gebhart/patrepeval huggingface dataset:
Double-stranded DNA homology produces a physical signature (2010)

DNA is found in the cell largely as a negatively supercoiled molecule. This high-energy form of the genetic material can engender sequence-dependent structures, such as cruciforms, Z-DNA, or H-DNA, even though they are not favored by conventional conditions in relaxed DNA. A key feature of DNA in living systems is the presence of homology. We have sought homology-dependent structural phenomena based on topological relaxation. Using two-dimensional electrophoresis, we demonstrate a structural transition in supercoiled plasmid molecules containing homologous segments. Atomic force microscopy (AFM) reveals a dumbbell structure in molecules whose linking difference is beyond the transition point. The position of the dumbbell shaft is a function of the site of homology, and its extent is proportional to the linking difference. Second-site-reversion electrophoresis data support the notion that the shaft contains PX-DNA. Predicted cross-linking patterns generated in vivo suggest that homology-dependent structures can occur within the cell.
Copackaged AAV9 Vectors Promote Simultaneous Immune Tolerance and Phenotypic Correction of Pompe Disease (2015)

Pompe disease is a progressive neuromuscular disorder caused by lysosomal accumulation of glycogen from a deficiency in acid alpha-glucosidase (GAA). Replacement of the missing enzyme is available by repeated protein infusions; however, efficacy is limited by immune response and inability to restore enzymatic function in the central nervous system. An alternative therapeutic option is adeno-associated virus (AAV)-mediated gene therapy, which results in widespread gene transfer and prolonged transgene expression. Both enzyme replacement therapy (ERT) and gene therapy can elicit anti-GAA immune reactions that dampen their effectiveness and pose life-threatening risks to patient safety. To modulate the immune responses related to gene therapy, we show that a human codon-optimized GAA (coGAA) driven by a liver-specific promoter (LSP) using AAV9 is capable of promoting immune tolerance in a Gaa(-/-) mouse model. Copackaging AAV9-LSP-coGAA with the tissue-restricted desmin promoter (AAV9-DES-coGAA) demonstrates the necessary cell autonomous expression in cardiac muscle, skeletal muscle, peripheral nerve, and the spinal cord. Simultaneous high-level expression in liver led to the expansion of GAA-specific regulatory T-cells (Tregs) and induction of immune tolerance. Transfer of Tregs into naïve recipients prevented pathogenic allergic reactions after repeated ERT challenges. Copackaged AAV9 also attenuated preexisting humoral and cellular immune responses, which enhanced the biochemical correction. Our data present a therapeutic design in which simultaneous administration of two copackaged AAV constructs may provide therapeutic benefit and resolve immune reactions in the treatment of multisystem disorders.
DNA polymerases as useful reagents for biotechnology â€“ the history of developmental research in the field (2014)

DNA polymerase is a ubiquitous enzyme that synthesizes complementary DNA strands according to the template DNA in living cells. Multiple enzymes have been identified from each organism, and the shared functions of these enzymes have been investigated. In addition to their fundamental role in maintaining genome integrity during replication and repair, DNA polymerases are widely used for DNA manipulation in vitro, including DNA cloning, sequencing, labeling, mutagenesis, and other purposes. The fundamental ability of DNA polymerases to synthesize a deoxyribonucleotide chain is conserved. However, the more specific properties, including processivity, fidelity (synthesis accuracy), and substrate nucleotide selectivity, differ among the enzymes. The distinctive properties of each DNA polymerase may lead to the potential development of unique reagents, and therefore searching for novel DNA polymerase has been one of the major focuses in this research field. In addition, protein engineering techniques to create mutant or artificial DNA polymerases have been successfully developing powerful DNA polymerases, suitable for specific purposes among the many kinds of DNA manipulations. Thermostable DNA polymerases are especially important for PCR-related techniques in molecular biology. In this review, we summarize the history of the research on developing thermostable DNA polymerases as reagents for genetic manipulation and discuss the future of this research field.
Examination of Strains of Lactobacilli for Properties that May Influence Bacterial Interference in the Urinary Tract (1987)

Lactobacilli strains vary in their ability to interfere with colonization of uroepithelial cells by pathogenic organisms. Bacterial size, adherence capability, competitive exclusion and inhibition of pathogenic growth were examined in selected strains of lactobacilli to assess their relative importance. We tested adherence to uroepithelial cells of 34 lactobacillus isolates originating from the urogenital tract, dairy sources and chickens, and 1 lactobacillus strain isolated from a commercially available preparation. The ability to adhere differed greatly among the 34 strains, with a range of 8 to 74 bacteria per cell, and the commercial strain attached poorly with a mean of 15 bacteria per cell. Eleven strains of lactobacilli were selected and found to differ in length and width dimensions. These strains were found to exclude competitively with varying efficiency 6 strains of uropathogens from adhering to uroepithelial cells. The effective ability of Lactobacillus casei GR-1 to exclude the uropathogens confirmed previous findings and other strains (GR-2, GR-3 and A-60) gave a similar range of exclusion. The lactobacillus isolates varied greatly in their ability to inhibit the growth of 11 uropathogens under the conditions of an agar overlay inhibition assay. A combination score was allocated to each of the 11 lactobacillus strains based on size, adherence, exclusion and inhibition. Lactobacillus casei GR-1 attained the highest score while the commercial strain attained the lowest score. The results of this study identified 4 properties that should be examined to select lactobacillus strains before embarking upon bacterial interference studies to prevent urinary tract and other infections in humans.
Structural Basis for Hijacking of Cellular LxxLL Motifs by Papillomavirus E6 Oncoproteins (2013)

E6 viral oncoproteins are key players in epithelial tumors induced by papillomaviruses in vertebrates, including cervical cancer in humans. E6 proteins target many host proteins by specifically interacting with acidic LxxLL motifs. We solved the crystal structures of bovine (BPV1) and human (HPV16) papillomavirus E6 proteins bound to LxxLL peptides from the focal adhesion protein paxillin and the ubiquitin ligase E6AP, respectively. In both E6 proteins, two zinc domains and a linker helix form a basic-hydrophobic pocket, which captures helical LxxLL motifs in a way compatible with other interaction modes. Mutational inactivation of the LxxLL binding pocket disrupts the oncogenic activities of both E6 proteins. This work reveals the structural basis of both the multifunctionality and the oncogenicity of E6 proteins.
A multicenter, randomized, double-blind, placebo-controlled, dose-titration study of oral pilocarpine for treatment of radiation-induced xerostomia in head and neck cancer patients. (1993)

It is concluded that pilocarpine produces clinically significant benefits for the symptomatic treatment of postradiation xerostomia. Best results were obtained with continuous treatment for 8 to 12 weeks with doses greater than 2.5 mg three times per day.
Cucurbitacins and cucurbitane glycosides: structures and biological activities (2005)

The natural cucurbitacins constitute a group of triterpenoid substances which are well-known for their bitterness and toxicity. Structurally, they are characterized by the tetracyclic cucurbitane nucleus skeleton, namely, 19-(10-->9beta)-abeo-10alpha-lanost-5-ene (also known as 9beta-methyl-19-norlanosta-5-ene), with a variety of oxygen substitutions at different positions. According to the characteristics of their structures, cucurbitacins are divided into twelve categories. The biological effects of the cucurbitacins are also covered.
Redundant and specialized roles for diacylglycerol kinases α and ζ in the control of T cell functions (2015)

The diacylglycerol kinases (DGKs) attenuate diacylglycerol (DAG)-mediated signals by catalyzing the conversion of DAG to phosphatidic acid. In T lymphocytes, the antigen-stimulated generation of DAG links signal strength to the intensity and duration of signaling by the Ras-extracellular signal-regulated kinase (ERK) and protein kinase C (PKC)-dependent pathways. The generation of DAG at the plasma membrane of T cells lies at the core of the mechanisms that delimit T cell functions. DGKα and DGKζ are the two main isoforms that are found in T cells, and several approaches define their precise contribution to T cell responses. Each of these isoforms has specialized and redundant functions that limit the intensity of DAG-regulated signals downstream of antigenic stimulation. This ability, which in normal T cells contributes to maintaining homeostasis and function, is exploited by tumors to evade immune surveillance. Modification of DGK activity offers new perspectives for the therapeutic manipulation of T cell functions for treatment of autoimmune pathologies, or for overcoming tumor-induced T cell tolerance. Precise knowledge of the mechanisms that sustain DGK isoform-specific regulation in T lymphocytes is indispensable for the development of new tools for pharmacological intervention.
The meso-angioblast: a multipotent, self-renewing cell that originates from the dorsal aorta and differentiates into most mesodermal tissues (2002)

We have previously reported the origin of a class of skeletal myogenic cells from explants of dorsal aorta. This finding disagrees with the known origin of all skeletal muscle from somites and has therefore led us to investigate the in vivo origin of these cells and, moreover, whether their fate is restricted to skeletal muscle, as observed in vitro under the experimental conditions used. To address these issues, we grafted quail or mouse embryonic aorta into host chick embryos. Donor cells, initially incorporated into the host vessels, were later integrated into mesodermal tissues, including blood, cartilage, bone, smooth, skeletal and cardiac muscle. When expanded on a feeder layer of embryonic fibroblasts, the clonal progeny of a single cell from the mouse dorsal aorta acquired unlimited lifespan, expressed hemo-angioblastic markers (CD34, Flk1 and Kit) at both early and late passages, and maintained multipotency in culture or when transplanted into a chick embryo. We conclude that these newly identified vessel-associated stem cells, the meso-angioblasts, participate in postembryonic development of the mesoderm, and we speculate that postnatal mesodermal stem cells may be derived from a vascular developmental origin.
Floating-body effect free concave SOI-MOSFETs (COSMOS) (2002)

In order to overcome the degradation induced by floating body effects and to suppress the increase in parasitic source/drain resistances in thin-film silicon-on-insulator (SOI) MOSFETs, a concave SOI-MOSFET (COSMOS) is proposed. This structure realizes a partially thin-film SOI region, which is used as a fully depleted channel, and thick-film SOI regions, which are used as source/drain. The unique features of the COSMOS are found to be (1) elimination of the floating-body effects, (2) less short channel effect, (3) excellent subthreshold characteristics, and (4) reduction in parasitic source/drain resistances. >
Crystal structure of the human O6-alkylguanine-DNA alkyltransferase (2000)

The mutagenic and carcinogenic effects of simple alkylating agents are mainly due to O(6)-alkylation of guanine in DNA. This lesion results in transition mutations. In both prokaryotic and eukaryotic cells, repair is effected by direct reversal of the damage by a suicide protein, O(6)-alkylguanine-DNA alkyltransferase. The alkyltransferase removes the alkyl group to one of its own cysteine residues. However, this mechanism for preserving genomic integrity limits the effectiveness of certain alkylating anticancer agents. A high level of the alkyltransferase in many tumour cells renders them resistant to such drugs. Here we report the X-ray structure of the human alkyltransferase solved using the technique of multiple wavelength anomalous dispersion. This structure explains the markedly different specificities towards various O(6)-alkyl lesions and inhibitors when compared with the Escherichia coli protein (for which the structure has already been determined). It is also used to interpret the behaviour of certain mutant alkyltransferases to enhance biochemical understanding of the protein. Further examination of the various models proposed for DNA binding is also permitted. This structure may be useful for the design and refinement of drugs as chemoenhancers of alkylating agent chemotherapy.
Production of monocyte chemoattractant protein-1 by inflamed synovial tissue and cultured synoviocytes (1992)

This study analyzes the expression of monocyte chemoattractant protein-1 (MCP-1) by inflamed synovial tissue and defines its regulation in cultured synoviocytes. Synoviocytes from patients with rheumatoid arthritis and osteoarthritis express the 0.7-kb MCP-1 mRNA. Stimulation of synoviocytes with IL-1, TNF-alpha, LPS, platelet-derived growth factor, and transforming growth factor-beta-1, but not with basic fibroblast growth factor causes a marked increase in MCP-1 mRNA levels. Expression of the MCP-1 gene is inducible by activators of the protein kinase A (cAMP) and C (PMA) signal transduction pathways and is differentially regulated by the steroids dexamethasone and retinoic acid. Cultured synoviocytes de novo synthesize 12-, 15-, and 15.2-kDa MCP-1 proteins, which increase after stimulation with IL-1. Synovial tissues from donors without joint disease and from patients with rheumatoid or osteoarthritis were analyzed for MCP-1 mRNA expression by in situ hybridization. In these samples MCP-1 mRNA expressing cells were predominantly found in the sublining cell layers, whereas specimens of normal synovial tissue contained only few positive cells. These results identify synoviocytes as a source of MCP-1. Its expression is controlled by peptide regulatory factors that are known to be present in arthritic joints. Detection of cells producing MCP-1 mRNA in synovial tissues from patients with arthritis shows that this gene is expressed in vivo and suggests that MCP-1 can play a role in recruiting monocytes in joint inflammation.
Managing Strategic Challenges of Green Marketing - a Conceptual View (2009)

All types of consumers, both individual and industrial are becoming more concerned and aware about the natural environment. Unfortunately, a majority of people believes that green marketing refers solely to the promotion or advertising of products with environmental characteristics. Terms like Phosphate Free, Recyclable, Refillable, Ozone Friendly, and Environmentally Friendly are some of the things consumers most often associate with green marketing. While these terms are green marketing claims, in general green marketing is a much broader concept, one that can be applied to consumer goods, industrial goods and even services. For example, around the world there are resorts that are beginning to promote themselves as "Ecotourist" facilities, i.e., facilities that "specialize" in experiencing nature or operating in a fashion that minimizes their environmental impact. The issues pertaining to green marketing came into prominence in the late 1980s and early 1990s.
Ytterbium-doped fiber laser as pulsed source of narrowband amplified spontaneous emission (2019)

We report random noise pulsed regime of an ytterbium-doped fiber laser arranged in common Fabry-Perot configuration. We show that the laser output obeys the photon statistics inherent to narrowband amplified spontaneous emission and that the noise pulsing is properly addressed in terms of probability density and autocorrelation functions. Our novel approach reveals, in particular, that the regime's coherence time dramatically shortens, from few ns to tens ps, with increasing laser power.
Previously Infected and Recovered Chimpanzees Exhibit Rapid Responses That Control Hepatitis C Virus Replication upon Rechallenge (2002)

Responses in three chimpanzees were compared following challenge with a clonal hepatitis C virus (HCV) contained in plasma from an animal that had received infectious RNA transcripts. Two of the chimpanzees (Ch1552 and ChX0186) had recovered from a previous infection with HCV, while the third (Ch1605) was a naïve animal. All animals were challenged by reverse titration with decreasing dilutions of plasma and became serum RNA positive following challenge. Ch1605 displayed a typical disease profile for a chimpanzee. We observed increasing levels of serum RNA from week 1 postinoculation (p.i.), reaching a peak of 10(6) copies/ml at week 9 p.i., and alanine aminotransferase (ALT) elevations and seroconversion to HCV antibodies at week 10 p.i. In contrast, both Ch1552 and ChX0186 exhibited much shorter periods of viremia (4 weeks), low serum RNA levels (peak, 10(3) copies/ml), and minimal ALT elevations. A comparison of intrahepatic cytokine levels in Ch1552 and Ch1605 showed greater and earlier gamma interferon (IFN-gamma) and tumor necrosis factor alpha responses in the previously infected animal, responses that were 30-fold greater than baseline responses at week 4 p.i. for IFN-gamma in Ch1552 compared to 12-fold in Ch1605 at week 10 p.i. These data indicate (i) that clonal HCV generated from an infectious RNA transcript will lead to a typical HCV infection in naïve chimpanzees, (ii) that there are memory immune responses in recovered chimpanzees that control HCV infection upon rechallenge, and (iii) that these responses seem to be T-cell mediated, as none of the animals had detectable antibody against the HCV envelope glycoproteins. These observations have encouraging implications for the development of a vaccine for HCV.
A new symmetric scanning tunneling microscope design (1988)

A new scanning tunneling microscope (STM) where the traditional xyz tripod is replaced with a central post activated by three symmetrically arranged piezo elements has been built. The sample and the tip are mounted in two easily exchangeable snap-in mounted holders, both accessible from the same side and with one single tool. The sample stage is activated by three differential screws corresponding to the same coordinate axes as the piezo elements. The STM is mounted on a single UHV flange and will fit into a 4-in.-diam vacuum chamber.
Increased myocardial collagen and ventricular diastolic dysfunction in relaxin deficient mice: a gender-specific phenotype (2003)

Male Rlx(-/-) mice had impeded LV diastolic filling and increased atrial weights, most likely due to an increase in ventricular collagen content and chamber stiffness. These phenotypes in the Rlx(-/-) males were not observed in Rlx(-/-) females, indicating the importance of other gender-related factors in cardiovascular function.
Using a liquid emulsion membrane system for the encapsulation of organic and inorganic substrates within inorganic microcapsules (2002)

We report the development of a novel technique for the encapsulation of molecular and condensed organic and inorganic substrates within hollow calcium carbonate microspheres; the process utilises precipitation at the oil-water interface of a pseudovesicular water-in-oil-in-water emulsion liquid membrane (ELM) system in order to create an inorganic shell around the pre-dispersed media.
Experimental surgery to create subgenomes of Bacillus subtilis  168 (1997)

The 4,188-kb circular genome of Bacillus subtilis 168 was artificially dissected into two stable circular chromosomes in vivo, one being the 3,878-kb main genome and the other the 310-kb subgenome that was recovered as covalently closed circular DNA in CsCl-ethidium bromide ultracentrifugation. The minimal requirements to physically separate the 310-kb DNA segment out of the genome were two interrepeat homologous sequences and an origin of DNA replication between them. The subgenome originated from the 1,255-1, 551-kb region of the B. subtilis genome was essential for the cell to survive because the subgenome was not lost from the cell. The finding that the B. subtilis genome has a potential to be divided and the resulting two replicons stably maintained may shed light on origins and formation mechanisms of giant plasmids or second chromosomes present in many bacteria. Similar excision or its reversal process, i.e., integration of large sized covalently closed circular DNA pieces into the main genome, implies significant roles of subgenomes in the exchange of genetic information and size variation of bacterial genomes in bacterial evolution.
KvLQT1, a voltage-gated potassium channel responsible for human cardiac arrhythmias (1997)

The clinical features of long QT syndrome result from episodic life-threatening cardiac arrhythmias, specifically the polymorphic ventricular tachycardia torsades de pointes. KVLQT1 has been established as the human chromosome 11-linked gene responsible for more than 50% of inherited long QT syndrome. Here we describe the cloning of a full-length KVLQT1 cDNA and its functional expression. KVLQT1 encodes a 676-amino acid polypeptide with structural characteristics similar to voltage-gated potassium channels. Expression of KvLQT1 in Xenopus oocytes and in human embryonic kidney cells elicits a rapidly activating, K+-selective outward current. The I(Kr)-specific blockers, E-4031 and dofetilide, do not inhibit KvLQT1, whereas clofilium, a class III antiarrhythmic agent with the propensity to induce torsades de pointes, substantially inhibits the current. Elevation of cAMP levels in oocytes nearly doubles the amplitude of KvLQT1 currents. Coexpression of minK with KvLQT1 results in a conductance with pharmacological and biophysical properties more similar to I(Ks) than other known delayed rectifier K+ currents in the heart.
The role and significance of lymphocyte activation gene-3 in malignant tumor (2013)

The lymphocyte activation gene-3 (LAG-3),an important negative costimulatory molecule of the immunoglobulin super family,is expressed primarily on activated T cells and NK T cells.LAG-3 negatively regulates activated T cell proliferation,function,and the maintenance of lymphocyte homeostasis by its MHC Ⅱ ligand.LAG-3,is abnormally expressed in the mouse model and a variety of tumor microenvironment and is closely related to clinicopathological parameters and prognosis.Thus,LAG-3 plays an important role in the regulation of tumor immune response.Interfering and blocking LAG-3/MHC-Ⅱ signaling pathway may provide new ideas for tumor immunotherapy.

Key words: 
Lymphocyte activation gene;  T cells;  Dendratic cells;  Tumor immunity
Towards semantically meaningful feature spaces for the characterization of video content (2002)

Efficient procedures for browsing, filtering, sorting or retrieving pictorial content require accurate content characterization. Of particular interest are representations based on semantically meaningful feature spaces, capable of capturing properties such as violence, sex or profanity. In this work we report on a first step towards this goal, the design of a stochastic model for video editing which provides a transformation from the image space to a low-dimensional feature space where categorization by degree of action can be easily accomplished.