gebhart/patrepeval huggingface dataset:
Differential gene expression profiles of scirrhous gastric cancer cells with high metastatic potential to peritoneum or lymph nodes. (2001)

Scirrhous gastric cancer is often accompanied by metastasis to the peritoneum and/or lymph nodes, resulting in the highest mortality rate among gastric cancers. Mechanisms involved in gastric cancer metastasis are not fully clarified because metastasis involves multiple steps and requires the accumulation of altered expression of many different genes. Thus, independent analysis of any single gene would be insufficient to understand all of the aspects of gastric cancer metastasis. In this study, we performed global analysis on differential gene expression of a scirrhous gastric cancer cell line (OCUM-2M) and its derivative sublines with high potential for metastasis to the peritoneal cavity (OCUM-2MD3) and lymph nodes (OCUM-2MLN) in a nude mice model. By applying a high-density oligonucleotide array method, expression of approximately 6800 genes was analyzed, and selected genes were confirmed by the Northern blot method. In our observations in OCUM-2MD3 cells, 12 genes were up-regulated, and 20 genes were down-regulated. In OCUM-2MLN cells, five genes were up-regulated, and five genes were down-regulated. The analysis revealed two functional gene clusters with altered expression: (a) down-regulation of a cluster of squamous cell differentiation marker genes such as small proline-rich proteins [SPRRs (SPRR1A, SPRR1B, and SPRR2A], annexin A1, epithelial membrane protein 1, cellular retinoic acid-binding protein 2, and mesothelin in OCUM-2MD3 cells; and (b) up-regulation of a cluster of antigen-presenting genes such as MHC class II (DP, DR, and DM) and invariant chain (II) in OCUM-2MLN cells through up-regulation of CIITA (MHC class II transactivator). We then analyzed six gastric cancer cell lines by Northern blot and observed preferential up-regulation of trefoil factor 1, alpha-1-antitrypsin, and galectin 4 and down-regulation of cytidine deaminase in cells prone to peritoneal dissemination. Genes highly correlated with invasion or peritoneal dissemination of gastric cancer, such as E-cadherin or integrin beta4, were down-regulated in both of the derivative cell lines analyzed in this study. This is the first demonstration of global gene expression analysis of gastric cancer cells with different metastatic potentials, and these results provide a new insight in the study of human gastric cancer metastasis.
Bacterial Delivery of siRNAs: A New Approach to Solid Tumor Therapy (2008)

RNAi is a powerful research tool for specific gene silencing and may also lead to promising novel therapeutic strategies. However, the development of RNAi-based therapies has been slow due to the lack of targeted delivery methods. The biggest challenge in the use of siRNA-based therapies is the delivery to target cells. There are many additional obstacles to in vivo delivery of siRNAs, such as degradation by endogenous enzymes and interaction with blood components leading to nonspecific uptake into cells, which govern biodistribution and availability of siRNA in the body. Naked unmodified synthetic siRNA including plasmid-carried-shRNA-expression constructs cannot penetrate cellular membranes, and therefore, systemic application is unlikely to be successful. The success of gene therapy by siRNAs relies on the development of safe, economical, and efficacious in vivo delivery systems into the target cells. Attenuated Salmonella have been employed recently as vectors to deliver silencing hairpin RNA (shRNA) expression plasmids into mammalian cells. This approach has achieved gene silencing in vitro and in vivo. The facultative anaerobic, invasive Salmonella have a natural tropism for solid tumors including metastatic tumors. Genetically modified, attenuated Salmonella have been used recently both as potential antitumor agents by themselves, and to deliver specific tumoricidal therapies. This chapter describes the use of attenuated bacteria as tumor-targeting delivery systems for cancer therapy.
Effects of Listeria monocytogenes Hemolysin on Phagocytic Cells and Lysosomes (1970)

The effects of Listeria monocytogenes hemolysin on lysosomes and phagocytic cells were investigated. Hemolysin caused release of beta-glucuronidase and acid phosphatase from suspensions of rabbit and rat lysosomes prepared from liver homogenates. The degree of lysis was proportional to the concentration of hemolysin added. There appeared to be no significant difference between the sensitivities of rat and rabbit lysosomes to disruption. Studies on the effect of pH and temperature on lytic activity suggested that hemolysin could function under conditions which might exist within phagocytic cells. Peritoneal exudates from rabbits and mice were exposed to hemolysin and observed by phase microscopy. Hemolysin possessed leucocidal activity and caused degranulation of both rabbit and mouse cells. Optimal activity against lysosomes and peritoneal exudate cells required activation of hemolysin with a reducing agent and could be prevented if hemolysin was previously incubated with cholesterol.
Properties of a DNA-dependent ATPase from rat mitochondria (1981)

A DNA-dependent ATPase has been highly purified from rat liver mitochondria and characterized. The enzyme catalyzes the hydrolysis of ATP or dATP in the presence of single-stranded DNA cofactor and a divalent cation. The Km values for ATP and dATP are 0.15 mM and 0.35 mM, respectively. The enzyme activity is highly sensitive to N-ethylmaleimide. The sedimentation coefficient of the enzyme is 8.3 S in a glycerol gradient. From this and data on Sephadex G-200 gel filtration, the molecular weight of the native enzyme was calculated to be about 190,000. All the natural single-stranded DNAs tested were equally effective for the ATPase activity, but synthetic deoxyhomopolymer poly(dC) was found to be more effective than natural single-stranded DNAs. Synthetic and natural RNAs had no effect on the activity.
The Novel Use of an Intravenous Proton Pump Inhibitor in a Patient With Short Bowel Syndrome (2002)

Recent evidence suggests that parenteral proton pump inhibitors (PPIs) can effectively control gastric acid hypersecretion. Intravenous PPI (omeprazole) can substantially reduce the risk of recurrent bleeding in patients with peptic ulcer disease. We describe a patient with short bowel syndrome who had recurrent life-threatening upper gastrointestinal bleeding from severe gastric and esophageal ulcerations. The patient had failed long-term, maximal-dose intravenous ranitidine therapy but was successfully treated and maintained on long-term therapy with an intravenous PPI (pantoprazole). To our knowledge, this is the first case report in the literature describing the use of an intravenous PPI to treat upper gastrointestinal bleeding in a patient with complete intestinal resection. Intravenous PPIs should be considered as the first line of treatment of erosive esophagitis and peptic ulcer disease in patients with short bowel syndrome and in patients who are nil per os and who fail intravenous H 2 -receptor antagonist treatment. Parenteral PPI may also be the drug of choice in intensive care patients who have erosive esophagitis. Furthermore, this is the first case report describing the novel use of intravenous pantoprazole to treat erosive esophagitis in a patient with short bowel syndrome, suggesting that intravenous PPI may also be useful for the treatment of ulcer prophylaxis in patients undergoing intestinal transplantation.
Informal Qualitative Models: A Systematic Approach to their Generation (1995)

This paper discusses the concept of an IQM (Informal Qualitative Model) which is seen as a bridge between rigorous, and often intractable, theories on the one hand, and experimental data on the other. We argue that the selection of variables to be explored using quantitative law discovery should be made using background knowledge. However, domain theories are often intractable, and to make progress it is therefore necessary to add assumptions; i.e. one is forced to take particular and often simplifying, perspectives on the domain. IQMs essentially capture these ideas. This paper demonstrates how a set of IQMs for a domain (colligative properties of solutions) can be generated from a base IQM and a set of operators. Introduction Early work in the physical sciences involved the investigation of quantitative relationships between variables (such as Newton&amp;apos;s and Kepler&amp;apos;s laws), and also qualitative relationships, such as objects of type A react chemically with objects of type...
Tumor Ablation with Irreversible Electroporation (2007)

We report the first successful use of irreversible electroporation for the minimally invasive treatment of aggressive cutaneous tumors implanted in mice. Irreversible electroporation is a newly developed non-thermal tissue ablation technique in which certain short duration electrical fields are used to permanently permeabilize the cell membrane, presumably through the formation of nanoscale defects in the cell membrane. Mathematical models of the electrical and thermal fields that develop during the application of the pulses were used to design an efficient treatment protocol with minimal heating of the tissue. Tumor regression was confirmed by histological studies which also revealed that it occurred as a direct result of irreversible cell membrane permeabilization. Parametric studies show that the successful outcome of the procedure is related to the applied electric field strength, the total pulse duration as well as the temporal mode of delivery of the pulses. Our best results were obtained using plate electrodes to deliver across the tumor 80 pulses of 100 micros at 0.3 Hz with an electrical field magnitude of 2500 V/cm. These conditions induced complete regression in 12 out of 13 treated tumors, (92%), in the absence of tissue heating. Irreversible electroporation is thus a new effective modality for non-thermal tumor ablation.
1 × 12 Unequally spaced waveguide array for actively tuned optical phased array on a silicon nanomembrane (2011)

We present an experimental demonstration of an optical phased array implementation on silicon nanomembrane. The integrated on-chip array configuration is non-uniform and avoids grating lobes inside the field of view during beam steering while allowing the waveguide separation to be large enough to prevent optical coupling. A 1 × 12 multimode interference beam splitter uniformly excites the arrayed waveguides. Individually controllable micro-heaters modulate the optical phase in the arrayed waveguides. A beam steering angle of 10.2° in a silicon planar guide equivalent to an effective steering angle of 31.9° in air is demonstrated at 1.55 μm.
Chimeric Mos1 and piggyBac transposases result in site‐directed integration (2006)

Genetic transformation systems based on Mos1 and piggyBac transposable elements are used to achieve stable chromosomal integration. However, integration sites are randomly distributed in the genome and transgene expression can be influenced by position effects. We developed a novel technology that utilizes chimeric transposases to direct integration into specific sites on a target DNA molecule. The Gal4 DNA binding domain was fused to the NH(2) terminus of the Mos1 and piggyBac transposases and a target plasmid was created that contained upstream activating sequences (UAS), to which the Gal4 DBD binds with high affinity. The transpositional activity of the Gal4-Mos1 transposase was 12.7-fold higher compared to controls where the Gal4-UAS interaction was absent and 96% of the recovered transposition products were identical, with integration occurring at the same TA site. In a parallel experiment, a Gal4-piggyBac transposase resulted in an 11.6-fold increase in transpositional activity compared to controls, with 67% of the integrations occurring at a single TTAA site. This technology has the potential to minimize nonspecific integration events that may result in insertional mutagenesis and reduced fitness. Site-directed integration will be advantageous to the manipulation of genomes, study of gene function, and for the development of gene therapy techniques.
Reactivation of arthritis induced by small bowel bacterial overgrowth in rats: role of cytokines, bacteria, and bacterial polymers (1995)

Arthritis is often associated with intestinal diseases, but the etiology is not known. We developed a rat model whereby arthritis was reactivated by experimental small bowel bacterial overgrowth (SBBO). Self-limited monoarticular arthritis was induced by intra-articular injection of 2 micrograms of rhamnose peptidoglycan-polysaccharide derived from group A streptococci into the ankle joints in female Lewis rats. Eleven days after intra-articular injection, when swelling was resolving, experimental SBBO induced by surgical creation of jejunal self-filling blind loops reactivated arthritis, but SBBO induced by creation of self-emptying blind loops, which minimally increases luminal bacteria, and sham operation did not (P < 0.001). Increased joint diameters in rats with self-filling blind loops persisted for at least 56 days after surgery. Reactivation of arthritis due to SBBO was prevented by anti-tumor necrosis factor alpha antiserum and interleukin 1 receptor antagonist (P < 0.001), indicating that these cytokines mediate joint swelling secondary to intestinal injury. Recombinant bactericidal/permeability-increasing protein, an agent which neutralizes endotoxin, and metronidazole, which is active against anaerobic bacteria, prevented arthritis (P < 0.001), but polymyxin B (which also neutralizes endotoxin) and gentamicin had no effect. Mutanolysin, an enzyme which degrades peptidoglycan-polysaccharide from group A streptococci, exacerbated arthritis for the first 6 days but then diminished joint swelling from 12 to 21 days after surgery (P < 0.001). These studies introduce a reproducible animal model of reactivation of arthritis secondary to intestinal injury and demonstrate a role for bacterial products from endogenous enteric organisms.
Inhibitory Effect of Some Triterpenoid Saponins on Glucose Transport in Tumor Cells and its Application toin vitroCytotoxic and Antiviral Activities (1994)

The effects of some triterpenoid saponins on glucose transport in Ehrlich ascites tumor (EAT) cells were examined by measuring 2-deoxy-D-glucose (2-DG) uptake. The correlation of the effects with those on the growth of a human T-cell line (MT-4) and the replication of human immunodeficiency virus in MT-4 cells was also studied. Chikusetsusaponin Ia isolated from rhizomes of Panax japonicus C. A. Meyer (Araliaceae) inhibited the 2-DG uptake (IC50 = 76.3 microM) in a competitive fashion with respect to 2-DG (Ki = 0.32 mM) and the growth of MT-4 cells with CC50 of 84.4 microM, whereas it did not show any significant anti-HIV-1 activity. In contrast, zingibroside R1 isolated from rhizomes of Panax zingiberensis Wu et Feng (Araliaceae) showed some anti-HIV-1 activity, which was found to be superior to that of glycyrrhizin, as well as the inhibitory effects on the 2-DG uptake by EAT cells (IC50 = 91.3 microM) and the growth of MT-4 cells (CC50 = 46.2 microM).
Stable expression of a functional homo-oligomeric Drosophila GABA receptor in a Drosophila cell line (1994)

A cloned Drosophila gamma-aminobutyric acid GABA receptor subunit (Rdl) has been stably expressed as a functional homo-oligomeric ion channel in a Drosophila cell line. Stably-transfected clonal cell lines which expressed high levels of GABA receptor were identified by specific [3H]-muscimol binding. Expression of functional GABA-gated ion channels in these cell lines was demonstrated by electrophysiological recording. Rapid and pronounced rundown of responses to GABA during whole-cell patch clamp recordings was overcome by the inclusion of EGTA in the pipette solution, indicating a possible role for calcium-dependent processes in the functional regulation of this GABA receptor. Relative agonist potencies of the expressed receptor were found to be in the order GABA = TACA > CACA. We have observed a reversible block of the receptor by the convulsant antagonists, picrotoxinin and EBOB, and by the insecticide fipronil. Potentiation of GABA responses was seen with the anaesthetic steroid 5 alpha-pregnan-3 alpha-ol-20-one. No significant effects (either agonist, antagonist or modulatory) were observed with bicuculline (a vertebrate GABAAR antagonist), benzodiazepines or barbiturates (vertebrate GABAAR modulators), or with glycine agonist of the closely related vertebrate glycine receptors). The suitability of this Drosophila stable expression system for the characterization of receptors and ion channels is discussed.
Fault detection in photovoltaic systems (2014)

This master’s thesis concerns three different areas in the field of fault detection in photovoltaic systems.Previous studies have concerned homogeneous systems with a large set of parameters being observed,while this study is focused on a more restrictive case. The first problem is to discover immediate faults occurring in solar panels. A new online algorithm is developed based on similarity measures with in a single installation. It performs reliably and is able to detect all significant faults over a certain threshold. The second problem concerns measuring degradation over time. A modified approachis taken based on repetitive conditions, and performs well given certain assumptions. Finally the third problem is to differentiate solar panel faults from partial shading. Here a clustering algorithm DBSCAN is applied on data in order to locate clusters of faults in the solar plane, demonstrating good performance in certain situations. It also demonstrates issues with misclassification of real faults due to clustering
Glu496Ala polymorphism of human P2X7receptor does not affect its electrophysiological phenotype (2003)

A glutamate to alanine exchange at amino acid position 496 of the human P2X(7) receptor was recently shown to be associated with a loss of function in human B lymphocytes in terms of ATP-induced ethidium(+) uptake, Ba(2+) influx, and induction of apoptosis (Gu BJ, Zhang WY, Worthington RA, Sluyter R, Dao-Ung P, Petrou S, Barden JA, and Wiley JS. J Biol Chem 276: 11135-11142, 2001). Here we analyzed the effect of the Glu(496) to Ala exchange on the channel properties of the human P2X(7) receptor expressed in Xenopus oocytes with the two-microelectrode voltage-clamp technique. The amplitudes of ATP-induced whole cell currents characteristic of functional expression, kinetic properties including ATP concentration dependence, and permeation behavior were not altered by this amino acid exchange. Also in HEK293 cells, the Ala(496) mutant mediated typical P2X(7) receptor-dependent currents like the parent Glu(496) hP2X(7) receptor. Because the function of the P2X(7) receptor as an ATP-gated channel for small cations including Ba(2+) remained unaffected by this mutation, we conclude that Glu(496) plays a critical role in pore formation but does not determine the ion channel properties of the human P2X(7) receptor.
Reversible Immortalization of Human Myogenic Cells by Site-Specific Excision of a Retrovirally Transferred Oncogene (1999)

Myogenic cells have a limited life span in culture, which prevents expansion at clinically relevant levels, and seriously limits any potential use in cell replacement or ex vivo gene therapy. We developed a strategy for reversibly immortalizing human primary myogenic cells, based on retrovirus-mediated integration of a wild-type SV40 large-T antigen (Tag), excisable by means of the Cre-Lox recombination system. Myogenic cells were transduced with a vector (LTTN-LoxP) expressing the SV40 Tag under the control of an LTR modified by the insertion of a LoxP site in the U3 region. Clonal isolates of Tag-positive cells showed modified growth characteristics and a significantly extended life span, while maintaining a full myogenic potential. Transient expression of Cre recombinase, delivered by transfection or adenoviral vector transduction, allowed excision of the entire provirus with up to >90% efficiency. Cultures of Cre-treated (Tag-) or untreated (Tag+) myogenic cells were genetically labeled with a lacZ retroviral vector, and injected into the regenerating muscle of SCID/bg immunodeficient mice. Tag- cells underwent terminal differentiation in vivo, giving rise to clusters of beta-Gal+ hybrid fibers with an efficiency comparable to that of control untransduced cells. Tag+ cells could not be detected after injection. Neither Tag+ nor Tag- cells formed tumor in this xenotransplantation model. Reversible immortalization by Tag therefore allows the expansion of primary myogenic cells in culture without compromising their ability to differentiate in vivo, and could represent a safe method by which to increase the availability of these cells for clinical application.
Mechanism of molnupiravir-induced SARS-CoV-2 mutagenesis (2021)

Molnupiravir is an orally available antiviral drug candidate currently in phase III trials for the treatment of patients with COVID-19. Molnupiravir increases the frequency of viral RNA mutations and impairs SARS-CoV-2 replication in animal models and in humans. Here, we establish the molecular mechanisms underlying molnupiravir-induced RNA mutagenesis by the viral RNA-dependent RNA polymerase (RdRp). Biochemical assays show that the RdRp uses the active form of molnupiravir, β-D-N<sup>4</sup>-hydroxycytidine (NHC) triphosphate, as a substrate instead of cytidine triphosphate or uridine triphosphate. When the RdRp uses the resulting RNA as a template, NHC directs incorporation of either G or A, leading to mutated RNA products. Structural analysis of RdRp-RNA complexes that contain mutagenesis products shows that NHC can form stable base pairs with either G or A in the RdRp active center, explaining how the polymerase escapes proofreading and synthesizes mutated RNA. This two-step mutagenesis mechanism probably applies to various viral polymerases and can explain the broad-spectrum antiviral activity of molnupiravir.
PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: Mechanisms, response biomarkers, and combinations (2016)

PD-L1 and PD-1 (PD) pathway blockade is a highly promising therapy and has elicited durable antitumor responses and long-term remissions in a subset of patients with a broad spectrum of cancers. How to improve, widen, and predict the clinical response to anti-PD therapy is a central theme in the field of cancer immunology and immunotherapy. Oncologic, immunologic, genetic, and biological studies focused on the human cancer microenvironment have yielded substantial insight into this issue. Here, we focus on tumor microenvironment and evaluate several potential therapeutic response markers including the PD-L1 and PD-1 expression pattern, genetic mutations within cancer cells and neoantigens, cancer epigenetics and effector T cell landscape, and microbiota. We further clarify the mechanisms of action of these markers and their roles in shaping, being shaped, and/or predicting therapeutic responses. We also discuss a variety of combinations with PD pathway blockade and their scientific rationales for cancer treatment.