gebhart/patrepeval huggingface dataset:
Human peripheral blood lymphocytes targeted with bispecific antibodies release cytokines that are essential for inhibiting tumor growth (1991)

We have compared the mechanisms by which human PBL targeted with bispecific antibodies either lyse tumor cells or block their growth in culture or in mice. We found that resting PBL were unable to mediate lysis, but were able to block tumor growth. Moreover, targeted PBL were unable to lyse bystander cells, whereas targeted PBL did block the growth of bystander tumor cells in culture and in nude mice. Supernatants from cultures of targeted PBL, or from PBL grown on anti-CD3-coated flasks, blocked the growth of tumor cells in the absence of added effector cells, and antibodies against TNF-alpha and IFN-gamma reversed the inhibition of tumor growth, but had no effect upon cytolysis mediated by targeted by PBL. Our results show that targeted human PBL mediate two different antitumor activities: lysis, which occurs rapidly and requires the direct attachment of the target cell to the cytotoxic cell, and tumor growth inhibition, which is mediated by cytokines released into the medium as a result of receptor cross-linking. The inhibition of bystander tumor growth in mice by targeted PBL suggests that factor release is sufficient to block tumor growth in vivo. Targeted factor release therefore provides a mechanism by which targeted PBL could block the growth of tumor cells in vivo that were not bound by the effector cells, but which were located in the vicinity of tumor cells that were bound.
The virtual source method: Theory and case study (2006)

Abstract We present a way to image through complex overburden. The method uses surface shots with downhole receivers placed below the most complex part of the troublesome overburden. No knowledge of the velocity model between shots and receivers is required. The method uses time-reversal logic to create a new downward-continued data set with virtual sources (VS's) at the geophone locations. Time reversal focuses energy that passes through the overburden into useful primary energy for the VS. In contrast to physical acoustics, our time reversal is done on a computer, utilizing conventional acquisition with surface shots and downhole geophones. With this approach, we can image below extremely complex (realistic) overburden — in fact, the more complex the better. We recast the data to those with sources where we actually know and can control the waveform that has a downward-radiation pattern that may also be controlled, and is reproducible for 4D even if the near-surface changes or the shooting geometry is altered slightly. To illustrate the method, we apply the VS technique to a synthetic, elastic example with extreme heterogeneity, where conventional approaches fail to image the data. A 4D field-data example shows that the VS method (VSM) enables sensitive reservoir monitoring below a complex, time-variant near surface that is not achievable with surface 4D seismic or conventional 4D vertical seismic profiling (VSP).
Nanostructures in Water-in-CO2 Microemulsions Stabilized by Double-Chain Fluorocarbon Solubilizers (2013)

High-pressure small-angle neutron scattering (HP-SANS) studies were conducted to investigate nanostructures and interfacial properties of water-in-supercritical CO2 (W/CO2) microemulsions with double-fluorocarbon-tail anionic surfactants, having different fluorocarbon chain lengths and linking groups (glutarate or succinate). At constant pressure and temperature, the microemulsion aqueous cores were found to swell with an increase in water-to-surfactant ratio, W0, until their solubilizing capacities were reached. Surfactants with fluorocarbon chain lengths of n = 4, 6, and 8 formed spherical reversed micelles in supercritical CO2 even at W0 over the solubilizing powers as determined by phase behavior studies, suggesting formation of Winsor-IV W/CO2 microemulsions and then Winsor-II W/CO2 microemulsions. On the other hand, a short C2 chain fluorocarbon surfactant analogue displayed a transition from Winsor-IV microemulsions to lamellar liquid crystals at W0 = 25. Critical packing parameters and aggregation numbers were calculated by using area per headgroup, shell thickness, the core/shell radii determined from SANS data analysis: these parameters were used to help understand differences in aggregation behavior and solubilizing power in CO2. Increasing the microemulsion water loading led the critical packing parameter to decrease to ~1.3 and the aggregation number to increase to >90. Although these parameters were comparable between glutarate and succinate surfactants with the same fluorocarbon chain, decreasing the fluorocarbon chain length n reduced the critical packing parameter. At the same time, reducing chain length to 2 reduced negative interfacial curvature, favoring planar structures, as demonstrated by generation of lamellar liquid crystal phases.
Bro: a system for detecting network intruders in real-time (1998)

We describe Bro, a stand-alone system for detecting network intruders in real-time by passively monitoring a network link over which the intruder&amp;apos;s traffic transits. We give an overview of the system&amp;apos;s design, which emphasizes highspeed (FDDI-rate) monitoring, real-time notification, clear separation between mechanism and policy, and extensibility. To achieve these ends, Bro is divided into an “event engine” that reduces a kernel-filtered network traffic stream into a series of higher-level events, and a “policy script interpreter” that interprets event handlers written in a specialized language used to express a site&amp;apos;s security policy. Event handlers can update state information, synthesize new events, record information to disk, and generate real-time notifications via syslog. We also discuss a number of attacks that attempt to subvert passive monitoring systems and defenses against these, and give particulars of how Bro analyzes the four applications integrated into it so far: Finger, FTP, Portmapper and Telnet. The system is publicly available in source code form.
Pyridines and Pyrimidines Mediating Activity against an Efflux-Negative Strain of Candida albicans through Putative Inhibition of Lanosterol Demethylase (2003)

The first step in ergosterol biosynthesis in Saccharomyces cerevisiae consists of the condensation of two acetyl coenzyme A (acetyl-CoA) moieties by acetoacetyl-CoA thiolase, encoded by ERG10. The inhibition of the sterol pathway results in feedback activation of ERG10 transcription. A cell-based reporter assay, in which increased ERG10 transcription results in elevated specific beta-galactosidase activity, was used to find novel inhibitors of ergosterol biosynthesis that could serve as chemical starting points for the development of novel antifungal agents. A class of pyridines and pyrimidines identified in this way had no detectable activity against the major fungal pathogen Candida albicans (MICs > 64 micro g. ml(-1)). However, a strain of C. albicans lacking the Cdr1p and Cdr2p efflux pumps was sensitive to the compounds (with MICs ranging from 2 to 64 micro g. ml(-1)), suggesting that they are efficiently removed from wild-type cells. Quantitative analysis of sterol intermediates that accumulated during growth inhibition revealed the accumulation of lanosterol at the expense of ergosterol. Furthermore, a clear correlation was found between the 50% inhibitory concentration at which the sterol profile was altered and the antifungal activity, measured as the MIC. This finding strongly suggests that the inhibition of growth was caused by a reduction in ergosterol synthesis. The compounds described here are a novel class of antifungal pyridines and pyrimidines and the first pyri(mi)dines to be shown to putatively mediate their antifungal activity against C. albicans via lanosterol demethylase.
Monocyte Chemoattractant Protein–1 Messenger RNA Expression in Rat Ischemic Cortex (1995)

The demonstration of induced MCP-1 mRNA expression early after focal ischemia suggests that MCP-1 may represent a locally expressed monocyte chemoattractant that plays an important role in monocyte infiltration into ischemic tissue and therefore may contribute to the tissue injury in ischemic stroke. Further studies must concentrate on identifying the induced expression of MCP-1 and its cellular localization in the ischemic brain when the appropriate antibodies become available.
Studies on the phosphorylation of myelin basic protein by protein kinase C and adenosine 3‘:5‘-monophosphate-dependent protein kinase. (1985)

The substrate specificity of protein kinase C was studied and compared with that of cyclic AMP-dependent protein kinase (protein kinase A) by using bovine brain myelin basic protein as a model substrate. This basic protein was phosphorylated at multiple sites by both of these protein kinases. In this analysis, the basic protein was thoroughly phosphorylated in vitro with [gamma-32P]ATP and each protein kinase, and then digested with trypsin. The resulting radioactive phosphopeptides were isolated by gel filtration followed by high performance liquid chromatography on a reverse-phase column. Subsequent amino acid analysis and/or sequential Edman degradation of the purified phosphopeptides, together with the known primary sequence of this protein, revealed that Ser-46 and Ser-151 were specifically phosphorylated by protein kinase C, whereas Thr-34 and Ser-115 were phosphorylated preferentially by protein kinase A. Both kinases reacted with Ser-8, Ser-11, Ser-55, Ser-110, Ser-132, and Ser-161 at various reaction velocities. Contrary to protein kinase A, protein kinase C appears to react preferentially with seryl residues that are located at the amino-terminal side close to lysine or arginine. The seryl residues that are phosphorylated commonly by these two protein kinases have basic amino acids at both the amino- and carboxyl-terminal sides. These results provide some clues to understanding the rationale that these kinases may show different but sometimes similar functions depending on the structure of target phosphate acceptor proteins.
Computational meta'omics for microbial community studies (2013)

Complex microbial communities are an integral part of the Earth's ecosystem and of our bodies in health and disease. In the last two decades, culture-independent approaches have provided new insights into their structure and function, with the exponentially decreasing cost of high-throughput sequencing resulting in broadly available tools for microbial surveys. However, the field remains far from reaching a technological plateau, as both computational techniques and nucleotide sequencing platforms for microbial genomic and transcriptional content continue to improve. Current microbiome analyses are thus starting to adopt multiple and complementary meta'omic approaches, leading to unprecedented opportunities to comprehensively and accurately characterize microbial communities and their interactions with their environments and hosts. This diversity of available assays, analysis methods, and public data is in turn beginning to enable microbiome-based predictive and modeling tools. We thus review here the technological and computational meta'omics approaches that are already available, those that are under active development, their success in biological discovery, and several outstanding challenges.
Characterization of tenascin secreted by human melanoma cells. (1991)

Tenascin is a large glycoprotein of the extracellular matrix. It shows a site-restricted expression during embryogenesis and can be found in adult tissues during wound healing and tumorigenesis. Because of the potential involvement of tenascin in adhesion and invasion during metastasis, the study of the interactions of tumor cells with tenascin is of considerable interest. Using five anti-melanoma monoclonal antibodies to four different epitopes of human tenascin, we found that most melanoma cells secrete tenascin in vitro constitutively. Transforming growth factor beta 1 in the medium increased secretion in tenascin-producing cells. Tenascin was present in sera of melanoma patients, with significantly elevated levels in patients with advanced melanomas as compared to patients with low tumor burden or to normal donors. Normal and malignant melanocytes did not attach to tenascin as substrate within 1 to 2 h and tenascin could also inhibit fibronectin-dependent adhesion. These results indicate that tenascin may play a critical role in cell-substrate interactions of melanoma cells.
Molecular Insights into Human Monoamine Oxidase B Inhibition by the Glitazone Antidiabetes Drugs (2011)

The widely employed anti-diabetic drug pioglitazone (Actos) is shown to be a specific and reversible inhibitor of human monoamine oxidase B (MAO B). The crystal structure of the enzyme-inhibitor complex shows the R-enantiomer is bound with the thiazolidinedione ring near the flavin. The molecule occupies both substrate and entrance cavities of the active site establishing non-covalent interactions with the surrounding amino acids. These binding properties differentiate pioglitazone from the clinically used MAO inhibitors, which act through covalent inhibition mechanisms and do not exhibit a high degree of MAO A versus B selectivity. Rosiglitazone (Avandia) and troglitazone, other members of the glitazone class, are less selective in that they are weaker inhibitors of both MAO A and MAO B These results suggest that pioglitazone may have utility as a "re-purposed" neuro-protectant drug in retarding the progression of disease in Parkinson's patients. They also provide new insights for the development of reversible isoenzyme-specific MAO inhibitors.
Modification of silica nanoparticles and their application in UDMA dental polymeric composites (2007)

Abstract Advancements in nanocomposites are highly dependent on the compatibility between the organic matrix and inorganic fillers, and the dispersion level of fillers throughout the matrix. Silane coupling agents are widely used to change the chemical structure of particles' surface in order to improve their compatibility and dispersion properties of particles. SiO 2 nanoparticles were modified by ζ potential, turbidity, and relative viscosity. The results indicate that the stability and dispersion degree in organic solvents have been improved after the modification. In addition, the mechanical properties of composites with modified silica were also studied, which indicated that, after the predispersion of particles in organic media, the mechanical properties of materials could be improved, even at low filler content. POLYM. COMPOS., 28:198–207, 2007. © 2007 Society of Plastics Engineers
Study of the resistance of tumor‐cell spheroids to penetration and lysis by activated effector cells (1994)

Tumor spheroids and growing cell monolayers were used as 2- and 3-dimensional targets in the in vitro study of the interactions of colorectal tumor cells with various in vitro Il-2-activated lymphocyte effectors. The study examined tumor-cell susceptibility to the cytotoxic activity of effector cells in correlation with the ability of the effectors to infiltrate spheroids. No restriction of lymphocyte activity was found when the susceptibility of tumor cells to the panel of autologous and allogeneic Il-2-stimulated PBL (LAK cells) and TIL was compared. Their activity against a given tumor specimen was similar, but differed against the various other tumor specimens. Thus, the tumor susceptibility and not the cytotoxic potential of the lymphocytes determined the interaction result. An inhibition of lymphocyte penetration was observed in some tumor spheroids, which considerably influenced the resistance to lymphocyte lysis. Apparently it is this inhibition of the migratory capacity of the effector cells by tumor cells that is responsible for tumor resistance to lymphocyte attack.
Recent progress in catalytic conversions of carbon dioxide (2014)

Chemical fixation of carbon dioxide (CO2), which is an inexpensive and renewable carbon source, is becoming more and more important. The development of both new reactions and new catalysts is needed to overcome the kinetic and thermodynamic stability of CO2. Organic and metal catalysts with unique and excellent activity and selectivity have been developed for various chemical conversions of CO2. In this perspective, we provide an overview of the recent progress in this field, classifying it into several categories, where each research is concisely summarized one by one using a single reaction scheme, a representative catalyst structure, and/or a catalytic cycle.
Myotonic Dystrophy: Increased expression of the normal allele in CDM infants muscle (1994)

Myotonic dystrophy (DM) is an autosomal dominant multisystemic disorder characterized by a highly variable clinical phenotype. The mutation has been identified as an unstable trinucleotide CTG repeat in the 3{prime} untranslated region of the myotonin-protein kinase (MT-PK) gene. Congenital myotonic dystrophy (CDM), which represents the most severe phenotype, is exclusively maternally inherited. Recent studies, analysis by Northern blots and RT-PCR provided apparently conflicting results on the mutated allele expression in samples from congenitally affected children. The level of expression of the mutant allele depends on the extent of the repeat in the adult form and is no longer expressed when over 800-1300 repeats, whether in adult forms or in CDM. Could this decrease account for the late onset forms? However, the differences between the two phenotypes cannot be explained by the same mechanism. Alternatively, these differences could be due to differences in expression of the normal allele. We analyzed by quantitative RT-PCR the expression of the MT-PK gene in muscle samples from four CDM infants and two aged-matched normal controls. In two of these, the mutant allele (3.3 and 8 kb) was undetectable on Northern blots. We observed an increased expression of the MT-PK gene (10- to 20-fold) in tissuesmore » of severely affected congenital patients which can be attributed to the normal allele. Since expression of the normal allele is either normal or slightly decreased in the adult form, the dramatic increase in the congenital form could reflect a disturbance in muscle differentiation. Expression studies of MT-PK at different stages of development and, especially after the 20th week, are therefore required.« less
Electrical Conductivity and Dielectric Properties of Solid Asphaltenes (2010)

Direct current (DC) and alternating current (AC) (120 and 1000 Hz) conductivity and AC dielectric properties of solid precipitated asphaltenes have been studied at temperatures of 5−105 °C. The temperature dependencies revealed the presence of a structural transition, ascribed to changes in the predominant type of intermolecular bonding. Apparently, at solid surfaces, this transition occurs at absolute temperatures about 20% lower than in the solid bulk. Analysis of conductivity mechanisms is supplemented by a comparison of UV−vis−NIR absorption spectra for solid asphaltenes and their solution in toluene. It is concluded that, in solid asphaltenes, surface conductivity is always predominant over the bulk one. The major transport mechanism of charge carriers at asphaltene surfaces appears to be unidirectional electron hopping between spatially close shallow localized traps. The dielectric constant of solid asphaltenes below 35−40 °C was found to be both frequency- and temperature-independent and was evaluated as ε = 4.3 − 5.4.
Rapid formation of secondary structure framework in protein folding studied by stopped‐flow circular dichroism (1987)

Kinetic refolding reactions of ferricytochrome c and beta-lactoglobulin have been studied by stopped-flow circular dichroism by monitoring rapid ellipticity changes of peptide backbone and side-chain chromophores. In both proteins, a transient intermediate accumulates within the dead time of stopped-flow mixing (18 ms), and the intermediate has an appreciable amount of secondary structure but possesses an unfolded tertiary structure. It is suggested that the rapid formation of a secondary structure framework in protein folding is a common property observed in a variety of globular proteins.
HyPursuit (1996)

HyPursuit is a new hierarchical network search engine that clusters hypertext documents to structure a given information space for browsing and search act ivities. Our content-link clustering algorithm is based on the semantic information embedded in hyperlink structures and document contents. HyPursuit admits multiple, coexisting cluster hierarchies based on different principles for grouping documents, such as the Library of Congress catalog scheme and automatically created hypertext clusters.
Immunization therapy for Alzheimer disease? (2005)

Alzheimer disease (AD) is characterized pathologically by the accumulation of cortical neuritic plaques and neurofibrillary tangles. Neuritic plaques are composed of a central core of amyloid-β (Aβ) peptide fibrils associated with swollen and tortuous dystrophic neurites, reactive microglia and astrocytes, and glial filaments. Neurofibrillary tangles are composed of abnormally phosphorylated intracellular tau proteins wound into paired helical filaments. Evidence suggests that deposition of Aβ is a primary step in a cascade of events that ultimately leads to the loss of memory and other cognitive abilities that characterizes AD.1–3⇓⇓ First, all three genetic mutations that cause early onset, autosomal dominant, familial AD in the amyloid precursor protein, presenilin 1, and presenilin 2 (chromosomes 21, 14, and 1) result in the increased production of Aβ. Second, the genetic risk factor for AD, apolipoprotein E (apoE) genotype (chromosome 19, e4 increases risk, e2 decreases risk), appears to result from apoE acting as an Aβ chaperone, differentially influencing Aβ clearance and fibrillogenesis. Third, in trisomy 21, Aβ appears to be deposited prior to the accumulation of neurofibrillary tangles. Finally, mutations in the tau gene cause a degenerative dementia with tangle formation but without deposition of Aβ. These data suggest that therapeutic interventions that prevent the deposition of Aβ or promote its clearance could be a viable strategy for disease treatment and/or prevention.

Much has been learned about the processing of the Aβ peptide in the 20 years since Glenner and Wong first purified the protein. The Aβ protein that accumulates in AD is a 38 to 43 amino acid peptide derived from a much larger transmembrane protein, the amyloid precursor protein. The Aβ peptide is produced by cleavage of the precursor protein by the enzymes β-secretase and γ-secretase. By contrast, cleavage of the precursor protein with α-secretase prevents the formation of …
A Weighted OFDM Signal Scheme for Peak-to-Average Power Ratio Reduction of OFDM Signals (2012)

In this paper, a peak-to-average-ratio (PAPR) reduction scheme based on a weighted orthogonal frequency-division multiplexing (OFDM) signal is proposed to reduce the PAPR without distortion in removing the weight at the receiver side. In the proposed scheme, a weight is imposed on each discrete OFDM signal via a certain kind of a bandlimited signal, and an OFDM signal formed with the weighted discrete data is then considered before a high power amplifier (HPA), whereas the original signal can be recovered completely at the receiver side. Meanwhile, the time duration needed to transmit the weighted OFDM signal is the same as the time duration for the original OFDM signal. The effectiveness of the proposed scheme is evaluated with computer simulations. According to numerical results, the PAPR of the weighted OFDM signal is smaller than that of the clipping and filtering (C&F) method, and the bit-error-rate (BER) performance of the weighted OFDM system is improved compared with the C&F method. Here, the proposed method is simpler than the C&F method.