gebhart/patrepeval huggingface dataset:
Abstract 2486: Site-specific antibody-drug conjugation through an engineered glycotransferase and a chemically reactive sugar (2015)

Abstract Conjugation of small molecule drugs to specific sites on the antibody molecule has been increasingly used for the generation of relatively homogenous preparations of antibody-drug conjugates (ADCs) with physicochemical properties similar or identical to those of the naked antibody. We previously developed a method for conjugation of small molecules to glycoproteins through existing glycans by using an engineered glycotransferase and a chemically reactive sugar as a handle to conjugate a small molecule. Here, for the first time, we report the use of this method with some modifications to generate an ADC from a monoclonal antibody, m860, which we identified from a human naïve phage display Fab library by panning against the extracellular domain of human HER2. M860 bound to cell surface-associated HER2 with affinity comparable to that of trastuzumab (Herceptin®), but to a different epitope. The ADC m860 was generated by enzymatically adding a reactive keto-galactose to galactose-free m860 using an engineered glycotransferase and conjugating the reactive m860 to aminooxy auristatin F with a non-cleavable linker. It exhibited exceptional serum stability and potent and specific cell-killing activity against HER2 positive cancer cells, including trastuzumab-resistant breast cancer cells. This unique ADC may have utility as a potential therapeutic for HER2 positive cancers alone or in combination with other drugs. Our results also validate the keto-galactose/engineered glycotransferase method for generation of functional ADCs, which could potentially also be used for preparation of ADCs targeting other disease markers. This project was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, and by federal funds from the National Cancer Institute, NIH, under contract N01-CO-12400, HHSN261200800001E as well as by the SU2C-St.Baldrick's Foundation. Citation Format: Zhongyu Zhu, Ramakrishnan Boopathy, Jinyu Li, Ponraj Prabakaran, Simona Colantonio, Yang Feng, Yanping Wang, Marzena A. Dyba, Dimiter S. Dimitrov. Site-specific antibody-drug conjugation through an engineered glycotransferase and a chemically reactive sugar. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2486. doi:10.1158/1538-7445.AM2015-2486
A vector-based method for drawing RNA secondary structure. (1999)

The executable code of VizQFolder is available at http://automation.inha.ac.kr/khan. It can also be obtained from the authors upon request.
Cooperative site specific binding of oligonucleotides to duplex DNA (1989)

Cooperative interactions between DNA binding ligands are critical to their specificity, affinity, and biological activity. Triple helix formation by oligonucleotides is the most powerful chemical approach to date for the sequence-specific recognition of double helical DNA. Hoogsteen hydrogen bonded base triplets, TAT and C+GC, result from pyrimidine oligonucleotides binding site specifically to purine duplex sequences. In the triple helical model, a binding site size of 18 purine base pairs affords 36 discrete sequence-specific hydrogen bonds for recognition of DNA in the major groove. As a possible mechanism for improving the specificity of triple helix formation, we tested whether oligonucleotides could cooperatively bind to a double-stranded DNA\ntemplate.
Inertial Navigation System Aiding with Orbcomm LEO Satellite Doppler Measurements (2018)

A tightly-coupled inertial navigation system aided by Orbcomm low Earth orbit (LEO) satellite signals is developed. The developed navigation framework enables a navigating vehicle to aid its inertial navigation system (INS) with Doppler measurements drawn from Orbcomm LEO satellite signals in a tightly coupled fashion when global navigation satellite system (GNSS) signals become unusable. Experimental results are presented showing an unmanned aerial vehicle (UAV) aiding its onboard INS with Doppler measurements drawn from two Orbcomm LEO satellites, reducing the final position error from 31.7 m to 8.8 m after 30 seconds of GNSS unavailability.
The Epigenome View: An Effort towards Non-Invasive Prenatal Diagnosis (2014)

Epigenetic modifications have proven to play a significant role in cancer development, as well as fetal development. Taking advantage of the knowledge acquired during the last decade, great interest has been shown worldwide in deciphering the fetal epigenome towards the development of methylation-based non-invasive prenatal tests (NIPT). In this review, we highlight the different approaches implemented, such as sodium bisulfite conversion, restriction enzyme digestion and methylated DNA immunoprecipitation, for the identification of differentially methylated regions (DMRs) between free fetal DNA found in maternal blood and DNA from maternal blood cells. Furthermore, we evaluate the use of selected DMRs identified towards the development of NIPT for fetal chromosomal aneuploidies. In addition, we perform a comparison analysis, evaluate the performance of each assay and provide a comprehensive discussion on the potential use of different methylation-based technologies in retrieving the fetal methylome, with the aim of further expanding the development of NIPT assays.
Discovery of a Highly Potent, Selective, and Orally Bioavailable Macrocyclic Inhibitor of Blood Coagulation Factor VIIa–Tissue Factor Complex (2016)

Inhibitors of the tissue factor (TF)/factor VIIa complex (TF-FVIIa) are promising novel anticoagulants which show excellent efficacy and minimal bleeding in preclinical models. Starting with an aminoisoquinoline P1-based macrocyclic inhibitor, optimization of the P' groups led to a series of highly potent and selective TF-FVIIa inhibitors which displayed poor permeability. Fluorination of the aminoisoquinoline reduced the basicity of the P1 group and significantly improved permeability. The resulting lead compound was highly potent, selective, and achieved good pharmacokinetics in dogs with oral dosing. Moreover, it demonstrated robust antithrombotic activity in a rabbit model of arterial thrombosis.
Identification of a Novel Guanine Nucleotide Exchange Factor for the Rho GTPase (1996)

The Rho GTPase promotes proliferation and cytoskeletal rearrangements in mammalian cells. To understand the regulation of Rho, it is important to characterize guanine nucleotide exchange factors (GEFs), which stimulate the dissociation of GDP and subsequent binding of GTP. Using Rho as an affinity ligand, we have isolated a 115-kDa protein (p115-RhoGEF) that binds specifically to the nucleotide-depleted state. A full-length cDNA encoding p115-RhoGEF was isolated, and its protein product, which exhibited sequence homology to Dbl and Lbc, catalyzed the exchange of GDP for GTP specifically on Rho and not on the Rac, Cdc42, or Ras GTPases. p115-RhoGEF is capable of regulating cell proliferation, as determined by its ability to induce the transformation of NIH 3T3 cells. Northern and Western analysis suggests that p115-RhoGEF is ubiquitously expressed. These results indicate that p115-RhoGEF may be a general regulator of Rho and its associated cellular phenotypes.
Water-based crosslinkable coatings via miniemulsion polymerization of acrylic monomers in the presence of unsaturated polyester resin (2000)

Hybrid miniemulsion polymerization was performed with a three-component acrylic system of methyl methacrylate, butyl acrylate, and acrylic acid in the presence of a Bayer® Roskydal TPLS2190 unsaturated polyester resin. Latexes were obtained in which the polyester resin was grafted to the acrylic polymer, forming a water-based crosslinkable coating. Grafting between the resinous component and the acrylic polymer is a feature different from the work of others who have attempted to combine the properties of both systems in water-based blends. Both emulsions and latexes were shelf-stable for over 6 months, shear-stable, and resistant to at least one freeze/thaw cycle. Resin-to-monomer ratios were studied as high as 1 : 1 (wt : wt), and total emulsion solids, as high as 45%. Monomer droplet and latex particle sizes were similar, suggesting evidence of the preponderance of droplet nucleation. A high level of crosslinking (>70%) during polymerization was observed in this particular hybrid system in contrast to those involving alkyd or polyurethane resins (<5%). Films, both homogeneous and hard, were achieved with exceptional adhesion. Electron microscopy showed the hybrid particle morphology to have internal domains of polyester resin in an acrylic matrix. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 75: 916–927, 2000
Genetic Determinants of Dabigatran Plasma Levels and Their Relation to Bleeding (2013)

URL: http://www.clinicaltrials.gov. Unique identifier: NCT00262600.
Scaling challenges for 0.13 μm generation shallow trench isolation (2002)

Scaling shallow trench isolation (STI) from the 0.18 /spl mu/m to 0.13 /spl mu/m generation has offered many new challenges for semiconductor manufacturing. Two are discussed in this paper. The first is delivering a capable gapfill process for high aspect ratio trenches while maintaining isolation punchthrough margin (as well as low junction capacitance). The second is trading off NMOS mobility degradation generated by the use of compressive HDP films against the improved gapfill, wet-etch, and polish properties of these films.
ARAPLBS: Robust and Efficient Elasticity‐Based Optimization of Weights and Skeleton Joints for Linear Blend Skinning with Parametrized Bones (2017)

Abstract We present a fast, robust and high‐quality technique to skin a mesh with reference to a skeleton. We consider the space of possible skeleton deformations (based on skeletal constraints, or skeletal animations), and compute skinning weights based on an optimization scheme to obtain as‐rigid‐as‐possible (ARAP) corresponding mesh deformations. We support stretchable‐and‐twistable bones (STBs) and spines by generalizing the ARAP deformations to stretchable deformers. In addition, our approach can optimize joint placements. If wanted, a user can guide and interact with the results, which is facilitated by an interactive feedback, reached via an efficient sparsification scheme. We demonstrate our technique on challenging inputs (STBs and spines, triangle and tetrahedral meshes featuring missing elements, boundaries, self‐intersections or wire edges).
Discovery of 2-[4-{{2-(2<i>S</i>,5<i>R</i>)-2-Cyano-5-ethynyl-1-pyrrolidinyl]-2-oxoethyl]amino]- 4-methyl-1-piperidinyl]-4-pyridinecarboxylic Acid (ABT-279):  A Very Potent, Selective, Effective, and Well-Tolerated Inhibitor of Dipeptidyl Peptidase-IV, Useful for the Treatment of Diabetes (2006)

Dipeptidyl peptidase-IV (DPP-IV) inhibitors are poised to be the next major drug class for the treatment of type 2 diabetes. Structure-activity studies of substitutions at the C5 position of the 2-cyanopyrrolidide warhead led to the discovery of potent inhibitors of DPP-IV that lack activity against DPP8 and DPP9. Further modification led to an extremely potent (Ki(DPP)(-)(IV) = 1.0 nM) and selective (Ki(DPP8) > 30 microM; Ki(DPP9) > 30 microM) clinical candidate, ABT-279, that is orally available, efficacious, and remarkably safe in preclinical safety studies.
Novel, Potent Luteinizing Hormone-Releasing Hormone Antagonists with Improved Solubility in Water (1994)

A series of luteinizing hormone-releasing hormone antagonists with new substitutions in position 6 or positions 5 and 6 that included lysine acylated at the epsilon-amino group with different heterocyclic carboxylic acids or amino-substituted heterocyclic carboxylic acids was synthesized. These novel analogs wee synthesized on a solid-phase support via the acylation of lysine residue in otherwise protected resin-bound peptides. All analogs were tested in the rat antiovulatory assay (AOA) and the best of them in in vitro histamine release assay. Introduction of lysine acylated with amino-substituted heterocyclic carboxylic acids yielded several water-soluble antagonists with good therapeutic ratio (high AOA to low histamine releasing activity). The best antagonist in terms of activity, histamine release, and solubility was nictide: NAcDNal-DCpa-DPal-Ser-PicLys-D(6ANic)-Orn- Leu-ILys-Pro-DAlaNH2 (6ANic = 6-aminonicotinoyl).
Heterogeneity in Rhesus Macaque Complement Factor H Binding to Meningococcal Factor H Binding Protein (FHbp) Informs Selection of Primates To Assess Immunogenicity of FHbp-Based Vaccines (2014)

Neisseria meningitidis causes disease only in humans. An important mechanism underlying this host specificity is the ability of the organism to resist complement by recruiting the complement downregulator factor H (FH) to the bacterial surface. In previous studies, binding of FH to one of the major meningococcal FH ligands, factor H binding protein (FHbp), was reported to be specific for human FH. Here we report that sera from 23 of 73 rhesus macaques (32%) tested had high FH binding to FHbp. Similar to human FH, binding of macaque FH to the meningococcal cell surface inhibited the complement alternative pathway by decreasing deposition of C3b. FH contains 20 domains (or short consensus repeats), with domains 6 and 7 being responsible for binding of human FH to FHbp. DNA sequence analyses of FH domains 6 and 7 from macaques with high or low FH binding showed a polymorphism at residue 352 in domain 6, with Tyr being associated with high binding and His with low binding. A recombinant macaque FH 6,7/Fc fragment with Tyr352 showed higher binding to FHbp than the corresponding fragment with His352. In previous studies in human FH transgenic mice, binding of FH to FHbp vaccines decreased protective antibody responses, and mutant FHbp vaccines with decreased FH binding elicited serum antibodies with greater protective activity. Thus, macaques with high FH binding to FHbp represent an attractive nonhuman primate model to investigate further the effects of FH binding on the immunogenicity of FHbp vaccines.
Passively mode-locked diode-pumped surface-emitting semiconductor laser (2000)

For the first time we passively mode-locked a vertical-extemal-cavity surface- emitting laser using a semiconductor saturable absorber mirror. We achieved 5-ps pulses with 15.3 mW average power or 12-ps pulses with 40 mW.
<i>Rps</i>8 Maps to a Resistance Gene Rich Region on Soybean Molecular Linkage Group F (2005)

Phytophthora root and stem rot caused by Phytophthora sojae M.J. Kaufmann & J.W. Gerdemann is a serious disease of soybean [ Glycine max (L.) Merr.] worldwide. Recently, a new locus for resistance to P. sojae , Rps 8, was identified and mapped in two small soybean populations. The objective of this study was to verify the genomic location of Rps 8 in a larger population. One hundred thirty‐eight F 2:3 families from a cross between ‘Williams’ ( rps 8/ rps 8) × PI 399073 ( Rps 8/ Rps 8) were genotyped by simple sequence repeat (SSR) and restriction fragment length polymorphism (RFLP) markers. From this set of families, 138 and 69 were phenotyped with P. sojae races 1 and 25, respectively. The segregation ratio for each race fit a 3:1 resistant:susceptible, confirming that Rps 8 segregated as a single dominant gene. On the basis of linkage analysis with SSR and RFLP markers, Rps 8 was located on molecular linkage group F in this population. This region of the soybean genome contains numerous other resistance gene loci as well as pathogen and pest resistance QTL.
Complete Protection against Pneumonic and Bubonic Plague after a Single Oral Vaccination (2015)

VTnF1 is an easy-to-produce, genetically stable plague vaccine candidate, providing a highly efficient and long-lasting protection against both bubonic and pneumonic plague caused by wild type or un-encapsulated (F1-negative) Y. pestis. To our knowledge, VTnF1 is the only plague vaccine ever reported that could provide high and durable protection against the two forms of plague after a single oral administration.
Mosaic decomposition method for detection and removal of inhomogeneously tagged regions in electronic cleansing for CT colonography (2008)

Electronic cleansing (EC) is a method that segments fecal material tagged by an X-ray-opaque oral contrast agent in CT colonography (CTC) images, and effectively removes the material for digitally cleansing the colon. In this study, we developed a novel EC method, called mosaic decomposition, for reduction of the artifacts due to incomplete cleansing of heterogeneously tagged fecal material in reduced- or non-cathartic fecal-tagging CTC examinations. In our approach, a segmented colonic lumen, including the tagged regions, was first partitioned into a set of local homogeneous regions by application of a watershed transform to the gradient of the CTC images. Then, each of the local homogeneous regions was classified into five different material classes, including air, soft tissue, tagged feces, air bubbles, and foodstuff, based on texture features of the tile. A single index, called a soft-tissue index, is formulated for differentiation of these materials from the submerged solid soft-tissue structures such as polyps and folds. Here, a larger value of the index indicates a higher likelihood of soft tissue. Then, EC is performed by first initializing the level-set front with the classified tagged regions, and the front is evolved by use of a speed function that was designed, based on the soft-tissue index, to reserve the submerged soft-tissue structures while suppressing the air bubbles and foodstuff. Visual assessment and application of our computer-aided detection (CAD) of polyps showed that the use of our new EC method substantially improved the detection performance of CAD, indicating the effectiveness of our EC method in reducing incomplete cleansing artifacts.
Inkblot Authentication (2004)

In this paper we present a system that helps users select, remember, and differentiate strong passwords. Similar in nature to a Rorchach inkblot test, the system asks the user to form semantic associations with a set of randomly generated inkblot-like images. These image associations can then be used to authenticate the user. This approach is based on evidence from the psychological literature that suggests users will both choose dissimilar associations and retain their associations for long periods of time. We report on two user studies which show that inkblot based passwords are both memorable and high in entropy.
YKL-40 expression in breast cancer (2005)

9665 Background: YKL-40, a heparinbinding glycoprotein, is a growth factor for connective tissue cells and stimulates migration of endothelial cells. High serum YKL-40 levels are associated with a poor prognosis in patients with metastatic breast cancer, colorectal, ovarian and small cell lung cancer. The function of YKL-40 in cancer is unknown, but in vitro observations suggest an involvement in cell proliferation, angiogenesis and extracellular matrix remodelling. The expression of YKL-40 in breast cancer tissue has never been described. The aim of this study was to determine the expression of YKL-40 in breast cancer by immunohistochemistry and in situ hybridisation. Methods: Tissue sections from 55 patients with primary breast cancer were stained using a monoclonal antibody against YKL-40. The intensity of YKL-40 staining in tumor cells was scored using a semi-quantitative method. Results: YKL-40 protein expression in tumor cells appeared as a dense cytoplasmic granular staining. No nuclear or membrane staining was found. 31 of 42 (74%) invasive ductal carcinomas and 7 of 11 (64%) invasive lobular carcinomas stained positive for YKL-40. Macrophages and leucocytes showed YKL-40 expression whereas lymphocytes were negative. In normal breast glands the epithelial cells appeared with a granular apical staining. The myoepithelial cells appeared negative. In the stroma the fibroblasts were weakly stained. YKL-40 protein expression was confirmed by in situ hybridisation. Conclusions: In the present study an overexpression of YKL-40 was found in the epithelial cells of both invasive ductal and lobular carcinomas of the breast compared to normal breast tissue. These data suggest that the tumor cells in breast cancer are the primary source of elevated serum YKL-40 levels as opposed to small cell lung cancer, where macrophages are the primary source of elevated serum YKL-40 levels. Further studies are needed to determine the significance of these findings in the clinical setting. No significant financial relationships to disclose.
System positioning error compensated by local scan in atomic force microscope based nanomanipulation (2008)

Atomic force microscopy (AFM) has been used as a nanomanipulation tool for a decade taking advantage of its high precision and resolution. But due to thermal drift, nonlinear and hysteresis of piezo scanner, a lot of spatial uncertainties associates with the motion of AFM tip, which makes it difficult to move the tip to a desired position accurately. A lot of work has been carried out to improve the positioning accuracy of AFM tip. But most of them only compensate the positioning error in horizontal space, seldom paper pays attention to the vertical positioning error caused by the system structure. To enhance the positioning precision in 3-D space, this paper mainly addresses what causes the position error in vertical direction and how to on-line compensates it. It reveals that when the tip is mounted with an offset to the tube axis, the bow-effect of the piezo scanners will increase the position error seriously. In addition, a local scan based method is proposed to compensate this error. The experimental results are presented to demonstrate the effectiveness of the proposed method.
Subtle effects in high-stability quartz resonators (1982)

The quest for high stability crystal resonators for advanced frequency control applications has led very recently to a number of far-reaching developments. As the level of frequency stability has improved over the years, various factors that were once imperceptible have become nonnegligible, and their influences have had to be eliminated, reduced, or compensated. At present the most obvious contributors to resonator performance have been enumerated. It is important to continue to catalog less obvious effects, and to evaluate critically at what level their influences make an appearance in the error budget of the resonator.We consider a number of influences that are more-or-less “subtle”. Each is examined to see what contribution it makes to resonator performance. It is apparent that some have to be taken into account in present-day applications; others may become important as future stability specifications become even more stringent.
Copper ion removal by almond shell carbons and commercial carbons: batch and column studies (2002)

Phosphoric acid-activated/oxidized, and steam-activated and steam-activated/oxidized almond shell granular activated carbons (GACs) were investigated for their utility in removing copper ion (Cu2+) from solution in both batch and column applications compared to commercially available GACs. Adsorption isotherms were developed and found to best fit the Freundlich model. Experimental and commercial carbons were packed into columns and exposed to two different empty bed contact times using a solution of 3 mM CuCl2 buffered at pH 4.8. The most effective GACs for removal of copper ions in batch mode were the phosphoric acid-activated/oxidized and steam-activated/oxidized experimental carbons. The most effective carbon in column mode appeared to be the phosphoric acid-activated/oxidized sample. A column packed with this carbon showed higher breakthrough volumes and greater estimated hours of operation than other experimental carbons and commercial carbons evaluated. This carbon could function as an effective metal ion adsorbent in water and wastewater treatment.