gebhart/patrepeval huggingface dataset:
Dynamics of Subgenomic Hepatitis C Virus Replicon RNA Levels in Huh-7 Cells after Exposure to Nucleoside Antimetabolites (2003)

Treatment with antimetabolites results in chemically induced low nucleoside triphosphate pools and cell cycle arrest in exponentially growing cells. Since steady-state levels of hepatitis C virus (HCV) replicon RNA were shown to be dependent on exponential growth of Huh-7 cells, the effects of antimetabolites for several nucleoside biosynthesis pathways on cell growth and HCV RNA levels were investigated. A specific anti-HCV replicon effect was defined as (i). minimal interference with the exponential cell growth, (ii). minimal reduction in cellular host RNA levels, and (iii). reduction of the HCV RNA copy number per cell compared to that of the untreated control. While most antimetabolites caused a cytostatic effect on cell growth, only inhibitors of the de novo pyrimidine ribonucleoside biosynthesis mimicked observations seen in confluent replicon cells, i.e., cytostasis combined with a sharp decrease in replicon copy number per cell. These results suggest that high levels of CTP and UTP are critical parameters for maintaining the steady-state level replication of HCV replicon in Huh-7 cells.
Role of Myeloperoxidase in the Neutrophil-Induced Oxidation of Low Density Lipoprotein as Studied by Myeloperoxidase-Knockout Mouse (2000)

Low density lipoprotein was oxidized by neutrophils derived from either C57BL/6 mice or myeloperoxidase (MPO)-knockout mice. The generation of superoxide from neutrophils of MPO-knockout mice was about 70% of that from wild-type mice. The extent of the oxidation of human low density lipoprotein (LDL) by phorbol myristate acetate (PMA)-activated neutrophils of wild-type and MPO-knockout mice was assessed by measuring consumption of a-tocopherol and formation of phosphatidylcholine hydroperoxide (PCOOH) and cholesteryl ester hydroperoxide (CEOOH). Little consumption of a-tocopherol was observed in both oxidations. It was found, however, that lipid hydroperoxides were accumulated with time in both oxidations and that the rates of formation of PCOOH and CEOOH in the oxidation by MPO-knockout neutrophils were about 66 and 44% of those by wild-type neutrophils, respectively. The lipid peroxidation was completely inhibited by adding superoxide dismutase (SOD) in both cases. The addition of L-tyrosine and SOD enhanced lipid peroxidation of LDL induced by wild-type neutrophils but not by MPO-knockout ones. These results suggest that, regardless of their MPO activity, neutrophils induce lipid peroxidation of LDL by a superoxide-dependent pathway, and that MPO-catalyzed lipid peroxidation is enhanced by the presence of an appropriate amount of free tyrosine and further enhanced by SOD.
Simulation: knowledge transfer from classroom to patient care (2011)

This paper is the second in a series that examines clinical simulation and its use within ODP education. This article explores representation and the reality of simulated learning - including discussion of the 'uncanny valley' - before looking at transference into patient care.
Synthesis and Pharmacology of Site-Specific Cocaine Abuse Treatment Agents:  2-(Aminomethyl)-3-phenylbicyclo[2.2.2]- and -[2.2.1]alkane Dopamine Uptake Inhibitors (1999)

As part of a program to develop site-specific medications for cocaine abuse, a series of 2-(aminomethyl)-3-phenylbicyclo[2.2.2]- and -[2.2.1]alkane derivatives was synthesized and tested for inhibitory potency in [3H]WIN 35,428 binding and [3H]dopamine uptake assays using rat striatal tissue. Selected compounds were tested for their ability to substitute for cocaine in rat drug discrimination tests. Synthesis was accomplished by a series of Diels−Alder reactions, using cis- and trans-cinnamic acid derivatives (nitrile, acid, acid chloride) with cyclohexadiene and cyclopentadiene. Standard manipulations produced the aminomethyl side chain. Many of the compounds bound with high affinity (median IC50 = 223 nM) to the cocaine binding site as marked by [3H]WIN 35,428. Potency in the binding assay was strongly enhanced by chlorine atoms in the 3- and/or 4-position on the aromatic ring and was little affected by corresponding methoxy groups. In the [2.2.2] series there was little difference in potency between cis and trans compounds or between N,N-dimethylamines and primary amines. In the [2.2.1] series the trans exo compounds tended to be least potent against binding, whereas the cis exo compounds were the most potent (4-Cl cis exo: IC50 = 7.7 nM, 27-fold more potent than 4-Cl trans-exo). Although the potencies of the bicyclic derivatives in the binding and uptake assays were highly correlated, some of the compounds were 5−7-fold less potent at inhibiting [3H]dopamine uptake than [3H]WIN 35,428 binding (for comparison, cocaine has a lower discrimination ratio (DR) of 2.5). The DR values were higher for almost all primary amines and for the trans-[2.2.2] series as compared to the cis-[2.2.2]. Most of the compounds had Hill coefficients approaching unity, except for the [2.2.2] 3,4-dichloro derivatives, which all had nH values of about 2.0. Two of the compounds were shown to fully substitute for cocaine in drug discrimination tests in rats, and one had a very long duration of action.
Efficient Transfer of Synthetic Ribozymes into Cells Using Hemagglutinating Virus of Japan (HVJ)-Cationic Liposomes (1997)

We investigated the usefulness of ribozymes in inhibiting the expression of human T-cell leukemia virus type I (HTLV-I) gene. Two hammerhead ribozymes that were against HTLV-I rex (RR) and tax (TR) mRNA were synthesized. Both ribozymes were sequence-specific in the in vitro cleavage analysis of run-off transcripts from tax/rex cDNA. Intracellular activities of the ribozymes were studied in HTLV-I tax cDNA-transfected rat embryonic fibroblasts (Rat/Tax cells), which expressed the Tax but not Rex. Ribozymes were delivered into cells using anionic or cationic liposomes fused with hemagglutinating virus of Japan (HVJ). Cellular uptake of ribozymes complexed with HVJ-cationic liposomes was 15-20 times higher cellular uptake than naked ribozymes, and 4-5 times higher than that of ribozymes complexed with HVJ-anionic liposomes. HVJ-cationic liposomes promoted accumulation of ribozymes in cytoplasm and accelerated transport to the nucleus. Tax protein levels were decreased about 95% and were five times lower when the same amount of TR was introduced into the cells using HVJ-cationic, rather than HVJ-anionic liposomes. Inactive ribozyme and tax antisense oligodeoxynucleotides reduced Tax expression by about 20%, whereas RR and tax sense oligodeoxynucleotides had no effect. These results suggest that the ribozymes' effect against tax mRNA was sequence-specific, and HVJ-cationic liposomes can be useful for intracellular introduction of ribozymes.
Using continuations to implement thread management and communication in operating systems (1991)

We have improved the performance of the Mach 3.0 operating system by redesigning its internal thread and interprocess communication facilities to use continuations as the basis for control transfer. Compared to previous versions of Mach 3.0, our new system consumes 85% less space per thread. Cross-address space remote procedure calls execute 14% faster. Exception handling runs over 60% faster.In addition to improving system performance, we have used continuations to generalize many control transfer optimizations that are common to operating systems, and have recast those optimizations in terms of a single implementation methodology. This paper describes our experiences with using continuations in the Mach operating system.
The Effect of Mask Edges on Dopant Diffusion into Semiconductors (1972)

A series of masked diffusions of Sn into and B into Si has been made through masks having stripe openings ranging in width from 20 mils (508 µm) down to 0.1 mils (2.5 µm). For Sn diffusion into from a pyrolytically deposited, doped source the junction depth depends strongly on mask opening width. It increases with decreasing mask opening size, passes through a maximum as large as 3 times the unmasked value and then decreases slightly at the smallest opening widths. These results are shown to be consistent with the presence of an accelerated diffusion at the mask edge. This "pull‐down" of the junction at the mask edge overlaps at narrow mask openings and produces the increase in junction depth. Diffusion of boron through an mask opening also results sporadically in the production of a junction profile which suggests that diffusion is accelerated at the mask edge with an accompanying change in junction depth with mask opening size. It is shown that the effect appears in a variety of diffusion source systems. Three possible mechanisms by which mask edges could affect diffusion of dopants into semiconductor substrates are described. Some tentative explanations of the observed effects have been made on the basis of these mechanisms.
Clinical events in the first decade in a cohort of infants with sickle cell disease. Cooperative Study of Sickle Cell Disease [see comments] (1995)

Within the Cooperative Study of Sickle Cell Disease, 694 infants with confirmed sickle cell disease were enrolled at less than 6 months of age. Information about the nature and frequency of complications was collected prospectively over a 10-year period. Painful crises and acute chest syndrome were the most common sickle cell-related events in homozygous sickle cell anemia (SS), hemoglobin SC disease (SC), and S beta thalassemia patients (overall incidence in SS patients of 32.4 and 24.5 cases per 100 person-years, respectively). Bacteremia occurred most frequently in SS children under 4 years of age and in SC patients less than 2 years of age. The mortality rate was low in this cohort compared with that found in previous reports. Twenty children, all with Hb SS, died (1.1 deaths per 100 person-years among SS patients). Infection, most commonly with Streptococcus pneumoniae and Hemophilus influenzae, caused 11 deaths. Two children died of splenic sequestration, 1 of cerebrovascular accident, and 6 of unclear causes. Two patients underwent cholecystectomies, and 17 underwent splenectomies after one or more splenic sequestration crises. The experience of this cohort should reflect closely the true clinical course of those children with Hb SS and Hb SC disease who are observed in sickle cell centers in the United States.
Current Density Profiles of Surface Mounted and Recessed Electrodes for Neural Prostheses (1987)

A Green's function approach has been used to solve Lapalce's equation for the quasi-static fields of a recessed, disk electrode. The resulting integral equation was solved numerically using the moment method. An analysis of the error in the approximate solution shows that it must be less than 7 percent for the cases studied. The calculations indicate that a recessed electrode has a more uniform current density profile than a surface mounted electrode. This is true both at the electrode surface, and at the electrode carrier-tissue junction. The significance of this finding is discussed as is its application to electrochemical, histopathological, and physiological studies of neural prostheses. The clinical use of recessed electrodes in cochlear implants is recommended.
Ross River Virus Glycoprotein-Pseudotyped Retroviruses and Stable Cell Lines for Their Production (2001)

Pseudotyped retroviruses have important applications as vectors for gene transfer and gene therapy and as tools for the study of viral glycoprotein function. Recombinant Moloney murine leukemia virus (Mo-MuLV)-based retrovirus particles efficiently incorporate the glycoproteins of the alphavirus Ross River virus (RRV) and utilize them for entry into cells. Stable cell lines that produce the RRV glycoprotein-pseudotyped retroviruses for prolonged periods of time have been constructed. The pseudotyped viruses have a broadened host range, can be concentrated to high titer, and mediate stable transduction of genes into cells. The RRV glycoprotein-pseudotyped retroviruses and the cells that produce them have been employed to demonstrate that RRV glycoprotein-mediated viral entry occurs through endocytosis and that membrane fusion requires acidic pH. Alphavirus glycoprotein-pseudotyped retroviruses have significant advantages as reagents for the study of the biochemistry and prevention of alphavirus entry and as preferred vectors for stable gene transfer and gene therapy protocols.
Modeling the effects of transforming growth factor‐β on extracellular matrix alignment in dermal wound repair (2001)

We present a novel mathematical model for collagen deposition and alignment during dermal wound healing, focusing on the regulatory effects of transforming growth factor-beta (TGFbeta.) Our work extends a previously developed model which considers the interactions between fibroblasts and an extracellular matrix composed of collagen and a fibrin based blood clot, by allowing fibroblasts to orient the collagen matrix, and produce and degrade the extracellular matrix, while the matrix directs the fibroblasts and control their speed. Here we extend the model by allowing a time varying concentration of TGFbeta to alter the properties of the fibroblasts. Thus we are able to simulate experiments which alter the TGFbeta profile. Within this model framework we find that most of the known effects of TGFbeta, i.e., changes in cell motility, cell proliferation and collagen production, are of minor importance to matrix alignment and cannot explain the anti-scarring properties of TGFbeta. However, we find that by changing fibroblast reorientation rates, consistent with experimental evidence, the alignment of the regenerated tissue can be significantly altered. These data provide an explanation for the experimentally observed influence of TGFbeta on scarring.
Evaluation of Optimized Biplane Pulmonary Cineangiography (1985)

Biplane pulmonary cineangiograms utilizing a short cine pulse width and automatic brightness control were performed in 47 patients during normal respiration. The diagnostic quality of the arteriograms was categorized as good in 33 patients, fair in 12 patients, and poor in two patients. Of the 18 patients in whom pulmonary emboli were identified, cineangiography displayed certain diagnostic features to advantage, including motion of emboli in ten and respiratory scissoring of vessels overcoming vascular superimposition in three. Optimized pulmonary cineangiography is an acceptable alternative to serial film pulmonary angiography for the diagnosis of pulmonary embolism.
The Role of a Second-Shell Residue in Modifying Substrate and Inhibitor Interactions in the SHV β-Lactamase: A Study of Ambler Position Asn276 (2009)

Inhibitor-resistant class A beta-lactamases of the TEM and SHV families that arise by single amino acid substitutions are a significant threat to the efficacy of beta-lactam/beta-lactamase inhibitor combinations. To better understand the basis of the inhibitor-resistant phenotype in SHV, we performed mutagenesis to examine the role of a second-shell residue, Asn276. Of the 19 variants expressed in Escherichia coli, only the Asn276Asp enzyme demonstrated reduced susceptibility to ampicillin/clavulanate (MIC increased from 50/2 --> 50/8 microg/mL) while maintaining high-level resistance to ampicillin (MIC = 8192 microg/mL). Steady-state kinetic analyses of Asn276Asp revealed slightly diminished k(cat)/K(m) for all substrates tested. In contrast, we observed a 5-fold increase in K(i) for clavulanate (7.4 +/- 0.9 microM for Asn276Asp vs 1.4 +/- 0.2 microM for SHV-1) and a 40% reduction in k(inact)/K(I) (0.013 +/- 0.002 microM(-1 )s(-1) for Asn276Asp vs 0.021 +/- 0.004 microM(-1) s(-1) for SHV-1). Timed electrospray ionization mass spectrometry of clavulanate-inhibited SHV-1 and SHV Asn276Asp showed nearly identical mass adducts, arguing for a similar pathway of inactivation. Molecular modeling shows that novel electrostatic interactions are formed between Arg244Neta2 and both 276AspOdelta1 and Odelta2; these new forces restrict the spatial position of Arg244, a residue important in the recognition of the C(3)/C(4) carboxylate of beta-lactam substrates and inhibitors. Testing the functional consequences of this interaction, we noted considerable free energy costs (+DeltaDeltaG) for substrates and inhibitors. A rigid carbapenem (meropenem) was most affected by the Asn276Asp substitution (46-fold increase in K(i) vs SHV-1). We conclude that residue 276 is an important second-shell residue in class A beta-lactamase-mediated resistance to substrates and inhibitors, and only Asn is able to precisely modulate the conformational flexibility of Arg244 required for successful evolution in nature.
Comparison of input shaping techniques for speed-critical multi-mode flexible systems (2002)

To achieve the highest level performance with computer controlled machines, the flexibility of the system must be taken into account. Feedforward methods are often the most desirable means of eliminating vibration. The fastest motions can be obtained by using the time-optimal flexible-body command. These commands depend on the system parameters, actuator limits, and the desired motion. Input shaping is another feedforward method which does not depend on actuator limits and motion parameters, only the system natural frequencies and damping ratios. Input shaping and time-optimal control are compared for use on multi-mode flexible systems. The two methods are compared in terms of moving speed, robustness to modeling errors, transient deflection, and ease of implementation.
Localized states in the mobility gap of amorphous quartz and glass (1974)

Abstract CdSe thin-film transistor structures have been used to determine the distribution, with energy, of ‘slow’ trapping states in the mobility gaps of the amorphous insulators quartz and 7059 glass. The results are in general agreement with the theoretical model proposed by Mott and Davis and do not support the model proposed by Cohen, Fritzsche and Ovshinsky for glassy materials, even in the case of 7059 glass.
Glucagon-like peptide-2 (GLP-2) receptor expression in the central nervous system and gastrointestinal tract (2001)

grantor: University of Toronto
Origin of the Gain-Bandwidth-Product Enhancement in Separate-Absorption-Charge-Multiplication Ge/Si Avalanche Photodiodes (2009)

A separate-absorption-charge-multiplication Ge/Si avalanche photodiode with very high gain-bandwidth-product over 800GHz is reported. The origin of this dramatically high value is explained using well consentient measurement and simulation results.
Hepatocytic Differentiation Potential of Human Fetal Liver Mesenchymal Stem Cells: In Vitro and In Vivo Evaluation (2016)

In line with the search of effective stem cell population that would progress liver cell therapy and because the rate and differentiation potential of mesenchymal stem cells (MSC) decreases with age, the current study investigates the hepatogenic differentiation potential of human fetal liver MSCs (FL-MSCs). After isolation from 11-12 gestational weeks' human fetal livers, FL-MSCs were shown to express characteristic markers such as CD73, CD90, and CD146 and to display adipocytic and osteoblastic differentiation potential. Thereafter, we explored their hepatocytic differentiation potential using the hepatogenic protocol applied for adult human liver mesenchymal cells. FL-MSCs differentiated in this way displayed significant features of hepatocyte-like cells as demonstrated in vitro by the upregulated expression of specific hepatocytic markers and the induction of metabolic functions including CYP3A4 activity, indocyanine green uptake/release, and glucose 6-phosphatase activity. Following transplantation, naive and differentiated FL-MSC were engrafted into the hepatic parenchyma of newborn immunodeficient mice and differentiated in situ. Hence, FL-MSCs appeared to be interesting candidates to investigate the liver development at the mesenchymal compartment level. Standardization of their isolation, expansion, and differentiation may also support their use for liver cell-based therapy development.
25-Hydroxycholesterol suppresses interleukin-1–driven inflammation downstream of type I interferon (2014)

Type I interferon (IFN) protects against viruses, yet it also has a poorly understood suppressive influence on inflammation. Here, we report that activated mouse macrophages lacking the IFN-stimulated gene cholesterol 25-hydroxylase (Ch25h) and that are unable to produce the oxysterol 25-hydroxycholesterol (25-HC) overproduce inflammatory interleukin-1 (IL-1) family cytokines. 25-HC acts by antagonizing sterol response element-binding protein (SREBP) processing to reduce Il1b transcription and to broadly repress IL-1-activating inflammasomes. In accord with these dual actions of 25-HC, Ch25h-deficient mice exhibit increased sensitivity to septic shock, exacerbated experimental autoimmune encephalomyelitis, and a stronger ability to repress bacterial growth. These findings identify an oxysterol, 25-HC, as a critical mediator in the negative-feedback pathway of IFN signaling on IL-1 family cytokine production and inflammasome activity.
High copy amplification of the aurora-A gene is associated with chromosomal instability phenotype in human colorectal cancers (2007)

Chromosomal instability (CIN) is a common but not universal feature of colorectal cancer (CRC); however, the molecular basis for CIN is controversial and poorly understood. There are many plausible mechanisms proposed for CIN, including disruption of G1/S and G2/M checkpoint regulation, and alterations in the spindle checkpoint genes. However, mutations in individual growth regulatory genes are not commonly observed in CRC. Therefore, a more comprehensive analysis of the genes involved in each cell cycle checkpoint regulatory pathway might be required to evaluate a possible role for involvement in CIN. We investigated the presence of high copy amplification of the cyclin E, Aurora-A, Skp2 genes, mutation of ubiquitin ligase CDC4, and promoter methylation of Mad2L1, as well as the expression of the gene products in a panel of 11 human CRC cell lines as well as 48 human CRC specimens. In the cell lines with CIN, we found amplification of the Aurora-A, cyclin E and Skp2 genes, and a mutation in the CDC4 gene, all of which resulted in altered expression of the cognate proteins. In the human CRC tissues, amplification of Aurora-A was frequent (29%), while alterations were rarely observed in cyclin E, Skp2 or CDC4. Aurora-A amplification was strongly associated with a high fractional allelic loss score (p = 0.0001), but not with microsatellite instability, nor with the promoter methylation phenotype in these tumors. Our data confirm involvement in the CDC4-cyclin E pathway of the development of the CIN phenotype in human CRC, and find that amplification of the Aurora-A is a common target for disruption of this pathway.