gebhart/patrepeval huggingface dataset:
Characterization of a restriction endonuclease, PhaI, from Pasteurella haemolytica serotype A1 and protection of heterologous DNA by a cloned PhaI methyltransferase gene (1994)

Pasteurella haemolytica is the leading cause of economic loss to the beef cattle industry in the United States and an important etiologic agent worldwide. Study of P. haemolytica is hindered by researchers' inability to genetically manipulate the organism. A new restriction endonuclease, PhaI, an isoschizomer of SfaNI (R. J. Roberts, Methods Enzymol. 65:19-36, 1980), was isolated from P. haemolytica serotype 1, strain NADC-D60, obtained from pneumonic bovine lung. PhaI recognizes the 5-base nonpalindromic sequences 5'-GCATC-3' and 5'-GATGC-3'. Cleavage occurs 5 bases 3' from the former recognition site and 9 bases 5' from the latter recognition site. A gene encoding a methyltransferase which protects against PhaI cleavage was cloned from P. haemolytica NADC-D60 into Escherichia coli. Whereas unmethylated plasmid DNA containing a P. haemolytica origin of replication was unable to transform P. haemolytica when introduced by electroporation, the same plasmid DNA obtained from E. coli which contained a cloned PhaI methyltransferase gene could do so. The data indicate that PhaI is an effective barrier to the introduction and establishment of exogenous DNA in P. haemolytica.
Foot-and-mouth disease virus 2A protease mediates cleavage in attenuated Sabin 3 poliovirus vectors engineered for delivery of foreign antigens (1996)

Poliovirus vectors are being studied as potential vaccine delivery systems, with foreign genetic sequences incorporated as part of the viral genome. The foreign sequences are expressed as part of the viral polyprotein. Addition of proteolytic cleavage sites at the junction of the foreign polypeptide and the viral proteins results in cleavage during polyprotein processing. The ability of foot-and-mouth disease virus (FMDV) 2A to mediate proteolytic cleavage in the context of poliovirus vectors was studied. The results demonstrate that FMDV 2A is able to generate cleavage of the foreign antigen from the viral polyprotein. A second cleavage event between the FMDV 2A peptide and the foreign protein was also observed.
Targeted Therapies in Systemic Lupus Erythematosus: A State-of-the Art Review (2013)

Systemic lupus erythematosus is a chronic multisystem autoimmune disease leading to substantial morbidity and mortality. In this disease, autoimmunity is triggered against universal cellular antigens. Dysfunction is found in both innate and adaptive immunity. While our previous therapies for lupus were nonspecific, a better understanding of the pathogenesis of lupus has led to an explosion of pharmaceutical research into targeted therapies. These new therapies hold great promise to improve treatment of this difficult disease and also provide insight into the dominant mechanisms of lupus immunopathogenesis.
A Six Degree-of-Freedom God-Object Method for Haptic Display of Rigid Bodies with Surface Properties (2007)

This paper describes a generalization of the god-object method for haptic interaction between rigid bodies. Our approach separates the computation of the motion of the six degree-of-freedom god-object from the computation of the force applied to the user. The motion of the god-object is computed using continuous collision detection and constraint-based quasi-statics, which enables high-quality haptic interaction between contacting rigid bodies. The force applied to the user is computed using a novel constraint-based quasi-static approach, which allows us to suppress force artifacts typically found in previous methods. The constraint-based force applied to the user, which handles any number of simultaneous contact points, is computed within a few microseconds, while the update of the configuration of the rigid god-object is performed within a few milliseconds for rigid bodies containing up to tens of thousands of triangles. Our approach has been successfully tested on complex benchmarks. Our results show that the separation into asynchronous processes allows us to satisfy the different update rates required by the haptic and visual displays. Force shading and textures can be added and enlarge the range of haptic perception of a virtual environment. This paper is an extension of [1].
Adenovirus vector-mediated in vivo gene transfer into adult murine retina. (1994)

These results demonstrate that high efficiency stable transfer of functional genes can be achieved in vivo in post-mitotic mammalian retina using recombinant adenoviral vectors. Adenovirus vectors appear to be a promising means for delivering therapeutic genes in vivo to the mammalian neural retina and particularly to the RPE.
Preclinical Evaluation of EC145, a Folate-Vinca Alkaloid Conjugate (2007)

We recently developed a new group of folate-conjugated Vinca alkaloids, one of which, EC145, emerged as a candidate for clinical development. Brief treatment of nude mice bearing approximately 100 mm(3) folate receptor-positive human xenografts led to complete response (CR) in 5/5 mice and cures (i.e., remission without a relapse for >90 days post-tumor implantation) in 4/5 mice. Multiple CRs and cures were also noted when EC145 was used to treat mice initially bearing tumors as large as 750 mm(3). Likewise, complete cures (5/5) resulted following the treatment of an aggressive folate receptor-positive J6456 lymphoma model. The activity of EC145 was not accompanied by noticeable weight loss or major organ tissue degeneration. Furthermore, no significant antitumor activity (0/5 CR) was observed in EC145-treated animals that were co-dosed with an excess of a benign folate ligand, thus demonstrating the target-specific activity of EC145. The enhanced therapeutic index due to folate conjugation was also evidenced by the fact that the unconjugated drug (desacetylvinblastine monohydrazide) was found to be completely inactive when administered at nontoxic dose levels and only marginally active when given at highly toxic dose levels. Subsequent dose regimen studies confirmed that EC145 given on a more frequent, qdx5 schedule resulted in the most effective antitumor response as compared with an equivalent total dose given on thrice- or single-injection-per-week schedule. Taken together, these studies show that EC145 has significant antiproliferative activity and tolerability, thus lending support to an ongoing phase 1 trial for the treatment of advanced malignancies.
Stability, frequency and multiplicity of transposon insertions in the pyoverdine region in the chromosomes of different fluorescent pseudomonads (1992)

Tn5 mutagenesis of different fluorescent pseudomonads was achieved by conjugational transfer of the suicide vector pSUP 10141. Pyoverdine negative (Pvd-) mutants were detected by the absence of fluorescence on King's B medium and by their inability to grow in the presence of the iron chelator EDDHA [ethylenediamine di(o-hydroxyphenylacetic acid)]. In P. fluorescens ATCC 17400 and three rhizosphere isolates (one P. putida and two P. fluorescens), the percentage of Pvd- mutants ranged between 0 and 0.54%. In a P. chlororaphis rhizosphere isolate, this percentage was higher (4%). In these mutants both of the Tn5 antibiotic resistances (Km and Tc) were stable and the transposon could be detected by hybridization. In Pvd- mutants of P. fluorescens ATCC 17400, the transposon was found to be inserted twice in the chromosome while single insertions were detected in the DNA of other, randomly tested mutants. In P. aeruginosa PAO1, where 13.1% of the mutants were Pvd-, both antibiotic resistances were rapidly lost and accordingly no transposon insertion could be detected by hybridization. However, the Pvd- phenotype was generally stable in these mutants. The plasmid pNK862 containing a mini-Tn10 transposon was introduced by electroporation into P. aeruginosa PAO1 and Kmr mutants were recovered, 89% of which were Pvd- and confirmed to be P. aeruginosa by PCR amplification of the P. aeruginosa lipoprotein gene. The mini-Tn10 insertions were also found to be unstable in PAO1.
Fab1p Is Essential for PtdIns(3)P 5-Kinase Activity and the Maintenance of Vacuolar Size and Membrane Homeostasis (1998)

The Saccharomyces cerevisiae FAB1 gene encodes a 257-kD protein that contains a cysteine-rich RING-FYVE domain at its NH2-terminus and a kinase domain at its COOH terminus. Based on its sequence, Fab1p was initially proposed to function as a phosphatidylinositol 4-phosphate (PtdIns(4)P) 5-kinase (). Additional sequence analysis of the Fab1p kinase domain, reveals that Fab1p defines a subfamily of putative PtdInsP kinases that is distinct from the kinases that synthesize PtdIns(4,5)P2. Consistent with this, we find that unlike wild-type cells, fab1Delta, fab1(tsf), and fab1 kinase domain point mutants lack detectable levels of PtdIns(3,5)P2, a phosphoinositide recently identified both in yeast and mammalian cells. PtdIns(4,5)P2 synthesis, on the other hand, is only moderately affected even in fab1Delta mutants. The presence of PtdIns(3)P in fab1 mutants, combined with previous data, indicate that PtdIns(3,5)P2 synthesis is a two step process, requiring the production of PtdIns(3)P by the Vps34p PtdIns 3-kinase and the subsequent Fab1p- dependent phosphorylation of PtdIns(3)P yielding PtdIns(3,5)P2. Although Vps34p-mediated synthesis of PtdIns(3)P is required for the proper sorting of hydrolases from the Golgi to the vacuole, the production of PtdIns(3,5)P2 by Fab1p does not directly affect Golgi to vacuole trafficking, suggesting that PtdIns(3,5)P2 has a distinct function. The major phenotypes resulting from Fab1p kinase inactivation include temperature-sensitive growth, vacuolar acidification defects, and dramatic increases in vacuolar size. Based on our studies, we hypothesize that whereas Vps34p is essential for anterograde trafficking of membrane and protein cargoes to the vacuole, Fab1p may play an important compensatory role in the recycling/turnover of membranes deposited at the vacuole. Interestingly, deletion of VAC7 also results in an enlarged vacuole morphology and has no detectable PtdIns(3,5)P2, suggesting that Vac7p functions as an upstream regulator, perhaps in a complex with Fab1p. We propose that Fab1p and Vac7p are components of a signal transduction pathway which functions to regulate the efflux or turnover of vacuolar membranes through the regulated production of PtdIns(3,5)P2.
Effect of Donepezil, Tacrine, Galantamine and Rivastigmine on Acetylcholinesterase Inhibition in Dugesia tigrina (2016)

Dugesia tigrina is a non-parasitic platyhelminth, which has been recently utilized in pharmacological models, regarding the nervous system, as it presents a wide sensitivity to drugs. Our trials aimed to propose a model for an in vivo screening of substances with inhibitory activity of the enzyme acetylcholinesterase. Trials were performed with four drugs commercialized in Brazil: donepezil, tacrine, galantamine and rivastigmine, utilized in the control of Alzheimer's disease, to inhibit the activity of acetylcholinesterase. We tested five concentrations of the drugs, with an exposure of 24 h, and the mortality and the inhibition of acetylcholinesterase planarian seizure-like activity (pSLA) and planarian locomotor velocity (pLMV) were measured. Galantamine showed high anticholinesterasic activity when compared to the other drugs, with a reduction of 0.05 μmol·min(-1) and 63% of convulsant activity, presenting screw-like movement and hypokinesia, with pLMV of 65 crossed lines during 5 min. Our results showed for the first time the anticholinesterasic and convulsant effect, in addition to the decrease in locomotion induced by those drugs in a model of invertebrates. The experimental model proposed is simple and low cost and could be utilized in the screening of substances with anticholinesterasic action.
A competitive and reversible deactivation approach to catalysis-based quantitative assays (2016)

Catalysis-based signal amplification makes optical assays highly sensitive and widely useful in chemical and biochemical research. However, assays must be fine-tuned to avoid signal saturation, substrate depletion and nonlinear performance. Furthermore, once stopped, such assays cannot be restarted, limiting the dynamic range to two orders of magnitude with respect to analyte concentrations. In addition, abundant analytes are difficult to quantify under catalytic conditions due to rapid signal saturation. Herein, we report an approach in which a catalytic reaction competes with a concomitant inactivation of the catalyst or consumption of a reagent required for signal generation. As such, signal generation proceeds for a limited time, then autonomously and reversibly stalls. In two catalysis-based assays, we demonstrate restarting autonomously stalled reactions, enabling accurate measurement over five orders of magnitude, including analyte levels above substrate concentration. This indicates that the dynamic range of catalysis-based assays can be significantly broadened through competitive and reversible deactivation.
Considerations regarding mass vaccination against typhoid fever as an adjunct to sanitation and public health measures: potential use in an epidemic in Tajikistan. (1999)

We report on the ongoing epidemic of typhoid fever in Tajikistan that started in 1996. It has involved more than 24,000 cases to date, and is characterized by multiple point sources, overflow of sewage, contaminated municipal water, and person-to-person spread. Of the Salmonella typhi isolates available for testing in western laboratories, more than 90% are multidrug-resistant (MDR). Most recently, 28 (82%) of 34 isolates are resistant to ciprofloxacin, representing the first reported epidemic of quinolone-resistant typhoid fever. In the past, mass immunization during typhoid fever epidemics has been discouraged. A review of this policy is recommended in light of the alarming emergence of quinolone-resistant strains of S. typhi, the availability of improved vaccines, and the ongoing epidemic in Tajikistan. Mass immunization may be a useful measure for the control of prolonged MDR typhoid fever epidemics, as an adjunct to correction of municipal infrastructure and public health intervention.
Identification of the IL-17 Receptor Related Molecule IL-17RC as the Receptor for IL-17F (2007)

The proinflammatory cytokines IL-17A and IL-17F have a high degree of sequence similarity and share many biological properties. Both have been implicated as factors contributing to the progression of inflammatory and autoimmune diseases. Moreover, reagents that neutralize IL-17A significantly ameliorate disease severity in several mouse models of human disease. IL-17A mediates its effects through interaction with its cognate receptor, the IL-17 receptor (IL-17RA). We report here that the IL-17RA-related molecule, IL-17RC is the receptor for IL-17F. Notably, both IL-17A and IL-17F bind to IL-17RC with high affinity, leading us to suggest that a soluble form of this molecule may serve as an effective therapeutic antagonist of IL-17A and IL-17F. We generated a soluble form of IL-17RC and demonstrate that it effectively blocks binding of both IL-17A and IL-17F, and that it inhibits signaling in response to these cytokines. Collectively, our work indicates that IL-17RC functions as a receptor for both IL-17A and IL-17F and that a soluble version of this protein should be an effective antagonist of IL-17A and IL-17F mediated inflammatory diseases.
Induction machine stator fault on-line diagnosis based on LabVIEW environment (2002)

The benefits of machine condition monitoring have been widely recognized as superior with respect to other alternative maintenance approaches. Condition monitoring is an operational strategy for machine integrity assessment, fault identification and life extension. The cost-benefit ratio will be reduced in progress owing to the commercial diagnostic environment availability. This paper presents the implementation of a diagnostic procedure to detect induction machine stator faults based on the LabVIEW environment. The diagnosis is performed by using a suitable neural network, trained by a faulted machine simulator, that has, as input variables, the negative sequence current component and the variation of the positive sequence current component between actual and healthy machine conditions. The statement of a trigger threshold that discerns between true faults and intrinsic dissymetry of the machine is discussed as well.
Thrombospondin‐1/HIV‐1 Tat protein interaction: modulation of the biological activity of extracellular Tat (2000)

Tat protein, a trans-activating factor of the human immunodeficiency virus type 1, acts also as an extracellular molecule modulating gene expression, cell survival, growth, transformation, and angiogenesis. Here we demonstrate that human thrombospondin-1 (TSP), a plasma glycoprotein and constituent of the extracellular matrix, binds to glutathione-S-transferase (GST)-Tat protein but not to GST. Scatchard plot analysis of the binding of free GST-Tat to immobilized TSP reveals a high-affinity interaction (Kd equal to 25 nM). Accordingly, TSP inhibits cell internalization and HIV-1 LTR trans-activating activity of extracellular Tat in HL3T1 cells with ID50 equal to 10-30 nM. Also, TSP inhibits cell interaction and mitogenic activity of extracellular Tat in T53 Tat-less cells. TSP is instead ineffective when administered after the interaction of Tat with cell surface heparan-sulfate proteoglycans has occurred, in keeping with its ability to prevent but not disrupt Tat/heparin interaction in vitro. Finally, TSP inhibits the autocrine loop of stimulation exerted by endogenous Tat in parental T53 cells. Accordingly, TSP overexpression inhibits cell proliferation, angiogenic activity, and tumorigenic capacity of stable T53 transfectants. Our data demonstrate the ability of TSP to bind to Tat protein and to affect its LTR trans-activating, mitogenic, angiogenic, and tumorigenic activity. These findings suggest that TSP may be implicated in the progression of AIDS and in AIDS-associated pathologies by modulating the bioavailability and biological activity of extracellular Tat.
Super-Nyquist-WDM transmission over 7,326-km seven-core fiber with capacity-distance product of 103 Exabit/s·km (2014)

We show super-Nyquist-WDM transmission technique, where optical signals with duobinary-pulse shaping can be wavelength-multiplexed with frequency spacing of below baudrate. Duobinary-pulse shaping can reduce the signal bandwidth to be a half of baudrate while controlling inter-symbol interference can be compensated by the maximum likelihood sequence estimation in a receiver. First, we experimentally evaluate crosstalk characteristics as a function of channel spacing between the dual-channel DP-QPSK signals with duobinary-pulse shaping. As a result, the crosstalk penalty can be almost negligible as far as the ratio of baudrate to frequency spacing is maintained to be less than 1.20. Next, we demonstrate 140.7-Tbit/s, 7,326-km transmission of 7 × 201-channel 25-GHz-spaced super-Nyquist-WDM 100-Gbit/s optical signals using seven-core fiber and full C-band seven-core EDFAs. To the best of our knowledge, this is one of the first reports of high-capacity transmission experiments with capacity-distance product in excess of 1 Exabit/s · km.
Phytochemical constituents of some leaves extract of Aloe vera and Azadirachta indica plant species (2012)

Chloroform and water extractions of Aloe vera and Neem Azadirachta indica leaves were carried out so as to quantify the phytochemical yields in such samples, and to identify their main constituents of active compounds.. The percentage yields obtained through the soxhlet (chloroform) extraction for the A. vera and neem plants were 8.6% and 14.3%, while the percentage yields for the aqueous extracts of the two plants were 5.4% and 6.2%, respectively. The result of the phytochemical screening showed the presence of tannins, flavonoids, terpenoids, carbohydrates, and alkaloids for the A. vera plant with saponins, glycosides phlobatannins, antiquinones carbohydrates, and steroids been absent, while the neem plant contains flavonoids, steroids, carbohydrates, glycosides, antiquinone, terpenoides and alkaloids, with saponins, tannins, phlobatannins been absent. The occurrence of these biologically active chemicals in Neem and A. vera plants may justify their wide usage in traditional medicine.
Studies on the Human Macula (1967)

Electron microscopy of 15 human eyes from patients aged 2 to 82, was done to study aging changes in Bruch's membrane and their relation to senile macular degeneration. The membrane increased twofold to threefold in thickness from childhood to adult life. The basal laminas did not change. With increasing age the membrane accumulated 640 A and 1,100 A type collagen. Clumps were found near the choriocapillaris, often indenting its wall, and in the intercapillary zones. With increasing age vesicular structures accumulated in all zones, mainly internally. Tube-like structures, possibly altered collagen also appeared in the outer collagen zone. Because of these new accumulations the elastic layer became less distinct. Crystal formation was seen on collagen and elastic fibers.
Organization of AMPA Receptor Subunits at a Glutamate Synapse: A Quantitative Immunogold Analysis of Hair Cell Synapses in the Rat Organ of Corti (1996)

Sensitive and high-resolution immunocytochemical procedures were used to investigate the spatial organization of AMPA receptor subunits (GluR1-4) at the synapse between the inner hair cells and the afferent dendrites in the rat organ of Corti. This is a synapse with special functional properties and with a presynaptic dense body that defines the center of the synapse and facilitates its morphometric analysis. A quantitative postembedding immunocytochemical analysis was performed on specimens that had been embedded in a metachrylate resin at low temperature after freeze substitution. Single- and double-labeling procedures indicated that GluR2/3 and GluR4 subunits were colocalized throughout the postsynaptic density, with a maximum distance of 300 nm from the presynaptic body and with higher concentrations peripherally than centrally. No receptor immunolabeling was found at extrasynaptic membranes, but some GluR4 subunits appeared to be expressed presynaptically. The synapses between outer hair cells and afferent dendrites were devoid of labeling. The present data indicate that AMPA receptor subunits are inserted into the postsynaptic membrane in a very precise manner and that their density increases on moving away from the center of the synapse.
New functional assignment of the carotenogenic genescrtBandcrtEwith constructs of these genes fromErwiniaspecies (1992)

The role of carotenoid genes crtB and crtE has been functionally assigned. These genes were cloned from Erwinia into Escherichia coli or Agrobacterium tumefaciens. Their functions were elucidated by assaying early isoprenoid enzymes involved in phytoene formation. In vitro reactions from extracts of E. coli carrying the crtE gene or a complete carotenogenic gene cluster in which crtB was deleted showed an elevated conversion of farnesyl pyrophosphate (FPP) into geranylgeranyl pyrophosphate (GGPP). These results strongly indicate that the crtE gene encodes GGPP synthase. Introduction of the crtB gene into A. tumefaciens led to the conversion of GGPP into phytoene. This activity was absent in similar transformants with the crtE gene. Thus, the crtB probably encodes phytoene synthase, which was further supported by demonstration that phytoene accumulated in E. coli harboring both the crtB genes.