gebhart/patrepeval huggingface dataset:
Comparative activities of several nucleoside analogs against duck hepatitis B virus in vitro (1990)

Duck hepatitis B virus (DHBV) replication in primary duck hepatocytes was monitored by examining the synthesis of both DHBV DNA and DHBV core antigen. Several nucleoside analogs which were previously shown to inhibit the replication of DNA viruses (i.e., herpesviruses) and retroviruses were examined for their inhibitory effects on the synthesis of DHBV core antigen in primary duck hepatocytes. (S)-9-(3-Hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine, 2',3'-dideoxyadenosine, and 2',3'-dideoxycytidine inhibited DHBV core antigen synthesis at concentrations that were significantly lower than those found to be toxic to the primary hepatocytes. Of all the compounds tested, (S)-HPMPA showed the lowest 50% effective concentration (0.5 micrograms/ml). The selectivity index or ratio of the 50% cytotoxic concentration to the 50% effective concentration of (S)-HPMPA was greater than 300. (S)-HPMPA not only inhibited DHBV core antigen but also DHBV DNA synthesis in DHBV-infected hepatocytes.
Crystal Structure of a 1 : 1 Aminopyrine-Cyclobarbital Complex (1974)

The crystal structure of a 1 : 1 complex of aminopyrine and cyclobarbital was determined from X-ray diffraction data. The triclinic unit cell dimensions are a=12.877, b=14.357, c=7.199Å, α=91.49°, β=104.42°, and γ=100.05°. The space group is P1 ; Z=2. The intensity data were collected on a single crystal diffractometer and the structure was solved directly by the symbolic addition procedure. Molecules in the crystals were arranged in the series of aminopyrine-cyclobarbital-cyclobarbital-aminopyrine linked by hydrogen bonds. A partially disordered structure was observed of the cyclobarbital molecule.
Inhibition of sodium butyrate‐induced apoptosis in recombinant Chinese hamster ovary cells by constitutively expressing antisense RNA of caspase‐3 (2002)

Sodium butyrate (NaBu) can enhance the expression of genes controlled by some of the mammalian promoters, but it can also inhibit cell growth and induce cellular apoptosis. Thus, the beneficial effect of using a higher concentration of NaBu on a foreign protein expression is compromised by its cytotoxic effect on cell growth. To overcome this cytotoxic effect of NaBu, the expression vector of antisense RNA of caspase-3 was constructed and transfected to recombinant Chinese hamster ovary (rCHO) cells producing a humanized antibody. Using this antisense RNA strategy, rCHO cells (B3) producing a low level of caspase-3 proenzyme were established. When batch cultures of both B3 cells and control cells transfected with antisense RNA-deficient plasmid were performed in the absence of NaBu, both cells showed similar profiles of cell growth and antibody production. Compared with control cell culture, under the condition of 5 mM NaBu addition at the exponential growth phase, expression of antisense RNA of caspase-3 significantly suppressed the NaBu-induced apoptosis of B3 cells and extended culture longevity by >2 days if the culture was terminated at cell viability of 50%. However, compared with control cell culture, the final antibody concentration of B3 cell culture was not increased in the presence of NaBu, which may be due to the loss of cellular metabolic capability resulted from the depolarization of mitochondrial membrane. Taken together, this study suggests that, although expression of antisense RNA of caspase-3 does not improve antibody productivity of rCHO cells, it can suppress NaBu-induced apoptotic cell death of rCHO cells and thereby may reduce problems associated with cellular disintegration.
polo encodes a protein kinase homolog required for mitosis in Drosophila. (1991)

We show that mutation in polo leads to a variety of abnormal mitoses in Drosophila larval neuroblasts. These include otherwise normal looking mitotic spindles upon which chromosomes appear overcondensed; normal bipolar spindles with polyploid complements of chromosomes; bipolar spindles in which one pole can be unusually broad; and monopolar spindles. We have cloned the polo gene from a mutant allele carrying a P-element transposon and sequenced cDNAs corresponding to transcripts of the wild-type locus. The sequence shows that polo encodes a 577-amino-acid protein with an amino-terminal domain homologous to a serine-threonine protein kinase. polo transcripts are abundant in tissues and developmental stages in which there is extensive mitotic activity. The transcripts show no obvious spatial pattern of distribution in relation to the mitotic domains of cellularized embryos but are specifically concentrated in dividing cells in larval discs and brains. In the cell cycles of both syncytial and cellularized embryos, the polo kinase undergoes cell cycle-dependent changes in its distribution: It is predominantly cytoplasmic during interphase; it becomes associated with condensed chromosomes toward the end of prophase; and it remains associated with chromosomes until telophase, whereupon it becomes cytoplasmic.
Characterization of a mouse/human chimeric monoclonal antibody (17-1A) to a colon cancer tumor-associated antigen. (1987)

Mouse monoclonal antibody 17-1A is specific for an antigen expressed on cells of human gastrointestinal malignancies and has been used in radioimmune imaging and therapy trials for patients with colon and pancreatic cancer. The cell line SG3/5 was generated by transfection of a nonproducing mouse myeloma line (SP2/0) with a chimeric gene construct composed of variable regions from the mouse 17-1A immunoglobulin (gamma 2a, kappa) and constant regions of human k and gamma 3 immunoglobulin genes. The secreted immunoglobulin was bound by mouse monoclonal antibodies to human IgG(Fc) and IgG3 but not by staphylococcal protein A. Gel filtration HPLC profiles of purified chimeric antibody were similar to normal human IgG3 but quite different from native 17-1A and normal human IgG1, 2, and 4. Native and chimeric 17-1A had similar patterns of reactivity with colon cancer, other adenocarcinoma, and leukemic cell lines. Competitive inhibition documented that native and chimeric 17-1A had identical capacities to inhibit radiolabeled native 17-1A binding to colon cancer cell lines. Thus, the chimeric 17-1A exhibits molecular characteristics of normal human IgG3 but retains the specificity and binding affinity of the native 17-1A murine monoclonal antibody. The native and chimeric 17-1A mediated similar modest degrees of human lymphocyte and monocyte ADCC in a 4-hr 51Cr release assay, and both failed to mediate complement lysis of colon carcinoma cell lines in the presence of human complement. This human/mouse chimeric monoclonal antibody may be a good candidate for use in clinical trials because it retains the tumor antigen specificity and human effector cell recognition of the native 17-1A, would presumably have a fivefold to 10-fold longer circulating half-life in man, and should be considerably less immunogenic as compared with native murine immunoglobulins.
Whole Genome Sequencing Reveals a Chromosome 9p Deletion Causing DOCK8 Deficiency in an Adult Diagnosed with Hyper IgE Syndrome Who Developed Progressive Multifocal Leukoencephalopathy (2014)

While several genes are impacted by the deletion, DOCK8 deficiency is the most probable cause of HIES in this patient. DOCK8 deficiency may have also predisposed the patient to develop PML.
Reconstructing specimens using DIC microscope images (2003)

Differential interference contrast (DIC) microscopy is a powerful visualization tool used to study live biological cells. Its use, however, has been limited to qualitative observations. The inherent nonlinear relationship between the object properties and the image intensity makes quantitative analysis difficult. Toward quantitatively measuring optical properties of objects from DIC images, we develop a method to reconstruct the specimen's optical properties over a three-dimensional (3-D) volume. The method is a nonlinear optimization which uses hierarchical representations of the specimen and data. As a necessary tool, we have developed and validated a computational model for the DIC image formation process. We test our algorithm by reconstructing the optical properties of known specimens.
Crystal Structure of the Heterodimeric Complex of the Adaptor, ClpS, with the N-domain of the AAA+ Chaperone, ClpA (2002)

Substrate selectivity and proteolytic activity for the E. coli ATP-dependent protease, ClpAP, is modulated by an adaptor protein, ClpS. ClpS binds to ClpA, the regulatory component of the ClpAP complex. We report the crystal structure of ClpS in complex with the isolated N-terminal domain of ClpA in two different crystal forms at 2.3- and 3.3-A resolution. The ClpS structure forms an alpha/beta-sandwich and is topologically analogous to the C-terminal domain of the ribosomal protein L7/L12. ClpS contacts two surfaces on the N-terminal domain in both crystal forms; the more extensive interface was shown to be favored in solution by protease protection experiments. The N-terminal 20 residues of ClpS are not visible in the crystal structures; the removal of the first 17 residues produces ClpSDeltaN, which binds to the ClpA N-domain but no longer inhibits ClpA activity. A zinc binding site involving two His and one Glu residue was identified crystallographically in the N-terminal domain of ClpA. In a model of ClpS bound to hexameric ClpA, ClpS is oriented with its N terminus directed toward the distal surface of ClpA, suggesting that the N-terminal region of ClpS may affect productive substrate interactions at the apical surface or substrate entry into the ClpA translocation channel.
Manipulation of Signal Transduction by Botulinum Neurotoxins and their Derivatives (2007)

Botulinum neurotoxins produced by various Clostridium sp are the most potent acute lethal toxins known, and yet they have found increasing use in the clinical treatment of diseases or conditions involving neuromuscular or autonomic neuronal transmission. By a process involving proteolytic cleavage of one or more SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins, botulinum toxins inhibit the release of acetylcholine from peripheral cholinergic nerve terminals. Cleavage of SNARE proteins is both specific and effective, and leads to blockade of secretory vesicle fusion that is maintained for many weeks or months. Though inhibition of release of transmitter is currently the most clinically-relevant endpoint, SNARE proteolysis can also inhibit presentation of receptors, channels and other surface-membrane located materials. The implications for signal transduction are only just becoming apparent, but are an important facet of the mechanism of action of botulinum neurotoxins. Additionally, the ubiquitous distribution of the SNARE proteins ensures that proteolysis-dependent inhibition of transmitter release and receptor/channel presentation is theoretically not confined to neuronal targets. This review will consider the potential of botulinum neurotoxins as inhibitors of intercellular communication, and highlight the general concept of deriving novel therapeutic molecules from the neurotoxins.
[Effect of low-molecular amines on DNA conformation and stability of the double helix]. (1976)

Interaction of low-molecular amines (cystamine, cysteamine, cystaphose, asparagine, beta-alanine) with DNA was studied. The amines change the positive circular dichroism (CD) band of DNA as well as temperature and range width of melting. Effect of amines on DNA depends on ionic strength of the solvent, concentration and structure of the ligand. Monamines cause destabilization of DNA double helix followed by stabilization as ligand concentration increases. At concentrations stabilizing the double helix DNA conformation undergoes transition from the B- to C-form. The results obtained enable to relate the stabilizing effect of low-molecular amines and conformational B leads to C-transition to the non-specific interaction of ligand amino groups with DNA phosphates, and the destabilizing effect of monoamines of low concentrations to their interaction with bases, mainly in the denaturated sites of DNA. It is proposed that a stronger effectiveness of amines as compared to monovalent metals in the conformational shift of DNA towards the C-form is due to the additional effect of disturbance of hydrophobic interactions in DNA double helix.
Vagus Nerve Stimulation in Humans: Neurophysiological Studies and Electrophysiological Monitoring (1990)

Evidence from studies of experimental animals indicates that electrical stimulation of the vagus nerve alters behavioral and electrographic seizure activity. We report on effects of electrical stimulation of the vagus nerve in five patients with medically intractable seizures as part of a clinical trial of chronic vagal stimulation for control of epilepsy. The mechanism of action of the vagal antiepileptic effect is unknown, and it is hoped that analysis of electrophysiological effects of vagal nerve stimulation will help elucidate which brain areas are affected. Stimulation of the left vagus nerve in the neck was accomplished with a programmable implanted stimulator. Effects of stimulus amplitude, duration, and rate were studied. Noncephalic reference recording of the vagus-nerve-evoked potential showed some unusual properties: a scalp negative component occurred with latency of 12 ms, very high amplitude (up to 60 microV), and widespread scalp distribution. Field distribution studies indicate that this potential is generated in the neck, in the region of the stimulating electrodes. Muscle paralysis confirms this observation. Stimulation at various frequencies had no noticeable effect on electroencephalographic (EEG) activity regardless of whether the patient was under general anesthesia, awake, or asleep.
Baculovirus Expression of the Small Genome Segment of Hantaan Virus and Potential Use of the Expressed Nucleocapsid Protein as a Diagnostic Antigen (1988)

Autographa californica nuclear polyhedrosis virus (AcNPV) was used as an expression vector for the nucleocapsid protein gene of Hantaan virus. Two different cDNA clones representing the small genome segment of Hantaan virus were inserted into the transfer vector pAcYM1, and recombinants were generated by replacement of a portion of the baculovirus polyhedrin gene with the foreign, Hantaan virus gene. Recombinants containing both the first and second ATG initiation codons of the Hantaan virus gene produced nucleocapsid protein, while those containing only the second codon did not. The expressed nucleocapsid protein was evaluated as a potential diagnostic antigen with a variety of hantavirus-immune sera. The high levels of expression obtained, specific serological reactivity with immune sera and the low level of biological containment required for production of this protein all suggest a significant advantage over authentic viral antigen for diagnosis of hantavirus infection.
Clinical considerations for biosimilar antibodies (2013)

Biosimilar agents are approximate copies of branded biologic therapies. Since the first biosimilar was authorized in the European Union in 2006, fifteen additional agents have been approved by the European Medicines Agency, including two biosimilar monoclonal antibodies (mAbs). Biosimilar mAbs represent a distinct class given their large molecular size, complex protein structure, and post-translational modifications. While guidelines have been established for the development, approval, and use of biosimilars, further scrutiny and discussion is necessary to fully understand their potential impact on clinical outcomes. This review takes a critical look at the structural complexity of biosimilar mABs, the feasibility of indication extrapolation, the impact of product variability on immunogenicity, the importance of comprehensive pharmacovigilance, and the potential for ongoing pharmacoeconomic impact.
Exciton−Plasmon Interaction and Hybrid Excitons in Semiconductor−Metal Nanoparticle Assemblies (2006)

We describe the physical properties of excitons in hybrid complexes composed of semiconductor and metal nanoparticles. The interaction between individual nanoparticles is revealed as an enhancement or suppression of emission. Enhanced emission comes from electric field amplified by the plasmon resonance, whereas emission suppression is a result of energy transfer from semiconductor to metal nanoparticles. The emission intensity and energy transfer rate depend strongly on the geometrical parameters of the superstructure and the physical and material properties of the nanoparticles. In particular, the emission enhancement effect appears for nanoparticles with relatively small quantum yield, and silver nanoparticles have stronger enhancement compared to gold ones. Using realistic models, we review and analyze available experimental data on energy transfer between nanoparticles. In hybrid superstructures conjugated with polymer linkers, optical emission is sensitive to environmental parameters such as, for example, temperature. This sensitivity comes from expansion or contraction of a linker. With increasing temperature, emission of polymer-conjugated complexes can decrease or increase depending on the organization of a superstructure. The structures described here have potential as sensors and actuators.
ANTIBODIES SPECIFIC FOR RIBONUCLEOSIDES AND RIBONUCLEOTIDES AND THEIR REACTION WITH DNA (1964)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Dynamic Node Creation in Backpropagation Networks (1989)

Abstract This paper introduces a new method called Dynamic Node Creation (DNC) which automatically grows BP networks until the target problem is solved. DNC sequentially adds nodes one at a time to the hidden layer(s) of the network until the desired approximation accuracy is achieved. Simulation results for parity, symmetry, binary addition, and the encoder problem are presented. The procedure was capable of finding known minimal topologies in many cases, and was always within three nodes of the minimum. Computational expense for finding the solutions was comparable to training normal BP networks with the same final topologies. Starting out with fewer nodes than needed to solve the problem actually seems to help find a solution. The method yielded a solution for every problem tried.
Ultrasound imaging of gene expression in mammalian cells (2019)

The study of cellular processes occurring inside intact organisms requires methods to visualize cellular functions such as gene expression in deep tissues. Ultrasound is a widely used biomedical technology enabling noninvasive imaging with high spatial and temporal resolution. However, no genetically encoded molecular reporters are available to connect ultrasound contrast to gene expression in mammalian cells. To address this limitation, we introduce mammalian acoustic reporter genes. Starting with a gene cluster derived from bacteria, we engineered a eukaryotic genetic program whose introduction into mammalian cells results in the expression of intracellular air-filled protein nanostructures called gas vesicles, which produce ultrasound contrast. Mammalian acoustic reporter genes allow cells to be visualized at volumetric densities below 0.5% and permit high-resolution imaging of gene expression in living animals.
Antiserum raised against a synthetic phosphotyrosine-containing peptide selectively recognizes p185neu/erbB-2 and the epidermal growth factor receptor. (1992)

Rabbits were immunized with a synthetic phosphopeptide corresponding to a major autophosphorylation site of p185neu/erbB2 to determine the feasibility of producing tyrosine-phosphopeptide-specific antibodies. A series of adsorption and affinity chromatography steps were used to select antibodies with the desired reactivity. Immunoblot experiments showed that the resulting serum is highly specific for tyrosine-phosphorylated forms of p185 and the related epidermal growth factor receptor. The serum recognized these two receptors selectively when compared to five other receptor tyrosine kinases and several phosphorylated substrates. The serum is compatible with tissue-based assays since it detected tyrosine phosphorylation of the epidermal growth factor receptor in immunofluorescence experiments on permeabilized cells. The generality of the procedures used means that similar anti-tyrosine phosphopeptide sera can be produced that recognize other tyrosine kinases and substrates. Such sera will have numerous applications in research and clinical settings.
Orientation and Dynamics of ZnO Nanorod Liquid Crystals in Electric Fields (2010)

ZnO nanorod polymer hybrids (i.e., ZnO nanorods coated with a block copolymer with a short anchor block (dopamine) and a longer solubilizing block of polystyrene (PS)) form liquid crystalline (LC) phases if they are dispersed at high concentration e.g., in a PS oligomer matrix. Due to the high mobility of the low T(g) -matrix the nanorod polymer hybrids show a switching behavior under an applied AC electric field. Hence, the orientation of the nanorod mesogens can be changed from planar (parallel to the substrate) to homeotropic (perpendicular) in full analogy to the switching of low molecular liquid crystals in an electric field. Dielectric measurements show that such a switching is mainly due to the cooperative LC behavior, because the rods themselves exhibit only a very small effective dipole moment. The process can be investigated by polarizing microscopy. SEM images show the orientations of the individual nanorods, which correspond to the Fredericks transition well known for liquid crystals aligned in an electric field. This was the first time such a transition could be visualized by electron microscopy due to the large nanorod mesogens. The observation is interesting to orient nanorods perpendicular to an electrode and can help to improve optoelectronic devices.
Platelet Glycoprotein IIb/IIIa Inhibition with Coronary Stenting for Acute Myocardial Infarction (2001)

As compared with placebo, early administration of abciximab in patients with acute myocardial infarction improves coronary patency before stenting, the success rate of the stenting procedure, the rate of coronary patency at six months, left ventricular function, and clinical outcomes.
Light‐induced transcriptional repression of the pea AS1 gene: identification of cis‐elements and transfactors (1997)

Here, we examine the cis-elements and trans-factors affecting the expression of asparagine synthetase (AS) genes whose transcription is negatively regulated by light. The promoters for the AS1 and AS2 genes of pea were isolated, sequenced, and functionally dissected for their ability to confer regulated expression to the GUS reporter gene in transgenic tobacco. Histochemical analysis of transgenic plants demonstrated that the AS1 and AS2 promoters show identical patterns of cell-specific expression. The more highly active AS1 promoter was further demonstrated to confer negative light-regulation to the GUS gene in transgenic tobacco. Deletion analysis and gain-of-function experiments showed that 124 bp of the AS1 promoter was sufficient to confer light-activated repression to a heterologous promoter. Potential conserved transcription regulatory elements, Box B, Box C, and Box C' within this region were shown to bind to nuclear proteins by gel shift analysis. A light-specific DNA:protein interaction was detected with Box B. The nuclear factors that bind to Box C and C' elements of AS1 are competed by a putative repressor element 'RE1' defined previously in the oat phytochrome gene whose transcription is also repressed by light. The Box B and C/C'-Box/RE1-binding factors were found in nuclear extracts of tobacco, pea, and Arabidopsis and may therefore be universal factors involved in light-activated transcriptional repression.