gebhart/patrepeval huggingface dataset:
Imprinted genes as potential genetic and epigenetic toxicologic targets. (2000)

Genomic imprinting is an epigenetic phenomenon in eutherian mammals that results in the differential expression of the paternally and maternally inherited alleles of a gene. Imprinted genes are necessary for normal mammalian development. This requirement has been proposed to have evolved because of an interparental genetic battle for the utilization of maternal resources during gestation and postnatally. The nonrandom requisite for monoallelic expression of a subset of genes has also resulted in the formation of susceptibility loci for neurobehavioral disorders, developmental disorders, and cancer. Since imprinting involves both cytosine methylation within CpG islands and changes in chromatin structure, imprinted genes are potential targets for dysregulation by epigenetic toxicants that modify DNA methylation and histone acetylation.
Antibiotic Resistance Is Prevalent in an Isolated Cave Microbiome (2012)

Antibiotic resistance is a global challenge that impacts all pharmaceutically used antibiotics. The origin of the genes associated with this resistance is of significant importance to our understanding of the evolution and dissemination of antibiotic resistance in pathogens. A growing body of evidence implicates environmental organisms as reservoirs of these resistance genes; however, the role of anthropogenic use of antibiotics in the emergence of these genes is controversial. We report a screen of a sample of the culturable microbiome of Lechuguilla Cave, New Mexico, in a region of the cave that has been isolated for over 4 million years. We report that, like surface microbes, these bacteria were highly resistant to antibiotics; some strains were resistant to 14 different commercially available antibiotics. Resistance was detected to a wide range of structurally different antibiotics including daptomycin, an antibiotic of last resort in the treatment of drug resistant Gram-positive pathogens. Enzyme-mediated mechanisms of resistance were also discovered for natural and semi-synthetic macrolide antibiotics via glycosylation and through a kinase-mediated phosphorylation mechanism. Sequencing of the genome of one of the resistant bacteria identified a macrolide kinase encoding gene and characterization of its product revealed it to be related to a known family of kinases circulating in modern drug resistant pathogens. The implications of this study are significant to our understanding of the prevalence of resistance, even in microbiomes isolated from human use of antibiotics. This supports a growing understanding that antibiotic resistance is natural, ancient, and hard wired in the microbial pangenome.
An Intercity Coaxial Cable Electronic Highway (1979)

Early in 1978 the Manitoba Telephone System announced its intention to proceed with the construction of a bi-directional coaxial cable intercity transmission network for the initial purpose of delivering television and FM broadcast signals to newly licensed CATV operators in more than twenty communities throughout southern Manitoba. This facility would provide a multi-purpose, user-shared "electronic highway" for the transmission of television, radio, data and new broadband tele-communications services.
Molecular Cloning of Human Intestinal Mucin cDNAs (1989)

A human small intestine lambda gt11 cDNA library was screened using antisera prepared against the deglycosylated protein backbone of human colon cancer xenograft mucin. Three cDNAs were isolated from this screening, designated SMUC 40-42. These cDNAs were all found to contain tandem repeats of 69 nucleotides which encoded a threonine- and proline-rich protein consensus sequence of PTTTPITTTTTVTPTPTPTGTQT. RNA blots probed with one of these cDNAs, SMUC 41, exhibited large, polydisperse hybridization bands at approximately 7,600 bases. Band intensities were strongest when human small intestine, colon, and colon cancer poly(A)+ RNA was used. In vitro translation of poly(A)+ RNA from human small intestine, colon, and colon cancer cells produced a 162,000-dalton peptide that was immunoprecipitated with antibodies to deglycosylated mucin. SMUC 41 was also used to probe DNA blots, which indicated the presence of restriction fragment length polymorphisms in the intestinal mucin gene. These findings may be important in assessing the abnormal mucins found associated with several human diseases.
DNA Vaccines for Emerging Infectious Diseases: What If? (1996)

A novel and powerful method for vaccine research, colloquially known as DNA vaccines, involves the deliberate introduction into tissues of a DNA plasmid carrying an antigen-coding gene that transfects cells in vivo and results in an immune response. DNA vaccines have several distinct advantages, which include ease of manipulation, use of a generic technology, simplicity of manufacture, and chemical and biological stability. In addition, DNA vaccines are a great leveler among re-searchers around the world because they provide unprecedented ease of experi-mentation. To facilitate diffusion of information, an Internet site has been established called THE DNA VACCINE WEB (URL:http://www.genweb.com/dnavax/dnavax.html). In this review, a brief survey is undertaken of the experimental models and preclinical work on DNA vaccines to contribute to a greater awareness of the possibilities for emerging infectious diseases.
Foundations of neuro-fuzzy systems (1997)

From the Publisher:
Foundations of Neuro-Fuzzy Systems reflects the current trend in intelligent systems research towards the integration of neural networks and fuzzy technology. The authors demonstrate how a combination of both techniques enhances the performance of control, decision-making and data analysis systems. Smarter and more applicable structures result from marrying the learning capability of the neural network with the transparency and interpretability of the rule-based fuzzy system. Foundations of Neuro-Fuzzy Systems highlights the advantages of integration making it a valuable resource for graduate students and researchers in control engineering, computer science and applied mathematics. The authors' informed analysis of practical neuro-fuzzy applications will be an asset to industrial practitioners using fuzzy technology and neural networks for control systems, data analysis and optimization tasks.
Automated Reasoning Support for SUMO/KIF (2008)

Formal ontologies play an increasingly important role in demanding knowledge representation applications like the Semantic Web. Although there exist extensive formal ontologies written in the Knowledge Interchange Format (KIF), such as for instance the Suggested Upper Merged Ontology (SUMO), automated reasoning support for SUMO has so far been limited. We propose a novel transformation scheme for a non-trivial subset of the KIF language that enables the meaningful application of model-generation automated reasoning systems. Our transformation features the handling of equality, the Unique Name Assumption and default values and it can be configured to guarantee the finiteness of the resulting models. 1
Breaking the diffraction resolution limit by stimulated emission: stimulated-emission-depletion fluorescence microscopy (1994)

We propose a new type of scanning fluorescence microscope capable of resolving 35 nm in the far field. We overcome the diffraction resolution limit by employing stimulated emission to inhibit the fluorescence process in the outer regions of the excitation point-spread function. In contrast to near-field scanning optical microscopy, this method can produce three-dimensional images of translucent specimens.
Suppression of Human Prostate Tumor Growth in Mice by a Cytolytic d-, l-Amino Acid Peptide (2004)

Gene-encoded host defense peptides are used as part of the innate immunity, and many of them act by directly lysing the cell membrane of the pathogen. A few of these peptides showed anticancer activity in vitro but could not be used in vivo because of their inactivation by serum. We designed a 15-amino acid peptide, composed of D- and L-amino acids (diastereomer), which targets both androgen-independent and androgen-dependent human prostate carcinoma cell lines (CL1, 22RV1, and LNCaP). Most importantly, we observed a complete arrest of growth in CL1 and 22RV1 xenografts treated intratumorally with the diastereomer. This was also accompanied by a lowering of prostate-specific antigen serum levels secreted by the 22RV1 xenograft. Furthermore, the diastereomer synergized with conventional chemotherapeutics. In contrast, the parental all l-amino acids peptide was highly active only in vitro and could not discriminate between tumor and nontumor cells. Fluorescent confocal microscopy, histopathologic examination, and cell permeability studies (depolarization of transmembrane potential and release of an encapsulated dye) suggest a necrotic mechanism of killing, after a threshold concentration of peptide has been reached. Its destructive killing effect and the simple sequence of the diastereomer make it an attractive chemotherapeutic candidate possessing a new mode of action, with potential to be developed additionally for the treatment of prostate carcinoma.
Koios++: A Query-Answering System for Handwritten Input (2012)

In this paper we propose KOIOS++, which automatically processes natural language queries provided by handwritten input. The system integrates several recent achievements in the area of handwriting recognition, natural language processing, information retrieval, and human computer interaction. It uses a knowledge base described by the resource description framework (RDF). Our generic approach first generates a lexicon as background information for the handwritten text recognition. After recognizing a handwritten query, several output hypotheses are sent to a natural language processing system in order to generate a structured query (SPARQL query). Subsequently, the query is applied to the given knowledge base and a result graph visualizes the retrieved information. At all stages, the user can easily adjust the intermediate results if there is any undesired outcome. The system is implemented as a web-service and therefore works for handwritten input on digital paper as well as on input on Pen-enabled interactive surfaces. Furthermore, we build on the generic RDF-representation of semantic knowledge which is also used by the linked open data (LOD) initiative. As such, our system works well in various scenarios. We have implemented prototypes for querying company knowledge bases, the DBPedia1, the DBLP computer science bibliography2, and a knowledge base of the DAS 2012.
Sports participation and juvenile delinquency: The role of the peer context among adolescent boys and girls with varied histories of problem behavior. (2011)

In a study of 1,344 urban adolescents, the authors examined the relation between participation in organized sports and juvenile delinquency. They compared youth who participated in sports to those who only participated in nonathletic activities and to those who did not participate in any organized activities. They also examined the indirect relations between sports and delinquency via 2 peer-related constructs-deviant peer affiliations and unstructured socializing. Finally, they examined the extent to which gender and prior externalizing problems moderated the direct and indirect relations between sports participation and delinquency. The authors found that the odds of nonviolent delinquency were higher among boys who participated in sports when compared to boys who participated only in nonathletic activities but not when compared to boys who did not participate in any organized activities. Deviant peer affiliations and unstructured socializing mediated the relation between sports participation and boys' nonviolent delinquency. Moreover, prior externalizing problems moderated the mediated path through peer deviance. The authors did not, however, find direct, mediated, or moderated relations between sports and boys' violent delinquency nor between sports and girls' violent or nonviolent delinquency.
Transgenic Mice with I-A on Islet Cells Are Normoglycemic But Immunologically Intolerant (1989)

Insulin-dependent diabetes mellitus (IDDM) is caused by a specific loss of the insulin-producing beta cells from pancreatic Langerhans islets. It has been proposed that aberrant expression of major histocompatibility complex (MHC) class II molecules on these cells could be a triggering factor for their autoimmune destruction. This proposal was tested in transgenic mice that express allogeneic or syngeneic class II molecules on the surface of islet cells at a level comparable with that normally found on resting B lymphocytes. These animals do not develop diabetes, nor is lymphocyte infiltration of the islets observed. This immunological inactivity does not result from tolerance to the "foreign" class II molecules.
Delivery of Large Heterologous Polypeptides across the Cytoplasmic Membrane of Antigen-Presenting Cells by the Bordetella RTX Hemolysin Moiety Lacking the Adenylyl Cyclase Domain (2012)

The Bordetella adenylate cyclase toxin-hemolysin (CyaA; also called ACT or AC-Hly) targets CD11b-expressing phagocytes and translocates into their cytosol an adenylyl cyclase (AC) that hijacks cellular signaling by conversion of ATP to cyclic AMP (cAMP). Intriguingly, insertion of large passenger peptides removes the enzymatic activity but not the cell-invasive capacity of the AC domain. This has repeatedly been exploited for delivery of heterologous antigens into the cytosolic pathway of CD11b-expressing dendritic cells by CyaA/AC(-) toxoids, thus enabling their processing and presentation on major histocompatibility complex (MHC) class I molecules to cytotoxic CD8(+) T lymphocytes (CTLs). We produced a set of toxoids with overlapping deletions within the first 371 residues of CyaA and showed that the structure of the AC enzyme does not contain any sequences indispensable for its translocation across target cell membrane. Moreover, replacement of the AC domain (residues 1 to 371) with heterologous polypeptides of 40, 146, or 203 residues yielded CyaAΔAC constructs that delivered passenger CTL epitopes into antigen-presenting cells (APCs) and induced strong antigen-specific CD8(+) CTL responses in vivo in mice and ex vivo in human peripheral blood mononuclear cell cultures. This shows that the RTX (repeats in toxin) hemolysin moiety, consisting of residues 374 to 1706 of CyaA, harbors all structural information involved in translocation of the N-terminal AC domain across target cell membranes. These results decipher the extraordinary capacity of the AC domain of CyaA to transport large heterologous cargo polypeptides into the cytosol of CD11b(+) target cells and pave the way for the construction of CyaAΔAC-based polyvalent immunotherapeutic T cell vaccines.
Aortic vessel wall magnetic resonance imaging at 3.0 Tesla: A reproducibility study of respiratory navigator gated free‐breathing 3D black blood magnetic resonance imaging (2008)

The purpose of this study was to evaluate a free-breathing three-dimensional (3D) dual inversion-recovery (DIR) segmented k-space gradient-echo (turbo field echo [TFE]) imaging sequence at 3T for the quantification of aortic vessel wall dimensions. The effect of respiratory motion suppression on image quality was tested. Furthermore, the reproducibility of the aortic vessel wall measurements was investigated. Seven healthy subjects underwent 3D DIR TFE imaging of the aortic vessel wall with and without respiratory navigator. Subsequently, this sequence with respiratory navigator was performed twice in 10 healthy subjects to test its reproducibility. The signal-to-noise (SNR), contrast-to-noise ratio (CNR), vessel wall sharpness, and vessel wall volume (VWV) were assessed. Data were compared using the paired t-test, and the reproducibility of VWV measurements was evaluated using intraclass correlation coefficients (ICCs). SNR, CNR, and vessel wall sharpness were superior in scans performed with respiratory navigator compared to scans performed without. The ICCs concerning intraobserver, interobserver, and interscan reproducibility were excellent (0.99, 0.94, and 0.95, respectively). In conclusion, respiratory motion suppression substantially improves image quality of 3D DIR TFE imaging of the aortic vessel wall at 3T. Furthermore, this optimized technique with respiratory motion suppression enables assessment of aortic vessel wall dimensions with high reproducibility.
Cumulative lifetime incidence of extracolonic cancers in Lynch syndrome: a report of 121 families with proven mutations (2009)

Lynch syndrome or hereditary non-polyposis colorectal cancer is caused by mutations of DNA mismatch repair (MMR) genes. The extracolonic tumour spectrum includes endometrial, ovarian, gastric, small bowel, pancreatic, hepatobiliary, brain, and urothelial neoplasms. Families were referred on the basis of clinical criteria. Tumour immunohistochemistry and microsatellite testing were performed. Appropriate patients underwent sequencing of relevant exons of the MMR genes. Proven and obligate mutation carriers and first-degree relatives (FDRs) with a Lynch syndrome spectrum cancer were considered mutation carriers, as were a proportion of untested, unaffected FDRs based on the proportion of unaffected relatives testing positive in each age group. Kaplan-Meier analysis of risk to 70 years was calculated. One hundred and eighty-four Lynch syndrome spectrum extracolonic cancers in 839 proven, obligate, or assumed mutation carriers were analysed. Cumulative risk for females of an extracolonic tumour is 47.4% (95% CI 43.9-50.8). The risk to males is 26.5% (95% CI 22.6-30.4). There was no reduction in gynaecological malignancies due to gynaecological screening (examination, transvaginal ultrasound scan, hysteroscopy and endometrial biopsy). Males have a higher risk of gastric cancer than females (p = 0.0003). Gastric cancer risk in those born after 1935 does not justify surveillance. These penetrance estimates have been corrected for ascertainment bias and are appropriate for those referred to a high-risk clinic.
Improved Amplification of Microbial DNA from Blood Cultures by Removal of the PCR Inhibitor Sodium Polyanetholesulfonate (1998)

Molecular methods are increasingly used to identify microbes in clinical samples. A common technical problem with PCR is failed amplification due to the presence of PCR inhibitors. Initial attempts at amplification of the bacterial 16S rRNA gene from inoculated blood culture media failed for this reason. The inhibitor persisted, despite numerous attempts to purify the DNA, and was identified as sodium polyanetholesulfonate (SPS), a common additive to blood culture media. Like DNA, SPS is a high-molecular-weight polyanion that is soluble in water but insoluble in alcohol. Accordingly, SPS tends to copurify with DNA. An extraction method was designed for purification of DNA from blood culture media and removal of SPS. Blood culture media containing human blood and spiked with Escherichia coli was subjected to an organic extraction procedure with benzyl alcohol, and removal of SPS was documented spectrophotometrically. Successful amplification of the extracted E. coli 16S rRNA gene was achieved by adding 5 microliter of undiluted processed sample DNA to a 50-microliter PCR mixture. When using other purification methods, the inhibitory effect of SPS could be overcome only by dilution of these samples. By our extraction technique, even uninoculated blood culture media were found to contain bacterial DNA when they were subjected to broad-range 16S rRNA gene consensus PCR. We conclude that the blood culture additive SPS is a potent inhibitor of PCR, is resistant to removal by traditional DNA purification methods, but can be removed by a benzyl alcohol extraction protocol that results in improved PCR performance.
Inverse correlation of epidermal growth factor receptor messenger RNA induction and suppression of anchorage-independent growth by OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in glioblastoma multiforme cell lines (2004)

The induction of EGFR mRNA may constitute a cellular mechanism to counteract the inhibitory effect of OSI-774 on the anchorage-independent growth of GBM cells. In contrast, no considerable correlation could be established between baseline expression levels of EGFR (both mRNA and protein) in GBM cell lines and their biological response to OSI-774. The OSI-774 induced greater (p53-independent) apoptosis in more malignant GBM phenotypes and may be a promising therapeutic agent against secondary GBM.
Seizure Prediction Methods: A Review of the Current Predicting Techniques (2014)

Epilepsy is a common neurological disorder affecting more than 1.5 percent worldwide. Twenty percent of epilepsies are drug resistant. Therefore, early detection of prediction of epileptic seizures is of prime significance to decrease the burdens of the disease. There is strong evidence indicating seizures develop minutes to hours before clinical onset. This change is based on quantitative studies of long term electroencephalographic monitoring (EEG) from patients administered for epilepsy surgery. The possibility of early prediction of seizure has drawn the research interest of diverse fields in medical, engineering, and patent publications. Techniques used to predict seizures include frequency-based methods, statistical analysis of EEG signals, non-linear dynamics (chaos), and intelligent expert systems. Developing efficient methods to predict seizures can lead to designing novel diagnostic and therapeutic techniques for the early diagnosis of seizure attack or preventing the attacks through appropriate modulations of brain activities. The present study reviews the most important and recent methods for seizure prediction. In line with introduction of different efficient seizure predicting approaches, great research interest has been focused on developing new modalities that incorporate these approaches to predict early onset of seizures minutes to hours before they initiate. These modalities will enable experts to develop new interventional treatments such as appropriate responsive electric stimulation applied immediately after the prediction to prevent the seizures or modulating stimulation in controlling the seizure attacks. In the near future, seizures can be predicted in time and prevented before clinical and physical indications.
Overcoming Transcription Activator-like Effector (TALE) DNA Binding Domain Sensitivity to Cytosine Methylation (2012)

Within the past 2 years, transcription activator-like effector (TALE) DNA binding domains have emerged as the new generation of engineerable platform for production of custom DNA binding domains. However, their recently described sensitivity to cytosine methylation represents a major bottleneck for genome engineering applications. Using a combination of biochemical, structural, and cellular approaches, we were able to identify the molecular basis of such sensitivity and propose a simple, drug-free, and universal method to overcome it.