gebhart/patrepeval huggingface dataset:
Spatial regulation of a zebrafish patched homologue reflects the roles of sonic hedgehog and protein kinase A in neural tube and somite patterning (1996)

Signalling by members of the Hedgehog family of secreted proteins plays a central role in the development of vertebrate and invertebrate embryos. In Drosophila, transduction of the Hedgehog signal is intimately associated with the activity of protein kinase A and the product of the segment polarity gene patched. We have cloned a homologue of patched from the zebrafish Danio rerio and analysed the spatiotemporal regulation of its transcription during embryonic development in both wild-type and mutant animals. We find a striking correlation between the accumulation of patched1 transcripts and cells responding to sonic hedgehog activity both in the neurectoderm and mesoderm, suggesting that like its Drosophila counterpart, patched1 is regulated by sonic hedgehog activity. Consistent with this interpretation, mis-expression of sonic hedgehog results in ectopic activation of patched1 transcription. Using dominant negative and constitutively active forms of the protein kinase A subunits, we also show that expression of patched1 as well as of other sonic hedgehog targets, is regulated by protein kinase A activity. Taken together, our findings suggest that the mechanism of signalling by Hedgehog family proteins has been highly conserved during evolution.
Senescent cells communicate via intercellular protein transfer (2015)

Mammalian cells mostly rely on extracellular molecules to transfer signals to other cells. However, in stress conditions, more robust mechanisms might be necessary to facilitate cell-cell communications. Cellular senescence, a stress response associated with permanent exit from the cell cycle and the development of an immunogenic phenotype, limits both tumorigenesis and tissue damage. Paradoxically, the long-term presence of senescent cells can promote tissue damage and aging within their microenvironment. Soluble factors secreted from senescent cells mediate some of these cell-nonautonomous effects. However, it is unknown whether senescent cells impact neighboring cells by other mechanisms. Here we show that senescent cells directly transfer proteins to neighboring cells and that this process facilitates immune surveillance of senescent cells by natural killer (NK) cells. We found that transfer of proteins to NK and T cells is increased in the murine preneoplastic pancreas, a site where senescent cells are present in vivo. Proteomic analysis and functional studies of the transferred proteins revealed that the transfer is strictly dependent on cell-cell contact and CDC42-regulated actin polymerization and is mediated at least partially by cytoplasmic bridges. These findings reveal a novel mode of intercellular communication by which senescent cells regulate their immune surveillance and might impact tumorigenesis and tissue aging.
Quantification of non-calcified coronary atherosclerotic plaques with dual-source computed tomography: comparison with intravascular ultrasound (2009)

Intra and interobserver variability for plaque volume measurements by DSCT were 6+/-5% and 11+/-7%, respectively. Mean total plaque volume by DSCT was 89+/-66 mm(3) (range 14-400 mm(3)). Mean total plaque volume by IVUS was 90+/-73 mm(3) (range 16-409 mm(3)). The mean difference between DSCT and IVUS was 1+/-34 mm(3) (range -131-85 mm(3)). Despite the good correlation for plaque volume measurements (r=0.89, p<0.001), agreement between the two methods was only modest (Bland-Altman limits of agreement -67 to +65 mm(3)). CONCLUSIONS ; Non-calcified plaque volumes as determined by DSCT yielded good correlation but only modest agreement in comparison with IVUS.
Parametric loudspeaker—characteristics of acoustic field and suitable modulation of carrier ultrasound (1991)

Abstract Due to the inherent nonlinearity of the medium, finite amplitude ultrasound interacts with itself and generates some secondary waves in the sound beam. The parametric loudspeaker, making use of this phenomenon, has a sharp directivity and might be applied to a speech transmission system under the limited environment. In this paper, a numerical analysis method available for high sound pressure levels, where the nonlinear interactions of ultrasound become greatly active, can be used successfully to theoretically design the parametric loudspeaker. It is reported that the numerical computations agree well with the experiments by a circular aperture projector of radius 21 cm and carrier frequency 27 kHz. To develop the parametric loudspeaker for practical uses, the problems on harmonic distortions and the physiological effect on human being must be solved. Based on the theoretical prediction, the reasonable solutions for such problems are considered in accordance with appropriate primary wave modulations.
Fluoroimmunoassay for Antigen Based on Fluorescence Quenching Signal of Gold Nanoparticles (2006)

A unique, sensitive, and highly specific fluoroimmunoassay system for antigen detection using gold and magnetic nanoparticles has been developed. The assay is based on the fluorescence quenching of fluorescein isothiocyanate caused by gold nanoparticles coated with monoclonal antibody. To demonstrate its analytical capabilities, the magnetic nanoparticles were coated with anti-alpha-fetoprotein polyclonal antibodies, which specifically bound with alpha-fetoprotein. Gold nanoparticles coated with anti-alpha-fetoprotein monoclonal antibodies could sandwich the alpha-fetoprotein captured by the magnetic nanoparticle probes. The sandwich-type immunocomplex was formed on the surface of magnetic nanoparticles and could be separated by a magnetic field. The supernatant liquid, which contained the unbound gold nanoparticle probes, was used to quench the fluorescence, and the fluorescence intensity of fluorescein isothiocyanate at 516 nm was proportional to the alpha-fetoprotein concentration. The result showed that the limit of detection of alpha-fetoprotein was 0.17 nM. This new system can be extended to detect target molecules with matched antibodies and has broad potential applications in immunoassay and disease diagnosis.
Divalent cation-dependent and independent surface expression of thrombospondin on thrombin-stimulated human platelets (1987)

Thrombospondin (TSP), a platelet alpha-granule protein, becomes expressed on the surface of thrombin-stimulated platelets. The surface expression of this protein occurs through two distinct mechanisms. At low platelet concentrations (1 X 10(8)/mL), a divalent ion-dependent, low-capacity mechanism predominates. At higher cell concentrations, a divalent ion-dependent, higher capacity mechanism prevails that can account for greater than 90% of all the TSP surface expression measured. This mechanism requires the presence of both calcium and magnesium (Ca + Mg). The dependence of the divalent ion-dependent surface expression on platelet concentration suggests that release of the molecule from the cell followed by its binding to the cell surface mediates this component of the endogenous TSP-platelet interaction. These data are consistent with a two-receptor model for the platelet- surface expression of the endogenous TSP pool.
Pre-clinical characterization of GMP grade CCL21-gene modified dendritic cells for application in a phase I trial in Non-Small Cell Lung Cancer (2008)

Viable and biologically active clinical grade CCL21 gene-modified DC can be generated from cryopreserved PBMC.
Additive manufacturing of magnetic shielding and ultra-high vacuum flange for cold atom sensors (2018)

Recent advances in the understanding and control of quantum technologies, such as those based on cold atoms, have resulted in devices with extraordinary metrological performance. To realise this potential outside of a lab environment the size, weight and power consumption need to be reduced. Here we demonstrate the use of laser powder bed fusion, an additive manufacturing technique, as a production technique relevant to the manufacture of quantum sensors. As a demonstration we have constructed two key components using additive manufacturing, namely magnetic shielding and vacuum chambers. The initial prototypes for magnetic shields show shielding factors within a factor of 3 of conventional approaches. The vacuum demonstrator device shows that 3D-printed titanium structures are suitable for use as vacuum chambers, with the test system reaching base pressures of 5 ± 0.5 × 10<sup>-10</sup> mbar. These demonstrations show considerable promise for the use of additive manufacturing for cold atom based quantum technologies, in future enabling improved integrated structures, allowing for the reduction in size, weight and assembly complexity.
HBXIP and LSD1 Scaffolded by lncRNA Hotair Mediate Transcriptional Activation by c-Myc (2016)

c-Myc is regarded as a transcription factor, but the basis for its function remains unclear. Here, we define a long noncoding RNA (lncRNA)/protein complex that mediates the transcriptional activation by c-Myc in breast cancer cells. Among 388 c-Myc target genes in human MCF-7 breast cancer cells, we found that their promoters could be occupied by the oncoprotein HBXIP. We confirmed that the HBXIP expression correlated with expression of the c-Myc target genes cyclin A, eIF4E, and LDHA. RNAi-mediated silencing of HBXIP abolished c-Myc-mediated upregulation of these target genes. Mechanistically, HBXIP interacted directly with c-Myc through the leucine zippers and recruited the lncRNA Hotair along with the histone demethylase LSD1, for which Hotair serves as a scaffold. Silencing of HBXIP, Hotair, or LSD1 was sufficient to block c-Myc-enhanced cancer cell growth in vitro and in vivo. Taken together, our results support a model in which the HBXIP/Hotair/LSD1 complex serves as a critical effector of c-Myc in activating transcription of its target genes, illuminating long-standing questions on how c-Myc drives carcinogenesis.
Basal-like breast cancer displays distinct patterns of promoter methylation (2010)

Recent microarray profiling studies on breast cancer have identified distinct subtypes that are associated with different clinical outcomes. Promoter hypermethylation of several known or putative tumor suppressor genes occurs frequently during the pathogenesis of breast cancer. We proposed that immunohistopathologic subtypes of breast cancer are likely to contain distinct promoter methylation patterns. A panel of 10 gene promoters was assessed by quantitative multiplex methylation-specific PCR in 114 invasive ductal carcinomas from Korea representing the three major subtypes [57 luminal, 24 human epidermal growth factor 2 (HER2), and 33 basal-like] based on immunohistochemical findings of estrogen receptor, progesterone receptor, HER2, cytokeratin 5/6 and epidermal growth factor receptor. The median methylation levels of HIN1, RASSF1A and TWIST, and the average methylation ratio were significantly lower in basal-like subtype compared to luminal or HER2 subtypes. In contrast, BRCA1 methylation level was significantly higher in basal-like subtype than in luminal subtype. The methylation status of a panel of four genes (APC1, CDH, BRCA1 and RAR-β) in luminal and HER2 subtypes were dissimilar, where HER2 tumors showed a significantly higher level of methylation compared to luminal tumors. These results suggest that gene methylation in breast cancer can potentially serve as epigenetic biomarkers and may contribute further to current breast cancer classification.
Protein lipidation (2007)

Proteins are covalently modified with a variety of lipids, including fatty acids, isoprenoids, and cholesterol. Lipid modifications play important roles in the localization and function of proteins. The focus of this review is S-palmitoylation, the reversible addition of palmitate and other long-chain fatty acids to proteins at cysteine residues in a variety of sequence contexts. The functional consequences of palmitoylation are diverse. Palmitoylation facilitates the association of proteins with membranes, mediates protein trafficking, and more recently has been appreciated as a regulator of protein stability. Members of a family of integral membrane proteins that harbor a DHHC cysteine-rich domain mediate most cellular palmitoylation events. Here we focus on DHHC proteins that modify Ras proteins in yeast and mammalian cells.
The nucleotide sequence, expression, and evolution of one member of a multigene family encoding the small subunit of ribulose-1,5-bisphosphate carboxylase in soybean. (1982)

We have examined the nuclear genes encoding the small subunit of ribulose-1,5-bisphosphate (RuBP) carboxylase from soybean. One member of this gene family, designated SRS1, has been isolated from a soybean DNA library constructed in the lambda vector Charon 4A. The complete nucleotide sequence and structure of this gene including its two introns and portions of the 5' and 3' flanking sequences were determined. The first exon encodes the entire transit peptide (55 amino acids) and the first 2 amino acids of the mature sequence. Based on analysis of the nucleotide sequence, we concluded that the precursor of the soybean small subunit consists of 178 amino acids. A gene-specific probe for SRS1 was used to show that this gene is transcribed and that steady-state levels of its transcript are strongly light regulated. S1 nuclease mapping was used to locate the potential start of transcription in the sequence and showed that the small subunit gene contains a cap site, TATA box, and -80 sequence, which match the consensus animal sequences. The mature SRS1 small subunit polypeptide of 123 amino acids contains 30 and 34 amino acid replacements relative to the previously determined amino acid sequences from pea and spinach, respectively. Southern blotting of restriction digests of soybean nuclear DNA and data on the complete structure of SRS1 suggest that a multigene family of at least 10 members encodes the RuBP carboxylase small subunit in soybean. Quantitative evolutionary comparison of the soybean small subunit sequence for SRS1 and the pea small subunit sequence suggests that these two genes diverged long before the divergence of pea and soybean.
Naturally Occurring Humoral Cytotoxicity Against Neuroblastoma (NB) Cells in Healthy Persons and Nb Patients (1996)

A novel cytotoxic mechanism against neuroblastoma (NB) cells based on natural immunoglobulin M serum antibodies is described. The occurrence of these antibodies, which are able to induce complement-mediated cytolysis of NB cells, has been investigated in several age groups of healthy persons and in patients with NB. The cytotoxicity of serum samples has been measured in terms of propidium iodide DNA incorporation using a FACScan. The prevalence of anti-NB 1gM antibodies shows a strong age dependence characterized by a nearly complete lack in the first year of life and a steep rise up to 82% beginning with the second year of life. In the sera of 11 NB-bearing patients no cytotoxicity has been found, despite the fact that 8 of these patients were older than 1 year. These findings lead to the hypothesis that natural 1gM antibodies could play a role as an immunological control mechanism against NB.
Temperature Modulation of Electric Fields in Biological Matter (2011)

Pulsed electric fields (PEF) have become an important minimally invasive surgical technology for various applications including genetic engineering, electrochemotherapy and tissue ablation. This study explores the hypothesis that temperature dependent electrical parameters of tissue can be used to modulate the outcome of PEF protocols, providing a new means for controlling and optimizing this minimally invasive surgical procedure. This study investigates two different applications of cooling temperatures applied during PEF. The first case utilizes an electrode which simultaneously delivers pulsed electric fields and cooling temperatures. The subsequent results demonstrate that changes in electrical properties due to temperature produced by this configuration can substantially magnify and confine the electric fields in the cooled regions while almost eliminating electric fields in surrounding regions. This method can be used to increase precision in the PEF procedure, and eliminate muscle contractions and damage to adjacent tissues. The second configuration considered introduces a third probe that is not electrically active and only applies cooling boundary conditions. This second study demonstrates that in this probe configuration the temperature induced changes in electrical properties of tissue substantially reduce the electric fields in the cooled regions. This novel treatment can potentially be used to protect sensitive tissues from the effect of the PEF. Perhaps the most important conclusion of this investigation is that temperature is a powerful and accessible mechanism to modulate and control electric fields in biological tissues and can therefore be used to optimize and control PEF treatments.
Recombinant soluble human interleukin‐6 receptor (1993)

The recombinant soluble human interleukin-6 receptor (srhIL-6R) was expressed in Escherichia coli as a non-glycosylated protein comprising the first 339 amino acids after the signal peptide. The protein accumulated within the cells as insoluble protein aggregates (inclusion bodies). After solubilization, 10% of the denatured srhIL-6R could be renaturated by an in vitro folding procedure using L-arginine and the glutathione-redox system. The native receptors were purified to near homogeneity by affinity chromatography on an IL-6-Sepharose column. The functional features of the recombinant soluble receptor were further analysed. A part of the extracellular domain (amino acids 145-345) of the human interleukin-6 receptor (IL-6R) was expressed in E. coli and the purified protein was used to raise antibodies in rabbits. Characterization of the antiserum obtained indicated that an epitope of 13 amino acids close to the transmembrane region is needed for recognition by the antibodies. Since the antiserum obtained did not interfere with IL-6 binding, it could be used to establish a cell-free IL-6-binding assay, In this assay, the srhIL-6R bound IL-6 with an affinity of Kd = 1.5 nM as measured by Scatchard-plot analysis. When 125I-IL-6 was chemically cross-linked to the purified srhIL-6R and analyzed by SDS/PAGE, several 125I-IL-6-containing bands were detected, indicating the possible existence of a multimeric structure of the natural IL-6/IL-6R complex. The srhIL-6R was shown to exhibit biological activity, i.e. it stimulated acute-phase protein synthesis in the recently established human hepatoma cell line HepG2-IL-6 which does not express the IL-6-binding subunit of the IL-6R complex on the cell surface.
Biosynthetic and functional properties of an Arg-Gly-Asp-directed receptor involved in human melanoma cell attachment to vitronectin, fibrinogen, and von Willebrand factor. (1987)

M21 human melanoma cells express an Arg-Gly-Asp-directed adhesion receptor composed of noncovalently associated alpha and beta chains. To establish the structural and functional properties of this receptor on M21 human melanoma cells, stable variant cell lines were selected that express altered alpha chain levels. One of these variants, M21-L, fails to synthesize alpha chain protein or its mRNA, yet does produce normal levels of the beta chain. In these cells the beta chain does not reach the cell surface but rather accumulates within the cell. M21-L cells lacking the alpha chain are incapable of attaching to vitronectin, von Willebrand factor, fibrinogen, or an Arg-Gly-Asp-containing heptapeptide yet attach normally to fibronectin, whereas the unselected M21 cells attach to all of these adhesive proteins. In addition, a monoclonal antibody, LM609 generated to a functional site on the intact receptor, is capable of preventing M21 cell attachment to vitronectin, von Willebrand factor, fibrinogen, and the Arg-Gly-Asp peptide but not to fibronectin. Following a 2-min biosynthetic pulse-label, the newly synthesized alpha chain remains in free form for 5 min and then associates with previously synthesized beta chain present in an intracellular pool. Once oligomerization takes place, the receptor gains the capacity to recognize Arg-Gly-Asp, and at this time the epitope recognized by monoclonal antibody LM609 is formed.
Neurovascular Protection Reduces Early Brain Injury After Subarachnoid Hemorrhage (2004)

The major effect of z-VAD-FMK on early brain injury after SAH was probably neurovascular protection of cerebral endothelial cells, which results in less damage on BBB.
Constitutive and inducible interleukin 8 expression by hypoxia and acidosis renders human pancreatic cancer cells more tumorigenic and metastatic. (1999)

The role and regulation of interleukin 8 (IL-8) in the growth and metastasis of SG, FG, and L3.3 variants derived from COLO 357 human pancreatic cancer cells were determined. After orthotopic implantation in the pancreas of nude mice, SG cells produced the smallest tumors, whereas L3.3 cells produced the largest tumors. SG cells produced no liver metastasis, whereas FG cells produced numerous liver metastases, and L3.3 cells produced more and larger liver metastases. In vitro analysis of IL-8 expression indicated that SG cells expressed the lowest level of IL-8 gene expression as determined by both Northern blot analysis and ELISA, whereas L3.3 cells expressed the highest level of IL-8. Immunohistochemical analysis of tumor lesions indicated that IL-8 overexpression was predominant in the regions surrounding necrotic areas, where cells were exposed to low oxygen tension (hypoxia) and acidic pH. In vitro treatment of FG tumor cells with hypoxia or acidosis led to an increased expression of IL-8. To directly determine the role of IL-8 in the growth and metastasis of pancreatic cancer, FG cells were transfected with IL-8 sense or antisense oligonucleotide expression vectors. The neo-resistance gene-transfected FG cells were used as controls. Decreased IL-8 expression after transfection with IL-8 antisense oligonucleotide expression vector retarded the growth of FG cells in mice after intrapancreatic implantation, which correlated with decreased tumor angiogenesis. Our data demonstrated that hypoxia and acidosis contribute to the overexpression of IL-8, which in turn plays an important role in tumor angiogenesis and contributes significantly to the aggressive biology of human pancreatic cancer.
Targeting of adenovirus E1A and E4-ORF3 proteins to nuclear matrix-associated PML bodies. (1995)

The PML protein was first identified as part of a fusion product with the retinoic acid receptor alpha (RAR alpha), resulting from the t(15;17) chromosomal translocation associated with acute promyelocytic leukemia (APL). It has been previously demonstrated that PML, which is tightly bound to the nuclear matrix, concentrates in discrete subnuclear compartments that are disorganized in APL cells due to the expression of the PML-RAR alpha hybrid. Here we report that adenovirus infection causes a drastic redistribution of PML from spherical nuclear bodies into fibrous structures. The product encoded by adenovirus E4-ORF3 is shown to be responsible for this reorganization and to colocalize with PML into these fibers. In addition, we demonstrate that E1A oncoproteins concentrate in the PML domains, both in infected and transiently transfected cells, and that this association requires the conserved amino acid motif (D)LXCXE, common to all viral oncoproteins that bind pRB or the related p107 and p130 proteins. The SV-40 large T antigen, another member of this oncoprotein family is also found in close association with the PML nuclear bodies. Taken together, the present data indicate that the subnuclear domains containing PML represent a preferential target for DNA tumor viruses, and therefore suggest a more general involvement of the PML nuclear bodies in oncogenic processes.