gebhart/patrepeval huggingface dataset:
The Effect of Glucagon-Like Peptide I (GLP-I) on Glucose Elimination in Healthy Subjects Depends on the Pancreatic Glucoregulatory Hormones (1996)

Glucagon-like peptide I (GLP-I) decreases plasma glucose in type II diabetic patients and in healthy subjects indirectly by stimulation of insulin and inhibition of glucagon secretion, whereby the hepatic glucose production decreases. However, recent studies indicate that GLP-I may also directly influence peripheral and hepatic glucose uptake. We infused somatostatin (SS) intravenously (500 or 1,000 microgram/h) in 13 healthy subjects to suppress insulin and glucagon secretion from the endocrine pancreas, together with infusion of either GLP-I (50 pmol / kg / h) or saline intravenously. After 30 min, a 25-g intravenous glucose tolerance test (IVGTT) was carried out, and plasma concentrations of glucose, insulin, glucagon, and GLP-I were measured during the following 2 h. IVGTT together with GLP-I infusion significantly elevated insulin during 500 microgram/h SS but not during 1,000 microgram/h SS. Plasma glucagon was strongly depressed in all experiments. During 500 microgram/h SS, the glucose disappearance constant, Kg, was 0.49 +/- 0.03% per minute with GLP-I and 0.39 +/- 0.04% per minute with saline (n = 8, P = 0.004). With 1,000 microgram/h SS, Kg was 0.42 +/- 0.03% per minute with GLP-I and 0.40 +/- 0.03% per minute without (NS). In conclusion, when endogenous insulin secretion is held at a constant low level, which may be accomplished only with very large doses of SS, GLP-I has no effect on glucose elimination. Thus, an insulin-independent effect of GLP-I on glucose disposal could not be demonstrated.
Encapsidation of genetically engineered poliovirus minireplicons which express human immunodeficiency virus type 1 Gag and Pol proteins upon infection (1993)

The use of recombinant viruses for the expression of a wide array of foreign proteins has become commonplace during the last few years. Recently, we have described the construction and characterization of chimeric human immunodeficiency virus type 1 (HIV-1)-poliovirus genomes in which the gag and pol genes of HIV-1 have been substituted for the VP2 and VP3 capsid genes of the P1 capsid precursor region of poliovirus. Transfection of these RNAs into tissue culture cells results in replication of the RNA genome and expression of HIV-1-P1 fusion proteins (W. S. Choi, R. Pal-Ghosh, and C. D. Morrow, J. Virol. 65:2875-2883, 1991). Here we report on the encapsidation and amplification of the minireplicons to obtain sufficient quantities for biological characterization. To do this, HIV-1-poliovirus minireplicon genomes containing the gag or pol gene were transfected into cells previously infected with a recombinant vaccinia virus (VV-P1) which expresses the poliovirus capsid precursor protein, P1 (D. C. Ansardi, D. C. Porter, and C. D. Morrow, J. Virol. 65:2088-2092, 1991). The chimeric minireplicons replicated and expressed the appropriate HIV-1-P1 fusion proteins as determined by immunoprecipitation with HIV-1-specific antibodies. The encapsidated genomes were isolated by ultracentrifugation. Reinfection of cells with the encapsidated chimeric RNA genomes resulted in expression of the HIV-1-Gag-P1 or HIV-1-Pol-P1 fusion protein. Serial passaging of the encapsidated chimeric HIV-1-poliovirus genomes was accomplished by coinfecting cells with the encapsidated minireplicons and VV-P1, resulting in stocks of the encapsidated minireplicons. Northern (RNA) blot analysis of passaged material revealed that no detectable deletions of the chimeric genomes occurred during 14 serial passages. Infection of cells by the encapsidated minireplicons was blocked by antipoliovirus antibodies. Coinfection of cells with encapsidated minireplicons and type 1 Sabin poliovirus resulted in encapsidation of the chimeric genomes by wild-type poliovirus as measured by immunoprecipitation of the HIV-1-P1 fusion proteins with HIV-1-specific antibodies. The results of this study demonstrate the encapsidation of poliovirus minireplicons which express foreign proteins and point to the future use of this system as a potential vaccine vector.
Chiral Kinetics and Dynamics of Ketorolac (1996)

It has been shown that the analgesic and cyclooxygenase inhibitor activity of ketorolac tromethamine (KT), which is marketed as the racemic mixture of (-)S and (+)R enantiomers, resides primarily with (-)S ketorolac and that the ulcerogenic activity of this agent also resides in (-)S ketorolac. Resolution of individual enantiomers for analysis in plasma samples has been accomplished by two methods: derivatization to form diastereomers that are separated by HPLC, or direct HPLC using a chiral phase column. When mice and rats were given oral solutions of (-)S and (+) KT, it was found that the kinetics and interconversion of the enantiomers were species and dose dependent. Interconversion was higher in mice than in rats; when (-)S KT was administered, 71% of the area under the concentration-time curve (AUC) was due to (+)R ketorolac in mice, compared with 12% in rats. More interconversion was observed at higher doses; the percent of AUC due to (-)S ketorolac when (+)R KT was administered increased from 12% to 25% in mice and from 2% to 8% in rats. In general, more interconversion occurred from (-)S to (+)R ketorolac in the animal studies. Human subjects were given single oral solution doses of racemic KT (30 mg), (-)S KT (15 mg), and (+)R KT (15 mg). The plasma concentrations of (-)S ketorolac were lower than (+)R ketorolac at all sample times after racemic KT (22% of the AUC was due to (-)S ketorolac). When (+)R KT was administered, (-)S ketorolac was not detectable and interconversion was essentially 0%. When (-)S KT was administered, significant levels of (+)R ketorolac were detectable and interconversion was 6.5%. After all doses, plasma half-life was shorter and clearance greater for (-)S ketorolac than for (+)R ketorolac. Thus, in humans very little or no interconversion of (+)R to (-)S was observed, and interconversion of (-)S to (+)R was minimal (6.5%). These data demonstrate that the kinetics and interconversion of the enantiomers of ketorolac is different in animals and humans as well as from most other NSAIDs. This may be due to more rapid excretion or metabolism of (-)S ketorolac and a different mechanism of interconversion.
The 60 degrees grid : routing channels in width d/ square root 3 (2002)

The 60 degrees grid consists of vertical columns and diagonal tracks running at slopes of +or-30 degrees . This model offers a potentially large reduction in channel width, without resorting to wire overlap. For a channel routing problem with density d, the availability of the diagonal tracks leads to a lower bound of d/ square root 3. The authors present two near-optimal channel routing algorithms. The first uses 5 layers and always routes in width at most d/ square root 3+ square root 3. The second algorithm uses at most 4 layers and routes in width omega , where d/ square root 3+O(1)<or= omega <or=d/ square root 3+O( square root d).<<ETX>>
Characterization of a Three-Component Vanillate O -Demethylase from Moorella thermoacetica (2001)

The Moorella thermoacetica aromatic O-demethylase was characterized as an inducible three-component system with similarity to the methanogenic methanol, methylamine, and methanethiol methyltransferases and to the O-demethylase system from Acetobacterium dehalogenans. MtvB catalyzes methyl transfer from a phenylmethylether to the cobalt center of MtvC, a corrinoid protein. MtvA catalyzes transmethylation from MtvC to tetrahydrofolate, forming methyltetrahydrofolate. Cobalamin can substitute for MtvC.
Uterine Artery Embolization for Treatment of Leiomyomata (2008)

III.
Regulation of tissue inhibitor of metalloproteinase-3 (Timp-3) mRNA expression during rat CNS development (2000)

To preserve tissue integrity during the structural rearrangements that occur during central nervous system (CNS) development, an intricate balance between extracellular matrix (ECM) synthesis and degradation must be maintained. The matrix metalloproteinases (MMPs) are believed to be the main mediators of ECM degradation. Because MMPs function in the turnover of a broad-spectrum of ECM proteins their activity is tightly regulated by interaction with tissue inhibitors of metalloproteinases (TIMPs). Whereas the primary function of TIMPs is to inhibit MMP activity, evidence is mounting that TIMPs are multifunctional molecules that exert diverse cell biological functions distinct from their MMP-inhibitory activities. Although the role of MMPs and TIMPs in the morphogenesis of non-neural tissues has been investigated, to date few studies have analyzed MMP or TIMP expression during CNS development. In the present report, we demonstrate the regulation of Timp-3 mRNA expression throughout the course of CNS development. In particular, Timp-3 mRNA is expressed in embryonic ventricular zones and the postnatal subventricular zone (SVZ). In addition, Timp-3 is expressed in the rostral migratory steam (RMS) to the olfactory bulb in a pattern similar to the ECM proteoglycan brevican. These data suggest that TIMP-3 and brevican may act in concert to guide neuronal migration along the RMS.
Extensive personal human gut microbiota culture collections characterized and manipulated in gnotobiotic mice (2011)

The proportion of the human gut bacterial community that is recalcitrant to culture remains poorly defined. In this report, we combine high-throughput anaerobic culturing techniques with gnotobiotic animal husbandry and metagenomics to show that the human fecal microbiota consists largely of taxa and predicted functions that are represented in its readily cultured members. When transplanted into gnotobiotic mice, complete and cultured communities exhibit similar colonization dynamics, biogeographical distribution, and responses to dietary perturbations. Moreover, gnotobiotic mice can be used to shape these personalized culture collections to enrich for taxa suited to specific diets. We also demonstrate that thousands of isolates from a single donor can be clonally archived and taxonomically mapped in multiwell format to create personalized microbiota collections. Retrieving components of a microbiota that have coexisted in single donors who have physiologic or disease phenotypes of interest and reuniting them in various combinations in gnotobiotic mice should facilitate preclinical studies designed to determine the degree to which tractable bacterial taxa are able to transmit donor traits or influence host biology.
Injectable Biopolymers Enhance Angiogenesis after Myocardial Infarction (2005)

Novel strategies by which to repair ischemic myocardium after myocardial infarction include the use of three-dimensional polymer scaffolds. A comparative study was carried out to assess the therapeutic potential of fibrin, collagen I, and Matrigel as injectable biopolymers for repair after myocardial infarction. Using a rat model of left coronary artery occlusion followed by reperfusion, local injection of the biopolymers into the infarct zone yielded significantly higher levels of capillary formation, when compared with the saline control group, at 5 weeks posttreatment. However, the degree of angiogenesis was not significantly different among the biopolymers. In addition, the collagen biopolymer significantly enhanced infiltration of myofibroblasts into the infarct area when compared with the control group. The results of this study highlight the potential clinical benefit of these biopolymers as injectable scaffolds or cell delivery vehicles to the infarct zone after infarction.
Words and worlds: form and the novel (2007)

One of the paradoxes of any artistic process is the transformation of the intensities of thought and sensation into the empirical fixities of form. For novelists, the sentence, paragraph and chapter are the standard textual forms that represent the richness of character, setting and event, and the insights into human nature they embody. In this paper I draw on approaches from literature, painting and poststructuralist philosophy to investigate the process by which words become worlds.
Third millenium ideal gas and condensed phase thermochemical database for combustion (with update from active thermochemical tables). (2005)

The thermochemical database of species involved in combustion processes is and has been available for free use for over 25 years. It was first published in print in 1984, approximately 8 years after it was first assembled, and contained 215 species at the time. This is the 7th printed edition and most likely will be the last one in print in the present format, which involves substantial manual labor. The database currently contains more than 1300 species, specifically organic molecules and radicals, but also inorganic species connected to combustion and air pollution. Since 1991 this database is freely available on the internet, at the Technion-IIT ftp server, and it is continuously expanded and corrected. The database is mirrored daily at an official mirror site, and at random at about a dozen unofficial mirror and 'finger' sites. The present edition contains numerous corrections and many recalculations of data of provisory type by the G3//B3LYP method, a high-accuracy composite ab initio calculation. About 300 species are newly calculated and are not yet published elsewhere. In anticipation of the full coupling, which is under development, the database started incorporating the available (as yet unpublished) values from Active Thermochemical Tables. The electronic version now also contains an XML file of the main database to allow transfer to other formats and ease finding specific information of interest. The database is used by scientists, educators, engineers and students at all levels, dealing primarily with combustion and air pollution, jet engines, rocket propulsion, fireworks, but also by researchers involved in upper atmosphere kinetics, astrophysics, abrasion metallurgy, etc. This introductory article contains explanations of the database and the means to use it, its sources, ways of calculation, and assessments of the accuracy of data.
Transforming Growth Factor-β: Master Regulator of the Respiratory System in Health and Disease (2016)

In this article, we review the biology and physiological importance of transforming growth factor-β (TGF-β) to homeostasis in the respiratory system, its importance to innate and adaptive immune responses in the lung, and its pathophysiological role in various chronic pulmonary diseases including pulmonary arterial hypertension, chronic obstructive pulmonary disease, asthma, and pulmonary fibrosis. The TGF-β family is responsible for initiation of the intracellular signaling pathways that direct numerous cellular activities including proliferation, differentiation, extracellular matrix synthesis, and apoptosis. When TGF-β signaling is dysregulated or essential control mechanisms are unbalanced, the consequences of organ and tissue dysfunction can be profound. The complexities and myriad checkpoints built into the TGF-β signaling pathways provide attractive targets for the treatment of these disease states, many of which are currently being investigated. This review focuses on those aspects of TGF-β biology that are most relevant to pulmonary diseases and that hold promise as novel therapeutic targets.
Blocking follistatin-like 1 attenuates bleomycin-induced pulmonary fibrosis in mice (2015)

Progressive tissue fibrosis is a cause of major morbidity and mortality. Pulmonary fibrosis is an epithelial-mesenchymal disorder in which TGF-β1 plays a central role in pathogenesis. Here we show that follistatin-like 1 (FSTL1) differentially regulates TGF-β and bone morphogenetic protein signaling, leading to epithelial injury and fibroblast activation. Haplodeletion of Fstl1 in mice or blockage of FSTL1 with a neutralizing antibody in mice reduced bleomycin-induced fibrosis in vivo. Fstl1 is induced in response to lung injury and promotes the accumulation of myofibroblasts and subsequent fibrosis. These data suggest that Fstl1 may serve as a novel therapeutic target for treatment of progressive lung fibrosis.
EMPLOYING COMPRITOL IN A MIXED MATRIX FOR SUSTAINING CHLORPHENIRAMINE MALEATE RELEASE: KINETIC STUDY (2013)

An investigational study aimed for studying the effect of compritol ATO888 (compritol) on the release of chlorpheniramine maleate (CPM) from hydrophilic matrix (HPMC) was conducted. Matrix tablets were manufactured by direct compression using different compritol -HPMC blends. The release kinetics showed anomalous release mechanism. All the tested matrices containing compritol showed an increase in the release of CPM when compared with tablets contain HPMC only. The results revealed that controlling the speed of water soluble drug CPM release from a hydrophilic polymer HPMC can be obtained through designing a mixed hydrophilic lipophilic matrix using compritol. Compritol showed the ability to affect the water uptake of the matrix. Also, compritol was found to affect the relaxation of HPMC. For matrix containing 50% mixture of HPMC and compritol, the contribution of compritol in 17.5 to 25% of this part will result in a suitable release.
Stable Complexes Involving Acetylcholinesterase and Amyloid-β Peptide Change the Biochemical Properties of the Enzyme and Increase the Neurotoxicity of Alzheimer’s Fibrils (1998)

Brain acetylcholinesterase (AChE) forms stable complexes with amyloid-beta peptide (Abeta) during its assembly into filaments, in agreement with its colocalization with the Abeta deposits of Alzheimer's brain. The association of the enzyme with nascent Abeta aggregates occurs as early as after 30 min of incubation. Analysis of the catalytic activity of the AChE incorporated into these complexes shows an anomalous behavior reminiscent of the AChE associated with senile plaques, which includes a resistance to low pH, high substrate concentrations, and lower sensitivity to AChE inhibitors. Furthermore, the toxicity of the AChE-amyloid complexes is higher than that of the Abeta aggregates alone. Thus, in addition to its possible role as a heterogeneous nucleator during amyloid formation, AChE, by forming such stable complexes, may increase the neurotoxicity of Abeta fibrils and thus may determine the selective neuronal loss observed in Alzheimer's brain.
Interleukin‐4 inhibits bone resorption through an effect on osteoclasts and proinflammatory cytokines in an ex vivo model of bone resorption in rheumatoid arthritis (1994)

The inhibitory effect of IL-4 on bone resorption extends our knowledge of its antiinflammatory properties and suggests that the inflammatory cytokine imbalance in rheumatoid synovium also contributes to defects in bone resorption in RA.
Chimeric Antigen Receptor Therapy (2018)

Interview with Dr. Carl June on chimeric antigen receptor therapy. (09:04)Download This review addresses T-cell engineering and synthetic immunity, with a focus on producing durable remissions in patients with treatment-refractory tumors. Toxic effects of chimeric antigen receptor therapies include cytokine release syndrome and neurologic dysfunction.
Synthesis and antitrichomonal activity of certain pyrazolo[1,5-a]pyrimidines (1975)

Several bridgehead nitrogen heterocycles were synthesized to be screened as antimicrobial agents, modeled after nalidixic acid. The activity of these new compounds, all derivatives of 3-nitro-4,6-disubstituted pyrazolo (1,5-a)pyrimidin-7-ones (3,7,8, and 9), however, was found to be highly specific for Trichomonas foetus and completely lacking in activity against bacteria, fungi, and parasites other than Trichomonas. Of the nine componds synthesized, including the intermediate 4,6-disubstituted pyrazolo (1,5-a) pyrimidin-7-ones (2-6) and the 6-substituted or unsubstituted pyrazolo (1,5-a) pyrimidin-7-ones (1 and 4), only 6-carbethoxy-4-ethyl-3-nitropyrazolo(1,5-a)pyrimidin-7-one (7) was found to be a potent antitrichomal agent, being comparable or perhaps better than metronidazole. From a tentative structure-activity relationship study, it was apparent that the combination of the 3-mitro, 4-ethyl, and 6-carbethoxy groups imparted specific activity, wheras other substitutions imparted little or no antitrichomonal activity.
Location, DNA sequence and transcriptional analysis of the DNA polymerase gene of orf virus (1996)

Degenerate oligonucleotides representing conserved regions of various DNA polymerases hybridized to a region located 26 kb from the left end of the orf virus (OV) strain NZ-2 genome. DNA sequence analysis of this region revealed a 3024 bp open reading frame able to encode a protein with 56 percent amino acid identity to the DNA polymerase of vaccinia virus (VAC) and with significant homology to other DNA polymerases. Early transcripts derived from the open reading frame were detected in RNA purified from OV-infected cells, and 5' ends were mapped to a region 8-19 nt downstream from an A/T-rich sequence that resembles VAC early promoters. Unlike the VAC gene, the OV DNA polymerase makes almost exclusive use of G/C coding options. Attempts to substitute the activity of the OV DNA polymerase for its VAC counterpart were unsuccessful. This may indicate that the OV DNA polymerase is incompatible with VAC accessory proteins.
Restoration of accommodation: surgical options for correction of presbyopia (2008)

Accommodation is a dioptric change in the power of the eye to see clearly at near. Ciliary muscle contraction causes a release in zonular tension at the lens equator, which permits the elastic capsule to mould the young lens into an accommodated form. Presbyopia, the gradual age-related loss of accommodation, occurs primarily through a gradual age-related stiffening of the lens. While there are many possible options for relieving the symptoms of presbyopia, only relatively recently has consideration been given to surgical restoration of accommodation to the presbyopic eye. To understand how this might be achieved, it is necessary to understand the accommodative anatomy, the mechanism of accommodation and the causes of presbyopia. A variety of different kinds of surgical procedures has been considered for restoring accommodation to the presbyopic eye, including surgical expansion of the sclera, using femtosecond lasers to treat the lens or with so-called accommodative intraocular lenses (IOLs). Evidence suggests that scleral expansion cannot and does not restore accommodation. Laser treatments of the lens are in their early infancy. Development and testing of accommodative IOLs are proliferating. They are designed to produce a myopic refractive change in the eye in response to ciliary muscle contraction either through a movement of an optic or through a change in surface curvature. Three general design principles are being considered. These are single optic IOLs that rely on a forward shift of the optic, dual optic IOLs that rely on an increased separation between the two optics, or IOLs that permit a change in surface curvature to produce an increase in optical power in response to ciliary muscle contraction. Several of these different IOLs are available and being used clinically, while many are still in research and development.