gebhart/patrepeval huggingface dataset:
Targeting the ATF-1/CREB Transcription Factors by Single Chain Fv Fragment in Human Melanoma: Potential Modality for Cancer Therapy (2001)

Activating transcription factor-1 (ATF-1) and cAMP-responsive element (CRE)-binding protein (CREB) have been implicated in cAMP and Ca2+-induced transcriptional activation. The expression of the transcription factors ATF-1 and CREB is upregulated in metastatic melanoma cells. However, how overexpression of ATF-1/CREB contributes to the acquisition of the metastatic phenotype is unclear. Previously we demonstrated that quenching of CREB activity in metastatic melanoma cells by means of a dominant-negative form of CREB (KCREB) led to a decrease in their tumorigenicity and metastatic potential in nude mice. We identified two mechanisms that explain how overexpression of CREB/ATF-1 contributes to the metastatic phenotype. The first is one in which CREB/ATF-1 play an essential role in invasion by regulating the CRE-dependent expression of the metalloproteinase MMP-2 and the adhesion molecule MCAM/MUC18 genes. In the second mechanism, CREB and ATF-1 act as survival factors for human melanoma cells. Here, the effect of disrupting ATF-1 activity was investigated using intracellular expression of an inhibitory anti-ATF-1 single chain antibody fragment (ScFv). Intracellular expression of ScFv anti-ATF-1 in MeWo melanoma cells caused significant reduction in CRE-dependent promoter activation. In addition, expression of ScFv anti-ATF-1 in melanoma cells suppressed their tumorigenicity and metastatic potential in nude mice. ScFv anti-ATF-1 rendered the melanoma cells susceptible to thapsigargin-induced apoptosis in vitro and caused massive apoptosis in tumors transplanted subcutaneously into nude mice, confirming that AFT-1/CREB act as survival factors for human melanoma cells. These studies demonstrate the potential usage of ScFv anti-ATF-1 as an inhibitor of tumor growth and metastasis of solid tumors in vivo.
The Pragmatic Influences on Thou and Ye in Some Middle English Romances (2010)

The standard explanation of the semantics of power and solidarity for second person Middle English pronoun choice, advanced by Roger Brown and Albert Gilman and accepted by many Middle English scholars since, has proven insufficient to explain many choices between thou and ye that fictional characters make. This paper applies the discourse theories of pragmatics and politeness, developed by Penelope Brown and Stephen C. Levinson, to the relatively untouched data set of non-Chaucerian romances in order to account for some of those anomalies. By examining the pronouns of address in Floris and Blancheflour, Havelok the Dane, Ywain and Gawain, Sir Launfal, and Sir Degrevant, this paper finds that the realm of politeness, specifically the desire to soften face-threatening acts and occasionally the desire to insult by ignoring politeness, often explains pronoun choice in many of those previously anomalous instances. The broader lens of pragmatics also lends itself to other insights into Middle English second person pronoun usage; the pronouns in these romances show that social deixis does occur within the Middle English address system and that at least a functional understanding of the power and solidarity semantics must have existed on a conscious level because speakers use these semantics for their own rhetorical purposes.
Streptomyces inside-out: a new perspective on the bacteria that provide us with antibiotics (2006)

Many of the antibiotics used today are made by a group of bacteria called Streptomyces. Streptomycetes evolved about 450 million years ago as branched filamentous organisms adapted to the utilization of plant remains. They reproduce by sending up specialized aerial branches, which form spores. Aerial growth is parasitic on the primary colony, which is digested and reused for aerial growth. The reproductive phase is coordinated with the secretion of antibiotics, which may protect the colony against invading bacteria during aerial growth. A clue to the integration of antibiotic production and aerial growth is provided by bldA mutants, which are defective in both processes. These mutants lack the ability to translate a particularly rare codon, UUA, in the genetic code. The UUA codon (TTA in DNA) is present in several regulatory genes that control sets of antibiotic production genes, and in one, bldH that controls aerial mycelium formation. The regulatory genes for antibiotic production are all involved in self-reinforcing regulatory systems that potentially amplify the regulatory significance of small changes in the efficiency of translation of UUA codons. One of the regulatory targets of bldH is an extracellular protease inhibitor protein that is likely to delay the digestion of the primary biomass until the colony is ready for aerial growth. The use of the UUA codon to orchestrate different aspects of extracellular biology appeared very early in Streptomyces evolution.
Genetic Screening for Synthetic Lethal Partners of Polynucleotide Kinase/Phosphatase: Potential for Targeting SHP-1–Depleted Cancers (2012)

A genetic screen using a library of 6,961 siRNAs led to the identification of SHP-1 (PTPN6), a tumor suppressor frequently mutated in malignant lymphomas, leukemias, and prostate cancer, as a potential synthetic lethal partner of the DNA repair protein polynucleotide kinase/phosphatase (PNKP). After confirming the partnership with SHP-1, we observed that codepletion of PNKP and SHP-1 induced apoptosis. A T-cell lymphoma cell line that is SHP-1 deficient (Karpas 299) was shown to be sensitive to a chemical inhibitor of PNKP, but resistance was restored by expression of wild-type SHP-1 in these cells. We determined that while SHP-1 depletion does not significantly impact DNA strand-break repair, it does amplify the level of reactive oxygen species (ROS) and elevate endogenous DNA damage. The ROS scavenger WR1065 afforded protection to SHP-1-depleted cells treated with the PNKP inhibitor. We propose that codisruption of SHP-1 and PNKP leads to an increase in DNA damage that escapes repair, resulting in the accumulation of cytotoxic double-strand breaks and induction of apoptosis. This supports an alternative paradigm for synthetic lethal partnerships that could be exploited therapeutically.
Molecular Controls of the Oxygenation and Redox Reactions of Hemoglobin (2012)

Significance: The broad classes of O2-binding proteins known as hemoglobins (Hbs) carry out oxygenation and redox functions that allow organisms with significantly different physiological demands to exist in a wide range of environments. This is aided by allosteric controls that modulate the protein's redox reactions as well as its O2-binding functions. Recent Advances: The controls of Hb's redox reactions can differ appreciably from the molecular controls for Hb oxygenation and come into play in elegant mechanisms for dealing with nitrosative stress, in the malarial resistance conferred by sickle cell Hb, and in the as-yet unsuccessful designs for safe and effective blood substitutes. Critical Issues: An important basic principle in consideration of Hb's redox reactions is the distinction between kinetic and thermodynamic reaction control. Clarification of these modes of control is critical to gaining an increased understanding of Hb-mediated oxidative processes and oxidative toxicity in vivo. Future Directions: This review addresses emerging concepts and some unresolved questions regarding the interplay between the oxygenation and oxidation reactions of structurally diverse Hbs, both within red blood cells and under acellular conditions. Developing methods that control Hb-mediated oxidative toxicity will be critical to the future development of Hb-based blood substitutes. Antioxid. Redox Signal. 18, 2298–2313.
Generation and Assembly of Secretory Antibodies in Plants (1995)

Four transgenic Nicotiana tabacum plants were generated that expressed a murine monoclonal antibody kappa chain, a hybrid immunoglobulin A-G heavy chain, a murine joining chain, and a rabbit secretory component, respectively. Successive sexual crosses between these plants and filial recombinants resulted in plants that expressed all four protein chains simultaneously. These chains were assembled into a functional, high molecular weight secretory immunoglobulin that recognized the native streptococcal antigen I/II cell surface adhesion molecule. In plants, single cells are able to assemble secretory antibodies, whereas two different cell types are required in mammals. Transgenic plants may be suitable for large-scale production of recombinant secretory immunoglobulin A for passive mucosal immunotherapy. Plant cells also possess the requisite mechanisms for assembly and expression of other complex recombinant protein molecules.
A hybrid image coder: adaptive intra-interframe prediction using motion compensation (2003)

A hybrid image predictive coding method is presented. The intraframe predictor is an adaptive finite impulse response (FIR) filter using the well-known least-mean-square (LMS) algorithm to track continuously the spatial local characteristics of the intensity. The interframe predictor is motion-adaptive, using a pel-recursive method estimating the displacement vector. A weight coefficient is adapted continuously in order to favor the prediction mode that performs better between intraframe and only-motion-compensation mode. A crucial problem in predictive coding, particularly with adaptive techniques, is that of sensitivity to transmission errors. A method ensuring the autoadjustment of the decoder in the presence of isolated transmission errors is proposed for the intraframe mode. Neither overhead information nor error-correcting code is needed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
C Language Integrated Production System (CLIPS) (1990)

Ideal for developing expert systems, CLIPS language easy to use and called from or make calls to other programs. Advanced features include cross-reference, style, and verification facility catching logic errors in large systems. Program machine independent.
Detailed Modeling, Design, and Evaluation of a Scalable Multi-level Checkpointing System (2010)

High-performance computing (HPC) systems are growing more powerful by utilizing more hardware components. As the system mean-time-before-failure correspondingly drops, applications must checkpoint more frequently to make progress. However, as the system memory sizes grow faster than the bandwidth to the parallel file system, the cost of checkpointing begins to dominate application run times. A potential solution to this problem is to use multi-level checkpointing, which employs multiple types of checkpoints with different costs and different levels of resiliency in a single run. The goal is to design light-weight checkpoints to handle the most common failure modes and rely on more expensive checkpoints for less common, but more severe failures. While this approach is theoretically promising, it has not been fully evaluated in a large-scale, production system context. To this end we have designed a system, called the Scalable Checkpoint/Restart (SCR) library, that writes checkpoints to storage on the compute nodes utilizing RAM, Flash, or disk, in addition to the parallel file system. We present the performance and reliability properties of SCR as well as a probabilistic Markov model that predicts its performance on current and future systems. We show that multi-level checkpointing improves efficiency on existing large-scale systems and that this benefit increases as the system size grows. In particular, we developed low-cost checkpoint schemes that are 100x-1000x faster than the parallel file system and effective against 85% of our system failures. This leads to a gain in machine efficiency of up to 35%, and it reduces the the load on the parallel file system by a factor of two on current and future systems.
The enhançon, black holes, and the second law (2001)

We reexamine the physics of five-dimensional black holes constructed from D5- and D1-branes and momentum modes in type IIB string theory compactified on K3. Since these black holes incorporate D5-branes wrapped on K3, an enhan\ifmmode \mbox{\c{c}}\else \c{c}\fi{}on locus appears in the spacetime geometry. With a ``small'' number of D1-branes, the entropy of a black hole is maximized by including precisely half as many D5-branes as there are D1-branes in the black hole. Any attempts to introduce more D5-branes, and so reduce the entropy, are thwarted by the appearance of the enhan\ifmmode \mbox{\c{c}}\else \c{c}\fi{}on locus above the horizon, which then prevents their approach. The enhan\ifmmode \mbox{\c{c}}\else \c{c}\fi{}on mechanism thereby acts to uphold the second law of thermodynamics. This result generalizes: For each type of bound state object which can be made of both types of brane, we show that a new type of enhan\ifmmode \mbox{\c{c}}\else \c{c}\fi{}on exists at successively smaller radii in the geometry, again acting to prevent any reduction of the entropy just when needed. We briefly explore the appearance of the enhan\ifmmode \mbox{\c{c}}\else \c{c}\fi{}on locus in the black hole interior.
“Bacteroides goldsteiniisp. nov.” Isolated from Clinical Specimens of Human Intestinal Origin (2005)

Phenotypic and phylogenetic studies were performed on an unknown gram-negative, strictly anaerobic, rod-shaped bacterium isolated from human clinical specimens. This organism was indole negative, resistant to 20% bile, produced acetic and a lesser amount of succinic acids as the major end products of glucose metabolism, and possessed a G+C content of approximately 43 mol%. Comparative 16S rRNA gene sequencing demonstrated that the unidentified bacterium was a member of the Cytophaga-Flavobacter-Bacteroides phylum of gram-negative bacteria and formed a close association (with an average sequence similarity of 93.6%) with the second subcluster of the Porphyromonas cluster in the Bacteroides subgroup. Phylogenetically and phenotypically it resembled Bacteroides merdae; however, a 16S rRNA gene sequence divergence of approximately 5.5% between the unknown bacterium and B. merdae, as well as distinguishable biochemical characteristics, demonstrate that the unknown bacterium is genotypically and phenotypically distinct and represents a previously unknown subline within the Porphyromonas phylogenetic cluster. Furthermore, a DNA-DNA reassociation value of 17.8% between isolates WAL 12034(T) (the type strain of this novel taxon) and ATCC 43184(T) (B. merdae type strain) also documented the separateness of the unknown species and B. merdae. Based on the phenotypic and phylogenetic findings, a new species, "Bacteroides goldsteinii sp. nov," is proposed. The G+C content of the DNA is 43 mol% for Bacteroides. The type strain of "B. goldsteinii" is WAL 12034(T) (= CCUG 48944(T) = ATCC BAA-1180(T)).
Assessment of patient satisfaction in activities of daily living using a modified stanford health assessment questionnaire (1983)

Patient satisfaction in performing activities of daily living (ADL) was assessed by using a self-administered questionnaire modified from the Stanford Health Assessment Questionnaire (HAQ). The HAQ includes questions to determine a patient's degree of difficulty and need for help and assistive devices in ADL. A modification of the HAQ (MHAQ) was developed to include questions concerning perceived patient satisfaction regarding the same ADL, along with perceived change in degree of difficulty. In order to add additional questions while maintaining the length of the questionnaire in a format suitable in routine care, the number of ADL included in the MHAQ was reduced from 20 to 8. Information regarding degree of difficulty derived from 8 questions in the MHAQ is comparable with that derived from 20 questions in the HAQ. The response of a patient that a specific activity is associated with difficulty in functional capacity was not inevitably associated with the absence of patient satisfaction; 43.7% of patients responding "with some difficulty" and 19.1% of patients responding "with much difficulty" expressed satisfaction with their functional capacity. A major determinant of expression of patient satisfaction was perceived change in difficulty: 81.4% of patients noting that their function was "less difficult now," in contrast to 16.9% of patients responding "more difficult now," expressed satisfaction. These studies suggest that data regarding patient satisfaction and perceived change in difficulty can be assessed to more completely characterize patients' functional status in ADL.
Discovery ofN-{1-[3-(3-Oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): An Allosteric Muscarinic M1Receptor Agonist with Unprecedented Selectivity and Procognitive Potential (2010)

The discovery and structure-activity relationship (SAR) of a series of allosteric muscarinic M(1) receptor agonists are described. Compound 17 (Lu AE51090) was identified as a representative compound from the series, based on its high selectivity as an agonist at the muscarinic M(1) receptor across a panel of muscarinic receptor subtypes. Furthermore, 17 displayed a high degree of selectivity when tested in a broad panel of G-protein-coupled receptors, ion channels, transporters, and enzymes, and 17 showed an acceptable pharmacokinetic profile and sufficient brain exposure in rodents in order to characterize the compound in vivo. Hence, in a rodent model of learning and memory, 17 reversed delay-induced natural forgetting, suggesting a procognitive potential of 17.
Complexing Mechanism of the Lanthanide Cations Eu3+, Gd3+, and Tb3+ with 1,4,7,10‐Tetrakis(carboxymethyl)‐1,4,7,10‐tetraazacyclododecane (dota)—Characterization of Three Successive Complexing Phases: Study of the Thermodynamic and Structural Properties of the Complexes by Potentiometry, Luminescence Spectroscopy, and EXAFS (2004)

Complexation of the lanthanides Eu3+, Gd3+, and Tb3+ with 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (dota) has been studied in solution by using potentiometry, luminescence spectrometry, and EXAFS. Three series of successive complexes were characterized by at least two of these methods: the immediate [LnHn(dota)](n-1)+** and intermediate [LnHn(dota)](n-1)+* complexes with 0 </= n </= 2, and the final [Ln(dota)]- complexes. The formation constants of the intermediate and final complexes were determined by using potentiometry. From the results, a complexation mechanism involving three steps has been proposed. In the [LnHn(dota)](n-1)+** complexes that are instantaneously formed, the lanthanide is bound to four oxygen atoms of the carboxylate groups and to five water molecules. These species evolve rapidly: the lanthanide moves into the macrocycle cavity, two new bonds are formed with two nitrogen atoms diametrically opposed in the tetraaza cycle and only three water molecules remain bound to the lanthanide in the [LnHn(dota)](n-1)+* (0 </= n </= 2) complexes, which appear after a two-day wait. These compounds are stable for about four days. After 4-8 weeks, a concerted rearrangement occurs which leads to the formation of thermodynamically stable [Ln(dota)]- complexes in which the lanthanide is bound to four nitrogen atoms, four carboxylate oxygen atoms, and one water molecule.
Introduction to Coccidiosis (2007)

This chapter contains sections titled: Diagnostic chart Coccidial life cycle Diagnostic procedure
A Randomized Controlled Trial of a High Support Hospital Discharge Team for Elderly People (1994)

The Home Treatment Team (HTT), a hospital discharge team for elderly patients, was created to provide practical help and promote independence of patients at home for up to 6 weeks after hospital discharge. Patients were those judged to be at particular risk of failing to resettle, and thus being readmitted to hospital or admitted to a residential or nursing home. An open randomized controlled trial compared patients receiving the HTT (n = 29) with controls (n = 25) receiving appropriate conventional community services. Fewer HTT patients were readmitted (four by 6 weeks and nine by 12 weeks) than controls (nine by 6 weeks and 14 by 12 weeks, p < 0.05) and more were at home at 6 weeks (24, 83% and 10, 40%, p < 0.05), 12 weeks (21, 72% and 11, 44%, p < 0.05) and 12 months (17, 58% and 10, 40%, p < 0.05). The HTT group spent fewer days in hospital than controls during 12 weeks (median difference 34 days, 95% confidence interval 0-75, p < 0.05) and more days at home during 12 months (90; 247-0, p = 0.02). Neither group showed any significant change in mental state or functional abilities over 12 weeks. Potentially confounding factors were considered insufficient explanation for the difference in outcome between the groups. It is concluded that the HTT was of benefit but the mechanism of its effect was not identified.
Hinge-thiol coupling of monoclonal antibody to silanized iron oxide particles and evaluation of magnetic cell depletion (1990)

Iron oxide particles of average size 0.5-1.5 microns, covered by a silane coat carrying amino groups (Bio-Mag, Advanced Magnetics, Boston), were derivatized by reaction with N-[(gamma-maleimidobutyryl)oxy]-succinimide (GMBS), N-hydroxysuccinimidyl iodoacetate (NHIA), 2-iminothiolane (2-It), or N-succinimidyl 3-(2-pyridyldithio)propionate (SPDP). The derivatized particles were suitable for the reaction with sulfhydryl groups and subsequently coated with monoclonal antibodies (MoAbs) of different classes and isotypes (IgM, IgG1, IgG2a, IgG2b, IgG3) as well as polyclonal rabbit anti-mouse IgG (RAM). The antibodies were reduced by dithiothreitol (DTT) and covalently conjugated to the BioMag derivatives via liberated sulfhydryls of the hinge region. The observed conjugation ratios, expressed as protein/iron (micrograms/mg), could be reproducibly varied for optimization. These ratios were dependent on the type and amount of antibody offered for coupling to the derivatized particles, decreasing as follows: polyclonal = IgM greater than IgG2b greater than IgG2a = IgG3 greater IgG1. The conjugation ratios were also dependent on the type and amount of the spacer used to derivatize the BioMag particles, decreasing as follows: GMBS greater than NHIA greater than 2-It greater than SPDP. The magnetically responsive magnetite-antibody conjugates ("magneto-beads"), carrying MoAb BMA 081 (anti-CD8; IgG2a), MoAb BB10 (anti-CD10/CALLA; IgG2b), MoAb VIL-A1 (anti-CD10; IgM), and polyclonal RAM, coupled similarly via 3.6 mumol of GMBS spacer per mg of Fe, were further investigated with respect to a depletion effect on specific cell subsets. The rates of cell depletion were found to be strongly dependent on the individual characteristics of the antibody used.(ABSTRACT TRUNCATED AT 250 WORDS)
Non-24-Hour Disorder in Blind Individuals Revisited: Variability and the Influence of Environmental Time Cues (2013)

Emens JS; Laurie AL; Songer JB; Lewy AJ. Non-24-hour disorder in blind individuals revisited: variability and the influence of environmental time cues. <i>SLEEP</i> 2013;36(7):1091-1100.