gebhart/patrepeval huggingface dataset:
A novel anti-CD37 antibody-drug conjugate with multiple anti-tumor mechanisms for the treatment of B-cell malignancies (2013)

CD37 has gathered renewed interest as a therapeutic target in non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL); however, CD37-directed antibody-drug conjugates (ADCs) have not been explored. Here, we identified a novel anti-CD37 antibody, K7153A, with potent in vitro activity against B-cell lines through multiple mechanisms including apoptosis induction, antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and complement-dependent cytotoxicity. The antibody was conjugated to the maytansinoid, DM1, a potent antimicrotubule agent, via the thioether linker, N-succinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC), and the resulting ADC, IMGN529, retained the intrinsic antibody activities and showed enhanced cytotoxic activity from targeted payload delivery. In lymphoma cell lines, IMGN529 induced G2/M cell cycle arrest after internalization and lysosomal processing to lysine-N(ε)-SMCC-DM1 as the sole intracellular maytansinoid metabolite. IMGN529 was highly active against subcutaneous B-cell tumor xenografts in severe combined immunodeficient mice with comparable or better activity than rituximab, a combination of cyclophosphamide, vincristine, and prednisone, or bendamustine. In human blood cells, CD37 is expressed in B cells at similar levels as CD20, and IMGN529 resulted in potent and specific depletion of normal and CLL B cells. These results support evaluation of the CD37-targeted ADC, IMGN529, in clinical trials in patients with B-cell malignancies including NHL and CLL.
An approach to digital image analysis of bending shapes of eukaryotic flagella and cilia (1985)

Abstract A novel method of digital image analysis of the bends of eukaryotic flagella and cilia was devised. In the analysis system, all image pixels were systematically extracted and processed to measure angular direction and curvature. Simulation experiments on theoretical model pictures of flagella with sine‐generated or arcstraight line bending waves demonstrated that the method can be used with considerable high accuracy. This method then revealed abrupt changes in slope of the curvature in sperm flagella and embryo cilia of the sea urchin, Hemicentrotus pulcherrimus. This indicates that the digital image processing used may be helpful in the study of flagellar and ciliary movements.
Serum amyloid A in the assessment of early inflammatory arthritis. (2000)

Compared with ESR or CRP, A-SAA correlates best with markers of disease activity, and in patients with recent onset arthritis, very high levels of SAA occur exclusively in RA. As A-SAA is sensitive to change and accurately reflects alterations in disease status, it is the best marker available for the assessment of inflammatory joint disease.
Beta-Adrenergic Agonists (1995)

The Ohio State University Medical Center Columbus, Ohio Correspondence: Jeffrey G. Boyle, MD. Department of Obstetrics and Gynecology, 561 Means Hall, 1654 Upham Drive, Columbus, OH 43210.
SFS, a Novel Fibronectin-Binding Protein fromStreptococcus equi, Inhibits the Binding between Fibronectin and Collagen (1999)

The obligate parasitic bacterium Streptococcus equi subsp. equi is the causative agent of strangles, a serious disease of the upper respiratory tract in horses. In this study we have, using shotgun phage display, cloned from S. equi subsp. equi and characterized a gene, called sfs, encoding a protein termed SFS, representing a new type of fibronectin (Fn)-binding protein. The sfs gene was found to be present in all 50 isolates of S. equi subsp. equi tested and in 41 of 48 S. equi subsp. zooepidemicus isolates tested. The sfs gene is down-regulated during growth in vitro compared to fnz, a previously characterized gene encoding an Fn-binding protein from S. equi subsp. zooepidemicus. Sequence comparisons revealed no similarities to previously characterized Fn-binding proteins, but high scores were obtained against collagen. Besides similarity due to the high content of glycine, serine, and proline residues present in both proteins, there was a nine-residue motif present both in collagen and in the Fn-binding domain of SFS. By searching the Oklahoma S. pyogenes database, we found that this motif is also present in a potential cell surface protein from S. pyogenes. Protein SFS was found to inhibit the binding between Fn and collagen in a concentration-dependent way.
Dimerization of the Calcium-sensing Receptor Occurs within the Extracellular Domain and Is Eliminated by Cys → Ser Mutations at Cys101 and Cys236 (1999)

Calcium-sensing receptors are present in membranes as dimers that can be reduced to monomers with sufhydryl reagents. All studies were carried out on the human calcium-sensing receptor tagged at the carboxyl terminus with green fluorescent protein (hCaR-GFP) to permit identification and localization of expressed proteins. Truncations containing either the extracellular agonist binding domain plus transmembrane helix 1 (ECD/TMH1-GFP) or the transmembrane domain plus the intracellular carboxyl terminus (TMD/carboxyl terminus-GFP) were used to identify the dimerization domain. ECD/TMH1-GFP was a dimer in the absence of reducing reagents, whereas TMD/carboxyl-terminal GFP was a monomer in the absence or presence of reducing agents, suggesting that dimerization occurs via the ECD. To identify the residue(s) involved in dimerization within the ECD, cysteine --> serine point mutations were made in residues that are conserved between hCaR and metabotropic glutamate receptors. Mutations at positions 60 and 131 were expressed at levels comparable to wild type in HEK 293 cells, had minimal effects on hCaR function, and did not eliminate dimerization, whereas mutations at positions 101 and 236 greatly decreased receptor expression and resulted in significant amounts of monomer in the absence of reducing agents. The double point mutant hCaR(C101S/C236S)-GFP was expressed more robustly than either C101S or C236S and covalent dimerization was eliminated. hCaR(C101S/C236S)-GFP had a decreased affinity for extracellular Ca2+ and slower response kinetics upon increases or decreases in agonist concentration. These results suggest that covalent, disulfide bond-mediated dimerization of the calcium-sensing receptor contributes to stabilization of the ECD and to acceleration of the transitions between inactive and active receptor conformations.
Adaptive bandwidth share estimation in TCP Westwood (2003)

TCP Westwood (TCPW) is a recently proposed sender side modification of TCP congestion control. TCPW relies an bandwidth share estimation techniques to enhance congestion control over high speed and/or wireless networks. The bandwidth share estimation methods turn out to be critical to guarantee both throughput improvement and friendliness towards widely used TCP protocols such as NewReno. In this paper we propose a new bandwidth share estimation technique, called "adaptive bandwidth share estimation", or ABSE. ABSE adapts to changing network congestion level, round trip times, and other relevant network conditions, as well as to the rate at which such changes occur. We compare the throughput gain and friendliness of ABSE with that of NewReno and previous estimation methods used for TCPW. We test the new technique using different simulation scenarios, including RED, to show the benefit of our proposed ABSE estimation method.
Using a 3-O-Sulfated Heparin Octasaccharide To Inhibit the Entry of Herpes Simplex Virus Type 1 (2008)

Heparan sulfate (HS) is a highly sulfated polysaccharide and is present in large quantities on the cell surface and in the extracellular matrix. Herpes simplex virus type 1 (HSV-1) utilizes a specialized cell surface HS, known as 3-O-sulfated HS, as an entry receptor to establish infection. Here, we exploit an approach to inhibiting HSV-1 infection by using a 3-O-sulfated octasaccharide, mimicking the active domain of the entry receptor. The 3-O-sulfated octasaccharide was synthesized by incubating a heparin octasaccharide (3-OH octasaccharide) with HS 3-O-sulfotransferase isoform 3. The resultant 3-O-sulfated octasaccharide has a structure of Delta UA2S-GlcNS6S-IdoUA2S-GlcNS6S-IdoUA2S-GlcNS3S6S-IdoUA2S-GlcNS6S (where Delta UA is 4-deoxy-alpha-L-threo-hex-4-enopyranosyluronic acid, GlcN is D-glucosamine, and IdoUA is L-iduronic acid). Results from cell-based assays revealed that the 3-O-sulfated octasaccharide has stronger activity in blocking HSV-1 infection than that of the 3-OH octasaccharide, suggesting that the inhibition of HSV-1 infection requires a unique sulfation moiety. Our results suggest the feasibility of inhibiting HSV-1 infection by blocking viral entry with a specific oligosaccharide.
A cdc2‐related kinase PSSALRE/cdk5 is homologous with the 30 kDa subunit of tau protein kinase II, a proline‐directed protein kinase associated with microtubule (1993)

We previously reported that tau protein kinase II (TPKII) from bovine brain was composed of 30 kDa and 23 kDa subunits. The 30 kDa subunit of TPKII can be regarded as a catalytic subunit because of its ATP-binding activity. Antibodies directed against TPKII-phosphorylated tau also reacted with tau phosphorylated by cdc2 kinase obtained from starfish oocytes, indicating that TPKII and cdc2 kinase phosphorylate the same sites. We determined the amino acid sequence of the 30 kDa subunit and found it to be homologous with a cdc2-related kinase, PSSALRE/cdk5. Moreover, an antibody against PSSALRE/cdk5 reacted with the 30 kDa subunit. These results indicate that the 30 kDa subunit of TPKII is bovine homologue of PSSALRE/cdk5. Expression of the 30 kDa subunit mRNA was enhanced in juvenile rat brain. This result supports our previous hypothesis that the kinase works actively in juvenile brain.
The Serine/Threonine Phosphatase PP5 Interacts with CDC16 and CDC27, Two Tetratricopeptide Repeat-containing Subunits of the Anaphase-promoting Complex (1997)

The evolutionarily conserved multisubunit complex known as the cyclosome or anaphase-promoting complex is involved in catalyzing the ubiquitination of diverse substrates in M phase, allowing their destruction by the 26 S proteasome and the completion of mitosis. Three of the eight subunits of the anaphase-promoting complex (CDC16, CDC23, and CDC27) have been shown to be phosphorylated in M phase, and their phosphorylation is required for the anaphase-promoting complex to be active as a ubiquitin ligase. Several subunits of the anaphase-promoting complex contain tetratricopeptide repeats, a protein motif involved in protein/protein interactions. PP5 is a serine/threonine phosphatase that also contains four copies of the tetratricopeptide repeats motif. Here we show by a combination of two-hybrid analysis and in vitro binding that PP5 interacts with CDC16 and CDC27, two subunits of the anaphase-promoting complex. Only the NH2-terminal domain of PP5, containing all four tetratricopeptide repeats, is required for this physical interaction. Deletion analysis suggests that the site of binding to PP5 is localized to the COOH-terminal block of tetratricopeptide repeats in CDC16 and CDC27. In addition, indirect immunofluorescence showed that PP5 localizes to the mitotic spindle apparatus. The direct interaction of PP5 with CDC16 and CDC27, as well as its overlapping spindle localization in mitosis, suggests that PP5 may be involved in the regulation of the activity of the anaphase-promoting complex.
A genetic screen identifies novel non-compatible loxP sites (2002)

The ability of the Cre/lox system to make precise genomic modifications is a tremendous accomplishment. However, recombination between cis-linked heterospecific lox sites limits the use of Cre- mediated exchange of DNA to systems where genetic selection can be applied. To circumvent this problem we carried out a genetic screen designed to identify novel mutant spacer-containing lox sites displaying enhanced incompatibility with the canonical loxP site. One of the mutant sites recovered appears to be completely stable in HEK293 cells constitutively expressing Cre recombinase and supports recombinase-mediated cassette exchange (RMCE) in bacteria and mammalian cell culture. By preventing undesirable recombination, these novel lox sites could improve the efficiency of in vivo gene transfer.
Differential Expression of M-CSF, G-CSF, and GM-CSF by Human Monocytes (1990)

The colony-stimulating factors (CSF) belong to a group of proteins which regulate blood cell production. Human monocytes allowed to adhere express high levels of M-CSF transcripts and secreted protein at 24 h in the presence but not in the absence of indomethacin (Indo), an inhibitor of prostaglandin E (PGE) production. When induced with lipopolysaccharide (LPS), adherent monocytes express M-CSF, G-CSF, and GM-CSF transcripts and secrete these proteins and TNF. M-CSF and GM-CSF messages increase in LPS-induced monocytes by the addition of Indo, while G-CSF mRNA appears to decrease. Exogenous addition of PGE-2 to LPS-induced monocytes down-modulates the expression of M-CSF and GM-CSF transcripts. G-CSF message is elevated, suggesting an alternate pathway to G-CSF regulation. PGE-2 inhibits the secretion of CSFs and TNF. In contrast, LPS-induced monocytes held 24 h in nonadherent culture express G- and GM-CSF but not M-CSF. Monocytes that are adhered for 24 h and then treated with LPS for an additional 24 h express only M-CSF message and secrete M-CSF and TNF. PGE-2 added with LPS during the 24-48 h induction blocks M-CSF and TNF production, but appears to enhance M-CSF message expression, in contrast to its effect on 0 h inductions. These results suggest that adherence alone induces M-CSF gene expression, but low levels of PGE or other arachidonic acid metabolites limit this expression. Other events in 1 d-cultured monocytes block the ability to induce G-CSF and GM-CSF expression with LPS, and block the suppressive effect of PGE-2 on M-CSF expression at the RNA level.
DNA Deaminating Ability and Genotoxicity of Nitric Oxide and its Progenitors (1991)

Nitric oxide (NO), a multifaceted bioregulatory agent and an environmental pollutant, can also cause genomic alterations. In vitro, NO deaminated deoxynucleosides, deoxynucleotides, and intact DNA at physiological pH. That similar DNA damage can also occur in vivo was tested by treating Salmonella typhimurium strain TA1535 with three NO-releasing compounds, including nitroglycerin. All proved mutagenic. Observed DNA sequence changes were greater than 99% C----T transitions in the hisG46 (CCC) target codon, consistent with a cytosine-deamination mechanism. Because exposure to endogenously and exogenously produced NO is extensive, this mechanism may contribute to the incidence of deamination-related genetic disease and cancer.
In Utero Environmental Tobacco Smoke Exposure Alters Gene Expression in Lungs of Adult BALB/c Mice (2007)

The differential lung gene expression reported here is consistent with previously reported functional changes in lungs of mice exposed in utero to ETS and as adults to the nontobacco allergen OVA.
DNA Cleavage by Photogenerated Rh2(O2CCH3)4(H2O)2+ (2001)

Irradiation of Rh2(O2CCH3)4(H2O)2 with visible light in the presence of electron acceptors results in the formation of the oxidized complex, Rh2(O2CCH3)4(H2O)2+. Photogenerated Rh2(O2CCH3)4(H2O)2+ is able to cleave plasmid DNA, whereas the Rh2(O2CCH3)4(L)2+ complexes with nonlabile axial ligands, L, such as py (pyridine) and PPh3 (triphenylphosphine), do not cleave the double helix.
The Photoshop Elements 3 Book for Digital Photographers (VOICES) (2004)

If you're ready for an Elements 3 book that breaks all the rules, this is it, because it does something for digital photographers that's never been done before--it cuts through the bull and shows you exactly to do it. It tells you, flat-out, which settings to use, when to use them, and why.This book is not a bunch of theory; it doesn't challenge you to come up with your own settings or figure things out on your own. It gives you the same settings used by some of the top digital pros, settings you can use today to get professional results you've always dreamed of.Plus, since this book is designed for photographers, it doesn't waste your time talking about how to frame a shot, setting your exposure, etc. and there's no talk which camera or printer to buy. It's all Elements, step-by-step, cover-to-cover in the only book of its kind, and you're gonna love it!Besides learning the inside tips and the tricks of the trade for correcting, editing, sharpening, retouching, and presenting your photos like a pro. You'll learn how to unlock the power of all the new Elements 3 features, including how to manage your photos using the new Organizer, how to use the new pro tools like the Healing Brush and the Shadow/Highlight controls, and how to master the new Creation section to take your photos to an entirely new level. Plus, you'll see it all step-by-step, in plain English, and you'll be absolutely amazed at how easy and effective these techniques are, once you know the secrets.You'll learn: The secrets of how the pros retouch portraits How to incorporate the amazing new features of Elements 3 into your work today! How to color correct any photo without breaking a sweat (you'll be amazed at how they do it!) How to repair and restore damaged photos The sharpening techniques the pros really use (there's an entire chapter just on this!) Dealing with common digital camera image problems, including removing noise and avoiding halos When to use Quick Fix, and when to do to it yourself (using our step-by-step methods). The most-requested photographic special effects and much more! But besides all that, this book has a secret weapon that makes it the most important, most useful Elements book yet. The reason is this--although Elements 3 offers some digital photography features Photoshop CS doesn't offer, there are plenty of features that Photoshop CS has, that Elements 3 still doesn't have (things like Layer Masking, Channel Mixer, etc.). But in this book, you'll learn some slick workarounds, cheats, and some fairly ingenious ways to replicate many of those Photoshop features from right within Elements. There's never been a book like it, and if you're a digital photographer using Photoshop Elements 3, this is the book you've been waiting for.
[Muscular atrophy associated with a contralateral parietal lobe lesions. Apropos of 2 cases]. (1977)

Two cases of parietal lobe tumours with contralateral muscle atrophy are discussed. Muscle biopsy demonstrated selective atrophy of Type II fibres. E.M.G. shows brief small polyphasic potentials. At autopsy in the second case no neurological lesion was found outside the brain, muscles and pyramidal tract.
Adaptive interpolation of discrete-time signals that can be modeled as autoregressive processes (1986)

This paper presents an adaptive algorithm for the restoration of lost sample values in discrete-time signals that can locally be described by means of autoregressive processes. The only restrictions are that the positions of the unknown samples should be known and that they should be embedded in a sufficiently large neighborhood of known samples. The estimates of the unknown samples are obtained by minimizing the sum of squares of the residual errors that involve estimates of the autoregressive parameters. A statistical analysis shows that, for a burst of lost samples, the expected quadratic interpolation error per sample converges to the signal variance when the burst length tends to infinity. The method is in fact the first step of an iterative algorithm, in which in each iteration step the current estimates of the missing samples are used to compute the new estimates. Furthermore, the feasibility of implementation in hardware for real-time use is established. The method has been tested on artificially generated auto-regressive processes as well as on digitized music and speech signals.
The effects of varying dietary n-6 to n-3 fatty acid ratios on platelet reactivity, coagulation screening assays, and antithrombin III activity in dogs (1997)

Thirty beagles were placed on diets containing ratios of n-6 to n-3 fatty acids ranging from 5:1 to 100:1 for 12 weeks to determine the effects of these diets on platelet reactivity, coagulation screening assays, and antithrombin III activity. Although small changes were observed in adenosine diphosphate (ADP)-, collagen-, and arachidonic acid-induced platelet aggregation and 14C-serotonin release, fibrinogen concentrations, and antithrombin III activities during the 12-week study, these changes were not of clinical significance and did not correlate with the varying ratios of n-6 to n-3 fatty acids.
Review of human studies on oxidative damage and antioxidant protection related to cardiovascular diseases. (2000)

Under oxidative stress, which is associated with atherosclerosis, oxidative modifications of LDL take place. A major effect of antioxidants in the LDL environment is to prevent the formation of oxidized LDL during atherogenesis. The question that arises is what are the body's capabilities to inhibit LDL oxidation and to remove and/or to neutralize atherogenic Ox-LDL when formed. Strategies to reduce LDL oxidation and atherogenesis can involve the enrichment of the LDL and arterial cells with potent antioxidants that can prevent oxidative damage to the arterial wall. There seems to be a clear cause and effect relationship between LDL oxidation and atherosclerosis. Atherosclerosis is a multifactorial disease and LDL is oxidized by all major cells of the arterial wall during the development of atherosclerosis via more than one mechanism. The various LDL oxidation pathways produce several lipid peroxidation products such as isoprostanes from arachidonic, eicosapentaenoic and docosahexaenoic acids, oxysterols from unesterified and esterified cholesterol, hydroxy fatty acids, lipid peroxides and aldehydes. Thus, one single assay of lipid peroxidation is probably not sufficient to serve as a marker for cardiovascular risk and there is a need for measurements of several markers. The use of biomarkers provides a logical scientific basis for major intervention trials of antioxidants; such trials will, in turn, eventually validate or disprove the biomarker concept. Any intervention trial that does take place should be accompanied by measurements of one or more relevant biomarkers at intervals during the study. If the endpoint of the trial is disease incidence or mortality, such studies will help to validate or disprove the biomarker concept. They might also help to explore the possibility that in vivo levels of oxidative lipid damage are early predictors of subsequent development of cardiovascular disease. In addition, specific antioxidants in serum, as well as serum paraoxonase activity can provide very useful information on the risk for cardiovascular diseases. For vascular disease risk, in addition to the markers in use for lipid peroxidation, there is a need to include also markers for endothelial dysfunction, monocyte adhesion, macrophage uptake of lipoproteins, thrombotic, and inflammatory processes.
Transformations of (Z)-2-benzoylamino-4-dimethylamino-2-oxo-3-butene and (E)-3-benzoylamino-4-cyano-2-oxo-3-butene into pyrimidine, pyrazole and isoxazole derivatives (2003)

Reaction of (Z)-2-Benzoylamino-4-dimethylamino-2-oxo-3-butene 1 with amidines 2a-e afforded pyrimidines 3a-e. Acid-catalysed treatment of 1 with potassium cyanide gave (E)-3benzoylamino-4-cyano-2-oxo-3-butene 4. 1,3-Dipolar cycloadditions of nitrile imines and 2,4,6trimethoxybenzonitrile oxide 7a to compound 4 afforded the corresponding pyrazole derivatives 6a-d and the isoxazole-4-carbonitrile 8a. In the reaction of 4 with 2,4,6-trimethylbenzonitrile oxide 7b, bis-cycloadduct 9 was formed and its structure was also determined by X-Ray analysis.