gebhart/patrepeval huggingface dataset:
Inhibition of β-Ketoacyl-Acyl Carrier Protein Synthase III (FabH) by Acyl-Acyl Carrier Protein in Escherichia coli (1996)

beta-Ketoacyl-acyl carrier protein (ACP) synthase III (the fabH gene product) condenses acetyl-CoA with malonyl-ACP to initiate fatty acid biosynthesis in the dissociated, type II fatty acid synthase systems typified by Escherichia coli. The accumulation of malonyl-acyl carrier protein (ACP) following the inhibition of a reconstituted fatty acid synthase system by acyl-ACP implicated synthase III (FabH) as a target for acyl-ACP regulation (Heath, R. J., and Rock, C. O. (1996) J. Biol. Chem. 271, 1833-1836); therefore, the FabH protein was purified and its biochemical and regulatory properties examined. FabH exhibited a Km of 40 microM for acetyl-CoA and 5 microM for malonyl-ACP. FabH also accepted other acyl-CoAs as primers with the rank order of activity being acetyl-CoA approximately propionyl-CoA >> butyryl-CoA. FabH utilized neither hexanoyl-CoA nor octanoyl-CoA. Acyl-ACPs suppressed Fabh activity, and their potency increased with increasing acyl chain length between 12 and 20 carbon atoms. Nonesterified ACP was not an inhibitor. Acyl-ACP inhibition kinetics were mixed with respect to acetyl-CoA, but were competitive with malonyl-ACP, indicating that acyl-ACPs decrease FabH activity by binding to either the free enzyme or the acyl-enzyme intermediate. These data support the concept that the inhibition of chain initiation at the beta-ketoacyl-ACP synthase III step contributes to the attenuation of fatty acid biosynthesis by acyl-ACP.
Fabrication of polymer microlens arrays using capillary forming with a soft mold of micro-holes array and UV-curable polymer (2006)

This paper reports a simple and effective method to fabricate microlens arrays with the ultraviolet-curable resins, and a soft mold of micro-holes array. During capillary forming operation, the surface of the soft mold of micro-holes array is being pressed against the ultraviolet-curable resin layer coated on the plastic substrate. An array of convex lense can be formed in the circular holes of the soft mold due to the capillary filling and surface tension. The microlens arrays have smooth surface and uniform focusing function. The shape and height of micolens can be controlled with a proper combination of pressing pressure, pressing duration and UV curing dose. This technique shows great potential for fabricating polymer microlens arrays with high productivity and low cost.
FAK and HAS Inhibition Synergistically Decrease Colon Cancer Cell Viability and Affect Expression of Critical Genes (2013)

Focal adhesion kinase (FAK), hyaluronan (HA), and hyaluronan synthase-3 (HAS3) have been implicated in cancer growth and progression. FAK inhibition with the small molecule inhibitor Y15 decreases colon cancer cell growth in vitro and in vivo. HAS3 inhibition in colon cancer cells decreases FAK expression and activation, and exogenous HA increases FAK activation. We sought to determine the genes affected by HAS and FAK inhibition and hypothesized that dual inhibition would synergistically inhibit viability. Y15 (FAK inhibitor) and the HAS inhibitor 4-methylumbelliferone (4-MU) decreased viability in a dose dependent manner; viability was further inhibited by treatment with Y15 and 4-MU in colon cancer cells. HAS inhibited cells treated with 2 μM of Y15 showed significantly decreased viability compared to HAS scrambled cells treated with the same dose (p < 0.05) demonstrating synergistic inhibition of viability with dual FAK/HAS inhibition. Microarray analysis showed more than 2-fold up- or down-regulation of 121 genes by HAS inhibition, and 696 genes by FAK inhibition (p < 0.05) and revealed 29 common genes affected by both signaling. Among the genes affected by FAK or HAS3 inhibition were genes, playing role in apoptosis, cell cycle regulation, adhesion, transcription, heatshock and WNT pathways. Thus, FAK or HAS inhibition decreases SW620 viability and affects several similar genes, which are involved in the regulation of tumor survival. Dual inhibition of FAK and HAS3 decreases viability to a greater degree than with either agent alone, and suggests that synergistic inhibition of colon cancer cell growth can result from affecting similar genetic pathways.
A monoclonal antibody against a myelin oligodendrocyte glycoprotein induces relapses and demyelination in central nervous system autoimmune disease. (1987)

The factors contributing to chronic relapsing inflammatory disease processes of the central nervous system (CNS) and demyelination are poorly understood. In addition to cellular immune reactions, humoral factors such as antibodies might quantitatively or qualitatively influence the disease process. We therefore investigated the effects of administration of a monoclonal antibody specific for a CNS autoantigen on both acute and chronic experimental autoimmune encephalomyelitis (EAE) in mice and rats. This monoclonal antibody, 8-18C5, specific for a myelin/oligodendrocyte glycoprotein, was observed to accelerate clinical and pathologic changes of CNS autoimmune disease. In SJL mice with chronic relapsing EAE, injection of antibody into animals recovering from an attack induced fatal relapses; in Lewis rats, acute EAE was enhanced and associated with a hyperacute inflammatory response with demyelination, a feature not commonly seen in acute EAE. The demonstration that relapses and demyelination can be induced by administration of a white matter-reactive monoclonal antibody offers new possibilities to study processes resulting in CNS damage during autoimmune disease. Furthermore, these findings support the immunopathogenic potential of antibody to myelin components in inflammatory CNS disease processes and, specifically, in causing demyelination.
Mucin gene expression in normal, preneoplastic, and neoplastic human gastric epithelium. (1995)

Mucins synthesized by malignant cells may contribute (via decreased cellular adhesion and immune recognition) to cancer invasion and metastases. Human mucins are derived from a heterogeneous family of genes, labeled MUC1-6. Our aim was to determine the pattern of mucin gene expression in normal, preneoplastic (intestinal metaplasia), and malignant gastric specimens. Probes and antibodies for specific mucin tandem repeat sequences were used for RNA and immunohistochemical analysis. Normal stomach mucosa was characterized by expression of MUC1, MUC5, and MUC6 mRNA and immunoreactive protein, without MUC2, MUC3, and MUC4 gene expression. In contrast, high levels of MUC2 and MUC3 mucin mRNA and immunoreactive protein were found in specimens with intestinal metaplasia. Gastric cancers exhibited markedly altered secretory mucin mRNA levels compared with adjacent normal mucosa, with decreased levels of MUC5 and MUC6 mRNA and increased levels of MUC3 and MUC4 mRNA. Overall, immunoreactive MUC1 mucin was detected in 72% of 33 gastric cancers, and secretory mucin core peptides were expressed in 34% (MUC2), 45% (MUC3), 19% (MUC5), and 57% (MUC6) of these specimens. Coexpression of multiple (three or more) mucin core proteins occurred in 15 of 25 (60%) advanced (stages III and IV) cancers compared with 1 of 8 (12.5%) early (stages I and II) cancers (P < 0.048). We conclude that human gastric epithelium has a unique mucin gene pattern, which becomes markedly altered in preneoplastic and neoplastic specimens. Increased mucin gene heterogeneity in gastric adenocarcinomas is associated with advanced cancer stage.
Cloning, expression and characterization of a sialidase gene from Arthrobacter ureafaciens (2005)

Sialidases have recently been used in the processing of clinically relevant asialoproteins. The Arthrobacter ureafaciens sialidase (EC 3.2.1.18) exhibits broad substrate specificity and is often used in such applications. We have employed an expression cloning strategy to isolate the A. ureafaciens sialidase. The clone encodes a 990-amino-acid 104 kDa open-reading-frame protein containing three domains: an N-terminal catalytic domain, a linker domain with an immunoglobulin-like fold and a C-terminal domain of unknown function. Expression in Escherichia coli indicates that the sialidase promoter was active in E. coli. Overexpression in E. coli resulted in several truncated forms. A 54 kDa truncated variant was generated, expressed and purified, and its feasibility for use in an erythropoietin desialylation process was demonstrated.
Feline leukemia virus subgroup B uses the same cell surface receptor as gibbon ape leukemia virus (1992)

Pseudotypes of gibbon ape leukemia virus/simian sarcoma-associated virus (GALV/SSAV) and feline leukemia virus subgroup B (FeLV-B) have been constructed by rescuing a Moloney murine leukemia virus vector genome with wild-type GALV/SSAV or FeLV-B. The resulting recombinant viruses utilized core and envelope proteins from the wild-type virus and conferred resistance to growth in L-histidinol upon infected cells by virtue of the HisD gene encoded by the vector genome. They displayed the host range specificity of the rescuing viruses and could be neutralized by virus-specific antisera. Receptor cross-interference was observed when the GALV/SSAV or FeLV-B pseudotypes were used to superinfect cells productively infected with either GALV/SSAV or FeLV-B. Although murine cells are resistant to FeLV-B infection, murine cells expressing the human gene for the GALV/SSAV receptor became susceptible to FeLV-B infection. Therefore GALV/SSAV and FeLV-B utilize the same cell surface receptor.
Purification of a thermostable DNA polymerase from Thermus thermophilus HB8, useful in the polymerase chain reaction. (1990)

A thermostable DNA polymerase, isolated from the thermophilic strain Thermus thermophilus HB 8 was purified by a five-step procedure which provides a high yield and a homogeneous preparation. The molecular weight was estimated to be 67,000 daltons and the extension rate was determined to be 1500 nucleotides per minute. The enzyme works in polymerase chain reaction conditions similar to those used for Taq polymerase from Thermus aquaticus.
The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools (1997)

CLUSTAL X is a new windows interface for the widely-used progressive multiple sequence alignment program CLUSTAL W. The new system is easy to use, providing an integrated system for performing multiple sequence and profile alignments and analysing the results. CLUSTAL X displays the sequence alignment in a window on the screen. A versatile sequence colouring scheme allows the user to highlight conserved features in the alignment. Pull-down menus provide all the options required for traditional multiple sequence and profile alignment. New features include: the ability to cut-and-paste sequences to change the order of the alignment, selection of a subset of the sequences to be realigned, and selection of a sub-range of the alignment to be realigned and inserted back into the original alignment. Alignment quality analysis can be performed and low-scoring segments or exceptional residues can be highlighted. Quality analysis and realignment of selected residue ranges provide the user with a powerful tool to improve and refine difficult alignments and to trap errors in input sequences. CLUSTAL X has been compiled on SUN Solaris, IRIX5.3 on Silicon Graphics, Digital UNIX on DECstations, Microsoft Windows (32 bit) for PCs, Linux ELF for x86 PCs, and Macintosh PowerMac.
Identification of the Epstein-Barr virus gp85 gene (1988)

The Epstein-Barr virus glycoprotein gp85 has been mapped to the Epstein-Barr virus DNA open reading frame BXLF2 (R. Baer, A. Bankier, M. Biggin, P. Deininger, P. Farrell, T. Gibson, G. Hatfull, G. Hudson, S. Stachwell, C. Sequin, P. Tufnell, and B. Barrell, Nature [London] 310:207-211, 1984). A gp85-specific monoclonal antibody reacts with the BXLF2 in vitro transcription-translation product. The monoclonal antibody also precipitates an 85-kilodalton protein from rodent cells transfected with the BXLF2 open reading frame DNA. In these cells, gp85 localizes to the cytoplasm and nuclear rim rather than to the plasma membrane as in lymphocytes. Northern (RNA) blot hybridization and analysis of a cDNA clone containing BXLF2 indicate that gp85 is translated from an unspliced, late, 2.5-kilobase transcript. Similarities between the predicted amino acid sequences of gp85 and herpes simplex virus gH (D. McGeoch and A. Davison, Nucleic Acids Res. 14:4281-4292, 1986) are noted.
Development, morphology, and function of the yolk‐sac placenta of laboratory rodents (1990)

A review of current knowledge of the unusual structure and several functions of the yolk-sac membranes of common laboratory rodents, viz., rats, mice, hamsters, guinea pigs and gerbils, enables a better assessment of the significance of this maternofetal exchange system in the experimental production of congenital anomalies. The anatomy of both visceral and parietal walls of the rodent yolk-sac placenta--specifically the anatomical relationships of each wall with maternal and with other fetal tissues--depends on the mode of origin and subsequent development of the yolk sac in these several species. Accordingly, the developmental biology of the rodent yolk sac is described. Since both fine structure and anatomical relationships also determine in large measure the functioning of the membrane as a whole in the absorption of selected materials either for intracellular digestion or for cellular translocation and transport to the developing embryo, the anatomy of the yolk sac is considered in detail. Similarly, since available evidence strongly suggests that teratogenic agents induce perturbations in the cellular mechanisms that control these several functions of the yolk-sac placental system in the production of birth defects, additionally an account is given of the cell biology of the membrane, i.e., endocytosis and targeting/trafficking of materials either for digestion within the epithelium at the maternal surface of the visceral yolk sac or for translocation across the yolk-sac membrane as a whole.
Energy intake following infusion of glucagon and GLP-1: a double-blind crossover study (2013)

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
Use of Neural Nets For Dynamic Modeling and Control of Chemical Process Systems (1989)

Neural nets are inherently parallel and they hold great promise because of their ability to "learn" nonlinear relationships. This paper discusses the use of backpropagation neural nets for dynamic modeling and control of chemical process systems. The backpropagation algorithm and its rationale are reviewed. The algorithm is applied succesfully to model the dynamic response of pH in a CSTR. The use of backpropagation models for control is briefly discussed.
Proteolytic Antibody Light Chains Alter β-Amyloid Aggregation and Prevent Cytotoxicity (2004)

Beta-amyloid (Abeta), a peptide generated by proteolytic cleavage of the amyloid precursor protein (APP), is a major constituent of the neuritic plaques associated with Alzheimer's disease (AD). Up-regulation of alpha-secretase, which can hydrolyze Abeta between Lys16 and Leu17, has been proposed as a potential therapeutic strategy in the treatment of AD. Previously, we identified two light-chain antibody fragments that had proteolytic activity against Abeta, one with alpha-secretase-like activity and one with carboxypeptidase-like activity. Here we show that cleavage of Abeta40 by hk14, the light-chain antibody having carboxypeptidase-like activity, alters aggregation of Abeta and neutralizes any cytotoxic effects of the peptide. Cleavage of Abeta40 with c23.5, the light chain having alpha-secretase-like cleavage, substantially increases the aggregation rate of Abeta; however, it does not show any corresponding increase in cytotoxicity. The increase in aggregation resulting from hydrolysis by c23.5 can be attributed to the decreased solubility of the hydrolyzed products relative to the parent Abeta40, primarily the Abeta17-40 fragment. These results demonstrate that antibody fragment mediated proteolytic degradation of Abeta peptide can be a potential therapeutic route to control Abeta aggregation and toxicity in vivo. Our results also suggest that increasing alpha-secretase activity as a therapeutic route must be approached with some caution because this can lead to a substantial increase in aggregation.
Gas chromatography-mass spectrometry for probing the structure and mechanism of action of enzyme active sites. Role of Glu-270 in carboxypeptidase A (1975)

A new technique for the study of the mechanism of enzymes has been developed. An enzyme, modified by an active-site directed reagent, is digested by one or more proteases. The resulting mixture of oligopeptides is then analyzed directly by gas chromatography-mass spectrometry without the use of separation or isolation procedures. A comparison with unmodified enzyme identifies the modified residue as well as quantifies the reaction. This approach has been applied to the identification of Glu-270 in the active site of carboxypeptidase A using a carbodiimide as modification reagent. Studies on the possible incorporation of 18O (from 18O-enriched water) into Glu-270 or other acidic residues near the active site of carboxypeptidase A show that the oxygens of the carboxyl groups of these residues are not exchangeable.
Event-Related Brain Potentials Following Incorrect Feedback in a Time-Estimation Task: Evidence for a “Generic” Neural System for Error Detection (1997)

We examined scalp-recorded event-related potentials following feedback stimuli in a time-estimation task. Six hundred msec after indicating the end of a 1 sec interval, subjects received a visual, auditory, or somatosensory stimulus that indicated whether the interval they had produced was correct. Following feedback indicating incorrect performance, a negative deflection occurred, whose characteristics corresponded closely to those of the component (the error-related negativity) that accompanies errors in choice reaction time tasks. Furthermore, equivalent dipole analysis suggested that, for all three modalities, the distribution of the scalp potential was consistent with a local source in the anterior cingulate cortex or a more distributed source in the supplementary motor areas. These loci correspond closely to those described previously for the error-related negativity. We conclude that the error-related negativity is the manifestation of the activity of a "generic" neural system involved in error detection.
Reciprocal Interaction between Two Cellular Proteins, Purα and YB-1, Modulates Transcriptional Activity of JCV CY in Glial Cells (1999)

Cross communication between regulatory proteins is an important event in the control of eukaryotic gene transcription. Here we have examined the structural and functional interaction between two cellular regulatory proteins, YB-1 and Puralpha, on the 23-bp sequence element derived from the enhancer-promoter of the human polyomavirus JCV. YB-1 and Puralpha are single-stranded DNA binding proteins which recognize C/T- and GC/GA-rich sequences, respectively. Results from band shift studies demonstrated that while both proteins interact directly with their DNA target sequences within the 23-bp motif, each protein can regulate the association of the other one with the DNA. Affinity chromatography and coimmunoprecipitation provide evidence for a direct interaction between Puralpha and YB-1 in the absence of the DNA sequence. Ectopic expression of YB-1 and Puralpha in glial cells synergistically stimulated viral promoter activity via the 23-bp sequence element. Results from mutational studies revealed that residues between amino acids 75 and 203 of YB-1 and between amino acids 85 and 215 of Puralpha are important for the interaction between these two proteins. Functional studies with glial cells indicated that the region within Puralpha which mediates its association with YB-1 and binding to the 23-bp sequence is important for the observed activation of the JCV promoter by the Puralpha and YB-1 proteins. The results of this study suggest that the cooperative interaction between YB-1 and Puralpha mediates the synergistic activation of the human polyomavirus JCV genome by these cellular proteins. The importance of these findings for cellular and viral genes which are regulated by Puralpha and YB-1 is discussed.
Enhancement mu opioid antinociception by oral delta9-tetrahydrocannabinol: dose-response analysis and receptor identification. (1999)

The antinociceptive effects of various mu opioids given p.o. alone and in combination with Delta-9-tetrahydrocannabinol (Delta9-THC) were evaluated using the tail-flick test. Morphine preceded by Delta9-THC treatment (20 mg/kg) was significantly more potent than morphine alone, with an ED50 shift from 28.8 to 13.1 mg/kg. Codeine showed the greatest shift in ED50 value when administered after Delta9-THC (139.9 to 5.9 mg/kg). The dose-response curves for oxymorphone and hydromorphone were shifted 5- and 12.6-fold, respectively. Methadone was enhanced 4-fold, whereas its derivative, l-alpha-acetylmethadol, was enhanced 3-fold. The potency ratios after pretreatment with Delta9-THC for heroin and meperidine indicated significant enhancement (4.1 and 8.9, respectively). Pentazocine did not show a parallel shift in its dose-response curve with Delta9-THC. Naloxone administration (1 mg/kg s.c.) completely blocked the antinociceptive effects of morphine p.o. and codeine p.o. The Delta9-THC-induced enhancement of morphine and codeine was also significantly decreased by naloxone administration. Naltrindole (2 mg/kg s.c.) did not affect morphine or codeine antinociception but did block the enhancement of these two opioids by Delta9-THC. No effect was seen when nor-binaltorphimine was administered 2 mg/kg s.c. before morphine or codeine. Furthermore, the enhancements of morphine and codeine were not blocked by nor-binaltorphimine. We find that many mu opioids are enhanced by an inactive dose of Delta9-THC p.o. The exact nature of this enhancement is unknown. We show evidence of involvement of mu and possibly delta opioid receptors as a portion of this signaling pathway that leads to a decrease in pain perception.
LAG-3 Regulates Plasmacytoid Dendritic Cell Homeostasis (2009)

Lymphocyte activation gene 3 (LAG-3) is a CD4-related, activation-induced cell surface molecule expressed by various lymphoid cell types and binds to MHC class II with high affinity. We have previously shown that LAG-3 negatively regulates the expansion of activated T cells and T cell homeostasis, and is required for maximal regulatory T cell function. In this study, we demonstrate for the first time that LAG-3 is also expressed on CD11c(low)/B220(+)/PDCA-1(+) plasmacytoid dendritic cells (pDCs). Lag3 expression, as determined by real time PCR, was approximately 10-fold greater in pDCs than in either regulatory T cells or activated T effector cells. Activated pDCs also generate approximately 5 times more sLAG-3 than activated T cells. LAG-3-deficient pDCs proliferate and expand more than wild-type pDCs in vivo in response to the TLR9 ligand, CpG. However, the effect of LAG-3 appears to be selective as there was no effect of LAG-3 on the expression of MHC class II, TLR9, and chemokine receptors, or on cytokine production. Lastly, adoptive transfer of either Lag3(+/+) or Lag3(-/-) T cells plus or minus Lag3(+/+) or Lag3(-/-) pDCs defined a role for LAG-3 in controlling pDC homeostasis as well as highlighting the consequences of deregulated Lag3(-/-) pDCs on T cell homeostasis. This raised the possibility of homeostatic reciprocity between T cells and pDCs. Collectively, our data suggests that LAG-3 plays an important but selective cell intrinsic and cell extrinsic role in pDC biology, and may serve as a key functional marker for their study.