gebhart/patrepeval huggingface dataset:
Molecular basis of the D variant phenotypes DNU and D<sup>II</sup> allows localization of critical amino acids required for expression of Rh D epitopes epD3, 4 and 9 to the sixth external domain of the Rh D protein (1997)

The discovery of Rh partial D variant red cells by discrepant reactions with different monoclonal anti-D has demonstrated the range of Rh D epitopes that have arisen due to alterations in Rh D protein structure. There are two current classification systems, one which uses a nine epitope model (epD1-epD9) whereas a more recent model proposes 30 different epitopes. We describe here the molecular basis of two D variants which lack epD4 and epD9 namely the DNU and D(II) phenotypes. These would have both been originally classified as D(II) phenotype individuals, but we have revealed subtle differences in the serological profile of these erythrocytes. Such a differential reactivity and determination of the molecular bases of these phenotypes allows us to predict critical amino acids for epD3, epD4 and epD9 expression. The DNU phenotype arises from a single point mutation in the RHD gene resulting in a single amino acid change (Gly353Arg). Sequence analysis of exon 7 of the RHD gene derived from the D(II) propositus indicates that there is a single point mutation in this exon resulting in a single amino acid change (Ala354Asp). It is likely that this point mutation gives rise to the D(II) phenotype. Both mutations result in the change to Rh D-specific residues. Our results indicate that the following amino acids are crucial for epD3a (Asp350), epD3b (Asp350 + Gly353), epD4a (Gly353 + Ala354), epD4b (Ala354), epD9a (Asp350 + Gly353 + Ala354) and epD9b (Asp350 + Ala354) expression. All of these amino acids reside on the predicted sixth external domain of the Rh D protein, so it is possible that epD3, 4 and 9 are continuous epitopes.
Differences in Substrate Specificities of Five Bacterial Wax Ester Synthases (2012)

Wax esters are produced in certain bacteria as a potential carbon and energy storage compound. The final enzyme in the biosynthetic pathway responsible for wax ester production is the bifunctional wax ester synthase/acyl-coenzyme A (acyl-CoA):diacylglycerol acyltransferase (WS/DGAT), which utilizes a range of fatty alcohols and fatty acyl-CoAs to synthesize the corresponding wax ester. We report here the isolation and substrate range characterization for five WS/DGAT enzymes from four different bacteria: Marinobacter aquaeolei VT8, Acinetobacter baylyi, Rhodococcus jostii RHA1, and Psychrobacter cryohalolentis K5. The results from kinetic studies of isolated enzymes reveal a differential activity based on the order of substrate addition and reveal subtle differences between the substrate selectivity of the different enzymes. These in vitro results are compared to the wax ester and triacylglyceride product profiles obtained from each organism grown under neutral lipid accumulating conditions, providing potential insights into the role that the WS/DGAT enzyme plays in determining the final wax ester products that are produced under conditions of nutrient stress in each of these bacteria. Further, the analysis revealed that one enzyme in particular from M. aquaeolei VT8 showed the greatest potential for future study based on rapid purification and significantly higher activity than was found for the other isolated WS/DGAT enzymes. The results provide a framework to test prospective differences between these enzymes for potential biotechnological applications such as high-value petrochemicals and biofuel production.
One reporter for in-cell activity profiling of majority of protein kinase oncogenes (2017)

In-cell profiling enables the evaluation of receptor tyrosine activity in a complex environment of regulatory networks that affect signal initiation, propagation and feedback. We used FGF-receptor signaling to identify <i>EGR1</i> as a locus that strongly responds to the activation of a majority of the recognized protein kinase oncogenes, including 30 receptor tyrosine kinases and 154 of their disease-associated mutants. The <i>EGR1</i> promoter was engineered to enhance <i>trans</i>-activation capacity and optimized for simple screening assays with luciferase or fluorescent reporters. The efficacy of the developed, fully synthetic reporters was demonstrated by the identification of novel targets for two clinically used tyrosine kinase inhibitors, nilotinib and osimertinib. A universal reporter system for in-cell protein kinase profiling will facilitate repurposing of existing anti-cancer drugs and identification of novel inhibitors in high-throughput screening studies.
Cloning and localization of the lepidopteran protoxin gene of Bacillus thuringiensis subsp. kurstaki. (1982)

Bacillus thuringiensis subsp. kurstaki produces a proteinaceous crystalline inclusion that is toxic for lepidopteran larvae. There are several size classes of plasmids in this organism and the presence of one or more has been correlated with production of this protein, defined as a protoxin. DNA fragments of B. thuringiensis subsp. kurstaki, obtained by EcoRI digestion, were cloned into the vector Charon 4A. Recombinant phage were screened immunologically for the production of protoxin. Cells infected with one phage, C4K6c, produced antigen that was the same size as the protoxin and was toxic to Manduca sexta larvae. A 4.6-kilobase-pair (kbp) EcoRI fragment from C4K6c was subcloned into pBR328 and in both orientations in pHV33. Both Escherichia coli and Bacillus subtilis containing these recombinant plasmids produced antigen that crossreacted with antibody directed against the protoxin. The various sized plasmids of B. thuringiensis were purified and only an EcoRI fragment from the 45-kbp plasmid hybridized to phage C4K6c. One of the pHV33 subclones, pSM36, hybridized to the same size EcoRI/HindIII restriction fragments from plasmid or chromosomal DNA. The cloned EcoRI fragment contained a 0.9-kbp Pvu II fragment that was also present in chromosomal but not in plasmid digests. The original clone was therefore of chromosomal origin, although very similar or identical protoxin genes were present in both the 45-kbp plasmid and the chromosome. Several acrystalliferous nontoxic mutants have been isolated that lacked the 45-kbp plasmid and in some cases all plasmids. All of the mutants contained the chromosomal gene but did not produce protoxin antigen.
Precision parts cleaning using supercritical fluids (1993)

Supercritical fluid extraction and chromatography measurements were made on pieces of disk drive actuator components in order to understand how to clean and analyse these parts. Extract analyses were made by Fourier transform infrared (FTIR) and flame ionization detector measurements. Hydrocarbons, silicones, and fluorocarbons were seen on various pieces of different samples using FTIR, time-of-flight static secondary-ion mass spectrometry (TOF-SSIMS), and x-ray photoelectron spectroscopy. In addition TOF-SSIMS detected di-isooctyl phthalate. Silicones and di-isooctyl phthalate could be removed by CO2 extraction.
Inflammatory cytokines in normal human tears (1998)

Purpose. To elucidate inflammatory cytokine levels in normal human tears, we investigated the concentrations of interleukin-1α (IL-lα), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-8 (IL-8) both in basal tears and reflex tears of normal healthy eyes.Methods. Tear samples were collected from 270 healthy, normal volunteers with no past history of ocular surface disease; the total number of eyes was 295. All tear samples were collected in graduated disposable microcapillaries from the conjunctival cul-de-sac. Reflex tear stimulation was carried out by inserting an applicator into each volunteer's nose. Cytokine levels in basal tears and reflex tears were determined by ELISA. Tears were not diluted, and pooled samples were used for the cytokine assays.Results. In basal tears, the concentrations of IL-1α, −1β, −6 and −8 were 10.9 ± 1.2, 12.9 ± 2.3, 226.2 ± 29.6 and 731.4 ± 116.2 pg/ml, respectively. In reflex tears, IL-1β was not detectable, and the concentrations of IL-1α, −6 and −8 were 9.3 ± 2.7, 11.6 ± 1.6 and 276.1 ± 47.5 pg/ml respectively. IL-1β, −6 and −8 levels in reflex tears were significantly lower than those in basal tears, except for IL-1α.Conclusions. In the present study, the normal concentration range of inflammatory cytokines in human basal tears was clarified, as a baseline for further studies to examine the levels of these cytokines in tears during disease states. Curr. Eye Res. 17: 673–676, 1998.
Public Attitudes regarding the Donation and Storage of Blood Specimens for Genetic Research (2001)

Understanding the various factors contributing to knowledge, attitudes and behavior regarding the donation and storage of blood specimens for genetic research will contribute to future actions in communication genetic research goals to the public and recruitment for population-based genetic studies.
Prandial Options to Advance Basal Insulin Glargine Therapy: Testing Lixisenatide Plus Basal Insulin Versus Insulin Glulisine Either as Basal-Plus or Basal-Bolus in Type 2 Diabetes: The GetGoal Duo-2 Trial (2016)

Short-acting glucagon-like peptide-1 receptor agonists as add-on to basal insulin may become a preferred treatment intensification option, attaining meaningful glycemic targets with fewer hypoglycemic events without weight gain versus basal-plus or basal-bolus in uncontrolled basal insulin-treated type 2 diabetes.
Mitochondrial electron transport as a source for nitric oxide in the unicellular green alga <i>Chlorella sorokiniana</i> (2004)

Wild type (WT), and nitrate reductase (NR)- and nitrite-reductase (NiR)-deficient cells of Chlorella sorokiniana were used to characterize nitric oxide (NO) emission. The NO emission from nitrate-grown WT cells was very low in air, increased slightly after addition of nitrite (200 microM), but strongly under anoxia. Importantly, even completely NR-free mutants, as well as cells grown on tungstate, emitted NO when fed with nitrite under anoxia. Therefore, this NO production from nitrite was independent of NR and other molybdenum cofactor enzymes. Cyanide and inhibitors of mitochondrial complex III, myxothiazol or antimycin A, but not salicylhydroxamic acid (inhibitor of alternative oxidase) inhibited NO production by NR-free cells. In contrast, NiR-deficient cells growing on nitrate accumulated nitrite and emitted NO at very high equal rates in air and anoxia. This NO emission was 50% inhibited by salicylhydroxamic acid, indicating that in these cells the alternative oxidase pathway had been induced and reduced nitrite to NO.
Policy Reform on Investment Climate: Case Analysis of Hangzhou (2004)

The reform of the investment climate in Hangzhou, China, was a long process that involved many players and groups. This comparative analysis describes the different waves of reform, the forces behind them, and the resulting effects. The study concludes that central government policy toward a market economy was a strong force in promoting the improvement of the investment climate and that the municipal government of Hangzhou played a key role by adopting a �focusing on certain tasks while putting others aside� policy. Whether the investment climate is good or bad has a strong impact on the economic development of the region.
Characterization of Cannabinoid Receptor 2 Transcript Expression in B Cells (2010)

Cannabinoids and cannabinoid receptors have been shown to play important roles in immune regulation particularly as modulators of anti-inflammatory cytokines and antibody production. The predominant cannabinoid receptor involved in this immune regulation is cannabinoid receptor 2 (CB2), which is robustly expressed in B cells. Utilizing a combination of bioinformatics, 5' RACE, real time RT-qPCR, and reporter assays, we showed that human B cells from peripheral blood mononuclear cells (PBMC) expressed one CB2 transcript while mouse B cells from spleen express three CB2 transcripts. Alignment of the sequenced B cell RACE products to either the mouse or human genome, along with the GenBank mRNA sequences, revealed that the transcripts isolated in this study contained previously unidentified transcriptional start sites (TSSs). In addition, expression construct testing of the genomic region containing the TSSs of the mouse CB2 exon 1 and 2 transcripts showed a significant increase of promoter activity. Bioinformatics analysis for cis-sequences in the promoter regions identified DNA binding sites for NF-kB, STAT6, and Elk1 transcription factors activated by LPS, IL-4 and anti-CD40. Regarding variations in CB2 transcript expression among the immune cell subtypes, RACE analysis showed that the exon 1b transcript is seen in B cells but not in T cells, dendritic cells or macrophages. Furthermore, RT-qPCR showed variations in transcript expression during B cell development as well as in resting versus LPS or IL-4/anti-CD40 stimulated B cells. The exon 1a transcript was predominant in pre-, immature and resting B cells whereas the exon 1b and 2 transcripts were enhanced in mature and activated B cells. These data showed for the first time that human B cells use one TSS for CB2 expression while mouse B cells use multiple TSSs for the expression of three CB2 transcripts, in which the expression of the individual transcript is related to immune cell type and/or cell activation state. Additionally, this is the first report in mouse B cells defining TSSs that are in genomic areas with promoter activity thus suggesting the location of two promoter regions. Defining the CB2 transcript expression during various stages of B cell activation provide clues to therapeutic methods.
Prevention of Restenosis by Gene Therapy (1997)

We have developed an efficient vector system based on the liposome for the delivery of oligonucleotides and genes into various organs. The liposome was decorated with fusion proteins of HVJ (Sendai virus) to introduce DNA directly into the cytoplasm and contained DNA and DNA-binding nuclear protein inside the particle to enhance its expression. Using the vector, called HVJ-liposome gene delivery system, we attempted to prevent the neointima formation of vascular walls after balloon injury. Antisense oligonucleotides against PCNA and cdc2 kinase transferred into injured arterial walls by protein-liposomes greatly reduced the message of those genes and inhibited neointima formation of the injured artery for 8 weeks. Moreover, double-stranded oligonucleotides containing the consensus sequence for E2F binding sites inhibited the growth of smooth muscle cells and prevented neointima formation. Finally, c-NOS gene was introduced into injured rat carotid artery by HVJ-liposome, and neointima formation was inhibited by 70% for 2-4 weeks.
Time‐resolved magnetic resonance angiography (1988)

A time-resolved phase contrast magnetic resonance angiography technique is described. This technique provides a series of angiograms obtained at different phases of the cardiac cycle. Such a series of angiograms can be used to evaluate blood flow dynamics. For example, turbulent flow in the regions of vessel bifurcations is easily demonstrated and followed during systole and diastole. Retrograde flow can also be observed. Dynamic angiography can be particularly useful in distinguishing transient image features, such as signal voids due to turbulent flow, from static features arising from vessel morphology.
Treatment of type 2 diabetes mellitus. (1999)

Type 2 diabetes mellitus (formerly called non-insulin-dependent diabetes) causes abnormal carbohydrate, lipid and protein metabolism associated with insulin resistance and impaired insulin secretion. Insulin resistance is a major contributor to progression of the disease and to complications of diabetes. Type 2 diabetes is a common and underdiagnosed condition that poses treatment challenges to family practitioners. The introduction of new oral agents within the past three years has expanded the range of possible combination regimens available for treating type 2 diabetes. Despite the choice of pharmacologic agents, physicians must stress the nonpharmacologic approaches of diet modification, weight control and regular exercise. Pharmacologic approaches must be based on patient characteristics, level of glucose control and cost considerations. Combinations of different oral agents may be useful for controlling hyperglycemia before insulin therapy becomes necessary. A stepped-care approach to drug therapy may provide the most rational, cost-efficient approach to management of this disease. Pharmaco-economic analyses of clinical trials are needed to determine cost-effective treatment strategies for management of type 2 diabetes.
Structure-Based Virtual Ligand Screening: Recent Success Stories (2009)

Today, computational methods are commonly used in all areas of health science research. Among these methods, virtual ligand screening has become an established technique for hit discovery and optimization. In this review, we first introduce structure-based virtual ligand screening and briefly comment on compound collections and target preparations. We also provide the readers with a list of resources, from chemoinformatics packages to compound collections, which could be helpful to implement a structure-based virtual screening platform. Then we discuss seventeen recent success stories obtained with various receptor-based in silico methods, performed on experimental structures (X-ray crystallography, 12 cases) or homology models (5 cases) and concerning different target classes, from the design of catalytic site inhibitors to drug-like compounds impeding macromolecular interactions. In light of these results, some suggestions are made about areas that present opportunities for improvements.
5‐Amidinoindoles as Dual Inhibitors of Coagulation Factors IXa and Xa. (2005)

Abstract For Abstract see ChemInform Abstract in Full Text.
FINE STRUCTURAL DEVELOPMENT OF THE MEGAGAMETOPHYTE OF ZEA MAYS FOLLOWING FERTILIZATION (1968)

The changes in cytoplasmic fine structure during the interval between pollination and zygotic division in the megagametophyte of Zea mays are reported. The rate of membrane synthesis appears to be low in the mature unfertilized megagametophyte. This megagametophyte is suggested to be in a state of relative metabolic inhibition. The rate of membrane synthesis is high in the zygote and free nuclear endosperm. After fertilization the swelling of the mitochondria in all cytoplasms is interpreted to reflect a presumed increase in metabolic rate relative to growth. In the zygote and endosperm, endoplasmic reticulum (ER) production is associated with the nuclear envelope. In all of the material the ribosomes not associated with the ER are helical polysomes which increase in length after fertilization. On the basis of permanganate staining, the ribonucleoprotein of the endosperm is suggested to be different from that of the other cytoplasms. The specific plastid form of each cell type does not change during the first few hours after fertilization. Dictyosomes are most numerous and active in the antipodals. They are least numerous in the egg and zygote. The smallest dictyosome vesicles are in the synergids. Dictyosome number and vesicle size increase in the egg and central cell after fertilization. Similarities among the megagametophytes of several angiosperms are enumerated.
Ankylosing spondylitis patients display altered dendritic cell and T cell populations that implicate pathogenic roles for the IL-23 cytokine axis and intestinal inflammation (2015)

CD14(-) CD16(+) mononuclear cells may contribute to AS by promoting Th17 responses, and antigen-presenting cells of mucosal origin are likely to contribute to systemic inflammation in AS.
Acid neutralization capacity of Canadian antacid formulations. (1985)

A study was designed to determine the acid neutralization capacities (ANCs) of the new Canadian antacid formulations and to compare these products with standard antacid products in terms of lot-to-lot consistency, ANC, sodium and "calorie" contents, and price to the pharmacist. Twenty-three liquid and 18 tablet antacids were tested. The concentrated liquid antacids (Mylanta-2 Extra Strength, Amphojel 500, Gelusil Extra Strength, Maalox TC and Diovol Ex) were found to have the highest ANCs. Six of the tablet antacids (Amphojel, Amphojel Plus, Camalox, Gelusil-400, Maalox and Mylanta-2) were found to have greater ANCs than 15 of the liquid antacids. Between-lot variation exceeded that of within-lot variation in 10 of the 14 liquid antacids for which this variation could be tested. The concentrated liquid antacids provide the highest ANCs with the lowest dosage volume and sodium and calorie contents. Some tablet antacids have the potential to be used as alternatives to liquid antacids because of their high ANC and patient convenience. The inclusion of ANC on the labels of antacid products would assist in the rational determination of the dose of these products.
Inflammatory mediators modulating the transient receptor potential vanilloid 1 receptor: therapeutic targets to treat inflammatory and neuropathic pain (2007)

The transient receptor potential vanilloid 1 receptor (TRPV1) plays an important role in inflammatory heat hyperalgesia. TRPV1 is a non-selective cation channel gated by noxious heat, protons and capsaicin, thus being regarded as a polymodal molecular integrator in nociception. Abundant evidence has demonstrated that TRPV1 is also modulated by numerous inflammatory mediators, including growth factors, neurotransmitters, peptides or small proteins, lipids, chemokines and cytokines. By activating multiple protein kinases to increase the phosphorylation of TRPV1, pronociceptive inflammatory mediators sensitise the TRPV1 response to noxious heat, protons and capsaicin, thus augmenting thermal hyperalgesia. In contrast, by inhibiting protein kinases or other mechanisms, antinociceptive inflammatory mediators suppress the response of TRPV1 to these stimuli, thus damping thermal hyperalgesia. The positive modulation of TRPV1 by inflammatory mediators may constitute a novel mechanism underlying sustained inflammatory or neuropathic pain. Blocking pronociceptive inflammatory mediator-exerted sensitising effects or boosting antinociceptive inflammatory mediator-induced suppressing effects on TRPV1 should be considered as sources of novel potential therapies to more effectively treat chronic pain conditions.
Suppression of human melanoma cell growth and metastasis by the melanoma‐associated antigen CD63 (ME491) (1995)

CD63 has been identified in human melanoma cells by a number of different monoclonal antibodies (MAbs). Studies with MAbs have shown that expression is most marked in naevi and early forms of cutaneous melanoma and reduced in vertical growth phase and metastatic lesions. To investigate further the role of CD63 in progression of melanoma, genomic CD63 was transfected into a CD63-negative human melanoma cell line using an episomal vector. The stable transfected melanoma cells had similar growth rates to control transfected melanoma cells in vitro but much lower growth rates when injected intradermally into athymic nude mice. The CD63-transfected cells also had a reduced number of metastases in the peritoneal cavity and subcutaneous sites when injected intravenously. MAb against CD63 did not influence the growth of CD63-transfected melanoma cells in vitro. Our results confirm previous studies using H-ras-transformed NIH3T3 fibroblasts and suggest that CD63 may have a role as a tumor suppressor gene in human melanoma that acts to limit invasion and progression of melanoma.