gebhart/patrepeval huggingface dataset:
Epstein Barr virus binding induces internalization of the C3d receptor: a novel immunotoxin delivery system. (1986)

Epstein Barr virus (EBV) infection of human B lymphocytes is initiated by selective binding of the virus to the C3d receptor (EBV/C3d receptor) on the cell surface and results in polyclonal proliferation of infected cells. In these studies we examined the fate of the EBV/C3d receptor during viral infection by using an immunotoxin made from a monoclonal antibody (HB5) reactive with the receptor and the potent toxin, gelonin. Binding of the HB5-gelonin conjugate to the EBV/C3d receptor before EBV infection (at concentrations as low as 10(-11) M) significantly inhibited the subsequent polyclonal proliferation of virus-infected B lymphocytes. HB5 antibody and gelonin alone did not inhibit proliferation. Because internalization of gelonin-antibody conjugates is required to cause cytotoxicity, these results indicate that infection of B lymphocytes with EBV selectively induced endocytosis of the EBV/C3d receptor with concomitant internalization of the immunotoxin. Proliferation of B lymphocytes that were activated by prior infection with EBV, or activated by cross-linking of their surface immunoglobulin molecules, was not inhibited by the antibody-toxin conjugate even at concentrations as high as 10(-7) M. Also, the growth of B lymphoblastoid cell lines cultured in the presence or absence of infectious EBV was not inhibited by HB5-gelonin. Thus, our results suggest that the EBV/C3d receptor is internalized only during the infection of normal B lymphocytes by EBV, with co-internalization of immunotoxin, and indicate that internalization of the EBV/C3d receptor-immunotoxin complex does not occur simply as a consequence of activation and proliferation of B lymphocytes. The use of a ligand to induce endocytosis of its receptor offers a new strategy for the selective delivery of immunotoxins to cells and may be more generally applicable.
Current treatment of pulmonary embolism (2007)

Pulmonary embolism is a common disease. Because mortality of untreated disease is high therapy with anticoagulants need to be started as soon as diagnosis is confirmed. Standard treatment of patients with hemodynamically stable pulmonary embolism consists of initial treatment with unfractionated heparin or low-molecular weight heparin, as well as treatment with vitamin K antagonists during a period depending on variable risk factors. Home treatment of pulmonary embolism is often suitable. Instable patients are treated with fibrinolytics. Bleeding is not only the main side effect of anticoagulants but also a reason to search for alternatives. .
Paired MEG data set source localization using recursively applied and projected (RAP) MUSIC (2000)

An important class of experiments in functional brain mapping involves collecting pairs of data corresponding to separate "Task" and "Control" conditions. The data are then analyzed to determine what activity occurs during the Task experiment but not in the Control. Here we describe a new method for processing paired magnetoencephalographic (MEG) data sets using our recursively applied and projected multiple signal classification (RAP-MUSIC) algorithm. In this method the signal subspace of the Task data is projected against the orthogonal complement of the Control data signal subspace to obtain a subspace which describes spatial activity unique to the Task. A RAP-MUSIC localization search is then performed on this projected data to localize the sources which are active in the Task but not in the Control data. In addition to dipolar sources, effective blocking of more complex sources, e.g., multiple synchronously activated dipoles or synchronously activated distributed source activity, is possible since these topographies are well-described by the Control data signal subspace. Unlike previously published methods, the proposed method is shown to be effective in situations where the time series associated with Control and Task activity possess significant cross correlation. The method also allows for straightforward determination of the estimated time series of the localized target sources. A multiepoch MEG simulation and a phantom experiment are presented to demonstrate the ability of this method to successfully identify sources and their time series in the Task data.
Serine-to-alanine substitutions at the amino-terminal region of phytochrome A result in an increase in biological activity. (1992)

We have used a tobacco transgenic plant system to assay the structure/function relationship of phytochrome A (phyA), a plant photoreceptor. The amino terminus of phyA from different plant species is very rich in serine residues. To investigate whether these serine residues are required for phytochrome function, the first 10 serine codons encoding amino acid residues 2-4, 10-14, 19, and 20 in the amino-terminal domain of the rice phyA gene (phyA) were changed to alanine codons. The mutant (S/A phyA), as well as the wild-type phyA cDNA, was placed under the control of the 35S promoter, and the chimeric genes were transferred into the tobacco genome by Agrobacterium-mediated transformation. Transgenic tobacco plants expressing either wild-type or S/A phyA showed similar phenotypic alterations, including dwarfism and dark-green leaves. However, hypocotyl elongation experiments revealed that transgenic seedlings expressing S/A phyA showed a higher amplitude of the red light response with respect to the inhibition of hypocotyl elongation. The observed difference is not correlated with expression levels of the transgene. The chromophore is attached to the mutant phyA apoprotein (PHY A), and the mutant photoreceptor is photoreversible, giving a difference spectrum indistinguishable from that of the rice phyA. Our results indicate that the S/A mutant has a higher biological activity as compared with the wild-type rice phyA.
A Speech Parameter Generation Algorithm Considering Global Variance for HMM-Based Speech Synthesis (2007)

This paper describes a novel parameter generation algorithm for an HMM-based speech synthesis technique. The conventional algorithm generates a parameter trajectory of static features that maximizes the likelihood of a given HMM for the parameter sequence consisting of the static and dynamic features under an explicit constraint between those two features. The generated trajectory is often excessively smoothed due to the statistical processing. Using the over-smoothed speech parameters usually causes muffled sounds. In order to alleviate the over-smoothing effect, we propose a generation algorithm considering not only the HMM likelihood maximized in the conventional algorithm but also a likelihood for a global variance (GV) of the generated trajectory. The latter likelihood works as a penalty for the over-smoothing, i.e., a reduction of the GV of the generated trajectory. The result of a perceptual evaluation demonstrates that the proposed algorithm causes considerably large improvements in the naturalness of synthetic speech.
Cross-sectional multicenter study of patients with urea cycle disorders in the United States (2008)

Inherited urea cycle disorders comprise eight disorders (UCD), each caused by a deficiency of one of the proteins that is essential for ureagenesis. We report on a cross-sectional investigation to determine clinical and laboratory characteristics of patients with UCD in the United States. The data used for the analysis was collected at the time of enrollment of individuals with inherited UCD into a longitudinal observation study. The study has been conducted by the Urea Cycle Disorders Consortium within the Rare Diseases Clinical Research Network (RDCRN) funded by the National Institutes of Health. One-hundred eighty-three patients were enrolled into the study. Ornithine transcarbamylase (OTC) deficiency was the most frequent disorder (55%), followed by argininosuccinic aciduria (16%) and citrullinemia (14%). Seventy-nine percent of the participants were white (16% Latinos), and 6% were African American. Intellectual and developmental disabilities were reported in 39% with learning disabilities (35%) and half had abnormal neurological examination. Sixty-three percent were on a protein restricted diet, 37% were on Na-phenylbutyrate and 5% were on Na-benzoate. Forty-five percent of OTC deficient patients were on L-citrulline, while most patients with citrullinemia (58%) and argininosuccinic aciduria (79%) were on L-arginine. Plasma levels of branched-chain amino acids were reduced in patients treated with ammonia scavenger drugs. Plasma glutamine levels were higher in proximal UCD and in neonatal type disease. The RDCRN allows comprehensive analyses of rare inherited UCD, their frequencies and current medical practices.
Solving the Input/Output Problem for Planar Mechanisms (1999)

This paper presents a method for solving the input/output problem for all planar mechanisms composed of revolute and slider joints. The solution procedure is a modification of the Dixon resultant method, which was developed to solve sets of polynomial equations; in this paper the method is applied to sets of equations which are linear in the sines and cosines of unknown angles. A particular planar multicircuit mechanism is analyzed to illustrate the solution procedure, and implementation details are discussed.
Japanese Encephalitis Immunization in South Korea: Past, Present, and Future (2000)

Japanese encephalitis (JE), once a major public health problem in South Korea, has declined since the 1980s, as a result of improved living conditions, a mosquito eradication program, and a national JE vaccination program, which includes annual booster vaccine for all children less than or equal to 15 years of age. Increased immunity has greatly reduced illness and death; however, vaccine adverse effects are increasing, and a National Compensation Program for Vaccine Injury was begun in 1995. This article reviews past successes, current problems, and future direction of the JE vaccination program in South Korea.
Interleukin-13 receptor alpha2 chain in human head and neck cancer serves as a unique diagnostic marker. (2003)

Previous studies have demonstrated that approximately 30% of squamous cell carcinoma of the head and neck (SCCHN) cell lines express high levels of interleukin-13 receptor(s) (IL-13R). However, the incidence, expression level, and significance of IL-13R expression in human tumor specimens is not known. In addition, it is not known whether normal head and neck tissues express IL-13R. In this study, we evaluated the expression of IL-13R subunits (IL-13Ralpha1, IL-13Ralpha2, and IL-4Ralpha) in 337 surgically excised specimens of SCCHN and normal head and neck tissues. Specimens were obtained from 139 patients with SCCHN and 16 patients with benign tonsil disorders from two centers in the United States and Japan and evaluated with immunohistochemistry and in situ hybridization. Extensive analysis demonstrated that the majority of SCCHN tumors uniformly expressed low levels of IL-13Ralpha1 chain; however, 77% of the tumors expressed moderate to high levels of IL-4Ralpha, which forms a signaling complex with IL-13Ralpha1 chain. On the other hand, 33% of SCCHN tumors expressed moderate to high levels of IL-13Ralpha2 chain. Using tissue array from 99 patients, we observed that the expression levels of IL-13Ralpha2 and IL-4Ralpha were significantly higher in SCCHN than in normal head and neck tissues (P < 0.005). Detailed analysis of clinicopathological features demonstrated a positive statistically significant correlation between IL-13Ralpha2 expression and clinically advanced primary SCCHN tumor (T(4); Tumor-Node-Metastasis classification; P < 0.05). However, there was no correlation among IL-13R expression and sex, age of patients, stage of lymph node metastasis, squamous cell carcinoma grade, or allergic history. Taken together, this study suggests that IL-13R may be involved in SCCHN tumor progression, and 33% of IL-13Ralpha2-positive SCCHN cases may be targeted by IL-13 cytotoxin and IL-13R-targeted agent.
Antisense Properties of Duplex- and Triplex-Forming PNAs (1996)

The potential of peptide nucleic acids (PNAs) as specific inhibitors of translation has been studied. PNAs with a mixed purine/pyrimidine sequence form duplexes, while homopyrimidine PNAs form (PNA)2/RNA triplexes with complementary sequences on RNA. We show here that neither of these PNA/RNA structures are substrates for RNase H. Translation experiments in cell-free extracts showed that a 15mer duplex-forming PNA blocked translation in a dose-dependent manner when the target was 5'-proximal to the AUG start codon on the RNA, whereas similar 10-, 15- or 20mer PNAs had no effect when targeted towards sequences in the coding region. Triplex-forming 10mer PNAs were efficient and specific antisense agents with a target overlapping the AUG start codon and caused arrest of ribosome elongation with a target positioned in the coding region of the mRNA. Furthermore, translation could be blocked with a 6mer bisPNA or with a clamp PNA, forming partly a triplex, partly a duplex, with its target sequence in the coding region of the mRNA.
The European Working Time Directive (2005)

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Characterization of estrogen responsive transforming activity in human breast cancer cell lines. (1986)

We have characterized the production of transforming growth factor (TGF) activities by five human breast cancer cell lines in culture. The presence of TGF-alpha and -beta activity in medium conditioned by these cells was detected by induction of anchorage-independent colony formation of normal rat kidney cells in soft agar and by epidermal growth factor and TGF-beta receptor competition studies. In MCF-7, an estrogen-receptor positive cell line which requires estrogen for tumorigenesis in vivo, 17 beta-estradiol induced a 2-5-fold increase in a TGF-alpha-like activity (apparent molecular weight, 68,000 and 30,000 by column chromatography). An estrogen induction of lower magnitude (1.5-2.5-fold) was also seen in two other estrogen responsive cell lines, ZR-75-B and T47D. TGF-beta was not induced by 17 beta-estradiol in any of the three cell lines and was decreased by up to 50% of control in the MCF-7 and T47D cell lines. TGF-beta was not detectable by radioreceptor assay in the ZR-75-B cell line. Two hormone-independent and highly tumorigenic cell lines were studied. The MDA-MB-231 cell line produced large amounts of both TGF-alpha-like (Mr 30,000) and TGF-beta activities. In the HS578T cell line, little TGF-alpha was detectable, while large amounts of TGF-beta were produced. No simple correlations between the tumorigenicity of the cell lines in nude mice and production of either TGF activity could be demonstrated.
Site-Directed Mutagenesis of Phosphoenolpyruvate Carboxylase from <italic>E. coli</italic>: The Role of His<sup>579</sup> in the Catalytic and Regulatory Functions<xref ref-type="fn" rid="fn1"><sup>1</sup></xref> (1991)

Phosphoenolpyruvate carboxylases (PEPC) [EC 4.1.1.31] from a wide variety of organisms contain a unique and highly conserved sequence, 578FHGRGGSIGRGGAP591 (coordinates for the Escherichia coli enzyme), which has been presumed to participate in the binding of phosphoenolpyruvate (PEP). Since previous chemical modification studies had suggested the importance of His for the catalytic activity, the role of His579 was investigated by constructing variants of E. coli PEPC, in which this residue was substituted to Asn (H579N) or Pro (H579P). Kinetic studies with partially purified enzymes revealed the following: (1) The apparent maximal velocities in the presence of acetyl-CoA (CoASAc, one of the allosteric activators) were 29% and 5.4% of the wild-type enzyme, for H579N and H579P, respectively. (2) The half-saturation concentration for PEP was increased about 40-fold by the substitutions, while those for another substrate (HCO3-) and the metal cofactor (Mg2+) were increased only 2- to 4-fold. (3) The half-saturation concentrations of four kinds of allosteric activators and of dioxane, an artificial activator, were also changed to various extents. Among them the most remarkable increase was observed for CoASAc (28-fold). (4) The concentration of an allosteric inhibitor, aspartate, required for 50% inhibition remained substantially unchanged. It was concluded that the imidazole group of His579 is not obligatory for the enzyme catalysis, but plays important roles in catalytic and regulatory functions.
Phenotypes of stem cells from diverse origin (2009)

Stem cells have turned into promising tools for studying the mechanisms of development, regeneration, and for cell therapy of various disorders. Stem cells are found in the embryo and in most adult tissues participating in endogenous tissue regeneration. They are capable of autorenovation, often maintain their multipotency of differentiation into various tissues of their germ line and are, therefore, ideal candidates for cellular therapy taken that they can be unequivocally identified and isolated. In this review, we report stem cell marker expression used for identification of various stem cell lineages, including very small embryonic stem cells, neural, hematopoietic, mesenchymal, epithelial and limbal epithelial stem cells, endothelial progenitor cells, supra-adventitial adipose stromal cells, adipose pericytes, and cancer stem cells. These cells usually cannot be distinguished by a single stem cell marker, because their expression partially overlaps between lineages. Recent advances in flow cytometry allowing the simultaneous detection of various markers have facilitated stem cell identification for clinical diagnosis and research. So far experimental evidence suggests the existence of cells with different properties, i.e., the capability to different in various cell types. Several studies indicate that expression of classical markers for stem cell classification, such as CD34, CD45, and CD133, may differ between the virtually same stem and progenitor cells, i.e., endothelial progenitor or mesenchymal stem cells, when they were obtained from different tissues. This finding raises questions whether phenotypic differences are due to the source or if it is only caused by different isolation and experimental conditions.
High-level beta-globin expression after retroviral transfer of locus activation region-containing human beta-globin gene derivatives into murine erythroleukemia cells. (1990)

The locus activation region (LAR) of the human beta-globin-like gene cluster is characterized by a group of four DNase I hypersensitive sites, which arise specifically in erythroid tissues and are required for a normal pattern of beta-globin-like gene expression. The hypersensitive sites are found at positions 6.1, 10.9, 14.7, and 18 kilobase pairs (kbp) 5' of the epsilon-globin gene. Recently functional assays of the LAR that tested determinants for all four hypersensitive sites showed that expression of the human beta-globin gene was increased to normal or near-normal levels in both transgenic mice and erythroid cells. We constructed retroviral vectors with a human beta-globin gene and the determinant for a single hypersensitive site and measured beta-globin gene expression after retroviral infection of murine erythroleukemia cells. Fragments for the hypersensitive sites at -18 or -10.9 kbp increased human beta-globin RNA levels respectively to 35% or 132% of the endogenous mouse beta maj-globin RNA level. In addition, greater expression was also observed for the neomycin phosphotransferase RNA, which was transcribed from the retroviral LTR, showing that the LAR fragments activated expression from a heterologous promoter. In the context of gene-transfer experiments ultimately aimed at gene therapy, our results show that LAR determinants lead to an increased level of human beta-globin RNA expression after retroviral transfer into erythroid cells. But inclusion of LAR determinants in retroviral vectors also entails the potential risk of activating the expression of nonglobin genes in erythroid cells.
Vaccinia Virus Inhibitors as a Paradigm for the Chemotherapy of Poxvirus Infections (2001)

Poxviruses continue to pose a major threat to human health. Monkeypox is endemic in central Africa, and the discontinuation of the vaccination (with vaccinia virus) has rendered most humans vulnerable to variola virus, the etiologic agent of smallpox, should this virus be used in biological warfare or terrorism. However, a large variety of compounds have been described that are potent inhibitors of vaccinia virus replication and could be expected to be active against other poxviruses as well. These compounds could be grouped in different classes: (i) IMP dehydrogenase inhibitors (e.g., EICAR); (ii) SAH hydrolase inhibitors (e.g., 5'-noraristeromycin, 3-deazaneplanocin A, and various neplanocin A derivatives); (iii) OMP decarboxylase inhibitors (e.g., pyrazofurin) and CTP synthetase inhibitors (e.g., cyclopentenyl cytosine); (iv) thymidylate synthase inhibitors (e.g., 5-substituted 2'-deoxyuridines); (v) nucleoside analogues that are targeted at viral DNA synthesis (e.g., Ara-A); (vi) acyclic nucleoside phosphonates [e.g., (S)-HPMPA and (S)-HPMPC (cidofovir)]; and (vii) polyanionic substances (e.g., polyacrylic acid). All these compounds could be considered potential candidate drugs for the therapy and prophylaxis of poxvirus infections at large. Some of these compounds, in particular polyacrylic acid and cidofovir, were found to generate, on single-dose administration, a long-lasting protective efficacy against vaccinia virus infection in vivo. Cidofovir, which has been approved for the treatment of cytomegalovirus retinitis in immunocompromised patients, was also found to protect mice, again when given as a single dose, against a lethal aerosolized or intranasal cowpox virus challenge. In a biological warfare scenario, it would be advantageous to be able to use a single treatment for an individual exposed to an aerosolized poxvirus. Cidofovir thus holds great promise for treating human smallpox, monkeypox, and other poxvirus infections. Anecdotal experience points to the efficacy of cidofovir in the treatment of the poxvirus infections molluscum contagiosum and orf (ecthyma contagiosum) in immunosuppressed patients.
Metabolic products of Aspergillus terreus. X. Biosynthesis of asterriquinones. (1990)

The biosynthesis of asterriquinones in Aspergillus terreus var. africanus IFO 8835 has been elucidated. Enzymatic activities for the formation of demethyl asterriquinone-D (asterriquinone synthase), prenyltransferase and methyltransferase on asterriquinone were detected in a crude extract of mycelium. Demethyl asterriquinone is biosynthesized from indolepyruvic acid and then methylation of the hydroxyl of group of the quinone moiety occurs.Prenylation proceeds simultaneously at the C-7, C-2 and N-1 positions of the indole moiety.