gebhart/patrepeval huggingface dataset:
Development of Small-Molecule Cyclin D1-Ablative Agents (2006)

Previously, we demonstrated that the peroxisome proliferator-activated receptor gamma (PPARgamma) agonist troglitazone mediated the repression of cyclin D1 in MCF-7 breast cancer cells by facilitating proteasome-facilitated proteolysis. This PPARgamma-independent mechanism provided a molecular basis for using troglitazone as scaffold to develop a novel class of cyclin D1-ablative agents. The proof of principle of this premise is provided by Delta2TG, in which the introduction of a double bond adjacent to the thiazolidinedione ring abrogated the PPARgamma activity while retaining the activity in cyclin D1 repression. Structural optimization of Delta2TG led to STG28 [(S)-5-(4-{[6-(allyloxy)-2,5,7,8-tetramethylchroman-2-yl]methoxy}-3-methoxybenzylidene)thiazolidine-2,4-dione], which exhibited low micromolar potency in ablating cyclin D1 and inhibiting MCF-7 cell proliferation. It is noteworthy that STG28 mediated the proteasomal degradation of cyclin D1 with a high degree of specificity. Exposure to STG28 did not cause any appreciable change in the expression levels of a series of other cyclins and CDK-dependent kinases. In light of the pivotal role of cyclin D1 in promoting tumorigenesis and drug resistance, this novel cyclin D1-ablating agent may have therapeutic relevance in cancer therapy.
Regional regulation of choroidal blood flow by autonomic innervation in the rat (2000)

Regional influences of parasympathetic and sympathetic innervation on choroidal blood flow were investigated in anesthetized rats. Parasympathetic pterygopalatine neurons were activated by electrically stimulating the superior salivatory nucleus, whereas sympathetic neurons were activated by cervical sympathetic trunk stimulation and uveal blood flow was measured by laser Doppler flowmetry. Parasympathetic stimulation increased flux in the anterior choroid and nasal vortex veins but not in the posterior choroid. Vasodilation was blocked completely by the neuronal nitric oxide synthase inhibitor 1-(2-trifluoromethylphenyl)imidazole but was unaffected by atropine. Sympathetic stimulation decreased flux in all regions, and this was blocked by prazosin. Parasympathetic stimulation did not affect vasoconstrictor responses to sympathetic stimulation in the posterior choroid but attenuated the decrease in blood flow through the anterior choroid and vortex veins via a nitrergic mechanism. We conclude that sympathetic alpha-noradrenergic vasoconstriction occurs throughout the choroid, whereas parasympathetic nitrergic vasodilation plays a selective role in modulating blood flow in anterior tissues of the eye.
GENETIC STUDIES ON THE LOSS OF Mu MUTATOR ACTIVITY IN MAIZE (1986)

Mutator activity of the Mu mutator system of maize can be lost by either outcrossing or inbreeding Mu stocks. The nature of these two kinds of Mu-loss phenomena was analyzed by testing the results of crossing Mu-loss stocks by active Mu lines. Outcross- Mu-loss stocks are capable of supporting Mu activity if crossed by an active mutator line. Inbred-Mu-loss stocks, however, inactivate the active Mu system contributed by a Mu line. Also, inbred- Mu-loss lines do not regain Mu activity after at least three generations of outcrossing to non-Mu stocks. These results suggest that, once the Mu system is inactivated by inbreeding, it remains inactivated for at least three generations of outcrossing. Further, once the system responsible for inactivation is established, it will, in turn, inactivate an active Mu system contributed by crossing with Mu plants. The outcross-Mu-loss does not seem to involve such an inactivation system. These results are interpreted in the light of recent evidence that Mu inactivation results from the modification of Mu 1 transposable elements involved in the Mu phenotype.
Autologous Osteochondral Grafting in the Knee: Indication, Results, and Reflections (2002)

The use of multiple autologous osteochondral plugs (mosaicplasty) for repair of articular cartilage defects is a well-accepted technique. Since 1995, the authors have used mosaicplasty to treat more than 110 patients with cartilage defects of the knee, hip, and ankle. The first 52 consecutive patients who had mosaicplasty of the knee and have an average followup of 37 months (range, 24-56 months) were examined. Indications for surgical treatment were osteochondritis dissecans, acute trauma, and posttraumatic lesions of the femorotibial joint, femoropatellar maltracking with recurrent episodes of patella dislocations, and distinct femoropatellar arthrosis. Preoperatively, cartilage defects were classified as International Cartilage Repair Society Grade III lesions in 23 patients and Grade IV lesions in 29 patients. Two years after surgery, an increased level of knee function was found in 86% of the patients. At the latest followup, improved knee function was observed in 92% of the patients. In four patients, reoperation was necessary because of graft failure. Complications and reoperation rate were related to large surface lesions. Autologous osteochondral transplantation is a valid option for the treatment of full-thickness osteochondral defects. However, the method is limited by the defect size and the number of plugs to be taken at the donor site.
Cell cycle-dependent dynamic localization of a bacterial response regulator with a novel di-guanylate cyclase output domain (2004)

Pole development is coordinated with the Caulobacter crescentus cell cycle by two-component signaling proteins. We show that an unusual response regulator, PleD, is required for polar differentiation and is sequestered to the cell pole only when it is activated by phosphorylation. Dynamic localization of PleD to the cell pole provides a mechanism to temporally and spatially control the signaling output of PleD during development. Targeting of PleD to the cell pole is coupled to the activation of a C-terminal guanylate cyclase domain, which catalyzes the synthesis of cyclic di-guanosine monophosphate. We propose that the local action of this novel-type guanylate cyclase might constitute a general regulatory principle in bacterial growth and development.
Migratory pattern of fetal rat brain cells and human glioma cells in the adult rat brain. (1993)

The migratory behavior of two human glioma cell lines (D-54MG and GaMG) and fetal rat brain cells grafted into the adult rat brain was studied. To trace the implanted cells, they were stained with the carbocyanine vital dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate before injecting them into the white matter above the corpus callosum. The animals were sacrificed 2 h and 7 and 21 days after injection, and the brains were removed and cryosectioned. Fluorescence microscopy showed that both the 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate-stained fetal and tumor cells had the same migratory pattern. Implanted cells were found along myelinated fibers in the corpus callosum and in the perivascular space. After immunostaining for several extracellular matrix (ECM) components (laminin, fibronectin, collagen type IV, and chondroitin sulfate), laminin deposits were observed in the border zone between the host tissue and implanted tumor cells as well as fetal cells. By using two different types of antibodies against fibronectin, it is shown that the fibronectin expression observed in the tumor matrix may be host derived. This was further supported by the fact that tumor spheroids obtained from the two glioma cell lines were negative when immunostained for these ECM components. Several of the ECM components may be host derived. This can be caused by neovascularization and repair synthesis or by a local production of guiding substrates which are important for tumor cell locomotion. The present data suggest that the migratory patterns of fetal and glioma cells are indistinguishable when transplanted into the adult rat brain. Thus, glioma cells may be routed by the same ECM components that play a major role during brain development.
Self-administered Topical 5% Imiquimod Cream for External Anogenital Warts (1998)

Five percent imiquimod cream is an effective and safe self-administered therapy for external anogenital warts when applied 3 times a week overnight for up to 16 weeks. The recurrence rate is low.
HUMAN LYMPHOCYTE AND LYMPHOMA HOMING RECEPTORS (1987)

The migration of normal and malignant lymphocytes is controlled in part by selective lymphocyte recognition of high endothelial venules (HEV) at sites of lymphocyte exit from the blood. Recirculating lymphocytes appear to utilize structurally related, yet functionally distinct, 90-kD receptors to interact in an organ-specific manner with HEV in peripheral lymph nodes, in mucosa-associated lymphoid tissues (Peyer's patches, appendix), and in inflamed joint tissue (synovium). These lymphocyte "homing receptors" constitute a family of glycoprotein endothelial cell recognition elements that regulate the extravasation of circulating normal and neoplastic lymphocytes into different organs of the body, and thus play an important role in determining the characteristics of local immune responses and the patterns of dissemination of lymphoid neoplasms.
Prediction of spontaneous autoimmune diabetes in NOD mice by quantification of autoreactive T cells in peripheral blood (2003)

Autoimmune (type 1) diabetes mellitus results from the destruction of insulin-producing pancreatic beta cells by T lymphocytes. Prediction of cell-mediated autoimmune diseases by direct detection of autoreactive T cells in peripheral blood has proved elusive, in part because of their low frequency and reduced avidity for peptide MHC ligands. This article was published online in advance of the print edition. The date of publication is available from the JCI website, http://www.jci.org.
Fate of aerosolized recombinant DNA-produced alpha 1-antitrypsin: use of the epithelial surface of the lower respiratory tract to administer proteins of therapeutic importance. (1989)

To evaluate the possibility of administering therapeutic proteins via the respiratory route, we administered an aerosol of recombinant DNA-produced human alpha 1-antitrypsin (rAAT) to anesthetized sheep and measured levels of the protein in epithelial lining fluid (ELF), lung lymph, blood, and urine. Using a nebulizer that generated aerosol droplets with a mass median aerodynamic diameter of 2.7 micron (55% of droplets were less than 3 micron, a particle size optimal for deposition on the alveolar epithelium), in vitro studies demonstrated that the aerosolized rAAT remained intact and fully functional as an inhibitor of neutrophil elastase. When aerosolized to sheep, the 45-kDa rAAT molecule diffused across the alveolar epithelium, as evidenced by its presence in lung lymph and in blood. Comparison of ELF, lymph, blood, and urine rAAT levels demonstrated that the process was concentration dependent, with highest levels in ELF and in descending concentrations with approximately 10-fold concentration differences in each consecutive compartment, respectively. Importantly, evaluation with aerosolized 125I-labeled rAAT demonstrated that the rAAT molecules that reached the lung lymph and the systemic circulation remained intact as a 45-kDa protein. These results demonstrate the feasibility of using aerosolization to the pulmonary epithelial surface to administer sizeable proteins of therapeutic interest, thus circumventing the necessity of the traditional parenteral modes of administration of such molecules.
Serum-Free Media for Neural Cell Cultures: Adult and Embryonic (2003)

The ability to grow primary neurons under serum-free conditions is facilitating better control in studies of neuronal development, mechanisms of neuronal signaling, electrophysiology, pharmacology, plasticity, in vitro growth requirements, gene expression, and neurotoxicity. Some of the new commercially available media combinations allow for the growth of sparse populations of neurons, which in turn allow for the study of individual neurons and synapses. This has not been possible using serum-supplemented media without a feeder layer of glial cells. In serum-supplemented media, glial cells continue to multiply, necessitating the use of cytotoxic mitotic inhibitors (). Serum also contains unknown and variable levels of growth factors, hormones, vitamins, and proteins.
Biomarkers of alopecia areata disease activity and response to corticosteroid treatment (2015)

Alopecia areata (AA) is a common inflammatory disease targeting the anagen-stage hair follicle. Different cytokines have been implicated in the disease profile, but their pathogenic role is not yet fully determined. We studied biopsies of pretreatment lesional and non-lesional (NL) scalp and post-treatment (intra-lesional steroid injection) lesional scalp of 6 patchy patients with AA using immunohistochemistry and gene expression analysis. Immunohistochemistry showed increases in CD3(+) , CD8(+) T cells, CD11c(+) dendritic cells and CD1a(+) Langerhans cells within and around hair follicles of pretreatment lesional scalp, which decreased upon treatment. qRT-PCR showed in pretreatment lesional scalp (compared to NL) significant increases (P < 0.05) in expression of inflammatory markers (IL-2, IL-2RA, JAK3, IL-15), Th1 (CXCL10 and CXCL9), Th2 (IL-13, CCL17 and CCL18), IL-12/IL-23p40 and IL-32. Among these, we observed significant downregulation with treatment in IL-12/IL-23p40, CCL18 and IL-32. We also observed significant downregulation of several hair keratins in lesional scalp, with significant upregulation of KRT35, KRT75 and KRT86 in post-treatment lesional scalp. This study shows concurrent activation of Th1 and Th2 immune axes as well as IL-23 and IL-32 cytokine pathways in lesional AA scalp and defined a series of response biomarkers to corticosteroid injection. Clinical trials with selective antagonists coupled with cytokine-pathway biomarkers will be necessary to further dissect pathogenic immunity.
Neurokinin-1 receptor antagonists: a comprehensive patent survey (2010)

The NK1 receptor research has led to the clinical introduction of aprepitant in 2003 and its water soluble injectable form, fosaprepitant dimeglumine, in 2009 by Merck for the prevention of postoperative nausea and vomiting and for inhibiting chemotherapy-induced nausea and vomiting. In addition, maropitant citrate received approval in 2007 for veterinary use.
IL-2, TNF-α, and Leptin: Local Versus Systemic Concentrations in NSCLC Patients (2006)

One recent line of cancer research shows increasing interest for biological factor such as IL-2, TNF-alpha, and leptin, which have been found to participate in the development and progression of non-small cell lung cancer (NSCLC). The aim of this study was to measure IL-2, TNF-alpha, and leptin concentrations in the airways and in the systemic circle of patients with NSCLC, investigating the role of these factors in the lung tumors. We enrolled 32 patients (17 men, 71 +/- 7 years) with a histological diagnosis of NSCLC and 20 healthy ex-smoker controls, negative for computed tomography of the chest (14 men, 69 +/- 8 years). IL-2, TNF-alpha, and leptin levels were measured in the serum, the urine, the bronchoalveolar lavage, the induced sputum, and exhaled breath condensate (EBC) of patients enrolled by means of a specific enzyme immunoassay kit. Higher concentrations of IL-2, TNF-alpha and leptin were found in NSCLC patients than in controls (p < 0.0001). A statistically significant increase of IL-2, TNF-alpha, and leptin concentrations was observed in patients from stage I to stage III of NSCLC. These findings suggest that IL-2, TNF-alpha, and the leptin play an important role in the cancerogenesis of NSCLC. Their measure in the EBC could be proposed as noninvasive markers for an early detection of NSCLC and in the follow-up of this tumor.
From Si Source Gas Directly to Positioned, Electrically Contacted Si Nanowires:  The Self-Assembling “Grow-in-Place” Approach (2004)

Our “grow-in-place” approach to Si nanowire devices uses a silicon precursor gas (e.g., SiH4) to directly produce self-assembled, electrically contacted, crystalline Si nanowires without any intervening silicon material formation or collection/positioning steps. The approach uses the vapor−liquid−solid (VLS) growth mechanism and lithographically fabricated, permanent, nanochannel growth templates to control the size, shape, orientation, and positioning of the nanowires and ribbons. These horizontal templates are an integral component of the final devices and provide contacts, interconnects, and passivation/encapsulation. The approach results in self-assembly of the Si nanowires (SiNWs) and nanoribbons (SiNRs) into interconnected devices without any “pick-and-place” or printing steps, thereby avoiding the most serious problems encountered in process control, assembly, contacting, and integration of SiNWs and SiNRs for IC applications. As an initial demonstration of our approach, we have fabricated SiNW and SiNR resistors with built-in electrical contacts and encapsulation and report conductivity measurements.
Amplification and expression of heterologous ornithine decarboxylase in Chinese hamster cells. (1988)

We have developed an amplifiable mammalian expression vector based on the enzyme ornithine decarboxylase (ODC). We show greater than 700-fold amplification of this vector in ODC-deficient Chinese hamster ovary cells. A passive coamplified marker, dihydrofolate reductase (dhfr), was amplified and overexpressed 1,000-fold. This ODC vector was a dominant marker in a variety of cell types and displayed at least 300-fold amplification in wild-type Chinese hamster ovary cells.
Detection of HIV-RNA-positive monocytes in peripheral blood of HIV-positive patients by simultaneous flow cytometric analysis of intracellular HIV RNA and cellular immunophenotype (1998)

Determinations of plasma HIV viral RNA copy numbers help to define the kinetics of HIV-1 infection in vivo and to monitor antiretroviral therapy. However, questions remain regarding the identity of various infected cell types contributing to this free virus pool and to the in vivo lifecycle of HIV during disease progression. Characterization of a novel fluorescence in situ hybridization (FISH) assay employing a pool of labeled oligonucleotide probes directed against HIV RNA was done followed by coupling of the FISH assay with simultaneous surface immunophenotyping to address these questions. In vitro characterizations of this assay using tumor necrosis factor-alpha stimulated and unstimulated ACH-2 cells demonstrated the ability to detect < 5% HIV RNA positive cells with a sensitivity of < 30 RNA copies per cell. Peripheral blood mononuclear cells from 39 HIV-seropositive patients on no, single, combination, or triple drug therapy and 8 HIV-seronegative patients were examined. The majority of HIV-positive patients (24/39) harbored monocytes positive for HIV RNA and a significantly higher fraction of patients with high plasma viral load carried positive monocytes (13/16) than did patients in the low plasma viral load group (11/23). These results demonstrate the effectiveness of a novel FISH assay for identifying and monitoring HIV-infected cell populations in the peripheral blood of HIV-positive patients. In addition, monocytes are a major source of cellular HIV virus in the peripheral blood of HIV patients, even with progression of disease.
Usefulness of Lipoprotein (a) for Predicting Progression of Non-Culprit Coronary Lesions After Acute Myocardial Infarction (2011)

Lp(a) levels could predict the progression of the non-culprit coronary lesions after AMI.
A critical role for ras-mediated, epidermal growth factor receptor-dependent angiogenesis in mouse skin carcinogenesis. (2002)

Epidermal growth factor receptor (EGFR) plays a critical role in epidermal biology. Abnormal EGFR function has been described in epithelial tumors including those induced by two-stage chemical carcinogenesis in mouse skin. A large body of evidence indicates that in this model, activation of Ha-ras is the critical event in papilloma formation, a process that involves epidermal proliferation and stroma remodeling, which includes angiogenesis. This study reports that activated Ha-ras results in a dramatic induction of EGFR in epidermal tumor cells and provides experimental evidence that EGFR signaling is responsible for Ha-ras-dependent vascular endothelial growth factor (VEGF) induction, as well as for the repression of other angiogenic factors such as angiopoietin 1. The pivotal role of functional EGFR in throwing the angiogenic switch necessary for tumor growth was confirmed by s.c. injection of immunodeficient mice with epidermal tumor cells carrying a dominant negative (dn) EGFR and by in vivo chemical skin carcinogenesis assays in transgenic mice expressing the same dn EGFR form in the epidermis. Immunohistochemical analysis of the tumors obtained by both ex vivo and in vivo approaches showed that dn EGFR expression abolished the changes in blood vessels that occurred during tumor progression. A strong reduction of VEGF expression in dn EGFR tumors appears to be the key event responsible for angiogenesis and tumor growth suppression. The apoptotic rate was increased, and Akt activity was decreased, suggesting that impaired nutrient and oxygen supply might contribute to diminished cell survival in dn EGFR tumors. Support for this mechanism is provided by the fact that the ectopic expression of VEGF in dn EGFR-expressing tumor cell lines restored tumor growth capacity. Although ras activation might suffice for epidermal transformation and the stroma-remodeling events of tumor induction, such effects may not be operative without a functional upstream EGFR. It is tempting to speculate that EGFR family members may function as angiogenic regulators in other epithelial tumors such as those of the colon, breast, and prostate, reinforcing their value as targets for therapeutic intervention.
Photoinduced Magnetization of a Cobalt-Iron Cyanide (1996)

Photoinduced magnetization was observed in a Prussian blue analog, K0.2Co1.4- [Fe(CN)6]&middot;6.9H2O. An increase in the critical temperature from 16 to 19 kelvin was observed as a result of red light illumination. Moreover, the magnetization in the ferrimagnetic region below 16 kelvin was substantially increased after illumination and could be restored almost to its original level by thermal treatment. These effects are thought to be caused by an internal photochemical redox reaction. Furthermore, blue light illumination could be used to partly remove the enhancement of the magnetization. Such control over magnetic properties by optical stimuli may have application in magneto-optical devices.
A putative protein kinase gene (kin1+) is important for growth polarity in Schizosaccharomyces pombe. (1990)

Mixed synthetic oligonucleotides encoding a sequence conserved among tyrosine-specific protein kinases were used to probe the genome of the fission yeast Schizosaccharomyces pombe. A single gene (kin1+) was isolated that encodes a putative protein kinase closely related to the KIN1- and KIN2-encoded serine/threonine-specific protein kinases of Saccharomyces cerevisiae. kin1+ is transcribed into a 3.5-kilobase mRNA that contains an uninterrupted open reading frame encoding a polypeptide of 98 kDa. In contrast to results obtained with kin mutants of S. cerevisiae, disruption of the Sc. pombe kin1+ gene resulted in recessive morphological and growth defects. kin1-disrupted cells grew slowly on enriched medium and grew as spheres, in contrast to wild-type Sc. pombe cells, which grow as rods. Relative to kin1+ cells, kin1-disrupted cells were differentially sensitive to lysis by treatment with alpha- and beta-glucanases, suggesting an alteration in either the composition or the organization of their cell walls.