gebhart/patrepeval huggingface dataset:
Creation of "Amyloid" Fibrils from Bence Jones Proteins in vitro (1971)

"Amyloid" fibrils have been created from some human Bence Jones proteins by proteolytic digestion under physiologic conditions. These fibrils with an antiparallel, beta-pleated sheet conformation consist of only a portion of the variable region of the immunoglobulin light polypeptide chain and share the physical properties of amyloid fibrils. The relation between amyloidosis and immunoglobulins is thus more firmly established and a pathogenetic mechanism for amyloid fibril formation is suggested.
Construction, replication, and chromatin structure of TRP1 RI circle, a multiple-copy synthetic plasmid derived from Saccharomyces cerevisiae chromosomal DNA. (1982)

Transformation studies with Saccharomyces cerevisiae (bakers' yeast) have identified DNA sequences which permit extrachromosomal maintenance of recombinant DNA plasmids in transformed cells. It has been hypothesized that such sequences (called ARS for autonomously replicating sequence) serve as initiation sites for DNA replication in recombinant DNA plasmids and that they represent the normal sites for initiation of replication in yeast chromosomal DNA. We have constructed a novel plasmid called TRP1 R1 Circle which consists solely of 1,453 base pairs of yeast chromosomal DNA. TRP1 RI Circle contains both the TRP1 gene and a sequence called ARS1. This plasmid is found in 100 to 200 copies per cell and is relatively stable during both mitotic and meiotic cell cycles. Replication of TRP1 RI Circle requires the products of the same genes (CDC28, CDC4, CDC7, and CDC8) required for replication of chromosomaL DNA. Like chromosomal DNA, its replication does not occur in cells arrested in the B1 phase of the cell cycle by incubation with the yeast pheromone alpha-factor. In addition, TRP1 RI Circle DNA is organized into nucleosomes whose size and spacing are indistinguishable from that of bulk yeast chromatin. These results indicate that TRP1 RI Circle has the replicative and structural properties expected for an origin of replication from yeast chromosomal DNA. Thus, this plasmid is a suitable model for further studies of yeast DNA replication in both cells and cell-free extracts.
ChemInform Abstract: N,N′‐Bis(2‐hydroxybenzyl)‐1‐(4‐bromoacetamidobenzyl)‐1,2‐ethylenediamine‐N,N′‐diacetic Acid: A New Bifunctional Chelate for Radiolabeling Antibodies. (1990)

Abstract The compound (IX) mentioned in the title is synthesized as outlined in the reaction scheme.
Elimination of cytokine production in stored platelet concentrate aliquots by photochemical treatment with psoralen plus ultraviolet A light (1999)

PCT that utilizes S-59 has been developed to inactivate potential viral and bacterial pathogens in PC aliquots while maintaining in vitro platelet function. These data demonstrate that PCT of aliquots of pooled PC aliquots before storage also prevents white cell cytokine synthesis during storage. PCT may therefore offer the potential for reducing cytokine-associated febrile nonhemolytic transfusion reactions.
Ketamine’s Antidepressant Efficacy is Extended for at Least Four Weeks in Subjects with a Family History of an Alcohol Use Disorder (2014)

Ketamine's extended antidepressant durability in FHP TRD should be considered in the design and analysis of ketamine depression trials.
Apolipoprotein E and Alzheimer disease. (1995)

Inheritance of specific apolipoprotein E (apoE) alleles determines, in large part, the risk and mean age of onset of late-onset familial and sporadic Alzheimer disease. The mechanism by which the apoE isoforms differentially contribute to disease expression is, however, unknown. Isoform-specific differences have been identified in the binding of apoE to the microtubule-associated protein tau, which forms the paired helical filament and neurofibrillary tangles, and to amyloid beta peptide, a major component of the neuritic plaque. These and other isoform-specific interactions of apoE give rise to testable hypotheses for the mechanism(s) of pathogenesis of Alzheimer disease. An unresolved issue of increasing importance is the relationship between the structural pathological lesions and the cellular pathogenesis responsible for the clinical disease phenotype, progressive dementia. The identification of apoE in the cytoplasm of human neurons and the characterization of isoform-specific binding of apoE to the microtubule-associated proteins tau and MAP-2 present the possibility that apoE may affect microtubule function in the Alzheimer brain.
SoDA2: a Hidden Markov Model approach for identification of immunoglobulin rearrangements (2010)

SoDA2 is available online at https://hippocrates.duhs.duke.edu/soda. Simulated sequences are available upon request.
Oligoribonuclease is a central feature of cyclic diguanylate signaling inPseudomonas aeruginosa (2015)

The second messenger cyclic diguanylate (c-di-GMP) controls diverse cellular processes among bacteria. Diguanylate cyclases synthesize c-di-GMP, whereas it is degraded by c-di-GMP-specific phosphodiesterases (PDEs). Nearly 80% of these PDEs are predicted to depend on the catalytic function of glutamate-alanine-leucine (EAL) domains, which hydrolyze a single phosphodiester group in c-di-GMP to produce 5'-phosphoguanylyl-(3',5')-guanosine (pGpG). However, to degrade pGpG and prevent its accumulation, bacterial cells require an additional nuclease, the identity of which remains unknown. Here we identify oligoribonuclease (Orn)-a 3'→5' exonuclease highly conserved among Actinobacteria, Beta-, Delta- and Gammaproteobacteria-as the primary enzyme responsible for pGpG degradation in Pseudomonas aeruginosa cells. We found that a P. aeruginosa Δorn mutant had high intracellular c-di-GMP levels, causing this strain to overexpress extracellular polymers and overproduce biofilm. Although recombinant Orn degraded small RNAs in vitro, this enzyme had a proclivity for degrading RNA oligomers comprised of two to five nucleotides (nanoRNAs), including pGpG. Corresponding with this activity, Δorn cells possessed highly elevated pGpG levels. We found that pGpG reduced the rate of c-di-GMP degradation in cell lysates and inhibited the activity of EAL-dependent PDEs (PA2133, PvrR, and purified recombinant RocR) from P. aeruginosa. This pGpG-dependent inhibition was alleviated by the addition of Orn. These data suggest that elevated levels of pGpG exert product inhibition on EAL-dependent PDEs, thereby increasing intracellular c-di-GMP in Δorn cells. Thus, we propose that Orn provides homeostatic control of intracellular pGpG under native physiological conditions and that this activity is fundamental to c-di-GMP signal transduction.
Expression profiling of cytogenetically normal acute myeloid leukemia identifies MicroRNAs that target genes involved in monocytic differentiation (2010)

MicroRNAs are short ribonucleic acids (RNAs) that play an important role in many aspects of cellular biology such as differentiation and apoptosis, due to their role in the regulation of gene expression. Using microRNA microarrays, we characterized the microRNA gene expression of 27 patients with acute myeloid leukemia (AML) with normal cytogenetics, focusing on the microRNAs differentially expressed between the M1 and M5 French-American-British (FAB) subtypes. An accurate delineation of these two AML entities was observed based on the expression of 12 microRNAs. We hypothesized that these microRNAs may potentially be involved in the differentiation block of M1 blasts and consequently monocytic differentiation. Using publically available mRNA data and microRNA target prediction software, we identified several key myeloid factors that may be targeted by our candidate microRNAs. The expression changes of the candidate microRNAs during monocytic differentiation of AML cell lines treated with Vitamin D and phorbol 12-myristate 13-acetate were examined. All six candidate microRNAs were significantly down-regulated over the time course by quantitative reverse transcriptase polymerase chain reaction suggesting a link between these microRNAs and monocytic differentiation. To further characterize these microRNAs, we confirmed by luciferase assays that these microRNA target several key myeloid factors such as MAFB, IRF8, and KLF4 identifying a possible mechanism for the control of differentiation by these microRNAs.
Controlled Comparison of Amikacin and Gentamicin (1977)

Amikacin or gentamicin was used to treat 174 patients with suspected severe gram-negative infections in a prospective, randomized, double-blind trial. Enteric gram-negative bacilli were pathogenic in 71 cases (39 treated with amikacin, and 32 with gentamicin). Amikacin was effective in 10 to 12 bacteremias, 21 of 24 urinary-tract infections, two of five pneumonias and four of six other serious tissue infections. The toal favorable response rate was 77 per cent for amikacin and 78 per cent for gentamicin. Nephrotoxicity and auditory toxicity could be evaluated in 124 and 67 cases respectively. Definite nephrotoxicity developed in five of 62 (8 per cent) receiving amikacin and seven of 62 (11 per cent) given gentamicin, and possible nephrotoxicity developed in four patients in both groups. Definite ototoxicity developed in four patients in both groups. Definite otoxicity developed in two of 34 (6 per cent) and three of 30 (10 per cent) respectively. These differences were not statistically significant (by chisquare analysis, P greater than 0.05). The results indicate that amikacin is effective against severe gram-negative infections and is not more and not less ototoxic or nephrotoxic than gentamicin.
Prostatic α1‐adrenoceptors and uroselectivity (1997)

BACKGROUND α1-adrenoceptor antagonists (blockers) are now commonly used in the treatment of the symptoms of lower urinary tract obstruction. Originally phenoxybenzamine, a non-selective antagonist at both α1- and α2-adrenoceptors, was used by Marco Caine. In an attempt to minimize side effects, selective α1-antagonists, e.g. prazosin, were subsequently developed. More recently, agents such as alfuzosin, doxazosin, terazosin, and tamsulosin have been introduced and claims of “uroselectivity” and “prostate” selectivity have emerged. METHODS This review attempts to put these claims into perspective and represents a comprehensive analysis of all pre-clinical and clinical data including several papers from the Japanese literature. An attempt is made to define what is meant by selectivity at various levels including the test tube, in the laboratory animal and, most importantly, in the clinical context of the whole patient. CONCLUSIONS The conclusions are interpreted within the context of the subdivision of the α1-adrenoceptor into α1A, α1B and α1D subtypes. Prostate 30:202–215, 1997. © 1997 Wiley-Liss, Inc.
A Simple Noninvasive Index Can Predict Both Significant Fibrosis and Cirrhosis in Patients With Chronic Hepatitis C (2003)

Information on the stage of liver fibrosis is essential in managing chronic hepatitis C (CHC) patients. However, most models for predicting liver fibrosis are complicated and separate formulas are needed to predict significant fibrosis and cirrhosis. The aim of our study was to construct one simple model consisting of routine laboratory data to predict both significant fibrosis and cirrhosis among patients with CHC. Consecutive treatment-naive CHC patients who underwent liver biopsy over a 25-month period were divided into 2 sequential cohorts: training set (n = 192) and validation set (n = 78). The best model for predicting both significant fibrosis (Ishak score > or = 3) and cirrhosis in the training set included platelets, aspartate aminotransferase (AST), and alkaline phosphatase with an area under ROC curves (AUC) of 0.82 and 0.92, respectively. A novel index, AST to platelet ratio index (APRI), was developed to amplify the opposing effects of liver fibrosis on AST and platelet count. The AUC of APRI for predicting significant fibrosis and cirrhosis were 0.80 and 0.89, respectively, in the training set. Using optimized cut-off values, significant fibrosis could be predicted accurately in 51% and cirrhosis in 81% of patients. The AUC of APRI for predicting significant fibrosis and cirrhosis in the validation set were 0.88 and 0.94, respectively. In conclusion, our study showed that a simple index using readily available laboratory results can identify CHC patients with significant fibrosis and cirrhosis with a high degree of accuracy. Application of this index may decrease the need for staging liver biopsy specimens among CHC patients.
Emerging antiviral drugs (2008)

Foremost among the newly described antiviral agents that may be developed into drugs are, for the treatment of human papilloma virus (HPV) infections, cPrPMEDAP; for the treatment of herpes simplex virus (HSV) infections, BAY 57-1293; for the treatment of varicella-zoster virus (VZV) infections, FV-100 (prodrug of Cf 1743); for the treatment of cytomegalovirus (CMV) infections, maribavir; for the treatment of poxvirus infections, ST-246; for the treatment of hepatitis B virus (HBV) infections, tenofovir disoproxil fumarate (TDF) (which in the meantime has already been approved in the EU); for the treatment of various DNA virus infections, the hexadecyloxypropyl (HDP) and octadecyloxyethyl (ODE) prodrugs of cidofovir; for the treatment of orthomyxovirus infections (i.e., influenza), peramivir; for the treatment of hepacivirus infections (i.e., hepatitis C), the protease inhibitors telaprevir and boceprevir, the nucleoside RNA replicase inhibitors (NRRIs) PSI-6130 and R1479, and various non-nucleoside RNA replicase inhibitors (NNRRIs); for the treatment of human immunodeficiency virus (HIV) infections, integrase inhibitors (INIs) such as elvitegravir, nucleoside reverse transcriptase inhibitors (NRTIs) such as apricitabine, non-nucleoside reverse transcriptase inhibitors (NNRTIs) such as rilpivirine and dapivirine; and for the treatment of both HCV and HIV infections, cyclosporin A derivatives such as the non-immunosuppressive Debio-025.
Chemistry of Aqueous Silica Nanoparticle Surfaces and the Mechanism of Selective Peptide Adsorption (2012)

Control over selective recognition of biomolecules on inorganic nanoparticles is a major challenge for the synthesis of new catalysts, functional carriers for therapeutics, and assembly of renewable biobased materials. We found low sequence similarity among sequences of peptides strongly attracted to amorphous silica nanoparticles of various size (15-450 nm) using combinatorial phage display methods. Characterization of the surface by acid base titrations and zeta potential measurements revealed that the acidity of the silica particles increased with larger particle size, corresponding to between 5% and 20% ionization of silanol groups at pH 7. The wide range of surface ionization results in the attraction of increasingly basic peptides to increasingly acidic nanoparticles, along with major changes in the aqueous interfacial layer as seen in molecular dynamics simulation. We identified the mechanism of peptide adsorption using binding assays, zeta potential measurements, IR spectra, and molecular simulations of the purified peptides (without phage) in contact with uniformly sized silica particles. Positively charged peptides are strongly attracted to anionic silica surfaces by ion pairing of protonated N-termini, Lys side chains, and Arg side chains with negatively charged siloxide groups. Further, attraction of the peptides to the surface involves hydrogen bonds between polar groups in the peptide with silanol and siloxide groups on the silica surface, as well as ion-dipole, dipole-dipole, and van-der-Waals interactions. Electrostatic attraction between peptides and particle surfaces is supported by neutralization of zeta potentials, an inverse correlation between the required peptide concentration for measurable adsorption and the peptide pI, and proximity of cationic groups to the surface in the computation. The importance of hydrogen bonds and polar interactions is supported by adsorption of noncationic peptides containing Ser, His, and Asp residues, including the formation of multilayers. We also demonstrate tuning of interfacial interactions using mutant peptides with an excellent correlation between adsorption measurements, zeta potentials, computed adsorption energies, and the proposed binding mechanism. Follow-on questions about the relation between peptide adsorption on silica nanoparticles and mineralization of silica from peptide-stabilized precursors are raised.
Modeling and dosimetry of monoclonal antibody M195 (anti-CD33) in acute myelogenous leukemia. (1993)

Individual patient response to radioimmunotherapy is influenced by each patient's tumor burden, antibody clearance kinetics and the antibody-antigen interaction. In hematologic malignancies, wherein antibody access to tumor-cell associated antigen is rapid, mathematical modeling may provide a quantitative basis for assessing the impact of patient variability on a particular therapeutic protocol. Compartmental modeling analysis of antibody pharmacokinetics from a Phase I trial of 131I-labeled monoclonal antibody, M195 (anti-CD33), was used to estimate tumor burden in cases of acute myelogenous leukemia and the absorbed dose in liver, spleen and red marrow. The suitability of a nonlinear, two-compartment model for simulating M195 distribution in leukemia patients was evaluated by comparing model predictions with patient measurements. The results demonstrate that for directly accessible, hematologically distributed tumor cells, a two-compartment model fits observed patient biodistribution data and may provide information regarding both total tumor burden and tumor burden in the liver, spleen and red marrow. The model also provides biodistribution information for absorbed dose calculations to tissues that are not directly sampled. Such information is important in determining the optimum therapeutic dose of radiolabeled antibody for a given patient.
Li+ transport properties of W substituted Li7La3Zr2O12 cubic lithium garnets (2013)

Lithium garnet Li7La3Zr2O12 (LLZ) sintered at 1230 °C has received considerable importance in recent times as result of its high total (bulk + grain boundary) ionic conductivity of 5 × 10−4 S cm−1 at room temperature. In this work we report Li+ transport process of Li7−2xLa3Zr2−xWxO12 (x = 0.3, 0.5) cubic lithium garnets. Among the investigated compounds, Li6.4La3Zr1.7W0.3O12 sintered relatively at lower temperature 1100 °C exhibits highest room temperature (30 °C) total (bulk + grain boundary) ionic conductivity of 7.89 × 10−4 S cm−1. The temperature dependencies of the bulk conductivity and relaxation frequency in the bulk are governed by the same activation energy. Scaling the conductivity spectra for both Li6.4La3Zr1.7W0.3O12 and Li6La3Zr1.5W0.5O12 sample at different temperatures merges on a single curve, which implies that the relaxation dynamics of charge carriers is independent of temperature. The shape of the imaginary part of the modulus spectra suggests that the relaxation processes are non-Debye in nature. The present studies supports the prediction of optimum Li+ concentration required for the highest room temperature Li+ conductivity in LixLa3M2O12 is around x = 6.4 ± 0.1.
Hyperoxia causes decreased expression of vascular endothelial growth factor and endothelial cell apoptosis in adult retina (1999)

Mice or humans with photoreceptor degenerations experience permeability and dropout of retinal capillaries. Loss of photoreceptors results in decreased oxygen usage and thinning of the retina with increased oxygen delivery to the inner retina. To investigate the possibility that increased tissue oxygen plays a role in the vascular damage, we exposed adult mice to hyperoxia, which also increases oxygen in the retina. After 1, 2, or 3 weeks of hyperoxia, there was a statistically significant decrease in retinal vascular density that was not reversible, and endothelial cell apoptosis was demonstrated by TUNEL staining. Mice exposed to hyperoxia and mice with photoreceptor degeneration both showed decreased expression of VEGF in the retina. After complete or near-complete degeneration of photoreceptors, there was increased expression of VEGF in RPE cells, which may explain the association of photoreceptor degeneration and neovascularization in or around the RPE. Increased expression of VEGF in photoreceptors of transgenic mice failed to prevent hyperoxia-induced retinal capillary dropout. These data suggest that increased oxygen in the retina, either by increased inspired oxygen or by photoreceptor degeneration, results in endothelial cell death and dropout of capillaries. Decreased expression of VEGF may be a contributing factor, but the situation may be more complicated for mature retinal vessels than it is for immature vessels, because VEGF replacement does not rescue mature retinal vessels, suggesting that other factors may also be involved.
Drug Delivery Systems (2006)

Abstract To obtain a given therapeutic response, the suitable amount of the active drug must be absorbed and transported to the site of action at the right time and the rate of input can then be adjusted to produce the concentrations required to maintain the level of the effect for as long as necessary. The distribution of the drug to tissues other than the sites of action and organs of elimination is unnecessary, wasteful, and a potential cause of toxicity. The modification of the means of delivering the drug by projecting and preparing new advanced drug delivery devices can improve therapy. The aim of advanced drug delivery devices is to control ( 1 ) the drug release rate from formulations or dosage forms, ( 2 ) the drug rate to reach absorbing membranes and surfaces, and ( 3 ) the site‐specific drug release. The control of drug release and the control of body distribution are the two most important features of the various drug delivery devices. The most important drug delivery devices were taken into consideration and their most usefull and successful applications in disease therapy were discussed. In particular, the attention was focused on the use of microelectro‐mechanical‐systems, cyclodextrins (the most representative of molecular drug delivery systems), microemulsion and organogel (supramolecular aggregates), and colloidal carriers (liposomes, niosomes, ethosomes, ultradeformable vesicles, nanoparticles) for delivery of drugs.
Inhibitors of glycoprotein processing alter T-cell proliferative responses to antigen and to interleukin 2. (1988)

Most of the cell-surface molecules involved in T-cell immune responses are N-linked glycoproteins. We have investigated the effects of inhibitors of glycoprotein processing on specific T-cell functions, with the dual aims of examining the functional role of carbohydrate and of testing the usefulness of such compounds as immunomodulators. Treatment of a cloned murine helper T-cell line with these inhibitors differentially affects the proliferative response of the cell, depending upon the nature of the stimulus. Treatment with the plant alkaloid swainsonine, which inhibits the processing mannosidase II and causes the accumulation of glycoproteins bearing hybrid-type oligosaccharide structures, enhances the proliferative response of the T-cell clone to antigen and to the mitogen concanavalin A. Treatment with another plant alkaloid, castanospermine, which inhibits glucosidase I and causes the accumulation of glucose-containing high-mannose structures, has the opposite effect and inhibits the proliferative response of the T cell to antigen. Cell-surface oligosaccharide alteration does not affect antigen recognition, as judged by the lack of effect of either drug on interleukin 2 production following antigen stimulation. Cells treated with either alkaloid proliferate poorly to exogenous interleukin 2 and may have defective interleukin 2 receptor function. Swainsonine-treated cells apparently have compensatory alterations that can overcome the reduced responsiveness to interleukin 2. Antibody-binding studies indicate that normal quantities of many cell-surface molecules, including the T-cell receptor for antigen, are expressed by the treated cells.