gebhart/patrepeval huggingface dataset:
Arabidopsis CYP707As Encode (+)-Abscisic Acid 8′-Hydroxylase, a Key Enzyme in the Oxidative Catabolism of Abscisic Acid (2004)

Abscisic acid (ABA) is involved in a number of critical processes in normal growth and development as well as in adaptive responses to environmental stresses. For correct and accurate actions, a physiologically active ABA level is controlled through fine-tuning of de novo biosynthesis and catabolism. The hydroxylation at the 8'-position of ABA is known as the key step of ABA catabolism, and this reaction is catalyzed by ABA 8'-hydroxylase, a cytochrome P450. Here, we demonstrate CYP707As as the P450 responsible for the 8'-hydroxylation of (+)-ABA. First, all four CYP707A cDNAs were cloned from Arabidopsis and used for the production of the recombinant proteins in insect cells using a baculovirus system. The insect cells expressing CYP707A3 efficiently metabolized (+)-ABA to yield phaseic acid, the isomerized form of 8'-hydroxy-ABA. The microsomes from the insect cells exhibited very strong activity of 8'-hydroxylation of (+)-ABA (K(m) = 1.3 microm and k(cat) = 15 min(-1)). The solubilized CYP707A3 protein bound (+)-ABA with the binding constant K(s) = 3.5 microm, but did not bind (-)-ABA. Detailed analyses of the reaction products confirmed that CYP707A3 does not have the isomerization activity of 8'-hydroxy-ABA to phaseic acid. Further experiments revealed that Arabidopsis CYP707A1 and CYP707A4 also encode ABA 8'-hydroxylase. The transcripts of the CYP707A genes increased in response to salt, osmotic, and dehydration stresses as well as ABA. These results establish that the CYP707A family plays a key role in regulating the ABA level through the 8'-hydroxylation of (+)-ABA.
On the mechanism of sensing unfolded protein in the endoplasmic reticulum (2005)

Unfolded proteins in the endoplasmic reticulum (ER) activate the ER transmembrane sensor Ire1 to trigger the unfolded protein response (UPR), a homeostatic signaling pathway that adjusts ER protein folding capacity according to need. Ire1 is a bifunctional enzyme, containing cytoplasmic kinase and RNase domains whose roles in signal transduction downstream of Ire1 are understood in some detail. By contrast, the question of how its ER-luminal domain (LD) senses unfolded proteins has remained an enigma. The 3.0-A crystal structure and consequent structure-guided functional analyses of the conserved core region of the LD (cLD) leads us to a proposal for the mechanism of response. cLD exhibits a unique protein fold and is sufficient to control Ire1 activation by unfolded proteins. Dimerization of cLD monomers across a large interface creates a shared central groove formed by alpha-helices that are situated on a beta-sheet floor. This groove is reminiscent of the peptide binding domains of major histocompatibility complexes (MHCs) in its gross architecture. Conserved amino acid side chains in Ire1 that face into the groove are shown to be important for UPR activation in that their mutation reduces the response. Mutational analyses suggest that further interaction between cLD dimers is required to form higher-order oligomers necessary for UPR activation. We propose that cLD directly binds unfolded proteins, which changes the quaternary association of the monomers in the membrane plane. The changes in the ER lumen in turn position Ire1 kinase domains in the cytoplasm optimally for autophosphorylation to initiate the UPR.
Wheeze Detection Using Cepstral Analysis in Gaussian Mixture Models (2007)

Traditional wheezes detection methods are based on the frequency and durations of acoustic signal or the location of peaks from successive spectra. In these methods, the discriminative threshold used to identify peaks usually is fixed empirically. Therefore, accuracy of detected wheeze is affected by environment noise and artificial factors. The objective of this study is to classify normal and abnormal (wheezing) respiratory sounds using Cepstral analysis in Gaussian Mixture Models. The sound signal is divided in overlapped segments, which are characterized by a reduced dimension feature vectors using Mel-Frequency Cepstral Coefficients. In this study the ;speaker' is wheeze. During the test phase, an unknown sound is compared to all the GMM models and the classification decision is based on the Maximum Likelihood criterion. In these processes, identification is based on threshold value. If the threshold is bigger than zero, the sound is normal. Otherwise, the sound is wheeze. From experimental results, when the Gaussian mix number is 16, the accuracy of identification of wheeze is up to 90%.
Adhesion-Related Kinase Induction of Migration Requires Phosphatidylinositol-3-Kinase and Ras Stimulation of Rac Activity in Immortalized Gonadotropin-Releasing Hormone Neuronal Cells (2007)

GnRH neurons migrate into the hypothalamus during development. Although migratory defects may result in disordered activation of the reproductive axis and lead to delayed or absent sexual maturation, specific factors regulating GnRH neuronal migration remain largely unknown. The receptor tyrosine kinase, adhesion-related kinase (Ark) (also known as Axl, UFO, and Tyro7), has been implicated in the migration of GnRH neuronal cells. Binding of its ligand, growth arrest-specific gene 6 (Gas6), promotes cytoskeletal remodeling and migration of NLT GnRH neuronal cells via Rac and p38 MAPK. Here, we examined the Axl effectors proximal to Rac in the signaling pathway. Gas6/Axl-induced lamellipodia formation and migration were blocked after phosphatidylinositol-3-kinase (PI3K) inhibition in GnRH neuronal cells. The p85 subunit of PI3K coimmunoprecipitated with Axl and was phosphorylated in a Gas6-sensitive manner. In addition, PI3K inhibition in GnRH neuronal cells diminished Gas6-induced Rac activation. Exogenous expression of a dominant-negative form of Ras also decreased GnRH neuronal lamellipodia formation, migration, and Rac activation. PI3K inhibition blocked Ras in addition to Rac activation and migration. In contrast, pharmacological blockade of the phospholipase C gamma effectors, protein kinase C or calcium/calmodulin protein kinase II, had no effect on Gas6/Axl signaling to promote Rac activation or stimulate cytoskeletal reorganization and migration. Together, these data show that the PI3K-Ras pathway is a major mediator of Axl actions upstream of Rac to induce GnRH neuronal cell migration.
A comparison of Affymetrix gene expression arrays (2007)

Despite noticeable differences in the probe-level reproducibility, gene-level reproducibility and differential expression detection are quite similar across the three platforms. The HuEx array, an all-encompassing array, has the flexibility of measuring all known or predicted exonic content. However, the HuEx array induces poorer reproducibility for genes with fewer exons. The HuGene measures just the well-annotated genome content and appears to perform well. The U133 array, though not able to measure across the full length of a transcript, appears to perform as well as the newer designs on the set of genes common to all 3 platforms.
Nicotine, cotinine, and anabasine inhibit aromatase in human trophoblast in vitro. (1986)

Epidemiologic studies suggest that women who smoke have lower endogenous estrogen than nonsmokers. To explore the possible link between cigarette smoking and decreased endogenous estrogens, we have examined the effects of constituents of tobacco on estrogen production in human choriocarcinoma cells and term placental microsomes. In choriocarcinoma cell cultures, nicotine, cotinine (a major metabolite of nicotine), and anabasine (a minor component of cigarette tobacco) all inhibited androstenedione conversion to estrogen in a dose-dependent fashion. Removal of nicotine, cotinine, and anabasine from the culture medium resulted in the complete reversal of the inhibition of aromatase. In the choriocarcinoma cell cultures, a supraphysiologic concentration of androstenedione (73 microM) in the culture medium blocked the inhibition of aromatase caused by nicotine, cotinine, and anabasine. In preparations of term placental microsomes, nicotine, cotinine, and anabasine inhibited the conversion of testosterone to estrogen. Kinetic analysis demonstrated the inhibition to be competitive with respect to the substrate. These findings suggest that some nicotinic alkaloids directly inhibit aromatase. This mechanism may explain, in part, the decreased estrogen observed in women who smoke.
Combining Ultrasound and Biochemistry in First‐Trimester Screening for Down's syndrome (1997)

Data on pregnancies with and without Down's syndrome between 10 and 14 weeks of pregnancy were used to determine the performance of combined ultrasound and biochemical markers in prenatal screening for Down's syndrome. We used three datasets: one published by Pandya et al. (1995) on nuchal translucency measurement in 86 Down's syndrome pregnancies; one published by Wald et al. (1996a) on free beta human chorionic gonadotrophin (hCG) and pregnancy-associated plasma protein A (PAPP-A) in 77 affected pregnancies and 385 unaffected pregnancies; and the third from Schuchter et al. on 561 unaffected pregnancies with nuchal translucency measurement. Combining the data from these three datasets showed that screening between 10 and 14 weeks by combining the serum markers with nuchal translucency measurement had a detection rate of 80 per cent for a 5 per cent false-positive rate, better than maternal age with two serum markers (62 per cent for 5 per cent) or maternal age with nuchal translucency measurement (63 per cent for 5 per cent). At this time in pregnancy, it appears that screening using the combined test is better than second-trimester serum screening (76 per cent for 5 per cent), though these estimates do not allow for any association between the markers and spontaneous fetal loss, an issue that needs to be clarified by further research. Meanwhile, these results provide a reasonable working estimate of screening performance using different combinations of these markers. © 1997 John Wiley & Sons, Ltd.
Synthesis and biological activity of some D-ring modified estrone derivatives (1999)

SCOPUS: ar.j
Adjuvant Chemotherapy of Breast Cancer (1981)

Adjuvant chemotherapy of breast cancer involves the use of cytotoxic drugs after local and regional therapy has been given. It received extensive notice throughout the last half of the 1970s and is now established as a therapeutic concept. Its purpose is to eradicate micrometastases and to permit long-term, disease-free survival (cure) in patients who would otherwise relapse with surgery alone.Adequate analysis of adjuvant trials will take many years of follow-up.1 Early analysis will compare relapse-free survival or time to recurrence against acute toxicity and economic and psychosocial costs. Late analysis will involve comparison of overall survival and pattern of . . .
A monoclonal antibody reacting with endothelial cells of budding vessels in tumors and inflammatory tissues, and non‐reactive with normal adult tissues (1986)

This report describes a monoclonal antibody (MAb) generated by immunization of mice with cell suspensions of capillary-rich fragments of mammary carcinomas. The antibody (EN 7/44) belongs to the IgM class and detects a 30.5 kDa antigen which is found in the cytoplasm of human placental and umbilical vein-endothelial cells (HUVEC) and on the surface of tumor endothelium. Using indirect immunofluorescence and immunoperoxidase techniques, we did not find the MAb in peripheral blood cells or in any human cell lines tested, nor in endothelial cells from normal, nonproliferating adult tissues. Positively staining endothelium was found in the placenta, the umbilical vein and in proliferating normal tissues (intestine). Positive endothelial cells were found in acute inflammatory reactions and in tumors. In the latter, the strongest reactions were seen in newly formed budding capillaries, which were identified by their reactivity with Ulex europaeus I-lectin and antibodies against F VIII-RAG. In tumor tissues, large vessels could be positively stained with the EN 7/44 antigen, in contrast to inflammatory tissues. It is concluded that endothelial cells at the tip of a budding capillary express distinct phenotypic characteristics.
The involvement of poly(ADP‐ribose) polymerase in the oxidative stress responses in plants (1998)

In plants many biotic and abiotic stresses can cause secondary oxidative stress. Earlier work showed that, depending on the severity of the oxidative stress, plants can activate either cell protective genes or programmed cell death (PCD). Poly(ADP-ribose) polymerase (PARP) has been implicated as one of the enzymes in the apoptotic pathways induced by DNA damaging agents or oxidative stress. We show that in cultured soybean cells, PARP is involved in responses to mild and severe oxidative stresses, by mediating DNA repair and PCD processes, respectively. Addition of PARP inhibitors reduced the degree of cell death triggered by H2O2. Two windows of NAD consumption after H2O2 treatment were detected. Experiments with transient overexpression of Arabidopsis PARP cDNA promoted DNA repair and inhibited cell death caused by mild oxidative stress. However, following severe stress PARP overexpression increased cell death. Expression of antisense PARP produced the opposite effects: an increase in DNA nicks and inhibition of cell death at high, but not mild doses of H2O2.
Noninvasive Markers in the Assessment of Intestinal Inflammation in Inflammatory Bowel Diseases: Performance of Fecal Lactoferrin, Calprotectin, and PMN-Elastase, CRP, and Clinical Indices (2007)

The fecal markers Lf, Cal, and PMN-e are able to differentiate active IBD from inactive IBD as well as from IBS. None of these three stool markers is consistently superior in its ability to reflect endoscopic inflammation, but all three are superior to CRP in their diagnostic accuracy. A combination of the stool markers with the CRP and a disease-specific activity index in a categorical comprehensive activity index can increase the diagnostic accuracy with reference to the endoscopic inflammation in UC.
Identification of toxS, a regulatory gene whose product enhances toxR-mediated activation of the cholera toxin promoter (1989)

We describe the cloning of the toxS gene from Vibrio cholerae E1 Tor strain E7946. This gene lies downstream from the toxR gene, which encodes the transcriptional activator for the cholera toxin (ctx) operon in V. cholerae. We show that ToxS acts in conjunction with ToxR to activate expression of the ctx operon in Escherichia coli. The classical strain 569B, which is attenuated for virulance but which synthesizes high levels of cholera toxin in vitro, carries a deletion of 1.2 kilobase pairs of DNA, downstream from the toxR gene, which removes toxS. We present evidence that toxS is the downstream gene in an operon with toxR.
Bispecific antibodies targeting cancer cells (2002)

In recent years, antibody therapy has become a new treatment modality for tumour patients, although the majority of responses are only partial and not long lasting. Based on evidence that effector-cell-mediated mechanisms significantly contribute to antibody efficacy in vivo, several approaches are currently pursued to improve the interaction between Fc receptor-expressing effector cells and tumour target antigens. These approaches include application of Fc receptor-directed bispecific antibodies, which contain one specificity for a tumour-related antigen and another for a cytotoxic Fc receptor on immune effector cells. Thereby, bispecific antibodies selectively engage cytotoxic trigger molecules on killer cells, avoiding, for example, interaction with inhibitory Fc receptors. In vitro, chemically linked bispecific antibodies directed against the Fc gamma receptors Fc gamma RIII (CD16) and Fc gamma RI (CD64), and the Fc alpha receptor Fc alpha RI (CD89), were significantly more effective than conventional IgG antibodies. Recent animal studies confirmed the therapeutic potential of these constructs. However, results from clinical trials have been less promising so far and have revealed clear limitations of these molecules, such as short plasma half-lives compared with conventional antibodies. In this review, we briefly summarize the scientific background for bispecific antibodies, and describe the rationale for the generation of novel recombinant molecules. These constructs may allow us to more specifically tailor pharmacokinetic properties to the demands of clinical applications.
Multiple, diverse senile plaque–associated proteins are ligands of an apolipoprotein e receptor, the α2‐macroglobulin receptor/low‐density‐lipoprotein receptor—related protein (1995)

Both apolipoprotein E and its receptor, the low-density-lipoprotein receptor-related protein (LRP), are associated with senile plaques in Alzheimer's disease. We examined the relationship of other LRP-related molecules to senile plaques. LRP is a multifunctional receptor that binds and rapidly internalizes at least seven ligands: apolipoprotein E, activated alpha 2-macroglobulin, tissue and urokinase-type plasminogen activators, plasminogen activator inhibitor-1, lipoprotein lipase, and lactoferrin. Using immunohistochemistry, we showed that all of these ligands, representing a diverse group of otherwise apparently unrelated proteins, accumulate on senile plaques. We also studied expression of the receptor-associated protein, a physiological inhibitor of LRP, in the hippocampal formation from normal subjects and Alzheimer's disease patients. Receptor-associated protein colocalizes with LRP on neuronal soma, but not on neuronal processes or reactive astrocytes. It is not present on senile plaques. These results suggest that senile plaque-associated LRP can bind its ligands, but clearance of these compounds may be impaired in the vicinity of senile plaques.
[PP.36.01] (2015)

Objective: The thrombolytic therapy in patients with intermediary risk pulmonary embolism is a debated subject. According to the ESC Guidelines for the Management of Acute Pulmonary Embolism (2014) the thrombolytic therapy in patients with intermediary – high risk pulmonary embolism (defined as PESI score >85, echocardiography signs of RV dysfunction, biochemical signs of RV dysfunction (NtproBNP and cTnT elevated)) - IIa class indication. Secondary to thrombolytic therapy a hypertensive rebound can occure as a result of the improvement of the RV systolic function (echocardiography assessed) Design and method: We selected 25 patients with intermediary-high risk pulmonary embolism with no contraindications for thrombolytic therapy, aged below 75yo, no severe renal failure, normal left ventricle systolic function. The patients received thrombolytic therapy 10 mg t-PA followed by 90 mg t-PA in 2 h. From this patients 66% were diagnosed with ambulatory primary hypertension. The echocardiographic makers of RV dysfunction were assessed on admission and on 72 h after thrombolytic treatment (TAPSE, S wave velocity assessed by TDI, RV diastolic diameter, dyskinetic IVS, the severity of tricuspid regurgitation). We assessed the hypertensive profile by 24 h hypertension monitoring on 72 h after thrombolytic therapy. Results: Only 25% of the included patients presented high blood pressure on admision, the medium SBP on admision was 135.8mmHg. The echocardiographic markers of RV dysfunction were concordant with the acute PE, as the mean S wave velocity by TDI was 10.8 cm/s, the medium TAPSE was 13.5 mm, the medium RV diastolic diameter 44.8 mm and 25% of the patients had dyskinetic IVS. Post-thrombolytic therapy the assessment of RV function revealed an increasing TAPSE by 54%, an increasing S wave velocity by 44.8%, the medium RV diameter 38.6 mm and only 2 patients with dyskinetic IVS. Regarding the hypertensive profile on 24 h the medium SBP was 158.5mmHg with a hypertensive load of 44.5%. It is obvious a correlation between the posthrombolytic hypertensive rebound and the improving markers of RV pressure overload. Conclusions: The results reveal a possible correlation between the improving RV dysfunction assessed by echocardiography and the posthrombolytic rebound in patients with acute intermediary-high risk PE.
[The loss of heterozygosity on the short arm of chromosome 3 in renal carcinoma]. (1999)

43.9% of the patients showed LOH on at least one locus. Thirty-four percent showed LOH only on one locus, 4.9% on two loci and 7.3% on the three loci tested. All the patients who showed LOH on 3p21 had a tumor size greater than 25 mm. There is a risk 1.76 times higher of no loss in tumors less than 25 mm in size than in tumors greater than 25 mm (Cl 95% 1.33-2.33).
进行中的全球贸易谈判（二）——对最新决定的初步评估 (2005)

(上续本刊2005年6期) 非农产品市场准人 WTO及其前身GATT在非农产品市场准入谈判领域有着最为丰富的经验.因此,人们或许认为在此领域就谈判模式达成一致将是轻而易举的.然而,在过去,就市场准入谈判存在许多不同的方法,这些不同方法因各种不同原因而有着各自的拥护者.
ACCELERATED DEACETYLATION OF CELLUYLOSE ACETATE BY METAL SALTS WITH AQUEOUS CHLORINE (1991)

Certain metal ions, when present with cellulose acetate in pH 7-buffered hypochlorite solutions, increased the rate of deacety lation. Cellulose acetate filter pads showed definite deterioration with cobalt and nickel ions compared with the other 3d transition metals tested. Cellulose acetate was synthesized with 14C-labeled acetyl groups and deacetylation was expressed as increased radioactivity in the aqueous phase. The 3,4,5d transition metal ions were examined. Cobalt and ru thenium had the greatest effect followed by iron, nickel, rhenium, pal ladium, and silver. Copper and gold had only a slight effect. Research by the U.S. Bureau of Reclamation reported in this paper suggests similar reactions are possible for cellulose acetate membranes used in reverse osmosis desalting technology. Res. J. Water Pollut. Control Fed., 63, 177(1991).
Synthetic Biology for Therapeutic Applications (2014)

Synthetic biology is a relatively new field with the key aim of designing and constructing biological systems with novel functionalities. Today, synthetic biology devices are making their first steps in contributing new solutions to a number of biomedical challenges, such as emerging bacterial antibiotic resistance and cancer therapy. This review discusses some synthetic biology approaches and applications that were recently used in disease mechanism investigation and disease modeling, drug discovery and production, as well as vaccine development and treatment of infectious diseases, cancer, and metabolic disorders.
Solubilization of Oxidized Single-Walled Carbon Nanotubes in Organic and Aqueous Solvents through Organic Derivatization (2002)

The solubilization of oxidized carbon nanotubes has been achieved through derivatization using a functionalized organic crown ether. The resultant synthesized adduct yielded concentrations of dissolved nanotubes on the order of ∼1 g/L in water as well as in methanol, according to optical measurements. The nanotube−crown ether adduct can be readily redissolved in 10 different organic solvents at substantially high concentrations. Characterization of these solubilized adducts was performed with 1H NMR spectroscopy; 7Li NMR was also used to examine the ability of the crown ether's macrocyclic ring to bind Li+ ions. The solutions were further analyzed using UV−visible, photoluminescence, and FT-IR spectroscopies and were structurally characterized using atomic force microscopy (AFM) and transmission electron microscopy (TEM). Adduct formation likely results from a noncovalent chemical interaction between carboxylic groups on the oxidized tubes and amine moieties attached to the side chain of the crown ether derivative.