gebhart/patrepeval huggingface dataset:
Human trabecular meshwork organ culture: morphology and glycosaminoglycan synthesis. (1988)

Human corneoscleral explants were maintained for several weeks in defined, serum-free media. Trabecular cell vitality, as judged by vital stain exclusion, is high for at least one month. Trabecular ultrastructure, as compared to that of fresh eyes, first shows minor cellular and extracellular matrix degradation after 3 weeks in culture. The biosynthetic profiles of trabecular glycosaminoglycans (GAGs) change significantly by 3 weeks in culture. Eyes that are stored at 5 degrees C for up to 48 hr postmortem exhibit changes in trabecular ultrastructure and in GAG profiles; both characteristics return to normal by 7 days in culture. The incorporation pattern of 35S-sulfate and 3H-glucosamine into the GAGs of the trabecular meshwork (TM) is distinct from corneal or scleral incorporation. The relative incorporation of 3H-glucosamine into trabecular GAGs, as determined by sequential enzymatic degradation, is: 22.3% hyaluronic acid (HA), 27.9% chondroitin sulfate (CS), 21.3% dermatan sulfate (DS), 5.9% keratan sulfate (KS), 17.7% heparan sulfate (HS) and 4.9% unidentified material. The relative incorporation of 35S-sulfate into trabecular GAGs is: 0% HA, 32.9% CS, 34.8% DS, 7.7% KS, 13.8% HS and 11.1% into unidentified material. This profile is in good agreement with the profile that was previously obtained for human and nonhuman primate meshworks prior to culture. We conclude that corneoscleral explant organ culture is a useful tool for extracellular matrix studies within a time window from 7 to at least 14 days in culture.
The fetal valproate syndrome (1984)

We evaluated seven children who had been exposed to sodium valproate (or valproic acid) in utero. A consistent facial phenotype was observed in all seven in addition to other birth defects in four. The facial changes consisted of epicanthal folds which continued inferiorly and laterally to form a crease or groove just under the orbit, flat nasal bridge, small upturned nose, long upper lip with a relatively shallow philtrum, a thin upper vermillion border, and downturned angles of the mouth. Hypospadias, strabismus, and psychomotor delay were found in two males; two children had nystagmus and two had low birth weight.
Identification, Evolution, and Essentiality of the Mevalonate Pathway for Isopentenyl Diphosphate Biosynthesis in Gram-Positive Cocci (2000)

The mevalonate pathway and the glyceraldehyde 3-phosphate (GAP)-pyruvate pathway are alternative routes for the biosynthesis of the central isoprenoid precursor, isopentenyl diphosphate. Genomic analysis revealed that the staphylococci, streptococci, and enterococci possess genes predicted to encode all of the enzymes of the mevalonate pathway and not the GAP-pyruvate pathway, unlike Bacillus subtilis and most gram-negative bacteria studied, which possess only components of the latter pathway. Phylogenetic and comparative genome analyses suggest that the genes for mevalonate biosynthesis in gram-positive cocci, which are highly divergent from those of mammals, were horizontally transferred from a primitive eukaryotic cell. Enterococci uniquely encode a bifunctional protein predicted to possess both 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and acetyl-CoA acetyltransferase activities. Genetic disruption experiments have shown that five genes encoding proteins involved in this pathway (HMG-CoA synthase, HMG-CoA reductase, mevalonate kinase, phosphomevalonate kinase, and mevalonate diphosphate decarboxylase) are essential for the in vitro growth of Streptococcus pneumoniae under standard conditions. Allelic replacement of the HMG-CoA synthase gene rendered the organism auxotrophic for mevalonate and severely attenuated in a murine respiratory tract infection model. The mevalonate pathway thus represents a potential antibacterial target in the low-G+C gram-positive cocci.
Overexpression of core 2 N‐acetylglycosaminyltransferase enhances cytokine actions and induces hypertrophic myocardium in transgenic mice (1999)

Elevated levels of glycocojugates, commonly observed in the myocardium of diabetic animals and patients, are postulated to contribute to the myocardial dysfunction in diabetes. Previously, we reported that UDP-GlcNAc: Galbeta1-3GalNAcalphaRbeta1-6-N-acetylglucosaminyltransferas e (core 2 GlcNAc-T), a developmentally regulated enzyme of O-linked glycans biosynthesis pathway, is specifically increased in the heart of diabetic animals and is regulated by hyperglycemia and insulin. In this study, transgenic mice overexpressing core 2 GlcNAc-T with severe increase in cardiac core 2 GlcNAc-T activities were normal at birth but showed progressive and significant cardiac hypertrophy at 6 months of age. The heart of transgenic mice showed elevation of sialylated O-glycan and increases of c-fos gene expression and AP-1 activity, which are characteristics of cardiac stress. Furthermore, transfection of PC12 cells with core 2 GlcNAc-T also induced c-fos promoter activation, mitogen activated-protein kinase (MAPK) phosphorylation, Trk receptor glycosylation, and cell differentiation. These results suggested a novel role for core 2 GlcNAc-T in the development of diabetic cardiomyopathy and modulation of the MAP kinase pathway in the heart.-Koya, D., Dennis, J. W., Warren, C. E., Takahara, N., Schoen, F. J., Nishio, Y., Nakajima, T., Lipes, M. A., King, G. L. Overexpression of core 2 N-acetylglycosaminyltransferase enhances cytokine actions and induces hypertrophic myocardium in transgenic mice.
Changing Stereochemistry for a Metabolic Pathway in Vivo (1995)

The biosphere is inherently built of chiral molecules, and once their metabolism is established, the stereochemical course of the reactions involved is seen to remain highly conserved. However, by replacing the yeast peroxisomal multifunctional enzyme (MFE), which catalyzes the second and third reactions of beta-oxidation of fatty acids via D-3-hydroxyacyl-CoA intermediates, with rat peroxisomal MFE, which catalyzes the same reactions via L-3-hydroxy intermediates, it was possible to change the chiralities of the intermediates in a major metabolic pathway in vivo. Both stereochemical alternatives allowed the yeast cells to grow on oleic acid, implying that when the beta-oxidation pathways evolved, the overall function was the determining factor for the acquisition of MFEs and not the stereospecificities of the reactions themselves.
Enhanced Condensation on Lubricant-Impregnated Nanotextured Surfaces (2012)

Nanotextured superhydrophobic surfaces have received significant attention due to their ability to easily shed liquid drops. However, water droplets have been shown to condense within the textures of superhydrophobic surfaces, impale the vapor pockets, and strongly pin to the surface. This results in poor droplet mobility and degrades condensation performance. In this paper, we show that pinning of condensate droplets can be drastically reduced by designing a hierarchical micro-nanoscale texture on a surface and impregnating it with an appropriate lubricant. The choice of lubricant must take into account the surface energies of all phases present. A lubricant will cloak the condensate and inhibit growth if the spreading coefficient is positive. If the lubricant does not fully wet the solid, we show how condensate-solid pinning can be reduced by proper implementation of nanotexture. On such a surface, condensate droplets as small as 100 μm become highly mobile and move continuously at speeds that are several orders of magnitude higher than those on identically textured superhydrophobic surfaces. This remarkable mobility produces a continuous sweeping effect that clears the surface for fresh nucleation and results in enhanced condensation.
Vascular Permeability Factor (Vascular Endothelial Growth Factor) Expression and Angiogenesis in Cervical Neoplasia (1995)

Background : Angiogenesis is a critical factor in the progression of solid tumors, including cervical cancers. The mechanisms reponsible for angiogenesis in cervical neoplasia, however, are not well defined. Purpose: Our goal was to determine the relationship between angiogenesis and the expression of the angiogenic cytokine vascular permeability factor (VPF), also known as vascular endothelial growth factor, and its receptors in cervical neoplasia. Methods: Sixtysix cervical biopsy specimens were evaluated; among these, 16 samples were designated as benign, 17 as low-grade squamous intraepithelial lesions, 18 as high-grade squamous intraepithelial lesions, and 15 as invasive squamous cell carcinomas. Histologic sections immunostained for factor VIIIrelated antigen were evaluated quantitatively for microvessel density and for the presence of epithelial stromal vascular cuffing. Sections were also evaluated for VPF messenger RNA (mRNA) expression by in situ hybridization. Results: VPF mRNA expression, epithelial stromal vascular cuffing, and microvessel density counts were significantly increased in invasive carcinoma and in high-grade intraepithelial lesions as compared with lowgrade intraepithelial lesions and benign squamous epithelium. Vascular cuffing and increased microvessel density counts were also significantly associated with increased VPF mRNA expression. Conclusions: These observations suggest that VPF is an important angiogenic factor in cervical neoplasia. [J Natl Cancer Inst 87:1237-1245,1995]
Selective Tryptophan Modification with Rhodium Carbenoids in Aqueous Solution (2004)

A new transition metal-based reaction has been developed for the selective modification of tryptophan residues on protein substrates. After activation of vinyl-substituted diazo compounds by Rh2(OAc)4, the resulting metallocarbenoid intermediates were found to modify indoles in aqueous media despite competing reactions with water. Both N- and 2-substituted indole products were observed in the reaction. Following initial small-molecule studies, the reaction was performed on two protein substrates. Both myoglobin and subtilisin Carlsberg were modified readily in aqueous solution, and the tryptophan selectivity of the reactions was confirmed through MS analyses of trypsin digest fragments. It was also demonstrated that myoblobin concentrations as low as 10 muM still led to appreciable levels of modification. Reconstitution experiments confirmed that myoglobin retained its ability to bind heme following modification.
Overexpression of metastasis-associated in colon cancer 1 predicts a poor outcome of hepatitis B virus-related hepatocellular carcinoma (2012)

High intratumoral MACC1 expression can be associated with enhanced tumor progression and poor outcome of HBV-related HCC. MACC1 may serve as a prognostic biomarker for postoperative HCC.
Dynamics of the Cytotoxic T Cell Response to a Model of Acute Viral Infection (2015)

The exhaustive investigation of pathogen-induced effector T cells is essential to accurately quantify the dynamics of the human immune response. The yellow fever vaccine (YFV) has been broadly used as a model to understand how a controlled, self-resolving acute viral infection induces an effective and long-term protective immune response. Here, we extend this previous work by reporting the identity of activated effector T cell clones that expand in response to the YFV 2 weeks postvaccination (as defined by their unique T cell receptor gene sequence) and by tracking clones that enter the memory compartment 3 months postvaccination. This is the first study to use high-throughput sequencing of immune cells to characterize the breadth of the antiviral effector cell response and to determine the contribution of unique virus-induced clones to the long-lived memory T cell repertoire. Thus, this study establishes a benchmark against which future vaccines can be compared to predict their efficacy.
Purification and Characterization of Neutral Trehalase from the Yeast ABYS1 Mutant (1989)

Neutral trehalase was purified from stationary yeast ABYSl mutant cells deficient in the vacuolar proteinases A and B and the carboxypeptidases Y and s.The purified electrophoretically homogeneous preparation of phosphorylated neutral trehalase exhibited a molecular mass of 160,000 Da on nondenaturing gel electrophoresis and of 80,000 Da on sodi.umdodecyl sulfategel electrophoresis.Maximal activity (1 14 rcmol of trehalose min-l X mg" at 37 "C) was observed at pH 6.8-7.0.The apparent K,,, for trehalose was 34.5 RIM.Among seven oligosaccharides studied, the enzyme formed glucose only from trehalose.Neutral trehalase is located in the cytosol.A polyclonal rabbit antiserum raised against neutral trehalase precipitates the enzyme in the presence of protein A. The antiserum does not react with acid trehalase.Dephosphorylation by alkaline phosphatase from Escherichia coli of the active phosphorylated enzyme is accompanied by 290% inactivation.Rephosphorylation by incubation with the catalytic subunit of beef heart protein kinase is accompanied by reactivation and incorporation of 0.85 mol of phosphate/mol subunit (80,000 Da).The phosphorylated amino a'cid residue was identified as phosphoserine.In yeast, the trehalose-hydrolyzing enzyme trehalase was first described by Ernil Fischer (1).An inactive (zymogen) form of trehalase, which is activated by cyclic AMP-dependent phosphorylation, was reported by van Solingen and van der Plaat (2).In 1982, Wiemken and co-workers (3, 4) demonstrated that the phosphorylatable trehalase was localized in the cytosol, whereas a second, permanently active, trehalase was found in the vacuoles.Londesborough and Varimo ( 5 ) separated these two a.ctivities and determined different pH optima of the two enzymes.The permanently active vacuolar trehalase, which has its maximal activity at pH 4.5 and which was therefore designated "acid trehalase," was purified and characterized in a previous paper from this laboratory (6).Partial purification of the cytosolic "neutral trehalase," which, when phosphorylated, has its maximal activity at pH 7.0, has been worked out by several groups ( 5 , 7, 8).In this paper, purification to homogeneity of the phosphorylated neutral trehalase and characterization of the purified enzyme are presented.In accordance with the recommendations of the
Trials of wireless, secure electronic mail (1995)

The US Department of Defense (DOD) is a large user of both e-mail and security services. The introduction of commercial wireless communications and networks, and the recognition by industry of the need for security has provided the opportunity for development and trials of a wireless, secure e-mail service. The Center for Systems Engineering at the Defense Information Systems Agency has developed this capability and conducted trials with a small community of DOD users who have requirements for mobility in the workplace. These trials have introduced DOD approved security into commercial wireless data networks, and have inserted advanced technology into the hands of DOD users. The objective of these trials was to validate the system design, evaluate performance and utilization, and obtain user feedback. To realize a broad-based trial, the authors selected multiple wireless services, e-mail packages, security packages, and mobile computers, which were integrated in various combinations to meet user needs and allow a thorough trial. Both packet radio (RAM and ARDIS) and cellular digital packet data (CDPD) services were employed for the wireless connection of the mobile unit to a mail server on the user's local area network (LAN). Two commercial e-mail packages (LOTUS CC:Mail and Microsoft Mail) were integrated with the wireless service and with the security packages. Two security packages were used, one based on commercial software (SecretAgent) and the other based on a PCMCIA card (FORTEZZA) developed by the National Security Agency.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Adult epidermal keratinocytes are endowed with pilosebaceous forming abilities (1997)

Pluristratified epithelia of adult vertebrate skin continuously regenerate from stem cells, and the question still arises as to whether those cells are committed to the production of only one cell lineage, or in contrast they conserve their embryonic pluripotentiality. In order to investigate the abilities of adult cultured as well as wound healing epidermis, heterospecific fibroblast-keratinocyte recombinations were performed, which allow unquestionable identification of the cells implicated in the structures that differentiate. Adult human cultured breast epidermal cells and full-thickness wound healing from human facial skin and foreskin were associated with either rabbit embryonic trichogenic dermis or cultured dermal papilla cells of adult rat, before grafting onto nude mice for two weeks to one month. In situ hybridization with a human specific sequence Alu probe labeled the human cells, whereas implanted rabbit or rat and host mouse cells were distinguished by the Hoechst staining of their nuclei. The results show that human adult cultured breast epidermal cells are able to form hair buds and to participate in hair follicle formation, while adult healing epidermis from a sparsely hairy skin as the human face or the dorsal skin of nude mouse, or even from a glabrous epidermis as the human foreskin, are able to differentiate pilosebaceous units. Although a follicular origin of the involved keratinocytes cannot be excluded in the three first cases, the formation of hair and sebaceous glands by foreskin keratinocytes of children 2 to 10 years-old establishes the cutaneous appendage ability of the interfollicular epidermal stem cells. The formation of interspecies mosaic follicles also highlights the fact that there must be a significant level of commonality in the interactive signaling molecules used by epithelial cells from different species.
Matrix metalloproteinase and proinflammatory cytokine production by chondrocytes of human osteoarthritic cartilage: Associations with degenerative changes (2001)

These results indicate that the superficial zone of OA cartilage specimens, which is characterized by fibrillations, chondrocyte clusters, and degenerative matrix changes, contains a variable proportion of cells that immunostain for IL-1beta, TNFalpha, and 6 different MMPs. These observations support the concept that cytokine-MMP associations reflect a modified chondrocyte phenotype and an intrinsic process of cartilage degradation in OA.
Enzymatic hydrolysis of pentaerythritoltetranicotinate and meso-inositolhexanicotinate in blood and tissues. (1979)

The esters between nicotinic acid and pentaerythritol (niceritrol, Perycit) or meso-inositol (MIHN) were hydrolyzed by enzymes present in plasma and tissues of man, rat and dog. Human plasma and rat tissues hydrolyzed niceritrol at a higher rate than did MIHN. The reversed relation was found with dog tissue. The ability of niceritrol and MIHN to raise the level of free nicotinic acid of plasma was studied on man, dog and rat and related with their hydrolysis in vitro and the different solubility of the esters. There was a relationship between these properties of the esters and their ability to increase the plasma level of nicotinic acid.
Synergy Between Expert and Machine‐Learning Approaches Allows for Improved Retrosynthetic Planning (2019)

When computers plan multistep syntheses, they can rely either on expert knowledge or information machine-extracted from large reaction repositories. Both approaches suffer from imperfect functions evaluating reaction choices: expert functions are heuristics based on chemical intuition, whereas machine learning (ML) relies on neural networks (NNs) that can make meaningful predictions only about popular reaction types. This paper shows that expert and ML approaches can be synergistic-specifically, when NNs are trained on literature data matched onto high-quality, expert-coded reaction rules, they achieve higher synthetic accuracy than either of the methods alone and, importantly, can also handle rare/specialized reaction types.
Out‐of‐synchrony speech entrainment in developmental dyslexia (2016)

Developmental dyslexia is a reading disorder often characterized by reduced awareness of speech units. Whether the neural source of this phonological disorder in dyslexic readers results from the malfunctioning of the primary auditory system or damaged feedback communication between higher-order phonological regions (i.e., left inferior frontal regions) and the auditory cortex is still under dispute. Here we recorded magnetoencephalographic (MEG) signals from 20 dyslexic readers and 20 age-matched controls while they were listening to ∼10-s-long spoken sentences. Compared to controls, dyslexic readers had (1) an impaired neural entrainment to speech in the delta band (0.5-1 Hz); (2) a reduced delta synchronization in both the right auditory cortex and the left inferior frontal gyrus; and (3) an impaired feedforward functional coupling between neural oscillations in the right auditory cortex and the left inferior frontal regions. This shows that during speech listening, individuals with developmental dyslexia present reduced neural synchrony to low-frequency speech oscillations in primary auditory regions that hinders higher-order speech processing steps. The present findings, thus, strengthen proposals assuming that improper low-frequency acoustic entrainment affects speech sampling. This low speech-brain synchronization has the strong potential to cause severe consequences for both phonological and reading skills. Interestingly, the reduced speech-brain synchronization in dyslexic readers compared to normal readers (and its higher-order consequences across the speech processing network) appears preserved through the development from childhood to adulthood. Thus, the evaluation of speech-brain synchronization could possibly serve as a diagnostic tool for early detection of children at risk of dyslexia. Hum Brain Mapp 37:2767-2783, 2016. © 2016 Wiley Periodicals, Inc.
17D Yellow Fever Virus Infection of P388D1 Cells Mediated by Monoclonal Antibodies: Properties of the Macrophage Fc Receptor (1983)

Thirteen IgG monoclonal antibodies to the envelope protein of 17D yellow fever virus (17D YF) were produced. All of the antibodies, whether type-specific to 17D YF or flavivirus cross-reactive, mediated antibody-dependent enhancement (ADE) of virus growth in P388D1 cells. There was no consistent relationship between ADE titres and the degree or pattern of neutralizing and/or haemagglutination inhibition activity. Monoclonal antibodies of different isotypes were used to investigate further the properties of P388D1 Fc receptors. The effects of trypsin treatment of P388D1 on ADE were similar to those previously described in experiments measuring direct binding of IgG proteins or rosetting of sheep red blood cells (SRBC) by macrophages, demonstrating sensitivity to digestion by trypsin of the Fc receptor for monomeric IgG2a but not for IgG2b. Aggregated myeloma proteins of IgG2a and IgG2b isotypes competed equally well with either IgG2a or IgG2b monoclonal antibodies to 17D YF in inhibition of ADE. However, selective inhibition by the homologous isotype was observed when rosetting by P388D1 of SRBC coated with IgG2a or IgG2b monoclonal antibodies was examined. These results may help to explain apparent discrepancies previously reported between experiments utilizing direct binding of IgG proteins and those using rosetting of antibody-coated SRBC to examine Fc receptor properties and indicate that immune complexes of virus and antibody resemble aggregated immunoglobulins with respect to macrophage Fc receptor function and differ from antibody-coated SRBCs.