gebhart/patrepeval huggingface dataset:
α‐Bungarotoxin Binds to Low‐Affinity Nicotine Binding Sites in Rat Brain (1986)

Reported differences in the pharmacology and distribution of [3H]nicotine and [125I]alpha-bungarotoxin binding sites in mammalian brain suggest that these ligands label separate receptor sites. Affinity purification of an alpha-bungarotoxin binding protein from rat brain failed to copurify the high-affinity nicotine binding site, which remained in the nonbound soluble fraction after the affinity chromatography step. This confirms the independence of these putative receptor sites. Nevertheless, the binding of [125I]alpha-bungarotoxin to P2 membranes was inhibited by (-)-nicotine (Ki = 9 X 10(-6) M), and this sensitivity was preserved after affinity purification. It is proposed that alpha-bungarotoxin binds to a population of low-affinity nicotine binding sites. Comparison of the enantiomers of nicotine in competition studies at both radioligand binding sites revealed an 80-fold preference for the (-) form at the high-affinity [3H]nicotine binding site, whereas the site labelled by [125I]alpha-bungarotoxin displayed little stereoselectivity. In this respect, the brain alpha-bungarotoxin binding site resembles the nicotinic acetylcholine receptor from Torpedo electric organ.
Parameters affecting solvent production by Clostridium acetobutylicum in continuous culture (1984)

Parameters affecting the production of acetone and butanol by Clostridium acetobutylicum have been studied using chemostats with phosphate, sulfate, or magnesium as growth-limiting factors.Only under phosphate and sulfate limitation and at a pH below 5.0 were the solvents found to be the major fermentation products. Lactate was produced under sulfate limitation above pH 5.0. Magnesium limitation was not appropriate for continuous solvent formation. It was found that a threshold concentration of acid products was required for solvent production. The concentration of the suitable growth-limiting factor had to be in a range which allowed sufficient growth and substrate consumption to obtain these threshold concentrations of butyrate and/or acetate.
The “Lotus Effect” Explained:  Two Reasons Why Two Length Scales of Topography Are Important (2006)

Surfaces containing 4 x 8 x 40 microm staggered rhombus posts were hydrophobized using two methods. One, using a dimethyldichlorosilane reaction in the vapor phase, introduces a smooth modified layer, and the other, a solution reaction using methyltrichlorosilane, imparts a second (nanoscopic) length scale of topography. The smooth modified surface exhibits contact angles of thetaA/thetaR = 176 degrees /156 degrees . Arguments are made that the pinning of the receding contact line by the post tops (with thetaA/thetaR = 104 degrees /103 degrees ) is responsible for the hysteresis. The second level of topography raises the contact angles of the post tops and the macroscopic sample to theta(A)/theta(R) = >176 degrees />176 degrees and eliminates hysteresis. The increase in Laplace pressure due to the increase in the advancing contact angle of the post tops is a second reason that two length scales of topography are important.
Interactive effects of the tumor necrosis factor promoter and 3’-untranslated regions (1991)

The tumor necrosis factor (TNF) promoter and 3'-untranslated region (3'-UTR) each contain sequence elements that mediate a response to bacterial endotoxin. Although the promoter contains sequences that permit augmented TNF gene transcription in response to LPS, the 3'-UTR contains sequences that normally confer translational repression, but which allow "derepression" to occur after cell contact with endotoxin. We now show that both genetic elements act in concert during activation of TNF gene expression in macrophages. In order to do so, we have made use of chloramphenicol acetyltransferase reporter constructs in which the TNF promoter and 3'-UTR are represented either independently or in combination with one another. Suppression of chloramphenicol acetyltransferase and TNF mRNA synthesis, observed after treatment of the macrophages with dexamethasone, 2-aminopurine, pentoxifylline, or dibutyryl cAMP, has also been studied in detail. Each class of inhibitor suppresses TNF biosynthesis through a separate mechanism. Interestingly, suppression by pentoxifylline is manifested partly (but not entirely) at the level of transcription, and depends upon the presence of both the TNF promoter and 3'-UTR. The data suggest that other sequences within the TNF gene could also be required for the full effect of pentoxifylline, which may act to prevent processing of the primary transcript. The suppressive effect of dexamethasone is manifested both at the level of transcription and at the level of translation, and is mediated both by sequences present in the TNF promoter and by sequences present in the 3'-UTR. Suppression by 2-aminopurine is solely dependent upon promoter sequences.
Genome-wide profiling at methylated promoters in pancreatic adenocarcinoma (2008)

Promoter and CpG island array analysis finds aberrant methylation of hundreds of promoters and CpG islands in pancreatic cancer cells.
Seed Dormancy in Red Rice (1992)

Exposure of dehulled, dormant red rice (Oryza sativa) seeds to dormancy-breaking treatments (10 mm sodium nitrite, 20 mm propionic acid, 30 mm methyl propionate, 40 mm propionaldehyde, or 70 mmn-propanol) induced tissue pH acidification during chemical contact at least 12 h before visible germination. During chemical contact, the onset of embryo acidification occurred before or coincident with the chemical contact interval necessary for subsequent germination. Upon seed transfer to H(2)O following chemical contact, embryo pH also decreased coincident with visible germination. During this period, the percentage of germination and embryo pH were closely linked irrespective of the dormancy-breaking compound used. Therefore, tissue acidification during the breaking of seed dormancy and the germination process may be analogous to similar tissue pH changes associated with the termination of developmental arrest in other multicellular systems, such as brine shrimp cysts and nematode larvae.
The specific direct interaction of helper T cells and antigen-presenting B cells. II. Reorientation of the microtubule organizing center and reorganization of the membrane-associated cytoskeleton inside the bound helper T cells. (1987)

We have produced and investigated cell couples formed between cloned Th cells or T hybridoma cells, and either Ag-presenting B hybridoma or B lymphoma cells. The specific direct interaction between a Th and B-APC is here demonstrated by two rearrangements occurring inside the bound Th cell; the MTOC (and presumably the GA) is oriented to face the cell contact region with the B cell, and a membrane-associated cytoskeletal protein, talin, becomes concentrated under the contacting Th membrane. In the absence of the specific Ag or the correct Ia determinant, nonspecific T-B cell couples form that are morphologically indistinguishable from specific cell couples in the light microscope, but neither the MTOC nor the talin rearrangement occurs inside the bound T cell of such nonspecific couples. Furthermore, Ag processing by the B cell is required to produce the MTOC and talin rearrangements within the T cell in specific T-B couples. In the case of allogeneic Th-B cell couples, similar specific MTOC and talin rearrangements are observed inside the Th. Extracellular Ca2+ is required for the MTOC orientation to occur inside the specifically bound Th cell, but not for the talin rearrangement. It is proposed that the MTOC (and GA) reorientation and the talin rearrangement are involved in the directed secretion of GA-derived lymphokines from the Th cell to the bound B cell.
Pharmacological manipulation of the complement system in human diseases (1996)

Complement is one of the powerful effector systems involved in the body's defense. When present in a dormant state it can, in concert with other components of immune system, protect the individual from foreign pathogens. However, inappropriately activated complement can cause disease. Several disease states such as immune complex and autoimmune diseases and deficiencies of some complement regulators are associated with inappropriate activation of complement. In some diseases complement is activated for a long or indefinite period while in others for a comparatively short time; in some it is activated systemically, in others locally; in some whole cascade is activated, in others only a few components are activated; in some classical pathway is activated, in others alternative pathway. In some diseases activation of complement takes place on cell and tissue surfaces. In many complement activating diseases biological activities of complement fragments become detrimental resulting in tissue injury and disease. Inhibition of complement by specific inhibitors is likely to arrest complement mediated disease processes. From this point of view, some laboratories are developing low molecular weight synthetic inhibitors whereas others are focusing on the development of high molecular weight plasma or cell surface complement inhibitors in their natural or recombinant forms for therapeutic purposes. A review concerning development of low molecular weight inhibitors with the eventual aim of manipulating complement system in human diseases was recently published (1,2). This review is concerned with high molecular weight natural or recombinant complement inhibitory molecules in human plasma or cell membranes, some of which are already in clinical use.
Geotagging with local lexicons to build indexes for textually-specified spatial data (2010)

The successful execution of location-based and feature-based queries on spatial databases requires the construction of spatial indexes on the spatial attributes. This is not simple when the data is unstructured as is the case when the data is a collection of documents such as news articles, which is the domain of discourse, where the spatial attribute consists of text that can be (but is not required to be) interpreted as the names of locations. In other words, spatial data is specified using text (known as a toponym) instead of geometry, which means that there is some ambiguity involved. The process of identifying and disambiguating references to geographic locations is known as geotagging and involves using a combination of internal document structure and external knowledge, including a document-independent model of the audience's vocabulary of geographic locations, termed its spatial lexicon. In contrast to previous work, a new spatial lexicon model is presented that distinguishes between a global lexicon of locations known to all audiences, and an audience-specific local lexicon. Generic methods for inferring audiences' local lexicons are described. Evaluations of this inference method and the overall geotagging procedure indicate that establishing local lexicons cannot be overlooked, especially given the increasing prevalence of highly local data sources on the Internet, and will enable the construction of more accurate spatial indexes.
Nanodelivery Strategies in Cancer Chemotherapy: Biological Rationale and Pharmaceutical Perspectives (2012)

Nanotechnology is revolutionizing our approach to drug delivery, a key determinant of drug efficacy. Here, we present cancer drug delivery strategies that exploit nanotechnology, providing first an overview of tumor biology aspects that critically affect the design of drug delivery carriers, namely the enhanced permeability and retention effect, the lower tumor extracellular pH and tumor-specific antigens. In general, nanoscience-based approaches have circumvented limitations in the delivery of cancer therapeutics, related to their poor aqueous solubility and toxicity issues with conventional vehicles and resulted in improved pharmacokinetics and biodistribution. Included in the discussion are promising examples and pharmaceutical perspectives on liposomes, nanoemulsions, solid lipid nanoparticles, polymeric nanoparticles, dendrimers, carbon nanotubes and magnetic nanoparticles. As the cardinal features of the ideal multifunctional cancer drug nanocarrier are becoming clear, and drug development challenges are proactively addressed, we anticipate that future advances will enhance therapeutic outcomes by refining the delivery and targeting of complex payloads.
In Vitro Effects of IL-12 on HIV-1-Specific CTL Lines from HIV-1-Infected Children (1998)

We studied the in vitro effects of IL-12 on HIV-1-specific CTL lines derived from PBMC of HIV-1-infected children. HIV-1-specific CTL lines were derived by limiting dilution following Ag-specific stimulation of PBMC from HIV-1-infected children and were maintained with repeated anti-CD3 stimulation. Following incubation with IL-12 for 5 to 7 days, HIV-1-specific cytotoxicity was augmented in a dose-dependent fashion (mean increase, 94 +/- 83 lytic units; p = 0.0006). Experiments performed with CD3-blocking Abs and MHC-mismatched targets demonstrated that the IL-12-enhanced activity was MHC restricted and dependent on cells bearing CD3. The effect of IL-12 on proliferation of the CTL lines as tested by [3H]TdR uptake was minimal, with stimulation indexes ranging from 1.25 to 4.9. The effects of IL-12 on cytotoxicity were not significantly altered by addition of Ab to the IL-2R (anti-Tac) in quantities sufficient to block exogenous IL-2 (p = 0.15), demonstrating that endogenous IL-2 activity is not required for IL-12-enhanced cytolytic activity. Likewise, addition of neutralizing Ab specific for IFN-gamma did not change IL-12-enhanced cytotoxicity (p = 0.61). The in vivo role of IL-12 in the generation and the stimulation of CTL remains to be determined; however, its ability to augment HIV-1-specific CTL in vitro adds additional support for IL-12 as a candidate for immune-based therapy of HIV-1.
Evidence for differential functions of the p50 and p65 subunits of NF-kappa B with a cell adhesion model. (1993)

The p50 and p65 subunits of NF-kappa B represent two members of a gene family that shares considerable homology to the rel oncogene. Proteins encoded by these genes form homo- and heterodimers which recognize a common DNA sequence motif. Recent data have suggested that homodimers of individual subunits of NF-kappa B can selectively activate gene expression in vitro. To explore this possibility in a more physiological manner, murine embryonic stem (ES) cells were treated with phosphorothio antisense oligonucleotides to either p50 or p65. Within 5 h after exposure to phosphorothio antisense p65 oligonucleotides, cells exhibited dramatic alterations in adhesion properties. Similar findings were obtained in a stable cell line that expressed a dexamethasone-inducible antisense mRNA to p65. Although antisense oligonucleotides raised against both p50 and p65 elicited a significant reduction in their respective mRNAs, only the cells treated with antisense p50 maintained a normal morphology. However, 6 days following removal of leukemia-inhibiting factor, a growth factor which suppresses embryonic stem cell differentiation, adhesion properties of cells treated with the antisense p50 oligonucleotides were markedly affected. The ability of the individual antisense oligonucleotides to elicit differential effects on cell adhesion, a property dependent upon the stage of differentiation, suggests that the p50 and p65 subunits of NF-kappa B regulate gene expression either as homodimers or as heterodimers with other rel family members. Furthermore, the finding that reduction in p65 expression alone had profound effects on cell adhesion properties indicates that p65 plays an important role in nonstimulated cells and cannot exist solely complexed with the cytosolic inhibitory protein I kappa B.
Lysyl oxidase activity regulates oncogenic stress response and tumorigenesis (2013)

Cellular senescence, a stable proliferation arrest, is induced in response to various stresses. Oncogenic stress-induced senescence (OIS) results in blocked proliferation and constitutes a fail-safe program counteracting tumorigenesis. The events that enable a tumor in a benign senescent state to escape from OIS and become malignant are largely unknown. We show that lysyl oxidase activity contributes to the decision to maintain senescence. Indeed, in human epithelial cell the constitutive expression of the LOX or LOXL2 protein favored OIS escape, whereas inhibition of lysyl oxidase activity was found to stabilize OIS. The relevance of these in vitro observations is supported by in vivo findings: in a transgenic mouse model of aggressive pancreatic ductal adenocarcinoma (PDAC), increasing lysyl oxidase activity accelerates senescence escape, whereas inhibition of lysyl oxidase activity was found to stabilize senescence, delay tumorigenesis, and increase survival. Mechanistically, we show that lysyl oxidase activity favors the escape of senescence by regulating the focal-adhesion kinase. Altogether, our results demonstrate that lysyl oxidase activity participates in primary tumor growth by directly impacting the senescence stability.
A unified approach to global program optimization (1973)

A technique is presented for global analysis of program structure in order to perform compile time optimization of object code generated for expressions. The global expression optimization presented includes constant propagation, common subexpression elimination, elimination of redundant register load operations, and live expression analysis. A general purpose program flow analysis algorithm is developed which depends upon the existence of an "optimizing function." The algorithm is defined formally using a directed graph model of program flow structure, and is shown to be correct. Several optimizing functions are defined which, when used in conjunction with the flow analysis algorithm, provide the various forms of code optimization. The flow analysis algorithm is sufficiently general that additional functions can easily be defined for other forms of global code optimization.
Genetic Variation in Sorghum for the Inhibition of Maize Pollen Tube Growth (1989)

Aniline blue fluorescence was used to study the growth of maize pollen tubes in the stigmas of 13 diverse sorghum accessions. In 12, only short maize pollen tubes were formed, but in the single exception (Sorghum nervosum Nr481) maize pollen tubes grew at least as far as the base of the style. The S. bicolor genotypes S9B and CMS (a cytoplasmic male sterile line) were hybridized with Nr481, and analysis of maize pollen tube growth in F1 plants, and BC1 plants using Nr481 as the recurrent parent, suggested that differences in inhibition of pollen tube growth were due to variation at a single locus, which we propose to designate lap (Inhibition of alien pollen tubes). Accession Nr481 appears to be homozygous for a recessive allele permitting maize pollen tube growth. Attempts were made to produce sorghum x maize hybrids using Nr481 and CMS derivatives which were known to allow maize pollen tube growth to the base of the style. A putative hybrid endosperm was obtained in one Nr481 × Seneca 60 maize cross, but this was not repeatable and no hybrid plants were produced. A fundamental problem may be the large size of the maize pollen tube, which could have difficulty growing through the sorghum ovary and in entering the micropyle.
Sodium pentosan polysulfate resulted in cartilage improvement in knee osteoarthritis - An open clinical trial- (2010)

Pentosan treatment in twenty patients with mild knee OA seemed to provide improvements in clinical assessments and C2C level of cartilage metabolism.
Strategies for stabilizing superoxide dismutase (SOD1), the protein destabilized in the most common form of familial amyotrophic lateral sclerosis (2010)

Amyotrophic lateral sclerosis (ALS) is a disorder characterized by the death of both upper and lower motor neurons and by 3- to 5-yr median survival postdiagnosis. The only US Food and Drug Administration-approved drug for the treatment of ALS, Riluzole, has at best, moderate effect on patient survival and quality of life; therefore innovative approaches are needed to combat neurodegenerative disease. Some familial forms of ALS (fALS) have been linked to mutations in the Cu/Zn superoxide dismutase (SOD1). The dominant inheritance of mutant SOD1 and lack of symptoms in knockout mice suggest a "gain of toxic function" as opposed to a loss of function. A prevailing hypothesis for the mechanism of the toxicity of fALS-SOD1 variants, or the gain of toxic function, involves dimer destabilization and dissociation as an early step in SOD1 aggregation. Therefore, stabilizing the SOD1 dimer, thus preventing aggregation, is a potential therapeutic strategy. Here, we report a strategy in which we chemically cross-link the SOD1 dimer using two adjacent cysteine residues on each respective monomer (Cys111). Stabilization, measured as an increase in melting temperature, of ∼20 °C and ∼45 °C was observed for two mutants, G93A and G85R, respectively. This stabilization is the largest for SOD1, and to the best of our knowledge, for any disease-related protein. In addition, chemical cross-linking conferred activity upon G85R, an otherwise inactive mutant. These results demonstrate that targeting these cysteine residues is an important new strategy for development of ALS therapies.
Random and continuous-access immunoassays with chemiluminescent detection by Access automated analyzer (1994)

The Access Immunoassay System is an automated random and continuous-access analyzer for use with heterogeneous enzyme immunoassays. The instrument stores refrigerated reagent packs for as many as 24 different immunoassays. Throughput is 50-100 tests per hour. One- and two-step, and sandwich and competitive formats, each with various incubation times, can be accommodated, and sample sizes can vary from 10 to 200 microL. A paramagnetic microparticle solid phase combines with a chemiluminescent substrate for signal generation. Within-run CVs for noninfectious disease assays were 2.0% to 9.2%; total CVs were 3.4% to 11.1%. Regression analysis of method comparison studies with established procedures yielded slopes of 0.84 to 1.12 and correlation coefficients > or = 0.94 for 12 of 14 assays (range 0.83-0.99). Compared with culture methods, the Access assay for Chlamydia in urogenital specimens demonstrated sensitivity, specificity, and positive and negative predictive values of 90%, 99.7%, 95%, and 99%, respectively.
Asymmetric oxidation of sulphides to sulphoxides catalysed by titanium complexes of N-salicylidene-L-amino acids (1987)

Oxidation of alkyl aryl and heterocyclic sulphides with ButOOH and a catalytic amount of titanium N-salicylidene-L-amino acids (0.1 mol equiv.) affords the corresponding sulphoxides with an enantiomeric excess (e.e.) up to 21%. The use of other metal complexes with the same ligands led to racemic products.
Secure function evaluation with ordered binary decision diagrams (2006)

Privacy-preserving protocols allow multiple parties with private inputs to perform joint computation while preserving the privacy of their respective inputs. An important cryptographic primitive for designing privacy-preserving protocols is secure function evaluation (SFE). The classic solution for SFE by Yao uses a gate representation of the function that the two parties want to jointly compute. Fairplay is a system that implements the classic solution for SFE. In this paper, we present a new protocol for SFE that uses a graph-based representation of the function. Specifically we use the graph-based representation called ordered binary decision diagrams (OBDDs). For a large number of Boolean functions, OBDDs are more succinct than the gate-based representation. Preliminary experimental results based on a prototype implementation shows that for several functions, our protocol results in a smaller bandwidth than Fairplay. For example, for the classic millionaire's problem, our new protocol results in a approximately $45$\% bandwidth reduction over Fairplay. Therefore, our protocols will be particularly useful for applications for environments with limited bandwidth, such as applications for wireless and sensor networks.