gebhart/patrepeval huggingface dataset:
Interleukin 9 is expressed by primary and cultured Hodgkin and Reed-Sternberg cells. (1992)

We show by mRNA hybridization analysis and immunostaining using a mouse monoclonal antibody (moAb) to recombinant human interleukin 9 (IL-9) that both primary and cultured Hodgkin and Reed-Sternberg (H-RS) cells produce IL-9 transcripts and protein and express surface binding sites for IL-9. In addition, the growth of H-RS cells obtained from the HDLM-2 line (abundantly producing IL-9 transcripts) was significantly inhibited when anti-IL-9 moAb or an IL-9 antisense oligodeoxyribonucleotide was added to cultures. Excess addition of recombinant human IL-9 relieved the effects of anti-IL-9 moAb on HDLM-2 growth. Growth of H-RS cells of the KM-H2 line, which displays only low amounts of IL-9 detectable upon hybridization of polyadenylic acid-selected RNA only, was not affected by anti-IL-9 moAb. The proliferative capacity of KM-H2 cells in soft agar and liquid suspension cultures was, however, augmented at least 3-fold when cells were exposed to recombinant human IL-9. In conclusion, our results show that IL-9 is expressed by H-RS cells and point to a possible role of this molecule as a growth factor for these cells.
Hierarchical Assembly of Porphyrins and Fullerenes for Solar Cells (2006)

The rapid consumption of fossil fuels has created unacceptable environmental problems such as greenhouse effects, which may lead to disastrous climate consequences. Thus, renewable and clean energy such as that obtained by using solar cells is required to maintain the quality of human life as well as the environment.
Translational enhancement of mdm2 oncogene expression in human tumor cells containing a stabilized wild-type p53 protein. (1997)

The mdm2 oncogene has transforming potential that is activated by overexpression. We previously reported the identification of human choriocarcinoma cell lines that have very high levels of mdm2 proteins as well as elevated levels of a stabilized wild-type p53 protein. Importantly, this mdm2 overexpression resulted from enhanced translation of mdm2 mRNA, a mechanism that had not previously been implicated in mdm2 expression control. The focus of this study was to investigate the breadth of enhanced translation of mdm2 mRNA in human cancers and to elucidate the basis for this translational activation. Here we present evidence that translational enhancement of mdm2 expression occurs in a variety of human tumor cells. Most of these samples also have high levels of wild-type p53 protein. However, there is no evidence for concomitant overexpression of the p53 target genes p21/waf1 and gadd45. Additionally, we demonstrate that the translational enhancement of mdm2 involves a preferential increase in mdm2 transcription that is initiated from the internal p53-responsive promoter region of this gene. The particular mdm2 transcripts that are generated contain a distinct 5' untranslated region and exhibit a significantly enhanced translational efficiency. These data provide a quantitative explanation for the overexpression of mdm2 proteins in this class of human tumors.
Effects of a low-fat, high-carbohydrate diet on VLDL-triglyceride assembly, production, and clearance (1999)

Low-fat, high-carbohydrate (LF/HC) diets commonly elevate plasma triglyceride (TG) concentrations, but the kinetic mechanisms responsible for this effect remain uncertain. Subjects with low TG (normolipidemic [NL]) and those with moderately elevated TG (hypertriglyceridemic [HTG]) were studied on both a control and an LF/HC diet. We measured VLDL particle and TG transport rates, plasma nonesterified fatty acid (NEFA) flux, and sources of fatty acids used for the assembly of VLDL-TG. The LF/HC diet resulted in a 60% elevation in TG, a 37% reduction in VLDL-TG clearance, and an 18% reduction in whole-body fat oxidation, but no significant change in VLDL-apo B or VLDL-TG secretion rates. Significant elevations in fasting apo B-48 concentrations were observed on the LF/HC in HTG subjects. In both groups, fasting de novo lipogenesis was low regardless of diet. The NEFA pool contributed the great majority of fatty acids to VLDL-TG in NL subjects on both diets, whereas in HTG subjects, the contribution of NEFA was somewhat lower overall and was reduced further in individuals on the LF/HC diet. Between 13% and 29% of VLDL-TG fatty acids remained unaccounted for by the sum of de novo lipogenesis and plasma NEFA input in HTG subjects. We conclude that (a) whole-food LF/HC diets reduce VLDL-TG clearance and do not increase VLDL-TG secretion or de novo lipogenesis; (b) sources of fatty acids for assembly of VLDL-TG differ between HTG and NL subjects and are further affected by diet composition; (c) the presence of chylomicron remnants in the fasting state on LF/HC diets may contribute to elevated TG levels by competing for VLDL-TG lipolysis and by providing a source of fatty acids for hepatic VLDL-TG synthesis; and (d) the assembly, production, and clearance of elevated plasma VLDL-TG in response to LF/HC diets therefore differ from those for elevated TG on higher-fat diets.
P1–257: Cerebral glucose metabolism, pathology and behaviour in the 5XFAD mouse model of Alzheimer's disease (2013)

A pathological hallmark of Alzheimer's disease (AD) is the deposition of β-amyloid (Aβ) plaques in the brain. The five times familial AD (5XFAD) mouse model is an aggressive model of brain amyloidosis. We hypothesized that the 5XFAD mouse would display changes in brain glucose metabolism compared to age-matched controls, and that these changes would be correlated with brain pathology and behavioural dysfunction. Recapitulating aspects of human AD in a mouse model at an early age will facilitate evaluation of diagnostics and therapeutics for this disease. Male 5XFAD mice and age-matched wild-type controls were injected with 18 F-FDG and imaged using PET, CT and MRI scans. The PET/CT/MRI fused data was co-registered to an MRI atlas for parcellation of specific brain regions. After decay of the isotope, the animals were perfused, the brains removed and cut in 40 um serial sections which were stained, using immunohistochemical methods, for Aβ and microglia (Iba-1). Visuo-spatial learning and memory and motor ability were assessed with the Morris water maze and rota-rod, respectively. FDG-PET imaging of the 5XFAD mice revealed a pattern of age-dependent altered brain metabolism compared to age-matched controls. β-amyloid staining revealed significant and widespread accumulation of Aβ plaques throughout the brain in the 5XFAD mice. Microglial response was elevated in aged animals and may be a contributing factor to the FDG uptake patterns observed in the brain. Modest impairments in learning and memory were observed at 6 months of age in the 5XFAD mice, while severe motor impairments were present after 12 months of age. The 5XFAD mouse develops an AD phenotype early in life. Similar to human AD, altered brain metabolism was observed in these mice compared to age matched controls. The 5XFAD mice displayed robust plaque pathology and microglial response that recapitulated characteristics of human AD. The most profound change in behavioural phenotype was motor impairment after 12 months of age. The 5XFAD mouse model may be a powerful tool for assessing efficacy of diagnostic and therapeutic agents being developed for AD.
Comprehensive DNA Microarray Analysis of Bacillus subtilis Two-Component Regulatory Systems (2001)

It has recently been shown through DNA microarray analysis of Bacillus subtilis two-component regulatory systems (DegS-DegU, ComP-ComA, and PhoR-PhoP) that overproduction of a response regulator of the two-component systems in the background of a deficiency of its cognate sensor kinase affects the regulation of genes, including its target ones. The genome-wide effect on gene expression caused by the overproduction was revealed by DNA microarray analysis. In the present work, we newly analyzed 24 two-component systems by means of this strategy, leaving out 8 systems to which it was unlikely to be applicable. This analysis revealed various target gene candidates for these two-component systems. It is especially notable that interesting interactions appeared to take place between several two-component systems. Moreover, the probable functions of some unknown two-component systems were deduced from the list of their target gene candidates. This work is heuristic but provides valuable information for further study toward a comprehensive understanding of the B. subtilis two-component regulatory systems. The DNA microarray data obtained in this work are available at the KEGG Expression Database website (http://www.genome.ad.jp/kegg/expression).
Immunosurveillance is active in colorectal cancer as downregulation but not complete loss of MHC class I expression correlates with a poor prognosis (2005)

Many colorectal tumors lose or downregulate cell surface expression of MHC class I molecules conferring resistance to T-cell-mediated attack. It has been suggested that this phenomenon is due to in vivo immune-tumor interactions. However, evidence of the impact of MHC class I loss on outcomes from colorectal cancer is scarce. In our study of more than 450 colorectal cancers in tissue microarray format, we have shown that both high levels of MHC class I expression and absent MHC class I expression are associated with similar disease-specific survival times, possibly due to natural killer cell-mediated clearance of MHC class I-negative tumor cells. However, tumors with low level expression of MHC class I were found to confer a significantly poorer prognosis, retaining independent significance on multivariate analysis. The existence of these poor prognosis tumors, which may avoid both NK- and T-cell-mediated immune surveillance, has important implications for the design of immunotherapeutic strategies in colorectal cancer.
Aging: A Theory Based on Free Radical and Radiation Chemistry (1956)

The phenomenon of growth, decline and death—aging—has been the source of considerable speculation (1, 8, 10). This cycle seems to be a more or less direct function of the metabolic rate and this in turn depends on the species (animal or plant) on which are superimposed the factors of heredity and the effects of the stresses and strains of life—which alter the metabolic activity. The universality of this phenomenon suggests that the reactions which cause it are basically the same in all living things. Viewing this process in the light of present day free radical and radiation chemistry and of radiobiology, it seems possible that one factor in aging may be related to deleterious side attacks of free radicals (which are normally produced in the course of cellular metabolism) on cell constituents.* Irradiation of living things induces mutation, cancer, and aging (9). Inasmuch as these also arise spontaneously in nature, it is natural to inquire if the processes might not be similar. It is believed that one mechanism of irradiation effect is through liberation of OH and HO 2 radicals (12). There is evidence, although indirect, that these two highly active free radicals are produced normally in living systems. In the first place, free radicals are present in living cells; this was recently demonstrated in vivo by a paramagnetic resonance absorption method (3). Further, it was shown that the concentration of free radicals increased with increasing metabolic activity in conformity with the postulates set forth some years ago that free radicals were involved in biologic oxidation-reduction reactions (11, 13). Are some of these free radicals OH and/or HO2, or radicals of a similar high order of reactivity, and where might they arise in the cell? The most likely source of OH and HO2 radicals, at least in the animal cell, would be the interaction of the respiratory enzymes involved
Development of high-titer retroviral producer cell lines by using Cre-mediated recombination (1997)

Retroviral gene transfer is widely used in experimental and human gene therapy applications. We have devised a novel method of generating high-titer retroviral producer cell lines based on the P1 bacteriophage recombinase system Cre-loxP. Incorporation of loxP sites flanking a Neo(r)-SVTK cassette in the proviral DNA allows excision of these selectable markers through expression of Cre recombinase after production of a high-titer producer cell line. The resultant producer line contains a single loxP site flanked by the viral long terminal repeats. Retransfection of this line with the Cre expression vector and a plasmid containing a gene of interest flanked by loxP sites allows insertional recombination of the gene into the favorable preexisting site in the genome and the generation of a new line with a titer equivalent to that of the parental producer cell line. The efficiency of the process is sufficient to allow the generation of multiple new producer lines without the addition of antibiotic resistance genes. We have successfully generated retroviral vectors carrying different genes by using this approach and discuss the potential applications of this method in gene therapy.
Papillary and Follicular Thyroid Carcinomas Show Distinctly Different Microarray Expression Profiles and Can Be Distinguished by a Minimum of Five Genes (2004)

PTC and FTC show distinctive microarray expression profiles, suggesting that either they have different molecular origins or they diverge distinctly from a common origin. Furthermore, if verified in a larger series of tumors, these genes could, in combination with known tumor-specific chromosome translocations, form the basis of a valuable diagnostic tool.
Validation of targeted sequencing of single‐nucleotide polymorphisms for non‐invasive prenatal detection of aneuploidy of chromosomes 13, 18, 21, X, and Y (2013)

cfDNA testing in maternal blood using targeted sequencing of polymorphic loci at chromosomes 13, 18, 21, X, and Y holds promise for accurate detection of fetal autosomal trisomies, sex chromosome aneuploidies, and triploidy.
Leishmania-induced increases in activation of macrophage SHP-1 tyrosine phosphatase are associated with impaired IFN-γ-triggered JAK2 activation (1999)

Leishmania-induced macrophage (Mphi) dysfunctions have been correlated with altered signaling events. Recent findings from our laboratory suggest that modulation of host protein tyrosine phosphatase (PTP) following Leishmania infection could lead to these Mphi defects. To address this issue, Mphi PTP activity and IFN-gamma-inducible signaling events were evaluated in Leishmania donovani (Ld)-infected cells. We observed that Ld promastigotes can rapidly trigger host PTP activity simultaneously with dephosphorylation of Mphi protein tyrosyl residues and inhibition of protein tyrosine kinase (PTK). Our results further revealed that Mphi SHP-1 PTP was rapidly activated by the infection. This Ld-evoked signaling alteration was reflected by absence of IFN-gamma-induced intracellular phosphorylation. IFN-gamma-inducible JAK2 PTK phosphorylation was also markedly diminished in Ld-infected cells. We also observed that co-immunoprecipitation of JAK2 with SHP-1 was considerably higher in infected as compared to uninfected cells. Altogether, these results suggest that SHP-1-mediated JAK2 dephosphorylation triggered by Leishmania is partly responsible for abnormal Mphi IFN-gamma signaling and represent an important mechanism supporting persistent parasitic infection.
Effect of histamine on the gene expression and biosynthesis of complement components C2, factor B and C3 in mouse peritoneal macrophages. (1987)

The gene expression and biosynthesis of C2, factor B and C3 have been investigated in vitro in mouse resident peritoneal macrophages after incubation with histamine. C2- and factor B-specific mRNA and the amount of the immunoprecipitated C2 and factor B were decreased by 10(-4) M and 10(-8) M histamine. These effects can be abrogated by the H2 antagonist cimetidine and mimicked by the H2 agonists impromidine and 4-methylhistamine. Since the H1 antagonist chlorpheniramine and the H1 agonists PEA and 2-methylhistamine have little effect on C2 and are ineffective on factor B, a strong H2 receptor dependence of the inhibition of C2 and factor B gene expression and biosynthesis is suggested. Conversely, the C3 gene expression and biosynthesis can be influenced through both H1 and H2 receptors, e.g. elevated by histamine + cimetidine, PEA and 2-methylhistamine through H1 receptors, and inhibited by histamine + chlorpheniramine, impromidine and 4-methylhistamine through H2 receptors. The data obtained by quantification of C2, factor B and C3 mRNA concentration of peritoneal macrophages suggest that the regulation of biosynthesis of these complement components by histamine in mouse peritoneal macrophages is under pretranslational control.
Configuration management with logical structures (1996)

When designing software, programmers usually think in terms of modules that are represented as functions and classes, but using existing configuration management systems, programmers have to deal with versions and configurations that are organized by files and directories. This is inconvenient and error-prone, since there is a gap between handling source code and managing configurations. We present a framework for programming environments that handles versions and configurations directly in terms of the functions and classes in source code. We show that with this framework, configuration management issues in software reuse and cooperative programming become easier. We also present a prototype environment that has been developed to verify our ideas.
Injectable bone marrow preparations to stimulate osteogenic repair. (1995)

The great versatility of bone marrow transplants based on stem cell activity has been demonstrated successfully for a variety of previously untreatable hemopoietic conditions. Autologous bone marrow delivered by percutaneous injection or by direct transplant as a composite graft also has proven effective for osteogenic stimulation in a series of 100 skeletal healing problems, including delayed unions and nonunions of fractures, arthrodeses, and bone defects. The efficiency of marrow to form bone can be increased by a number of methods, including differential centrifugation and composite grafts of marrow with demineralized bone matrix and other carriers or stimulatory factors.
N ε-(Carboxyethyl)lysine, a product of the chemical modification of proteins by methylglyoxal, increases with age in human lens proteins (1997)

Advanced glycation end-products and glycoxidation products, such as Nepsilon-(carboxymethyl)lysine (CML) and pentosidine, accumulate in long-lived tissue proteins with age and are implicated in the aging of tissue proteins and in the development of pathology in diabetes, atherosclerosis and other diseases. In this paper we describe a new advanced glycation end-product, Nepsilon-(carboxyethyl)lysine (CEL), which is formed during the reaction of methylglyoxal with lysine residues in model compounds and in the proteins RNase and collagen. CEL was also detected in human lens proteins at a concentration similar to that of CML, and increased with age in parallel with the concentration of CML. Although CEL was formed in highest yields during the reaction of methylglyoxal and triose phosphates with lysine and protein, it was also formed in reactions of pentoses, ascorbate and other sugars with lysine and RNase. We propose that levels of CML and CEL and their ratio to one another in tissue proteins and in urine will provide an index of glyoxal and methylglyoxal concentrations in tissues, alterations in glutathione homoeostasis and dicarbonyl metabolism in disease, and sources of advanced glycation end-products in tissue proteins in aging and disease.
The calibration of wide-angle lens cameras using perspective and non-perspective projections in the context of real-time tracking applications (2011)

In most close-range photogrammetry applications, the cameras are modelled as imaging systems with perspective projection combined with the lens distortion correction as proposed by Brown in 1971. In the 1980s, the calibration of video cameras received considerable attention. This required compensation for further systematic effects caused by the digitization of the analogue image signal. Modelling the image process in that manner has become the widely-applied standard since then. To take advantage of the increased field of view of individual cameras, the use of wide angle as well as fisheye lenses became common in computer vision and close-range photogrammetry, again requiring appropriate modelling of the imaging process to ensure high accuracies. A.R.T. provides real-time tracking systems with infra-red cameras, which are in some cases equipped with short focal length lenses for the purpose of increased fields of view, resulting in larger trackable object volumes. Unfortunately the lens distortion of these cameras reaches magnitudes which can not be sufficiently modelled with the customary Brown model as - mainly at high excentricities such as image corners - the calculation of the correction is not applicable. Considerations to avoid modelling these lenses as fisheye projections led to an alternate and rather pragmatic approach, where the distortion model is extended by a fourth radial distortion coefficient. Due to numeric instabilities, a stepwise camera calibration is required to achieve convergence in the bundle adjustment process. This paper presents the modified lens distortion model, describes the stepwise calibration procedure and compares results in respect to the conventional approach. The results are also compared to the approach wherein the camera lens is modelled as a fisheye projection. The introduction of a fourth radial lens distortion parameter allows the correction of lens distortion effects over the full sensor area of wide angle lenses, which increases the usable field of view of that specific camera and therefore the size of the trackable observed object volume. The approaches with the extended lens distortion model and the fisheye projection were successfully implemented and tested, and are on target to become part of the A.R.T. product range.
DaxibotulinumtoxinA for Injection for the Treatment of Glabellar Lines: Results from Each of Two Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Studies (SAKURA 1 and SAKURA 2) (2019)

Therapeutic, I.
The convertases furin and PC1 can both cleave the human immunodeficiency virus (HIV)-1 envelope glycoprotein gp160 into gp120 (HIV-1 SU) and gp41 (HIV-I TM). (1994)

Intracellular proteolytic processing of human immunodeficiency virus envelope glycoprotein precursor (gp160) is an essential step for virus infectivity. Northern blot analysis provided evidence that furin and PC1, but not PC2, are expressed in the CD4+ human lymphoblastoid H9 cell line, suggesting the possible participation of these convertases in human immunodeficiency virus (HIV) gp160 proteolytic processing. Purified PC1 and furin cleaved specifically in vitro gp160 into gp120 (HIV-I SU) and gp41 (HIV-I TM). NH2-terminal sequence analysis of the produced gp41 (HIV-I TM) demonstrated that the cleavage occurred within the sequence Arg-Glu-Lys-Arg decreases Ala-Val-Gly-Ile, which is identical to the bond cleaved in vivo. Transition state analog peptides were designed and tested in vitro for their ability to inhibit the PC1- or furin-mediated gp160 cleavage. The best inhibitor was decanoyl-Arg-Lys-Arg-Arg-psi [CH2NH]-Phe-Leu-Gly-Phe-NH2.