gebhart/patrepeval huggingface dataset:
Lack of Attenuation of a Candidate Dengue 1 Vaccine (45AZ5) in Human Volunteers (1987)

A dengue type 1, candidate live virus vaccine (45AZ5) was prepared by serial virus passage in fetal rhesus lung cells. Infected cells were treated with a mutagen, 5-azacytidine, to increase the likelihood of producing attenuated variants. The vaccine strain was selected by cloning virus that produced only small plaques in vitro and showed reduced replication at high temperatures (temperature sensitivity). Although other candidate live dengue virus vaccines selected for similar growth characteristics have been attenuated for humans, two recipients of the 45AZ5 virus developed unmodified acute dengue fever. Viremia was observed within 24 hr of inoculation and lasted 12 to 19 days. Virus isolates from the blood produced large plaques in cell culture and showed diminished temperature sensitivity. The 45AZ5 virus is unacceptable as a vaccine candidate. This experience points out the uncertain relationship between in vitro viral growth characteristics and virulence factors for humans.
Neuromuscular transmission after immunization against acetylcholine receptors (1975)

Abstract Injection of acetylcholine receptors from the electric organ of Torpedo into rabbits or rats, produces antibodies which bind to acetylcholine receptors in the muscle membrane or in solution. Binding of antibody to the receptors results in diminished acetylcholine sensitivity of the muscle fibres, reduced amplitude of miniature end-plate potentials, block of neuromuscular transmission and a decrease in the ability of the receptors to bind a-bungarotoxin. Antibodies raised against acetylcholine receptors from Torpedo cross-react with acetylcholine receptors from rabbit, rat and frog muscle.
Immunoassay of insulin-like growth factor binding protein-1. (1997)

Accurate measurement of insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) is important for precise definition of its physiological roles and potential diagnostic values. Because altered phosphorylation results in altered IGFBP-1 immunoreactivity, current assays may significantly underestimate or fail to detect physiological changes in the IGFBP-1 concentrations. We developed three ELISAs (ELISA 1-3) using a common capture but three different detection antibodies. IGFBP-1 in serum, synovial fluid (SF), cerebrospinal fluid (CSF), and amniotic fluid (AF) were measured before and after treatment with alkaline phosphatase (ALP). Among the methods, only ELISA-1 was unaffected by IGFBP-1 phosphorylation and generated identical results before and after ALP treatment. The serum and SF values by ELISA-2 and -3 were lower by approximately 4- to 10-fold, but increased after ALP treatment to within 66-98% of those by ELISA-1. The medians in AF, and to a lesser extent in CSF, by all methods were similar and did not change significantly after dephosphorylation. ELISA-1 showed excellent correlation with ELISA-2, ELISA-3, and a commercial IGFBP-1 IRMA only after ALP-treated samples were analyzed by the comparative methods. ELISA-1 is highly specific for IGFBP-1 and demonstrated acceptable analytical performance characteristics.
A retrofit 60 Hz current sensor for non-intrusive power monitoring at the circuit breaker (2010)

We present a new sensor for power monitoring that measures current flow in a circuit breaker without permanent modification of the breaker panel or the circuit breaker itself. The sensor consists of three parts: an inductive pickup for sensing current from the breaker face, an inductive link designed to transmit power through the steel breaker panel door, and a passive, balanced JFET modulator circuit for transmitting information through the inductive link. The demodulated breaker current signal is available outside of the breaker panel door. This sensor provides a solution for low-cost, non-intrusive retrofit of any circuit breaker panel for centralized power monitoring.
CSPG4 in Cancer: Multiple Roles (2010)

Chondroitin sulfate proteoglycan 4 (CSPG4), also known as High Molecular Weight-Melanoma Associated Antigen, is a cell surface proteoglycan which has been recently shown to be expressed not only by melanoma cells, but also by various types of human carcinoma and sarcoma. Furthermore, at least in squamous cell carcinoma of head and neck and in basal breast carcinoma, CSPG4 is expressed by cancer stem cells. CSPG4 plays an important role in tumor cell growth and survival. These CSPG4-associated functional properties of tumor cells are inhibited by CSPG4-specific monoclonal antibodies (mAb) in vitro. Moreover, CSPG4-specific mAb can also inhibit tumor growth and metastasis in vivo. The anti-tumor effects of CSPG4-specific mAb are likely to reflect the blocking of important migratory, mitogenic and survival signaling pathways in tumor cells. These results indicate that CSPG4 is a promising new target to implement mAb-based immunotherapy of various types of cancer.
Studies of the 5′ Exonuclease and Endonuclease Activities of CPSF-73 in Histone Pre-mRNA Processing (2008)

Processing of histone pre-mRNA requires a single 3' endonucleolytic cleavage guided by the U7 snRNP that binds downstream of the cleavage site. Following cleavage, the downstream cleavage product (DCP) is rapidly degraded in vitro by a nuclease that also depends on the U7 snRNP. Our previous studies demonstrated that the endonucleolytic cleavage is catalyzed by the cleavage/polyadenylation factor CPSF-73. Here, by using RNA substrates with different nucleotide modifications, we characterize the activity that degrades the DCP. We show that the degradation is blocked by a 2'-O-methyl nucleotide and occurs in the 5'-to-3' direction. The U7-dependent 5' exonuclease activity is processive and continues degrading the DCP substrate even after complete removal of the U7-binding site. Thus, U7 snRNP is required only to initiate the degradation. UV cross-linking studies demonstrate that the DCP and its 5'-truncated version specifically interact with CPSF-73, strongly suggesting that in vitro, the same protein is responsible for the endonucleolytic cleavage of histone pre-mRNA and the subsequent degradation of the DCP. By using various RNA substrates, we define important space requirements upstream and downstream of the cleavage site that dictate whether CPSF-73 functions as an endonuclease or a 5' exonuclease. RNA interference experiments with HeLa cells indicate that degradation of the DCP does not depend on the Xrn2 5' exonuclease, suggesting that CPSF-73 degrades the DCP both in vitro and in vivo.
The centrifugal microfluidic Bio-Disk platform (2007)

This paper reviews the centrifugal 'Bio-Disk' platform which is based on rotationally controlled, multi-scale liquid handling to fully integrate and automate complex analysis and synthesis protocols in the life sciences. The platform offers the crucial ingredients for a rapid development of applications: a coherent library of fluidic unit operations, a device technology for actuation, liquid interfacing and detection as well as a developer toolbox providing experimental testing, rapid prototyping and simulation capabilities. Various applications in the fields of life science, in vitro diagnostics and micro-process engineering are demonstrated.
Studies on the metabolism of unsaturated fatty acids. V. Isomerization of thiol esters of cis-2-alkenoic acids during their preparation and alkaline hydrolysis. (1982)

N-Acetylcysteamine and coenzyme A esters of cis-2-alkenoic acids have been found to undergo isomerization to the corresponding trans-isomers during their preparation by the mixed anhydride method and also during their alkaline hydrolysis. The isomerization might proceed by interaction of the free thiol group and the cis-double bond of 2-alkenoic thiol esters. The use of pyridine as a base and three or more equivalents of the mixed anhydride to the thiol compound prevented the formation of the trans-isomer. Addition of hydrogen peroxide during alkaline hydrolysis also prevented the isomerization completely.
-Catenin contributes to leukemogenesis induced by AML-associated translocation products by increasing the self-renewal of very primitive progenitor cells (2004)

Acute myeloid leukemia (AML) is characterized by the block of differentiation, deregulated apoptosis, and an increased self-renewal of hematopoietic precursors. It is unclear whether the self-renewal of leukemic blasts results from the cumulative effects of blocked differentiation and impaired apoptosis or whether there are mechanisms directly increasing self-renewal. The AML-associated translocation products (AATPs) promyelocytic leukemia/retinoic acid receptor alpha (PML/RAR alpha), promyelocytic leukemia zinc finger (PLZF)/RAR alpha (X-RAR alpha), and AML-1/ETO block hematopoietic differentiation. The AATPs activate the Wnt signaling by up-regulating gamma-catenin. Activation of the Wnt signaling augments self-renewal of hematopoietic stem cells (HSCs). Therefore, we investigated how AATPs influence self-renewal of HSCs and evaluated the role of gamma-catenin in the determination of the phenotype of HSCs expressing AATPs. Here we show that the AATPs directly activate the gamma-catenin promoter. The crucial role of gamma-catenin in increasing the self-renewal of HSCs upon expression of AATPs is demonstrated by (i) the abrogation of replating efficiency upon hindrance of gamma-catenin expression through RNA interference, and (ii) the augmentation of replating efficiency of HSCs upon overexpression of gamma-catenin itself. In addition, the inoculation of gamma-catenin-transduced HSCs into irradiated recipient mice establishes the clinical picture of AML. These data provide the first evidence that the aberrant activation of Wnt signaling by the AATP decisively contributes to the pathogenesis of AML.
Acetylated Low-Density Lipoprotein Stimulates Human Vascular Smooth Muscle Cell Calcification by Promoting Osteoblastic Differentiation and Inhibiting Phagocytosis (2002)

These studies suggest that modified lipoproteins stimulate calcification by enhancing osteogenic differentiation of VSMCs and by a novel mechanism whereby acLDL interacts with SRA on VSMCs and blocks phagocytic removal of apoptotic bodies.
Thrombin-stimulated events in cultured vascular smooth-muscle cells (1991)

Thrombin is present in high concentrations at sites of clots and may have important post-clotting effects on adjacent vascular tissue. This may be particularly important for vascular smooth-muscle cells (VSMC), whose growth and contractility are altered following atherosclerotic-associated thromboses. To study the cellular signal events by which thrombin exerts its actions, the effects of purified human alpha-thrombin were examined in cultured rat aortic VSMC. alpha-Thrombin stimulated a biphasic change in intracellular pH (pHi), causing an early rapid acidification, followed by a sustained alkalinization. The increase in pHi was dependent on extracellular Na+ and inhibited by 5'-(NN-dimethyl)amiloride, consistent with mediation by Na+/H+ exchange. alpha-Thrombin rapidly increased free intracellular [Ca2+] ([Ca2+]i). The increase in [Ca2+]i was secondary to activation of phospholipase C, as demonstrated by increases in InsP3 (226%) and InsP2 (387%) and decreases in polyphosphoinositides at 15 s. Expression of the mRNA for the proto-oncogene c-fos was induced by alpha-thrombin. Stimulation of c-fos mRNA was not dependent on alterations in pHi, but required a rise in [Ca2+]i. Despite many growth-related signals shared by alpha-thrombin with platelet-derived growth factor, alpha-thrombin failed to stimulate [3H]thymidine incorporation or cell division, although there was a maximal increase of 52% in protein synthesis. The data suggest that there are cellular signal events not activated by alpha-thrombin which are required for proliferation of these aortic VSMC.
The clinical characteristics of headache in patients with pituitary tumours (2005)

The clinical characteristics of 84 patients with pituitary tumour who had troublesome headache were investigated. The patients presented with chronic (46%) and episodic (30%) migraine, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT; 5%), cluster headache (4%), hemicrania continua (1%) and primary stabbing headache (27%). It was not possible to classify the headache according to International Headache Society diagnostic criteria in six cases (7%). Cavernous sinus invasion was present in the minority of presentations (21%), but was present in two of three patients with cluster headache. SUNCT-like headache was only seen in patients with acromegaly and prolactinoma. Hypophysectomy improved headache in 49% and exacerbated headache in 15% of cases. Somatostatin analogues improved acromegaly-associated headache in 64% of cases, although rebound headache was described in three patients. Dopamine agonists improved headache in 25% and exacerbated headache in 21% of cases. In certain cases, severe exacerbations in headache were observed with dopamine agonists. Headache appears to be a significant problem in pituitary disease and is associated with a range of headache phenotypes. The presenting phenotype is likely to be governed by a combination of factors, including tumour activity, relationship to the cavernous sinus and patient predisposition to headache. A proposed modification of the current classification of pituitary-associated headache is given.
Differences in Clinical Parameters and Tear Film of Tolerant and Intolerant Contact Lens Wearers (2003)

Contact lens intolerance appears to be best predicted by a combination of clinical variables, including tear film stability, tear volume, and symptom reporting.
An alkali-labile substituted benzyloxycarbonyl amino-protecting group (1973)

4-Isopropyloxycarbonyloxybenzyloxycarbonyl, Z(4-PriOCO), a new amino-protecting group stable under the conditions which cause cleavage of the t-butoxy-carbonyl and 2-(p-biphenylyl)isopropyloxycarbonyl groups, can be removed in a slightly alkaline medium via a 1,6-elimination, by hydrogenolysis, or by HBr in acetic acid.
Epstein-Barr virus nuclear protein 2 transactivates a cis-acting CD23 DNA element (1991)

Epstein-Barr virus (EBV) nuclear protein 2 (EBNA-2) is essential for B-lymphocyte growth transformation. EBNA-2 upregulates mRNAs encoding CD23, a B-lymphocyte surface protein closely associated with EBV-induced growth transformation. To further investigate this EBNA-2 effect, we searched in the genomic DNA spanning the type a and type b CD23 mRNA start sites for a cis-acting fragment that would render a promoter transactivatable by EBNA-2. An 800-bp CD23 DNA fragment (-335 to +465 relative to the type a CD23 mRNA start site) conferred EBNA-2 responsiveness to the herpes simplex virus thymidine kinase (TK) promoter when transfected into EBV-negative B-lymphoma cells. Deletional analysis identified a -275/-89 subfragment that was EBNA-2 responsive when cloned in either orientation and at variable distances upstream of the heterologous promoter. EBNA-2 and the cis-acting CD23 element increased TK-promoted mRNA and did not alter the herpes simplex virus TK promoter transcription start site. As expected, a type a CD23 promoter (-335/+80) which contained the EBNA-2-responsive element was transactivated by EBNA-2. As in EBV infection and stable EBNA-2 transfection, the CD23 DNA element in cis with heterologous or homologous promoters was less responsive to type 2 than to type 1 EBNA-2, whereas the EBNA-2-responsive DNA fragment from the EBV latent membrane protein 1 promoter was more responsive to the type 2 EBNA-2. These experiments delineate a 186-bp, EBNA-2-responsive cell DNA fragment and provide firm evidence that EBNA-2 transactivates transcription of cell genes. The greater type 1 versus type 2 EBNA-2 responsiveness of the CD23 promoter and the lack of a similar effect on the latent membrane protein 1 promoter is consistent with the hypothesis that greater cell gene transactivation by type 1 EBNA-2 is the basis for the more efficient growth-transforming properties of type 1 EBV.
A Selective Small Molecule DNA2 Inhibitor for Sensitization of Human Cancer Cells to Chemotherapy (2016)

Cancer cells frequently up-regulate DNA replication and repair proteins such as the multifunctional DNA2 nuclease/helicase, counteracting DNA damage due to replication stress and promoting survival. Therefore, we hypothesized that blocking both DNA replication and repair by inhibiting the bifunctional DNA2 could be a potent strategy to sensitize cancer cells to stresses from radiation or chemotherapeutic agents. We show that homozygous deletion of DNA2 sensitizes cells to ionizing radiation and camptothecin (CPT). Using a virtual high throughput screen, we identify 4-hydroxy-8-nitroquinoline-3-carboxylic acid (C5) as an effective and selective inhibitor of DNA2. Mutagenesis and biochemical analysis define the C5 binding pocket at a DNA-binding motif that is shared by the nuclease and helicase activities, consistent with structural studies that suggest that DNA binding to the helicase domain is necessary for nuclease activity. C5 targets the known functions of DNA2 in vivo: C5 inhibits resection at stalled forks as well as reducing recombination. C5 is an even more potent inhibitor of restart of stalled DNA replication forks and over-resection of nascent DNA in cells defective in replication fork protection, including BRCA2 and BOD1L. C5 sensitizes cells to CPT and synergizes with PARP inhibitors.
Human endothelial cells contain one type of plasminogen activator (1984)

At least two types of animal plasminogen activating enzymes exist, differing in amino acid sequence, molecular mass and immunological reactivity: the urokinase-type and the tissue-type plasminogen activators. By affinity chromatography with monoclonal antibodies, we have purified the human activators of both types to homogeneity. Using immunocytochemistry with rabbit antibodies raised against these preparations, we now demonstrate that the plasminogen activator present in endothelium of veins and other blood vessels is of the tissue-type. No urokinase-type plasminogen activator immunoreactivity was detected in endothelial cells in the intact organism. These findings support the assumption that mobilization of plasmin for different purposes may involve different types of plasminogen activators, and that the plasminogen activator involved in thrombolysis is of the tissue-type.
Expression of the murine prostaglandin (PGH) synthase-1 and PGH synthase-2 isozymes in cos-1 cells. (1993)

Plasmid vectors were constructed which allowed expression of the mouse prostaglandin endoperoxide (PGH) synthase-1 and PGH synthase-2 isozymes in cos-1 cells. Efficient expression of the PGHS-2 isozyme required the truncation of the entire 3'-untranslated region of the PGHS-2 cDNA, possibly due to the presence of multiple AUUUA sequences which may destabilize the PGHS-2 mRNA. The length of the 3'-untranslated regions of the murine and ovine PGHS-1 isozymes, which do not contain AUUUA sequences, did not affect the efficiency of expression of these proteins. The murine PGHS-2 isozyme catalyzes the same cyclooxygenase and hydroperoxidase activities as the ovine and murine PGHS-1 isozymes. The maximal activities of the mouse enzymes expressed in cos-1 cells was about equal, but both were only about a third that seen with the sheep enzyme. Whether this reflects differences in the turnover rate of the mouse and sheep enzymes, or differences in the efficiency of expression in cos-1 cells is not known.
High-Rate Overcharge Protection of LiFePO[sub 4]-Based Li-Ion Cells Using the Redox Shuttle Additive 2,5-Ditertbutyl-1,4-dimethoxybenzene (2005)

Li-ion cells have been investigated by many groups and their behavior in standard electrolytes such as 1 M ethylene carbonate: diethyl carbonate (EC:DEC) is well known. Here we report on the behavior of these cells with 2,5-ditertbutyl-1,4-dimethoxybenzene added to the electrolyte as a redox shuttle additive to prevent overcharge and overdischarge. We explore methods to increase the current-carrying capacity of the shuttle and explore the heating of practical cells during extended overcharge. The solubility of 2,5-ditertbutyl-1,4-dimethoxybenzene was determined as a function of salt concentration in lithium bis-oxolatoborate-(LiBOB) and -containing electrolytes based on propylene carbonate (PC), EC, DEC, and dimethyl carbonate (DMC) solvents. Concentrations of 2,5-ditertbutyl-1,4-dimethoxybenzene up to 0.4 M can be obtained in 0.5 M LiBOB PC:DEC (1:2 by volume). Coin-type test cells were tested for extended overcharge protection using an electrolyte containing 0.2 M 2,5-ditertbutyl-1,4-dimethoxybenzene in 0.5 M LiBOB PC:DEC. Sustained overcharge protection at a current density of was possible and hundreds of 100% shuttle-protected overcharge cycles were achieved at current densities of about . The diffusion coefficient of the shuttle molecule in this electrolyte was determined to be from cyclic voltammetry and also from measurements of the shuttle potential vs. current density. The power produced during overcharge was measured using isothermal microcalorimetry and found to be as expected, where is the charging current and is the cell terminal voltage during shuttle-protected overcharge. Calculations of the temperature of 18650-sized Li-ion cells as a function of time during extended shuttle-protected overcharge at various -rates are presented. These show that Li-ion cells need external cooling during extended shuttle-protected overcharge if currents exceed about rates.
A method for introducing random single point deletions in specific DNA target sequences using oligonucleotides (1989)

We describe a method for the generation of random point deletions in any target DNA sequence using synthetic mixed oligonucleotides. A mixed pool of oligonucleotides, which contain single nucleotide deletions randomly distributed throughout the full length, was generated by a modification of the synthesis cycle of an automated DNA synthesiser that allowed the inefficient incorporation of nucleotide monomers during each cycle of synthesis. A family of oligonucleotides was used to prime in vitro synthesis of the complementary strand of a cloned DNA fragment in an M13 vector which had previously been passaged through a dut-, ung- Escherichia coli host. Strong selection for progeny from the newly synthesised strand is provided by transforming the heteroduplex into a dut+, ung+ host. This procedure introduced point deletions at 10-25% efficiency. It has been used to introduce point deletions into operator sequences which bind the yeast regulatory proteins encoded by MATa1 and MAT alpha 2.
Seminal Plasma Protein p30: Simplified Purification and Evidence for Identity with Prostate Specific Antigen (1990)

A rapid high yield purification scheme is described for the major 30,000 molecular weight glycoprotein (p30) in human seminal plasma. Immunological and protein sequence evidence demonstrates the identity of this protein with prostate specific antigen (PSA) and gamma-seminoprotein (gamma SM).
Deoxyglucose Analysis of Retinotopic Organization in Primate Striate Cortex (1982)

We have anatomically analyzed retinotopic organization using the 14C-labeled 2-deoxy-D-glucose method. The method has several advantages over conventional electrophysiological mapping techniques. In the striate cortex, the anatomical substrate for retinotopic organization is surprisingly well ordered, and there seems to be a systematic relationship between ocular dominance strips and cortical magnification. The 2-deoxyglucose maps in this area appear to be largely uninfluenced by known differences in long-term metabolic activity. This method should prove useful in analyzing retinotopic organization in various visual areas of the brain and in different species.