gebhart/patrepeval huggingface dataset:
The forkhead transcription factor Foxo1 (Fkhr) confers insulin sensitivity onto glucose-6-phosphatase expression (2001)

Type 2 diabetes is characterized by the inability of insulin to suppress glucose production in the liver and kidney.Insulin inhibits glucose production by indirect and direct mechanisms.The latter result in transcriptional suppression of key gluconeogenetic and glycogenolytic enzymes, phosphoenolpyruvate carboxykinase (Pepck) and glucose-6-phosphatase (G6p).The transcription factors required for this effect are incompletely characterized.We report that in glucogenetic kidney epithelial cells, Pepck and G6p expression are induced by dexamethasone (dex) and cAMP, but fail to be inhibited by insulin.The inability to respond to insulin is associated with reduced expression of the forkhead transcription factor Foxo1, a substrate of the Akt kinase that is inhibited by insulin through phosphorylation.Transduction of kidney cells with recombinant adenovirus encoding Foxo1 results in insulin inhibition of dex/cAMP-induced G6p expression.Moreover, expression of dominant negative Foxo1 mutant results in partial inhibition of dex/cAMP-induced G6p and Pepck expression in primary cultures of mouse hepatocyes and kidney LLC-PK1-FBPase + cells.These findings are consistent with the possibility that Foxo1 is involved in insulin regulation of glucose production by mediating the ability of insulin to decrease the glucocorticoid/cAMP response of G6p.
The Ability of the Inhibitory Domain of the POU Family Transcription Factor Oct-2 to Interfere with Promoter Activation by Different Classes of Activation Domains Is Dependent upon the Nature of the Basal Promoter Elements (1996)

The Oct-2 transcription factor contains an inhibitory domain which is able to repress transcription following DNA binding. Here we show that within the neuronally expressed Oct-2.5 form, the inhibitory domain can strongly inhibit activation by transcription factor activation domains which are either composed predominantly of acidic residues or contain the HOB motif, whereas it has a weaker effect or no effect on proline-rich activation domains and on a glutamine-rich domain. In contrast, the isolated inhibitory domain of Oct-2 can efficiently repress all types of activation domains. This effect is observed however, only on TATA box-containing promoters and not on promoters containing an initiator motif. This widespread inhibition of different activation domains and its dependence on the nature of the basal promoter elements indicate that the inhibitory domain is likely to act by contacting a common downstream target of activation domains within the basal transcriptional complex bound at the TATA box rather than quenching specific activation domains by direct interaction. These effects are discussed in terms of the functional role of the inhibitory domain within Oct-2.5 and the mechanism by which it acts.
The action of antimitotic herbicides on flagellar regeneration in Chlamydomonas reinhardtii: a comparison with the action of colchicine. (1980)

The effect of the antimitotic herbicides amiprophosmethyl, trifluralin, and oryzalin upon flagellar regeneration in Chlamydomonas reinhardtii has been studied. After flagellar amputation colchicine completely blocks its regeneration at 2.5 mM whereas the herbicides do so at 5 microM. When applied to regenerating flagella, one hour after amputation, the action of the herbicides is different of that of colchicine. Colchicine stops further regeneration, whereas the herbicides induce a gradual shortening of the partly regenerated flagella. Fully developed flagella also shorten after herbicide application. The induction of shortening is concentration and temperature dependent. A 30 to 50% inhibition of photosynthesis and respiration as well as calcium uptake was caused by the herbicides, whereas colchicine did not affect these metabolic processes.
Challenges of designing a low-cost indoor localization system using active beacons (2013)

Localization is very helpful for goal-oriented navigation of a mobile robot. In this article, we describe the challenges we faced when designing a low-cost indoor localization system that can be employed on consumer and domestic robots for the systematic navigation in household environments. Our system uses active beacons that project a pair of infrared (IR) spots onto the ceiling and a sensor on the robot which observes them. In order to reduce cost, we designed a 3-diode sensor, i.e. a three pixel camera, that measures directions to the spots. In contrast to e.g. a typical camera with VGA or higher resolution that would allow for a precise tracking of the beacon spots, our low-cost sensor suffers from multi-path, i.e. light not only reaches the sensor directly but also through reflections from walls and other furniture. We tackle this problem by a localization method that learns the light distribution in the room through a simultaneous localization and mapping (SLAM) approach. Our experiments provide numbers on the accuracy and consistency of this method. The presented system is implemented on our Mint robot equipped with an ARM 7 processor and 64 kByte of RAM for the autonomous cleaning of floors.
The Role of Interferon in Cancer Therapy: A Current Perspective (1988)

Recombinant interferon alpha has now been established as having a distinct if narrow role when used as a single agent in cancer therapy. The responses to single-agent therapy can be grouped as shown in Table 7. Interferon is likely to be the treatment of choice for hairy cell leukemia and possibly also for symptomatic nodular lymphoma. Interferon is very useful in treating papillomas and condylomas, and its role as a local agent will probably expand. The list of responding cancers for alpha interferon or other subtypes as a single agent is unlikely to expand greatly over the next few years. Nevertheless, in both melanoma and renal carcinoma, meaningful responses do occur. It is important to be aware of the possibility of both delayed and increasing extent of response with duration of treatment; adequate trials of interferon may therefore require longer periods of treatment than does conventional chemotherapy. Furthermore, because prior failure to respond to chemotherapy does not predict response to interferon, its use as a second-line agent should also be considered. The future of such biological agents, however, clearly lies in combination with other agents as the "fourth arm" of cancer therapy. The challenge is to define what the role of that fourth arm will be. There seems to be a clear choice with the interferons. They can be used at pharmacological doses, in which case their antiproliferative effect is likely to be due to induction of certain enzymes that result in a cytostatic effect in susceptible cancers, of which there are a limited but therapeutically important number. Alternatively, the interferons can be used at physiological doses, which are more likely to cause immunological and cell membrane effects such as NK-cell stimulation, as well as Fc-receptor and tumor-antigen expression. Thus, combination with cytotoxic agents may well require high doses, whereas combination with other biological agents, such as monoclonal antibodies or LAK cells, may be most effective at much lower doses. Over the next few years it will be important to establish the optimal biological doses of the interferons, so that we can maximize their usefulness in therapy and avoid the trap of thinking of them as purely cytotoxic agents.
Serum MicroRNAs Are Promising Novel Biomarkers (2008)

Considering the central role of microRNAs in development and disease, our results highlight the medically relevant potential of determining microRNA levels in serum and other body fluids. Thus, microRNAs are a new class of CNAs that promise to serve as useful clinical biomarkers.
Roles of FGF19 in Liver Metabolism (2011)

Fibroblast growth factor 19 (FGF19) is an ileum-derived postprandial enterokine that governs bile acid and nutrient metabolism. Synthesis of FGF19 is up-regulated by bile acids and, conversely, bile acid synthesis is down-regulated by FGF19. FGF19 also controls gallbladder volume. FGF19 has been shown to have profound effects on glucose and lipid metabolism. Recent studies have described FGF19 as a postprandial regulator of hepatic glucose and protein metabolism. Like insulin, FGF19 induces protein and glycogen synthesis and suppresses gluconeogenesis in liver. However, unlike insulin, FGF19 does not stimulate lipogenesis. A key difference between FGF19 and insulin lies in their use of different cellular signaling pathways. The beneficial effects of FGF19 on liver metabolism raise the question of whether FGF19 and its variants can be used as therapeutic agents in the treatment of diabetes.
Expression of an IGF‐I receptor dominant negative mutant induces apoptosis, inhibits tumorigenesis and enhances chemosensitivity in Ewing's sarcoma cells (2002)

IGF-IR plays an essential role in the establishment and maintenance of the transformed phenotype of ES cells and interference with the IGF-IR pathways causes reversal of the malignant potential of this neoplasm. In this report, we stably transfected a dominant negative IGF-IR expression plasmid in an ES cell line to determine the effectiveness of this strategy against the in vitro and in vivo growth of ES cells. DXR sensitivity of TC-71 cells expressing dominant negative mutants of IGF-IR was also examined. The mutated IGF-IR that we used carries a mutation in the ATP-binding domain of the intracellular beta subunit, while the extracellular, ligand-binding alpha subunit remains unchanged. Cells carrying the dominant mutant IGF-IR had a marked decrease in proliferation, a significant increase in anoikis-induced apoptosis and a severely reduced ability to form colonies in soft agar. In vivo, when cells carrying dominant negative IGF-IR were injected into nude mice, the tumor formation and metastatic abilities of ES cells were reduced and survival increased. Furthermore, transfected clones showed significantly higher sensitivity to DXR, a major drug in the treatment of ES. These results indicate that the IGF/IGF-IR stimulation of ES cells may be inhibited by expression of mutated IGF-IR on their surfaces and that this strategy may be considered a possible alternative to impair this important target of ES cells, whose therapeutic potential was further confirmed.
Primary structural comparison of RNA-dependent polymerases from plant, animal and bacterial viruses (1984)

Possible alignments for portions of the genomic codons in eight different plant and animal viruses are presented: tobacco mosaic, brome mosaic, alfalfa mosaic, sindbis, foot-and-mouth disease, polio, encephalomyocarditis, and cowpea mosaic viruses. Since in one of the viruses (polio) the aligned sequence has been identified as an RNA-dependent polymerase, this would imply the identification of the polymerases in the other viruses. A conserved fourteen-residue segment consisting of an Asp-Asp sequence flanked by hydrophobic residues has also been found in retroviral reverse transcriptases, a bacteriophage, influenza virus, cauliflower mosaic virus and hepatitis B virus, suggesting this span as a possible active site or nucleic acid recognition region for the polymerases. Evolutionary implications are discussed.
Fatty acid synthesis in mitochondria of Euglena gracilis (1984)

A malonyl-CoA-independent fatty acid synthetic system, different from the systems in other subcellular fractions, occurred in mitochondria of Euglena gracilis. The system had ability to synthesize fatty acids directly from acetyl-CoA as both primer and C2 donor using NADH as an electron donor. Fatty acids were synthesized by reversal of beta-oxidation with the exception that enoyl-CoA reductase functioned instead of acyl-CoA dehydrogenase in degradation system. A fairly high activity of enoyl-CoA reductase was found on various enoyl-CoA substrates (C4-C12) with NADH or NADPH. Three species of enoyl-CoA reductase, distinct from each other by their chain-length specificity, were found in Euglena mitochondria, and one of them was highly specific for crotonyl-CoA. It is also discussed that the mitochondrial fatty-acid synthetic system contributes to wax ester fermentation, the anaerobic energy-generating system found in the organism.
Glucagon-like peptide-1 receptor (GLP1-R) mRNA in the rat hypothalamus. (1996)

GLP-1 has been shown to dramatically reduce food intake in fasted rats and is thought to exert its effects by modulating neuronal function in the hypothalamus. To date, little is known about the distribution of GLP1-R and its mRNA in the rodent hypothalamus. The purpose of the present study was to utilize in situ hybridization histochemistry to determine the anatomical distribution of GLP1-R mRNA in the rat hypothalamus. The results of these studies revealed an extensive distribution of GLP1-R mRNA throughout the rostral-caudal extent of the hypothalamus; with a dense accumulation of labeled cells in the supraoptic, paraventricular, and arcuate nuclei. Additional labeled cells were also detected in medial and lateral preoptic areas, periventricular nucleus, ventral division of the bed nucleus of the stria terminalis, lateral hypothalamus, and dorsomedial nucleus. The results of these in situ hybridization histochemical studies have provided detailed and novel information about the distribution of GLP1-R mRNA in the rat hypothalamus. In addition, this morphological data provides important information about the neuronal systems modulated by GLP-1 and their potential role in feeding behavior.
Discovery of ARD-69 as a Highly Potent Proteolysis Targeting Chimera (PROTAC) Degrader of Androgen Receptor (AR) for the Treatment of Prostate Cancer (2019)

We report herein the discovery of highly potent PROTAC degraders of androgen receptor (AR), as exemplified by compound 34 (ARD-69). ARD-69 induces degradation of AR protein in AR-positive prostate cancer cell lines in a dose- and time-dependent manner. ARD-69 achieves DC50 values of 0.86, 0.76, and 10.4 nM in LNCaP, VCaP, and 22Rv1 AR+ prostate cancer cell lines, respectively. ARD-69 is capable of reducing the AR protein level by >95% in these prostate cancer cell lines and effectively suppressing AR-regulated gene expression. ARD-69 potently inhibits cell growth in these AR-positive prostate cancer cell lines and is >100 times more potent than AR antagonists. A single dose of ARD-69 effectively reduces the level of AR protein in xenograft tumor tissue in mice. Further optimization of ARD-69 may ultimately lead to a new therapy for AR+, castration-resistant prostate cancer.
Cytokines and Cardiomyocyte Death (1997)

Cytokines have been associated with the pathogenesis of acute coronary syndromes and chronic heart failure (CHF), which are both associated with cardiomyocyte loss.In CHF, increased serum concentrations of proinflammatory cytokines, including tumour necrosis factor a (TNF-a) and also soluble TNF receptor have been found.Both TNF and Fas-ligand have been able to induce programmed cell death (apoptosis) of cardiomyocytes in various experimental studies.In ischaemic conditions of the heart, increased serum levels of soluble Fas receptor have been found.The proinflammatory cytokines interleukin 1 (IL-l), 11-2 and interferon-y can induce TNF production from target cells, including myocytes.TNF and some other cytokines are able to induce nitric oxide production, which depresses cardiac function and can induce apoptosis.However, anti-inflammatory cytokines such as IL-10, 11-4 and 11-13, secreted by T-helper type 2 lymphocytes and other cells, inhibit the production of proinflammatory cytokines.Preliminary studies suggest that cardiotrophin-1 , produced by cardiomyocytes, is able to inhibit cytokine-induced cardiomyocyte apoptosis in vitro.As growth hormone is able to inhibit the production of proinflammatory cytokines in many cell types, it may also play an important role in the regulation of apoptosis induced by these cytokines.When the cytokine-induced pathways leading to altered gene expression of cardiomyocytes are understood, this knowledge may aid in the development of drugs that prevent progressive cardiomyocyte loss, in particular by inhibiting cytokine-induced apoptosis.
Quantum error correction via codes over GF(4) (1998)

The problem of finding quantum error correcting codes is transformed into the problem of finding additive codes over the field GF(4) which are self-orthogonal with respect to a certain trace inner product. Many new codes and new bounds are presented, as well as a table of upper and lower bounds on such codes of length up to 30 qubits.
Pathological features of glycogen storage disease type II highlighted in the knockout mouse model (1999)

Glycogen storage disease type II (GSDII; Pompe's disease) is an autosomal recessive disease caused by lysosomal alpha-glucosidase deficiency. Skeletal muscle weakness is the most conspicuous clinical symptom of patients suffering from GSDII and skeletal muscle also is prominently involved in the knockout mouse model of this disease. Thus far, however, little detailed information has been published on the pathological changes in other mouse tissues. This paper aims to provide these data and gives a record of the clinical course of the mouse model over a 2-year period. Four-month-old affected mice perform worse in a running wheel than their unaffected littermates, but do not yet display other clear signs of disease. The lysosomal glycogen storage, already evident at birth, becomes more severe in time, leading to muscle wasting by 9-10 months of age and then limb girdle weakness and kyphosis. The disease does not markedly shorten the animal's life span despite the serious tissue pathology, which is not limited to heart and skeletal muscle, but is also seen in the smooth muscle of blood vessels and of the respiratory, digestive, and urogenital tracts. In addition, the mice have lysosomal glycogen storage in the liver, kidney, spleen, and salivary gland; in Schwann cells of the peripheral nerves, and in a subset of neurons in the central nervous system. By pathological criteria, the knockout mouse model parallels the human infantile form of GSDII and is attractive for studying the possible reversal of tissue pathology and symptomatology under different therapeutic regimes.
Rapid Communication: Increased Frequency of TCRγδ+ T Cells in Disease-Free Survivors Following T Cell-Depleted, Partially Mismatched, Related Donor Bone Marrow Transplantation for Leukemia (1996)

Recent interest has focused on the function of gamma delta + T cells in immune responses. However, their role in allogeneic bone marrow transplantation (BMT) remains undefined. We report on a group of 43 leukemia patients who survived for at least 100 days following transplantation using partially HLA-mismatched grafts from related donors that were T cell depleted with the anti-TCR alpha beta monoclonal antibody T10B9.1A-31 and complement. Ten patients (23.2%) were found to have an increased (> or = 10%) proportion of gamma delta + T cells in the peripheral blood at 60-270 days after BMT. All of these patients remain alive, and 9 (90% of patients with > or = 10% gamma delta + cells) are free of disease at 2.5 years compared with a disease-free survival probability of 31% among patients with a normal proportion and concentration of gamma delta + T cells. No other factor was found to be independently associated with improved survival in these patients. These data suggest a possible association between an increase in the percentage and number of gamma delta + T cells and improved disease-free survival following transplantation from a partially mismatched related donor.
Dielectric Resonator Antennas: Basic Concepts, Design Guidelines, and Recent Developments at Millimeter-Wave Frequencies (2016)

An up-to-date literature overview on relevant approaches for controlling circuital characteristics and radiation properties of dielectric resonator antennas (DRAs) is presented. The main advantages of DRAs are discussed in detail, while reviewing the most effective techniques for antenna feeding as well as for size reduction. Furthermore, advanced design solutions for enhancing the realized gain of individual DRAs are investigated. In this way, guidance is provided to radio frequency (RF) front-end designers in the selection of different antenna topologies useful to achieve the required antenna performance in terms of frequency response, gain, and polarization. Particular attention is put in the analysis of the progress which is being made in the application of DRA technology at millimeter-wave frequencies.
Molecular stop signs: regulation of cell-cycle arrest by C/EBP transcription factors (2005)

The CCAAT/enhancer-binding protein (C/EBP) family of transcription factors plays an important role in controlling cell proliferation and differentiation. C/EBPalpha is a particularly potent regulator of cell-cycle exit and is induced in terminally differentiating adipocytes and myeloid cells, where it also activates differentiation-specific genes. The growth-inhibiting activity of C/EBPalpha suppresses tumorigenesis in myeloid cells and possibly other tissues. In addition, recent work has identified C/EBPalpha as a component of the p53-regulated growth arrest response elicited by DNA damage in epidermal keratinocytes. Several studies have explored the mechanism by which C/EBPalpha blocks cell-cycle progression at the G1-S boundary, and several models have been proposed but no universally accepted mechanism has emerged. Controversial issues include whether C/EBPalpha acts through an 'off-DNA' mechanism to inhibit cyclin-dependent kinases, and whether and how it functions with the RB-E2F system to repress transcription of S-phase genes. Other C/EBP-family members have also been implicated in positive and negative control of cell proliferation, and the mechanisms underlying their growth-regulatory activities are beginning to be elucidated.
Induction of Neutralizing Antibodies against Diphtheria Toxin by Priming with Recombinant Mycobacterium bovis BCG Expressing CRM 197 , a Mutant Diphtheria Toxin (2001)

ABSTRACT BCG, the attenuated strain of Mycobacterium bovis , has been widely used as a vaccine against tuberculosis and is thus an important candidate as a live carrier for multiple antigens. With the aim of developing a recombinant BCG (rBCG) vaccine against diphtheria, pertussis, and tetanus (DPT), we analyzed the potential of CRM 197 , a mutated nontoxic derivative of diphtheria toxin, as the recombinant antigen for a BCG-based vaccine against diphtheria. Expression of CRM 197 in rBCG was achieved using Escherichia coli -mycobacterium shuttle vectors under the control of p BlaF*, an upregulated β-lactamase promoter from Mycobacterium fortuitum . Immunization of mice with rBCG-CRM 197 elicited an anti-diphtheria toxoid antibody response, but the sera of immunized mice were not able to neutralize diphtheria toxin (DTx) activity. On the other hand, a subimmunizing dose of the conventional diphtheria-tetanus vaccine, administered in order to mimic an infection, showed that rBCG-CRM 197 was able to prime the induction of a humoral response within shorter periods. Interestingly, the antibodies produced showed neutralizing activity only when the vaccines had been given as a mixture in combination with rBCG expressing tetanus toxin fragment C (FC), suggesting an adjuvant effect of rBCG-FC on the immune response induced by rBCG-CRM 197 . Isotype analysis of the anti-diphtheria toxoid antibodies induced by the combined vaccines, but not rBCG-CRM 197 alone, showed an immunoglobulin G1-dominant profile, as did the conventional vaccine. Our results show that rBCG expressing CRM 197 can elicit a neutralizing humoral response and encourage further studies on the development of a DPT vaccine with rBCG.