gebhart/patrepeval huggingface dataset:
Effects on RNA Interference in Gene Expression (RNAi) in Cultured Mammalian Cells of Mismatches and the Introduction of Chemical Modifications at the 3′-Ends of siRNAs (2002)

The highly specific posttranscriptional silencing of gene expression induced by double-stranded RNA (dsRNA) is known as RNA interference (RNAi) and has been demonstrated in plants, nematodes, Drosophila, and protozoa, as well as in mammalian cells. The suppression of expression of specific genes by chemically synthesized 21-nucleotide (21-nt) RNA duplexes has been achieved in various lines of mammalian cells, and this technique might prove to be a valuable tool in efforts to analyze biologic functions of genes in mammalian cells. In order to investigate the utility of potential modifications that can be introduced into small interfering RNAs (siRNAs) and also to study their functional anatomy, we synthesized different types of siRNA targeted to mRNA of Jun dimerization protein 2 (JDP2). Our detailed analysis demonstrated that siRNAs with only one mismatch, relative to the target, on the antisense strand had reduced RNAi effect, whereas the corresponding mutation on the sense strand did not interfere with the RNAi. Moreover, one 2-hydroxyethylphosphate (hp) substitution at the 3'-end of the antisense strand but not of the sense strand also prevented RNAi, whereas a related modification at the 3'-end of either strand, using 2'-O,4'-C-ethylene thymidine (eT), which is a component of ethylene-bridge nucleic acids (ENA), completely abolished RNAi. These results support the hypothesis that the two strands have different functions in RNAi in cultured mammalian cells and indicate that their chemical modification of siRNAs at the 3'-end of the sense strand exclusively is possible, without loss of RNAi activity, depending on the type of modification. Because modification at the 3'-end of the antisense strand by hp or eT abolished the RNAi effect, it appears possible that the 3'-end is recognized by the RNA-induced silencing complex (RISC).
A gene therapy strategy using a transcription factor decoy of the E2F binding site inhibits smooth muscle proliferation in vivo. (1995)

The application of DNA technology to regulate the transcription of disease-related genes in vivo has important therapeutic potentials. The transcription factor E2F plays a pivotal role in the coordinated transactivation of cell cycle-regulatory genes such as c-myc, cdc2, and the gene encoding proliferating-cell nuclear antigen (PCNA) that are involved in lesion formation after vascular injury. We hypothesized that double-stranded DNA with high affinity for E2F may be introduced in vivo as a decoy to bind E2F and block the activation of genes mediating cell cycle progression and intimal hyperplasia after vascular injury. Gel mobility-shift assays showed complete competition for E2F binding protein by the E2F decoy. Transfection with E2F decoy inhibited expression of c-myc, cdc2, and the PCNA gene as well as vascular smooth muscle cell proliferation both in vitro and in the in vivo model of rat carotid injury. Furthermore, 2 weeks after in vivo transfection, neointimal formation was significantly prevented by the E2F decoy, and this inhibition continued up to 8 weeks after a single transfection in a dose-dependent manner. Transfer of an E2F decoy can therefore modulate gene expression and inhibit smooth muscle proliferation and vascular lesion formation in vivo.
Juxtaparanodal clustering of Shaker-like K+ channels in myelinated axons depends on Caspr2 and TAG-1 (2003)

In myelinated axons, K+ channels are concealed under the myelin sheath in the juxtaparanodal region, where they are associated with Caspr2, a member of the neurexin superfamily. Deletion of Caspr2 in mice by gene targeting revealed that it is required to maintain K+ channels at this location. Furthermore, we show that the localization of Caspr2 and clustering of K+ channels at the juxtaparanodal region depends on the presence of TAG-1, an immunoglobulin-like cell adhesion molecule that binds Caspr2. These results demonstrate that Caspr2 and TAG-1 form a scaffold that is necessary to maintain K+ channels at the juxtaparanodal region, suggesting that axon-glia interactions mediated by these proteins allow myelinating glial cells to organize ion channels in the underlying axonal membrane.
Interleukin-1 Receptor Blockade in Perinatal Brain Injury (2014)

Interleukin-1 (IL-1) is a potent inflammatory cytokine that can be produced by a variety of cell types throughout the body. While IL-1 is a central mediator of inflammation and response to infection, the role of IL-1 signaling in adult and pediatric brain injury is becoming increasingly clear. Although the mechanisms of IL-1 expression are largely understood, the downstream effects and contributions to excitotoxicity and oxidative stress are poorly defined. Here, we present a review of mechanisms of IL-1 signaling with a focus on the role of IL-1 in perinatal brain injury. We highlight research models of perinatal brain injury and the use of interleukin-1 receptor antagonist (IL-1RA) as an agent of therapeutic potential in preventing perinatal brain injury due to exposure to inflammation.
THE APPLICATION OF LIPASES IN MODIFYING THE COMPOSITION, STRUCTURE AND PROPERTIES OF LIPIDS - A REVIEW (2004)

Structured triacylglycerols (sTAG), not so long ago called “lipids of the future”, have become functional food available on the market. In the nearest future, some fatty products designed for infant and children nutrition in the USA will contain increased concentrations of arachidonic (AA) and docosahexaenoic (DHA) acids. Many formulae and dietetic products containing triacylglycerols with modified chemical structure and composition – structured triacylglycerols (sTAG) – are available as supplements to human nutrition. This paper reports on the directions and possibilities of lipid modification catalyzed by lipases. Two basic methods for the synthesis and modification of triacylglycerols to obtain sTAG are characterized. The main properties of sTAG are also discussed.
Life in Hot Carbon Monoxide: the Complete Genome Sequence of Carboxydothermus hydrogenoformans Z-2901 (2005)

We report here the sequencing and analysis of the genome of the thermophilic bacterium Carboxydothermus hydrogenoformans Z-2901. This species is a model for studies of hydrogenogens, which are diverse bacteria and archaea that grow anaerobically utilizing carbon monoxide (CO) as their sole carbon source and water as an electron acceptor, producing carbon dioxide and hydrogen as waste products. Organisms that make use of CO do so through carbon monoxide dehydrogenase complexes. Remarkably, analysis of the genome of C. hydrogenoformans reveals the presence of at least five highly differentiated anaerobic carbon monoxide dehydrogenase complexes, which may in part explain how this species is able to grow so much more rapidly on CO than many other species. Analysis of the genome also has provided many general insights into the metabolism of this organism which should make it easier to use it as a source of biologically produced hydrogen gas. One surprising finding is the presence of many genes previously found only in sporulating species in the Firmicutes Phylum. Although this species is also a Firmicutes, it was not known to sporulate previously. Here we show that it does sporulate and because it is missing many of the genes involved in sporulation in other species, this organism may serve as a ''minimal'' model for sporulation studies. In addition, using phylogenetic profile analysis, we have identified many uncharacterized gene families found in all known sporulating Firmicutes, but not in any non-sporulating bacteria, including a sigma factor not known to be involved in sporulation previously.
Issues in packet radio network design (1987)

There are many design choices that must be made in the development of a packet radio network. There is usually no single correct choice, and the decisions are dependent on the environment that the network must work in, the requirements for performance and other functionalities, and the cost and other limitations, in addition, as new hardware and software technologies become available, the parameters governing the decisions change and often result in different selections. This paper outlines a number of design issues and choices available. The intent is to provide an overview of the design decisions that must be made so as to provide a context for the decisions made in a number of existing and developing packet radio networks. It is hoped that this will allow future designs to take advantage of both the wealth of experience available as well as new technologies. Three areas of design decisions are identified. The first area deals with the physical aspects of the network and concentrates on the radio connectivity and channel sharing. The second area deals with the automated management of the network and concentrates on issues such as link management and routing. The third area deals with the interface of the network to the users and some practical aspects of operating and maintaining a network.
Cyclooxygenase-2 expression is up-regulated in squamous cell carcinoma of the head and neck. (1999)

The purpose of this study was to determine whether cyclooxygenase-2 (COX-2) was overexpressed in squamous cell carcinoma of the head and neck (HNSCC). Quantitative reverse transcription-PCR, immunoblotting, and immunohistochemistry were used to assess the expression of COX-2 in head and neck tissue. Mean levels of COX-2 mRNA were increased by nearly 150-fold in HNSCC (n = 24) compared with normal oral mucosa from healthy volunteers (n = 17). Additionally, there was about a 50-fold increase in amounts of COX-2 mRNA in normal-appearing epithelium adjacent to HNSCC (n = 10) compared with normal oral mucosa from healthy volunteers. Immunoblotting demonstrated that COX-2 protein was present in six of six cases of HNSCC but was undetectable in normal oral mucosa from healthy subjects. Immunohistochemical analysis showed that COX-2 was expressed in both HNSCC and adjacent normal-appearing epithelium. Taken together, these results suggest that COX-2 may be a target for the prevention or treatment of HNSCC.
Liposome-associated tumor necrosis factor retains bioactivity in the presence of neutralizing anti-tumor necrosis factor antibodies. (1989)

Cell-associated TNF-alpha, either bound to its receptor on monocyte membranes or expressed as an integral membrane protein, can exert potent tumor cytolytic activity. We assessed the interaction of TNF with the lipid bilayer membrane system, liposomes, and the effects of membrane association on TNF bioactivity. High levels of TNF can be encapsulated within liposomes. At neutral pH, TNF binds to the surface of preformed liposomes (liposome-associated TNF), but does not partition into the lipid bilayer. TNF appears to bind to negatively charged phospholipid head groups of the outer membrane leaflet. Free TNF, liposome-associated TNF, and liposome-encapsulated TNF display comparable abilities to activate human peripheral blood monocytes and to lyse tumor cells. However, liposome-encapsulated TNF, as well as TNF bound to the outer surface of preformed liposomes, retains bioactivity in the presence of anti-TNF antibodies that neutralize free TNF. The interaction of liposomal TNF with cell surface TNF receptors thus appears to be preserved in the presence of neutralizing antibodies.
Heterogeneous expression of the tumor-associated antigens RAGE-1, PRAME, and glycoprotein 75 in human renal cell carcinoma: candidates for T-cell-based immunotherapies? (1998)

It has recently been shown that tumor-associated antigens (TAAs) can evoke tumor-specific T-cell-defined immune responses in cancer patients, thereby offering the possibility of treating patients with such antigens. To develop T-cell-based immunotherapeutic approaches for renal cell carcinoma (RCC), we studied the mRNA expression profile of the TAAs RAGE-1, tyrosinase, MAGE-1, MAGE-2, NY-ESO-1, Melan-A/MART-1, glycoprotein (gp) 75, gp100, beta-catenin, PRAME, and MUM-1 in 14 human RCC cell lines and in tissue specimens of 37 primary RCCs, 2 related metastases, and 33 specimens of normal renal epithelium. Reverse transcription-PCR was performed with TAA-reactive primers, and the specificity of the PCR products was confirmed by Southern blot and/or direct sequencing. PRAME (10 of 14 cell lines), RAGE-1 (7 of 14 cell lines), and gp75 (4 of 14 cell lines) antigens were expressed in a high percentage of RCC cell lines, although the level of TAA expression varied among the different RCC cell lines. However, low levels of TAA expression in RCC cells are sufficient for recognition by TAA-specific CTLs. Transcription of tyrosinase, Melan-A/MART-1, MAGE-1, MAGE-2, NY-ESO-1, gp100, beta-catenin, and MUM-1 was not detected in any RCC cell line. Approximately 50% of surgically removed neoplasias expressed at least one TAA. RAGE-1 mRNA expression was found in 8 of 39 (21%) RCC samples, PRAME mRNA expression was found in 15 of 39 (40%) RCC samples, and gp75 mRNA expression was found in 4 of 39 (11%) RCC samples, but the expression levels of these TAAs were heterogeneous in the different RCC lesions. One RCC specimen expressed MAGE-2, whereas transcription was not detected in any RCC specimen for MAGE-1, NY-ESO-1, tyrosinase, Melan-A/MART-1, gp100, beta-catenin, and MUM-1. The normal kidney epithelium samples were negative for any TAA tested. Thus, RAGE-1, PRAME, and gp75 expression is found with a different frequency in surgically removed lesions and in RCC cell lines, suggesting that a subgroup of RCC patients could be selected for immunotherapeutic strategies that may benefit from immunization against the RAGE-1, gp75, and/or PRAME antigens. However, additional targets for T-cell-based immunotherapy of RCC have yet to be identified.
Regulation of the SLT-1A toxin operon by a ferric uptake regulatory protein in toxinogenic strains of Shigella dysenteriae type 1. (1992)

The regulation of Shiga toxin expression in a clinical isolate of S. dysenteriae 1 by the Fe-Fur (Iron-ferric uptake regulatory protein) repressor complex was investigated. The presence of an endogenous Fur repressor protein capable of binding to either a Fur binding consensus sequence or the regulatory region of SLT-1A was determined in toxinogenic strains of S. dysenteriae. Plasmid constructs bearing Fur binding sites fused to readily assayable reporter genes were used. Plasmid pSC27.1 contains a 21 bp synthetic oligonucleotide Fur protein binding consensus sequence located upstream to the gene for beta-galactosidase. Plasmid pSC105 contains the regulatory sequences of Shiga-like toxin-1A located upstream to the gene for alkaline phosphatase. In an analogous fashion to Shiga toxin regulation in S. dysenteriae 1, transformants bearing either pSC27.1 or pSC105 plasmid DNA were repressed in gene product expression when grown in minimal medium supplemented with iron. Conversely, transformants were de-repressed when grown under iron limiting conditions. These data suggest the presence of Fe-Fur mediated regulation of toxinogenesis in clinical isolates of S. dysenteriae.
Fluid sketches (2000)

We describe a new sketching interface in which shape recognition and morphing are tightly coupled. Raw input strokes are continuously morphed into ideal geometric shapes, even before the pen is lifted. By means of smooth and continual shape transformations the user is apprised of recognition progress and the appearance of the final shape, yet always retains a sense of control over the process. At each time t the system uses the trajectory traced out thus far by the pen coupled with the current appearance of the time-varying shape to classify the sketch as one of several pre-defined basic shapes. The recognition operation is performed using shape-specific fits based on least-squares or relaxation, which are continuously updated as the user draws. We describe the time-dependent transformation of the sketch, beginning with the raw pen trajectory, using a family of first-order ordinary differential
equations that depend on time and the current shape
of the sketch. Using this formalism, we describe several possible behaviors that result by varying the relative significance of new and old portions of a stroke, changing the “viscosity” of the morph, and enforcing different end conditions. A preliminary user study suggests that the new interface is particularly effective for rapidly constructing diagrams consisting of simple shapes.
A Chimeric Human-Bovine Parainfluenza Virus Type 3 Expressing Measles Virus Hemagglutinin Is Attenuated for Replication but Is Still Immunogenic in Rhesus Monkeys (2001)

The chimeric recombinant virus rHPIV3-N(B), a version of human parainfluenza virus type 3 (HPIV3) that is attenuated due to the presence of the bovine PIV3 nucleocapsid (N) protein open reading frame (ORF) in place of the HPIV3 ORF, was modified to encode the measles virus hemagglutinin (HA) inserted as an additional, supernumerary gene between the HPIV3 P and M genes. This recombinant, designated rHPIV3-N(B)HA, replicated like its attenuated rHPIV3-N(B) parent virus in vitro and in the upper and lower respiratory tracts of rhesus monkeys, indicating that the insertion of the measles virus HA did not further attenuate rHPIV3-N(B) in vitro or in vivo. Monkeys immunized with rHPIV3-N(B)HA developed a vigorous immune response to both measles virus and HPIV3, with serum antibody titers to both measles virus (neutralizing antibody) and HPIV3 (hemagglutination inhibiting antibody) of over 1:500. An attenuated HPIV3 expressing a major protective antigen of measles virus provides a method for immunization against measles by the intranasal route, a route that has been shown with HPIV3 and respiratory syncytial virus vaccines to be relatively refractory to the neutralizing and immunosuppressive effects of maternally derived virus-specific serum antibodies. It should now be possible to induce a protective immune response against measles virus in 6-month-old infants, an age group that in developing areas of the world is not responsive to the current measles virus vaccine.
Bloodhound: Searching Out Malicious Input in Network Flows for Automatic Repair Validation (2006)

Many current systems security research efforts focus on mechanisms for Intrusion Prevention and Self-Healing Software. Unfortunately, such systems find it difficult to gain traction in many deployment scenarios. For self-healing techniques to be realistically employed, system owners and administrators must have enough confidence in the quality of a generated fix that they are willing to allow its automatic deployment. In order to increase the level of confidence in these systems, the efficacy of a 'fix' must be tested and validated after it has been automatically developed, but before it is actually deployed. Due to the nature of attacks, such verification must proceed automatically. We call this problem Automatic Repair Validation (ARV). As a way to illustrate the difficulties faced by ARV, we propose the design of a system, Bloodhound, that tracks and stores malicious network flows for later replay in the validation phase for self-healing software
Mutations in the chromatin-associated protein ATRX (2008)

ATRX belongs to the SNF2 family of proteins, many of which have been demonstrated to have chromatin remodeling activity. Constitution mutations in the X-encoded gene give rise to alpha thalassemia mental retardation (ATR-X) syndrome and a variety of related conditions that are often associated with profound developmental delay, facial dysmorphism, genital abnormalities, and alpha thalassemia. Acquired mutations in ATRX are observed in the preleukemic condition alpha thalassemia myelodysplastic syndrome (ATMDS). Mutations in ATRX have been shown to perturb gene expression and DNA methylation. This is a comprehensive report of 127 mutations including 32 reported here for the first time. Missense mutations are shown to cluster in the two main functional domains. The truncating mutations appear to be "rescued" to some degree and so it appears likely that most if not all constitutional ATRX mutations are hypomorphs.
Immune Cell Involvement inAnti-c-mycDNA Prevention of Tumor Formation in a Mouse Model of Burkitt'S Lymphoma (1997)

Abstract Prophylactic therapy with 5′-dCACGTTGAGGGGCAT phosphorothioate, (2.5 nmol/hr) strongly inhibited tumorigenesis in Eμ-myc transgenic mice, and ablated spleen cell MYC antigen. However, the anti-c-myc DNA also stimulated proliferation of spleen cells in vitro, though much less so than a positive CG motif control, 5′-dGCATGACGTTGAGCT.
Methods for linking and mining massive heterogeneous databases (1998)

Many real-world KDD expeditions involve investigation of relationships between variables in different, heterogeneous databases. We present a dynamic programming technique for linking records in multiple heterogeneous databases using loosely defined fields that allow free-style verbatim entries. We develop an interestingness measure based on non-parametric randomization tests, which can be used for mining potentially useful relationships among variables. This measure uses distributional characteristics of historical events, hence accommodating variable-length records in a natural way. As an illustration, we include a successful application of the proposed methodology to a real-world data mining problem at Lucent Technologies. 1
Novel Sulfated Oligosaccharides Containing 3-O-Sulfated Glucuronic Acid from King Crab Cartilage Chondroitin Sulfate K (1996)

We prepared a series of oligosaccharides from king crab cartilage chondroitin sulfate K after exhaustive digestion with testicular hyaluronidase, and determined the structures of four tetrasaccharides and a pentasaccharide by fast atom bombardment mass spectrometry, high performance liquid chromatography analysis of chondroitinase AC-II digests, and 500-MHz 1H NMR spectroscopy. The tetrasaccharides shared the common core structure GlcAbeta1-3GalNAcbeta1-4GlcAbeta1-3GalNAc with various sulfation profiles. One structure was GlcAbeta1-3GalNAc(4S)beta1-4GlcAbeta1-3GalNAc(4S), whereas three of them have the following hitherto unreported structures including a novel glucuronate 3-O-sulfate: GlcA(3S)beta1-3GalNAc(4S)beta1-4GlcAbeta1-3GalNAc(4S), GlcAbeta1-3GalNAc(4S)beta1-4GlcA(3S)beta1-3GalNAc(4S), and GlcA(3S)beta1-3GalNAc(4S)beta1-4GlcA(3S)beta1-3GalNAc(4S), where 3S or 4S represents 3-O- or 4-O-sulfate, respectively. The structure of the pentasaccharide was determined as GlcA(3S)beta1-3GalNAc(4S)beta1-4GlcA(3S)beta1- 3GalNAc(4S)beta1-4GlcA. Chondroitinase ABC digestion of the tetrasaccharides with GlcA(3S) at the internal position destroyed the disaccharide unit containing GlcA(3S) derived from the reducing side and resulted in only the disaccharide unit from the non-reducing side. In contrast, these tetrasaccharides remained totally resistant to chondroitinase AC-II. The results indicated that it is necessary to reevaluate the disaccharide composition of chondroitin sulfate poly- or oligosaccharides purified from various biological sources, since they were usually determined after chondroitinase ABC digestion. It is probable that the structures containing GlcA(3S) would not have been detected.