gebhart/patrepeval huggingface dataset:
Frequent deletion of chromosome 12p12.3 in children with acute lymphoblastic leukaemia (1997)

Cytogenetic deletions of the short arm of chromosome 12 are common recurring alterations found in a wide range of haematological neoplasias, including childhood acute lymphoblastic leukaemia (ALL), the most frequent paediatric malignancy. Such a loss of genetic material suggests the presence of a tumour suppressor gene which plays an important role in growth regulation or in the differentiation of haemopoietic stem cells. To substantiate this hypothesis and to determine more precisely the chromosomal location of this putative gene, we applied a deletion mapping strategy based on the detection of loss of heterozygosity (LOH) at specific genomic loci in tumour cells. 13 polymorphic markers were used to screen DNA samples from 20 children with ALL. LOHs at 12p12.3 were observed in almost 50% of informative B-cell precursor ALL patients analysed. This is one of the most frequent genetic alterations found in this disease. A common region of LOH was delimited by the markers D12S89 (distal) and D12S358 (proximal), separated by a genetic interval of approximately 3 cM. We refined the position of the putative 12p tumour suppressor gene to a physical interval of <1.3 Mb, a crucial step towards the identification of candidate genes. A yeast artificial chromosome clone contig that spans the entire critically deleted region includes two known genes: TEL, a member of the ets family of transcription factors, and p27KIP1, a cyclin-dependent kinase inhibitor.
Intranasal M Cell Uptake of Nanoparticles Is Independently Influenced by Targeting Ligands and Buffer Ionic Strength (2010)

In mucosal tissues, epithelial M cells capture and transport microbes across the barrier to underlying immune cells. Previous studies suggested that high affinity ligands targeting M cells may be used to deliver mucosal vaccines; here, we show that particle composition and dispersion buffer ionic strength can independently influence their uptake in vivo. First, addition of a poloxamer 188 to nanoparticle formulations increased uptake of intranasally administered nanoparticles in vivo, but the effect was dependent on the presence of the M cell-targeting ligand. Second, solvent ionic strength is known to effect electrostatic interactions; accordingly, reduced ionic strength increased the electrostatic potential between the epithelium and the particles. Interestingly, below a critical ionic strength, intranasal particle uptake in vivo significantly was increased even when controlled for osmolarity. Similar results were obtained for uptake of bacterial particles. Surprisingly, at low ionic strength, the specific enhancement effect by the targeting peptide was negligible. Modeling of the electrostatic forces predicted that the enhancing effects of the M cell-targeting ligand only are enabled at high ionic strength, as particle electrostatic forces are reduced through Debye screening. Thus, electrostatic forces can have a dramatic effect on the in vivo M cell particle uptake independent of the action of targeting ligands. Examination of these forces will be helpful to optimizing mucosal vaccine and drug delivery.
Inverse Relationship Between Electrode Size and Lesion Size During Radiofrequency Ablation With Active Electrode Cooling (1998)

The smaller electrode resulted in transmission of a greater fraction of the radiofrequency power to the tissue and resulted in higher tissue temperature, larger lesions, and lower dependency of lesion size on the electrode orientation.
Immunogenicity of recombinant IL-2 modified by covalent attachment of polyethylene glycol. (1990)

Human rIL-2, expressed and purified from Escherichia coli, is currently being tested as an anticancer therapeutic agent. Some of the patients undergoing clinical trials with rIL-2 have developed antibodies to rIL-2. We describe a chemical modification of rIL-2 that reduces its immunogenicity. rIL-2 has been chemically modified with a water soluble polymer, monomethoxy polyethylene glycol (PEG). This covalent conjugate PEG-rIL-2 has enhanced solubility and extended in vivo circulation. Attachment of PEG to rIL-2 reduces its immunogenicity when tested in rabbits and in mice. Ag-specific IgG antibody titers were 100 to 1000-fold lower when PEG-rIL-2 was used as the Ag, compared to rIL-2. In a long term study, 7 of 10 rabbits injected with PEG-rIL-2 had no Ag-specific IgG antibody response. In these seven rabbits, the in vivo behavior of the injected PEG-rIL-2 remained essentially unchanged after repeated immunizations. PEG-rIL-2 injected before rIL-2 injections, immunosuppressed the antibody response to rIL-2 in rabbits. The maintenance of the systemic exposure of PEG-rIL-2 after repetitive dosing is related to its decreased immunogenicity. Thus, the PEGylation (covalent attachment of PEG) of rIL-2-enhances its potential as an anticancer therapeutic.
OOONEIDA: An Open, Object-Oriented Knowledge Economy for Intelligent Industrial Automation (2005)

Open knowledge economy in intelligent industrial automation (OOONEIDA) is a new initiative for enabling decentralized, reconfigurable industrial control and automation in discrete manufacturing and continuous process systems. The goal of the OOONEIDA project is the creation of the technological infrastructure for a new, open knowledge economy for automation components and automated industrial products. This will be done by further development of the concept of reusable portable software modules (function blocks) and by their application in the time- and cost-effective specification, design, validation, realization, and deployment of intelligent mechatronic components in distributed industrial automation and control systems.
Detection and Characterization of Shiga Toxigenic Escherichia coli by Using Multiplex PCR Assays for stx 1 , stx 2 , eaeA , Enterohemorrhagic E. coli hlyA , rfb O111 , and rfb O157 (1998)

Shiga toxigenic Escherichia coli (STEC) comprises a diverse group of organisms capable of causing severe gastrointestinal disease in humans. Within the STEC family, certain strains appear to be of greater virulence for humans, for example, those belonging to serogroups O111 and O157 and those with particular combinations of other putative virulence traits. We have developed two multiplex PCR assays for the detection and genetic characterization of STEC in cultures of feces or foodstuffs. Assay 1 utilizes four PCR primer pairs and detects the presence of stx1, stx2 (including variants of stx2), eaeA, and enterohemorrhagic E. coli hlyA, generating amplification products of 180, 255, 384, and 534 bp, respectively. Assay 2 uses two primer pairs specific for portions of the rfb (O-antigen-encoding) regions of E. coli serotypes O157 and O111, generating PCR products of 259 and 406 bp, respectively. The two assays were validated by testing 52 previously characterized STEC strains and observing 100% agreement with previous results. Moreover, assay 2 did not give a false-positive O157 reaction with enteropathogenic E. coli strains belonging to clonally related serogroup O55. Assays 1 and 2 detected STEC of the appropriate genotype in primary fecal cultures from five patients with hemolytic-uremic syndrome and three with bloody diarrhea. Thirty-one other primary fecal cultures from patients without evidence of STEC infection were negative.
Monoclonal antibody 425 inhibits growth stimulation of carcinoma cells by exogenous EGF and tumor‐derived EGF/TGF‐α (1990)

Carcinoma cells frequently coexpress transforming growth factor (TGF)-alpha and its receptor, the epidermal growth factor (EGF) receptor, implicating an autocrine function of carcinoma-derived TGF-alpha. Using a monoclonal antibody (425) to the EGF-receptor, we investigated the role of exogenous and tumor cell-derived EGF/TGF-alpha mitogenic activities in proliferation of cell lines derived from solid tumors. Monoclonal antibody 425 was chosen for these studies because it inhibits binding of EGF/TGF-alpha to the EGF-receptor and effectively blocks activation of the EGF-receptor by EGF/TGF-alpha. Seven malignant cell lines originating from carcinomas of colon, pancreas, breast, squamous epithelia, and bladder expressed surface EGF-receptor and secreted EGF/TGF-alpha-like mitogenic activities into their tissue culture media. All cell lines were maintained in a defined medium free of exogenous EGF/TGF-alpha. EGF and TGF-alpha added to the culture medium stimulated proliferation of five cell lines to comparable levels. EGF/TGF-alpha-dependent proliferation was significantly reduced by addition of MAb 425 to culture media. In addition, monoclonal antibody 425 reduced proliferation of the five EGF/TGF-alpha responsive cell lines in the absence of exogenous EGF/TGF-alpha. Antiproliferative effects induced by monoclonal antibody 425 were reversible and could be overcome by addition of EGF to culture media. Our results indicate that tumor-derived EGF-receptor-reactive mitogens can promote proliferation of carcinoma cells in an autocrine fashion.
HIV-1 Protease Inhibitors Based on Acyclic Carbohydrates (1998)

A series of acyclic C2-symmetric HIV protease inhibitors readily accessible from d-mannitol have been developed. Several of the compounds synthesized showed significant in vitro activity against HIV-1 protease.
Nicotinic Acid Receptor Agonists Differentially Activate Downstream Effectors (2007)

Nicotinic acid remains the most effective therapeutic agent for the treatment and prevention of atherosclerosis resulting from low high density lipoprotein cholesterol. The therapeutic actions of nicotinic acid are mediated by GPR109A, a Gi protein-coupled receptor, expressed primarily on adipocytes, Langerhans cells, and macrophage. Unfortunately, a severe, cutaneous flushing side effect limits its use and patient compliance. The mechanism of high density lipoprotein elevation is not clearly established but assumed to be influenced by an inhibition of lipolysis in the adipose. The flushing side effect appears to be mediated by the release of prostaglandin D2 from Langerhans cells in the skin. We hypothesized that the signal transduction pathways mediating the anti-lipolytic and prostaglandin D2/flushing pathways are distinct and that agonists may be identified that are capable of selectively eliciting the therapeutic, anti-lipolytic pathway while avoiding the activation of the parallel flush-inducing pathway. We have identified a number of GPR109A pyrazole agonists that are capable of fully inhibiting lipolysis in vitro and in vivo and not only fail to elicit a flushing response but can antagonize the ability of nicotinic acid to elicit a flush response in vivo. In contrast to flushing agonists, exposure of cells expressing GPR109A to the non-flushing agonists fails to induce internalization of the receptor or to activate ERK 1/2 mitogen-activated protein kinase phosphorylation.
Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors (2012)

Small-molecule inhibitors of PARP are thought to mediate their antitumor effects as catalytic inhibitors that block repair of DNA single-strand breaks (SSB). However, the mechanism of action of PARP inhibitors with regard to their effects in cancer cells is not fully understood. In this study, we show that PARP inhibitors trap the PARP1 and PARP2 enzymes at damaged DNA. Trapped PARP-DNA complexes were more cytotoxic than unrepaired SSBs caused by PARP inactivation, arguing that PARP inhibitors act in part as poisons that trap PARP enzyme on DNA. Moreover, the potency in trapping PARP differed markedly among inhibitors with niraparib (MK-4827) > olaparib (AZD-2281) >> veliparib (ABT-888), a pattern not correlated with the catalytic inhibitory properties for each drug. We also analyzed repair pathways for PARP-DNA complexes using 30 genetically altered avian DT40 cell lines with preestablished deletions in specific DNA repair genes. This analysis revealed that, in addition to homologous recombination, postreplication repair, the Fanconi anemia pathway, polymerase β, and FEN1 are critical for repairing trapped PARP-DNA complexes. In summary, our study provides a new mechanistic foundation for the rational application of PARP inhibitors in cancer therapy.
Differentiation of Human Induced Pluripotent Stem Cells to Mammary-like Organoids (2017)

Human induced pluripotent stem cells (iPSCs) can give rise to multiple cell types and hold great promise in regenerative medicine and disease-modeling applications. We have developed a reliable two-step protocol to generate human mammary-like organoids from iPSCs. Non-neural ectoderm-cell-containing spheres, referred to as mEBs, were first differentiated and enriched from iPSCs using MammoCult medium. Gene expression profile analysis suggested that mammary gland function-associated signaling pathways were hallmarks of 10-day differentiated mEBs. We then generated mammary-like organoids from 10-day mEBs using 3D floating mixed gel culture and a three-stage differentiation procedure. These organoids expressed common breast tissue, luminal, and basal markers, including estrogen receptor, and could be induced to produce milk protein. These results demonstrate that human iPSCs can be directed in vitro toward mammary lineage differentiation. Our findings provide an iPSC-based model for studying regulation of normal mammary cell fate and function as well as breast disease development.
Caveolin-1 is a negative regulator of tumor growth in glioblastoma and modulates chemosensitivity to temozolomide (2013)

Caveolin-1 (Cav-1) is a critical regulator of tumor progression in a variety of cancers where it has been shown to act as either a tumor suppressor or tumor promoter. In glioblastoma multiforme, it has been previously demonstrated to function as a putative tumor suppressor. Our studies here, using the human glioblastoma-derived cell line U-87MG, further support the role of Cav-1 as a negative regulator of tumor growth. Using a lentiviral transduction approach, we were able to stably overexpress Cav-1 in U-87MG cells. Gene expression microarray analyses demonstrated significant enrichment in gene signatures corresponding to downregulation of MAPK, PI3K/AKT and mTOR signaling, as well as activation of apoptotic pathways in Cav-1-overexpressing U-87MG cells. These same gene signatures were later confirmed at the protein level in vitro. To explore the ability of Cav-1 to regulate tumor growth in vivo, we further show that Cav-1-overexpressing U-87MG cells display reduced tumorigenicity in an ectopic xenograft mouse model, with marked hypoactivation of MAPK and PI3K/mTOR pathways. Finally, we demonstrate that Cav-1 overexpression confers sensitivity to the most commonly used chemotherapy for glioblastoma, temozolomide. In conclusion, Cav-1 negatively regulates key cell growth and survival pathways and may be an effective biomarker for predicting response to chemotherapy in glioblastoma.
Multiple imaging techniques demonstrate the manipulation of surfaces to reduce bacterial contamination and corrosion (2004)

Surface imaging techniques were combined to determine appropriate manipulation of technologically important surfaces for commercial applications. The complementarity of the microscopy methods, scanning electron microscopy, electron probe microanalysis and atomic force microscopy assessed and correlated form and function of the surface modifications. Stainless steel disks (1 cm in diameter) were laser-cut from the same sheets of stainless steel and treated by electropolishing or left untreated for controls. Each treatment was analysed separately using each technique. First, the disks were examined by visual inspection and electron probe microanalysis for surface characteristics and elemental composition, respectively. Aliquots of bacterial suspensions (saline rinses of poultry carcasses from a commercial broiler processing plant) were then diluted in broth and monitored for growth by spectrophotometry. Stainless steel disks (1 cm in diameter) were added and the cultures were grown to sufficient density to allow attachment of bacterial cells to test surfaces. Relative differences in the surface morphology shown by atomic force microscopy, including Z ranges, roughness and other measurements, corresponded by treatment with the differences in reduction of bacterial counts shown by scanning electron microscopy. A model of wet-processing conditions tested the effects of corrosive treatment of surfaces. Less bacterial attachment occurred after corrosive treatment on controls and electropolished samples. Electropolishing significantly reduced bacterial numbers and the effects of corrosive action compared to the controls. Thus, the multiple imaging techniques showed that engineered changes on stainless steel surfaces improved the resistance of the surface finish to bacterial attachment, biofilm formation, and corrosive action.
Reversible Cellular Senescence: Implications for Immortalization of Normal Human Diploid Fibroblasts (1989)

IMR-90 normal human diploid fibroblasts, transfected with a steroid inducible mouse mammary tumor virus-driven simian virus 40 T antigen, were carried through crisis to yield an immortal cell line. Growth was dependent on the presence of the inducer (dexamethasone) during both the extended precrisis life span of the cells and after immortalization. After dexamethasone removal, immortal cells divided once or twice and then accumulated in G1. These results are best explained by a two-stage model for cellular senescence. Mortality stage 1 (M1) causes a loss of mitogen responsiveness and arrest near the G1/S interface and can be bypassed or overcome by the cellular DNA synthesis-stimulating activity of T antigen. Mortality stage 2 (M2) is an independent mechanism that is responsible for the failure of cell division during crisis. The inactivation of M2 is a rare event, probably of mutational origin in human cells, independent of or only indirectly related to the expression of T antigen. Under this hypothesis, T-antigen-immortalized cells contain an active but bypassed M1 mechanism and an inactivated M2 mechanism. These cells are dependent on the continued expression of T antigen for the maintenance of immortality for the same reason that precrisis cells are dependent on T antigen for growth: both contain an active M1 mechanism.
Amino acid sequence of human platelet factor 4. (1977)

Human platelet factor 4, a protein that binds heparin, has been purified to apparent homogeneity and the complete amino acid sequence of the protein has been determined. The 70-residue polypeptide chain contains no methionine, tryptophan, or phenylalanine, and contains only a single tyrosyl residue. The sequence analysis demonstrates a highly negatively charged amino-terminal region. The carboxyl-terminal region of the polypeptide is unusual in that it contains a repetitive clustering of positively charged and hydrophobic pairs of amino acids; preliminary evidence suggests that this domain may play a role in the binding of heparin.
Granulocyte colony-stimulating factor increases expression of adhesion receptors on endothelial cells through activation of p38 MAPK. (2004)

Our results demonstrate that G-CSF increases the expression of adhesion receptors on EC, promoting leukocyte adhesion. This effect seems to be triggered by the signaling events that follow receptor binding. Results from experiments using specific inhibitors suggest that activation of p38 MAPK is required to promote expression of adhesion receptors in endothelial cells and the recruitment of leukocytes in response to G-CSF.
STING-Dependent Type I IFN Production Inhibits Cell-Mediated Immunity to Listeria monocytogenes (2014)

Infection with Listeria monocytogenes strains that enter the host cell cytosol leads to a robust cytotoxic T cell response resulting in long-lived cell-mediated immunity (CMI). Upon entry into the cytosol, L. monocytogenes secretes cyclic diadenosine monophosphate (c-di-AMP) which activates the innate immune sensor STING leading to the expression of IFN-β and co-regulated genes. In this study, we examined the role of STING in the development of protective CMI to L. monocytogenes. Mice deficient for STING or its downstream effector IRF3 restricted a secondary lethal challenge with L. monocytogenes and exhibited enhanced immunity that was MyD88-independent. Conversely, enhancing STING activation during immunization by co-administration of c-di-AMP or by infection with a L. monocytogenes mutant that secretes elevated levels of c-di-AMP resulted in decreased protective immunity that was largely dependent on the type I interferon receptor. These data suggest that L. monocytogenes activation of STING downregulates CMI by induction of type I interferon.
Inhibition of dextran sulphate sodium (DSS)-induced colitis in mice by intracolonically administered antibodies against adhesion molecules (endothelial leucocyte adhesion molecule-1 (ELAM-1) or intercellular adhesion molecule-1 (ICAM-1)) (1999)

We examined the effect of intracolonic administration of anti-adhesion molecule antibodies on DSS-induced colitis in mice. Immunohistochemical staining in mice with colitis showed increased expression of ELAM-1 and ICAM-1 on endothelial cells of vessels in the lamina propria and submucosa at sites of inflamed lesions. Intracolonic administration of anti-ELAM-1 or anti-ICAM-1 antibody decreased bloody stools, anaemia, and histologically evident damage, as well as myeloperoxidase activity and IL-1beta content. We concluded that adhesion molecule expression is important in the development of DSS-induced colitis in mice and that intracolonic administration of anti-adhesion molecule antibodies, especially anti-ELAM-1 antibody, effectively inhibits the colonic inflammation. Intracolonic administration of anti-adhesion molecule antibodies may show therapeutic promise in ulcerative colitis.
Recurrence of OTT–MAL fusion in t(1;22) of infant AML‐M7 (2001)

Translocation t(1;22)(p13;q13) is associated with a peculiar subtype of acute megakaryocytic leukemia (M7) occurring in infants. We have recently characterized a fusion gene, OTT-MAL, resulting from this translocation. We now report three additional cases and show that this gene fusion is present in all five t(1;22) cases studied to date. Nucleotide sequence analysis of two translocation breakpoints suggests a nonhomologous end joining mechanism in the genesis of this translocation and reveals a noncanonical topoisomerase II-like consensus sequence within the OTT gene. FISH and PCR techniques described in this work are useful for identifying t(1;22) associated with M7.
Myotonic heart disease (1991)

We followed 37 patients with myotonic dystrophy for a mean of 6 years. Two developed atrial flutter or fibrillation, 6 developed a new bundle branch block, 1 developed complete heart block requiring a pacemaker, and another with progressive 1st-degree heart block and a widening QRS interval had a sudden death. Most patients had predictable, gradually progressive disease of their cardiac conduction system. We recommend that patients with progressive atrioventricular block or widening QRS interval due to myotonic heart disease have yearly ECGs and be questioned about syncope or presyncope to determine the need for a cardiac pacemaker.
Aspirin and the Risk of Colorectal Cancer in Women (1995)

Regular aspirin use, at doses similar to those recommended for the prevention of cardiovascular disease, substantially reduces the risk of colorectal cancer. However, this benefit may not be evident until after at least a decade of regular aspirin consumption.