gebhart/patrepeval huggingface dataset:
The safety and efficacy of oral methylnaltrexone in preventing morphine-induced delay in oral-cecal transit time* (1997)

Methylnaltrexone is a quaternary opioid antagonist with limited ability to cross the blood-brain barrier that has the potential to antagonize the peripherally mediated gastrointestinal effects of opioids. In recent trials in human volunteers, we demonstrated that intravenous methylnaltrexone prevented morphine-induced changes in gastroin-testinal motility and transit, without affecting analgesia. In this study, 14 healthy volunteers were first given three ascending oral doses of methylnaltrexone to obtain safety and tolerance data (phase A study). In phase B, these subjects were then given single-blind oral placebo and intravenous placebo, followed by randomized, double-blind oral placebo and intravenous morphine (0.05 mg/kg) or oral methylnaltrexone (19.2 mg/kg, an established highest and safe dose based on previous administrations of two smaller doses of 0.64 mg/kg and 6.4 mg/kg in phase A) and intravenous morphine (0.05 mg/kg). Oral-cecal transit time was assessed by the pulmonary hydrogen measurement technique after lactulose ingestion. Morphine significantly increased oral-cecal transit time from 114.6 ± 37.0 minutes (mean ± SD) to 158.6 ± 50.2 minutes (p < 0.001). Oral methylnaltrexone (19.2 mg/kg) completely prevented morphine-induced increase in oral-cecal transit time (110.4 ± 45.0 minutes; not significant compared with baseline; p < 0.005 compared with morphine alone). These sessions were then followed by single-blind evaluations of descending doses of methylnaltrexone. We observed that 6.4 mg/kg oral methylnaltrexone significantly attenuated the morphine-induced delay in oral-cecal transit time (p < 0.005 compared with morphine alone), and a dose-dependent response was obtained. There was no correlation between oral methylnaltrexone effects on the transit time and the drug plasma concentration, suggesting direct preferential luminal effects of oral methylnaltrexone. Oral methylnaltrexone may have a clinical value in the prevention and treatment of constipation induced by long-term opioid use. Clinical Pharmacology & Therapeutics (1997) 61, 467–475; doi:
Protein deamidation (2002)

A completely automatic computerized technique for the quantitative estimation of the deamidation rates of any protein for which the three-dimensional structure is known has been developed. Calculations of the specific deamidation rates of 170,014 asparaginyl residues in 13,335 proteins have been carried out. The calculated values have good quantitative reliability when compared with experimental measurements. These rates demonstrate that deamidation may be a biologically relevant phenomenon in a remarkably large percentage of proteins.
Fixed combinations of topical glaucoma medications (2004)

Fixed combinations offer benefits of convenience, cost, and safety, but limit individualization of dosing. Understanding the advantages and disadvantages of prescribing fixed combinations facilitates success in using these products in clinical practice.
Angiogenesis: Implications for rheumatoid arthritis (1998)

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In Vitro Infection of Human Peripheral Blood Mononuclear Cells by GB Virus C/Hepatitis G Virus (1999)

GB virus C (GBV-C), also known as hepatitis G virus, is a recently discovered flavivirus-like RNA agent with unclear pathogenic implications. To investigate whether human peripheral blood mononuclear cells (PBMC) are susceptible to in vitro GBV-C infection, we have incubated PBMC from four healthy blood donors with a human GBV-C RNA-positive serum. By means of (i) strand-specific reverse transcription-PCR, cloning, and sequencing; (ii) sucrose ultracentrifugation and RNase sensitivity assays; (iii) fluorescent in situ hybridization; and (iv) Western blot analysis, it has been demonstrated that GBV-C is able to infect in vitro cells and replicate for as long as 30 days under the conditions developed in our cell culture system. The concentration of GBV-C RNA increased during the second and third weeks of culture. The titers of the genomic strand were 10 times higher than the titers of the antigenomic strand. In addition, the same predominant GBV-C sequence was found in all PBMC cultures and in the in vivo-GBV-C-infected PBMC isolated from the donor of the inoculum. GBV-C-specific fluorescent in situ hybridization signals were confined to the cytoplasm of cells at different times during the culture period. Finally, evidence obtained by sucrose ultracentrifugation, RNase sensitivity assays, and Western blot analysis of the culture supernatants suggests that viral particles are released from in vitro-GBV-C-infected PBMC. In conclusion, our study has demonstrated, for the first time, GBV-C replication in human lymphoid cells under experimental in vitro infection conditions.
Serratia marcescens chitobiase is a retaining glycosidase utilizing substrate acetamido group participation (1997)

The stereochemistry of the reaction catalysed by Serratia marcescens chitobiase was determined by HPLC separation of the anomers of N-acetylglucosamine produced during the hydrolysis of p-nitrophenyl N-acetyl-beta-d-glucosaminide (PNP-GlcNAc). In the early stages of the reaction, the beta-anomer was found to prevail, whereas the alpha-anomer dominated at mutarotation equilibrium. This established that chitobiase hydrolyses glycosidic bonds with overall retention of the anomeric configuration. Chitobiase-catalysed hydrolysis of PNP-GlcNAc was competitively inhibited by a series of chito-oligosaccharides (degree of polymerization 2-5) that were selectively de-N-acetylated at their non-reducing end. The results are in accord with the participation of the acetamido group at C-2 of the substrate in the catalytic mechanism of chitobiase and related enzymes.
Protein A Reactivity of Various Mammalian Immunoglobulins (1978)

Serum samples and immunoglobulin fractions of eight mammalian species were applied to a Sepharose--protein A column. As with the human immunoglobulin subclasses IgG1, IgG2 and IgG4, all examined IgG classes and subclasses were bound to a greater or lesser extent to protein A. However, the binding of IgG1 of ruminants was very poor. Polyclonal IgM and IgA of the pig, the dog and the cat may be separated in protein A reactive and protein A non-reactive fractions. In addition, monoclonal canine IgM and IgA partially reacted with protein A. In combination with methods such as ammonium sulphate precipitation, ion exchange chromatography and gel-filtration, affinity chromatography with protein A is recommended for the rapid purification of certain Ig (sub)classes of a number of mammalian species.
Cardiac MR image segmentation using deformable models (2002)

Describes efficient and robust deformable model based techniques for segmentation of ventricular boundaries in cardiac MR images. Starting with a user specified approximate boundary or an interior point of the left ventricle for one ED slice, the authors' algorithms generate contours for inner and outer walls, and automatically propagate them to other slices in the ED phase (spatial propagation) and to slices in all the phases (temporal propagation) of the cardiac study. The algorithms are based on steepest descent as well as dynamic programming strategies integrated via multiscale analysis. The ventricular boundaries are used to construct a 3-D model for visualization and to compute volume based diagnostic quantities. The algorithms have been incorporated into a user interface which can load, sort, visualize, and analyze a cardiac study an less than 10 minutes. The system has been tested on a dozen volunteers and patients (1000+ images) with excellent results.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Overexpression of the insulin-like growth factor-1 receptor and autocrine stimulation in human cervical cancer cells. (1996)

We characterized mechanisms of growth control involving insulin-like growth factor-1 (IGF-1), IGF-2, and IGF-1 receptor (IGF-1R) by investigating their expression in human cervical cancer cell lines, primary cervical tumor cell cultures, and normal ectocervical epithelial cells maintained in short-term culture. By reverse transcription followed by PCR, IGF-1 mRNA was not detected in any of the cell lines, whereas IGF-2 mRNA transcripts were detected in all of them. Using the RNase protection assay, low levels of IGF-2 mRNA were also detected in all of the cervical cancer cell lines, primary cervical tumor cell cultures, and normal ectocervical cultures tested, but no IGF-1 transcripts were detected. Scatchard analysis revealed 3- and 5-fold increases in IGF-1R expression by the primary cervical cancer cell cultures and cervical cancer cell lines, respectively, compared with the normal ectocervical cells. In proliferation assays, epidermal growth factor (EGF) consistently enhanced cervical cancer cell growth, but an antisense oligonucleotide to IGF-2 uniformly inhibited the EGF-induced mitogenic effect. These studies suggest that autocrine production of IGF-2 and overexpression of the IGF-1R are important components controlling the proliferation of cervical carcinoma cells, and that autocrine IGF-2 production in cervical cancer cells may participate in the mitogenic signaling of EGF.
Protective effect of injinhotang and its components on acetaminophen-induced hepatoxicity in rats (2005)

Acetaminophen, which causes acute liver min in humans and animals, has made useful inducer of hepatoxicity for studying hepatopreventive drugs. Injinhotang is known as one of the hepatopreventive drugs. However, its mechanism of recovery of hepatoxicity treated with acetaminophen is poorly understood. this study was performed to observe the antioxidative effect of injinhotang extract and its several combination groups. The results were obtained as follows:1. In the study on free radical scavenging effect in vitro(the suppressing effect on peroxidation of linoleic acid on concentration, the scavenging effect of DPPH radical, inhibitory effect of superoxide in xanthine-xanthine oxidase system and the inhibitory effect on lipid peroxidation reaction by hydroxy radical in H2O2-Fe2+system, injinhotang have more effect than its components groups relatively. 2. In the study on antioxidants system in vivo(the level of serum LPO, the level of hepatic LPO, catalase, GSH, GST), only injnhotang has a significant effect. 3. In the study on hepatotoxicity(GOT, GPT, -GTP, ALP, LDH, b ilirubin), only injinhotang has a significant effect. These results suggest that injinhotang has the protective effect on acetaminophen-induced hepatoxicity. The mechanisms of these are supposed to be involved in antioxidant and three drugs' cooperative synergy effect.
Chimerization of mu‐9 (1997)

Mu-9 is a murine monoclonal antibody that is directed against
Multiple subpial transection: a new approach to the surgical treatment of focal epilepsy (1989)

A new operative approach has been designed for the relief of medically intractable focal epilepsy. It is intended particularly to be used in those cases where the epileptogenic lesion lies in "unresectable" cortex; that is, those cerebral regions subserving speech, memory, and primary motor and sensory function. The procedure is based upon experimental evidence indicating 1) that epileptogenic discharge requires substantial side-to-side or horizontal interaction of cortical neurons, and 2) that the major functional properties of cortical tissue depend upon the vertical fiber connections of the columnar units. The technique requires severing of tangential intracortical fibers while preserving the vertical fiber connections of both incoming and outgoing nerve pathways and of the penetrating blood vessels which also have a vertical orientation. In this study, the effect of multiple subpial transection was assessed on both function and seizure control. The effect on function was reviewed in 32 cases; only 20 cases were evaluated with respect to seizure control, since a follow-up period of 5 years or more (5 to 22 years) is required before conclusions can be drawn. Multiple subpial transection was applied to the precentral gyrus in 16 cases, the postcentral gyrus in six, Broca's area in five, and Wernicke's area in five. With respect to function, the major finding was that none of the 32 patients has suffered a clinically significant behavioral deficit (although subtle deficits could be detected by careful neurological examination). Complete control of seizures has been obtained in 11 (55%) of the 20 cases evaluated. Nine patients developed recurrent seizures consequent to progressive disease unsuspected before operation (Rasmussen's encephalitis in five, tumor in three, and subacute sclerosing panencephalitis in one). In none of these cases, however, did the recurrent seizures arise in the transected zone. Thus, the results indicate that multiple subpial transection is about as effective as standard excisional therapy, and can be successfully employed when epileptogenic lesions encroach upon cortical territories, the removal of which would be functionally incapacitating.
Eosinophil Sequestration and Activation Are Associated with the Onset and Severity of Systemic Adverse Reactions following the Treatment of Onchocerciasis with Ivermectin (1999)

To investigate the role of eosinophil activation and sequestration in the development and severity of adverse reactions after the treatment of Onchocerca volvulus infection, 40 O. volvulus-infected Ghanaians were randomized to receive placebo or standard- or high-dose ivermectin. Subjects were examined for typical physiologic and clinical events before and up to 48 h after treatment. Plasma samples were tested for interleukin (IL)-5 and eosinophil degranulation products (e.g., eosinophil-derived neurotoxin, EDN). After treatment, peripheral eosinophil counts declined in ivermectin-treated groups (P<.001), whereas circulating levels of IL-5 (P<.01) and EDN (P<.05) increased. Cumulative levels of IL-5 and EDN correlated with reaction scores (P<.01). High-dose ivermectin was associated with more-severe reactions, more-profound eosinopenia, and higher circulating levels of IL-5 and EDN, compared with the standard dose. These results suggest that eosinophil sequestration and activation/degranulation are associated with the initiation and severity of ivermectin-associated adverse reactions.
Listeria monocytogenes-infected human umbilical vein endothelial cells: internalin-independent invasion, intracellular growth, movement, and host cell responses (1997)

The interaction of Listeria monocytogenes with human umbilical vein endothelial cells was studied. We show that L. monocytogenes invades human umbilical vein endothelial cells independently of internalin A, internalin B, internalin C, and ActA. L. monocytogenes replicates efficiently inside the cells and moves intracellularly by the induction of actin polymerization. We further show that L. monocytogenes-infection of human umbilical vein endothelial cells induces interleukin-6 and interleukin-8 expression during the first 6 h of infection. The expression of MCP-1 and the adhesion molecules VCAM-1 and ICAM-1 was not altered under the experimental conditions used here.
Methyl Ethers of Podophyllotoxin-Related Cyclolignans (1995)

Methyl ethers of podophyllotoxin [1] and its epimers at positions 7 and 8' were obtained through the corresponding chlorinated or brominated derivatives at position 7. Additionally, the corresponding diol methyl ethers were obtained by reducing the lactone with LiAlH4. 7-O-Methylepipicropodophyllotoxin [12], 7-O-methylpicropodophyllotoxin [13], the diol methyl ethers 15-18 and the corresponding diacetates are described here for the first time. Most of the cyclolignans obtained were evaluated for their cytotoxic activity.
Gene transfer of truncated NGF receptor clones leads to cell surface expression in mouse fibroblasts (1989)

Transfection of recombinant bacteriophage clones encoding human NGF receptor sequences resulted in cell surface expression in mouse fibroblasts. Unexpectedly, receptors were expressed even after transfection with phage clones which lack 5' gene sequences. Stable transformants were purified and analyzed in detail. S1 nuclease protection and primer extension analysis revealed that an initiation site lies within an intron sequence in the middle of the receptor gene. A truncated mRNA transcript was detected that allowed for the expression of NGF receptors capable of binding to NGF. Since the original phage clones lacked the first two exons, these results suggest that the normal N-terminal sequences may not be necessary for cell surface expression and binding to NGF.
Modular Access to Structurally Switchable 3D Discrete DNA Assemblies (2007)

In this contribution we describe a facile method to access a large number of three-dimensional discrete DNA assemblies. The approach involves the use of single-stranded and cyclic 2D DNA building blocks, of predefined geometry, as the faces or sides of the objects to be constructed. Any target three-dimensional discrete object that could be retrosynthetically broken down into a combination of the discrete 2D shapes, could in principle be easily accessed using this method. Using triangle 3, square 4, pentagon 5, and hexamer 6, we constructed triangular, cubic, pentameric, and hexameric prisms, as well as the more complex heteroprism HP and biprism BP assemblies in quantitative yields. The use of single-stranded DNA building blocks inherently allows for dynamic character and addressability. Using a series of rigidifying and eraser strands, we generated a triangular prism capable of structural oscillation between three predefined lengths. The easy access to a large number of complex three-dimensional discrete DNA objects that are also dynamic, in response to external stimuli, promises to expand the applications of 3D DNA construction in many areas of nanoscience, drug delivery, and biological chemistry.
In Vitro Fibrinolytic Activity of Recombinant Tissue-Type Plasminogen Activator in the Plasma of Various Primate Species (1984)

The ratio of fibrinolytic to fibrinogenolytic effect of recombinant human tissue-type plasminogen activator was investigated at several concentrations in an in vitro system consisting of 125I-fibrin labeled autologous plasma clots immersed in the plasma of several different primate species. A concentration-dependent fibrinolysis was obtained in each case; however, the degree of fibrinolysis differed markedly from one primate species to the other. At a concentration of 30 IU/ml (300 ng/ml) of recombinant tissue-type plasminogen activator nearly complete thrombolysis was achieved within 4 hr in human plasma, in the chimpanzee, in the cynomolgus macaque, in the bonnet macaque and in the rhesus macaque. The common baboon, the olive baboon and the squirrel monkey were rather resistant to thrombolysis. In all species the thrombolysis achieved was not associated with fibrinogenolysis nor with significant decreases in plasminogen or alpha 2-antiplasmin.
Identification of a Long-Chain Polyunsaturated Fatty Acid Acyl-Coenzyme A Synthetase from the Diatom Thalassiosira pseudonana (2005)

The draft genome of the diatom Thalassiosira pseudonana was searched for DNA sequences showing homology with long-chain acyl-coenzyme A synthetases (LACSs), since the corresponding enzyme may play a key role in the accumulation of health-beneficial polyunsaturated fatty acids (PUFAs) in triacylglycerol. Among the candidate genes identified, an open reading frame named TplacsA was found to be full length and constitutively expressed during cell cultivation. The predicted amino acid sequence of the corresponding protein, TpLACSA, exhibited typical features of acyl-coenzyme A (acyl-CoA) synthetases involved in the activation of long-chain fatty acids. Feeding experiments carried out in yeast (Saccharomyces cerevisiae) transformed with the algal gene showed that TpLACSA was able to activate a number of PUFAs, including eicosapentaenoic acid and docosahexaenoic acid (DHA). Determination of acyl-CoA synthetase activities by direct measurement of acyl-CoAs produced in the presence of different PUFA substrates showed that TpLACSA was most active toward DHA. Heterologous expression also revealed that TplacsA transformants were able to incorporate more DHA in triacylglycerols than the control yeast.
Deep Speaker: an End-to-End Neural Speaker Embedding System (2017)

We present Deep Speaker, a neural speaker embedding system that maps utterances to a hypersphere where speaker similarity is measured by cosine similarity. The embeddings generated by Deep Speaker can be used for many tasks, including speaker identification, verification, and clustering. We experiment with ResCNN and GRU architectures to extract the acoustic features, then mean pool to produce utterance-level speaker embeddings, and train using triplet loss based on cosine similarity. Experiments on three distinct datasets suggest that Deep Speaker outperforms a DNN-based i-vector baseline. For example, Deep Speaker reduces the verification equal error rate by 50% (relatively) and improves the identification accuracy by 60% (relatively) on a text-independent dataset. We also present results that suggest adapting from a model trained with Mandarin can improve accuracy for English speaker recognition.
Voltage-Driven DNA Translocations through a Nanopore (2001)

We measure current blockade and time distributions for single-stranded DNA polymers during voltage-driven translocations through a single alpha-hemolysin pore. We use these data to determine the velocity of the polymers in the pore. Our measurements imply that, while polymers longer than the pore are translocated at a constant speed, the velocity of shorter polymers increases with decreasing length. This velocity is nonlinear with the applied field. Based on this data, we estimate the effective diffusion coefficient and the energy penalty for extending a molecule into the pore.
Structure Based Design of Non-Natural Peptidic Macrocyclic Mcl-1 Inhibitors (2016)

Mcl-1 is a pro-apoptotic BH3 protein family member similar to Bcl-2 and Bcl-xL. Overexpression of Mcl-1 is often seen in various tumors and allows cancer cells to evade apoptosis. Here we report the discovery and optimization of a series of non-natural peptide Mcl-1 inhibitors. Screening of DNA-encoded libraries resulted in hit compound <b>1</b>, a 1.5 μM Mcl-1 inhibitor. A subsequent crystal structure demonstrated that compound <b>1</b> bound to Mcl-1 in a β-turn conformation, such that the two ends of the peptide were close together. This proximity allowed for the linking of the two ends of the peptide to form a macrocycle. Macrocyclization resulted in an approximately 10-fold improvement in binding potency. Further exploration of a key hydrophobic interaction with Mcl-1 protein and also with the moiety that engages Arg256 led to additional potency improvements. The use of protein-ligand crystal structures and binding kinetics contributed to the design and understanding of the potency gains. Optimized compound <b>26</b> is a <3 nM Mcl-1 inhibitor, while inhibiting Bcl-2 at only 5 μM and Bcl-xL at >99 μM, and induces cleaved caspase-3 in MV4-11 cells with an IC<sub>50</sub> of 3 μM after 6 h.