gebhart/patrepeval huggingface dataset:
IgG autoantibodies against C1q are correlated with nephritis, hypocomplementemia, and dsDNA antibodies in systemic lupus erythematosus. (1991)

We investigated the association between serum titers of IgG antibodies against C1q (C1qAb) and clinical and laboratory variables of disease activity in systemic lupus erythematosus (SLE). C1qAb were measured by ELISA in serum samples of 88 patients. Thirty patients (34%) had increased C1qAb titers. No correlation between C1qAb titers and a score for general disease activity was found. However, significant positive correlations were found between C1qAb titers and the presence of several clinical and laboratory variables of disease activity. These included nephritis, dermatitis, hypocomplementemia, antibodies against dsDNA, and circulating immune complexes. A negative correlation was found with neurological disease manifestations. The correlations between C1qAb titers and clinical features indicate that the pathogenetic role for C1qAb in certain disease manifestations of SLE deserves further study.
The effect of oversampling on aperture jitter in bandpass sampling receivers (2001)

Bandpass sampling allows for the digitisation of bandpass signals at RF or intermediate frequencies. This is desirable for reconfigurable radio systems, where, as many radio functions as possible should be defined in software to create a flexible transceiver. However, the effects of aperture jitter limit sampling at high carrier frequencies. This paper investigates the effects of jitter in bandpass sampling systems, and describes how oversampling the information signal has an impact on the effects of jitter.
Uterine Remodeling During Pregnancy - Studies on the Effect of Heparin/Heparan Sulfate (2009)

During pregnancy, the uterine tissues must go through a major transformation to be able to first hold the growing fetus and then, at term, expel it through the opened birth canal (cervix). It is a requirement for successful labor that there is adequate cervical softening combined with effective myometrial contractions. This is accomplished by an extensive remodeling of the extracellular matrix in both the cervix and the uterus, executed by different types of cells and mediators in a complex interplay. The overall purpose of this project was to investigate mechanisms controlling the remodeling of the uterus and cervix before parturition. This thesis demonstrates that fibroblasts with an active pro-inflammatory phenotype are important for the transformation of the uterine cervix preceding labor. Moreover, heparan sulfate proteoglycans appear to be central for the remodeling of the cervix and uterus before parturition, as shown by the finding that heparin fragments can be used in a clinical setting to prevent protracted labor.
In Silico Reconstruction of the Viral Evolutionary Lineage Yields a Potent Gene Therapy Vector (2015)

Adeno-associated virus (AAV) vectors have emerged as a gene-delivery platform with demonstrated safety and efficacy in a handful of clinical trials for monogenic disorders. However, limitations of the current generation vectors often prevent broader application of AAV gene therapy. Efforts to engineer AAV vectors have been hampered by a limited understanding of the structure-function relationship of the complex multimeric icosahedral architecture of the particle. To develop additional reagents pertinent to further our insight into AAVs, we inferred evolutionary intermediates of the viral capsid using ancestral sequence reconstruction. In-silico-derived sequences were synthesized de novo and characterized for biological properties relevant to clinical applications. This effort led to the generation of nine functional putative ancestral AAVs and the identification of Anc80, the predicted ancestor of the widely studied AAV serotypes 1, 2, 8, and 9, as a highly potent in vivo gene therapy vector for targeting liver, muscle, and retina.
Macrophages: Modulators of Breast Cancer Progression (2004)

In many solid tumour types the abundance of tumour associated macrophages (TAMs) is correlated with poor prognosis. Macrophages are recruited through the local expression of chemoattractants such as colony stimulating factor 1 (CSF-1) and macrophage chemoattractant protein 1. Over-expression of both of these factors is correlated with poor prognosis in a variety of tumours. Macrophages also play an important physiological role in the development and function of many tissues ranging from the brain to the mammary gland. Thus we hypothesized that TAMs are recruited to tumours through the expression of potent chemoattractants and in this site their normal trophic functions are subverted to promote tumour progression and metastasis. To test this hypothesis we crossed mice deficient in macrophages owing to being homozygous for a null mutation in the CSF-1 gene with mice pre-disposed to mammary cancer due to the epithelial restricted expression of the polyoma middle T oncoprotein. The absence of macrophages did not change the incidence or growth of the primary tumour but decreased its rate of progression and inhibited metastasis. These data are explicable through the known macrophage functions in matrix remodelling, angiogenesis and stimulation of tumour growth and motility through the synthesis of growth and chemotactic factors. Interestingly, these functions are also normally found in wound healing or pathologically during chronic inflammation. This supports the notion that tumours are 'wounds that never heal' and suggests that chronic inflammation through persistent infection or by other means might be an important cofactor in the genesis and promotion of tumours. Macrophages might therefore be important targets for cancer therapies.
Disassembling and Bleaching of Chloride-FreepharaonisHalorhodopsin by Octyl-β-glucoside (2005)

Natronomonas (Natronobacterium) pharaonis halorhodopsin (NpHR) is a transmembrane, seven-helix retinal protein of the archaeal bacterium and acts as an inward light-driven chloride ion pump in the membrane. The denaturation process of NpHR solubilized with n-octyl-beta-d-glucopyranoside (OG) was investigated to clarify the effects of the chloride ion and pH on the stability and bleaching of the NpHR chromophore. Initially, active NpHR solubilized with n-dodecyl-beta-d-maltopyranoside (DM) was obtained from the recombinant halo-opsin (NpHO), which was expressed in Escherichia coli cells, by adding all-trans retinal to the medium. Apparent molecular weight of the active NpHR solubilized with DM, which was determined by gel-filtration chromatography and dynamic light scattering, indicated the oligomeric state. The bleaching of NpHR in the dark by the addition of 50 mM OG in the presence and absence of chloride was investigated. In the presence of 256 mM NaCl, the bleaching of NpHR was strongly inhibited. On the other hand, in the absence of NaCl, an immediate decrease of absorbance at 600 nm was observed. Stopped-flow rapid-mixing analysis clarified the bleaching process in the absence of chloride as DM-NpHR (oligomeric) <--> OG-NpHR (disassembled) <--> intermediate --> NpHO and free retinal, and each rate constant were determined. The formation of an intermediate (450 nm) in the dark was found to be strongly dependent on pH, as well as anion and detergent concentrations. The disassembling and protonation of a Schiff base corresponding to the bleaching intermediate is also discussed.
Collagenolytic cathepsin B and L activity in experimental fibrotic liver and human liver. (1992)

To clarify the role of individual collagenolytic cathepsin in hepatic collagen degradation, cathepsin B and L activities were determined in normal and CCl4-induced fibrotic liver, together with non-collagenolytic cathepsin H. Cathepsin B and L activities increased 1.9- and 2.0- fold, respectively, in the fibrotic liver as compared with the normal liver, and were significantly correlated with hepatic hydroxyproline levels. By contrast, cathepsin H activity was not altered in fibrotic rats. Similar results were also obtained from autopsied human livers. These results suggest that cathepsin B and L are similarly induced by hepatic collagen levels and are implicated in degrading collagens, especially soluble collagen.
Xenograft models for the preclinical evaluation of new therapies in acute leukemia (2007)

Major advances in understanding the pathophysiology of acute leukemia have resulted in a dramatic increase in the availability of novel compounds for clinical trials. However, since the number of new drugs far exceeds the number of clinical trials that can be conducted because of the availability of eligible patients, there is an urgent need to utilize reliable preclinical models for the prioritization of the most promising potential therapies for those clinical trials. The most widely used preclinical models for the acute leukemias are human tumor xenografts established in immune-deficient mice, and genetically engineered mouse strains. This review summarizes the recent developments and considerations in the use of xenograft models of acute lymphoblastic leukemia, acute myeloid leukemia, and acute promyelocytic leukemia for the preclinical testing of new therapies.
A novel strategy to design binding molecules harnessing the modular nature of repeat proteins (2003)

Repeat proteins, such as ankyrin or leucine-rich repeat proteins, are ubiquitous binding molecules, which occur, unlike antibodies, intra- and extracellularly. Their unique modular architecture features repeating structural units (repeats), which stack together to form elongated repeat domains displaying variable and modular target-binding surfaces. Based on this modularity, we developed a novel strategy to generate combinatorial libraries of polypeptides with highly diversified binding specificities. This strategy includes the consensus design of self-compatible repeats displaying variable surface residues and their random assembly into repeat domains. We envision that such repeat protein libraries will be highly valuable sources for novel binding molecules especially suitable for intracellular applications.
Pluripotency and nuclear reprogramming (2008)

Embryonic stem cells are promising donor cell sources for cell transplantation therapy, which may in the future be used to treat various diseases and injuries. However, as is the case for organ transplantation, immune rejection after transplantation is a potential problem with this type of therapy. Moreover, the use of human embryos presents serious ethical difficulties. These issues may be overcome if pluripotent stem cells are generated from patients' somatic cells. Here, we review the molecular mechanisms underlying pluripotency and the currently known methods of inducing pluripotency in somatic cells.
Imaging glioma extent with 131I-TM-601. (2005)

131I-TM-601 provides a reliable estimate for primary tumor extent. Further modification of this radiopeptide with other better imaging isotopes may provide an important tool for determining tumor extent and differentiating regions of viable tumor from necrosis.
2'-O-Acyl-6-thioinosine cyclic 3',5'-phosphates as prodrugs of thioinosinic acid (1979)

A series of 2'-O-acyl derivatives of 6-thioinosine cyclic 3',5'-phosphate (6-HS-cRMP) were prepared and examined for their cytotoxic effects on S49 mouse lymphoma cells which were deficient in hypoxanthine-guanine phosphoribosyltransferase (HGPRTase). Cytotoxicity increased with the lipophilicity of the acyl group to a lowest EC50 of 65 micrometer for the 2'-O-palmityl derivative. Addition of a mutation in the gene for cAMP-dependent protein kinase to the HGPRTase-deficient cell line confers resistance to 2'-O-butyryl-cAMP but not to 2'-O-butyryl-6-HS-cRMP, indicating that the latter does not exert its toxic effect via activation of protein kinase. The time course of cell kill by 2'-O-palmityl-6-HS-cRMP resembled that of 6-mercaptopurine and not that of cyclic AMP in these cells. The data suggest that the intact cyclic nucleotides are penetrating the cells and being converted, by phosphodiesterase action and deacylation, to the first toxic metabolite of 6-mercaptopurine, thioinosinic acid.
Non-Pathogenic Mopeia Virus Induces More Robust Activation of Plasmacytoid Dendritic Cells than Lassa Virus (2019)

Lassa virus (LASV) causes a viral haemorrhagic fever in humans and is a major public health concern in West Africa. An efficient immune response to LASV appears to rely on type I interferon (IFN-I) production and T-cell activation. We evaluated the response of plasmacytoid dendritic cells (pDC) to LASV, as they are an important and early source of IFN-I. We compared the response of primary human pDCs to LASV and Mopeia virus (MOPV), which is very closely related to LASV, but non-pathogenic. We showed that pDCs are not productively infected by either MOPV or LASV, but produce IFN-I. However, the activation of pDCs was more robust in response to MOPV than LASV. In vivo, pDC activation may support the control of viral replication through IFN-I production, but also improve the induction of a global immune response. Therefore, pDC activation could play a role in the control of LASV infection.
Association of Human Bocavirus 1 Infection with Respiratory Disease in Childhood Follow-up Study, Finland (2012)

Human bocavirus 1 (HBoV1) DNA is frequently detected in the upper airways of young children with respiratory symptoms. Because of its persistence and frequent co-detection with other viruses, however, its etiologic role has remained controversial. During 2009-2011, using HBoV1 IgM, IgG, and IgG-avidity enzyme immunoassays and quantitative PCR, we examined 1,952 serum samples collected consecutively at 3- to 6-month intervals from 109 constitutionally healthy children from infancy to early adolescence. Primary HBoV1 infection, as indicated by seroconversion, appeared in 102 (94%) of 109 children at a mean age of 2.3 years; the remaining 7 children were IgG antibody positive from birth. Subsequent secondary infections or IgG antibody increases were evident in 38 children and IgG reversions in 10. Comparison of the seroconversion interval with the next sampling interval for clinical events indicated that HBoV1 primary infection, but not secondary immune response, was significantly associated with acute otitis media and respiratory illness.
Recombinant derivatives of Pasteurella multocida toxin: candidates for a vaccine against progressive atrophic rhinitis (1991)

Potential vaccine components for protection against atrophic rhinitis in pigs were developed. This was achieved by deletion mutagenesis of the gene encoding the Pasteurella multocida toxin. Four purified toxin derivatives lacking different and widely separated regions in the amino acid sequence were characterized by a lack of toxic activity. One such component was shown to induce efficient protection of vaccinated female mice and their offspring against challenge with purified P. multocida toxin.
The path forward for anti-programmed cell death-1 therapy in gliomas (2019)

Even though anti-PD-1 therapy does not seem to provide a benefit for molecularly unselected GBM patients, the success of PD-1 blockade in certain subsets of patients is encouraging.
A novel nanoionics-based switch for microwave applications (2008)

This paper reports the development and characterization of a novel switching device for use in microwave systems. The device utilizes a switching mechanism based on nanoionics, in which mobile ions within a solid electrolyte undergo an electrochemical process to form and remove a conductive metallic “bridge” to define the change of state. The nanoionics-based switch has demonstrated an insertion loss of ∼0.5dB, isolation of ≫0dB, low voltage operation (1V), low power (∼¼W) and low energy (∼nJ) consumption, and excellent linearity up to 6 GHz. The switch requires fewer bias operations (due to non-volatile nature) and has a simple planar geometry allowing for novel device structures and easy integration into microwave power distribution circuits.
[Interaction of synthetic ligands containing N,4-disubstituted mono- and diphthalimides with DNA]. (1995)

Nevel synthetic DNA binding ligands containing N,4-disubstituted mono- and diphthalimide fragments and carrying positively charged groups at both ends of the molecules were characterized by various physiochemical methods. All the ligands were shown to have fluorescence maximum at about 460 nm for excitation at 340 nm. Interaction of these compounds with DNA and synthetic polydeoxyribonucleotides was studied using spectrophotometry, CD and fluorescence measurements. It was shown, that the ligand containing phthalimide fragment connected by flexible chain to dipyrrolcarboxamide fragment, binds to DNA narrow groove covering 5 base pairs. This type of complex formation was found to be followed by increasing of CD band at 280 nm and increasing in fluorescence intensity. If the ligand backbone contains only phthalimide fragments there is no binding in the DNA narrow groove. In this case the weakly fluorescent outside binding type complex is formed, which is characterized by the binding of one ligand molecule with two base pairs.
Cytokines link osteoblasts and inflammation: microarray analysis of interleukin-17- and TNF-α-induced genes in bone cells (2004)

The novel cytokine interleukin (IL)-17 has been implicated in many infectious and autoimmune settings, especially rheumatoid arthritis. Consistent with its proinflammatory effects on bone, osteoblast cells are highly responsive to IL-17, particularly in combination with other inflammatory cytokines. To better understand the spectrum of activities controlled by IL-17, we globally profiled genes regulated by IL-17 and tumor necrosis factor alpha (TNF-alpha) in the preosteoblast cell line MC3T3-E1. Using Affymetrix microarrays, 80-90 genes were up-regulated, and 19-50 genes were down-regulated with IL-17 and TNF-alpha as compared with TNF-alpha alone. These included proinflammatory chemokines and cytokines, inflammatory genes, transcriptional regulators, bone-remodeling genes, signal transducers, cytoskeletal genes, genes involved in apoptosis, and several unknown or unclassified genes. The CXC family chemokines were most dramatically induced by IL-17 and TNF-alpha, confirming the role of IL-17 as a potent mediator of inflammation and neutrophil recruitment. Several transcription factor-related genes involved in inflammatory gene expression were also enhanced, including molecule possessing ankyrin repeats induced by lipopolysaccharide/inhibitor of kappaBzeta (MAIL/kappaBzeta), CCAAT/enhancer-binding protein delta (C/EBPdelta), and C/EBPbeta. We also identified the acute-phase gene lipocalin-2 (LCN2/24p3) as a novel IL-17 target, which is regulated synergistically by TNF-alpha and IL-17 at the level of its promoter. A similar but not identical pattern of genes was induced by IL-17 and TNF-alpha in ST2 bone marrow stromal cells and murine embryonic fibroblasts. This study provides a profile of genes regulated by IL-17 and TNF-alpha in osteoblasts and suggests that in bone, the major function of IL-17 is to cooperate and/or synergize with other cytokines to amplify inflammation.
NG2/HMP Proteoglycan as a Cancer Therapeutic Target (2006)

Neuroepithelial cells of the central nervous system constitute neuroglia (astrocytes, oligodendrocytes, and microglia), ependyma, and neurons, which make up the stromal cells of the brain. The stromal tissue organization of the brain is tightly regulated, but occasionally the signals that define the normal contexts become disrupted and result in cancer. Malignant progression is then maintained by cross-talks between the tumor and its stroma, where the activated stroma nurtures the proliferative and invasive neoplastic cells, by providing neovasculature, extracellular matrix components, and stimulatory growth factors. The NG2/HMP plays a major role in tumor-stroma activation through alterations in cellular adhesion, migration, proliferation, and vascular morphogenesis. Therapeutic strategies specifically targeting NG2/HMP may be useful in normalizing the tumor stroma and may reduce the toxic side effects when used in combination with conventional treatments.
Benzoquinone imines. Part 13. Reactions of N-methylated 2-aminoindamines in aqueous solution (1977)

N-Methylated 2-aminoindamines (2-amino-N-(4-aminophenyl)-p-benzoquinone di-imines) undergo hydrolysis at the azomethine bridge at pH < 4, intramolecular cyclization to diaminophenazines at pH 4–9.5, and hydrolysis of the terminal imino-group at high pH. The effect of N-methylation of either amino- or imino-group on the rate of these reactions is consistent with the proposed mechanisms. Acid hydrolysis involves reaction of the dication with a hydroxonium ion and with water, cyclization involves an intramolecular coupling of the 2-aminonitrogen of the monocation, to the 2-carbon atom, followed by oxidation, and alkaline hydrolysis involves reaction of a hydroxide ion with the monocation. The N4N4-dimethylindaminium ions form a neutral species at pH > 11 by loss of a proton from the tautomeric form 4-dimethylamino-N1-(4-aminophenyl)-o-benzoquinone di-imine. 2-Dimethylaminoindamines undergo rapid intramolecular cyclization to give the colourless 2,8-diamino-10.10 dimethyl-5,10-dihydrophenazinium ion. This is slowly converted into a 10-methylphenazinium salt, a methyl group being eliminated as methanol.
The search for new COX-2 inhibitors: a review of 2002 – 2008 patents (2009)

Structural analogues of the COX-2 inhibitors celecoxib and valdecoxib, and novel potential pyridazine, triazole, indole and thione derivatives emerge as promising leads for the treatment of inflammation, pain and other diseases.
A chimeric protein comprised of IL-4 and Pseudomonas exotoxin is cytotoxic for activated human lymphocytes. (1994)

IL4-Pseudomonas exotoxin (IL4-PE4E) is a chimeric molecule in which human IL-4 is genetically fused to the mutated binding domain of Pseudomonas exotoxin. This molecule binds specifically to human IL-4 receptor-bearing cells. IL4-PE4E was extremely cytotoxic to highly purified anti-CD3-activated CD8+ T lymphocytes. The cytotoxic activity of this molecule was dependent on the activation state of CD8+ T cells: 3- and 4-day activated T cells were very susceptible to the cytotoxic activity of IL4-PE4E compared with 0- to 2-day activated cells. PHA-activated lymphocytes and PBL activated in mixed lymphocyte reaction were also highly sensitive to IL4-PE4E. CD16+ and/or CD56+ highly purified NK cells or highly purified, IL-2-activated NK cells were also very sensitive to the cytotoxic effect of IL4-PE4E. IL-2-activated LAK cells had little susceptibility after 1 day but were very sensitive to IL4-PE4E after 3 days. The cytotoxic effects of IL4-PE4E were mediated through a ligand receptor interaction because excess rIL-4 abrogated these effects as did a neutralizing Ab to human IL-4. A chimeric mutant protein that can bind to IL-4 receptors but lacks the ability to inhibit protein synthesis was not cytotoxic to activated lymphocytes. The IL4-PE4E-mediated cytotoxicity of activated T cells correlated with the level of expression of IL-4 receptors on these cells. CD8+ T cells activated for 3 days expressed the highest density of IL-4 receptors compared with 1- or 2-day activated cells. Among two chimeric toxins tested only IL4-PE4E was cytotoxic to 2-day anti-CD3-activated CD8+ T lymphocytes, whereas IL6-PE4E was not active at all. These studies suggest that human IL4 toxin could be a potent agent for the elimination of activated lymphocytes in allograft rejection, some autoimmune diseases, or treatment of lymphomas and leukemias.