gebhart/patrepeval huggingface dataset:
Both the immunosuppressant SR31747 and the antiestrogen tamoxifen bind to an emopamil-insensitive site of mammalian Delta8-Delta7 sterol isomerase. (1998)

SR31747 is a novel agent that elicits immunosuppressive and anti-inflammatory effects. This drug was shown to inhibit Delta8-Delta7 sterol isomerase in yeast. To test whether this enzyme could also be an SR31747 target in mammals, the binding, antiproliferative and sterol biosynthesis inhibitory properties of various drugs were studied in recombinant sterol isomerase-producing yeast cells. Our results clearly show that SR31747 is a high affinity ligand of recombinant mammalian sterol isomerase (Kd = 1 nM). Tridemorph, a sterol biosynthesis inhibitor that is widely used in agriculture as an antifungal agent, is also a powerful inhibitor of murine and human sterol isomerases (IC50 value in the nanomolar range). Some drugs, like cis-flupentixol, trifluoperazine, 7-ketocholestanol and tamoxifen, inhibit SR31747 binding only with the mammalian enzymes, whereas other drugs, like haloperidol and fenpropimorph, are much more effective with the yeast enzyme than with the mammalian ones. Emopamil, a high affinity ligand of human sterol isomerase, is inefficient in inhibiting SR31747 binding to its mammalian target, suggesting that the SR31747 and emopamil binding sites on mammalian sterol isomerase do not overlap. In contrast, SR31747 binding inhibition by tamoxifen is very efficient and competitive (IC50 value in the nanomolar range), indicating that mammalian sterol isomerase contains a so-called antiestrogen binding site. Tamoxifen is found to selectively inhibit sterol biosynthesis at the sterol isomerase step in the cells that are producing the mammalian enzyme in place of their own sterol isomerase. Finally, we also show that tridemorph, a sterol biosynthesis inhibitor widely used in agriculture as an antifungal agent, is not selective of yeast Delta8-Delta7 sterol isomerase but is also highly efficient against murine Delta8-Delta7 sterol isomerase or human Delta8-Delta7 sterol isomerase. This observation contrasts with our already published results showing that fenpropimorph, another sterol isomerase inhibitor used in agriculture, is only poorly efficient against the mammalian enzymes.
miR-142 acts as a tumor suppressor in osteosarcoma cell lines by targeting Rac1 (2014)

Although the 5-year survival rate of osteosarcoma (OS) has risen to ~60-70%, a substantial portion of patients still respond poorly to chemotherapy and have a high risk of relapse or metastasis even after curative resection. In this study, we found that the expression of miR-142 was significantly reduced in OS tissues and OS cell lines, while Ras-related C3 botulinum toxin substrate 1 (Rac1) expression was increased in the OS tissues and OS cell lines compared with expression in the controls. We then demonstrated that miR-142 regulated Rac1 expression at the transcriptional and translational levels by directly targeting its 3'-untranslated region (3'UTR). In addition, by loss- and gain-of function experiments, we investigated the role of miR-142 in OS cell lines and found that miR-142 acted as a tumor suppressor in the OS cell lines and inhibited cell proliferation and cell invasion and arrested cell cycle in the S phase. Furthermore, miR-142 inhibited osteosarcoma cell invasion by inducing E-cadherin expression and reducing expression of matrix metalloproteinase 2 (MMP2) and MMP9. Thus, overexpression of miR-142 and/or knockdown of Rac1 would be a novel target for OS therapy in the future.
Measurement of lipid oxidation: A review (1978)

Abstract Lipids become rancid as a result of oxidation, and this oxidative rancidity is a major cause of food deterioration. The acceptability of a food product depends on the extent to which this deterioration has occurred. Thus some criterion for assessing the extent of oxidation is required. This paper reviews the experimental techniques for the measurement of lipid oxidation. The spectrum of tests ranges from simple organoleptic evaluations to chemical and physical methods. There is no ideal chemical method which correlates well with changes in organoleptic properties of oxidized lipids throughout the entire course of autoxidation. The methods discussed each give information about particular stages of the autoxidative process, and some are more applicable to certain lipid systems than others. The method of choice depends on a number of factors including the nature and history of the oxidized sample, the type of information required, the time available, and the test conditions. Clearly, there is a need for a more thorough assessment of the available methods so that unreliable, cumbersome methods may be discarded and modifications made to the remaining methods to maximize the information obtained. The ultimate criterion for the suitability of any test is its agreement with sensory perception of rancid flavors and odors.
Deacylation of echinocandin B by Actinoplanes utahensis. (1989)

Echinocandin B (ECB) is a lipopeptide antifungal agent produced by several species of Aspergillus. The lipid side chain of cyclic lipopeptides is known to be an important determinant of their antibiotic activity and toxicity. Deacylation of another lipopeptide antibiotic, A21978C, had formerly been accomplished with Actinoplanes utahensis. In spite of the structural dissimilarities between the peptide cores and acyl side chains of A21978C and ECB, A. utahensis also removed the linoleoyl acyl unit from the amino terminus of ECB to yield the bioinactive cyclic peptide core, or "nucleus". The ECB nucleus, which contained a new titratable group at the N-terminus, was subsequently employed for chemical reacylation with other side chains to yield a variety of novel ECB analogs. One of these, cilofungin (LY121019), containing an N-(4-n-octyloxybenzoyl)acyl unit, is currently undergoing clinical evaluation.
Clinical Decisions for Psychiatric Inpatients and Their Evaluation by a Trained Neural Network (1993)

Ninety-two consecutive treatment decisions regarding psychotic and depressed inpatients were evaluated by a trained neural network. Simultaneous evaluations according to the Brief Psychiatric Rating Scale (BPRS), the Hamilton scale, and the neural network were performed. A 15-point decrease in the BPRS for psychotic patients or a 10-point decrease in the Hamilton scale for depressed patients was the cut-off point for treatment success. The neural network performed similarly to the clinicians. The combined clinician-network success rate reached 79% and was significantly higher than that for each alone. Clinicians and neural network disagreed on 62% of decisions made for depressed patients and on 55% of decisions made for psychotic patients. The proportion of agreement was lower in both diagnostic groups than expected by chance. However, the high success of the combined clinician and neural network decisions and the high rate of mutual disagreement may imply that a combined decision is fruitful.
Production and the characterization of monoclonal antibody against CD43, K06 (2003)

Abstract: A monoclonal antibody against human CD43 has been developed and designated as K06. Its reactivity in the lymphoid organs was different from that of known anti‐CD43 monoclonal antibodies suggesting that this may recognize a novel epitope of human CD43 molecule. The CD43 epitope detected by anti‐K06 monoclonal antibody was highly expressed in cortical thymocytes, platelets, and myeloid cells of normal peripheral blood, and its reactivity was comparable to that of known anti‐CD43 monoclonal antibodies. However, the density of this epitope was lower in the medullary thymocytes. Biochemical studies indicated that anti‐K06 monoclonal antibody could recognize glycosylated moiety of CD43 antigen. The expression profile of anti‐K06 monoclonal antibody in several cell lines was somewhat different from that of known anti‐CD43 antibodies. In addition, CD43 ligation through the K06 epitope appeared to induce apoptosis in human leukemic cell line, Molt‐4. We therefore assume that K06 epitope of human CD43 might have some role in T‐cell development.
Early diagnosis to enable early treatment of pre-osteoarthritis (2012)

Osteoarthritis is a prevalent and disabling disease affecting an increasingly large swathe of the world population. While clinical osteoarthritis is a late-stage condition for which disease-modifying opportunities are limited, osteoarthritis typically develops over decades, offering a long window of time to potentially alter its course. The etiology of osteoarthritis is multifactorial, showing strong associations with highly modifiable risk factors of mechanical overload, obesity and joint injury. As such, characterization of pre-osteoarthritic disease states will be critical to support a paradigm shift from palliation of late disease towards prevention, through early diagnosis and early treatment of joint injury and degeneration to reduce osteoarthritis risk. Joint trauma accelerates development of osteoarthritis from a known point in time. Human joint injury cohorts therefore provide a unique opportunity for evaluation of pre-osteoarthritic conditions and potential interventions from the earliest stages of degeneration. This review focuses on recent advances in imaging and biochemical biomarkers suitable for characterization of the pre-osteoarthritic joint as well as implications for development of effective early treatment strategies.
Absorption Spectra of Phenolazopyrazolones in KCI Pellets (1967)

フェノールアゾピラゾロン誘導体は溶液中と結晶状態とでは色調が異なる。今回は可視吸収スペクトルを,結晶型に変化が起きないよう種々条件を検討しながら,塩化カリウム錠剤中で測定した。この吸収スペクトルと溶液中でのスペクトルとの違いを調べるため,フェノール基の中の置換基が吸収最大位置におよぼす効果の差を,両状態聞で比較検討してみた。そして,差の原因を赤外吸収スペクトルによって得られる官能基の挙動と結びつけることにより広い意味での構造と色調との関係を明らかにすることができた。フェノール核中のOH基がヒドラゾン基と強い水素結合をしている化合物類では最大吸収位置λmaxは,フェノール核中の置換基のHammettのσ定数が増大するにつれて短波長から430mμに収敷する。OH基がヒドラゾン基と水素結合をしていない化合物類では,λmaxはσが増加するにつれて,短波長側に移動しOH基をもたないベンゼンアゾピラゾロン誘導体の場合と同じであった。λmaxとOH伸縮振動数λmaxとC=O伸縮振動数,との関係においても,上記二つのものを区別して考えることができた。したがって,OH基がヒドラゾン基と水素結合するか,否かによって,フェノール核中の置換基が色調におよ曝す影響は異なっているといえる。
Dopamine-modified α-synuclein blocks chaperone-mediated autophagy (2008)

Altered degradation of alpha-synuclein (alpha-syn) has been implicated in the pathogenesis of Parkinson disease (PD). We have shown that alpha-syn can be degraded via chaperone-mediated autophagy (CMA), a selective lysosomal mechanism for degradation of cytosolic proteins. Pathogenic mutants of alpha-syn block lysosomal translocation, impairing their own degradation along with that of other CMA substrates. While pathogenic alpha-syn mutations are rare, alpha-syn undergoes posttranslational modifications, which may underlie its accumulation in cytosolic aggregates in most forms of PD. Using mouse ventral medial neuron cultures, SH-SY5Y cells in culture, and isolated mouse lysosomes, we have found that most of these posttranslational modifications of alpha-syn impair degradation of this protein by CMA but do not affect degradation of other substrates. Dopamine-modified alpha-syn, however, is not only poorly degraded by CMA but also blocks degradation of other substrates by this pathway. As blockage of CMA increases cellular vulnerability to stressors, we propose that dopamine-induced autophagic inhibition could explain the selective degeneration of PD dopaminergic neurons.
Current Status and Issues in Cancer Stem Cell Study (2008)

Cancer stem cells (CSCs) have been positively identified and successfully isolated from some but not all cancers. The studies on CSCs to date suggest that these cells are rare among the tumor cell population, and they are capable of self-renewing and maintaining tumor growth and heterogeneity. Therapies aimed at CSCs have shown some promise, but their further development will require a more thorough understanding of the biology of CSCs and methods for identifying and isolating this cell subpopulation. This review examines what is known to date regarding the similarities and differences between cancer and somatic stem cells: CSC surface marker development and cell isolation (including a model isolation from our lab), the frequency, potential origin, and signal transduction of CSCs, and the current state of CSC-targeting therapeutic strategies.
Partial protection against genital reinfection by immunization of guinea-pigs with isolated outer-membrane proteins of the chlamydial agent of guinea-pig inclusion conjunctivitis (1993)

Because partial protection against reinfection is induced by experimental infection in the guinea-pig model of genital chlamydial infection, we sought to induce immunity by immunization. Female guinea-pigs were immunized subcutaneously with the major outer-membrane protein (MOMP) and the 61 kDa cysteine-rich outer-membrane protein (61 kDa) of the agent of guinea-pig inclusion conjunctivitis (GPIC) eluted from SDS-polyacrylamide gels (SDS-MOMP, SDS-61 kDa). Post-immunization sera and secretions contained antibodies to the SDS-purified proteins at high titre as measured by immunoblotting, whereas enzyme immunoassays (EIA) using whole elementary bodies as antigen showed significantly lower titres (P < 0.001). Likewise, blastogenic responses of peripheral mononuclear cells to GPIC elementary bodies were weak. Animals immunized with SDS-MOMP and SDS-61 kDa were fully susceptible to intravaginal challenge, as were control animals immunized with buffer without protein. Another group of animals were immunized with material prepared by extraction of chlamydial outer-membrane complexes with octyl beta-D-glucopyranoside (OGP) and dithiothreitol, which consisted largely of MOMP (OGP-MOMP). In contrast to the SDS-MOMP group, sera and secretions in the OGP-MOMP group showed high titres in EIA, and high titre antibodies to MOMP by immunoblot; however, most animals also had antibodies to 61 kDa, 72 kDa and ca. 84 kDa outer-membrane proteins. OGP-MOMP animals were partially protected against genital challenge as evidenced by low inclusion scores compared to control animals, although duration of infection measured by culture isolation was similar to controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Neuroprotective Function of the PGE2EP2 Receptor in Cerebral Ischemia (2004)

The cyclooxygenases COX-1 and COX-2 catalyze the first committed step of prostaglandin synthesis from arachidonic acid. Previous studies in rodent stroke models have shown that the inducible COX-2 isoform promotes neuronal injury, and the administration of COX-2 inhibitors reduces infarct volume. We investigated the function of PGE2, a principal prostaglandin product of COX-2 enzymatic activity, in neuronal survival in cerebral ischemia. PGE2 exerts its downstream effects by signaling through a class of four distinct G-protein-coupled EP receptors (for E-prostanoid: EP1, EP2, EP3, and EP4) that have divergent effects on cAMP and phosphoinositol turnover and different anatomical distributions in brain. The EP2 receptor subtype is abundantly expressed in cerebral cortex, striatum, and hippocampus, and is positively coupled to cAMP production. In vitro studies of dispersed neurons and organotypic hippocampal cultures demonstrated that activation of the EP2 receptor was neuroprotective in paradigms of NMDA toxicity and oxygen glucose deprivation. Pharmacologic blockade of EP2 signaling by inhibition of protein kinase A activation reversed this protective effect, suggesting that EP2-mediated neuroprotection is dependent on cAMP signaling. In the middle cerebral artery occlusion-reperfusion model of transient forebrain ischemia, genetic deletion of the EP2 receptor significantly increased cerebral infarction in cerebral cortex and subcortical structures. These studies indicate that activation of the PGE2 EP2 receptor can protect against excitotoxic and anoxic injury in a cAMP-dependent manner. Taken together, these data suggest a novel mechanism of neuroprotection mediated by a dominant PGE2 receptor subtype in brain that may provide a target for therapeutic intervention.
Multilayered Gold-Nanoparticle/Polyimide Composite Thin Film through Layer-by-Layer Assembly (2007)

A novel type of composite thin film consisting of gold nanoparticles (AuNPs) and polymide (PI) was fabricated through layer-by-layer (LBL) assembly. To fabricate such films, bare AuNPs and a poly (amic acid) bearing pendant amine groups, namely, amino poly (amic acid) or APAA, were synthesized and assembled in an LBL fashion. Without any organic encapsulation layer on their surface, AuNPs were bound directly to APAA chains at the amine sites; X-ray photoelectron spectroscopy study suggested that the binding was based on a combined effect of metal-ligand coordination and electrostatic interaction, with the former dominating over the latter. An approximately linear growth of the film started from the second layer of AuNP as revealed by the UV-vis spectroscopy, and the degree of particle aggregation was higher in the first AuNP layer than in the subsequent layers due to the differences in the density of binding sites. The resultant assembly was heated to imidize the APAA, thereby creating a robust composite structure.
Design and experiments of a high-conversion-efficiency 5.8-GHz rectenna (1998)

A high-efficiency rectenna element has been designed and tested at 5.8 GHz for applications involving microwave-power transmission. The dipole antenna and filtering circuitry are printed on a thin duroid substrate. A silicon Schottky-barrier mixer diode with a low breakdown voltage is used as the rectifying device. The rectenna element is tested inside a waveguide simulator and achieves an RF-to-DC conversion efficiency of 82% at an input power level of 50 mW and 327 /spl Omega/ load. Closed-form equations are given for the diode efficiency and input impedance as a function of input RF power. Measured and calculated efficiency results are in good agreement. The antenna and circuit design are based on a full-wave electromagnetic simulator. Second harmonic power levels are 21 dB down from the fundamental input power.
Octadentate catecholamide ligands for Pu(IV) based on linear or preorganized molecular backbones (1996)

Nine new octadentate ligands based on cyclic, spermine (3,4,3-LI), desferrioxamine (DFO), or H-shaped tetrakisamine (penten) molecular backbones were prepared containing catecholamide (CAM), carboxycatecholamide (CAM(C)), or terephthalamide (TAM) chelating units. Mice were injected intravenously with 239Pu(i.v.) citrate, treated with 30 mumol kg-1 of a ligand by intraperitoneal injection at 1 h or by gastric intubation at 3 min, and Pu retention in tissues and Pu transfer to excreta were measured at 24 h. Given by injection, three soluble ligands composed of MeTAM (3,4,3-LIMeTAM, DFO-MeTAM, H(2,2)-MeTAM) reduced Pu retention in the body to 27-28% of control compared with 32 and 37% of control obtained in mice similarly treated with 3,4,3-LICAM(C) or CaNa3-DTPA, respectively. The MeTAM ligands reduced Pu retention in the skeleton as much as an equimolar amount of CaNa3-DTPA, while Pu retention in the liver (on average, 16% of control) was significantly less than was obtained with CaNa3-DTPA (35% of control). Given orally, H(2,2)-MeTAM reduced Pu retention in the whole body to 58% of control compared with reductions to 62 and 94% of control achieved with 3,4,3-LICAM(C) or CaNa3-DTPA, respectively. Penten is both partially preorganized for metal binding and spatially suitable for encapsulation of actinide(IV), and ligands with the penten backbone are easier and less costly to prepare than those based on spermine or DFO. The biological results confirmed that penten is a suitable as well as practical structural backbone for new octadentate ligands. In agreement with the great stability of the ferric complex with MeTAM, as determined in vitro, the small, simple, soluble penten-based octadentate ligand, H(2,2)-MeTAM, was shown to be, overall, the most effective catecholamide ligand for enhancing Pu excretion. Either combined in H(2,2)-MeTAM or separately, the penten backbone and the MeTAM chelating unit are potentially useful additions to the set of backbones and binding units of multidentate ligands identified as effective for in vivo chelation of the actinides.
Hydrogel adhesives for wound-care applications. (2002)

This review of pressure-sensitive adhesives used in wound dressings describes the properties of recently developed hydrogel adhesives. The findings of a study comparing the adhesion and moisture vapour transition rates of the hydrogel adhesives with some existing wound-dressing products are reported.
Human Biliverdin IXα Reductase is a Zinc‐Metalloprotein (1996)

Biliverdin IXalpha reductase (BVR) catalyzes the conversion of the heme b degradation product, biliverdin, to bilirubin. BVR is unique among enzymes characterized to date in that it has dual pH/cofactor (NADH, NADPH) specificity. A cDNA clone encoding human BVR was isolated from a gamma library using a probe generated via reverse transcription and the polymerase chain reaction from human placental RNA. This approach was taken because the more direct approach of using the previously isolated rat BVR cDNA as the hybridization probe did not succeed. The human cDNA was cloned and sequenced; it was shown to have an open reading frame encoding a 296-amino-acid protein in which could be identified four peptides previously identified by micro-sequencing purified protein. The cDNA hybridized with a single message of approximately 1.2 kb in human kidney poly(A)-rich RNA, and appeared, by Southern blot analysis, to be the product of a single-copy gene. Sequence analysis indicated that the human reductase shows approximately 83% identity, at both the nucleotide and amino acid levels, with rat BVR. In some regions including the carboxyl terminus, protein sequence identity drops to 45%. Also noteworthy is the presence of two additional cysteine residues in the encoded human reductase (five compared to three for rat). The protein produced by an expression plasmid in which the insert was cloned in frame with lacZ sequences was characterized, and demonstrated dual pH and cofactor dependence. However, as suggested by kinetic analysis, the human enzyme may also use NADH as cofactor, as opposed to the rat reductase, which most likely utilizes only NADPH under physiological conditions. Western blot analysis and isoelectric focusing demonstrate that, although migrating as a single band on SDS/PAGE, the expressed protein, like that purified from tissue, consists of several isoelectric charge variants. Atomic absorption spectroscopy indicates that the protein purified from human liver contains Zn at an approximately 1:1 molar ratio. That human BVR is a Zn metalloprotein was further substantiated by 65Zn exchange analysis of both the purified and the fusion protein expressed in Escherichia coli. Exogenous Zn also inhibits NADPH-dependent, but not NADH-dependent, activity. Hence, the NADH and NADPH binding regions are differentiated by their ability to interact with Zn; Fe-hematoporphyrin, however, inhibited both NADH- and NADPH-dependent activity.
Recombinant nucleases CEL I from celery and SP I from spinach for mutation detection (2007)

The insect cell-expressed CEL I orthologs may not be identical to their native counterparts purified from plant tissues. The present expression system should facilitate further development of CEL I-based mutation detection technologies.