gebhart/patrepeval huggingface dataset:
Rapid Delivery of Drug Carriers Propelled and Navigated by Catalytic Nanoshuttles (2010)

This paper reports the first proof-of-concept of using catalytic nanoshuttles to pick up, transport, and release common drug carriers including biocompatible and biodegradable polymeric particles and liposomes. The rapid transport of a wide size range of drug-loaded particles (100 nm-3.0 μm) with a speed approximately three orders of magnitude faster than that of the particles transported by Brownian motion demonstrates the high propulsion power of the nanoshuttles. The nanoshuttles' navigation ability is illustrated by the transport of the drug carriers through a microchannel from the pick-up to the release microwell. Such ability of nanomotors to rapidly deliver drug-loaded polymeric particles and liposomes to their target destination represents a novel approach towards transporting drug carriers in a target-specific manner. This also potentially addresses the obstacles of current nanoparticle drug delivery, such as off-targeting of particles. While an initial concept of actively transporting therapeutic particles is demonstrated in vitro in this paper, future efforts will focus on practical in vivo motor-based targeted drug delivery in connection to fuel-free nanovehicles.
Mechanism of Action of Proteasome Inhibitors and Deacetylase Inhibitors and the Biological Basis of Synergy in Multiple Myeloma (2011)

Novel agents, including the proteasome inhibitor bortezomib, have significantly improved the response and survival of patients with multiple myeloma over the last decade. Despite these advances, many patients relapse or do not benefit from the currently available therapies; thus, multiple myeloma remains an incurable disease. Deacetylase inhibitors (DACi), including panobinostat and vorinostat, have recently emerged as novel agents being evaluated in the treatment of multiple myeloma. Deacetylases are a group of enzymes with effects on various intracellular proteins, including histones, transcription factors, and molecular chaperones. Although DACi inhibit cell growth and induce apoptosis in multiple myeloma cells as a single agent, synergistic activity has been observed when they were used in combination with bortezomib. The mechanistic basis of synergy is multifactorial and includes disruption of protein degradation and inhibition of the interaction of multiple myeloma cells with the tumor microenvironment. This review summarizes recent advancements in the understanding of the mechanism of action of proteasome inhibitors and DACi in multiple myeloma and examines the biological basis of their synergistic effects. Data from the studies summarized here have been used as the rationale for the implementation of phase II and III clinical trials of DACi, alone and combined with bortezomib, in relapsed and refractory multiple myeloma.
Flux3D, a finite element package for magnetic computation (1985)

In this paper, we describe a finite element package for the computation of three-dimensional magnetostatic field. The finite element mesh is automatically built in two steps using a Delaunay tetrahedrization Step 1. The user gives interactively a first set of nodes located on interfaces and boundaries, and the program compute a coarse tetrahedral mesh Step 2. The program adds new nodes automatically to refine the initial mesh and regularizes it. The implemented finite element formulations use either scalar or vector potential. The post processor allows interactive computation and visualization of any local or global quantities given by closed formulae.
Molecular characteristics of nerve growth factor receptors on PC12 cells. (1985)

Cross-linking of 125I-nerve growth factor (NGF) to PC12 cells with the photoreactive heterobifunctional agent N-hydroxysuccinimidyl-4-azidobenzoate results in the labeling of two major bands with Mr 158,000 and 100,000 and a minor band with Mr 225,000 as determined by polyacrylamide gel electrophoresis under denaturing and reducing conditions. Binding of 125I-NGF to and cross-linking into all these species is abolished in the presence of excess unlabeled NGF but not in the presence of unlabeled epidermal growth factor, insulin, or bovine pancreatic trypsin inhibitor. When PC12 cells with bound 125I-NGF are incubated in excess unlabeled NGF at 0 degree C prior to cross-linking, only the Mr 158,000 species remains. In addition, binding of 125I-NGF to the Mr 158,000 complex is trypsin-resistant, whereas binding to the Mr 100,000 complex is not. These experiments identify the Mr 158,000 species as the slow NGF-receptor complex (chase stable at 0 degree C) and the smaller Mr 100,000 species as the fast NGF-receptor complex (trypsin sensitive). Furthermore, 125I-NGF bound to the former but not to the latter species is displaced by very-low concentrations of NGF, showing that at least a significant fraction of the high-molecular-weight slow receptor is also a high-affinity receptor. This identification is supported by the finding that chick sensory neurons which possess both high- and low-affinity receptors exhibit two major labeled bands with Mr 145,000 and 105,000 as a result of cross-linking with 125I-NGF, whereas a cell population enriched in non-neuronal cells, which possess only low-affinity receptors, exhibits only the Mr 105,000 component. A shift in molecular weight of both species after pretreatment with neuraminidase indicates that both complexes contain sialoglycoproteins and rules out the possibility that differences in sialic acid content are responsible for the difference in molecular weight of the two complexes. The relative amount of the labeling of these two complexes is not affected by the presence of protease inhibitors nor by a variation of 5000-fold in cross-linker concentration. These results place some limits on possible models for the NGF receptors and their interconversion.
Cloning of a Novel Family of Mammalian GTP-binding Proteins (RagA, RagBs, RagB1) with Remote Similarity to the Ras-related GTPases (1995)

cDNA clones of two novel Ras-related GTP-binding proteins (RagA and RagB) were isolated from rat and human cDNA libraries. Their deduced amino acid sequences comprise four of the six known conserved GTP-binding motifs (PM1, -2, -3, G1), the remaining two (G2, G3) being strikingly different from those of the Ras family, and an unusually large C-terminal domain (100 amino acids) presumably unrelated to GTP binding. RagA and RagB differ by seven conservative amino acid substitutions (98% identity), and by 33 additional residues at the N terminus of RagB. In addition, two isoforms of RagB (RagBs and RagB1) were found that differed only by an insertion of 28 codons between the GTP-binding motifs PM2 and PM3, apparently generated by alternative mRNA splicing. Polymerase chain reaction amplification with specific primers indicated that both long and short form of RagB transcripts were present in adrenal gland, thymus, spleen, and kidney, whereas in brain, only the long form RagB1 was detected. A long splicing variant of RagA was not detected. Recombinant glutathione S-transferase (GST) fusion proteins of RagA and RagBs bound large amounts of radiolabeled GTP gamma S in a specific and saturable manner. In contrast, GTP gamma S binding of GST-RagB1 hardly exceeded that of recombinant GST. GTP gamma S bound to recombinant RagA, and RagBs was rapidly exchangeable for GTP, whereas no intrinsic GTPase activity was detected. A multiple sequence alignment indicated that RagA and RagB cannot be assigned to any of the known subfamilies of Ras-related GTPases but exhibit a 52% identity with a yeast protein (Gtr1) presumably involved in phosphate transport and/or cell growth. It is suggested that RagA and RagB are the mammalian homologues of Gtr1 and that they represent a novel subfamily of Ras-homologous GTP binding proteins.
Motion compensation with higher order motion models for HEVC (2015)

In recent video compression standards only translational motion is accurately compensated, constraining any higher order motion to be approximated by being split into smaller translational units. The objective of this paper is to improve the coding efficiency for video sequences containing complex motion.Various higher order motion models are considered and evaluated to this end. Motivated by the higher maximum block size introduced by the High Efficiency Video Coding Standard (HEVC) and a suitable combination of motion parameter estimation, interpolation and coding, a higher order motion compensation framework for the HEVC is proposed. Through this an average data reduction of 2.9% as well as an increase in average block size is achieved.
Micro-electrospray mass spectrometry: Ultra-high-sensitivity analysis of peptides and proteins (1994)

A "micro-electrospray" ionization source has been developed that markedly increases the sensitivity of the conventional electrospray source. This was achieved by optimization of the source to accommodate nanoliter flow rates from 300 to 800-nL/min spraying directly from a capillary needle that, for the analysis of peptides, contained C18 liquid chromatography packing as an integrated concentration-desalting device. Thus, a total of 1 fmol of methionine enkephalin was desorbed from the capillary column spray needle, loaded as a 10-μL injection of 100-amol/μL solution. The mass spectrum showed the [M + H](+) ion at m/z 574.2 with a signal-to-noise ratio of better than 5:1 from a chromatographic peak with a width of about 12 s. A narrow range (15-u) tandem mass spectrum was obtained for methionine enkephalin from the injection of 500 amol, and a full-scan tandem-mass spectrum was obtained from 50 fmol. For proteins, the average mass measurement accuracy was approximately 100-200 ppm for the injection of 2.5 fmol of apomyoglobin and 20-40 ppm for 200 fmol. Carbonic anhydrase B and bovine serum albumin showed similar mass measurement accuracies.
Effects of the Method of Preparation on the Compression, Mechanical, and Release Properties of Khaya Gum Matrices (2006)

A study has been made of the compression properties of khaya gum matrices and the effects of drug concentration and method of preparation of the material on the compression, mechanical and the drug release characteristics of the matrices. Khaya gum matrix tablets were prepared by direct compression and wet granulation methods. The compression properties of the formulations were assessed using the equations of Heckel and Kawakita. The mechanical properties of the tablets were evaluated using crushing strength and friability of the tablets, whereas the release properties of the tablets were evaluated by using the disintegration and dissolution times. The results obtained show that khaya gum deformed mainly by plastic deformation. The compression properties of the formulations were affected by the concentration of the drug and the method of preparation of the materials for compression. Tablets prepared by wet granulation showed faster onset and higher amount of plastic deformation during compression than those prepared by direct compression. Tablets containing dicalcium phosphate showed higher mechanical strength and disintegration and dissolution times. Wet granulation also increased the mechanical strength of the tablet without significantly affecting the drug release characteristics from the matrix tablets. Thus, the wet granulation method could be useful in the preparation of khaya gum matrix tablet with acceptable mechanical properties and drug release properties.
GraphScope (2007)

How can we find communities in dynamic networks of socialinteractions, such as who calls whom, who emails whom, or who sells to whom? How can we spot discontinuity time-points in such streams of graphs, in an on-line, any-time fashion? We propose GraphScope, that addresses both problems, using information theoretic principles. Contrary to the majority of earlier methods, it needs no user-defined parameters. Moreover, it is designed to operate on large graphs, in a streaming fashion. We demonstrate the efficiency and effectiveness of our GraphScope on real datasets from several diverse domains. In all cases it produces meaningful time-evolving patterns that agree with human intuition.
ChemInform Abstract: Synthesis, Structure, and Biological Applications of α‐Fluorinated β‐Amino Acids and Derivatives (2013)

Abstract Review: 133 refs.
Single-Cell Analysis by a Scanning Thermal Lens Microscope with a Microchip:  Direct Monitoring of Cytochrome c Distribution during Apoptosis Process (2002)

We developed a microsystem for cell experiments consisting of a scanning thermal lens microscope detection system and a cell culture microchip. The microchip system was good for liquid control in microspace, and this results in secure cell stimulation and coincident in vivo observation of the cell responses. The system could detect nonfluorescent biological substances with extremely high sensitivity without any labeling materials and had a high spatial resolution of approximately 1 microm. This system was applied to monitoring of cytochrome c distribution in a neuroblastoma-glioma hybrid cell cultured in the microflask (1 mm x 10 mm x 0.1 mm; 1 microL) fabricated in a glass microchip. Cytochrome c release from mitochondria to cytosol during the apoptosis process was successfully monitored with this system. The cytochrome c detected with this system was estimated to be approximately 10 zmol. We concluded that the system was suitable for measuring the distribution of chemical substances in a single cell because the microchip is good for liquid handling in microspace and the thermal lens microscope has high sensitivity and spatial resolution.
Novel 3D display using an array of LCD panels (2003)

Sixty-four color LCD panels were employed to implement a natural 3D display. Sixty-four images displayed on the LCD panels are projected in the different horizontal directions by using modified 2D aligned telecentric optical systems. Because the projection angle pitch in the horizontal direction is as small as 0.33 degree, observers’ eyes can focus on the 3D images. Because the projection systems are telecentric, images are defocused little so that clear 3D images are generated in the 3D space. The horizontal viewing angle is 21.2 degrees, and the 3D screen size is 192 mm X 151 mm (9.6 inch.) The 3D objects can be displayed in the range of ~ 400 mm both in front of and behind the 3D screen. The prototype 3D display has following features: a) no need of wearing 3D glasses, b) simultaneous observation by multiple persons, c) no restriction on observing position, d) compatible with human 3D perception, e) providing high presence, and f) offering photorealistic and moving 3D images. The human accommodation responses to the prototype 3D display are very similar to those obtained for real 3D objects.
Heterocyclization of Orthoaminoester and Orthoamino-nitrile-thieno[2, 3-c]pyridine: The Facile Synthesis of Fused Pyridothienopyrimidines (2006)

A highly efficient and versatile synthetic approach to the synthesis of pyrido[4′, 3′: 4]thieno[2,3-d]pyrimidines (4, 14, 15, 21) and their heterofused (e.g., triazolo-, triazino-, imidazo-, and tetrazolo-,) pyridothienopyrimidines (5–9, 16, 17, 22–24) is described utilizing 2-amino-3-cyano-4,5,6,7-tetrahydro-thieno[2,3-c]pyridine-6-carboxylic acid ethyl ester ( 2 ) and diethyl 2-isothio-cyanate-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3,6-dicarboxylate ( 10 ) as starting materials.
Cloning and molecular characterization of the ontogeny of a rat ileal sodium-dependent bile acid transporter. (1995)

Sodium-dependent bile acid transport in the rat ileum is abruptly expressed at weaning. Degenerate oligonucleotides, based on amino acid sequence identities between the rat liver and hamster ileal transporters, were used to amplify a rat ileal probe. A 1.2-kb cDNA clone, which contains the full coding region (348 amino acids, 38 kD), was isolated by hybridization screening. In vitro translation yielded a 38-kD protein which glycosylated to 48 kD. Sodium-dependent uptake of taurocholate was observed in oocytes injected with cRNA. Northern blot analysis revealed a 5.0-kb mRNA in ileum, kidney, and cecum. A 48-kD protein was detected in ileal brush border membranes and localized to the apical border of villus ileal enterocytes. mRNA and protein expression, which were negligible before weaning, increased dramatically at weaning. Nuclear transcription rates for the transporter increased 15-fold between postnatal days 7 and 28. The apparent molecular weight of the transporter also increased between days 19 and 28. In summary, the developmental regulation of the rat ileal sodium-dependent bile acid cotransporter is characterized by transcriptionally regulated increases in mRNA and protein levels at the time of weaning with changes in apparent molecular weight of the protein after weaning.
Toll-like Receptor 4 Resides in the Golgi Apparatus and Colocalizes with Internalized Lipopolysaccharide in Intestinal Epithelial Cells (2002)

Toll-like receptor (TLR) 4 is mainly found on cells of the myelopoietic lineage. It recognizes lipopolysaccharide (LPS) and mediates cellular activation and production of proinflammatory cytokines. Less is known about the distribution and role of TLR4 in epithelial cells that are continuously exposed to microbes and microbial products. Here we show that the murine small intestinal epithelial cell line m-IC(cl2) is highly responsive to LPS and expresses both CD14 and TLR4. Transcription and surface membrane staining for CD14 were up-regulated upon LPS exposure. Surprisingly, TLR4 immunostaining revealed a strictly cytoplasmic paranuclear distribution. This paranuclear compartment could be identified as the Golgi apparatus. LPS added to the supernatant was internalized by m-IC(cl2) cells and colocalized with TLR4. Continuous exposure to LPS led to a tolerant phenotype but did not alter TLR4 expression nor cellular distribution. Thus, intestinal epithelial cells might be able to provide the initial proinflammatory signal to attract professional immune cells to the side of infection. The cytoplasmic location of TLR4, which is identical to the final location of internalized LPS, further indicates an important role of cellular internalization and cytoplasmic traffic in the process of innate immune recognition.
Nuclear Imaging of Met-Expressing Human and Canine Cancer Xenografts with Radiolabeled Monoclonal Antibodies (MetSeekTM) (2005)

We conclude that radioiodinated Met3 and Met5 offer qualitatively similar nuclear images in xenograft-bearing mice, but quantitative considerations indicate that Met5 might be more useful for radioimmunotherapy. Moreover, canine prostate cancer seems to be a suitable model for second-stage preclinical evaluation of Met5.
Different Intensities of Oral Anticoagulant Therapy in the Treatment of Proximal-Vein Thrombosis (1982)

We have previously reported that long-term therapy with warfarin is effective for preventing recurrent venous thromboembolism in patients with proximal-vein thrombosis but that there is an appreciable risk of hemorrhage. To determine whether that risk could be reduced without a loss of effectiveness, we randomly allocated 96 patients with proximal-vein thrombosis to a group receiving less intense anticoagulant therapy, with a mean prothrombin time of 26.9 seconds using the Manchester comparative reagent (corresponding Simplastin time, 15 seconds), or a group given more intense therapy, with a mean Simplastin time of 19.4 seconds (corresponding prothrombin time 41 seconds with the Manchester comparative reagent) (P less than 0.001). Two of 47 patients (4 per cent) in the less intensely treated group had hemorrhagic complications, as compared with 11 of 49 patients (22 per cent) in the more intensely anticoagulated group (P = 0.015 by the two-tailed test). This difference was due to minor bleeding episodes. The frequency of recurrent venous thromboembolism was low in both groups (2 per cent). Our findings indicate that less intense anticoagulant therapy is associated with a low frequency of recurrent venous thromboembolism (2 per cent) and a reduced risk of hemorrhage.
A Phase 1 and pharmacokinetic clinical trial of paclitaxel for the treatment of refractory leukemia in children: A Children's Oncology Group study (2007)

Paclitaxel was tolerated at 430 mg/m(2) every 21 days and at 182 mg/m(2)/dose weekly x 3 every 28 days in pediatric patients. The objective response rate across all dose levels and schedules was <10%.
Norm-Product Belief Propagation: Primal-Dual Message-Passing for Approximate Inference (2010)

Inference problems in graphical models can be represented as a constrained optimization of a free-energy function. In this paper, we treat both forms of probabilistic inference, estimating marginal probabilities of the joint distribution and finding the most probable assignment, through a unified message-passing algorithm architecture. In particular we generalize the belief propagation (BP) algorithms of sum-product and max-product and tree-reweighted (TRW) sum and max product algorithms (TRBP) and introduce a new set of convergent algorithms based on “convex-free-energy” and linear-programming (LP) relaxation as a zero-temperature of a convex-free-energy. The main idea of this work arises from taking a general perspective on the existing BP and TRBP algorithms while observing that they all are reductions from the basic optimization formula of <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">f</i> +Σ <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">ihi</i> where the function <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">f</i> is an extended-valued, strictly convex but nonsmooth and the functions <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">hi</i> are extended-valued functions (not necessarily convex). We use tools from convex duality to present the “primal-dual ascent” algorithm which is an extension of the Bregman successive projection scheme and is designed to handle optimization of the general type <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">f</i> + Σ <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">ihi</i> . We then map the fractional-free-energy variational principle for approximate inference onto the optimization formula above and introduce the “norm-product” message-passing algorithm. Special cases of the norm-product include sum-product and max-product (BP algorithms), TRBP and NMPLP algorithms. When the fractional-free-energy is set to be convex (convex-free-energy) the norm-product is globally convergent for the estimation of marginal probabilities and for approximating the LP-relaxation. We also introduce another branch of the norm-product which arises as the “zero-temperature” of the convex-free-energy which we refer to as the “convex-max-product”. The convex-max-product is convergent (unlike max-product) and aims at solving the LP- relaxation.