gebhart/patrepeval huggingface dataset:
Sulindac sulfide-induced apoptosis involves death receptor 5 and the caspase 8-dependent pathway in human colon and prostate cancer cells. (2001)

Sulindac is the most extensively investigated clinically relevant chemopreventive nonsteroidal anti-inflammatory drug. Sulindac sulfide is one of the major metabolites of sulindac that is believed to mediate its antitumorigenic effects by inducing apoptosis. Recent evidence suggests that sulindac sulfide engages the mitochondrial pathway involving caspase 9 and Bax to mediate its apoptotic effects [Zhang et al., Science (Wash. DC), 290: 989-992, 2000]. In this report, we demonstrate that sulindac sulfide also engaged the membrane death receptor (DR) pathway to mediate apoptosis. Sulindac sulfide up-regulated DR5 and activated the proximal caspase 8 in various different colon and prostate cancer cell lines. Sulindac sulfide specifically up-regulated the DR5 levels but had no effect on the levels of other DRs including DR4, Fas, and tumor necrosis factor receptor 1. To further delineate the role of DR5 in sulindac sulfide-induced apoptosis, we used JCA-1 prostate cancer cells that are deficient in mounting a Fas and tumor necrosis factor receptor 1-dependent apoptotic response but are proficient in mediating DR5-dependent apoptosis. JCA-1 cells were stably transfected with dominant-negative Fas-associated death domain to block the flow of apoptotic signals originating from the endogenous DR5, and sulindac sulfide-induced apoptosis was investigated. Our results indicated that by blocking the DR5-dependent apoptotic pathway, dominant-negative Fas-associated death domain did indeed inhibit sulindac sulfide-induced apoptosis. Furthermore, exogenous tumor necrosis factor-related apoptosis-inducing ligand, the ligand for DR5, also potentiated sulindac sulfide-induced apoptosis in all of the cell lines tested, thereby further supporting the involvement of DR5 in sulindac sulfide-induced apoptosis. Thus, our results demonstrate that sulindac sulfide also engages the membrane DR pathway involving DR5 and proximal caspase 8 to induce apoptosis.
Listening to what is said – transcribing what is heard: the impact of speech recognition technology (SRT) on the practice of medical transcription (MT) (2009)

Medical records have become central to nearly all aspects of healthcare. However, little research exists on their creation. Using data from an ongoing ethnographic study of healthcare documentation production, this paper examines the process of medical record creation through the use of speech recognition technology (SRT) and subsequent editing by medical transcriptionists (MTs). Informed by ethnomethodology (EM) and conversation analysis (CA), the results demonstrate the professional knowledge involved in the work of medical transcription, which includes a combination of skilled worksite practices and an orientation toward the social order properties of recorded dictation. Furthermore, we examine how the advantages and limitations of SRTs can impact the work of transcription. We conclude with strategic recommendations for using SRTs to support medical records production and recommend against total automation.
Scan line display of algebraic surfaces (1989)

A robust algorithm is presented for scan line display of algebraic surfaces of arbitrary degree and topology. The algorithm correctly displays singularities of any complexity, even those missed by ray tracing or polygonization, and (for surfaces of degree less than eight) offers a significant speed improvement over ray tracing. Antialiasing can generally be accomplished very quickly. In addition to its typical function of shaded raster display, the algorithm is particularly adept at quickly plotting silhouette and intersection curves. A practical use for the algorithm is to display boolean combinations of algebraic half spaces, including blend surfaces.A new polynomial basis is introduced, referred to as the Bernstein pyramid polynomial basis, which enhances numerical stability and which simplifies several computations such as scan planesurface intersection and silhouette detection.
Molecular Hardware of Copper Homeostasis in Enterococcus hirae (2002)

In the past, copper transport in bacteria has been considered only in terms of resistance mechanisms to permit survival of the cells in adverse copper-rich environments. Indeed, most of the systems characterized early on are plasmid encoded, as is typical for defense mechanisms of prokaryotes. Recently, similar copper “resistance” systems were also identified in chromosomal locations, giving rise to the concept that bacteria may need systems for copper homeostasis not only in extreme environments but also under normal growth conditions.
Intrusion detection and honeypots in nested virtualization environments (2013)

Several research projects in the past have built intrusion detection systems and honeypot architectures based on virtual machine introspection (VMI). These systems directly benefit from the use of virtualization technology. The VMI approach, however, requires direct interaction with the virtual machine monitor, and typically is not available to clients of current public clouds. Recently, nested virtualization has gained popularity in research as an approach that could enable cloud customers to use virtualization-based solutions within a cloud by nesting two virtual machine monitors, with the inner one under control of the client. In this paper, we compare the performance of existing nested-virtualization solutions and analyze the impact of the performance overhead on VMI-based intrusion detection and honeypot systems.
Repositioning the Catalytic Triad Aspartic Acid of Haloalkane Dehalogenase:  Effects on Stability, Kinetics, and Structure (1997)

Haloalkane dehalogenase (DhlA) catalyzes the hydrolysis of haloalkanes via an alkyl-enzyme intermediate. The covalent intermediate, which is formed by nucleophilic substitution with Asp124, is hydrolyzed by a water molecule that is activated by His289. The role of Asp260, which is the third member of the catalytic triad, was studied by site-directed mutagenesis. Mutation of Asp260 to asparagine resulted in a catalytically inactive D260N mutant, which demonstrates that the triad acid Asp260 is essential for dehalogenase activity. Furthermore, Asp260 has an important structural role, since the D260N enzyme accumulated mainly in inclusion bodies during expression, and neither substrate nor product could bind in the active-site cavity. Activity for brominated substrates was restored to D260N by replacing Asn148 with an aspartic or glutamic acid. Both double mutants D260N+N148D and D260N+N148E had a 10-fold reduced kcat and 40-fold higher Km values for 1,2-dibromoethane compared to the wild-type enzyme. Pre-steady-state kinetic analysis of the D260N+N148E double mutant showed that the decrease in kcat was mainly caused by a 220-fold reduction of the rate of carbon-bromine bond cleavage and a 10-fold decrease in the rate of hydrolysis of the alkyl-enzyme intermediate. On the other hand, bromide was released 12-fold faster and via a different pathway than in the wild-type enzyme. Molecular modeling of the mutant showed that Glu148 indeed could take over the interaction with His289 and that there was a change in charge distribution in the tunnel region that connects the active site with the solvent. On the basis of primary structure similarity between DhlA and other alpha/beta-hydrolase fold dehalogenases, we propose that a conserved acidic residue at the equivalent position of Asn148 in DhlA is the third catalytic triad residue in the latter enzymes.
Mobility of cholera toxin receptors on rat lymphocyte membranes. (1975)

Fluorescein-labeled cholera toxin binds detectably to 40-60% of rat mesenteric lymph node cells and induces a temperature-dependent redistribution (patch and cap formation) of cell surface toxin receptors. The redistribution is inhibited by several "metabolic," "microtubule," and "microfilament" inhibitors, by concanavalin A, and by anticholera toxin IgG. Various studies indicate that cholera toxin is at least bivalent, and that this property may be related to both the induction of receptor redistribution and to the activation of adenylate cyclase. Membrane components which are probably identical to the sialo-glycolipid, GM1 ganglioside, appear to be mobile in the plane of the membrane. The possible role of toxin multivalency and receptor mobility in the mechanism of toxin action is considered.
Propagation and second-harmonic generation of electromagnetic waves in a coupled-resonator optical waveguide (2000)

Using both the tight-binding approximation and the finite-difference time domain method, we analyze two types of coupled-resonator optical waveguide (CROW), a coupled-microdisks waveguide and a waveguide composed of coupled defect cavities in a two-dimensional photonic crystal. We find that the dispersion relation of the CROW band can be simply described by a small coupling parameter κ, and the spatial characteristics of the CROW modes remain the same as those of the single-resonator high Q modes. As applications of these unique properties, we demonstrate that CROW’s can be utilized in constructing waveguides without cross talk and enhance the efficiency of second-harmonic generation.
Compartmental organization of Golgi-specific protein modification and vacuolar protein sorting events defined in a yeast sec18 (NSF) mutant. (1991)

The sec18 and sec23 secretory mutants of Saccharomyces cerevisiae have previously been shown to exhibit temperature-conditional defects in protein transport from the ER to the Golgi complex (Novick, P., S. Ferro, and R. Schekman, 1981. Cell. 25:461-469). We have found that the Sec18 and Sec23 protein functions are rapidly inactivated upon shifting mutant cells to the nonpermissive temperature (less than 1 min). This has permitted an analysis of the potential role these SEC gene products play in transport events distal to the ER. The sec-dependent transport of alpha-factor (alpha f) and carboxypeptidase Y (CPY) biosynthetic intermediates present throughout the secretory pathway was monitored in temperature shift experiments. We found that Sec18p/NSF function was required sequentially for protein transport from the ER to the Golgi complex, through multiple Golgi compartments and from the Golgi complex to the cell surface. In contrast, Sec23p function was required in the Golgi complex, but only for transport of alpha f out of an early compartment. Together, these studies define at least three functionally distinct Golgi compartments in yeast. From cis to trans these compartments contain: (a) An alpha 1----6 mannosyltransferase; (b) an alpha 1----3 mannosyltransferase; and (c) the Kex2 endopeptidase. Surprisingly, we also found that a pool of Golgi-modified CPY (p2 CPY) located in a compartment distal to the alpha 1----3 mannosyltransferase does not require Sec18p function for final delivery to the vacuole. This compartment appears to be equivalent to the Kex2 compartment as we show that a novel vacuolar CPY-alpha f-invertase fusion protein undergoes efficient Kex2-dependent cleavage resulting in the secretion of invertase. We propose that this Kex2 compartment is the site in which vacuolar proteins are sorted from proteins destined to be secreted.
PEG−Doxorubicin Conjugates:  Influence of Polymer Structure on Drug Release, in Vitro Cytotoxicity, Biodistribution, and Antitumor Activity (2005)

Polymer-drug conjugates (polymer therapeutics) are finding increasing use as novel anticancer agents. Here a series of poly(ethylene glycol) PEG-doxorubicin (Dox) conjugates were synthesized using polymers of linear or branched architecture (molecular weight 5000-20000 g/mol) and with different peptidyl linkers (GFLG, GLFG, GLG, GGRR, and RGLG). The resultant conjugates had a drug loading of 2.7-8.0 wt % Dox and contained <2.0% free drug (% total drug). All conjugates containing a GFLG linker showed approximately 30% release of Dox at 5 h irrespective of PEG molecular weight or architecture. The GLFG linker was degraded more quickly (approximately 57% Dox release at 5 h), and the other linkers more slowly (<16% release at 5 h), by lysosomal enzymes in vitro. In vitro there was no clear relationship between cytotoxicity toward B16F10 cells and the observed Dox release rate. All PEG conjugates were more than 10-fold less toxic (IC50 values > 2 microg/mL) than free Dox (IC50 value = 0.24 microg/mL). Biodistribution in mice bearing sc B16F10 tumors was assessed after administration of PEGs (5000, 10000, or 20000 g/mol) radioiodinated using the Bolton and Hunter reagent or PEG-Dox conjugates by HPLC. The 125I-labeled PEGs showed a clear relationship between Mw and blood clearance and tumor accumulation. The highest Mw PEG had the longest plasma residence time and consequently the greatest tumor targeting. The PEG-Dox conjugates showed a markedly prolonged plasma clearance and greater tumor targeting compared to free Dox, but there was no clear molecular weight-dependence on biodistribution. This was consistent with the observation that the PEG-Dox conjugates formed micelles in aqueous solution comprising 2-20 PEG-Dox molecules depending on polymer Mw and architecture. Although PEG-Dox showed greater tumor targeting than free Dox, PEG conjugation led to significantly lower anthracycline levels in heart. Preliminary experiments to assess antitumor activity against sc B16F10 in vivo showed the PEG5000linear (L)-GFLG-Dox and PEG10000branched (B)-GLFG-Dox (both 5 mg/kg Dox-equiv) to be the most active with T/C values of 146 and 143%, respectively. Free Dox did not show significant activity in this model (T/C = 121%). Dose escalation of PEG5000(L)-GFLG-Dox to 10 mg/kg Dox-equiv prolonged further animal survival (T/C = 161%). Using the Dox-sensitive model ip L1210 (where Dox displayed a T/C = 150% after single ip dose), the PEG5000(L)-GFLG-Dox displayed a maximum T/C of 141% (10 mg/kg Dox-equiv) using a once a day (x3) schedule. Further studies are warranted with PEG5000(L)-GFLG-Dox to determine its spectrum of antitumor activity and also the optimum dosing schedule before clinical testing.
Maintenance of remission with leflunomide in Wegener's granulomatosis (2003)

Leflunomide appears to be safe and well tolerated for the maintenance of complete or partial remission of WG. The results of this pilot study encourage further controlled trials comparing leflunomide with alternative remission maintenance therapies.
Differential stable isotope labeling of peptides for quantitation and de novo sequence derivation (2001)

We have demonstrated the use of per-methyl esterification of peptides for relative quantification of proteins between two mixtures of proteins and automated de novo sequence derivation on the same dataset. Protein mixtures for comparison were digested to peptides and resultant peptides methylated using either d0- or d3-methanol. Methyl esterification of peptides converted carboxylic acids, such as are present on the side chains of aspartic and glutamic acid as well as the carboxyl terminus, to their corresponding methyl esters. The separate d0- and d3-methylated peptide mixtures were combined and the mixture subjected to microcapillary high performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS). Parent proteins of methylated peptides were identified by correlative database searching of peptide tandem mass spectra. Ratios of proteins in the two original mixtures could be calculated by normalization of the area under the curve for identical charge states of d0- to d3-methylated peptides. An algorithm was developed that derived, without intervention, peptide sequence de novo by comparison of tandem mass spectra of d0- and d3-peptide methyl esters.
Crystalline Covalent Organic Frameworks with Hydrazone Linkages (2011)

Condensation of 2,5-diethoxyterephthalohydrazide with 1,3,5-triformylbenzene or 1,3,5-tris(4-formylphenyl)benzene yields two new covalent organic frameworks, COF-42 and COF-43, in which the organic building units are linked through hydrazone bonds to form extended two-dimensional porous frameworks. Both materials are highly crystalline, display excellent chemical and thermal stability, and are permanently porous. These new COFs expand the scope of possibilities for this emerging class of porous materials.
Mutant-Selective Thyromimetics for the Chemical Rescue of Thyroid Hormone Receptor Mutants Associated with Resistance to Thyroid Hormone (2005)

The thyroid hormone receptors (TRs) are ligand-dependent transcription factors that control the expression of multiple genes involved in development and homeostasis in response to thyroid hormone (triiodothyronine, T3). Mutations to TRbeta that reduce or abolish ligand-dependent transactivation function are associated with resistance to thyroid hormone (RTH), an autosomal dominant human genetic disease. A series of neutral alcohol-based compounds, based on the halogen-free thyromimetic GC-1, have been designed, synthesized, and evaluated in cell-based assays for their ability to selectively rescue three of the most common RTH-associated mutations (i.e., Arg320 --> Cys, Arg320 --> His, and Arg316 --> His) that affect the basic carboxylate-binding arginine cluster of TRbeta. Several analogues show improved potency and activity in the mutant receptors relative to the parent compound GC-1. Most significantly, two of these mutant-complementing thyromimics show high potency and activity with a strong preference for the mutant receptors over wild-type TRalpha(wt), that is associated with the cardiotoxic actions of T3. The compounds were evaluated in reporter gene assays using the four common thyroid hormone response elements, DR4, PAL, F2 (LAP), and TSH, and show activities and selectivites consistent with their unique potential as agents to selectively rescue thyroid function to these RTH-associated mutants.
In situ with bystanders of augmented reality glasses (2014)

Augmented reality (AR) devices are poised to enter the market. It is unclear how the properties of these devices will affect individuals' privacy. In this study, we investigate the privacy perspectives of individuals when they are bystanders around AR devices. We conducted 12 field sessions in cafés and interviewed 31 bystanders regarding their reactions to a co-located AR device. Participants were predominantly split between having indifferent and negative reactions to the device. Participants who expressed that AR devices change the bystander experience attributed this difference to subtleness, ease of recording, and the technology's lack of prevalence. Additionally, participants surfaced a variety of factors that make recording more or less acceptable, including what they are doing when the recording is being taken. Participants expressed interest in being asked permission before being recorded and in recording-blocking devices. We use the interview results to guide an exploration of design directions for privacy-mediating technologies.
Renal uptake of bismuth-213 and its contribution to kidney radiation dose following administration of actinium-225-labeled antibody (2011)

Clinical therapeutic studies using (225)Ac-labeled antibodies have begun. Of major concern is renal toxicity that may result from the three alpha-emitting progeny generated following the decay of (225)Ac. The purpose of this study was to determine the amount of (225)Ac and non-equilibrium progeny in the mouse kidney after the injection of (225)Ac-huM195 antibody and examine the dosimetric consequences. Groups of mice were sacrificed at 24, 96 and 144 h after injection with (225)Ac-huM195 antibody and kidneys excised. One kidney was used for gamma ray spectroscopic measurements by a high-purity germanium (HPGe) detector. The second kidney was used to generate frozen tissue sections which were examined by digital autoradiography (DAR). Two measurements were performed on each kidney specimen: (1) immediately post-resection and (2) after sufficient time for any non-equilibrium excess (213)Bi to decay completely. Comparison of these measurements enabled estimation of the amount of excess (213)Bi reaching the kidney (γ-ray spectroscopy) and its sub-regional distribution (DAR). The average absorbed dose to whole kidney, determined by spectroscopy, was 0.77 (SD 0.21) Gy kBq(-1), of which 0.46 (SD 0.16) Gy kBq(-1) (i.e. 60%) was due to non-equilibrium excess (213)Bi. The relative contributions to renal cortex and medulla were determined by DAR. The estimated dose to the cortex from non-equilibrium excess (213)Bi (0.31 (SD 0.11) Gy kBq(-1)) represented ∼46% of the total. For the medulla the dose contribution from excess (213)Bi (0.81 (SD 0.28) Gy kBq(-1)) was ∼80% of the total. Based on these estimates, for human patients we project a kidney-absorbed dose of 0.28 Gy MBq(-1) following administration of (225)Ac-huM195 with non-equilibrium excess (213)Bi responsible for approximately 60% of the total. Methods to reduce renal accumulation of radioactive progeny appear to be necessary for the success of (225)Ac radioimmunotherapy.
Novel methods improve prediction of species’ distributions from occurrence data (2006)

Prediction of species’ distributions is central to diverse applications in ecology, evolution and conservation science. There is increasing electronic access to vast sets of occurrence records in museums and herbaria, yet little effective guidance on how best to use this information in the context of numerous approaches for modelling distributions. To meet this need, we compared 16 modelling methods over 226 species from 6 regions of the world, creating the most comprehensive set of model comparisons to date. We used presence‐only data to fit models, and independent presence‐absence data to evaluate the predictions. Along with well‐established modelling methods such as generalised additive models and GARP and BIOCLIM, we explored methods that either have been developed recently or have rarely been applied to modelling species’ distributions. These include machine‐learning methods and community models, both of which have features that may make them particularly well suited to noisy or sparse information, as is typical of species’ occurrence data. Presence‐only data were effective for modelling species’ distributions for many species and regions. The novel methods consistently outperformed more established methods. The results of our analysis are promising for the use of data from museums and herbaria, especially as methods suited to the noise inherent in such data improve.
Immunobiology of natural killer cells and bone marrow transplantation: merging of basic and preclinical studies (2001)

Natural killer (NK) cells mediate acute rejection of bone marrow, but not solid tissue, allografts in lethally irradiated mice. Precisely how and why this rejection occurs is still unclear. In allogeneic bone marrow transplantation (BMT), a spectrum of results is possible; one result can be marrow graft failure due to host rejection of the graft by NK and T cells and, at the opposite spectrum, the occurrence of graft-versus-host disease (GVHD). Donor NK cells, however, appear capable of improving donor engraftment without giving rise to GVHD and thus may be of use as an immunotherapy following BMT. As NK-cell inhibitory receptors play a role in bone marrow cell rejection, these same inhibitory receptors may also affect NK responses towards tumor cells. It has been demonstrated that blocking the interaction of inhibitory receptors with MHC determinants on tumor cells can result in greater antitumor effects. Thus, NK cells are capable of mediating both positive and negative effects during BMT depending on whether they are of host versus donor origin and their state of activation. Understanding their role in BMT provides insights as to their physiological roles and points the way to potential clinical uses.