gebhart/patrepeval huggingface dataset:
Ab Initio and in Situ Comparison of Caffeine, Triclosan, and Triclocarban as Indicators of Sewage-Derived Microbes in Surface Waters (2008)

Three organic wastewater compounds (OWCs) were evaluated in theory and practice for their potential to trace sewage-derived microbial contaminants in surface waters. The underlying hypothesis was that hydrophobic OWCs outperform caffeine as a chemical tracer, due to their sorptive association with suspended microorganisms representing particulate organic carbon (POC). Modeling from first principles (ab initio) of OWC sorption to POC under environmental conditions suggested an increasing predictive power: caffeine (0.2% sorbed) < triclosan (9-60%; pH 6-9) < triclocarban (76%). Empirical evidence was obtained via analysis of surface water from three watersheds in a rural-to-urban gradient in Baltimore, MD. Mass spectrometric OWC detections were correlated to microbial plate counts for 40 monitoring sites along 14 streams, including multiple chronic sewage release sites and the local wastewater treatment plant. Consistent with ab initio calculations, correlation analyses of 104 observations for fecal coliforms, enterococci, and Escherichia coli in natural surface waters showed that the particle-active antimicrobials triclosan and triclocarban (R2 range, 0.45-0.55) were indeed superior to caffeine (0.16-0.37) for tracking of microbial indicators. It is concluded that chemical monitoring of microbial risks is more effective when using hydrophobic OWCs such as triclosan and triclocarban in place of, or in conjunction with, the traditional marker caffeine.
Materials and Fabrication Processes for Transient and Bioresorbable High‐Performance Electronics (2013)

Abstract Materials and fabrication procedures are described for bioresorbable transistors and simple integrated circuits, in which the key processing steps occur on silicon wafer substrates, in schemes compatible with methods used in conventional microelectronics. The approach relies on an unusual type of silicon on insulator wafer to yield devices that exploit ultrathin sheets of monocrystalline silicon for the semiconductor, thin films of magnesium for the electrodes and interconnects, silicon dioxide and magnesium oxide for the dielectrics, and silk for the substrates. A range of component examples with detailed measurements of their electrical characteristics and dissolution properties illustrate the capabilities. In vivo toxicity tests demonstrate biocompatibility in sub‐dermal implants. The results have significance for broad classes of water‐soluble, “transient” electronic devices.
Indanocine, a Microtubule-Binding Indanone and a Selective Inducer of Apoptosis in Multidrug-Resistant Cancer Cells (2000)

The sensitivity of stationary multidrug-resistant cancer cells to indanocine suggests that indanocine and related indanones be considered as lead compounds for the development of chemotherapeutic strategies for drug-resistant malignancies.
Tracking Alzheimerʼs disease in transgenic mice using fluorodeoxyglucose autoradiography (2000)

While transgenic mice have great promise in the study of Alzheimer's disease (AD), uncertainties remain about the extent to which they provide a model of the disorder or the best way to characterize disease progression. Using fluorodeoxyglucose (FDG) autoradiography, we found that transgenic mice over-expressing a mutant form of the human amyloid precursor protein have preferentially and progressively reduced activity in the posterior cingulate cortex and relatively spared activity in visual cortex, sensorimotor cortex, cerebellum and brain stem, a pattern previously demonstrated in FDG PET studies of persons with Alzheimer's disease, Brain imaging of posterior cingulate activity could provide an indicator of AD in suitable animals, helping to clarify disease mechanisms and screen candidate treatments.
Human Immunodeficiency Virus Type 1 (HIV-1) Accessory Protein Vpr Induces Transcription of the HIV-1 and Glucocorticoid-Responsive Promoters by Binding Directly to p300/CBP Coactivators (2002)

The accessory Vpr protein of human immunodeficiency virus type 1 (HIV-1) is a promiscuous activator of viral and cellular promoters. We report that Vpr enhances expression of the glucocorticoid receptor-induced mouse mammary tumor virus (MMTV) promoter and of the Tat-induced HIV-1 long terminal repeat promoter by directly binding to p300/CBP coactivators. In contrast, Vpr does not bind to p/CAF or to members of the p160 family of nuclear receptor coactivators, such as steroid receptor coactivator 1a and glucocorticoid receptor (GR)-interacting protein 1. Vpr forms a stable complex with p300 and also interacts with the ligand-bound glucocorticoid receptor in vivo. Mutation analysis showed that the C-terminal part of Vpr binds to the C-terminal portion of p300/CBP within amino acids 2045 to 2191. The same p300 region interacts with the p160 coactivators and with the adenovirus E1A protein. Accordingly, E1A competed for binding to p300 in vitro. Coexpression of E1A or of small fragments of p300 containing the Vpr binding site resulted in inhibition of Vpr's transcriptional effects. The C-terminal part of p300 containing the transactivating region is required for Vpr transactivation, whereas the histone acetyltransferase enzymatic region is dispensable. Vpr mutants that bind p300 but not the GR did not activate expression of the MMTV promoter and had dominant-negative effects. These results indicate that Vpr activates transcription by acting as an adapter linking transcription components and coactivators.
That's What Friends Are For: Inferring Location in Online Social Media Platforms Based on Social Relationships (2021)

Social networks are often grounded in spatial locality where individuals form relationships with those they meet nearby. However, the location of individuals in online social networking platforms is often unknown. Prior approaches have tried to infer individuals' locations from the content they produce online or their online relations, but often are limited by the available location-related data. We propose a new method for social networks that accurately infers locations for nearly all of individuals by spatially propagating location assignments through the social network, using only a small number of initial locations. In five experiments, we demonstrate the effectiveness in multiple social networking platforms, using both precise and noisy data to start the inference, and present heuristics for improving performance. In one experiment, we demonstrate the ability to infer the locations of a group of users who generate over 74% of the daily Twitter message volume with an estimated median location error of 10km. Our results open the possibility of gathering large quantities of location-annotated data from social media platforms.
A retinoic acid-triggered cascade of HOXB1 gene activation. (1995)

Retinoic acid (RA) has been proposed to be a direct regulator of HOX gene complexes. However, the molecular mechanism of the RA signaling pathway during normal development is unclear. We have identified an RA-responsive element in the promoter of HOXB1 gene composed of two functionally separable sites: (i) a DR-2 sequence, which is the direct target of the RA receptor retinoid X receptor heterodimer; and (ii) a motif for an RA-inducible and tissue-specific coactivator termed retinoid-inducible protein. Through neither enhancer alone is functional, this combined element strongly activates the HOXB1 promoter in a cell-specific and retinoid-dependent manner. Finally, this activation is potentiated by a proximal autoregulatory site for HOXB1 gene itself. These data define a tripartite cascade leading to the establishment of HOXB1 gene activation.
A new C‐peptide correction model used to assess bioavailability of regular human insulin (2010)

The clinical assessment of new formulations of human insulin is problematic due to the inability to distinguish between endogenous insulin and exogenously administered insulin. The usual methods to surmount the problem of distinguishing between endogenous and exogenous human insulin include evaluation in subjects with no or little endogenous insulin, hyper-insulinemic clamp studies or the administration of somatostatin to suppress endogenous insulin secretion. All of these methods have significant drawbacks. This paper describes a method for C-Peptide correction based upon a mixed effects linear regression of multiple time point sampling of C-Peptide and insulin. This model was able to describe each individual's insulin to C-Peptide relationship using the data from four different phase I clinical trials involving both subjects with and without type 2 diabetes in which insulin and C-Peptide were measured. These studies used hyper-insulinemic euglycemic clamps or meal challenges and subjects received insulin or Glucagon-like peptide 1 (GLP-1). It was possible to determine the exogenously administered insulin concentration from the measured total insulin concentration. A simple statistical technique can be used to determine each individual's insulin to C-Peptide relationship to estimate exogenous and endogenous insulin following the administration of regular human insulin. This technique will simplify the assessment of new formulations of human insulin.
Discovery and Optimization of Small-Molecule Ligands for the CBP/p300 Bromodomains (2014)

Small-molecule inhibitors that target bromodomains outside of the bromodomain and extra-terminal (BET) sub-family are lacking. Here, we describe highly potent and selective ligands for the bromodomain module of the human lysine acetyl transferase CBP/p300, developed from a series of 5-isoxazolyl-benzimidazoles. Our starting point was a fragment hit, which was optimized into a more potent and selective lead using parallel synthesis employing Suzuki couplings, benzimidazole-forming reactions, and reductive aminations. The selectivity of the lead compound against other bromodomain family members was investigated using a thermal stability assay, which revealed some inhibition of the structurally related BET family members. To address the BET selectivity issue, X-ray crystal structures of the lead compound bound to the CREB binding protein (CBP) and the first bromodomain of BRD4 (BRD4(1)) were used to guide the design of more selective compounds. The crystal structures obtained revealed two distinct binding modes. By varying the aryl substitution pattern and developing conformationally constrained analogues, selectivity for CBP over BRD4(1) was increased. The optimized compound is highly potent (Kd = 21 nM) and selective, displaying 40-fold selectivity over BRD4(1). Cellular activity was demonstrated using fluorescence recovery after photo-bleaching (FRAP) and a p53 reporter assay. The optimized compounds are cell-active and have nanomolar affinity for CBP/p300; therefore, they should be useful in studies investigating the biological roles of CBP and p300 and to validate the CBP and p300 bromodomains as therapeutic targets.
3-Aminopyrazole Inhibitors of CDK2/Cyclin A as Antitumor Agents. 2. Lead Optimization (2005)

Inhibitors of cyclin-dependent kinases (CDK) such as CDK2/cyclin A-E are currently undergoing clinical trials to verify their potential as new anticancer agents. In a previous article we described the lead discovery process of a 3-aminopyrazole class of CDK2/cyclin A-E inhibitors. The endpoint of this process was PNU-292137, a compound endowed with in vivo antitumor activity in a mouse tumor xenograft model. We optimized this lead compound to improve some physicochemical properties, notably solubility and plasma protein binding. This lead optimization process brought us to the discovery of (2S)-N-(5-cyclopropyl-1H-pyrazol-3-yl)-2-[4-(2-oxo-1-pyrrolidinyl)phenyl]propanamide (PHA-533533, 13), a compound with a balanced activity vs druglike profile. Compound 13 inhibited CDK2/cyclin A with a K(i) of 31 nM, counteracting tumor cell proliferation of different cell lines with an IC(50) in the submicromolar range. Solubility was improved more than 10 times over the starting lead, while plasma protein binding was decreased from 99% to 74%. With exploitation of this globally enhanced in vitro profile, 13 was more active than PNU-292137 in vivo in the A2780 xenograft model showing a tumor growth inhibition of 70%. Proof of mechanism of action was obtained in vivo by immunohistochemical analysis of tumor slices of 13-treated vs untreated animals.
Individual adenovirus type 5 early region 1A gene products elicit distinct alterations of cellular morphology and gene expression (1985)

Adenovirus early region 1A (E1A), which gives rise to three overlapping transcripts, was inserted into a murine leukemia virus-derived vector, and recombinant viruses were used to prepare permanent cell lines of NIH 3T3 cells containing DNA copies of the individual 13S, 12S, and 9S mRNAs. Integrated proviral copies of the recombinant genomes were rescued as bacterial plasmids from each of the cell lines, and the DNA sequence of E1A was demonstrated to be a precise copy of the individual transcripts. The DNA copies were shown to be expressed as part of the full-length retroviral transcript by S1 nuclease analysis, and the synthesis of their encoded polypeptides was demonstrated by immunoprecipitation. Those cell lines expressing the polypeptide encoded by the 13S transcript were shown to contain that function required for regulating the accumulation of mRNAs from adenovirus early genes by their ability to complement the adenovirus type 5 E1A deletion mutant dl312. Cell lines expressing polypeptides encoded by the 13S, 12S, and 9S transcripts showed characteristic alterations in morphology. Two-dimensional gel electrophoresis of total cellular protein derived from the three cell lines demonstrated that each E1A gene product elicits specific alterations in the patterns of proteins expressed. Studies of the expression of two specific genes, those encoding fibronectin and collagen type 1, indicated that the observed alteration in levels of the two proteins results from a reduction in RNA levels induced by E1A functions.
New insights on mammalian phospholipase A 2 (s); comparison of arachidonoyl‐selective and ‐nonselective enzymes (1993)

With the recent discoveries of novel forms of phospholipases A2 (PLA2s),2 new schemes for the roles of various PLA2s in lipid metabolism must be considered. The type II 14-kDa PLA2 isolated from human synovial fluid or platelet has many of the biochemical characteristics of the homologous snake venom and mammalian pancreatic PLA2s. It appears to function both as a cell-associated enzyme and extracellularly, where its expression and/or release is regulated by a variety of mediators such as cytokines or growth factors. The mammalian 85-kDa PLA2 purified from monocytic cells or platelets has no sequence homology to the 14-kDa PLA2 and exhibits biochemically different characteristics. It translocates from cytosol to particulate cell fractions in the presence of submicromolar levels of Ca2+ and has a substrate preference for sn-2-arachidonoyl-containing phospholipids. The cellular function and relative importance of these two enzymes in lipid metabolism remain to be determined. In this review, the biochemistry, localization, function, and regulation of these two distinct mammalian Ca(2+)-dependent PLA2 are compared.
Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade (2005)

Systemic onset juvenile idiopathic arthritis (SoJIA) encompasses approximately 10% of cases of arthritis that begin in childhood. The disease is unique in terms of clinical manifestations, severity of joint involvement, and lack of response to tumor necrosis factor blockade. Here, we show that serum from SoJIA patients induces the transcription of innate immunity genes, including interleukin (IL)-1 in healthy peripheral blood mononuclear cells (PBMCs). Upon activation, SoJIA PBMCs release large amounts of IL-1beta. We administered recombinant IL-1 receptor antagonist to nine SoJIA patients who were refractory to other therapies. Complete remission was obtained in seven out of nine patients and a partial response was obtained in the other two patients. We conclude that IL-1 is a major mediator of the inflammatory cascade that underlies SoJIA and that this cytokine represents a target for therapy in this disease.
Extraction of ε-Cycles from Finite-State Transducers (2008)

Abstract. Much attention has been brought to determinization and ε-removal in previous work. This article describes an algorithm for extracting all ε-cycles, which are a special type of non-determinism, from an arbitrary finite-state transducer (FST). The algorithm factorizes (decomposes) the FST, T, into two FSTs, T1 and T2, such that T1 contains no ε-cycles and T2 contains all ε-cycles of T. Since ε-cycles are an obstacle for some algorithms such as the factorization of ambiguous FSTs, the proposed approach allows us to by-pass this problem. ε-Cycles can be extracted before and re-inserted (by composition) after such algorithms. 1
Assessment, management, and prevention of early childhood caries (2009)

Clinicians need to understand the dental caries process, including the process of enamel demineralization and remineralization, and the factors contributing to caries balance. The importance of early identification and intervention for infants and toddlers at high risk for dental caries and primary care health provider-delivered anticipatory guidance during well-child care visits cannot be overestimated.
Metabolic engineering of proanthocyanidins through co‐expression of anthocyanidin reductase and the PAP1 MYB transcription factor (2006)

Proanthocyanidins (PAs) and their monomeric building blocks, the (epi)-flavan-3-ols, are plant antioxidants that confer multiple human health benefits. The presence of PAs in forage crops is an important agronomic trait, preventing pasture bloat in ruminant animals. However, many consumed plant materials lack PAs, and there has been little success to date in introducing monomeric or polymeric flavan-3-ols de novo into plant tissues for disease prevention by dietary means or development of 'bloat-safe' forages. We report the introduction of PAs into plants by combined expression of a MYB family transcription factor and anthocyanidin reductase for conversion of anthocyanidin into (epi)-flavan-3-ol. Tobacco leaves expressing both transgenes accumulated epicatechin and gallocatechin monomers, and a series of dimers and oligomers consisting primarily of epicatechin units. The levels of PAs reached values that would confer bloat reduction in forage species. Expression of anthocyanidin reductase in anthocyanin-containing leaves of the forage legume Medicago truncatula resulted in production of a specific subset of PA oligomers.
ATR and ATM play both distinct and additive roles in response to ionizing radiation (2006)

The ATR and ATM protein kinases are known to be involved in a wide variety of responses to DNA damage. The Arabidopsis thaliana genome includes both ATR and ATM orthologs, and plants with null alleles of these genes are viable. Arabidopsis atr and atm mutants display hypersensitivity to gamma-irradiation. To further characterize the roles of ATM and ATR in response to ionizing radiation, we performed a short-term global transcription analysis in wild-type and mutant lines. We found that hundreds of genes are upregulated in response to gamma-irradiation, and that the induction of virtually all of these genes is dependent on ATM, but not ATR. The transcript of CYCB1;1 is unique among the cyclin transcripts in being rapidly and powerfully upregulated in response to ionizing radiation, while other G(2)-associated transcripts are suppressed. We found that both ATM and ATR contribute to the induction of a CYCB1;1:GUS fusion by IR, but only ATR is required for the persistence of this response. We propose that this upregulation of CYCB1;1 does not reflect the accumulation of cells in G(2), but instead reflects a still unknown role for this cyclin in DNA damage response.
FEXT cancellation for twisted-pair transmission (2002)

This paper discusses a far-end crosstalk (FEXT) canceller for twisted-pair transmission. Many twisted-pair systems such as fiber-to-the-curb, very high-speed digital subscriber line, and high-speed LAN systems, use frequency-division duplexing (FDD) for duplex transmission. It is shown that the maximum reach of FDD twisted-pair system is limited by the performance of its upstream channel, which is assumed to be located at higher frequencies than the downstream channel. In order to improve the performance of such an FDD transceiver, FEXT cancellation is introduced for the channel at higher frequencies. A system arrangement and its blind startup procedure are studied when the FEXT canceller and equalizer are jointly adapted to combat channel intersymbol interference, FEXT, and other additive noise. We investigate the initial convergence and the steady-state behavior of the proposed twisted-pair system without requiring transmission of an ideal training sequence. Measured characteristics as well as analytical model of the FEXT channel are used to estimate the time span needed for the FEXT canceller. It is also shown that the memory span for the FEXT canceller is almost independent of the channel, thus making our results useful for the twisted-pair system over all different channels.
Toward a Smoke-free OR (2008)

The hazards of surgical smoke are well documented. So why are many smoke evacuation systems going unused? You can write all the surgical smoke evacuation policies in the world, spell out exactly what you expect to be done and provide the resources needed for compliance, but if you ignore the human element — the surgeons and staff who populate your ORs — then you aren't going to change behavior. Here's how you can educate your teams about the hazards of surgical smoke and get them to use evacuators when necessary.
Upregulation of Endogenous Heparin-Binding EGF-Like Growth Factor (HB-EGF) Expression after Intestinal Ischemia/Reperfusion Injury (2003)

Expression of endogenous heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), a proven intestinal cytoprotective molecule, was examined in intestinal epithelial cells (IEC) in vitro, and in intestine undergoing ischemia/reperfusion (I/R) injury in vivo. In vitro, cells were exposed to anoxia for 90 min followed by reoxygenation for 1-3 h (A/R). In vivo, total midgut I/R injury was produced in rats by occlusion of the superior mesenteric artery for 30 or 90 min followed by reperfusion for 4 h. In situ hybridization and immunohistochemistry were used to study HB-EGF mRNA expression and protein production. In vitro, normal IEC had no detectable HB-EGF mRNA or protein expression. After anoxia, cells expressed HB-EGF mRNA and protein, with expression reaching a peak 2-3 h after reoxygenation. In vivo, only very low levels of HB-EGF mRNA and no detectable protein were found in normal intestine. Four hours after I/R, HB-EGF protein was detected in villous epithelia subjected to 30 min but not 90 min of ischemia, whereas HB-EGF mRNA was highly expressed after both ischemic intervals. Endogenous HB-EGF is immediately upregulated in IEC after A/R injury and in intestine after I/R injury. Thus, HB-EGF acts as an immediate early gene under these conditions.
Age-Associated Testosterone Decline in Men: Clinical Issues for Psychiatry (1998)

Testosterone decline/deficiency is not a state strictly analogous to female menopause and may exhibit considerable overlap with primary and other secondary psychiatric disorders.
Electron mobility and energy gap of In0.53Ga0.47As on InP substrate (1976)

Very uniform In0.53Ga0.47As was grown on InP by liquid phase epitaxy. The electron mobility is 8450 cm2/V sec at 300 K and 27700 cm2/V sec at 77 K. The mobility increases with decreasing temperature from 300 to 77 K in contrast to the results of In1−xGaxAs grown directly on GaAs by vapor phase epitaxy. The energy gap of this high-mobility material is 0.750 eV at room temperature.