gebhart/patrepeval huggingface dataset:
Multifunctional interleukin‐1β promotes metastasis of human lung cancer cells in SCID mice via enhanced expression of adhesion‐, invasion‐ and angiogenesis‐related molecules (2003)

We examined whether interleukin-1 (IL-1), a multifunctional proinflammatory cytokine, progresses or regresses metastasis of lung cancer. Exogenous IL-1beta enhanced expression of various cytokines (IL-6, IL-8, and vascular endothelial growth factor (VEGF)) and intracellular adhesion molecule-1 (ICAM-1) by A549, PC14, RERF-LC-AI, and SBC-3 cells expressing IL-1 receptors. A549 cells transduced with human IL-1beta-gene with the growth-hormone signaling-peptide sequence (A549/IL-1beta) secreted a large amount of IL-1beta protein. Overexpression of IL-1beta resulted in augmentation of expression of the cytokines, ICAM-1, and matrix metalloproteinase-2 (MMP-2). A549/IL-1beta cells intravenously inoculated into severe combined immunodeficiency (SCID) mice distributed to the lung more efficiently and developed lung metastasis much more rapidly than did control A549 cells. Treatment of SCID mice with anti-IL-1beta antibody inhibited formation of lung metastasis by A549/IL-1beta cells. Moreover, A549/IL-1beta cells inoculated in the subcutis grew more rapidly, without necrosis, than did control A549 cells, which produced smaller tumors with central necrosis, suggesting involvement of angiogenesis in addition to enhanced binding in the high metastatic potential of A549/IL-1beta cells. Histological analyses showed that more host-cell infiltration, fewer apoptotic cells, more vascularization, and higher MMP activity were observed in tumors derived from A549/IL-1beta cells, compared with tumors derived from control A549 cells. These findings suggest that IL-1beta facilitates metastasis of lung cancer via promoting multiple events, including adhesion, invasion and angiogenesis.
Studies on Tertiary Amine Oxides. L. Reactions of Isoquinoline and Pyridine N-Oxides' Derivatives with Cyanogen Bromide (1975)

Isoquinoline 2-oxide (I) reacts with cyanogen bromide in ethanol to give ethyl N-(1- and 4-isoquinolyl) carbamates (II and III) accompanied with some by-products (IV, V, or V' and VI). The amount of II is always larger than that of III and the best yield (42.6%) of II is obtained from the reaction at room temperature for 5 days. 1-Chloroisoquinoline 2-oxide (VII) gives no carbamate and 4-bromoisoquinoline 2-oxides (VIII) afforded 2-isoquinolylcarbamate (IX) in a small yield. While 1-hydroxyisoquinoline 2-oxide (XI) gives only the 4-bromo derivative (XII) by the usual procedure, 4-ethoxycarbonylamino-isocarbostyril (XIII) is produced in 22% yield when sodium acetate is added to the reactants. Although pyridine 1-oxides generally resist this reaction, only 4-hydroxypyridine 1-oxide is highly reactive and ethyl N-(4-hydroxy-3-pyridyl) carbamate hydrobromide (XVIII·HBr) is obtained in 57 % yield. Reactions of 1-aminoisoquinoline 2-oxide (XIV) and 2-aminopyridine 1-oxide (XX) are quite similar to that of 2-aminoquinoline 1-oxide, and the corresponding oxadiazolo derivatives (XV and XXI) are produced without the participation of ethanol.
Surgical Mesh as a Scaffold for Tissue Regeneration in the Esophagus (2004)

The results indicate that PVDF mesh structure gives the opportunity of local tissue regeneration in the esophagus. Though re-epithelialization and muscle cell ingrowth could be detected for absorbable polyglactin 910 mesh, this implant was accompanied by a high and early rate of anastomotic leakage.
Host-Parasite Interaction in Flax Rust—Its Genetics and Other Implications (2025)

The pathogenicity of 67 F<sub>2</sub> cultures of a cross of race 6 with race 22 of the flax rust pathogen was determined on 32 varieties of flax that had been selected as carrying single genes for rust reaction. Two varieties were resistant and 6 were susceptible to all F<sub>2</sub> cultures. On 23 of the 24 varieties on which the F<sub>2</sub> cultures segregated for pathogenicity, the ratio of avirulent to virulent cultures approximated the 3:1 expected if virulence on each was conditioned by a pair of recessive genes. On Ottawa 770B, 2 pairs of genes may have conditioned pathogenicity. Fifty-four pathogenic races were identified from the 67 cultures. Host-parasite interaction in flax rust may be explained by assuming a gene-for-gene relationship between rust reaction in the host and pathogenicity in the parasite. Pustule type, the criterion of both reaction and pathogenicity, is conditioned by specific pairs of genes, one in the host and the other in the parasite. In flax and the flax rust fungus, 25 such pairs of genes have been identified. Because of the gene-for-gene relationship between reaction in the host and pathogenicity in the parasite, the recessive gene complement of a uredial clone (culture) is established by determining its pathogenicity on differential varieties with single rust-conditioning genes. The homozygosity or heterozygosity of the dominant genes is established by selfing the uredial clone. Thus, a method for identifying the pathogenic genotype of races of the rust fungi has been devised. This makes possible the use of the biotype as the basic concept of race. The gene-for-gene relationship of rust reaction and pathogenicity in host and parasite facilitates the development of rust-resistant varieties and opens new approaches to studies of the origin of new races, mutation for rust reaction in the host and pathogenicity in the parasite, and the evaluation of epidemiology data, and the nature of resistance.
Clinical status of methylnaltrexone, a new agent to prevent and manage opioid-induced side effects. (2004)

Opioids are associated with a number of adverse effects, constipation being the most common long-term adverse effect in patients with advanced cancer. Significant progress has been made over the past several decades in understanding the mechanisms of action of opioid compounds; however, these advances have yielded few new treatments for the bowel dysfunction caused by opioids. Methylnaltrexone, the first peripheral opioid receptor antagonist and currently under clinical investigation, has the potential to prevent or treat opioid-induced peripherally mediated side effects, such as constipation, without interfering with analgesia. This article reviews existing clinical data on methylnaltrexone, focusing on the antagonism of opioid-induced adverse effects in the gut.
A Re-examination of Tetrodotoxin for Prolonged Duration Local Anesthesia (1998)

Combinations of epinephrine or bupivacaine with tetrodotoxin or with other high-potency toxins active on sodium channels should be examined for the potential to provide clinically useful, prolonged nerve blockade.
Inhibition of the metastatic spread and growth of B16‐BL6 murine melanoma by a synthetic matrix metalloproteinase inhibitor (1994)

The synthetic matrix metalloproteinase inhibitor batimastat was tested for its ability to inhibit growth and metastatic spread of the B16-BL6 murine melanoma in syngeneic C57BL/6N mice. Intraperitoneal administration of batimastat resulted in a significant inhibition in the number of lung colonies produced by B16-BL6 cells injected i.v. The effect of batimastat on spontaneous metastases was examined in mice inoculated in the hind footpad with B16-BL6 melanoma. The primary tumor was removed surgically after 26-28 days. Batimastat was administered twice a day from day 14 to day 28 (pre-surgery) or from day 26 to day 44 (post-surgery). With both protocols, the median number of lung metastases was not significantly affected, but there was a significant reduction in the weight of the metastases. Finally, the effect of batimastat was examined on s.c. growth of B16-BL6 melanoma. Batimastat administered daily, starting at day of tumor transplantation, resulted in a significant growth delay, whereas treatment starting at advanced stage tumor only reduced tumor growth marginally. Our results indicate that a matrix metalloproteinase inhibitor can not only prevent the colonization of secondary organs by B16-BL6 cells but also limit the growth of solid tumors.
New Methodology for Profiling Combinatorial Libraries and Screening Sets:  Cleaning Up the Design Process with HARPick (1997)

Combinatorial chemistry is a tool of increasing importance in the field of ligand design, as it can yield huge increases in the number of compounds available for screening. Unfortunately, it is often the case that the number of molecules which could theoretically be constructed greatly exceeds potential synthesis and screening capacity. For this new technology to be fully exploited, it will become vital to design libraries with reference to the properties of compounds already in existence, if the added value of each new molecular collection is truly to be maximized. Similarly, if we are to take full advantage of the potential of combinatorial chemistry in lead optimization, it is important that our library design paradigms are flexible, with diversity scoring functions that can be modified to suit particular projects. Here these challenges are addressed through the introduction of a novel computer-aided library design tool known as HARPick (heuristic algorithm for reagent picking). The program is accessible to the bench chemist, and incorporates several significant advances over currently available approaches. These include product-based diversity calculations that can be constrained at the reagent level; diversity measures constructed from multiple descriptors; improved pharmacophore key information and full pharmacophore profiling of entire molecular databases. The potential of these improvements to aid in diversity profiling is illustrated through comparison with established methodology, and possible further enhancements are discussed.
Adsorption of Biomolecules to Ice and Their Effects upon Ice Growth. 2. A Discussion of the Basic Mechanism of “Antifreeze” Phenomena (2001)

Different fish, insects, and plants have evolved a range of peptides and glycopeptides that adsorb to ice from water solution and dramatically influence ice growth in ways that benefit the organisms. These “antifreeze” biomolecules are fairly large, the smallest so far discovered having a MW of 1600, and they prevent ice crystal growth from water at values of supercooling up to several degrees Celsius. Dealing with their interaction with the ice/water interface, one is faced with the choice of treating it as an adsorption-equilibrium phenomenon, in which the surface concentration adjusts easily to the solution concentration, or as irreversible adsorption, as if the molecules are very small particles that can achieve essentially permanent, equilibrium configurations at the ice/water interface. The two viewpoints each have areas of validity and usefulness, but the particle viewpoint is argued here to be the more insightful for the problem of understanding how the antifreezes produce their effects upon ice growth and recrystallization. Small particles have been found to have size thresholds below which they migrate with a growth interface and above which they are engulfed, in experiments carried out at controlled crystal growth rates. Part 1 (Knight, C. A.; Wierzbicki, A.; Laursen, R. A.; Zhang, W. Cryst. Growth Des. 2001, 1, 429−438) presents evidence that adsorption to ice that allows the ice to grow but without engulfing the adsorbed molecules is quite common. By analogy with small particles, much of this probably represents permanent adsorption at the interface, but migration of the adsorbate with the interface as the ice grows. For adsorption−inhibition of crystal growth to be effective, a necessary property of “antifreeze” molecules is that they be unable to migrate. Accordingly, an essential property for a material to produce freezing hysteresis may be that it fits almost perfectly onto ice. A nearly perfect fit may be needed to prevent entry of water molecules into the interface, where they can exert the systematic “force of crystallization” that causes the migration. While most modeling studies have focused on the strength and type of bonding of antifreeze molecules to ice surfaces, this “snugness” of the ice−antifreeze contact may be as, or even more, important.
Effects of IL-12 on in vivo cytokine gene expression and Ig isotype selection. (1994)

The effects of murine rIL-12 on cytokine gene expression and Ig secretion were studied in vivo. In untreated mice IL-12 enhanced IFN-gamma and IL-10 gene expression and protein secretion, reduced base line IL-3 and IL-4 gene expression, and increased serum IgG2a concentration. In mice that had been injected with goat anti-mouse IgD antibody (G alpha M delta) to induce increases in IL-3, IL-4, and IL-10 gene expression and serum IgE, IgG1, IgG2a, and IgG3 concentrations, the simultaneous injection of IL-12 enhanced IFN-gamma and IL-10 gene expression and suppressed IL-3 and IL-4 gene expression and serum IgG and IgE responses. Anti-IFN-gamma mAb neutralized most, but not all, IFN-gamma produced by mice treated with G alpha M delta and IL-12. Anti-IFN-gamma mAb enhanced IL-3 and IL-4 gene expression, did not affect IL-10 or IFN-gamma gene expression, and increased serum IgG1, IgG2a, and IgG3 levels, but had relatively little effect on serum IgE in these mice. In contrast to its effects in G alpha M delta-treated mice, IL-12 failed to inhibit the IgE response to G alpha M epsilon antibody, which stimulates mIgE+ B cells to secrete IgE. These observations demonstrate that: 1) IL-12 may limit its own effects by inducing the production of a cytokine (IL-10) that down-regulates both IL-12 production and IL-12-induced IFN-gamma production; 2) IL-12 inhibits the production of at least one cytokine, IL-3, that is not generally regarded to be strictly Th1- or Th2-associated; 3) IL-12 inhibits switching to IgE secretion to a greater extent than it inhibits switching to other Ig isotypes; and 4) the in vivo effects of IL-12 are, to a large extent, IFN-gamma-dependent.
C‐Reactive Protein (CRP)‐Lowering Agents (2006)

C-reactive protein (CRP) plays a role in the pathogenesis of cardiovascular disease. It is a marker and predictor of cardiovascular disease. CRP possesses numerous cardiovascular effects (clotting, generation of oxygen radicals, increase in the expression of adhesion molecules and plasminogen activator inhibitor-1, plaque destabilization) that could result in cardiovascular disease. This review describes the effects of various cardiovascular drugs on the levels of CRP in health and disease. Cyclooxygenase inhibitors (aspirin, rofecoxib, celecoxib), platelet aggregation inhibitors (clopidogrel, abciximab), lipid lowering agents (statins, ezetimibe, fenofibrate, niacin, diets), beta-adrenoreceptor antagonists and antioxidants (vitamin E), as well as angiotensin converting enzyme (ACE) inhibitors (ramipril, captopril, fosinopril), reduce serum levels of CRP; while enalapril and trandolapril have not been shown to have the same effect. Angiotensin receptor blockers (ARBs) (valsartan, irbesartan, olmesartan, telmisartan) markedly reduce serum levels of CRP. The findings with other ARBs (losartan and candesartan) were inconsistent. Antidiabetic agents (rosiglitazone and pioglitazone) reduce CRP levels, while insulin is ineffective. Calcium channel antagonists have variable effects on CRP levels. Hydrochlorothiazide and oral estrogen do not affect CRP. The CRP-lowering effect of statins is more pronounced than their lipid lowering effect and is not dependent on their hypolipemic activity. The effect of atorvastatin on CRP seems to be dose-dependent. CRP-lowering effect of statins is likely to contribute to the favorable outcome of statin therapy. The data suggest that lipid lowering agents, ACE inhibitors, ARBs, antidiabetic agents, antiinflammatory and antiplatelet agents, vitamin E, and beta-adrenoreceptor antagonists lower serum or plasma levels of CRP, while vitamin C, oral estrogen and hydrochlorothiazide do not affect CRP levels.
Slow optical changes in human photoreceptors induced by light. (2000)

The basic assumption of fundus reflection densitometry is that changes in reflectance are solely determined by photolysis and regenerating visual pigments. This study was undertaken to investigate small but systematic deviations from this rule.Spectral reflectance changes (450-740 nm) of the fovea were measured during light and dark adaptation over a period of 66 minutes in five healthy subjects. The directional properties of the fundus reflection were examined with a custom-built scanning laser ophthalmoscope (SLO) at 514, 633, and 790 nm. The same instrument was also used to find the spatial distribution of the reflectance changes.In addition to fast changes consistent with visual pigment, slower reflectance changes (lasting 10-20 minutes) were observed at all wavelengths including 740 nm. Because visual pigment does not absorb at 740 nm, a second mechanism must be involved. Factor analysis generated two factors (i.e., spectral curves) that explained more than 97% of the variations in the time course of the spectral reflectance. Total reflectance was modeled by means of an existing model for fundus reflection, and it was found that the first factor strongly resembled the rapid changes in absorption of the cone pigments. The second factor seems linked to slow changes in cone reflectance. Measurements with the SLO showed a clear increase in directionally dependent reflectance from 6 to 30 minutes in the dark. This was observed only in the central 6 degrees of the retina.The characteristics of the slow reflectance changes all point to the cone photoreceptors as the origin. Most likely, alterations in the index of refraction between the interphotoreceptor matrix and photoreceptors lie at the base of this hitherto unknown phenomenon.
The role of gicerin, a novel cell adhesion molecule, in development, regeneration and neoplasia. (2001)

Neurite outgrowth factor (NOF) is an extracellular matrix (ECM) protein in the laminin family and its ligand, gicerin, is a novel cell adhesion molecule in the immunoglobulin superfamily. Gicerin has a homophilic adhesive activity as well as a heterotypic manner to NOF. In the nervous systems, gicerin is expressed during developmental stage when neurons migrate or extend neurites to form a neural network. Gicerin promotes neurite extension and migration of embryonic neurons in vitro by its homophilic and heterophilic adhesion activities. Introduction of antigicerin antibody into early developing eyes perturbs the layer formation of neural retina. These data suggest that gicerin participates in the formation of neural tissues. Gicerin is also expressed in other non-neural tissues; in epithelia of trachea, kidney and oviduct, gicerin expression is restricted in the developmental period. In contrast, muscular tissues and endothelial cells express gicerin continuously even after maturation. Interestingly, gicerin re-appears strongly in the regenerating epithelia of trachea, kidney and oviduct, and also anti-gicerin antibody disrupts the healing process of trachea. Furthermore, gicerin and NOF are overexpressed in the chicken nephroblastomas (Wilm's tumor) and oviductal adenocarcinomas. In vitro analyses show that gicerin adhesive activities can promote binding among tumor cells and adhesion of tumor cells to NOF. A polyclonal antibody against gicerin also perturbs the re-attachment of cancer cells onto metastasizing sites. It is clear from these studies that gicerin is a potential effector for pathological tissue formation as well as for normal development.
Aryl Hydrocarbon Hydroxylase Induction in Rat Tissues by Naturally Occurring Indoles of Cruciferous Plants<xref ref-type="fn" rid="fn2">2</xref> (1975)

A phytochemical investigation to identify inducers of increased aryl hydrocarbon hydroxylase (AHH) activity from three cruciferous vegetables, Brussels sprouts, cabbage, and cauliflower, resulted in the identification of indole-3-acetonitrile, indole-3-carbinol, and 3,3'-diindolylmethane as naturally occurring inducers. These compounds are produced during the hydrolysis of indolyl-methyl glucosinolate by the plant enzyme myrosinase.
Recurrent Hemizygous Deletions in Cancers May Optimize Proliferative Potential (2012)

Tumors exhibit numerous recurrent hemizygous focal deletions that contain no known tumor suppressors and are poorly understood. To investigate whether these regions contribute to tumorigenesis, we searched genetically for genes with cancer-relevant properties within these hemizygous deletions. We identified STOP and GO genes, which negatively and positively regulate proliferation, respectively. STOP genes include many known tumor suppressors, whereas GO genes are enriched for essential genes. Analysis of their chromosomal distribution revealed that recurring deletions preferentially overrepresent STOP genes and underrepresent GO genes. We propose a hypothesis called the cancer gene island model, whereby gene islands encompassing high densities of STOP genes and low densities of GO genes are hemizygously deleted to maximize proliferative fitness through cumulative haploinsufficiencies. Because hundreds to thousands of genes are hemizygously deleted per tumor, this mechanism may help to drive tumorigenesis across many cancer types.
Photovoltaic DC-DC module integrated converter for novel cascaded and bypass grid connection topologies - design and optimisation (2006)

Grid connected photovoltaic (PV) inverters fall into three broad categories - central, string and module integrated converters (MICs). MICs offer many advantages in performance and flexibility, but are at a cost disadvantage. Two alternative novel approaches proposed by the author - cascaded dc-dc MICs and bypass dc-dc MICs - integrate a simple non-isolated intelligent dc-dc converter with each PV module to provide the advantages of dc-ac MICs at a lower cost. A suitable universal 150 W 5 A dc-dc converter design is presented based on two interleaved MOSFET half bridges. Testing shows zero voltage switching (ZVS) keeps losses under 1 W for bi-directional power flows up to 15 W between two adjacent 12 V PV modules for the bypass application, and efficiencies over 94% for most of the operational power range for the cascaded converter application. Based on the experimental results, potential optimizations to further reduce losses are discussed.
Rapid diagnosis of chronic myeloid leukemia by flow cytometric detection of BCR-ABL1 protein (2011)

A definitive diagnosis of CML requires either the demonstration of the t(9;22) Philadelphia chromosome translocation (by FISH), or BCR-ABL1 fusion gene (qRT-PCR). Both techniques provide important clinical information, but are usually confined to specialist regional laboratories as they are costly,
Isolation of Staphylococcus aureus clumping factor (1985)

Immunochemically identical components were isolated from water-soluble phases of five Staphylococcus aureus strains by affinity chromatography on fibrinogen-linked Sepharose 4B. The elution was performed with 1 M MgCl2. The component could be isolated from sonicated preparations of whole cells, cell walls, and extracellular products of S. aureus but not from sonicated preparations of staphylococcal L-forms or from Staphylococcus epidermidis. Investigations of the eluted component by immunoelectrophoresis and Western blot analysis by use of different polyspecific antibodies to S. aureus raised in rabbits revealed only one immunoprecipitate or one band. By means of gel filtration on Sepharose CL 6B and sodium dodecyl sulfate-polyacrylamide gel electrophoresis a molecular mass of 420,000 and 360,000 was found, respectively. Chemical analysis showed a carbohydrate content of about 20% by weight. By crossed immunoelectrophoresis the isolated component was demonstrated to bind to human fibrinogen. The finding that this purified component inhibited the fibrinogen-induced clumping of staphylococci strongly suggests that the component is the S. aureus clumping factor.