gebhart/patrepeval huggingface dataset:
Estimate of the Frequency of Human Immunodeficiency Virus Type 1 Protease Inhibitor Resistance within Unselected Virus Populations In Vitro (1998)

The frequency of drug-resistant human immunodeficiency virus type 1 (HIV-1) variants in virus populations not previously exposed to drug was determined in vitro by using HIV-1RF and the protease inhibitor SC-55389A. Two variants with single mutations responsible for drug resistance (V82A and N88S) were quantifiably isolated after only one round of replication, yielding a crude frequency estimate of at least 1 SC-55389A-resistant variant per 3.5 x 10(5) wild-type infectious units.
Mitochondrial and peroxisomal fatty acid oxidation in liver homogenates and isolated hepatocytes from control and clofibrate-treated rats. (1979)

Mitochondrial and peroxisomal fatty acid oxidation were compared in whole liver homogenates. Oxidation of 0.2 mM palmitoyl-CoA or oleate by mitochondria increased rapidly with increasing molar substrate:albumin ratios and became saturated at ratios below 3, while peroxisomal oxidation increased more slowly and continued to rise to reach maximal activity in the absence of albumin. Under the latter condition mitochondrial oxidation was severely depressed. In homogenates from normal liver peroxisomal oxidation was lower than mitochondrial oxidation at all ratios tested except when albumin was absent. In contrast with mitochondrial oxidation, peroxisomal oxidation did not produce ketones, was cyanide-insensitive, was not dependent on carnitine, and was not inhibited by (+)-octanoylcarnitine, malonyl-CoA and 4-pentenoate. Mitochondrial oxidation was inhibited by CoASH concentrations that were optimal for peroxisomal oxidation. In the presence of albumin, peroxisomal oxidation was stimulated by Triton X-100 but unaffected by freeze-thawing; both treatments suppressed mitochondrial oxidation. Clofibrate treatment increased mitochondrial and peroxisomal oxidation 2- and 6- to 8-fold, respectively. Peroxisomal oxidation remained unchanged in starvation and diabetes. Fatty acid oxidation was severely depressed by cyanide and (+)-octanoylcarnitine in hepatocytes from normal rats. Hepatocytes from clofibrate-treated rats, which displayed a 3- to 4-fold increase in fatty acid oxidation, were less inhibited by (+)-octanoylcarnitine. Hydrogen peroxide production was severalfold higher in hepatocytes from treated animals oxidizing fatty acids than in control hepatocytes. Assuming that all H2O2 produced during fatty acid oxidation was due to peroxisomal oxidation, it was calculated that the contribution of the peroxisomes to fatty acid oxidation was less than 10% both in cells from control and clofibrate-treated animals.
Self-Management Education for Adults With Type 2 Diabetes (2002)

Self-management education improves GHb levels at immediate follow-up, and increased contact time increases the effect. The benefit declines 1-3 months after the intervention ceases, however, suggesting that learned behaviors change over time. Further research is needed to develop interventions effective in maintaining long-term glycemic control.
Abstract 4523: Population pharmacokinetic (PPK) modeling of onapristone in patients (pts) with progesterone receptor (PR)-expressing cancers (2015)

Abstract Background: Onapristone is a type I PR antagonist, which prevents PR-induced DNA transcription. Onapristone anti-cancer activity is well documented. An extended-release (ER) tablet formulation of onapristone was designed to address the liver function test (LFT) elevations seen with immediate-release (IR) onapristone. A phase 1 study with onapristone in patients with tumors expressing PR is underway. Objectives included determining the PK profile of ER onapristone using a PPK approach. Materials and methods: This is an ongoing multi-center, open-label, randomized, parallel-group, 2-stage ph1 study. Female pts ≥18 yrs with tumors expressing PR are eligible. The Stage 1 primary endpoint is the recommended ph2 dose of ER onapristone; secondary endpoints include: safety, efficacy, and PK. Pts received onapristone ER 10, 20, 30, 40 or 50 mg BID, or onapristone IR tablets 100 mg QD until progressive disease or intolerability. PK blood samples from 8 time points were collected over 12 h post-dose Day 1 for the ER and 9 blood samples over 24 h post-dose for the IR formulation. Onapristone plasma concentrations were measured using validated UPLC with tandem mass spectrometry detection (range 1-250 ng/mL). Monolix V4.1 was used to calculate absorption constant (Ka); apparent clearance (CL/F); inter-compartmental clearance (Q); apparent distribution volume (V1/F), 2nd compartment distribution volume (V2) and bioavailability (F) of ER vs IR. Results: Stage 1 is complete. 42 pts have validated PK data. A 2-compartment open model adequately described the total onapristone time-concentration curve with linear elimination. Results are in Table 1. Table 1.Estimated PK parameters for onapristone in pts with PR-expressing cancers (n = 42)ParameterValueRelative standard error (%)Ka0.191 h-114CL/F1.51 L/h20Q3.11 L/h25V1/F5.41 L25V241.1 L45F60%20 Conclusions: The PPK modeling described the plasma onapristone time-concentration curves well. A central volume equivalent to the circulating blood volume and a large volume of the deep compartment suggest a large tissue diffusion. PPK/PD modeling to explore safety and efficacy is ongoing, with no overt PK/safety relationship detected. Citation Format: Keyvan Rezai, Paul Cottu, Samuel Huguet, Mario Campone, Antoine Italiano, Andrea Varga, Jacques Bonneterre, Alexandra Leary, Marie-Paule Sablin, Stefan Proniuk, Alice Bexon, Erard Gilles, Joseph Bisaha, Alexander Zukiwski, Francois Lokiec. Population pharmacokinetic (PPK) modeling of onapristone in patients (pts) with progesterone receptor (PR)-expressing cancers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4523. doi:10.1158/1538-7445.AM2015-4523
Dissection of Autophagosome Formation Using Apg5-Deficient Mouse Embryonic Stem Cells (2001)

In macroautophagy, cytoplasmic components are delivered to lysosomes for degradation via autophagosomes that are formed by closure of cup-shaped isolation membranes. However, how the isolation membranes are formed is poorly understood. We recently found in yeast that a novel ubiquitin-like system, the Apg12-Apg5 conjugation system, is essential for autophagy. Here we show that mouse Apg12-Apg5 conjugate localizes to the isolation membranes in mouse embryonic stem cells. Using green fluorescent protein-tagged Apg5, we revealed that the cup-shaped isolation membrane is developed from a small crescent-shaped compartment. Apg5 localizes on the isolation membrane throughout its elongation process. To examine the role of Apg5, we generated Apg5-deficient embryonic stem cells, which showed defects in autophagosome formation. The covalent modification of Apg5 with Apg12 is not required for its membrane targeting, but is essential for involvement of Apg5 in elongation of the isolation membranes. We also show that Apg12-Apg5 is required for targeting of a mammalian Aut7/Apg8 homologue, LC3, to the isolation membranes. These results suggest that the Apg12-Apg5 conjugate plays essential roles in isolation membrane development.
Terminal Base Pairs of Oligodeoxynucleotides: Imino Proton Exchange and Fraying (1995)

We have estimated the dissociation constant of the terminal base pairs of the B-DNA duplexes formed by 5'-d(CGCGATCGCG) and 5'-d(TAGCGCTA) by two methods, one based on the change in imino proton chemical shift with temperature and the other on the apparent pK shift of the imino proton, as monitored by the change in chemical shift of aromatic protons. These methods do not rely on imino proton exchange, whose rate was also measured. (1) The effect of ammonia on the imino proton exchange rate of the terminal pair of the 5'-d(CGCGATCGCG) duplex is 67 times less than on the isolated nucleoside. This provides an upper limit on the exchange rate from the closed pair. In fact, the effect is just as predicted from the dissociation constant, assuming that there is no exchange at all from the closed pair and that, as has been argued previously, external catalysts act on the open state as they do on the isolated nucleoside. The inhibition of catalyzed proton exchange in the closed pair, despite exposure of one face of the pair to solvent, is a new feature of the exchange process. It will allow determination of the dissociation constant of terminal pairs from the exchange rate. (2) Intrinsic catalysis of proton exchange is less efficient for the terminal pair than for an internal one. A possible explanation is that proton transfer across the water bridge responsible for intrinsic catalysis is slower, as expected if the open-state separation of the bases is larger in a terminal pair. This observation may lead to a direct method for the study of fraying. (3) At 0 degrees C, the dissociation constant of the second pair of the 5'-d(CGCGATCGCG) duplex is close to the square of the constant for the terminal pair, as predicted from a simple model of fraying. The enthalpy and entropy of opening of the terminal pairs may be compared with those of nearest neighbor interactions derived from calorimetry [Breslauer, K. J., et al. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 3746-3750].
In-network live snapshot service for recovering virtual infrastructures (2011)

Infrastructure as a Service (IaaS) has become an increasingly popular type of service for both private and public clouds. The virtual infrastructures that enable IaaS support multitenancy by multiplexing the computational resources of data centers and result in substantial reductions in operational costs. Since hardware and software failures occur on a routine basis in large-scale systems, it is imperative for cloud providers to offer various failure recovery options for distributed services hosted on such infrastructures. In this article we present GENI-VIOLIN, a new cloud capability that can checkpoint a stateful distributed service while incurring very low overhead. The unique aspect of GENI-VIOLIN compared to previous work is that GENI-VIOLIN exploits programmable OpenFlow switches to provide checkpointing services in the network, thereby requiring minimal changes to the end host virtualization framework. We have developed a prototype of GENI-VIOLIN using the GENI infrastructure, and have demonstrated GENI-VIOLIN's checkpoint and restore capability across multiple GENI sites.
Nucleoside triphosphate-dependent restriction enzymes (2001)

The known nucleoside triphosphate-dependent restriction enzymes are hetero-oligomeric proteins that behave as molecular machines in response to their target sequences. They translocate DNA in a process dependent on the hydrolysis of a nucleoside triphosphate. For the ATP-dependent type I and type III restriction and modification systems, the collision of translocating complexes triggers hydrolysis of phosphodiester bonds in unmodified DNA to generate double-strand breaks. Type I endonucleases break the DNA at unspecified sequences remote from the target sequence, type III endonucleases at a fixed position close to the target sequence. Type I and type III restriction and modification (R-M) systems are notable for effective post-translational control of their endonuclease activity. For some type I enzymes, this control is mediated by proteolytic degradation of that subunit of the complex which is essential for DNA translocation and breakage. This control, lacking in the well-studied type II R-M systems, provides extraordinarily effective protection of resident DNA should it acquire unmodified target sequences. The only well-documented GTP-dependent restriction enzyme, McrBC, requires methylated target sequences for the initiation of phosphodiester bond cleavage.
Multistage nanoparticle delivery system for deep penetration into tumor tissue (2011)

Current Food and Drug Administration-approved cancer nanotherapeutics, which passively accumulate around leaky regions of the tumor vasculature because of an enhanced permeation and retention (EPR) effect, have provided only modest survival benefits. This suboptimal outcome is likely due to physiological barriers that hinder delivery of the nanotherapeutics throughout the tumor. Many of these nanotherapeutics are ≈ 100 nm in diameter and exhibit enhanced accumulation around the leaky regions of the tumor vasculature, but their large size hinders penetration into the dense collagen matrix. Therefore, we propose a multistage system in which 100-nm nanoparticles "shrink" to 10-nm nanoparticles after they extravasate from leaky regions of the tumor vasculature and are exposed to the tumor microenvironment. The shrunken nanoparticles can more readily diffuse throughout the tumor's interstitial space. This size change is triggered by proteases that are highly expressed in the tumor microenvironment such as MMP-2, which degrade the cores of 100-nm gelatin nanoparticles, releasing smaller 10-nm nanoparticles from their surface. We used quantum dots (QD) as a model system for the 10-nm particles because their fluorescence can be used to demonstrate the validity of our approach. In vitro MMP-2 activation of the multistage nanoparticles revealed that the size change was efficient and effective in the enhancement of diffusive transport. In vivo circulation half-life and intratumoral diffusion measurements indicate that our multistage nanoparticles exhibited both the long circulation half-life necessary for the EPR effect and the deep tumor penetration required for delivery into the tumor's dense collagen matrix.
PEG-Labeled Nucleotides and Nanopore Detection for Single Molecule DNASequencing by Synthesis (2012)

We describe a novel single molecule nanopore-based sequencing by synthesis (Nano-SBS) strategy that can accurately distinguish four bases by detecting 4 different sized tags released from 5'-phosphate-modified nucleotides. The basic principle is as follows. As each nucleotide is incorporated into the growing DNA strand during the polymerase reaction, its tag is released and enters a nanopore in release order. This produces a unique ionic current blockade signature due to the tag's distinct chemical structure, thereby determining DNA sequence electronically at single molecule level with single base resolution. As proof of principle, we attached four different length PEG-coumarin tags to the terminal phosphate of 2'-deoxyguanosine-5'-tetraphosphate. We demonstrate efficient, accurate incorporation of the nucleotide analogs during the polymerase reaction, and excellent discrimination among the four tags based on nanopore ionic currents. This approach coupled with polymerase attached to the nanopores in an array format should yield a single-molecule electronic Nano-SBS platform.
Quantitative evaluation of fucose reducing effects in a humanized antibody on Fcγ receptor binding and antibody-dependent cell-mediated cytotoxicity activities (2012)

The presence or absence of core fucose in the Fc region N-linked glycans of antibodies affects their binding affinity toward FcγRIIIa as well as their antibody-dependent cell-mediated cytotoxicity (ADCC) activity. However, the quantitative nature of this structure-function relationship remains unclear. In this study, the in vitro biological activity of an afucosylated anti-CD20 antibody was fully characterized. Further, the effect of fucose reduction on Fc effector functions was quantitatively evaluated using the afucosylated antibody, its "regular" fucosylated counterpart and a series of mixtures containing varying proportions of "regular" and afucosylated materials. Compared with the "regular" fucosylated antibody, the afucosylated antibody demonstrated similar binding interactions with the target antigen (CD20), C1q and FcγRIa, moderate increases in binding to FcγRIIa and IIb, and substantially increased binding to FcγRIIIa. The afucosylated antibodies also showed comparable complement-dependent cytotoxicity activity but markedly increased ADCC activity. Based on EC 50 values derived from dose-response curves, our results indicate that the amount of afucosylated glycan in antibody samples correlate with both FcγRIIIa binding activity and ADCC activity in a linear fashion. Furthermore, the extent of ADCC enhancement due to fucose depletion was not affected by the FcγRIIIa genotype of the effector cells.
A PARALLEL FAST MULTIPOLE METHOD FOR THE HELMHOLTZ EQUATION (1995)

Presented is a parallel algorithm based on the fast multipole method (FMM) for the Helmholtz equation. This variant of the FMM is useful for computing radar cross sections and antenna radiation patterns. The FMM decomposes the impedance matrix into sparse components, reducing the operation count of the matrix-vector multiplication in iterative solvers to O(N 3/2 ) (where N is the number of unknowns). The parallel algorithm divides the problem into groups and assigns the computation involved with each group to a processor node. Careful consideration is given to the communications costs. A time complexity analysis of the algorithm is presented and compared with empirical results from a Paragon XP/S running the lightweight Sandia/University of New Mexico operating system (SUNMOS). For a 90,000 unknown problem running on 60 nodes, the sparse representation fits in memory and the algorithm computes the matrix-vector product in 1.26 seconds. It sustains an aggregate rate of 1.4 Gflop/s. The corresponding dense matrix would occupy over 100 Gbytes and, assuming that I/O is free, would require on the order of 50 seconds to form the matrix-vector product.
Investigation of Phenolic Bioisosterism in Opiates:  3-Sulfonamido Analogues of Naltrexone and Oxymorphone (2000)

[formula: see text] The phenolic hydroxy group of opiate-derived ligands is of known importance for biological activity. On the basis of its putative role as a hydrogen-bonding donor in the interaction with opioid receptors, it was replaced with a sulfonamide group because of their similar pKa values. The first thebaine-derived 3-amino (8a, 8b) and subsequent sulfonamide analogues (10a, 10b) were synthesized from naltrexone (1a) and oxymorphone (1b) in a linear nine-step synthesis. The sulfonamides were tested in vitro and found inactive.
Emergence of a New Norovirus Genotype II.4 Variant Associated with Global Outbreaks of Gastroenteritis (2006)

Norovirus (NoV) is highly infectious and is the major cause of outbreak gastroenteritis in adults, with pandemic spread of the virus being reported in 1995 and 2002. The NoV genome is genetically diverse, which has hampered development of sensitive molecular biology-based methods. In this study we report on a nested reverse transcriptase PCR (nRT-PCR) that was designed to amplify the highly conserved 3' end of the polymerase region and the 5' end of the capsid gene of NoV genogroup II (GII). The nRT-PCR was validated with strains isolated from sporadic and outbreak cases between 1997 and 2004 in New South Wales, Australia. Phylogenetic analysis identified six genotypes circulating in New South Wales, GII.1, GII.3, GII.4, GII.6, GII.7, and GII.10, with GII.4 being the predominant genotype. In 2004, there was a marked increase in NoV GII activity in Australia, with a novel GII.4 variant being identified as the etiological agent in 18 outbreaks investigated. This novel GII.4 variant, termed Hunter virus, differed by more than 5% at the amino acid level across the capsid from any other NoV strain in the GenBank and EMBL databases. The Hunter virus was subsequently identified as the etiological agent in large epidemics of gastroenteritis in The Netherlands, Japan, and Taiwan in 2004 and 2005.
Research on resource scheduling for development process of complicated product (2005)

In order to realize the optimization selection and utilization of manufacturing resource in the development process of complicated product, a kind of multipurpose optimization decision-making method based on stratification was brought forth. Facing towards hierarchy and decomposition of task in the development process, this paper combined the restrictions and evaluation criterions of resource selection with product development task, and guaranteed the practicability of resource selection. By improved method of multipurpose optimization decision-making, combining with two utility evaluation functions under the standard of gain target and profit loss target, the principle and process of resource optimization selection were depicted in detail which based on the targets such as response time, service quality, cost and security, etc, and the sort and selection of resource dispatch were realized. Finally, the feasibility of algorithm was verified by a real instance in the engineering field.
Antitumor activity of alpha-galactosylceramide, KRN7000, in mice with EL-4 hepatic metastasis and its cytokine production. (1998)

Liver metastasis of primary tumor is a clinically major problem. KRN7000, an alpha-galactosylceramide, significantly augments natural killer (NK) activity of spleen cells and shows strong antitumor activity in mice with lung metastasis of melanoma B16 cells. To test whether KRN7000 has an antitumor activity in mice with hepatic metastasis of tumors, we examined the effect of KRN7000 on NK activity of hepatic mononuclear cells (MNC) and the antitumor activity in mice with liver metastasis of EL-4 cells. The in vivo administration of KRN7000 significantly augmented NK activity of hepatic MNC and inhibited tumor growth of EL-4 cells in the liver more markedly than chemotherapeutic agents, leading to a relatively high rate of cured mice. In addition, it appeared that the KRN7000 treatment is effective in mice with established EL-4 tumors. Moreover, we found that KRN7000 can produce significant amounts of interleukin 2 (IL-2), IL-4, IL-12, and interferon-gamma in a dose-dependent manner. These results suggest that KRN7000 will be useful for the treatment of cancer liver metastasis.
Using Soluble Polymers To Recover Catalysts and Ligands (2002)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTUsing Soluble Polymers To Recover Catalysts and LigandsDavid E. BergbreiterView Author Information Department of Chemistry, Texas A&M University, P.O. Box 30012, College Station, Texas 77842-3012 Cite this: Chem. Rev. 2002, 102, 10, 3345–3384Publication Date (Web):August 30, 2002Publication History Received5 March 2002Published online30 August 2002Published inissue 1 October 2002https://pubs.acs.org/doi/10.1021/cr010343vhttps://doi.org/10.1021/cr010343vresearch-articleACS PublicationsCopyright © 2002 American Chemical SocietyRequest reuse permissionsArticle Views4383Altmetric-Citations487LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Catalysts,Ligands,Polyethylene,Polymers,Solvents Get e-Alerts