gebhart/patrepeval huggingface dataset:
Fc receptor targeting in the treatment of allergy, autoimmune diseases and cancer (2005)

Immune activation and inhibitory receptors play an important role in the maintenance of an adequate activation threshold of various cells in our immune system. Analyses of murine models show that the inhibitory Fcreceptor, FcgammaRIIB plays an indispensable role in the suppression of anti-body-mediated allergy and autoimmunity. In contrast, the activating-type Fcreceptors (FcRs) are essential for the development of these diseases, suggesting that regulation of inhibitory or activating FcR is an ideal target as a therapeutic agent. In addition, recent crystal structural analyses of FcR-Ig-Fc fragment complexes provide an effective approach for developing FcR-targeting drugs. This review summarises recent advances of FcR, which were mainly obtained by murine studies, and highlights novel antibodies as possible FcR-targeting therapies for allergy, autoimmune diseases and cancer.
Drosophila acetylcholinesterase (1992)

In insects, acetylcholinesterase is mainly found in the central nervous system. It is expressed in the synapse where it hydrolyzes the neurotransmitter acetylcholine. Maturation of this protein involves several post-translational modifications. The precursor polypeptide is cut at three sites; the N-terminal signal peptide is removed, the C-terminal hydrophobic polypeptide is clipped off and replaced by a glycolipid anchor and the resulting peptide is cut into two polypeptides, corresponding to active subunits. Two of these active subunits are associated to form the final active glycosylated protein. We have expressed the protein via microinjection of an expression vector into Xenopus oocyte nuclei. When the complete cDNA is injected, the acetylcholinesterase formed is biochemically similar to the Drosophila-head acetylcholinesterase. However, the hydrophobic C-terminal peptide is not replaced by a glycolipid anchor. As a consequence, the enzyme is no longer externalized, the proteolytic cutting of the main peptide does not occur and a new polymerization form occurs. Although incompletely processed, this protein is enzymatically active. When a cDNA lacking the coding region of the C-terminal hydrophobic peptide is injected, the resulting acetylcholinesterase is hydrophilic, cleaved into two subunits and secreted into the incubation medium free of contaminants.
Cytochrome P450 1B1 Expression in Glial Cell Tumors: An Immunotherapeutic Target (2007)

CYP1B1 is frequently expressed in a variety of gliomas and could be used as a target for immunotherapy.
Synthesis and Biological Activity of Novel Nonnucleoside Inhibitors of HIV-1 Reverse Transcriptase. 2-Aryl-Substituted Benzimidazoles (1997)

The development of new nonnucleoside inhibitors of human immunodeficiency virus type-1 (HIV-1) reverse transcriptase (RT) active against the drug-induced mutations in RT continues to be a very important goal of AIDS research. We used a known inhibitor of HIV-1 RT, 1-(2,6-difluorophenyl)-1H,3H-thiazolo[3,4-alpha]benzimidazole (TZB), as the lead structure for drug design with the objective of making more potent inhibitors against both wild-type (WT) and variant RTs. A series of structurally related 1,2-substituted benzimidazoles was synthesized and evaluated for their ability to inhibit in vitro polymerization by HIV-1 WT RT. A structure-activity study was carried out for the series of compounds to determine the optimum groups for substitution of the benzimidazole ring at the N1 and C2 positions. The best inhibitor, 1-(2,6-difluorobenzyl)-2-(2,6-difluorophenyl)-4-methylbenzimida zole (35), has an IC50 = 200 nM against HIV-1 WT RT in an in vitro enzyme assay. Cytoprotection assays utilizing HIV-infected MT-4 cells revealed that 35 had strong antiviral activity (EC50 = 440 nM) against wild-type virus while retaining broad activity against many clinically observed HIV-1 strains resistant to nonnucleoside inhibitors. Overall, the activity of 35 against wild-type and resistant strains with amino acid substitution in RT is 4-fold or greater than that of TZB and is comparable to that of other nonnucleoside inhibitors currently undergoing clinical trials, most of which do not have the capacity to inhibit the variant forms of the enzyme.
Why do we not have an HIV vaccine and how can we make one? (1998)

Last year, President Clinton made clear the urgent need for an effective HIV vaccine, and suggested that it should be possible to create one within ten years. The authors agree. Although recent progress should not be underestimated, many obstacles remain some technical, others not. Here, Dennis Burton (Scripps Research Institute) and John Moore (Aaron Diamond AIDS Research Center) outline their views on the state of development of an HIV vaccine and the areas in which more effort should be focused.
Scaling the Heights of Moral Humbug (2006)

The article explores the standards often pursued by moral guardians. It is believed that these personalities often adopt a high moral ground and deal with themselves in much of what they condemn.
Galectin-3 is upregulated in microglial cells in response to ischemic brain lesions, but not to facial nerve axotomy (2000)

We have recently demonstrated that the beta-galactoside-specific lectin galectin-3 is expressed by microglial cells in vitro, but not by normal resting microglia in vivo. In the present study, we have analyzed the expression of galectin-3 by microglia under traumatic conditions in vivo using two experimental rat models which substantially differ in the severity of lesion related to a breakdown of the blood-brain barrier (BBB) and the occurrence of inflammatory processes. These two features are absent after peripheral nerve lesion and present after cerebral ischemia. Here we show that, following facial nerve axotomy under conditions allowing (nerve anastomosis) or not subsequent regeneration (nerve resection), galectin-3 is not expressed by microglia in the corresponding facial nucleus 1-112 days after lesion. Galectin-3 is also absent in microglia at sites of a defective BBB in the normal brain, such as the circumventricular organs. Following experimental ischemia (i.e., permanent occlusion of the middle cerebral artery), in contrast, galectin-3 becomes strongly expressed by activated microglia as early as 48 hours after trauma, as determined by immunohistochemistry and Western blot analysis. Our findings suggest that the expression of galectin-3 by microglia in vivo correlates with the state of microglial activation.
MSF: An Efficient Mobile Phone Sensing Framework (2013)

Recent evolutions in smartphones, today provided with several sensors, have the strong processing capabilities needed to extract from raw sensed data sensor meaningful high-level views of the physical context around the user. A new promising research area called mobile sensing promotes completely decentralized sensing based on smartphone capabilities only. However, current mobile sensing solutions are not very mature; yet, because they are based on ad hoc software solutions tailored to one specific technical problem (e.g., power management, resource locking, etc.), they are difficult to reuse and integrate in different projects, and they do not focus on the performance efficiency of the monitoring support. To overcome those limitations, this paper proposes Mobile Sensing Framework (MSF), a flexible platform to ease the development of mobile sensing applications through the definition of a common set of facilities that mask all low-level technical details in reading and processing raw sensor data. MSF has been optimized also to enhance performances for Android-based systems, and we report an extensive set of experimental results that assess our architecture and quantitatively compare it with a selection of other mobile sensing systems by showing that MSF outperforms them by presenting lower CPU usage and memory footprints.
Quantitation and intracellular localization of the 85K heat shock protein by using monoclonal and polyclonal antibodies. (1984)

Two monoclonal antibodies have been produced against the human 85,000-molecular-weight heat shock protein (hsp85). One of these, 16F1, cross-reacts with the murine homolog and is shown by peptide map immunoblots to be directed against an epitope different from that recognized by the other monoclonal antibody, 9D2. Both monoclonal antibodies recognize only a single Mr-85,000 species in two-dimensional immunoblots. Immunoprecipitation did not reveal an association of this heat shock protein with any other protein in HeLa cells. Immunoperoxidase staining showed a purely cytosolic distribution at both light and electron microscopic levels and no association with membranes, mitochondria, or other organelles. The 9D2 monoclonal and a polyclonal antimurine hsp85 antibody were used to identify the antigens and to quantitate their levels in a variety of normal tissues by immunoautoradiography. Relative abundance in the various tissues as determined by Coomassie blue staining correlates reasonably well with the immunoreactivity. Testis and brain, for example, have high hsp85 levels, whereas heart and skeletal muscle have little or none. The Mr-85,000 sodium dodecyl sulfate-polyacrylamide gel band in testis and brain lysates was further confirmed to be hsp85 by one-dimensional partial proteolytic peptide mapping. Based on these data and our previous observations showing that synthesis and levels of the protein are altered by depriving cultured cells of glucose, we speculate that intracellular hsp85 levels depend on differences in the intermediary metabolism of glucose in the various tissues. Furthermore, it appears that high basal levels of this heat shock protein may not necessarily protect cells against heat shock, since testis is one of the most heat-sensitive tissues and has the highest hsp85 level.
Serum Iodothyronines in the Human Fetus and the Newborn: Evidence for an Important Role of Placenta in Fetal Thyroid Hormone Homeostasis (1999)

The pattern of circulating iodothyronines in the fetus differs from that in the adult, being characterized by low levels of serum T(3). In this study, concentrations of various iodothyronines were measured in sera from neonates of various postconceptional age (PA). Results obtained in cord sera at birth (PA, 24-40 weeks), reflecting the fetal pattern, were compared with those found during extrauterine life in newborns of 5 days or more of postnatal life (PA, 27-46 weeks). The main findings are: Starting at 30 weeks of PA, serum levels increase linearly during extrauterine life; and at 40 weeks, they are more than 200% of those measured in cord sera from newborns of equivalent PA. Serum reverse T(3) (rT3) levels during fetal life are higher than those measured during extrauterine life; but they significantly decrease, starting at 30 weeks of PA. Serum T(3) sulfate (T3S) does not significantly differ between the two groups, showing the highest values at 28-30 weeks of PA, and significantly decreasing at 30-40 weeks. T3S levels are directly correlated with rT3, both in fetal and extrauterine life, whereas a significant negative correlation between T3S and T(3) is found only during extrauterine life. In conclusion: 1) changes in serum concentrations of iodothyronines in umbilical cord and during postnatal life indicate that maturation of extrathyroidal type I-iodothyronine monodeiodinase (MD) accelerates, starting at 30 weeks of PA; 2) high levels of type III-MD activity in fetal tissues prevent the rise of serum T(3), whereas they maintain high levels of rT3 during intrauterine life; 3) an important mechanism leading to the transition from the fetal to the postnatal thyroid hormone balance is a sudden decrease in type III-MD activity; iv) because placenta contains a high amount of type III-MD, it is conceivable that placenta contributes to maintain low T(3) and high rT3 serum concentrations during fetal Life and that its removal at birth is responsible for most changes in iodothyronine metabolism occurring afterwards.
Antibodies to citrullinated proteins in rheumatoid arthritis (2006)

Rheumatoid arthritis (RA) is a systemic autoimmune disease of unknown etiology, characterized by chronic joint inflammation that often leads to joint destruction. Diagnosis of RA is currently based on the revised classification criteria of the American College of Rheumatology (ACR); however, it remains imprecise, especially early in the course of disease. Rheumatoid factor (RF) has been widely used in clinical practice as a useful serological marker for diagnosis of RA. Although RF is the only serological test in the criteria of the ACR, its specificity is limited since RF can be also detected in other rheumatic diseases. Because the current therapeutic strategies in RA employ increasingly aggressive regimens from early stage of the disease, more specific serological markers than RF are desirable. Recently, anti-cyclic citrullinated peptide (anti-CCP) antibodies have attracted attention as a useful marker for the diagnosis of RA with high specificity. In addition to the diagnostic properties, anti-CCP antibodies showed to be a good prognostic marker for joint destructions. In this review, we will explain about the clinical usefulness of anti-CCP antibodies for the daily practice of RA.
Association analysis of cysteinyl-leukotriene receptor 2 (CYSLTR2) polymorphisms with aspirin intolerance in asthmatics (2005)

CYSLTR2 polymorphisms are associated with aspirin intolerance in asthmatics.
Deep Ultraviolet Lithography of Monolayer Films with Selective Electroless Metallization (1992)

A top surface imaging approach for the fabrication of submicron features on solid substrates has been developed. A monolayer film is exposed to patterned deep ultraviolet radiation, then selectively metallized using electroless deposition such that a thin metal layer (200–400 Å) is deposited only in the unexposed areas. The film/metal assembly is a highly effective mask for reactive ion etching which can subsequently be stripped from the substrate after feature definition. Features with 0.3 μm line width in polysilicon and working transistor test structures have been produced using this process.
Structure determination of a nucleoside Q precursor isolated from E. coli tRNA: 7-{aminomethyl)-7-deazaguanosine (1978)

A precursor of modified nucleoside Q isolated from E. coli methyl-deficient tRNA was determined to be 7-(aminomethyl)-7-deazaguanosine. The structure was deduced by means of its chromatographic and electrophoretic mobilities, and UV and mass spectra, in addition to comparison with the synthesized authentic compound. The same molecule is also found in tRNA of an E. coli mutant selected for deficient synthesis of modified nucleosides.
Three Distinct Types of Monoclonal Antibodies After Long‐Term Immunization of Rats with Mouse Nerve Growth Factor (1988)

This article reports the results of a systematic investigation of the different types of antibodies produced in the course of a long-term immunization of rats with mouse nerve growth factor (NGF). We have characterized three types of monoclonal antibodies, namely: (1) antibodies that bind to NGF and inhibit its binding to target cells and its biological activity in culture (type A); (2) antibodies that bind to and precipitate NGF but do not inhibit its binding to target cells or its biological activity (type B); (3) antibodies that fail to recognize NGF itself, but inhibit nonetheless its binding to target cells (type C). These antibodies bind to an antigen present on NGF target cells and not on rat fibroblasts lacking NGF receptor. They appear thus to be antiidiotypic antibodies directed against the NGF receptor, developed as a consequence of the long-term immunization with NGF.
Clusterin is highly expressed in pancreatic endocrine tumours but not in solid pseudopapillary tumours (2007)

The expression of clusterin in all ENTs is of interest and could be an additional useful marker in the differential diagnosis with SPPTs. However, the lack of correlation between clusterin expression and clinicopathological parameters rules out a role as a predictive marker for endocrine tumour aggressiveness.
Changes in gene expression induced by a phorbol diester: expression of IL 2 receptor, T3, and T cell antigen receptor. (1987)

Phorbol esters cause an apparent differentiation of human T leukemic cell lines. It was shown previously that TPA induces the expression of the interleukin 2 (IL 2) receptor and the T3 complex on some T cell lines, including CCRF-CEM. We demonstrate that expression of the IL 2 receptor correlated with an induction of the 3.5 and 1.5 kb IL 2 receptor mRNA. In addition, the TPA-induced expression of the T3 polypeptides was found to be accompanied by induction of a putative T cell antigen receptor heterodimer on CEM cells. This was demonstrated by the co-precipitation of the T cell receptor with T3 from digitonin-solubilized cells. The cells expressed high levels of T3 delta- and T cell receptor beta-chain mRNA in the absence of TPA. The effect of TPA was to cause a rapid accumulation of T cell receptor alpha-chain mRNA. This suggested that the alpha-chain gene was rearranged before TPA induction and that expression of the T cell receptor/T3 complex on the cell surface was regulated by the level of alpha-chain expression. It was also shown that cloned sublines of CEM cells which expressed different T cell antigen phenotypes differed in their response to TPA.
BdCESA7, BdCESA8, and BdPMT Utility Promoter Constructs for Targeted Expression to Secondary Cell-Wall-Forming Cells of Grasses (2016)

Utility vectors with promoters that confer desired spatial and temporal expression patterns are useful tools for studying gene and cellular function and for industrial applications. To target the expression of DNA sequences of interest to cells forming plant secondary cell walls, which generate most of the vegetative biomass, upstream regulatory sequences of the Brachypodium distachyon lignin biosynthetic gene BdPMT and the cellulose synthase genes BdCESA7 and BdCESA8 were isolated and cloned into binary vectors designed for Agrobacterium-mediated transformation of monocots. Expression patterns were assessed using the β-glucuronidase gene GUSPlus and X-glucuronide staining. All three promoters showed strong expression levels in stem tissue at the base of internodes where cell wall deposition is most active, in both vascular bundle xylem vessels and tracheids, and in interfascicular tissues, with expression less pronounced in developmentally older tissues. In leaves, BdCESA7 and BdCESA8 promoter-driven expression was strongest in leaf veins, leaf margins, and trichomes; relatively weaker and patchy expression was observed in the epidermis. BdPMT promoter-driven expression was similar to the BdCESA promoters expression patterns, including strong expression in trichomes. The intensity and extent of GUS staining varied considerably between transgenic lines, suggesting that positional effects influenced promoter activity. Introducing the BdPMT and BdCESA8 Open Reading Frames into BdPMT and BdCESA8 utility promoter binary vectors, respectively, and transforming those constructs into Brachypodium pmt and cesa8 loss-of-function mutants resulted in rescue of the corresponding mutant phenotypes. This work therefore validates the functionality of these utility promoter binary vectors for use in Brachypodium and likely other grass species. The identification, in Bdcesa8-1 T-DNA mutant stems, of an 80% reduction in crystalline cellulose levels confirms that the BdCESA8 gene is a secondary-cell-wall-forming cellulose synthase.
USP9X destabilizes pVHL and promotes cell proliferation (2016)

Numerous mutations of the Von Hippel-Lindau (VHL) gene have been reported to cause dysfunction of VHL protein (pVHL) and lead to processes related to tumor progression. pVHL acts as an E3 ligase and degrades downstream targets, such as hypoxia-inducible transcription factor (HIF) which is essential for tumor growth. Previous studies reported reduction of VHL protein, rather than mRNA in VHL-related tumor patients, suggesting that instability of the pVHL protein itself is a primary cause of dysfunction. Regulation of pVHL stability has therefore been a major focus of research. We report that ubiquitin-specific protease 9X (USP9X), which is a deubiquitinase binds and promotes degradation of both wild-type and mutants of pVHL that retain E3 ligase function, thus activating the HIF pathway. USP9X degrades pVHL through protection of its substrate, the newly identified pVHL E3 ligase Smurf1. In addition, USP9X activates glycolysis and promotes cell proliferation through pVHL. Treatment with a USP9X inhibitor shows an effect similar to USP9X knockdown in pVHL induction, and suppresses HIF activity. Our findings demonstrate that USP9X is a novel regulator of pVHL stability, and USP9X may be a therapeutic target for treatment of VHL-related tumors.
Microelectrode measurements of pericellular PO2 in erythropoietin-producing human hepatoma cell cultures (1993)

On the basis of Fick's law of gas diffusion, it has been proposed that cells in conventional monolayer cultures may be severely hypoxic. Because knowledge of the cellular O2 availability is important for the interpretation of biochemical and toxicological cell culture work, microelectrode measurements of the pericellular PO2 were carried out using the erythropoietin (Epo)-producing human hepatoma cell lines Hep G2 and Hep 3B as an in vitro model. In confluent hepatoma cultures grown in polystyrene dishes and incubated in air with 5% CO2, the pericellular steady-state PO2 was < 1 mmHg. The rates of the production of immunoreactive Epo and lactate were high due to a misproportion between O2 supply and O2 requirements. Epo production decreased when shaken instead of static cultures were studied, or when the O2 concentration in the gas atmosphere was increased gradually up to 95%. In cultures grown on gas-permeable supports, pericellular and gas PO2 values were very similar, with increased Epo production at lowered PO2. In agreement with mathematical models, our experimental data make PO2 measurements desirable for studies of O2-dependent biological functions in cell cultures.
Effects of Dietary Nucleotides on the Fatty Acid Composition of Erythrocyte Membrane Lipids in Term Infants (1987)

Human milk contains relatively high amounts of acid-soluble nucleotides, mainly CMP, AMP, UMP, IMP, and UDP sugars, and lacks orotate. On the contrary, cow's milk and adapted formulas contain high amounts of orotate and very low amounts of CMP and AMP. Nucleotides may be modulators of metabolic functions in gut and liver. To evaluate the possible role of dietary nucleotides in newborn fatty acid metabolism, we studied the polyunsaturated fatty acid (PUFA) composition of erythrocyte membrane phospholipids in 58 term infants at 30 days of age. Twenty of them were fed human milk (HM), 19 an adapted formula (MF), and 19 with the same formula supplemented with nucleotides (NMF) in an amount similar to that present in HM. Relative content of omega 6 and 3 PUFA greater than 18 carbon atoms was significantly reduced especially in phosphatidylethanolamine and phosphatidylserine for infants fed regular MF compared with those fed HM or NMF. Unsaturation index of red blood cell phospholipids showed a similar effect. These results suggest that dietary nucleotides play a role in the in vivo desaturation and elongation of essential fatty acids to long chain PUFA during early life for the human newborn.