gebhart/patrepeval huggingface dataset:
Dual Roles for Regulatory T-cell Depletion and Costimulatory Signaling in Agonistic GITR Targeting for Tumor Immunotherapy (2016)

Agonistic monoclonal antibodies (mAb) targeting the T-cell receptor coregulatory molecule GITR exert potent therapeutic activities in preclinical tumor models. Although anti-GITR mAb are thought to act by depleting and destabilizing the intratumoral T regulatory cell (Treg) population, the precise mechanism of action is obscure. Here, we addressed this issue using a Treg fate-mapping approach, which revealed that Treg loss was primarily due to cell depletion, with minimal evidence of Treg conversion to a non-Foxp3-expressing population. Further characterization of persisting Tregs following anti-GITR mAb treatment showed that a highly activated subpopulation of CD44<sup>hi</sup>ICOS<sup>hi</sup> intratumoral Tregs were preferentially targeted for elimination, with the remaining Tregs exhibiting a less suppressive phenotype. With these changes in the Treg population, intratumoral CD8<sup>+</sup> T cells acquired a more functional phenotype characterized by downregulation of the exhaustion markers PD-1 and LAG-3. This reversal of CD8<sup>+</sup> T-cell exhaustion was dependent on both agonistic GITR signaling and Treg depletion, as neither mechanism by itself could fully rescue the exhaustion phenotype. Tests of anti-human GITR antibody MK-4166 in a humanized mouse model of cancer mimicked many of the effects of anti-mouse GITR mAb in syngeneic tumor models, decreasing both Treg numbers and immune suppressor phenotype while enhancing effector responsiveness. Overall, our results show how anti-GITR mAb shifts Treg populations to enable immune attack on tumors, with clinical implications for molecular markers to modify emerging treatments. <i>Cancer Res; 77(5); 1108-18. ©2016 AACR</i>.
Aristolochene synthase. Isolation, characterization, and bacterial expression of a sesquiterpenoid biosynthetic gene (Ari1) from Penicillium roqueforti. (1993)

Aristolochene is the likely precursor of the sesquiterpenoid toxins produced by a number of filamentous fungi. One of these, PR-toxin, is produced by Penicillium roqueforti. We report here the isolation of a gene (Ari1) coding for the sesquiterpene cyclase, aristolochene synthase (AS), from P. roqueforti. Nucleotide sequence analysis of genomic and cDNA clones revealed that the Ari1 gene contains two introns. A Protein A/AS fusion enzyme was expressed in Escherichia coli and shown to have sesquiterpene cyclase activity. Analysis of the Protein A/AS fusion enzyme reaction mixtures by TLC and gas chromatography/mass spectrometry identified aristolochene as a major product. The Ari1 gene encodes a polypeptide of molecular weight 39,200. Expression of Ari1 occurs in stationary phase cultures of P. roqueforti and appears to be transcriptionally regulated.
Characterization of Crosslinked Gel Kinetics and Gel Strength Using NMR (2004)

Abstract Highly crosslinked gels are used in high-permeability reservoirs to achieve good fluid-loss control during well completion and workover operations. Crosslinked gels are also commonly used for shutting off unwanted gas and/or water influx into production wells, and for improving the conformance of the near wellbore injection profile in naturally fractured or in high-permeability reservoirs. In all such applications, the appropriate design of the gel treatment is critical to ensure an efficient gel placement. One important variable of the gel application design is the rheology of the gel system for establishing the crosslinking kinetics and the gel strength after gelation is complete. Rheology of gels and gelation rates are commonly determined by rheological methods or in a qualitative mode through bottle testing using a well-known gel strength code (i.e., the Sydansk&amp;s Code). The rheological measurements can be both time consuming and expensive, while bottle testing can lead to an inconsistent gel description as a result of the subjective nature of the gel strength code. This paper describes the use of low field nuclear magnetic resonance (NMR0 to monitor gelation rates and to characterize gel strength. This technique provides fast and accurate gel strength characterization and gelation monitoring. Through calibration with polymer concentration, crosslinker concentration, aging of gels, and the effect of brine, it is possible to predict NMR parameters. This then allows for a standardized method for the rheological categorization of gels. The results of this work present the correlation between the NMR spectra, rheological measurements, and the qualitative codification of gel strength.
Aqueous RDRP in the Presence of Cu0: The Exceptional Activity of CuI Confirms the SARA ATRP Mechanism (2014)

Polymerizations and mechanistic studies have been performed to understand the kinetic pathways for the polymerization of the monomer oligo(ethylene oxide) monomethyl ether acrylate (OEOA) in aqueous media. Typically, the medium consisted of 18 wt % OEOA in water, in the presence of Cu catalysts coordinated by tris[2-(dimethylamino)ethyl]amine (Me6TREN). Well-controlled polymerization of OEOA can be achieved in the presence of halide anions and Cu wire with ≲600 ppm of soluble CuII species, rather than previously reported ca. 10 000 ppm of CuII and Cu0 particles formed by predisproportionation of CuI prior to monomer and initiator addition. The mechanistic studies conclude that even though disproportionation is thermodynamically favored in aqueous media, the SARA ATRP, not SET-LRP, mechanism holds in these reactions. This is because alkyl halides are much more rapidly activated by CuI than by Cu0 (contribution of Cu0 to activation is <1%). Because of the high activity of CuI species toward alkyl halide activation, [CuI/Me6TREN] in solution is very low (<5 μM) and classical ATRP equilibrium between CuI and CuII species is maintained. Although in aqueous media disproportionation of CuI/Me6TREN is thermodynamically favored over comproportionation, unexpectedly, in the presence of alkyl halides, i.e., during polymerization, disproportionation is kinetically minimized. Disproportionation is slow because its rate is proportional to [CuI/Me6TREN]2 and [CuI/Me6TREN] is very small. Thus, during polymerization, comproportionation is 104 times faster than disproportionation, and the final thermodynamic equilibrium between disproportionation and comproportionation could be reached only after polymerization is completed. Activation of alkyl halides by CuI/Me6TREN in aqueous media occurs 8 orders of magnitude faster than disproportionation.
Diagnosing Schistosomiasis by Detection of Cell-Free Parasite DNA in Human Plasma (2009)

PCR for detection of CFPD in human plasma may provide a new laboratory tool for diagnosing schistosomiasis in all phases of clinical disease, including the capacity to rule out Katayama syndrome and active disease. Further studies are needed to confirm the clinical usefulness of CFPD quantification in therapy monitoring.
Ethanol Gelation: A Rapid Screening Test for Intravascular Coagulation (1968)

The ability of ethanol to gel soluble fibrin (fibrin monomer) in an in vitro test system and its further applicability in clinical situations are reported. Five patients with clinically documented disseminated intravascular coagulation had positive ethanol gelation tests. Thirty-six others, including four with hypofibrinogenemia from primary fibrinolysis, were negative. The ethanol test described is a simple, rapid screening procedure to distinguish between hypofibrinogenemia due to disseminated intravascular coagulation and hypofibrinogenemia due to primary fibrinolysis.
Finite-state transducers in language and speech processing (1997)

Finite-state machines have been used in various domains of natural language processing. We consider here the use of a type of transducers that supports very efficient programs: sequential transducers. We recall classical theorems and give new ones characterizing sequential string-to-string transducers. Transducers that output weights also play an important role in language and speech processing. We give a specific study of string-to-weight transducers, including algorithms for determinizing and minimizing these transducers very efficiently, and characterizations of the transducers admitting determinization and the corresponding algorithms. Some applications of these algorithms in speech recognition are described and illustrated.
Thromboerythrocytes. In vitro studies of a potential autologous, semi-artificial alternative to platelet transfusions. (1992)

In an attempt to overcome the limitations and drawbacks of using fresh platelets for transfusion therapy of thrombocytopenic patients, we have performed in vitro experiments on an autologous, semi-artificial alternative to platelet transfusions. Based on our previous studies of the interactions of unactivated and activated platelets with beads coated with peptides of various lengths, all of which contained the arginine-glycine-aspartic acid (RGD) cell recognition sequence, the peptide Ac-CGGRGDF-NH2 was chosen for covalent coupling to erythrocytes. A heterobifunctional crosslinking reagent (N-maleimido-6-aminocaproyl ester of 1-hydroxy-2-nitrobenzene-4-sulfonic acid) was used to crosslink via the peptide's free sulfhydryl group and the erythrocyte's surface amino groups. Approximately 0.5-1.5 x 10(6) peptide molecules bound per erythrocyte after 2 h of incubation, and most of the peptides appeared to crosslink to glycophorin A. The resulting cells, termed thromboerythrocytes, interacted selectively with activated platelets to form mixed aggregates. Studies with fluid phase RGD peptides and monoclonal antibodies indicated that the RGD peptides on the thromboerythrocytes interacted with the GPIIb/IIIa receptors on activated platelets. Thromboerythrocytes could also bind to platelets adherent to collagen. There was minimal erythrocyte hemolysis during the formation of thromboerythrocytes and studies of thromboerythrocyte osmotic fragility and cellular deformability showed no significant changes from control erythrocytes. Whereas there is a 20:1 ratio of erythrocytes to platelets in the circulation of normal individuals, the erythrocytes from as little as 50 ml of blood could be transformed into the equivalent of 2 U of platelets by numbers (equivalent to 18 U of platelets by mass), and reinfused into the same individual within several hours. These data encourage us to proceed to in vivo studies to assess the hemostatic efficacy of thromboerythrocytes in thrombocytopenic animals.
3,4,3-LI(1,2-HOPO): In vitro formation of highly stable lanthanide complexes translates into efficacious in vivo europium decorporation (2011)

The spermine-based hydroxypyridonate octadentate chelator 3,4,3-LI(1,2-HOPO) was investigated for its ability to act as an antenna that sensitizes the emission of Sm(III), Eu(III), and Tb(III) in the Visible range (Φ(tot) = 0.2-7%) and the emission of Pr(III), Nd(III), Sm(III), and Yb(III) in the Near Infra-Red range, with decay times varying from 1.78 μs to 805 μs at room temperature. The particular luminescence spectroscopic properties of these lanthanide complexes formed with 3,4,3-LI(1,2-HOPO) were used to characterize their respective solution thermodynamic stabilities as well as those of the corresponding La(III), Gd(III), Dy(III), Ho(III), Er(III), Tm(III), and Lu(III) complexes. The remarkably high affinity of 3,4,3-LI(1,2-HOPO) for lanthanide metal ions and the resulting high complex stabilities (pM values ranging from 17.2 for La(III) to 23.1 for Yb(III)) constitute a necessary but not sufficient criterion to consider this octadentate ligand an optimal candidate for in vivo metal decorporation. The in vivo lanthanide complex stability and decorporation capacity of the ligand were assessed, using the radioactive isotope (152)Eu as a tracer in a rodent model, which provided a direct comparison with the in vitro thermodynamic results and demonstrated the great potential of 3,4,3-LI(1,2-HOPO) as a therapeutic metal chelating agent.
Morphological heterogeneity among Salmonella lipopolysaccharide chemotypes in silver-stained polyacrylamide gels (1983)

The morphological heterogeneity of lipopolysaccharides (LPSs) among salmonella mutants with different LPS chemotypes was analyzed in silver-stained polyacrylamide gels. The biochemical differences in the LPS chemotypes were reflected in the unique profiles of the purified LPSs. The LPS profiles in the whole-cell lysates were also unique for each chemotype. (Whole-cell lysates were assessed by a method which preferentially silver stains LPS and by a proteinase K digest of whole-cell lysates. The silver-stained LPS profiles of proteinase K-digested lysates were similar to the homologous purified LPS and could be used to preliminarily characterize the LPS chemotype before purification.) In summary, biochemical variation in LPS composition can be detected in silver-stained polyacrylamide gels.
In vivo Phosphoproteome of Human Skeletal Muscle Revealed by Phosphopeptide Enrichment and HPLC−ESI−MS/MS (2009)

Protein phosphorylation plays an essential role in signal transduction pathways that regulate substrate and energy metabolism, contractile function, and muscle mass in human skeletal muscle. Abnormal phosphorylation of signaling enzymes has been identified in insulin-resistant muscle using phosphoepitope-specific antibodies, but its role in other skeletal muscle disorders remains largely unknown. This may be in part due to insufficient knowledge of relevant targets. Here, we therefore present the first large-scale in vivo phosphoproteomic study of human skeletal muscle from 3 lean, healthy volunteers. Trypsin digestion of 3-5 mg human skeletal muscle protein was followed by phosphopeptide enrichment using SCX and TiO(2). The resulting phosphopeptides were analyzed by HPLC-ESI-MS/MS. Using this unbiased approach, we identified 306 distinct in vivo phosphorylation sites in 127 proteins, including 240 phosphoserines, 53 phosphothreonines, and 13 phosphotyrosines in at least 2 out of 3 subjects. In addition, 61 ambiguous phosphorylation sites were identified in at least 2 out of 3 subjects. The majority of phosphoproteins detected are involved in sarcomeric function, excitation-contraction coupling (the Ca(2+)-cycle), glycolysis, and glycogen metabolism. Of particular interest, we identified multiple novel phosphorylation sites on several sarcomeric Z-disk proteins known to be involved in signaling and muscle disorders. These results provide numerous new targets for the investigation of human skeletal muscle phosphoproteins in health and disease and demonstrate feasibility of phosphoproteomics research of human skeletal muscle in vivo.
Extreme-ultraviolet harmonic generation near 13 nm with a two-color elliptically polarized laser field (2000)

Theoretical results for high-harmonic generation by a two-color elliptically polarized laser field are presented. Special emphasis is placed on coherent radiation near 13 nm in connection with the development of extreme-ultraviolet lithography. Linearly polarized radiation at this wavelength can be obtained with a linearly polarized bichromatic laser field, whereas circularly polarized radiation can be generated with a bichromatic circularly polarized field with counterrotating coplanar components. In both cases the harmonic emission efficiencies at the saturation intensity are more than 1 order of magnitude larger than for harmonic generation with a monochromatic linearly polarized field.
Application of capillary electrophoresis for trace ion analysis in rain water (2000)

Solving the problem due to transition metals' comigration during electrokinetic injection, the transient isotachophoresis (ITP) procedure was developed to preconcentrate and focus transition metals during electrokinetic injection. It was found to provide a suitable method for trace metals' preconcentration from rainwater at sub-μg/L level from buffer system consisting of 30 mM hydroxylamine hydrochloride, 0.1 mM 1,10-phenanthroline, 1% methanol, 15 mM ammonium chloride, and 0.08 M urea at pH=3.7. Trace metals as Cd2+, Zn2+, Cu2+, Co2+, and Fe2+ (total Fe determined as Fe2+) are determined with working range from 0.5–80 μg/L, repeatability less than 7%, and detection limits from 0.1 to 0.5 μg/L under optimized operation conditions as follows: Injection at 3 kV for 40 s prior to CE run at +15 kV in buffer system developed and with 0.4 mM tetrabutyl ammonium bromide added to rain sample as terminating ion. Leading and terminating ion effect, buffer additive, and operation conditions on performance of ITP procedure were investigated. Procedure developed was applied for trace metals' determination in rain water collected in Hong Kong. It provides fast, efficient, and economic method determining transition metals in rain sample down to sub-μg/L level, reducing sample pretreatment time and eliminating off-column preconcentration steps often leading to contamination problems for transition metals determination at μg/L level. © 2000 John Wiley & Sons, Inc. J Micro Sep 12: 337–344, 2000
Medical Academia and the Pharmaceutical Industry (2007)

Bob was feeling happy. He had just received the prescriber profiling information that he had requested. It appeared sales of Vivre had gone up after the dinner talk last week. Bob had expected this. The speaker, Dr. Johnson, an eminent academic psychiatrist, was employed by MedCorp to give talks on Vivre. He was a charismatic, much respected clinician with an impeccable CV. He had been involved in the company-sponsored trials for Vivre and had been impressed by the medication. Subsequently, he had become involved in doing many industry-sponsored educational activities for the medication. Dr. Johnson was paid for his time and received tens of thousands of dollars a year in additional income from these activities. Having seen the encouraging figures, Bob called Dr. Johnson to arrange several more speaking engagements over the coming months.
Selective Reduction of Blood Flow to White Matter During Hypercapnia Corresponds With Leukoaraiosis (2008)

This steal phenomenon likely represents the physiological correlate of the previously anatomically defined internal border zones. Spatial concordance with white matter changes in the elderly raises the possibility that this steal phenomenon may have a pathogenetic role.
Decrease of Vanillin Flavor Perception in the Presence of Casein and Whey Proteins (1991)

Abstract The effect of sodium caseinate and whey protein concentrate on vanillin flavor intensity was determined by quantitative descriptive analysis deviation from reference. A 12-member trained panel marked a horizontal line to rate vanillin, sodium caseinate, and whey protein concentrate flavor intensities in vanillin-sodium caseinate or vanillin-whey protein concentrate solutions using vanillin (78.5 ppm), sodium caseinate (.25%), or whey protein concentrate (.25%) references. The vanillin-sodium caseinate and vanillin-whey protein concentrate solutions contained 78.5 ppm vanillin, 2.5% sucrose, and .125, .25, and .5% sodium caseinate or whey protein concentrate, which were held 17 h at 6°C. The panel evaluated samples at room temperature and found that vanillin flavor intensity was moderately less than the reference for all sodium caseinate levels. As whey protein concentrate concentration increased from .125 to .5%, vanillin flavor decreased from moderately less than vanillin reference to much less than vanillin reference. This decrease in vanillin flavor intensity in the presence of sodium caseinate or whey protein concentrate may be due to cysteine-aldehyde condensation or Schiff base formation.
Oral tolerance in a murine model of relapsing experimental autoimmune uveoretinitis (EAU): induction of protective tolerance in primed animals (1997)

Oral administration of uveitogenic retinal antigens suppresses the expression of EAU induced by a subsequent immunization with these antigens. Effectiveness and mechanisms of oral tolerance in EAU have mainly been studied in the acute, monophasic model in Lewis rats by feeding antigen prior to induction of disease. In this study we investigated the effect of oral tolerance induction in the acute as well as the chronic-relapsing models in the B10.A mouse. In acute murine EAU we could effectively suppress disease by induction of oral tolerance prior to immunization. In the chronic-relapsing EAU, antigen feeding was started only after the animals had recovered from their first attack of uveitis. Under these experimental conditions the subsequent relapse was largely prevented. These experiments demonstrate that oral tolerance may have practical clinical implications in uveitis, which is predominantly a chronic-relapsing condition in humans.
A Structured Retroviral RNA Element That Mediates Nucleocytoplasmic Export of Intron-Containing RNA (1997)

A common feature of gene expression in all retroviruses is that unspliced, intron-containing RNA is exported to the cytoplasm despite the fact that cellular RNAs which contain introns are usually restricted to the nucleus. In complex retroviruses, the export of intron-containing RNA is mediated by specific viral regulatory proteins (e.g., human immunodeficiency virus type 1 [HIV-1] Rev) that bind to elements in the viral RNA. However, simpler retroviruses do not encode such regulatory proteins. Here we show that the genome of the simpler retrovirus Mason-Pfizer monkey virus (MPMV) contains an element that serves as an autonomous nuclear export signal for intron-containing RNA. This element is essential for MPMV replication; however, its function can be complemented by HIV-1 Rev and the Rev-responsive element. The element can also facilitate the export of cellular intron-containing RNA. These results suggest that the MPMV element mimics cellular RNA transport signals and mediates RNA export through interaction with endogenous cellular factors.
2p15-p16.1 microdeletions encompassing and proximal to BCL11A are associated with elevated HbF in addition to neurologic impairment (2015)

Elevated fetal hemoglobin (HbF) ameliorates the clinical severity of hemoglobinopathies such as β-thalassemia and sickle cell anemia. Currently, the only curative approach for individuals under chronic transfusion/chelation support therapy is allogeneic stem cell transplantation. However, recent analyses of heritable variations in HbF levels have provided a new therapeutic target for HbF reactivation: the transcriptional repressor BCL11A. Erythroid-specific BCL11A abrogation is now actively being sought as a therapeutic avenue, but the specific impact of such disruption in humans remains to be determined. Although single nucleotide polymorphisms in BCL11A erythroid regulatory elements have been reported, coding mutations are scarcer. It is thus of great interest that patients have recently been described with microdeletions encompassing BCL11A. These patients display neurodevelopmental abnormalities, but whether they show increased HbF has not been reported. We have examined the hematological phenotype, HbF levels, and erythroid BCL11A expression in 3 such patients. Haploinsufficiency of BCL11A induces only partial developmental γ-globin silencing. Of greater interest is that a patient with a downstream deletion exhibits reduced BCL11A expression and increased HbF. Novel erythroid-specific regulatory elements in this region may be required for normal erythroid BCL11A expression, whereas loss of separate elements in the developing brain may explain the neurological phenotype.