gebhart/patrepeval huggingface dataset:
Formation of a supramolecular complex is involved in the reconstitution of basement membrane components (1983)

Basement membrane macromolecules, including type IV collagen, laminin, and heparan sulfate proteoglycan, do not aggregate when incubated alone. Rather, precipitation occurs in the presence of equimolar amounts of laminin and type IV collagen but variable amounts of heparan sulfate proteoglycan. This interaction requires native laminin and type IV collagen. Heparan sulfate proteoglycan increases the precipitation of laminin particularly in the presence of type IV collagen. Fibronectin does not cause type IV collagen to precipitate. These studies show that the components of basement membrane interact in a highly specific manner and suggest that such interactions may be involved in the deposition of basement membrane in situ.
Influence of laser parameters and staining on femtosecond laser-based intracellular nanosurgery (2010)

Femtosecond (fs) laser-based intracellular nanosurgery has become an important tool in cell biology, albeit the mechanisms in the so-called low-density plasma regime are largely unknown. Previous calculations of free-electron densities for intracellular surgery used water as a model substance for biological media and neglected the presence of dye and biomolecules. In addition, it is still unclear on which time scales free-electron and free-radical induced chemical effects take place in a cellular environment. Here, we present our experimental study on the influence of laser parameters and staining on the intracellular ablation threshold in the low-density plasma regime. We found that the ablation effect of fs laser pulse trains resulted from the accumulation of single-shot multiphoton-induced photochemical effects finished within a few nanoseconds. At the threshold, the number of applied pulses was inversely proportional to a higher order of the irradiance, depending on the laser repetition rate and wavelength. Furthermore, fluorescence staining of subcellular structures before surgery significantly decreased the ablation threshold. Based on our findings, we propose that dye molecules are the major source for providing seed electrons for the ionization cascade. Consequently, future calculations of free-electron densities for intracellular nanosurgery have to take them into account, especially in the calculations of multiphoton ionization rates.
Restriction fragment analysis of chromosomal DNA defines different strains of Mycobacterium tuberculosis. (1986)

As an initial step in gaining a better understanding of the important clinical properties that vary between strains of mycobacteria, we attempted to find molecular markers that would define different strains of Mycobacterium tuberculosis. We used restriction fragment analysis with the endonuclease MboI and hybridization with total M. tuberculosis DNA to examine DNA differences between 15 strains of M. tuberculosis. We were able to identify different strains using this method. In order to assess the sensitivity of this method in identifying different strains, we compared it with phage typing. The 2 methods appear to be similar in sensitivity and also to be complementary. There were 2 examples where restriction fragment analysis did not separate strains with different phage types. In addition, there were 2 examples where phage typing did not separate strains with different restriction patterns. Finally, there were 2 epidemiologically unrelated strains with the same restriction pattern and the same phage type. This method of restriction fragment analysis of chromosomal DNA is potentially useful for epidemiologic studies of tuberculosis. Additionally, by analyzing the genome of M. tuberculosis, molecular markers may well be defined that will be useful in discovering the pathogenesis of the clinical properties of M. tuberculosis, which previously have been poorly understood.
Alterations in gene expression induced by cyclic mechanical stress in trabecular meshwork cells. (2009)

CMS activated many genes that could influence the aqueous humor outflow facility, specifically genes involved in ECM synthesis and remodeling (e.g. MMPs), cytoskeletal organization, and cell adhesion. Induction of MMP3 has the potential to increase the aqueous humor outflow facility and could be part of a homeostatic mechanism involved in the maintenance of normal intraocular pressure (IOP) levels. Other observed changes are more likely to be related to general cellular responses to stress (e.g., HSP70, ECSM1, and BMP2). Although these latter changes may initially help to repair mechanical damage, some of them such as the induction of BMP2 could eventually increase tissue rigidity and compromise the ability of the TM to maintain normal levels of outflow resistance.
Association between neutrophil functions and periparturient disorders in cows (1994)

Neutrophil functions were examined in healthy periparturient dairy cows (n = 46) and in cows with retained placenta and metritis complex (n = 20); metritis (n = 18); or mastitis (n = 13). Blood samples (50 ml) were collected from each cow via jugular vein twice weekly from 1.5 weeks before to 4 weeks after parturition. Neutrophil function was evaluated, using 6 tests: random migration, chemotaxis, ingestion, myeloperoxidase activity (iodination), superoxide production (cytochrome C reduction), and antibody-dependent cell-mediated cytotoxicity. Ability to ingest bacteria and random migration activity of neutrophils from clinically normal cows were high around parturition and increased immediately after parturition, whereas myeloperoxidase activity and antibody-dependent cell-mediated cytotoxicity ability of neutrophils from these cows decreased after parturition. Measurement of neutrophil function in 4 ovariectomized cows revealed significant (P < 0.0005) seasonal changes in results of all 6 functional assays. We observed various defects of neutrophil function in all cows with abnormal conditions after parturition. Before parturition, superoxide production activity by neutrophils from cows with metritis and chemotaxis by neutrophils from cows with mastitis were significantly (P < 0.001 and P < 0.05, respectively) lower, indicating that a defect of neutrophil function may be a predisposing factor in the development of these disorders. In conclusion, the host defense role of neutrophils in periparturient cows was impaired, principally because of a defect in killing capacity, which may increase susceptibility to infections. We also investigated the in vitro effects of arachidonic acid metabolites and recombinant human colony-stimulating factors (rhCSF) on functions of neutrophils from clinically normal and postparturient cows with abnormalities, including retained placenta, metritis, or mastitis (n = 5/group). Each abnormal cow was matched for postpartum period with a clinically normal cow. Neutrophils from individual cows were preincubated with arachidonic acid metabolites (prostaglandin F2 alpha, 10(-7) M; prostaglandin E2, 10(-6) M; leukotriene B4, 10(-8) M; and lipoxin B, 10(-8) M) and rhCSF (rh-granulocyte-CSF, 1,000 or 6,000 U/ml; rh-granulocyte-macrophage-CSF, 5 or 15 ng/ml) in a 37 C water bath for 30 minutes before submitting them to function assays. There was no response by neutrophils from either clinically normal or abnormal postparturient cows to treatment with either arachidonic acid metabolites or rhCSF in any of the 6 functional assays. However, preincubation of neutrophils alone in a 37 C water bath for 30 minutes resulted in some alteration of neutrophil function.(ABSTRACT TRUNCATED AT 400 WORDS)
Catechol O-methyltransferase. 8. Structure-activity relationships for inhibition by 8-hydroxyquinolines (1976)

A series of 5- and 7-substituted 8-hydroxyquinolines was evaluated as inhibitors of catechol O-methyltransferase (COMT, E.C. 2.1.1.6). The electronic character of the substituents in the 5 position appeared to have only a small effect if any on the inhibitory activity of these compounds. A significant factor which contributes to the inhibitory activity of these compounds appears to be the nature of the 7-substituent. The structure-activity relationship for this series of inhibitors is discussed relative to the nature of the enzymatic binding site.
Recent Advances in the Medicinal Chemistry of Antifungal Agents (1996)

The need for new antifungal agents has never been greater. Over the last 10 years the incidence of life-threatening fungal infections has increased dramatically as the population of immunocompromised individuals induding cancer, organ transplant, and AIDS patients has increased. Present therapeutic options for· the treatment of these infections are limited to compounds in two classes, the polyenes and the azoles. Some polyene research still continues with analogs of amphotericin B in the hopes of decreasing toxicity. Much work continues in the azole area with follow-up compounds to fluconazole and itraconazole in order to expand the spectrum and provide oral and iv formulation potential. A newer class of cell wall active agents that has been developed to the point of seeing clinical candidates is the cyclic lipopeptide echinocandin family. This group has the potential of providing broad spectrum fungicidal activity with a much lower toxicity level than .the current agents. Another newer class of natural products known as the aureobasidins has potent, oral fungicidal activity against Candida spp. Research has continued with the pradimicins to produce several new semisynthetic derivatives with comparable activity and spectrum to the parent compound but with improved water-solubility. Work with the nikkomycin class has delineated points of the SAR but has not produced compounds of sufficient potency for clinical use. The allylamines have been examined further to provide analogs of terbinafine with increased Candida activity but are still most highly potent versus dermatophytes. Several other newer classes with unique mechanisms of action have also been identified.
Dimer structure of magainin 2 bound to phospholipid vesicles (2002)

Magainin 2 from African clawed frog Xenopus laevis is an antimicrobial peptide with broad spectra and action mechanisms considered to permeabilize bacterial membranes. CD, vibration, and solid-state NMR spectroscopies indicate the peptide adopts an alpha-helical conformation on binding to phospholipid bilayers, and its micelle-bound conformation, being monomeric and alpha-helical, is well detailed. We showed, however, that the peptide dimerizes on binding to phospholipid bilayers. This difference in the conformation and aggregation state between micelle- and bilayer-bound states prompted us to analyze the conformation of an equipotent analog of magainin 2 (F5Y,F16W magainin 2) bound to phosphatidylcholine vesicles using transferred nuclear Overhauser enhancement (TRNOE) spectroscopy. While observed medium-range TRNOE cross peaks were characteristic of alpha-helix, many long-range cross peaks were not compatible with the peptide's monomeric state. Simulated annealing calculations generated dimer structures indicating (1) two peptide molecules have a largely helical conformation in antiparallel orientation forming a short coiled-coil structure, (2) residues 4-20 are well converged and residues 9-20 are in an alpha-helical conformation, and (3) the interface of the two peptide molecules is formed by well-defined side chains of hydrophobic residues. Finally, determined structures are compatible with numerous investigations examining magainin-phospholipid interactions.
Low pressure, light initiated, glow discharge switch for high power applications (1986)

A low pressure glow discharge switch that has a number of features that are desirable for high power applications is described. The switch has achieved high stand-off voltage and peak current, has potential for very fast current rate of rise, and operates near the glow-to-arc transition in hydrogen or helium. Closure is initiated by light incident on the back of the cathode, and it is observed that surface damage within the area of illumination is less than surrounding areas. Several aspects of the switch are similar to thyratrons and pseudosparks.
Genetic analysis of the inheritance of B cell hyperactivity in relation to the development of autoantibodies and glomerulonephritis in NZB x SWR crosses. (1983)

Autoimmune NZB mice have a primary B cell abnormality manifested by spontaneous hypersecretion of IgM in short-term cultures. The purpose of this study was to characterize the genes that specify this intrinsic B cell defect and determine their relationship to "autoimmunity" genes. The increase in IgM secretion was shown to result from two independently segregating genetic traits: a) an increased number of IgM-containing cells, and b) an increased rate of secretion of IgM per cell. In this study, approximately 600 NZB, SWR, F1, F2, and reciprocal back-cross mice were hemisplenectomized at 5 to 6 months of age to determine the number of IgM-containing cells and the secretion of IgM in 4-hr cultures. These animals were followed prospectively for the development of anti-DNA (native and denatured) and anti-red blood cell autoantibodies, and proteinuria, and studied at autopsy for the development of glomerulonephritis. The severity and incidence of renal lesions was influenced to some extent by the presence of B cell hyperactivity. However, a proportion of F2 and backcross progeny mice that did not show B cell hyperactivity eventually developed autoantibodies and autoimmune disease.
Fusobacterium nucleatum (2011)

The Gram-negative, non-sporulating, obligately anaerobic species, Fusobacterium nucleatum, is rapidly gaining notoriety as a pathogen with a surprising number of associated diseases. Recently, we have found that F. nucleatum is a more common resident of the GI tract than originally thought, and thus, through several studies, we have attempted to determine its gut-relevant potential for virulence. We have found that F. nucleatum possesses a number of pathogenic traits with relevance to gut diseases such as inflammatory bowel disease (IBD), however, we have also documented strain-associated differences in virulence. An intriguing picture emerges that paints F. nucleatum as both conferring beneficial as well as detrimental effects on host cells; and we suggest that the ultimate effects of F. nucleatum infection in the gut are a consequence of the microbes with which this species aggregates.
Casein Phosphopeptides in Oral Health - Chemistry and Clinical Applications (2007)

The casein phosphopeptides (CPP) are derived from the milk protein casein by tryptic digestion. The CPP, containing the sequence -Pse-Pse-Pse-Glu-Glu- where Pse is a phosphoseryl residue, stabilize calcium and phosphate ions in aqueous solution and make these essential nutrients bioavailable. Under alkaline conditions the calcium phosphate is present as an alkaline amorphous phase complexed by the CPP, referred to as casein phosphopeptide-amorphous calcium phosphate (CPP-ACP). The CPP-ACP complexes readily incorporate fluoride ions forming casein phosphopeptide-amorphous calcium fluoride phosphate (CPP-ACFP). A mechanism is discussed which provides a rationale for the ability of the CPP-ACP to remineralize carious lesions in dental enamel. Clinical applications of the CPP-ACP as agents in the treatment of dental caries and other hypomineralized conditions are reviewed. It is concluded that the CPP are a safe and novel carrier for calcium, phosphate and hydroxide (fluoride) ions to promote enamel remineralization with application in oral care products, dental professional products and foodstuffs.
Glatiramer acetate ameliorates inflammatory bowel disease in mice through the induction of Qa‐1‐restricted CD8+ regulatory cells (2012)

Inflammatory bowel diseases (IBDs) are complex multifactorial immunological disorders characterized by dysregulated immune reactivity in the intestine. Here, we investigated the contribution of Qa-1-restricted CD8(+) Treg cells in regulating experimental IBD in mice. We found that CD8(+) T cells induced by T-cell vaccination ameliorated the pathological manifestations of dextran sulfate sodium induced IBD when adoptively transferred into IBD mice. In addition, CD8(+) cell suppressive activity was induced by vaccination with glatiramer acetate (GA), an FDA-approved drug for multiple sclerosis (MS). We next showed that GA-induced CD8(+) Treg cells worked in a Qa-1-dependent manner and their suppressive activity depends on perforin-mediated cytotoxicity. Finally, we confirmed the role of CD4(+) T cells in dextran sulfate sodium induced colitis progression, and clarified that GA-induced CD8(+) T cells exerted their therapeutic effects on colitis by targeting pathogenic CD4(+) T cells. Our results reveal a new regulatory role of Qa-1-restricted CD8(+) Treg cells in IBD and suggest their induction by GA vaccination as a potential therapeutic approach to IBD.
Analysis of gene expression microarrays for phenotype classification. (2000)

Several microarray technologies that monitor the level of expression of a large number of genes have recently emerged. Given DNA-microarray data for a set of cells characterized by a given phenotype and for a set of control cells, an important problem is to identify "patterns" of gene expression that can be used to predict cell phenotype. The potential number of such patterns is exponential in the number of genes. In this paper, we propose a solution to this problem based on a supervised learning algorithm, which differs substantially from previous schemes. It couples a complex, non-linear similarity metric, which maximizes the probability of discovering discriminative gene expression patterns, and a pattern discovery algorithm called SPLASH. The latter discovers efficiently and deterministically all statistically significant gene expression patterns in the phenotype set. Statistical significance is evaluated based on the probability of a pattern to occur by chance in the control set. Finally, a greedy set covering algorithm is used to select an optimal subset of statistically significant patterns, which form the basis for a standard likelihood ratio classification scheme. We analyze data from 60 human cancer cell lines using this method, and compare our results with those of other supervised learning schemes. Different phenotypes are studied. These include cancer morphologies (such as melanoma), molecular targets (such as mutations in the p53 gene), and therapeutic targets related to the sensitivity to an anticancer compounds. We also analyze a synthetic data set that shows that this technique is especially well suited for the analysis of sub-phenotype mixtures. For complex phenotypes, such as p53, our method produces an encouragingly low rate of false positives and false negatives and seems to outperform the others. Similar low rates are reported when predicting the efficacy of experimental anticancer compounds. This counts among the first reported studies where drug efficacy has been successfully predicted from large-scale expression data analysis.
Discovery of a New Efficient Chiral Ligand for Copper-Catalyzed Enantioselective Michael Additions by High-Throughput Screening of a Parallel Library (2000)

The optimal ligand 1 for the enantioselective copper-catalyzed 1,4-addition of Et2Zn to cyclic enones [Eq. (1)] was established by multisubstrate (high-throughput) screening of a parallel library of chiral Schiff base ligands. The screening data show how the ligand structure is finely tuned by mutual influences of stereogenic center a (which controls the absolute configuration of the reaction product), stereogenic center b, and the substitution pattern of the aromatic ring. Tf=F3CSO2.
Preparation and Physisorption Characterization of d-Glucose-Templated Mesoporous Silica Sol−Gel Materials (1999)

The synthesis of mesoporous silica materials has been achieved with d-glucose as a nonsurfactant pore-forming agent in the sol−gel reactions of tetraethyl orthosilicate under basic or near neutral (pH 6) conditions. Regardless of the pH values of the medium, transparent and monolithic glucose-containing silica gels could be obtained. d-Glucose was removed by water extraction to afford silica materials with high specific surface area of ∼800 m2/g, pore volume of ∼0.5 cm3/g, and narrow pore distribution with BJH pore diameter of 3.2−3.5 nm, indicative of the mesoporosity. As the glucose concentration is increased in the synthesis, these pore parameters generally increase, and the N2 sorption isotherms gradually transform from reversible type I to type IV-like isotherms with H2 hysteresis. At low glucose concentrations (<36 wt %), both micropores and mesopores contribute to the porosity of the materials. However, at high glucose concentrations (36−64 wt %), mesopores are dominant. The characteristics of pore structures are similar to those for the materials obtained under acid catalysis. The aggregation or assembly of the aggregates of the glucose molecules and their hydrogen-bonding interactions with the silicate species might direct the mesophase formation.
A framework for the quantitative evaluation of disentangled representations (2018)

Recent AI research has emphasised the importance of learning disentangled representations of the explanatory factors behind data. Despite the growing interest in models which can learn such representations, visual inspection remains the standard evaluation metric. While various desiderata have been implied in recent definitions, it is currently unclear what exactly makes one disentangled representation better than another. In this work we propose a framework for the quantitative evaluation of disentangled representations when the ground-truth latent structure is available. Three criteria are explicitly defined and quantified to elucidate the quality of learnt representations and thus compare models on an equal basis. To illustrate the appropriateness of the framework, we employ it to compare quantitatively the representations learned by recent state-of-the-art models.
Formation of aggregates from a thermolabile in vivo folding intermediate in P22 tailspike maturation. A model for inclusion body formation. (1988)

The in vivo accumulation of polypeptide chains in the form of aggregated non-native states is a problem in many applications of biotechnology. In the maturation pathway of the thermostable P22 tailspike endorhamnosidase, the folding and chain association intermediates can be distinguished from the native tailspikes in crude extracts of phage-infected Salmonella cells. Temperature-sensitive folding mutations, at many sites in the chain, destabilize these conformational intermediates preventing the formation of native tailspikes at restrictive temperatures (Goldenberg, D. P., Smith, D. H., and King, J. (1983) Proc. Natl. Acad. Sci. U. S. A. 80, 7060-7064). We report here that both wild type and mutant tailspike polypeptide chains which fail to reach the native state accumulate in an aggregated state. These off-pathway aggregates form from a thermolabile intermediate in the productive folding pathway. These aggregation reactions are suppressed by lowering the temperature of maturation. Similar off-pathway steps from folding intermediates may account for the non-native aggregates often found in the expression of cloned genes in heterologous hosts.