gebhart/patrepeval huggingface dataset:
AMXI-5001, a novel dual parp1/2 and microtubule polymerization inhibitor for the treatment of human cancers. (2020)

Poly (ADP-ribose) polymerase (PARP) has recently emerged as a central mediator in cancer resistance against numerous anticancer agents to include chemotherapeutic agents such as microtubule targeting agents and DNA damaging agents. Here, we describe AMXI-5001, a novel, highly potent dual PARP1/2 and microtubule polymerization inhibitor with favorable metabolic stability, oral bioavailability, and pharmacokinetic properties. The potency and selectivity of AMXI-5001 were determined by biochemical assays. Anticancer activity either as a single-agent or in combination with other antitumor agents was evaluated in vitro. In vivo antitumor activity as a single-agent was assessed in a triple-negative breast cancer (TNBC) model. AMXI-5001 demonstrates comparable IC50 inhibition against PARP and microtubule polymerization as clinical PARP inhibitors (Olaparib, Rucaparib, Niraparib, and Talazoparib) and the potent polymerization inhibitor (Vinblastine), respectively. In vitro, AMXI-5001 exhibited selective antitumor cytotoxicity across a wide variety of human cancer cells with much lower IC50s than existing clinical PARP1/2 inhibitors. AMXI-5001 is highly active in both BRCA mutated and wild type cancers. AMXI-5001 is orally bioavailable. AMXI-5001 elicited a remarkable In vivo preclinical anti-tumor activity in a BRCA mutated TNBC model. Oral administration of AMXI-5001 induced complete regression of established tumors, including exceedingly large tumors. AMXI-5001 resulted in superior anti-tumor effects compared to either single agent (PARP or microtubule) inhibitor or combination with both agents. AMXI-5001 will enter clinical trial testing soon and represents a promising, novel first in class dual PARP1/2 and microtubule polymerization inhibitor that delivers continuous and synchronous one-two punch cancer therapy with one molecule.
Overexpression of multidrug resistance-associated protein (MRP) increases resistance to natural product drugs. (1994)

Amplification of the gene encoding multidrug resistance-associated protein (MRP) and overexpression of its cognate mRNA have been detected in multidrug-resistant cell lines derived from several different tumor types. To establish whether or not the increase in MRP is responsible for drug resistance in these cell lines, we have transfected HeLa cells with MRP expression vectors. The transfectants display an increase in resistance to doxorubicin that is proportional to the levels of a M(r) 190,000, integral membrane protein recognized by anti-MRP antibodies. The transfectants are also resistant to vincristine and VP-16 but not to cisplatin. The results demonstrate that MRP overexpression confers a multidrug resistance phenotype similar to that formerly associated exclusively with elevated levels of P-glycoprotein.
Colitis in calves: natural and experimental infection with a verotoxin-producing strain of Escherichia coli O111:NM. (1988)

Verotoxin-producing Escherichia coli O111:NM were isolated from two five week old Holstein calves with dysentery. On necropsy both calves had pseudomembranous ileitis, mucohemorrhagic colitis and proctitis. Large numbers of E. coli O111:NM were isolated from the colon and lesions typical of attaching-and-effacing E. coli were evident. The isolates from both calves had identical biochemical reactions and antimicrobial resistance patterns. Oral inoculation of a four day old colostrum deprived calf with 1 x 10(10) organisms of E. coli O111:NM produced a mild, focal colitis with typical attachment and effacement lesions. We conclude that the strain of E. coli O111:NM isolated from the clinical cases has the ability to produce colitis characterized by attachment and effacement of the colonic mucosa.
Synthesis and heparin‐like biological activity of amino acid‐based polymers (2000)

Biological macromolecules are important regulators of physiological functions. Most of the biologically active macromolecules are charged linear polymers like some proteins, DNA and glycosaminoglycans (GAG). Heparin, the first GAG applied in medicine, is a natural polyanion composed of repeating disaccharide units of glucosamine and uronic acid. The amino and hydroxyl groups of the glucosamine units are partially sulfated. Heparin is a potent anticoagulant, and is also active as an antimethastatic and antiproliferative agent. Sulfatation of other polysaccharides such as laminarin yielded very potent new anticoagulans. It was hypothesized that macromolecules based on N-acryl L-amino acids bearing hydrophobic or charged side groups, such as NH2, COOH, SH, OH and phenols, arranged into a configuration determined by the chirality of the amino acid α-carbon, may express heparin-like biological activities. Homo-poly(N-acryl amino acids) were synthesized from the corresponding monomers. Polymers with different charge densities, nature of the amino acid side group, stereoselectivity and polymeric backbone were tested for their activity as anticoagulants, heparanase inhibition agents, and to basic fibroblast growth factor (b-FGF) release agents bound to the extracellular matrix (ECM). The type of amino acid, the polymer backbone, the charge density and distribution strongly affect the biological activity exerted by these polyanions. All polymers being active either as heparanase inhibitors and/or as b-FGF release agents have at least a negative charge density of 1 per amino acid residue. Polymers bearing hydrophilic side chains that inhibited heparanase, i.e., hydroxyproline, glycine and serine, did not release b-FGF from ECM. The absence of high acidic sulfate-ester groups existing in heparin (hydrophilic) must be compensated by some kind of lipophilic interactions between the polyanion and b-FGF in order to effectively compete with heparan sulfate proteoglycanes, causing its release from ECM. Heparanase inhibitors may have clinical applications in preventing tumor metastasis and inflammatory/autoimmune processes due to the involvement of this enzyme in the extravasation of blood-borne tumor cells and activated cells of the immune system. Molecules that release ECM-bound b-FGF may be applied to accelerate neovascularization and tissue repair. Copyright © 2000 John Wiley & Sons, Ltd.
Broadly Neutralizing Antiviral Antibodies (2013)

A fascinating aspect of viral evolution relates to the ability of viruses to escape the adaptive immune response. The widely held view has been that the great variability of viral glycoproteins would be an absolute obstacle to the development of antibody-based therapies or vaccines that could confer broad and long-lasting protection. In the past five years, new approaches have been developed to interrogate human memory B cells and plasma cells with high efficiency and to isolate several broadly neutralizing antiviral antibodies against highly variable pathogens such as HIV-1 and influenza virus. These antibodies not only provide new tools for prophylaxis and therapy for viral diseases but also identify conserved epitopes that may be used to design new vaccines capable of conferring broader protection.
Purification and Characterization of Phosphatase I from Aspergillus nidulans (1968)

Abstract A procedure for the purification of alkaline phosphatase I from Aspergillus nidulans is described. The final preparation is homogeneous by chromatography, gel filtration, density gradient sedimentation, starch gel, and acrylamide electrophoresis. Several physical-chemical properties of the purified enzyme are reported. The enzyme is a classical alkaline phosphomonoesterase.
Elevated Transferrin Receptor Content in Human Prostate Cancer Cell Lines Assessed in Vitro and in Vivo (1990)

Transferrin receptors (TfR) were measured in benign and malignant prostatic cells by performing Scatchard analysis following the administration of 125I-transferrin. Established human prostate cancer cell lines (PC-3 and DU-145) as well as biologically aggressive variants (PC-3 ASC and PC-3 DES) were shown to possess significant levels of high affinity TfR when assessed in vitro. In contrast, TfR content was negligible in cultured stromal cell fractions derived from human benign prostatic hyperplasia (BPH) specimens. Scatchard analysis was also performed on in vivo derived prostatic tissues: tumors resulting from the subcutaneous xenografting of PC-3 ASC cells into athymic, nude mice and fresh BPH surgical specimens. These tissues were dissociated and their stromal and epithelial components separated. TfR were only detected in the epithelial component of both malignant and benign epithelial cells. PC-3 ASC tumor cells exhibited TfR levels comparable to their in vitro expression and these levels were 10-fold greater than in the BPH cells. These findings suggest that elevated TfRs may serve as another useful marker of the transformed phenotype within human prostate tumor systems.
Dendritic cell targeting ofBacillus anthracisprotective antigen expressed byLactobacillus acidophilusprotects mice from lethal challenge (2009)

Efficient vaccines potentiate antibody avidity and increase T cell longevity, which confer protection against microbial lethal challenge. A vaccine strategy was established by using Lactobacillus acidophilus to deliver Bacillus anthracis protective antigen (PA) via specific dendritic cell-targeting peptides to dendritic cells (DCs), which reside in the periphery and mucosal surfaces, thus directing and regulating acquired immunity. The efficiency of oral delivery of L. acidophilus expressing a PA-DCpep fusion was evaluated in mice challenged with lethal B. anthracis Sterne. Vaccination with L. acidophilus expressing PA-DCpep induced robust protective immunity against B. anthracis Sterne compared with mice vaccinated with L. acidophilus expressing PA-control peptide or an empty vector. Additionally, serum anti-PA titers, neutralizing PA antibodies, and the levels of IgA-expressing cells were all comparable with the historical recombinant PA plus aluminum hydroxide vaccine administered s.c. Collectively, development of this strategy for oral delivery of DC-targeted antigens provides a safe and protective vaccine via a bacterial adjuvant that may potentiate mucosal immune responses against deadly pathogens.
Sporulation and time course expression of sigma-factor homologous genes in Clostridium acetobutylicum (1998)

The gene for the vegetative sigma factor A of Clostridium acetobutylicum was constitutively transcribed during growth and formed an operon together with dnaE. Sporulation-specific sigma factors E, G, and K were sequentially induced shortly before mature endospores could be detected. Maximal transcription in the course of spore formation was found to be in the order sigE-sigG-sigK, thus matching the pattern described for Bacillus subtilis. From primer extension experiments promoter structures could be deduced with high homology to the Bacillus consensus. Upstream of the spoIIGA-sigE operon a gene with significant similarity to ftsZ could be detected.
Near Infrared Analysis (1985)

Abstract Near-infrared analysis (NIRA) is an analytical technique which uses the diffuse reflectance of a sample to determine spectrophotometrically the chemical concentrations or physical properties of a sample. Because NIRA uses a series of multiple linear regressions to deduce automatically corrections for background or sample-matrix interferences. it can analyze many sample types that would be difficult by another spectroscopic technique. An automatic correction of interferences allows NIRA to operate independently of fully understood chemistry or spectroscopy. The present work lists and defines the practical considerations involved in developing and utilizing NIRA as well as presenting a cross-section of current applications. Among the considerations addressed are selecting the analyte. choosing “training” samples, and creating a calibration Throughout each discussion, the advantages of NIRA are detailed.
[Structure determination of three saponins from the stem bark of Albizzia julibrissin Durazz]. (1997)

Three new saponins named Julibroside J1, J2 and J3 were isolated from the stem bark of Albizzia julibrissin Durazz (Albizziae Cortex). Based on chemical and spectral methods, e.g. 1H- and 13C-NMR, DEPT, COSY CH-COSY, TOCSY, HMQC-COSY, HMQC-TOCSY, NOESY, HMBC, their structures have been identified as; Julibroside J1 (one triterpene, nine sugars, two monoterpenes I); Julibroside J2(one triterpene, eight sugars two monoterpenes II); Julibroside J3(one triterpene, nine sugars two monoterpenes III).
Phosphonomycin: Structure and Synthesis (1969)

Synthesis and resolution of the antibiotic phosphonomycin are described. The structure is (-)(IR, 2S)-1,2-epoxypropylphosphonic acid.
A Graphene Oxide Based Immuno‐biosensor for Pathogen Detection (2010)

Rotaviren auf der Spur: Die empfindliche und selektive Detektion von Rotaviren gelingt mithilfe der Photolumineszenz eines Graphenoxid(GO)-Arrays. Die Zielzelle wurde vom Rotavirus-spezifischen, auf dem GO-Array immobilisierten Antikörper eingefangen, und der Bindevorgang wurde anhand der Fluoreszenzlöschung verfolgt, die aus dem resonanten Fluoreszenzenergietransfer (FRET) zwischen GO und Goldnanopartikeln an den Antikörpern resultiert (siehe Bild).
A method for dead reckoning parameter correction in pedestrian navigation system (2003)

This paper presents a method for correcting dead reckoning parameters, which are heading and step size, for a pedestrian navigation system. In this method, the compass bias error and the step size error can be estimated during the period that the Global Positioning System (GPS) signal is available. The errors are used for correcting those parameters to improve the accuracy of position determination using only the dead reckoning system when the GPS signal is not available. The results show that the parameters can be estimated with reasonable accuracy. Moreover, the method also helps to increase the positioning accuracy when the GPS signal is available.
Carbonic anhydrase-9 expression levels and prognosis in human breast cancer: association with treatment outcome (2003)

Here, we set out to assess CA9 expression levels by real-time quantitative RT-PCR in breast cancer tissue samples obtained from 253 patients, and correlated those with relapse-free (RFS) survival. The median follow-up time was 75 months (range 2-168 months). CA9 expression was mainly found in high-grade, steroid receptor negative cancer tissues. CA9 levels were not significantly associated with RFS (P=0.926, hazard ratio (HR)=0.99, 95% CI=0.80-1.22) in the total cohort of 253 patients. In multivariate analysis with other clinicopathological factors, CA9 (P=0.018, HR=0.77, 95% CI=0.62-0.96), the interaction of adjuvant chemotherapy with CA9 (P=0.009, HR=1.31, 95% CI=1.07-1.61) and the interaction of adjuvant endocrine therapy with CA9 (P<0.001, HR=1.41, 95% CI=1.20-1.66) all contributed significantly to the final model. These results indicate that patients with low CA9 levels benefit more from adjuvant treatment than do patients with high levels. Thus, the determination of CA9 levels could aid in the selection of patients who will not benefit from adjuvant therapy, and whose prognosis will more likely improve with other treatment modalities.
Evaluation of the antibiotic biosynthetic potential of the genus Amycolatopsis and description of Amycolatopsis circi sp. nov., Amycolatopsis equina sp. nov. and Amycolatopsis hippodromi sp. nov (2011)

Three new species of Amycolatopsis are described, and the knowledge of the antibiotic biosynthetic potential of the genus has been extended.
Phage Display of Antibody Fragments (2000)

In recent years, phage display of peptides and proteins has become a very popular method in oncology, immunology, protein engineering and ligand-receptor studies among others. Antibody fragments, as Fabs or single chain Fv, have been among the first proteins to be displayed on the surface of a filamentous bacteriophage with a procedure initially described in 1990 by McCafferty et al. (Nature, 348, 552-554). From that time, molecular biology techniques have allowed the creation of large repertoires of antibody fragments from antibody V genes, bypassing hybrydoma technology and even immunisation. A large number of phage antibody libraries, from which molecules of the desired functional properties can be rapidly selected, have been built and distributed in many laboratories world-wide. Antibody fragments recovered from phage libraries generally show moderate binding strength; with different systems of biopanning binders can be obtained with dissociation constant ranged between 10-(5) to 10-(8) M. Nevertheless, antibody fragments can be furtherly modified to improve affinity or avidity, respectively by mutating crucial residues of complementarity determining regions or by increasing the number of binding sites making dimeric, trimeric or multimeric molecules. Here, we summarise the latest progress in this field, with particular reference to applications of scFv in the diagnosis and therapy of solid tumours and in the molecular mimicry of viral antigens and membrane receptors. In fact, the production of artificial protein epitopes by phage antibodies is becoming a valid system to overcome problems caused by difficult cloning and low expression of particular recombinant proteins.
Biological activity of oligonucleotide-poly(L-lysine) conjugates: mechanism of cell uptake (1990)

We have previously shown that antisense oligomers linked to poly(L-lysine) (PLL) exhibit antiviral properties against vesicular stomatitis virus (VSV) at concentrations lower than 1 microM. The conjugation to PLL provides an interesting alternative to natural or neutral oligomers to increase the biological effects of antisense oligomers. The internalization pathway of oligomer-PLL conjugates as compared to unconjugated oligomers has been studied in L929 cells. In parallel to their enhanced antiviral activity, PLL increases greatly the uptake of fluorescently tagged oligomers. This internalization follows a classical endocytic pathway and the oligomer has to be cleaved from PLL in the cell to exhibit an antiviral effect.
Sequence and expression analysis of bovine pigment epithelium-derived factor (1998)

PEDF, a member of the serpin superfamily of proteins related through their highly conserved folded conformation, has neurotrophic properties, including promotion of neurite-outgrowth and neuronal survival. Previously, we have purified and characterized PEDF protein from extracellular matrixes of bovine eyes. Here, we show the cDNA sequence and expression analysis of bovine PEDF. Northern analysis of RNA from bovine retinal pigment epithelium (RPE) and neural retina using a human PEDF cDNA fragment reveals expression of the PEDF gene only for RPE. Sequence analysis of a cDNA clone isolated from bovine RPE predicts a polypeptide of 416 amino acid residues that shares 88.6% and 85% amino acid identity with human and mouse PEDF, respectively. It has an N-terminal signal peptide, a consensus glycosylation site and homology with serpins including the conserved residues required for maintaining the serpin tertiary structure. Cell-free expression of the bovine PEDF cDNA by in vitro transcription and translation yields a precursor polypeptide of 45,000-Mr that immunoprecipitates with an antibody to human PEDF. Expression analysis in stably transfected baby hamster kidney cells shows that the recombinant bovine protein is secreted to the culture media as a mature 50,000-Mr protein, which induces neurite-outgrowth on retinoblastoma cells, like the naturally-occurring PEDF protein. Thus, the bovine PEDF cDNA isolated here codes for a functional soluble secreted PEDF glycoprotein.
The cardiovascular effects of erythropoietin (2003)

Erythropoietin is a hypoxia-induced hormone that is essential for normal erythropoiesis. The production of recombinant human erythropoietin (rHuEpo) has revolutionized the treatment of anemia associated with chronic renal failure and chemotherapy, and has been used as prophylaxis to prevent anemia after surgery. The erythropoietin receptor is widely distributed in the cardiovascular system, including endothelial cells, smooth muscle cells and cardiomyocytes. Epo has potentially beneficial effects on the endothelium including anti-apoptotic, mitogenic and angiogenic activities. On the other hand, some reports suggest that rHuEpo may have pro-thrombotic or platelet-activating effects. Hypertension develops in 20-30% of renal patients treated with rHuEpo. Many patients with heart failure have anemia. Despite some potential adverse effects, early studies in heart failure patients with anemia suggest that rHuEpo therapy is safe and effective in reducing left ventricular hypertrophy, enhancing exercise performance and increasing ejection fraction. Further studies are warranted to define the role of rHuEpo in chronic heart failure and other cardiovascular settings.
Interactive design of complex time dependent lighting (1995)

Visualizing complicated lighting sequences while designing large theatrical productions proves difficult. The author provides some techniques that achieve fast interaction regardless of scene and lighting complexity, even when used with costly rendering algorithms.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Absence of p300 induces cellular phenotypic changes characteristic of epithelial to mesenchyme transition (2006)

p300 is a transcriptional cofactor and prototype histone acetyltransferase involved in regulating multiple cellular processes. We generated p300 deficient (p300-) cells from the colon carcinoma cell line HCT116 by gene targeting. Comparison of epithelial and mesenchymal proteins in p300- with parental HCT116 cells showed that a number of genes involved in cell and extracellular matrix interactions, typical of 'epithelial to mesenchyme transition' were differentially regulated at both the RNA and protein level. p300- cells were found to have aggressive 'cancer' phenotypes, with loss of cell-cell adhesion, defects in cell-matrix adhesion and increased migration through collagen and matrigel. Although migration was shown to be metalloproteinase mediated, these cells actually showed a downregulation or no change in the level of key metalloproteinases, indicating that changes in cellular adhesion properties can be critical for cellular mobility.
Albumin microspheres as drug carriers. (1985)

In order to improve the therapeutic index in cancer chemotherapy, it is necessary to deliver antitumor agents to target sites (tumor sites). One of the methods used to deliver those agents to target sites is to employ nontoxic and biodegradable drug carriers. Considerable efforts have been directed toward the development of drug carriers, i.e., DNA complexes, protein-drug conjugates, lactic/glycolic acid polymer, liposomes, emulsion, etc. Albumin microsphere is one of those drug carriers. This review describes the progress which has been made during the last 10 to 15 years in the application of albumin microspheres as drug carriers to cancer chemotherapy. It will cover a wide range of subjects including the preparation and physicochemical properties of microspheres containing antitumor agents, pharmacokinetics of the microspheres in experimental animals, and the antitumor efficacy by intra-arterial use against human primary metastatic liver tumor.