy with a RMS error of 0.09 /spl sim/ 0.3 m. The RMS errors of DEMs derived by photogrammetric and radar interferometric techniques are 1.03 /spl sim/ 3.75m and 4.26 /spl sim/ 27.81 m respectively.
Novel pharmacogenetic markers for treatment outcome in azathioprine‐treated inflammatory bowel disease (2009)

These findings have important implications for clinical practice and our understanding of AZA metabolism.
Enzyme-Cleavable Polymeric Micelles for the Intracellular Delivery of Proapoptotic Peptides (2017)

Peptides derived from the third Bcl-2 homology domain (BH3) renormalize apoptotic signaling by antagonizing prosurvival Bcl-2 family members. These potential peptide drugs exhibit therapeutic activities but are limited by barriers including short circulation half-lives and poor penetration into cells. A diblock polymeric micelle carrier for the BIM BH3 peptide was recently described that demonstrated antitumor activity in a B-cell lymphoma xenograft model [Berguig et al., Mol. Ther. 2015, 23, 907-917]. However, the disulfide linkage used to conjugate the BIM peptide was shown to have nonoptimal blood stability. Here we describe a peptide macromonomer composed of BIM capped with a four amino acid cathepsin B substrate (FKFL) that possesses high blood stability and is cleaved to release the drug inside of target cells. Employing RAFT polymerization, the peptide macromonomer was directly integrated into a multifunctional diblock copolymer tailored for peptide delivery. The first polymer block was made as a macro-chain transfer agent (CTA) and composed of a pH-responsive endosomolytic formulation of N,N-diethylaminoethyl methacrylate (DEAEMA) and butyl methacrylate (BMA). The second polymer block was a copolymer of the peptide and polyethylene glycol methacrylate (PEGMA). PEGMA monomers of two sizes were investigated (300 Da and 950 Da). Protein gel analysis, high performance liquid chromatography, and coupled mass spectrometry (MS) showed that incubation with cathepsin B specifically cleaved the FKFL linker and released active BIM peptide with PEGMA<sub>300</sub> but not with PEGMA<sub>950</sub>. MALDI-TOF MS showed that incubation of the peptide monomers alone in human serum resulted in partial cleavage at the FKFL linker after 12 h. However, formulation of the peptides into polymers protected against serum-mediated peptide degradation. Dynamic light scattering (DLS) demonstrated pH-dependent micelle disassembly (25 nm polymer micelles at pH 7.4 versus 6 nm unimers at pH 6.6), and a red blood cell lysis assay showed a corresponding increase in membrane destabilizing activity (<1% lysis at pH 7.4 versus 95% lysis at pH 6.6). The full carrier-drug system successfully induced apoptosis in SKOV3 ovarian cancer cells in a dose-dependent manner, in comparison to a control polymer containing a scrambled BIM peptide sequence. Mechanistic analysis verified target-dependent activation of caspase 3/7 activity (8.1-fold increase), and positive annexin V staining (72% increase). The increased blood stability of this enzyme-cleavable peptide polymer design, together with the direct polymerization approach that eliminated postsynthetic conjugation steps, suggests that this new carrier design could provide important benefits for intracellular peptide drug delivery.
HYPER-RECOMBINING RECIPIENT STRAINS IN BACTERIAL CONJUGATION (1986)

Using a direct enrichment and screening procedure, mutants of Escherichia coli have been isolated in which recombination frequencies for several intragenic Hfr X F- crosses are significantly higher (twofold to sixfold) than in the parental strains. These hyper-recombination mutations comprised five new mutS- and one new mutL- allele. Together with other known mut- alleles, they were analyzed for effects on intragenic recombination using several types of crosses. Hyper-recombination was found for mutS-, mutL-, mutH (= mutR)- and mutU (= uvrD)-, with the largest effects seen for certain alleles of uvrD; these resulted in over 20-fold excesses in recombinant production for Hfr X F- crosses and F'-chromosome homogenotization. Spontaneous mutator ability was not always correlated with degree of hyper-recombination.
The Role of Hypoxia-Induced Factors in Tumor Progression (2004)

Hypoxia is a common characteristic of locally advanced solid tumors that has been associated with diminished therapeutic response and, more recently, with malignant progression, that is, an increasing probability of recurrence, locoregional spread, and distant metastasis. Emerging evidence indicates that the effect of hypoxia on malignant progression is mediated by a series of hypoxia-induced proteomic and genomic changes activating angiogenesis, anaerobic metabolism, and other processes that enable tumor cells to survive or escape their oxygen-deficient environment. The transcription factor hypoxia-inducible factor 1 (HIF-1) is a major regulator of tumor cell adaptation to hypoxic stress. Tumor cells with proteomic and genomic changes favoring survival under hypoxic conditions will proliferate, thereby further aggravating the hypoxia. The selection and expansion of new (and more aggressive) clones, which eventually become the dominant tumor cell type, lead to the establishment of a vicious circle of hypoxia and malignant progression.
A spiral antenna backed by a conducting plane reflector (1986)

An Archimedean planar spiral antenna is numerically analyzed in the presence of a conducting plane reflector. The analysis shows that the spiral antenna backed by the plane reflector has two distinct regions in the current distribution, which explain the radiation of a circularly polarized wave for the outer circumference <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">C</tex> ranging over about <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1.3 \lambda &lt; C &lt; 1.5 \lambda</tex> and <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">C &gt; 2.9 \lambda</tex> , where <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">\lambda</tex> is a free-space wavelength. Further consideration is given to a truncated spiral antenna whose outer circumference is on the order of <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1.4 \lambda</tex> . The truncated spiral antenna maintains a decaying current distribution and radiates a circularly polarized wave over a 1:1.2 frequency bandwidth. It is also demonstrated that a power gain on the order of 8.5 dB is realized over the same frequency range.
Tumor-inhibitory antibodies to HER-2/ErbB-2 may act by recruiting c-Cbl and enhancing ubiquitination of HER-2. (2000)

Overexpression of HER-2/ErbB-2, a homologue of the epidermal growth factor receptor, is associated with poor prognosis, and an ErbB-2-specific antibody is therapeutic when administered to patients with metastatic breast cancer. To understand the mechanism underlying immunotherapy, we concentrated on antibody- and epidermal growth factor-induced degradation of ErbB-2. We show that enhanced degradation is preceded by poly-ubiquitination of ErbB-2. This process necessitates recruitment of the c-Cbl ubiquitin ligase to tyrosine 1112 of ErbB-2. Consequently, mutagenesis of this site retards antibody-induced degradation. Thus, the therapeutic potential of certain antibodies may be due to their ability to direct ErbB-2 to a c-Cbl-regulated proteolytic pathway.
Hash-AV: fast virus signature scanning by cache-resident filters (2007)

Fast virus scanning is becoming increasingly important in today's internet. While Moore's law continues to double CPU cycle speed, virus scanning applications fail to ride on the performance wave due to their frequent random memory accesses. This paper proposes Hash-AV, a virus scanning 'booster' technique that aims to take advantage of improvements in CPU performance. Using a set of hash functions and a Bloom filter array that fits in CPU second-level (L2) caches, Hash-AV determines the majority of 'no-match' cases without accesses to main memory. Experiments show that Hash-AV improves the performance of the open-source virus scanner Clam-AV by a factor of 2–10. The key to Hash-AV's success lies in a set of 'bad but cheap' hash functions that are used as initial hashes. The speed of Hash-AV makes it well suited for 'on-access' virus scanning, providing greater protections to the user. Through intercepting system calls and wrapping glibc libraries, we have implemented an 'on-access' version for Hash-AV+Clam-AV. The on-access scanner can examine input data at a throughput of over 200 Mb/s, making it suitable for network-based virus scanning.
DNA binding properties of the purified Antennapedia homeodomain. (1990)

The in vitro DNA binding properties of a purified 68-amino acid Antennapedia homeodomain (Antp HD) peptide have been analyzed. Equilibrium and kinetic binding studies showed that stable DNA-protein complexes are formed with a Kd of 1.6 x 10(-9) M and 1.8 x 10(-10) M, respectively. Heterodimer analysis led to the conclusion that Antp HD interacts in vitro as a monomer with the DNA target sites used in our study. The results of methylation and ethylation interference studies indicated that the Antp HD closely approaches the target DNA primarily from one side in a region extending across three phosphate backbones. The DNA binding properties of the Antp HD and prokaryotic DNA binding domains that share a helix-turn-helix motif are compared.
Mycoplasma hominis and Ureaplasma species brain abscess in a neonate (2002)

We report an infant with a mixed Mycoplasma and Ureaplasma brain abscess who was successfully treated with intravenous doxycycline and erythromycin. Therapeutic concentrations of doxycycline were demonstrated in cerebrospinal fluid. This report is evidence of the potential for Mycoplasma and Ureaplasma to produce focal central nervous system infection, as well as meningitis, in neonates and that use of doxycycline can be efficacious in the therapy of such infections.
Nd:YAG laser‐Induced interstitial hyperthermia using a long frosted contact probe (1990)

The heating potential of a closed loop interstitial hyperthermia system employing 1,064 nm laser light in conjunction with a long frosted contact probe was investigated in hind limb muscle of anesthetized dogs. The laser system was an Nd:YAG surgical laser modified with a single channel thermometry unit, a computer, a printer, and a computer-controlled laser exposure shutter. The long frosted laser probe was implanted into the muscle, and 3.12-5.00 Watts of laser power was delivered interstitially. Temperature distribution was measured in three dimensions around the frosted probe. The temperature distributions generated by this technique were satisfactory for producing desired hyperthermia temperatures in an approximately 3.5 cm3 cylindrical tissue volume. A multiple laser delivery system is needed to induce interstitial hyperthermia in large tumors. A significant potential for the long frosted contact probe may be its use in combining interstitial hyperthermia and interstitial photodynamic therapy. Using this technique, both modalities may be delivered while employing the same treatment setup.