gebhart/patrepeval huggingface dataset:
A fast statistical mixture algorithm for on-line handwriting recognition (1994)

The automatic recognition of online handwriting is considered from an information theoretic viewpoint. Emphasis is placed on the recognition of unconstrained handwriting, a general combination of cursively written word fragments and discretely written characters. Existing recognition algorithms, such as elastic matching, are severely challenged by the variability inherent in unconstrained handwriting. This motivates the development of a probabilistic framework suitable for the derivation of a fast statistical mixture algorithm. This algorithm exhibits about the same degree of complexity as elastic matching, while being more flexible and potentially more robust. The approach relies on a novel front-end processor that, unlike conventional character or stroke-based processing, articulates around a small elementary unit of handwriting called a frame. The algorithm is based on (1) producing feature vectors representing each frame in one (or several) feature spaces, (2) Gaussian K-means clustering in these spaces, and (3) mixture modeling, taking into account the contributions of all relevant clusters in each space. The approach is illustrated by a simple task involving an 81-character alphabet. Both writer-dependent and writer-independent recognition results are found to be competitive with their elastic matching counterparts.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Influence of microwaves on different types of receptors and the role of peroxidation of lipids on receptor‐protein shedding (1994)

The effects of a continuous wave or pulse-modulated, 900 MHz microwave field were studied by in vitro assays of rat chemoreceptors. The pulsed field was modulated as rectangular waves at rates of 1, 6, 16, 32, 75, or 100 pps. The pulse-period to pulse-duration ratio was 5 in all cases, and specific absorption rates (SARs) ranged from 0.5 to 18 W/kg. Binding of ligands to cell membranes was differentially affected by exposure to microwaves. For example, binding of H3-glutamic acid to hippocampal cells was not altered by a 15 min exposure to a continuous wave field at 1 W/kg, but binding of H3-dihydroalprenolol to liver-cell membranes of neonates underwent a fivefold decrease under the same field conditions. This effect was not dependent on modulation or on a change in the constant of stimulus-receptor binding but depended on a shedding of the membrane's receptor elements into solution. The magnitude of inhibition correlated with the oxygen concentration in the exposed suspension. Antioxidants (dithiothreitol and ionol) inhibited the shedding of receptor elements. The microwave exposure did not cause an accumulation of products from the peroxidation of lipids (POL). Ascorbate-dependent or non-enzymatic POL was not responsible for the inhibition, and POL was not found in other model systems. However, enzymatic POL mechanisms in localized areas of receptor binding remain a possibility.
Pathogenicity and immunogenicity of Listeria monocytogenes small-plaque mutants defective for intracellular growth and cell-to-cell spread (1992)

Listeria monocytogenes strains previously generated by transposon mutagenesis were examined with respect to virulence and induction of protective immunity in BALB/c mice. The phenotypic defects observed in these mutant L. monocytogenes strains included decreased hemolysin (listeriolysin O [LLO]) production, phospholipase C activity, intracellular growth, and/or cell-to-cell spread in vitro. While 50% lethal dose determinations performed with these mutant strains indicated reduced virulence for BALB/c mice, sublethal infection with the majority of these mutant strains provided protection against a subsequent challenge with the fully virulent L. monocytogenes parent strain. In addition, in vitro infection of the J774 cell line with most of these mutant strains converted these phagocytic cells to targets of L. monocytogenes-immune cytotoxic cells. The exceptions to these findings were two LLO-negative, avirulent mutant strains which were unable to immunize mice against a secondary challenge with virulent L. monocytogenes. One of these mutants contained a transposon insertion within the structural gene for LLO, and the other contained a transposon insertion in the structural gene for the transcriptional activator of the LLO gene. These two LLO-negative mutant strains also were unable to escape phagolysosomes in infected J774 cells and could not transform these phagocytic cells into targets of L. monocytogenes-immune cytotoxic cells. These findings confirm the importance of LLO in the induction of antilisterial immunity and suggest that a cytoplasmic localization of these pathogenic bacteria is required for the development of protective immunity.
Novel Insulin Promoter- and Enhancer-Binding Proteins That Discriminate between Pancreatic α- and β-Cells (1991)

In the mouse insulin is first detected on embryonic day 12 (e12) in a subpopulation of the cells that on e10 start to produce glucagon. During the continued embryonic development, the number of cells that coexpress the two hormones is gradually decreased, and in adults the expression of these two hormone genes is segregated to the beta- and alpha-cells. To begin to understand the process of terminal differentiation that restricts insulin gene expression to beta-cells, we have assayed for the presence of nuclear proteins that interact with transcriptional regulatory sequences of the rat insulin I gene in pancreatic alpha- and beta-cell lines. All except one of the previously identified insulin enhancer-binding proteins were found to be present in both cell types. A new insulin promoter-binding protein, IPF1, which was present in beta-cells but absent in alpha-cells, was identified. The beta-cell specificity of IPF1 implies that the insulin promoter is involved in the restriction of insulin gene expression to the beta-cells. The binding sites for IPF1 and the beta-cell-specific enhancer-binding protein IEF2 are both recognized by the previously isolated homeodomain-containing LIM protein isl-1, but these three proteins were all shown to be different entities.
Convection-enhanced delivery for the treatment of brain tumors (2009)

The brain is highly accessible for nutrients and oxygen, however delivery of drugs to malignant brain tumors is a very challenging task. Convection-enhanced delivery (CED) has been designed to overcome some of the difficulties so that pharmacological agents that would not normally cross the BBB can be used for treatment. Drugs are delivered through one to several catheters placed stereotactically directly within the tumor mass or around the tumor or the resection cavity. Several classes of drugs are amenable to this technology including standard chemotherapeutics or novel experimental targeted drugs. The first Phase III trial for CED-delivered, molecularly targeted cytotoxin in the treatment of recurrent glioblastoma multiforme has been accomplished and demonstrated objective clinical efficacy. The lessons learned from more than a decade of attempts at exploiting CED for brain cancer treatment weigh critically for its future clinical applications. The main issues center around the type of catheters used, number of catheters and their exact placement; pharmacological formulation of drugs, prescreening patients undergoing treatment and monitoring the distribution of drugs in tumors and the tumor-infiltrated brain. It is expected that optimizing CED will make this technology a permanent addition to clinical management of brain malignancies.
Fibrinogen Binds to Integrin 5 1via the Carboxyl-Terminal RGD Site of the A -Chain (2000)

Fibrinogen interactions with vascular endothelial cells are implicated in various physiological and pathophysiological events, including angiogenesis and wound healing. We have shown previously that integrin alpha(5)beta(1) is a fibrinogen receptor on endothelial cells [Suehiro, K., Gailit, J., and Plow, E.F. (1997) J. Biol. Chem. 272, 5360-5366]. In the present study, we have characterized fibrinogen interactions with purified alpha(5)beta(1) and have identified the recognition sequence in fibrinogen for alpha(5)beta(1). The binding of fibrinogen to immobilized alpha(5)beta(1) was selectively supported by Mn(2+). Fibrinogen bound to purified alpha(5)beta(1) in a time-dependent, specific, and saturable manner in the presence of Mn(2+), and the binding was blocked completely by Arg-Gly-Asp (RGD)-containing peptides and by anti-alpha(5) and anti-alpha(5)beta(1) monoclonal antibodies. A monoclonal antibody directed to the C-terminal RGD sequence at Aalpha572-574 significantly inhibited the binding of fibrinogen to alpha(5)beta(1), whereas monoclonal antibodies directed to either the N-terminal RGD sequence at Aalpha95-97 or the C-terminus of the gamma-chain did not. Furthermore, substituting RGE for RGD at position Aalpha95-97 in recombinant fibrinogen had a minimal effect on binding, whereas substituting RGE for RGD at position Aalpha572-574 decreased binding by 90%. These results demonstrate that the C-terminal RGD sequence at Aalpha572-574 is required for the interaction of fibrinogen with alpha(5)beta(1).
Mechanism of action of the anticonvulsant felbamate: Opposing effects on N‐methyl‐D‐aspartate and γ‐aminobutyric acidA receptors (1994)

Felbamate is a promising new antiepileptic drug whose mechanism of action is unknown. In whole-cell voltage clamp recordings from cultured rat hippocampal neurons, clinically relevant concentrations of felbamate (0.1-3 mM) inhibited N-methyl-D-aspartate (NMDA) responses and potentiated gamma-aminobutyric acid (GABA) responses. Single-channel recordings indicated that the effect on NMDA responses occurred via a channel blocking mechanism. Felbamate is the first anticonvulsant drug with dual actions on excitatory (NMDA) and inhibitory (GABA) brain mechanisms. This unique combination of effects could account for felbamate's broad spectrum of anticonvulsant activity in animal seizure models and its distinctive clinical efficacy and safety profile.
The proliferative effect of estradiol on human prostate stromal cells is mediated through activation of ERK (2008)

The results indicated that estrogen could activate ERK pathway through the non-genomic ERalpha pathway, leading to proliferation of PrSCs.
Interleukin-6 Regulates Androgen Synthesis in Prostate Cancer Cells (2009)

These results suggest that IL-6 increases levels of intracrine androgens through enhanced expression of genes mediating androgen metabolism in prostate cancer cells.
Chemical vectors for gene delivery: a current review on polymers, peptides and lipids containing histidine or imidazole as nucleic acids carriers (2009)

DNA/cationic lipid (lipoplexes), DNA/cationic polymer (polyplexes) and DNA/cationic polymer/cationic lipid (lipopolyplexes) electrostatic complexes are proposed as non-viral nucleic acids delivery systems. These DNA-nanoparticles are taken up by the cells through endocytosis processes, but the low capacity of DNA to escape from endosomes is regarded as the major limitations of their transfection efficiency. Here, we present a current report on a particular class of carriers including the polymers, peptides and lipids, which is based on the exploitation of the imidazole ring as an endosome destabilization device to favour the nucleic acids delivery in the cytosol. The imidazole ring of histidine is a weak base that has the ability to acquire a cationic charge when the pH of the environment drops bellow 6. As it has been demonstrated for poly(histidine), this phenomena can induce membrane fusion and/or membrane permeation in an acidic medium. Moreover, the accumulation of histidine residues inside acidic vesicles can induce a proton sponge effect, which increases their osmolarity and their swelling. The proof of concept has been shown with polylysine partially substituted with histidine residues that has caused a dramatic increase by 3-4.5 orders of magnitude of the transfection efficiency of DNA/polylysine polyplexes. Then, several histidine-rich polymers and peptides as well as lipids with imidazole, imidazolinium or imidazolium polar head have been reported to be efficient carriers to deliver nucleic acids including genes, mRNA or SiRNA in vitro and in vivo. More remarkable, histidylated carriers are often weakly cytotoxic, making them promising chemical vectors for nucleic acids delivery.
Generation of Dwarf Goat (Capra hircus) Clones Following Nuclear Transfer with Transfected and Nontransfected Fetal Fibroblasts and In Vitro-Matured Oocytes1 (2001)

The developmental potential of caprine fetal fibroblast nuclei after in vitro transfection and nuclear transfer (NT) into enucleated, in vitro-matured oocytes was evaluated. Fetal fibroblasts were isolated from Day 27 to Day 30 fetuses from a dwarf breed of goat (BELE: breed early lactate early). Cells were transfected with constructs containing the enhanced green fluorescent protein (eGFP) and neomycin resistance genes and were selected with G418. Three eGFP lines and one nontransfected line were used as donor cells in NT. Donor cells were cultured in Dulbecco minimum Eagle medium plus 0.5% fetal calf serum for 4-8 days prior to use in NT. Immature oocytes were recovered by laparoscopic ovum pick-up and matured for 24 h prior to enucleation and NT. Reconstructed embryos were transferred as cleaved embryos into synchronized recipients. A total of 27 embryos derived from transgenic cells and 70 embryos derived from nontransgenic cells were transferred into 13 recipients. Five recipients (38%) were confirmed pregnant at Day 35 by ultrasound. Of these, four recipients delivered five male kids (7.1% of embryos transferred) derived from the nontransfected line. One recipient delivered a female kid derived from an eGFP line (7.7% of embryos transferred for that cell line). Presence of the eGFP transgene was confirmed by polymerase chain reaction, Southern blotting, and fluorescent in situ hybridization analyses. Nuclear transfer derivation from the donor cells was confirmed by single-strand confirmation polymorphism analysis. These results demonstrate that both in vitro-transfected and nontransfected caprine fetal fibroblasts can direct full-term development following NT.
Somatic Mutations in BRCA1 and BRCA2 Could Expand the Number of Patients That Benefit From Poly (ADP Ribose) Polymerase Inhibitors in Ovarian Cancer (2010)

BRCA(1/2) somatic and germline mutations and expression loss are sufficiently common in ovarian cancer to warrant assessment for prediction of benefit in clinical trials of PARP1 inhibitors.
The conformation of loop E of eukaryotic 5S ribosomal RNA (1993)

The solution structure of a 27-nucleotide duplex, including the internal loop E from Xenopus laevis 5S ribosomal RNA, has been studied by two-dimensional NMR spectroscopy, followed by restrained molecular dynamics. The highly conserved internal loop closes to form a G.A base pair and a reverse-Hoogsteen A.U base pair. Extensive interstrand stacking between these uncommon base pairs provides a structural explanation for an interstrand ultraviolet-induced cross-link. A guanosine residue is bulged into the major groove and may form a base-triple with the adjacent reverse-Hoogsteen A.U pair. The structure of the less highly-conserved portion of the loop is less well-defined by the NMR data. A single-nucleotide deletion mutant has a very different, open conformation without mismatched base pairs [Varani, G., Wimberly, B., & Tinoco, I. Jr. (1989) Biochemistry 28, 7760-7772]. The implications of the structure for binding of the transcription factor TFIIIA and the cytotoxin alpha-sarcin are discussed.
Purification and physicochemical characterization of a human cytotoxic factor produced by a human haemic cell line (1981)

A cytotoxic factor, produced by a human lymphoblastoid cell line [Karpas (1977) Br. J. Cancer 35, 152--160; Karpas (1977) Br. J. Cancer 36, 437--445], was purified both from the cell extracts and from the culture medium containing the cell lysate, by using ammonium sulphate precipitation, DEAE-cellulose chromatography, gel filtration and affinity chromatography on concanavalin A--Sepharose and on [3H]amino-ethanol--glass beads. Two factors, Factor I and Factor II, were separated by DEAE-cellulose chromatography. Factor I was eluted from this column at 30 mM-aminoethanol/HCl buffer, pH 8.0, whereas Factor II was bound strongly to DEAE-cellulose and was eluted only at 325 mM-aminoethanol/HCl buffer, pH 8.0. The purified Factor I migrated as a single band on polyacrylamide-gel electrophoresis. Its isoelectric point, pI, was 8.0 +/- 0.3. Its sedimentation coefficient, S20,w, was 3.5 +/- 0.1 S and its apparent molecular weight, Mr, was 65 000 +/- 1000 as determined by sedimentation-velocity and sedimentation-equilibrium measurements. A linear relationship between molecular weight and concentration was found in equilibrium runs, suggesting a non-spherical shape of the molecule. Factor I is not a glycoprotein, inasmuch as it does not bind to concanavalin A--Sepharose. It consists of two subunits (Mr 32 000 +/- 4000), migrating on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis as a single band. Factor II had pI 6.0 +/- 0.4 and Mr 75 000 +/- 3000. Factors I and II are thus different proteins.
Functional regions of the cauliflower mosaic virus 35S RNA promoter determined by use of the firefly luciferase gene as a reporter of promoter activity (1987)

The cauliflower mosaic virus (CaMV) 35S RNA promoter has been dissected and examined in a transient expression system using the firefly luciferase gene as a reporter of promoter activity. Deletion analysis has shown that the 35S RNA promoter is composed of at least three regions-distal, medial, and proximal-which are essential for activity. The distal region contains three smaller elements homologous to the simian virus 40 "core" enhancer element, the medial region possesses a CCAAT-like box, and the proximal region contains a TATA box. A DNA segment encompassing the distal region is capable of activating the CaMV 35S core promoter in an orientation-independent, but not position-independent, fashion. The distal region can also activate a heterologous weak promoter, the CaMV 19S RNA promoter, albeit not to the high levels of the 35S RNA promoter. Multimers of the distal region are able to activate the 35S RNA promoter core to even greater levels of expression than the native 35S promoter. These experiments demonstrate that elements outside the boundaries of the core promoter (composed of proximal and medial elements) are recognized in a plant cell transient expression system.
Two proline porters in Escherichia coli K-12 (1983)

Escherichia coli mutants defective at putP and putA lack proline transport via proline porter I and proline dehydrogenase activity, respectively. They retain a proline uptake system (proline porter II) that is induced during tryptophan-limited growth and are sensitive to the toxic L-proline analog, 3,4-dehydroproline. 3,4-Dehydroproline-resistant mutants derived from a putP putA mutant lack proline porter II. Auxotrophic derivatives derived from putP+ or putP bacteria can grow if provided with proline at low concentration (25 microM); those derived from the 3,4-dehydroproline-resistant mutants require high proline for growth (2.5 mM). We conclude that E. coli, like Salmonella typhimurium, possesses a second proline porter that is inactivated by mutations at the proP locus.
Molecular mechanisms involved in the regulation of the endothelial nitric oxide synthase (2003)

The endothelial nitric oxide synthase (eNOS), the expression of which is regulated by a range of transcriptional and posttranscriptional mechanisms, generates nitric oxide (NO) in response to a number of stimuli. The physiologically most important determinants for the continuous generation of NO and thus the regulation of local blood flow are fluid shear stress and pulsatile stretch. Although eNOS activity is coupled to changes in endothelial cell Ca(2+) levels, an increase in Ca(2+) alone is not sufficient to affect enzyme activity because the binding of calmodulin (CaM) and the flow of electrons from the reductase to the oxygenase domain of the enzyme is dependent on protein phosphorylation and dephosphorylation. Two amino acids seem to be particularly important in regulating eNOS activity and these are a serine residue in the reductase domain (Ser(1177)) and a threonine residue (Thr(495)) located within the CaM-binding domain. Simultaneous alterations in the phosphorylation of Ser(1177) and Thr(495) in response to a variety of stimuli are regulated by a number of kinases and phosphatases that continuously associate with and dissociate from the eNOS signaling complex. eNOS associated proteins, such as caveolin, heat shock protein 90, eNOS interacting protein, and possibly also motor proteins provide the scaffold for the formation of the protein complex as well as its intracellular localization.
Effect of Some Materials on the Content of Nitrate, Nitrite and Vitamin C in Kimchi during Fermentation (1989)

This study was intended to observe the changes of the nitrate, nitrite and vitamin C content during the fermentation of Kimchies by some added materials. Eight different types of Kimchi, were prepared with chinese cabbage and seasonings, to which added respectively materials such as soused anchovy, soused shrimp, garlic, mustard leaf, K-sorbate, ascorbic acid, radish. After they were prefermented at for 24 hours, stored 35 days at . Generally optimal maturity of Kimchi showed pH 4.4 to 4.6, lactic acid content 0.3 to 0.4% at salt content belows 2.5%. The content of total vitamin C in Kimchies was approximately 19.8-24.7 mg/100g at the initial stage of fermentation and then slightly decreased. When the process of the fermentation was active, the content of total vitamin C increased up to the same level or higher than that of the initial stage and then gradually decreased. In the case of Kimchi which added garlic, the content of vitamin C was relatively higher then the other samples. In the initial stage of fermentation, the nitrate and nitrite content in the Kimchi which added garlic and raddish were relatively higher than other samples. Nitrate content reached its minimum by the 21st day, at that time content was 290-342 ppm. At this time, the nitrite was not detected and total vitamin C content in all samples decreased.
Transition of T cell receptor gamma/delta expressing double negative (CD4-/CD8-) lymphocytes after allogeneic bone marrow transplantation. (1994)

We studied peripheral blood CD4-CD8- gamma/delta T cells in recipients of allogeneic marrow grafts, using three-color immunofluorescence and flow cytometry, and investigated changes in their numbers in relation to the administration of hematopoietic growth factors or chronic graft-versus-host disease (GVHD). In the early post-bone marrow transplantation (BMT) period, the relative and absolute numbers of peripheral CD4-CD8- gamma/delta T cells in 22 allogeneic marrow graft recipients in relation to the use of hematopoietic growth factors were studied. During the first 4 weeks, increased numbers of CD4-CD8- gamma/delta T cells were observed in recipients of either recombinant human granulocyte colony-stimulating factor (rhG-CSF) or granulocyte macrophage colony-stimulating factor (GM-CSF). However, 4-8 weeks after BMT, the number of these cells was similar in both groups whether or not growth factors had been administered. At a later stage after BMT (3-12 months), peripheral CD4-CD8- gamma/delta T cells from 43 allogeneic BMT recipients were studied. These cells were markedly decreased in patients with chronic GVHD, and this decrease correlated closely with the clinical signs of chronic GVHD. These results suggest that CD4-CD8- gamma/delta T cells may play an important role in the recovery of neutrophils associated with growth factors during the very early post-BMT period, and in the immunodeficient state of chronic GVHD at a later stage after BMT.