gebhart/patrepeval huggingface dataset:
IL-12 is expressed and released by human keratinocytes and epidermoid carcinoma cell lines. (1994)

IL-12 is a 70-kDa heterodimeric cytokine composed of two covalently linked chains, p40 and p35. IL-12 has multiple effects on T and NK cells and recently was found to be required for optimal Th1 cell development. In a variety of inflammatory skin disorders including delayed type hypersensitivity and contact hypersensitivity, Th1 cells appear to be critically involved. Because keratinocytes are well known to exhibit the capacity to release a variety of proinflammatory and immunologic cytokines, and thereby to be able to modulate inflammatory and immune reactions within the skin, it was investigated whether human keratinocytes and keratinocyte cell lines can release IL-12. Supernatants of phorbol-12,13-dibutyrate (PDBu) stimulated human epidermoid carcinoma cell lines (KB, A431) induced IFN-gamma production by PBL. This activity could be completely blocked by the addition of an anti-IL-12 Ab directed against the p40 subunit of IL-12 (C8.6). Release of IL-12 by keratinocyte cell lines was further confirmed by an RIA specific for p40. Immunoprecipitation under reducing conditions using the C8.6 Ab yielded specific bands at 40 kDa in supernatants of both KB cells and normal human keratinocytes. Northern blot analysis revealed IL-12-specific mRNA transcripts in PDBu-treated KB cells using cDNA probes encoding for p35 and p40. Moreover, by reverse transcription PCR specific transcripts for p35 and p40 were found in keratinocytes. These data indicate that keratinocyte cell lines and, although to a much lesser degree, normal human keratinocytes, exhibit the capacity to make IL-12; thus demonstrating for the first time IL-12 production by nonhemopoietic cells. Thus, one may speculate that keratinocytes via this capacity may influence the fate of Th-mediated immune responses, favoring Th1 responses by enhanced production of IL-12 or Th2 responses by reduced IL-12 release.
Collagenase clostridium histolyticum for Dupuytren's contracture (2010)

Phase III, clinical trials on collagenase for treatment of Dupuytren's contractures have recently been completed. Meeting primary and secondary objectives, collagenase has obtained FDA approval for clinical use. Collagenase now provides a non-operative option for Dupuytren's disease. Although short-term results show that collagenase is safe and efficacious, long-term effects of repeat injections and contracture recurrence rates have yet to be examined.
The Taste of Monosodium Glutamate: Membrane Receptors in Taste Buds (1996)

Receptor proteins for photoreception have been studied for several decades. More recently, putative receptors for olfaction have been isolated and characterized. In contrast, no receptors for taste have been identified yet by molecular cloning. This report describes experiments aimed at identifying a receptor responsible for the taste of monosodium glutamate (MSG). Using reverse transcriptase (RT)-PCR, we found that several ionotropic glutamate receptors are present in rat lingual tissues. However, these receptors also could be detected in lingual tissue devoid of taste buds. On the other hand, RT-PCR and RNase protection assays indicated that a G-protein-coupled metabotropic glutamate receptor, mGluR4, also is expressed in lingual tissues and is limited only to taste buds. In situ hybridization demonstrated that mGluR4 is detectable in 40-70% of vallate and foliate taste buds but not in surrounding nonsensory epithelium, confirming the localization of this metabotropic receptor to gustatory cells. Expression of mGluR4 in taste buds is higher in preweaning rats compared with adult rats. This may correspond to the known higher sensitivity to the taste of MSG in juvenile rodents. Finally, behavioral studies have indicated that MSG and L-2-amino-4-phosphonobutyrate (L-AP4), a ligand for mGluR4, elicit similar tastes in rats. We conclude that mGluR4 may be a chemosensory receptor responsible, in part, for the taste of MSG.
Abstract A92: Effects of lenvatinib on tumor-associated macrophages enhance antitumor activity of PD-1 signal inhibitors (2015)

Abstract [Background] Lenvatinib mesylate (lenvatinib) is an orally administrated multiple receptor tyrosine kinase inhibitor that selectively inhibits the kinase activities of VEGFR1-3, FGFR1-4, KIT, PDGF-Rα and RET, which are involved in tumor angiogenesis and proliferation of several cancer types such as thyroid cancer. In order to investigate whether lenvatinib has effects on immune cell population in tumors, we examined antitumor effects and immune modulating abilities of lenvatinib in syngeneic murine tumor models. [Materials and methods] We examined antitumor activity of lenvatinib against BNL 1ME A.7R.1 murine hepatocellular carcinoma cell line in syngeneic and immune-deficient mice model. Combination treatment with lenvatinib at 10mg/kg (qd) plus anti-PD-1 mAb at 500μg/ml (twice weekly) was conducted in LL/2 murine Lewis lung carcinoma cell line syngeneic model. For immune population analyses, lenvatinib at 10mg/kg was orally administrated in BNL 1ME A.7R.1 or LL/2 mice model. On Day 7 after starting treatment, percentages of immune populations were analyzed by flow cytometer. For cytokine analysis, IFNγ in CD8+ T cells was intracellularly stained and analyzed by flow cytometer. The expression of immune related molecules in tumors was analyzed by quantitative PCR. [Results] Lenvatinib showed more potent inhibition of BNL 1ME A.7R.1 tumor growth in immune functional mice than in immune-deficient mice when given the same dose. A flow-cytometry analysis of immune populations in both BNL 1ME A.7R.1 and LL/2 tumors indicated that lenvatinib significantly decreased the percentage of tumor associated macrophages (TAM) with CD45+CD11b+Ly6GlowLy6ClowF4/80+ markers. In addition, immune inhibitory molecules were downregulated in tumors. Lenvatinib significantly increased the percentage of IFNγ-secreting CD8+ T cells in regional lymph node. In LL/2 tumor model, the combination effect of lenvatinib with anti-PD-1 mAb showed a superior antitumor activity to each monotherapy. [Conclusion] These results indicate that lenvatinib has more potent antitumor effect in immune functional environment. It was noteworthy that lenvatinib decreased TAM population in tumors. Furthermore, lenvatinib enhanced antitumor activity of PD-1 signal inhibitors with combination treatment. Citation Format: Yu Kato, Kimiyo Tabata, Yusaku Hori, Sho Tachino, Kiyoshi Okamoto, Junji Matsui. Effects of lenvatinib on tumor-associated macrophages enhance antitumor activity of PD-1 signal inhibitors. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A92.
Demonstration of two distinct high molecular weight proteases in rabbit reticulocytes, one of which degrades ubiquitin conjugates. (1987)

Reticulocytes contain a nonlysosomal proteolytic pathway that requires ATP and ubiquitin. By DEAE chromatography and gel filtration, we were able to fractionate the ATP-dependent system into a 30-300-kDa fraction that catalyzes the ATP-dependent conjugation of ubiquitin to substrates ("Conjugation Fraction") and a high mass fraction (greater than 450 kDa) necessary for hydrolysis of the conjugated proteins. The latter contains two distinct proteases. One protease is unusually large, approximately 1500 kDa, and degrades proteins only when ATP and the conjugating fractions are added. This activity precipitates at 0-38% (NH4)2SO4 saturation and is essential for ATP-dependent proteolysis. Like crude extracts, it is labile in the absence of nucleotides and is inhibited by heparin, poly(Glu-Ala-Tyr), 3,4-dichloroisocoumarin, hemin, decavanadate, N-ethylmaleimide, and various peptide chloromethyl ketones. It lacks amino-peptidase and insulin-degrading activities and does not require tRNA for activity. The ubiquitin-conjugate degrading enzyme, which we suggest be named UCDEN, is inactive against substrates that cannot undergo ubiquitin conjugation. The smaller protease (670 kDa), which precipitates at 40-80% (NH4)2SO4 saturation, does not require ATP or ubiquitin and is therefore not required for ATP-dependent proteolysis. It is stimulated by N-ethylmaleimide and 3,4-dichloroisocoumarin and is stable at 37 degrees C. It hydrolyzes fluorometric tetrapeptides and proteins, including proteins which cannot be conjugated to ubiquitin. Thus, reticulocytes contain two large cytosolic proteases: one is essential for the degradation of ubiquitin conjugates, while the function of the other is uncertain.
Accurate and exact CNV identification from targeted high-throughput sequence data (2011)

Application of this method allows for identification of gains and losses in targeted sequence data, providing comprehensive mutation screening when combined with a short read aligner.
Quantitation of TIMP-1 in plasma of healthy blood donors and patients with advanced cancer (1999)

A kinetic enzyme-linked immunosorbent assay (ELISA) for plasma tissue inhibitor of metalloproteinase (TIMP)-1 was developed in order to examine the potential diagnostic and prognostic value of TIMP-1 measurements in cancer patients. The ELISA enabled specific detection of total TIMP-1 in EDTA, citrate and heparin plasma. The assay was rigorously tested and requirements of sensitivity, specificity, stability and good recovery were fulfilled. TIMP-1 levels measured in citrate plasma (mean 69.2+/-13.1 microg I(-1)) correlated with TIMP-1 measured in EDTA plasma (mean 73.5+/-14.2 microg I(-1)) from the same individuals in a set of 100 healthy blood donors (Spearman's rho = 0.62, P< 0.0001). The mean level of TIMP-1 in EDTA plasma from 143 patients with Dukes' stage D colorectal cancer was 240+/-145 microg I(-1) and a Mann-Whitney test demonstrated a highly significant difference between TIMP-1 levels in healthy blood donors and colorectal cancer patients (P < 0.0001). Similar findings were obtained for 19 patients with advanced breast cancer (mean 292+/-331 microg I(-1)). The results show that TIMP-1 is readily measured in plasma samples by ELISA and that increased levels of TIMP-1 are found in patients with advanced cancer. It is proposed that plasma measurements of TIMP-1 may have value in the management of cancer patients.
Prospective Study of the Association between Sleep-Disordered Breathing and Hypertension (2000)

We found a dose-response association between sleep-disordered breathing at base line and the presence of hypertension four years later that was independent of known confounding factors. The findings suggest that sleep-disordered breathing is likely to be a risk factor for hypertension and consequent cardiovascular morbidity in the general population.
A low-voltage folded-switching mixer in 0.18-/spl mu/m CMOS (2005)

Scaling of CMOS technologies has a great impact on analog design. The most severe consequence is the reduction of the voltage supply. In this paper, a low voltage, low power, AC-coupled folded-switching mixer with current-reuse is presented. The main advantages of the introduced mixer topology are: high voltage gain, moderate noise figure, moderate linearity, and operation at low supply voltages. Insight into the mixer operation is given by analyzing voltage gain, noise figure (NF), linearity (IIP3), and DC stability. The mixer is designed and implemented in 0.18-/spl mu/m CMOS technology with metal-insulator-metal (MIM) capacitors as an option. The active chip area is 160 /spl mu/m/spl times/200 /spl mu/m. At 2.4 GHz a single side band (SSB) noise figure of 13.9 dB, a voltage gain of 11.9 dB and an IIP3 of -3 dBm are measured at a supply voltage of 1 V and with a power consumption of only 3.2 mW. At a supply voltage of 1.8 V, an SSB noise figure of 12.9 dB, a voltage gain of 16 dB and an IIP3 of 1 dBm are measured at a power consumption of 8.1 mW.
INSTRUMENTATION FOR FLUORESCENCE MICROSCOPY WITH PICOSECOND TIME RESOLUTION (1985)

Abstract— Time‐resolved fluorescence microscopy using excitation by actively mode‐locked dye lasers and analysis by time‐correlated single photon counting is shown to be an effective way of obtaining a high degree of spatial and temporal resolution. The imaging capabilities of the microscope make for optimal instrument response functions even with inexpensive photomultiplier tubes. Thus far limited (by the laser source) to long wavelength visible excitation, the excellent light collection and imaging, coupled with the sensitivity of single photon counting make it highly probable that the much weaker U‐V second harmonics of the visible dyes will be useable. Certainly the potential of using the third harmonic line (355 nm) of a mode‐locked c.w. Nd: YAG laser, or fundamental lines from mode‐locked c.w. ion lasers as excitation sources will enhance the technique. Nevertheless, with visible‐absorbing dyes only it is possible to excite such fluorochromes as chlorophylls, porphyrins, xanthenes (rose bengal, erythrosin B), phycobiliproteins, thionine dyes, ethidium bromide, and so on. Furthermore, this technique can be straightforwardly extended for polarized light measurements thereby allowing determinations of rotational diffusion of fluorochromes in cells and organelles. The extension to variable temperature situations is easy to conceive. In addition to its use for examination of cellular and sub‐cellular entities, the equipment described can be profitably employed wherever spatial resolution may provide extra information, such as studies of powders and the structures of surfaces and interfaces.
[Gene diagnosis with an affinity sensor, BIACORE--principle and applications]. (1997)

We are developing new techniques for detecting point mutations by DNA-DNA hybridization and DNA-protein interaction analysis with an affinity sensor, BIACORE. To detect point mutations by the hybridization method using synthetic oligonucleotides, we already found that the length of the probe and the location of mismatches were important. The PCR products of the N-ras gene derived from Hep G2 cells, which have heterozygous point mutations at codon 61 in the gene, were analyzed and the point mutations were detected with 13-mer probes. We suggest that the detection method using DNA-DNA hybridization is useful for detecting known point mutations. However, detect unknown mutations, E. coli mismatch recognition protein, MutS, was employed. All mismatches in immobilized 20 base pairs of double-strand DNA could be detected by MutS binding. We have started to apply of the MutS to the detection of point mutations in PCR products.
Analysis of neutralizing antigenic sites on the surface of type A12 foot-and-mouth disease virus (1989)

A series of seven neutralizing monoclonal antibodies (nMAbs) directed against type A12 foot-and-mouth disease virus was used to generate neutralization-resistant variants. Both plaque reduction neutralization and microneutralization assays showed that the variants were no longer neutralized by the nMAbs used to generate them, although some of the variants still reacted with the nMAbs at high antibody concentrations. Results of cross-neutralization studies by both plaque reduction neutralization and microneutralization assays suggested the presence of at least one immunodominant antigenic site on the surface of type A12 foot-and-mouth disease virus, along with evidence of a second antigenic site on the viral surface. Two of the variants had reduced virulence in tissue culture as evidenced by their inability to inhibit cellular protein synthesis and a marked reduction in virus-induced cellular morphological alterations. Nucleotide sequencing of the variant genomes placed three epitopes of the major antigenic site on VP1 and the fourth epitope on VP3 and VP1. The one epitope of the minor site appears to reside only on VP1.
Studies on Antidiabetic Agents. XII. Synthesis and Activity of the Metabolites of (.+-.)-5-(p-(2-(5-Ethyl-2-pyridyl)ethoxy)benzyl)-2,4-thiazolidinedione (Pioglitazone). (1995)

The metabolites of (+/-)-5(-)[p(-)[2-(5-ethyl-2- pyridyl)ethoxy]benzyl]-2,4-thiazolidinedione (1, pioglitazone), which is a representative insulin-sensitizing agent, were synthesized to confirm their structures and for studies of their pharmacological properties. Of the metabolites identified, a compound hydroxylated at the 2-position of the ethoxy chain (3) and compounds oxygenated at the ethyl side chain attached to the pyridine ring (4, 5) were found to be active, although the potency was slightly lower than that of the parent compound.
Detective quantum efficiency dependence on x‐ray energy weighting in mammography (1999)

An evaluation of the dependence of detective quantum efficiency (DQE) on the incident energy spectrum has been made for mammography. The DQE dependence on the energy spectrum has been evaluated for energy-integrating detectors, photon-counting detectors, and detectors that measure the energy of each photon. To isolate the effect of the x-ray energy spectrum the detector has been assumed to be ideal, i.e., all noise sources are assumed to be zero except for quantum fluctuations. The result shows that the improvement in DQE, if the energy-integrating detector is compared to a single-photon counting detector, is of the order of 10%. Comparing the energy-integrating detector and the detector measuring the energy for each photon the improvement is around 30% using a molybdenum anode spectrum typical in mammography. It is shown that the optimal weight factors to combine the data in the case the energy is measured are very well approximated if the weight factors are proportional to E(-3). Another conclusion is that in calculating the DQE, a detector should be compared to one that uses ideal energy weighting for each photon since this provides the best signal-to-noise ratio. This has generally been neglected in the literature.
Synthetic Mimicking of Plant Oils and Comparison with Naturally Grown Products in Polyurethane Synthesis (2008)

The use of plant oils as industrial feedstocks can often be hampered by their lack of optimization towards a particular process, as well as their development being risky; growing suitable volumes of crops to test can take up to five years. To circumvent this, we aimed to discover a method that would mimic plant oil profiles in the laboratory, and show that they exhibited similar properties to the naturally grown plant oils in a given process. Using the synthesis of polyurethanes as an example, we have synthesized six different polymers and demonstrated that plant oils will produce polymers with similar physical properties to those oils mimicked in the laboratory. The use of this mimicking process can be extended to other types of polymers to obtain a method for predicting the properties of a given material based on the plant oil composition of a crop before it is grown in bulk.
Rationalization and Design of the Complementarity Determining Region Sequences in an Antibody-Antigen Recognition Interface (2012)

Protein-protein interactions are critical determinants in biological systems. Engineered proteins binding to specific areas on protein surfaces could lead to therapeutics or diagnostics for treating diseases in humans. But designing epitope-specific protein-protein interactions with computational atomistic interaction free energy remains a difficult challenge. Here we show that, with the antibody-VEGF (vascular endothelial growth factor) interaction as a model system, the experimentally observed amino acid preferences in the antibody-antigen interface can be rationalized with 3-dimensional distributions of interacting atoms derived from the database of protein structures. Machine learning models established on the rationalization can be generalized to design amino acid preferences in antibody-antigen interfaces, for which the experimental validations are tractable with current high throughput synthetic antibody display technologies. Leave-one-out cross validation on the benchmark system yielded the accuracy, precision, recall (sensitivity) and specificity of the overall binary predictions to be 0.69, 0.45, 0.63, and 0.71 respectively, and the overall Matthews correlation coefficient of the 20 amino acid types in the 24 interface CDR positions was 0.312. The structure-based computational antibody design methodology was further tested with other antibodies binding to VEGF. The results indicate that the methodology could provide alternatives to the current antibody technologies based on animal immune systems in engineering therapeutic and diagnostic antibodies against predetermined antigen epitopes.
Oxygen delivery using self???inflating resuscitation bags (2005)

Carter, Bradley G.; Fairbank, Bronwyn; Tibballs, James; Hochmann, Mark; Osborne, Anthony Author Information
High-Level Bacterial Expression and 15N-Alanine-Labeling of Bovine Trypsin. Application to the Study of Trypsin−Inhibitor Complexes and Trypsinogen Activation by NMR Spectroscopy (2001)

We describe here the high-level expression of bovine trypsinogen in E. coli, its refolding and activation to beta-trypsin, and the selective incorporation of (15)N-labeled alanine through supplementation of the growth medium. Using this procedure, we expressed (15)N-labeled S195A trypsinogens, both on a wild-type and on a D189S background, in amounts suitable for NMR spectroscopy. 2D [(1)H-(15)N]-HSQC NMR was used to follow conformational changes upon activation of trypsinogen and formation of noncovalent complexes between S195A or S195A/D189S trypsin and protein proteinase inhibitors of different structural families and different sizes, as well as to examine the effects of introduction of the D189S mutation. Spectra of good quality were obtained for both trypsins alone and in complexes of increasing size with the proteinase inhibitors BPTI (total molecular mass 31 kDa), SBTI (total molecular mass 44 kDa), and the serpin alpha(1)-proteinase inhibitor Pittsburgh (alpha(1)PI Pittsburgh) (total molecular mass 69 kDa). Assignments of alanines 55 and 56, close to the active site histidine, and of alanine 195, present in the S195A variant used for most of the studies, were made by mutagenesis. These three alanines, together with two others, probably close to the S1 specificity pocket, were very sensitive to complex formation. In contrast, the remaining 10 alanines were invariant in chemical shift in all 3 of the noncovalent complexes formed, reflecting the conservation of structure in complexes with BPTI and SBTI known from X-ray crystal structures, but also indicating that there is no change in backbone conformation for the noncovalent complex with alpha(1)PI, for which there is no crystal structure. This was true both for S195A and for S195A/D189S trypsins. This high-level expression and labeling approach will be of great use for solution NMR studies on trypsin-serpin complexes, as well as for structural and mechanistic studies on trypsin variants.