gebhart/patrepeval huggingface dataset:
Progesterone Action in Human Tissues: Regulation by Progesterone Receptor (PR) Isoform Expression, Nuclear Positioning and Coregulator Expression (2009)

Progesterone is a critical regulator of normal female reproductive function, with diverse tissue-specific effects in the human. The effects of progesterone are mediated by its nuclear receptor (PR) that is expressed as two isoforms, PRA and PRB, which are virtually identical except that PRA lacks 164 amino acids that are present at the N-terminus of PRB. Considerable in vitro evidence suggests that the two PRs are functionally distinct and in animals, tissue-specific distribution patterns of PRA and PRB may account for some of the diversity of progesterone effects. In the human, PRA and PRB are equivalently expressed in most target cells, suggesting that alternative mechanisms control the diversity of progesterone actions. PR mediates the effects of progesterone by association with a range of coregulatory proteins and binding to specific target sequences in progesterone-regulated gene promoters. Ligand activation of PR results in redistribution into discrete subnuclear foci that are detectable by immunofluorescence, probably representing aggregates of multiple transcriptionally active PR-coregulator complexes. PR foci are aberrant in cancers, suggesting that the coregulator composition and number of complexes is altered. A large family of coregulators is now described and the range of proteins known to bind PR exceeds the complement required for transcriptional activation, suggesting that in the human, tissue-specific coregulator expression may modulate progesterone response. In this review, we examine the role of nuclear localization of PR, coregulator association and tissue-specific expression in modulating progesterone action in the human.
Proliferation of cultured fibroblasts is inhibited byL‐Iduronate—containing glycosaminoglycans (1991)

We have modified a method (Gilles et al: Anal. Biochem., 159:109-113, 1986) for measuring cell number, that is based on the binding of crystal violet to cell nuclei and used it to assay effects of various glycosaminoglycans on growth of human lung fibroblasts. The procedure was modified by growing cells in microcultures (96 well microplates) and by measuring the amount of adsorbed dye using a microplate photometer after solubilisation of the cells with detergent. There was a linear relationship between absorbance and cell number measured by a Coulter Counter. The method is rapid and sensitive and can be used for screening many samples as well as measuring growth rates at low initial cell densities. Even the low growth rates obtained in the absence of serum can be detected. Human lung fibroblasts were growth arrested by serum deprivation and then grown for periods of up to 4 days in the presence of serum and exogenously added glycosaminoglycans (range, 0.1-100 micrograms/ml). Hyaluronan, chondroitin sulfate, and dextran sulfate were without effects, whereas dermatan sulfate, certain heparan sulfates, and heparin suppressed growth (20%-50% inhibition). The antiproliferative activity of dermatan sulfate increased with increasing iduronate content. Certain heparan sulfates, with moderately high sulfate and L-iduronate contents were better inhibitors than heparin despite the fact that the latter glycan has even higher sulfate and L-iduronate contents. The antiproliferative effect of exogenous glycans appeared after a lag period of 3-4 days, suggesting that they interfered with factors produced by the cells. Furthermore, the degree of inhibition was greater when the initial cell density was low. Above a certain level of seeded cells (approx. 10,000 cells/well), there was no inhibition by any of the glycosaminoglycans. It is possible that exogenous glycans cannot overcome endogenous growth-promoting effects in densely seeded cultures.
Modulation of human fibroblast gap junction intercellular communication by hyaluronan (2003)

The composition of the extracellular matrix changes during dermal repair. Initially, hyaluronan (HA) concentration is high, however, by day 3, HA is eliminated. HA optimizes collagen organization within granulation tissue. One possible mechanism of HA modulation of collagen packing is through the promotion of gap junction intercellular communication (GJIC). Gap junctions are gated channels that allow rapid intercellular communication and synchronization of coupled cell activities. The gap junction channel is composed of connexin (Cx) proteins that form a gated channel between coupled cells. HA is reported to enhance Cx43 expression in transformed fibroblasts. GJIC was quantified by the scrape loading technique and reported as a coupling index. The coupling index for human dermal fibroblasts was 4.6 +/- 0.2, while the coupling index for fibroblasts treated with HA more than doubled to 10.6 +/- 0.7. By Western blot analysis no differences were appreciated in the protein levels of Cx43 or beta-catenin, a protein involved in the translocation of Cx to the cell surface. By immuno-histology Cx43 and beta-catenin were evenly distributed throughout the cell in controls, but in cells treated with HA these proteins were co-localized to the cell surface. Coupled fibroblasts are reported to enhance the organization of collagen fibrils. It is proposed that HA increases the accumulation of Cx43 and beta-catenin on the cell surface, leading to greater GJIC and enhanced collagen organization.
Viruses with Circular Single-Stranded DNA Genomes Are Everywhere! (2017)

Circular single-stranded DNA viruses infect archaea, bacteria, and eukaryotic organisms. The relatively recent emergence of single-stranded DNA viruses, such as chicken anemia virus (CAV) and porcine circovirus 2 (PCV2), as serious pathogens of eukaryotes is due more to growing awareness than to the appearance of new pathogens or alteration of existing pathogens. In the case of the ubiquitous human circular single-stranded DNA virus family Anelloviridae, there is still no convincing direct causal relation to any specific disease. However, infections may play a role in autoimmunity by changing the homeostatic balance of proinflammatory cytokines and the human immune system, indirectly affecting the severity of diseases caused by other pathogens. Infections with CAV (family Anelloviridae, genus Gyrovirus) and PCV2 (family Circoviridae, genus Circovirus) are presented here because they are immunosuppressive and affect health in domesticated animals. CAV shares genomic organization, genomic orientation, and common features of major proteins with human anelloviruses, and PCV2 DNA may be present in human food and vaccines.
Derivation and Comparative Assessment of Retinal Pigment Epithelium from Human Embryonic Stem Cells Using Transcriptomics (2004)

Human stem-cell derivatives are likely to play an important role in the future of regenerative medicine. Evaluation and comparison to their in vivo counterparts is critical for assessment of their therapeutic potential. Transcriptomics was used to compare a new differentiation derivative of human embryonic stem (hES) cells--retinal pigment epithelium (RPE)--to human fetal RPE. Several hES cell lines were differentiated into putative RPE, which expressed RPEspecific molecular markers and was capable of phagocytosis, an important RPE function. Isolated hES cell-derived RPE was able to transdifferentiate into cells of neuronal lineage and redifferentiate into RPE-like cells through multiple passages (>30 Population doublings). Gene expression profiling demonstrated their higher similarity to primary RPE tissue than of existing human RPE cell lines D407 and ARPE-19, which has been shown to attenuate loss of visual function in animals. This is the first report of the isolation and characterization of putative RPE cells from hES cells, as well as the first application of transcriptomics to assess embryonic stem-cell derivatives and their in vivo counterparts--a "differentiomics" outlook. We describe for the first time, a differentiation system that does not require coculture with animal cells or factors, thus allowing the production of zoonoses-free RPE cells suitable for subretinal transplantation in patients with retinal degenerative diseases. With the further development of therapeutic cloning, or the creation of the banks of homozygous human leucocyte antigen (HLA) hES cells using parthenogenesis, RPE lines could be generated to overcome the problem of immune rejection and could be one of the nearest term applications of stem-cell technology.
Comparing Public-Cloud Providers (2011)

As cloud computing becomes increasingly popular among enterprises, developers, and organizations, it's time to consider the practical problem: how do you choose from the growing number of providers? To help users make this decision, researchers first determined the basic types of services that providers offer. They then devised a set of metrics related to application performance in a cloud and created tools for measuring them.
3-Cycloalkenylindoles (1975)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT3-CycloalkenylindolesKurt FreterCite this: J. Org. Chem. 1975, 40, 17, 2525–2529Publication Date (Print):August 1, 1975Publication History Published online1 May 2002Published inissue 1 August 1975https://pubs.acs.org/doi/10.1021/jo00905a023https://doi.org/10.1021/jo00905a023research-articleACS PublicationsRequest reuse permissionsArticle Views360Altmetric-Citations40LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
NLRP3 inflammasome activation promotes inflammation-induced carcinogenesis in head and neck squamous cell carcinoma (2017)

Our study demonstrates that NLRP3 inflammasome was upregulated and associated with the carcinogenesis and CSCs self-renewal activation in SCCHN. NLRP3 inflammasome can be a potential target in the development of novel approaches for head and neck squamous cell carcinoma therapy.
Solid-Phase Proteoliposomes Containing Human Immunodeficiency Virus Envelope Glycoproteins (2002)

The human immunodeficiency virus type 1 (HIV-1) exterior envelope glycoprotein gp120 mediates receptor binding and is the major target for neutralizing antibodies. A broadly neutralizing antibody response is likely to be a critical component of the immune response against HIV-1. Although antibodies against monomeric gp120 are readily elicited in immunized individuals, these antibodies are inefficient in neutralizing primary HIV-1 isolates. As a chronic pathogen, HIV-1 has evolved to avoid an optimal host response by a number of immune escape mechanisms. Monomeric gp120 that has dissociated from the functional trimer presents irrelevant epitopes that are not accessible on functional trimeric envelope glycoproteins. The resulting low level of antigenic cross-reactivity between monomeric gp120 and the functional spike may contribute to the inability of monomeric gp120 to elicit broadly neutralizing antibodies. Attempts to generate native, trimeric envelope glycoproteins as immunogens have been frustrated by both the lability of the gp120-gp41 interaction and the weak association between gp120 subunits. Here, we present solid-phase HIV-1 gp160DeltaCT (cytoplasmic tail-deleted) proteoliposomes (PLs) containing native, trimeric envelope glycoproteins in a physiologic membrane setting. We present data that indicate that the gp160DeltaCT glycoproteins on PLs are trimers and are recognized by several relevant conformational ligands in a manner similar to that for gp160DeltaCT oligomers expressed on the cell surface. The PLs represent a significant advance over present envelope glycoprotein formulations as candidate immunogens for HIV vaccine design and development.
STAT5 is a potent negative regulator of TFH cell differentiation (2012)

Follicular helper T cells (T(FH) cells) constitute the CD4(+) T cell subset that is specialized to provide help to germinal center (GC) B cells and, consequently, mediate the development of long-lived humoral immunity. T(FH) cell differentiation is driven by the transcription factor Bcl6, and recent studies have identified cytokine and cell-cell signals that drive Bcl6 expression. However, although T(FH) dysregulation is associated with several major autoimmune diseases, the mechanisms underlying the negative regulation of T(FH) cell differentiation are poorly understood. In this study, we show that STAT5 inhibits T(FH) cell differentiation and function. Constitutive STAT5 signaling in activated CD4(+) T cells selectively blocked T(FH) cell differentiation and GCs, and IL-2 signaling was a primary inducer of this pathway. Conversely, STAT5-deficient CD4(+) T cells (mature STAT5(fl/fl) CD4(+) T cells transduced with a Cre-expressing vector) rapidly up-regulated Bcl6 expression and preferentially differentiated into T(FH) cells during T cell priming in vivo. STAT5 signaling failed to inhibit T(FH) cell differentiation in the absence of the transcription factor Blimp-1, a direct repressor of Bcl6 expression and T(FH) cell differentiation. These results demonstrate that IL-2, STAT5, and Blimp-1 collaborate to negatively regulate T(FH) cell differentiation.
GRAVITY FIELD DETERMINATION FOR THE TERRITORY OF CROATIA - PRELIMINARY RESULTS - (1992)

As a independent state, Croatia needs much better knowledge of the gravity field pa­ rameters, especially in connection with the present realization of GPS-measurements on its territory. In order to get the best possible gravity field solution in the case of really large relief variety, different kind of data - gravity anomalies, vertical deflec­ tions, satellite altimetry - has to be appropriately combined, taking also into account the topographic/bathymetric information. In this paper some preliminary results for the gravimetric geoid are presented for the first time. It's comparison with the existing astrogeodetic solution for Slovenia and a part of Croatia is given and future possible steps described.
Multivirus-Specific CTl for Adoptive Transfer Using in Vitro Pepmix Stimulation (2011)

We and others have shown that viral infections in allo-HSCT recipients can be prevented/treated by the adoptive transfer of virus-specific CTL. However, conventional CTL manufacture has taken > 3 months. We recently developed a protocol to rapidly generate CTLs (rCTLs) using DCs nucleofected with viral antigen-encoding DNA plasmids as APCs and expansion in a gas permeable bioreactor (G-Rex) in IL7+IL4, which reduces manufacturing time to 16 days. To further streamline production without affecting potency, we are now assessing whether multivirus CTL can be generated by directly stimulating donor PBMCs with clinically applicable pepmixes (15mer peptide libraries) spanning viral antigens. We isolated PBMCs from 4 healthy donors and generated rCTL using plasmid-nucleofected DCs or by directly stimulating bulk PBMCs using pepmixes spanning the same antigens encoded by the plasmids (EBV-EBNA1, LMP2, BZLF1; CMV-IE1, pp65 and Adv-Hexon, Penton) (pCTL). Subsequently the activated cells were expanded as outlined above. We compared the phenotype, proliferation, specificity and function of each cell population. There was no significant difference in the rate of expansion (rCTL vs pCTL, 8.6 vs 7.1 fold). Similarly, both were phenotypically indistinguishable, with a dominance of CD4 T cells (70.5 vs 74.2%) expressing CD62L (77 vs 61%). Both rCTL and pCTL were specific for the stimulating antigens as measured by IFNγ ELIspot with a median of 100 vs 55 EBNA1, 45 vs 47 LMP2, 55 vs 32 BZLF1, 195 vs 232 IE1, 3927 vs 4472 pp65, 525 vs 535 Hexon, 372 vs 782 Penton SFC/1x106 CTL. rCTL and pCTL lysed EBV (16 vs 19%), Adv (27 vs 34%) and CMV targets (42 vs 49% E:T 80:1). Finally, to evaluate whether stimulation using 15mer peptides, which contain all CD8 but possibly not all CD4 epitopes, results in loss of CD4+ specificity we generated pCTL using either 15-or 30mer peptides spanning a region of Hexon predominantly recognized by CD4+ T cells. Phenotypically the CTL were similar (CD4+ 56 vs 60%; CD8+ 21 vs 16%) and epitope specificity, as evaluated by stimulation with peptide pools, demonstrated slightly broader specificity using 15-over 30mer peptides with a mean of 10 vs 7 pools recognized. In summary, we can efficiently generate polyclonal multivirus CTLs by directly stimulating PBMCs with pepmixes. This approach is clinically applicable, requires a starting blood volume of only 15ml, and reduces manufacturing time to < 10 days, with a consequent reduction in cost and complexity.
Mediators of Innate Immunity That Target Immature, But Not Mature, Dendritic Cells Induce Antitumor Immunity When Genetically Fused with Nonimmunogenic Tumor Antigens (2001)

Chemokine receptors are differentially expressed on immature and mature dendritic cells (DC). Herein, we demonstrate for the first time that murine antimicrobial peptides beta-defensins 2 and 3 bind murine CCR6, similarly to inflammatory chemokine macrophage-inflammatory protein 3alpha, and they chemoattract bone marrow-derived immature, but not mature DC. Using various chemokines or defensins fused with nonimmunogenic tumor Ags, we studied their capacity to delivery Ags to subsets of immune cells to elicit antitumor immunity. We demonstrate that DNA immunizations with fusion constructs with beta-defensin 2 or inflammatory chemokines that target immature DC, but not homeostatic chemokines secondary lymphoid tissue chemokine, CCL21, or stromal cell-derived factor 1, CXCL12, which chemoattract mature DC, elicit humoral, protective, and therapeutic immunity against two different syngeneic lymphomas.
Regulation of oligodendrocyte differentiation: a role for retinoic acid in the spinal cord (1994)

During development, oligodendrocyte precursors undergo sequential stages of differentiation characterized by expression of distinct cell surface properties and proliferative responses. Although both PDGF and bFGF are mitogenic for these cells, the factors that regulate the progression of oligodendrocyte precursors through their differentiative program remain unclear. One factor present in the embryonic spinal cord that may regulate differentiation of oligodendrocyte precursors is retinoic acid. Here we show that retinoic acid inhibits the maturation of embryonic spinal cord oligodendrocyte precursors in vitro at an early, highly motile stage of differentiation, characterized by the expression of A2B5 immunoreactivity. Basic FGF acts both as a mitogen and an inhibitor of spinal cord oligodendrocyte precursor maturation, but at a significantly later stage of differentiation, characterized by the expression of O4 immunoreactivity. In the presence of RA both the mitogenic and differentiation inhibiting effects of bFGF are abolished, consistent with RA acting as an early regulator of oligodendrocyte differentiation. During embryonic development, oligodendrocyte precursors arise initially from a distinct group of cells at the ventral ventricular zone of the spinal cord. Myelination of the entire spinal cord is dependent on the migration of immature precursor cells to peripheral developing white matter. Since the embryonic spinal cord has the capacity to release relatively high levels of retinoids, we propose that RA inhibits oligodendrocyte differentiation during early embryonic development permitting their dispersal throughout the entire spinal cord.
<title>Quantitative stepper metrology using the focus monitor test mask</title> (1994)

A new lithographic test pattern, the focus monitor, is introduced. Through the use of phase shift techniques, focus errors translate into easily measurable overlay shifts in the printed pattern. Each individual focus monitor pattern can be directly read for the sign and magnitude of the focus error. This paper presents a detailed verification of the validity of this approach, along with several preliminary applications.
Mixing fixed and reconfigurable logic for array processing (1996)

This paper describes the architecture of the MIX system that was designed to investigate the trade-off between the use of reconfigurable and fixed logic. The calculation of the dot-product of two vectors of 32 bit floating point numbers, that forms the basis of array processing in many engineering applications, is used as the basic algorithm for the investigation. The results indicate that fixed logic is more suited for floating point units and memories while reconfigurable logic is useful for implementing control logic providing significant flexibility. It was also found that the additional delay in reconfigurable logic can effectively overlap with the operating time of the fixed logic subsystems. The advantage of reconfigurability of the control is therefore combined with the high bandwidth properties of the fixed logic.
Steric effects of methoxy-groups in 2,2′-bridged biphenyls. Part II (1972)

Three o,o′-dimethoxy-bridged biphenyls, 5,7-dihydro-1,11-dimethoxydibenz[c,e]oxepin, 6,7-dihydro-1,11-dimethoxy-6,6-dimethyl-5H-dibenz[c,e]azepinium bromide (and iodide), and diethyl 6,7-dihydro-1,11-dimethoxy-5H-dibenzo[a,c]cycloheptene-6,6-dicarboxylate, have been prepared, each in both enantiomeric forms, starting from (+)- and (–)-6,6′-dimethoxydiphenic acid. Their optical stabilities have been determined and the anomalously large steric effect of the o-methoxy-groups is discussed. Their o.r.d. spectra have been measured and assignment of absolute configuration has been made; the great variation of the specific rotation of the dibenzocycloheptene with solvent (on the sodium D line) is seen as the effect of solvent on a Cotton effect situated below 220 nm.
Activation‐dependent expression of the insulin‐like growth factor binding protein‐2 in human lymphocytes (1998)

The expression of the insulin-like growth factor binding protein-2 (IGFBP-2) was assayed in mononuclear cells originating from different organs of the immune system. All mononuclear cells studied did express IGFBP-2, but the expression level was found to be dependent on the cell type and origin of the cell. T cells showed a higher expression of IGFBP-2 mRNA than did B cells, and CD34+ stem cells expressed IGFBP-2 mRNA at a high level. Expression was highest in bone marrow and thymus. Stimulation of peripheral mononuclear cells resulted in a marked increase of IGFBP-2 mRNA and also intracellular IGFBP-2, as analysed by fluorescence staining. This increase parallels the increase of other known T-cell activation markers. Furthermore, the increase of intracellular IGFBP-2 seems to precede T-cell blast formation and all T cells in active phases of the cell cycle have high levels of IGFBP-2. Our results provide a basis for further investigations on the contribution of the IGF-system to the regulation of T-cell proliferation and differentiation. IGFBP-2, in particular, may have an important influence in the regulation of T-cell activation and proliferation.
Multiple PCR analyses on trace amounts of DNA extracted from fresh and paraffin wax embedded tissues after random hexamer primer PCR amplification. (1994)

This method is simple and reliable, and permits multiple genetic analyses when only a limited amount of tissue is available.