gebhart/patrepeval huggingface dataset:
A computational approach to identify genes for functional RNAs in genomic sequences (2001)

Currently there is no successful computational approach for identification of genes encoding novel functional RNAs (fRNAs) in genomic sequences. We have developed a machine learning approach using neural networks and support vector machines to extract common features among known RNAs for prediction of new RNA genes in the unannotated regions of prokaryotic and archaeal genomes. The Escherichia coli genome was used for development, but we have applied this method to several other bacterial and archaeal genomes. Networks based on nucleotide composition were 80â90% accurate in jackknife testing experiments for bacteria and 90â99% for hyperthermophilic archaea. We also achieved a significant improvement in accuracy by combining these predictions with those obtained using a second set of parameters consisting of known RNA sequence motifs and the calculated free energy of folding. Several known fRNAs not included in the training datasets were identified as well as several hundred predicted novel RNAs. These studies indicate that there are many unidentified RNAs in simple genomes that can be predicted computationally as a precursor to experimental study. Public access to our RNA gene predictions and an interface for user predictions is available via the web.
373. The chemistry of fungi. Part XXXV. A preliminary investigation of ergoflavin (1958)

G. Eglinton, F. E. King, G. Lloyd, J. W. Loder, J. R. Marshall, A. Robertson and W. B. Whalley, J. Chem. Soc., 1958, 1833 DOI: 10.1039/JR9580001833
MK2 Targets AU-rich Elements and Regulates Biosynthesis of Tumor Necrosis Factor and Interleukin-6 Independently at Different Post-transcriptional Levels (2002)

We demonstrate that lipopolysaccharide-induced tumor necrosis factor (TNF) biosynthesis becomes independent of MAPKAP kinase 2 (MK2) when the AU-rich element (ARE) of the TNF gene is deleted. In spleen cells and macrophages where TNF biosynthesis is restored as a result of this deletion, interleukin (IL)-6 biosynthesis is still dependent on MK2. In MK2-deficient macrophages the half-life of IL-6 mRNA is reduced more than 10-fold, whereas the half-life of TNF mRNA is only weakly decreased. It is shown that the stability of a reporter mRNA carrying the AU-rich 3'-untranslated region (3'-UTR) of IL-6 is increased by MK2. The data provide in vivo evidence that the AU-rich 3'-UTRs of TNF and IL-6 are downstream to MK2 signaling and make MK2 an essential component of mechanisms that regulate biosynthesis of IL-6 at the levels of mRNA stability, and of TNF mainly through TNF-ARE-dependent translational control.
Transcriptional Regulatory Sequences of Carcinoembryonic Antigen: Identification and Use with Cytosine Deaminase for Tumor-Specific Gene Therapy (1995)

The 5' sequences from the human carcinoembryonic antigen gene (CEA) were analyzed using luciferase reporter gene assays. This analysis identified important cis-acting sequences needed for selective expression in CEA-positive cells. Over 50 CEA/luciferase reporter clones were constructed and analyzed in two CEA-positive and two CEA-negative cell lines. The CEA sequences analyzed extended from the translational start to 14.5 kb 5' of the CEA gene. A 408-bp region from the CEA 3' untranslated region was also examined for its effect on reporter gene activity. The CEA promoter was located between bases -90 and +69 of the transcriptional start site. Sequences between -41 and -18 were essential for expression from the CEA promoter. Multimerization of sequences between -89 and -40 resulted in copy number-related increases in both expression level and selectivity for CEA-positive cells. Two upstream regions of CEA, -13.6 to -10.7 kb or -6.1 to -4.0 kb, when linked to the multimerized promoter led to high-level, selective expression in CEA-positive cell lines. Several CEA/luciferase constructs demonstrated 80- to 120-fold higher expression in CEA-positive cell lines compared to expression in CEA-negative Hep3B cells. The expression from these constructs was quite strong in CEA-positive cells, being two- to four-fold higher than an SV40 enhancer/promoter construct. The most promising CEA transcriptional regulatory sequences were used to regulate the expression of cytosine deaminase (CD) in stable cell lines. The expression of CD was assessed directly by an enzymatic assay and indirectly by determining the in vitro IC50 to 5-fluorocytosine (5FC). The chimeric gene pCEA/CD-145 displayed the desired expression spectrum--high-level expression in the CEA-positive cells and low-level expression in CEA-negative cells. CD expression from this chimera correlated well with the expression of the endogenous CEA gene. Treatment of mice bearing NCI H508 pCEA/CD-145 tumor xenografts with 5FC lead to significant antitumor effects in vivo. The CEA/CD chimeric gene should be useful for tumor-specific suicide gene therapy of CEA-positive tumors.
High resolution measurement of cerebral blood flow using intravascular tracer bolus passages. Part II: Experimental comparison and preliminary results (1996)

This report evaluates several methods to map relative cerebral blood flow (rCBF) by applying both parametric and nonparametric techniques to deconvolve high resolution dynamic MRI measurements of paramagnetic bolus passages with noninvasively determined arterial inputs. We found a nonparametric (singular value decomposition (SVD)) deconvolution technique produced the most robust results, giving mean gray:white flow ratio of 2.7 +/- 0.5 (SEM) in six normal volunteers, in excellent agreement with recent PET literature values for age-matched subjects. Similar results were obtained by using a model-dependent approach that assumes an exponential residue function, but not for a Gaussian-shaped residue function or for either Fourier or regularization-based model-independent approaches. Pilot studies of our CBF mapping techniques in patients with tumor, stroke, and migraine aura demonstrated that these techniques can be readily used on data routinely acquired by using current echo planar imaging technology. By using these techniques, the authors visualized important regional hemodynamic changes not detectable with rCBV mapping algorithms.
Expression of epidermal growth factor receptors in human brain tumors. (1984)

The expression of receptors for epidermal growth factor (EGF-R) was determined in 29 samples of brain tumors from 22 patients. Primary gliogenous tumors, of various degrees of cancer, five meningiomas, and two neuroblastomas were examined. Tissue samples were frozen in liquid nitrogen immediately after the operation and stored at -70 degrees until use. Cerebral tissue samples from 11 patients who died from diseases not related to the central nervous system served as controls. Immunoprecipitation of functional EGF-R-kinase complexes revealed high levels of EGF-R in all of the brain tumors of nonneuronal origin that were examined. The level of EGF-R varied between tumors from different patients and also between specimens prelevated from different areas of the same tumor. In contrast, the levels of EGF-R from control specimens were invariably low. The biochemical properties of EGF-R in brain tumor specimens were found to be indistinguishable from those of the well-characterized EGF-R from the A-431 cell line, derived from human epidermoid carcinomas. Human brain EGF-R displays a molecular weight of 170,000 by polyacrylamide-sodium dodecyl sulfate gel electrophoresis. It is phosphorylated mainly in tyrosine residues and shows a 2-dimensional phosphopeptide map similar to that obtained with the phosphorylated EGF-R from membranes of A-431 cells. Our observations suggest that induction of EGF-R expression may accompany the malignant transformation of human brain cells of nonneuronal origin.
Internet Key Exchange Protocol Version 2 (IKEv2) (2010)

This document describes version 2 of the Internet Key Exchange (IKE) protocol. IKE is a component of IPsec used for performing mutual authentication and establishing and maintaining Security Associations (SAs). This document replaces and updates RFC 4306, and includes all of the clarifications from RFC 4718.
Silencing of the PTEN tumor‐suppressor gene in anaplastic thyroid cancer (2002)

Germline mutations in the tumor-suppressor gene PTEN (MMAC1, TEP1) are found in Cowden syndrome, which predisposes to hamartomas, breast cancer, trichilemmomas, and thyroid tumors of follicular epithelium. PTEN has also been found to be somatically deleted, mutated, and/or silenced in various sporadically occurring cancers such as glioblastoma, breast cancer, kidney cancer, malignant melanoma, and endometrial cancer. Loss or reduction of PTEN protein expression as well as inappropriate subcellular compartmentalization is seen in non-medullary thyroid cancers. However, although allelic loss of the PTEN locus in 10q23.3 is frequently seen, this is not coupled with mutations in the PTEN gene. To approach further the frequency and mechanism behind PTEN silencing, we screened a panel of 87 sporadic thyroid tumors for PTEN mRNA expression, including 14 anaplastic carcinomas, 37 follicular carcinomas, 21 atypical adenomas, and 15 ordinary adenomas. Complete loss of PTEN mRNA expression was evident in six of the tumors, including four anaplastic carcinomas, one widely invasive carcinoma, and one ordinary adenoma. The transcriptional silencing of PTEN was significantly associated with the anaplastic subtype, suggesting that PTEN is involved in the carcinogenesis of highly malignant or late-stage thyroid cancers, whereas this particular mechanism appears to be of minor importance in differentiated follicular thyroid tumors. No association was observed between the expression, loss of heterozygosity, and mutation status in the 33 cases in which these parameters were compared. This indicates that PTEN silencing is a result of a wide variety of epigenetic and/or structural silencing mechanisms rather than a consequence of structural biallelic inactivation of the classical type. Furthermore, the high rate of alterations in the 10q23 region might indicate the presence of an as-yet unknown tumor-suppressor gene with an important role in the development of thyroid tumors.
Phosphatidylinositol 3-kinase binds to α-actinin through the p85 subunit (1994)

Phosphatidylinositol 3-kinase (PI 3-kinase) has been shown to play an important role in the signal transduction of cell growth. It is also suggested that it is involved in cytoskeletal reorganization. We have found that alpha-actinin copurifies with PI 3-kinase from bovine thymus. The antibody against PI 3-kinase 85 kDa subunit (p85) also co-immunoprecipitates alpha-actinin from lysates of NIH/3T3 cells. In addition, anti-alpha-actinin antibody coprecipitates PI 3-kinase activity. This coprecipitation was observed even after depolymerization of actin fibres, suggesting that PI 3-kinase binds directly to alpha-actinin. As alpha-actinin is a phosphatidylinositol 4,5-bisphosphate (PI4,5P2)-binding protein, binding experiments using various constructs of truncated p85 were carried out in the presence or absence of PI4,5P2. In the absence of PI4,5P2, chicken gizzard alpha-actinin binds only to the whole p85 construct, but it binds to the proline-rich region of p85 fragments in the presence of PI4,5P2. This binding is enhanced with increased concentrations of Pi4,5P2 up to 10 microM, whereas phosphatidylinositol and phosphatidylinositol 4-phosphate were not good activators of alpha-actinin binding. These results suggest that PI 3-kinase binds to alpha-actinin and regulates cytoskeletal reorganization.
Phylogenetic analysis and rapid identification of Candida dubliniensis based on analysis of ACT1 intron and exon sequences (1999)

The phylogenetic position of Candida dubliniensis has previously been established on the basis of the sequence of rRNA genes. In order to confirm the relationship between C. dubliniensis and other yeast species, particularly Candida albicans, using non-rRNA gene sequences the ACT1 gene was chosen for analysis. Three overlapping fragments that together span the entire C. dubliniensis ACT1 gene (CdACT1) were amplified from a recombinant phage isolated from a genomic DNA lambda library using PCR. These were cloned and used to determine the contiguous sequence of the gene. Analysis of the sequence data revealed the presence of a 1131 bp ORF interrupted by a single 632 bp intron at the 5' extremity of the gene. Comparison of the CdACT1 sequence with the C. albicans homologue (CaACT1) revealed that although the exons are 97.9% identical the introns are only 83.4% identical. Phylogenetic trees generated using ACT1 exon and intron sequences from a range of yeast species unequivocally confirmed the phylogenetic position of C. dubliniensis as a unique taxon within the genus Candida. Analysis of the ACT1-associated intron sequences from 10 epidemiologically unrelated C. dubliniensis isolates from disparate geographical locations showed a very low level of intraspecies sequence variation. In order to develop an accurate and rapid method to identify C. dubliniensis from primary isolation plates the significant divergence between the C. dubliniensis and C. albicans ACT1 intron sequences was exploited by designing C. dubliniensis-specific PCR primers. Using a rapid boiling method to produce template DNA directly from colonies from primary isolation plates in 10 min, these primers were used in a blind test with 122 isolates of C. dubliniensis, 53 isolates of C. albicans, 10 isolates of C. stellatoidea and representative isolates of other clinically relevant Candida and other yeast species. Only the C. dubliniensis isolates yielded the C. dubliniensis-specific 288 bp amplimer. Use of this technique on colonies suspected to be C. dubliniensis allows their correct identification as C. dubliniensis in as little as 4 h.
The application of locked nucleic acids in the treatment of cancer. (2006)

Locked nucleic acid (LNA) is a novel high-affinity and biologically stable RNA analog in which the normally flexible ribose sugar ring is fixed in a rigid conformation through a methylene 2'-O, 4'-C linkage. This fixed conformation brings substantial advantages to the design of effective RNA binding drugs, and enables single-stranded LNA oligonucleotides, termed 'RNA antagonists', to have superior efficacies in vivo in downregulating target mRNA when compared to oligonucleotides based on other chemistries or to published short interfering RNA. The features that allow LNA to be a valuable drug platform include unprecedented RNA binding affinity, excellent specificity, resistance to enzymatic degradation, safety, and ease of manufacture. Santaris Pharma A/S holds worldwide rights to the application of LNA in therapeutics, and is engaged in the clinical development of a series of drug candidates against cancer and metabolic diseases. SPC-2996, the company's most advanced product in development, entered an international, open-label, multicenter, phase I/II clinical trial in patients with severe chronic lymphocytic leukemia in May 2005. This trial is the first clinical evaluation of LNA chemistry. Two other LNA compounds have completed good laboratory practice safety studies with satisfactory outcome, and are likely to commence undergoing clinical development by 2007.
Phosphatidylinositol 3-Kinase Is Required for Rhinovirus-induced Airway Epithelial Cell Interleukin-8 Expression (2005)

Rhinovirus (RV) is a common cause of asthma exacerbations. The signaling mechanisms regulating RV-induced airway epithelial cell responses have not been well studied. We examined the role of phosphatidylinositol (PI) 3-kinase in RV-induced interleukin (IL)-8 expression. Infection of 16HBE14o- human bronchial epithelial cells with RV39 induced rapid activation of PI 3-kinase and phosphorylation of Akt, a downstream effector of PI 3-kinase. RV39 also colocalized with cit-Akt-PH, a citrogen-tagged fluorescent fusion protein encoding the pleckstrin homology domain of Akt, indicating that 3-phosphorylated PI accumulates at the site of RV infection. Inhibition of PI 3-kinase and Akt attenuated RV39-induced NF-kappaB transactivation and IL-8 expression. Inhibition of PI 3-kinase also blocked internalization of labeled RV39 into 16HBE14o- cells, suggesting that the requirement of PI 3-kinase for RV39-induced IL-8 expression, at least in part, relates to its role in viral endocytosis.
Antithrombin Reduces Ischemia/Reperfusion Injury of Rat Liver by Increasing the Hepatic Level of Prostacyclin (1999)

We investigated whether antithrombin (AT) can reduce ischemia/reperfusion (I/R)-induced injury of rat liver by promoting prostacyclin release from endothelial cells. Although intravenous administration of AT (250 U/kg) markedly reduced hepatic injury, neither dansyl-Glu-Gly-Arg-chloromethyl ketone-treated factor Xa (DEGR-Xa), a selective inhibitor of thrombin generation, nor Trp49-modified AT, which lacks affinity for heparin, had any effect. Hepatic levels of 6-keto-PGF1, a stable prostacyclin (PGI2) metabolite, were increased significantly after I/R of the rat liver. AT significantly increased the hepatic level of 6-keto-PGF1, whereas neither DEGR-Xa nor Trp49-modified AT increased it. Hepatic tissue blood flow was markedly reduced after I/R. Although AT significantly increased the hepatic tissue blood flow after I/R, neither DEGR-Xa nor Trp49-modified AT increased the blood flow. Hepatic levels of cytokine-induced neutrophil chemoattractant (CINC) and myeloperoxidase (MPO) were significantly increased after hepatic I/R. The levels of these two indicators were reduced by AT but were unaffected by either DEGR-Xa or Trp49-modified AT. Pretreatment of animals with indomethacin (IM) completely inhibited the protective effects of AT on the I/R-induced hepatic damage and the leukocyte activation as well as the AT-induced increase in hepatic 6-keto-PGF1 levels after I/R. Iloprost, a stable analog of PGI2, exhibited effects similar to those of AT and also significantly inhibited the exacerbation of liver injury, the decrease in hepatic tissue blood flow, and the increases in hepatic CINC and MPO levels seen in rats subjected to I/R but pretreated with IM. These findings suggest that AT may prevent I/R-induced hepatic injury by increasing the hepatic levels of PGI2 through the interaction of AT with cell-surface glycosaminoglycans, thus increasing hepatic tissue blood flow and inhibiting leukocyte activation in animals subjected to I/R.
Prevention of Type 1 Diabetes from Laboratory to Public Health (1999)

Despite recent progress in immunology and genetics, the causes of type 1 diabetes remain unknown. Prevention of autoimmune diseases through immunomodulation or gene therapy has not yet been successful in humans. In contrast, some autoimmune diseases such as celiac disease, rheumatic fever, and congenital rubella induced diabetes can be avoided through modification of environmental factors. Candidate environmental causes of type 1 diabetes are now being characterized in cohort studies and clinical trials. An alternative approach to prevention of type 1 diabetes may include a "vaccination" in early childhood to induce tolerance to critical autoantigen(s). This paper reviews the status of current diabetes prevention trials in humans and selected new interventions that are being tested in animal models. We estimate the cost of public health implementation of selected screening and intervention scenarios. The ethical, logistic, and funding issues underlying these scenarios are discussed.
Cellular Encapsulation Enhances Cardiac Repair (2013)

Alginate encapsulation improved retention of hMSCs and facilitated paracrine effects such as increased peri-infarct microvasculature and decreased scar. Encapsulation of MSCs improved cardiac function post-MI and represents a new, translatable strategy for optimization of regenerative therapies for cardiovascular diseases.
A new mesh generation scheme for arbitrary planar domains (1985)

Abstract This paper describes a new algorithm to generate interior nodes within any arbitrary multi‐connected regions. The boundary nodes and the interior nodes are then linked up to form the best possible triangular elements by a completely revised technique in an efficient and stable manner. Owing to the generality of the central generation program, the global domain is allowed to be divided into as many irregular subdomains as desired, in order to model closely the actual physical situation. Moreover, the boundaries of the sub‐domains are updated from time to time when necessary to include the possibilities of progressive refinement around a sharp corner, generating radiating mesh from a prescribed node, generating mesh between two circular arcs, etc. Despite its flexibility and capabilities, data for triangulation have been kept to a minimum by a logical input module; no connectivity information between subregions is needed, and common boundaries are defined once only . All these features have contributed to a powerful method to generate 3‐node or 6‐node triangular element meshes of great variety within the most irregular heterogeneous regions.
Reinforcement Learning for UAV Attitude Control (2019)

Autopilot systems are typically composed of an “inner loop” providing stability and control, whereas an “outer loop” is responsible for mission-level objectives, such as way-point navigation. Autopilot systems for unmanned aerial vehicles are predominately implemented using Proportional-Integral-Derivative (PID) control systems, which have demonstrated exceptional performance in stable environments. However, more sophisticated control is required to operate in unpredictable and harsh environments. Intelligent flight control systems is an active area of research addressing limitations of PID control most recently through the use of reinforcement learning (RL), which has had success in other applications, such as robotics. Yet previous work has focused primarily on using RL at the mission-level controller. In this work, we investigate the performance and accuracy of the inner control loop providing attitude control when using intelligent flight control systems trained with state-of-the-art RL algorithms—Deep Deterministic Policy Gradient, Trust Region Policy Optimization, and Proximal Policy Optimization. To investigate these unknowns, we first developed an open source high-fidelity simulation environment to train a flight controller attitude control of a quadrotor through RL. We then used our environment to compare their performance to that of a PID controller to identify if using RL is appropriate in high-precision, time-critical flight control.
Application of fuzzy synthetic evaluation on the civil servants performance (2008)

The civil servant performance appraisal is an appraisal of official quality and working result. It is an important measure which realizes systematized management. Through the analysis on some drawbacks in civil servant performance appraisal and based on the principle of fuzzy sets, in this paper, we adopt the methods of qualitative and quantitative, establish the model of fuzzy synthetic evaluation and analyze the model through a concrete example. The result indicates that the model posses the features of easy operation, strong explanation and so on, and it can effectively realize the performance examination of the civil servant. So it is convenient for further analysis.