gebhart/patrepeval huggingface dataset:
Organization and genesis of dihydrofolate reductase amplicons in the genome of a methotrexate-resistant Chinese hamster ovary cell line. (1988)

We have recently isolated overlapping recombinant cosmids that represent the equivalent of two complete dihydrofolate reductase (dhfr) amplicon types from the methotrexate-resistant Chinese hamster ovary (CHO) cell line CHOC 400. In the work described in this report, we used pulse-field gradient gel electrophoresis to analyze large SfiI restriction fragments arising from the amplified dhfr domains. The junction between the 260-kilobase type I amplicons (which are arranged in head-to-tail configurations in the genome) has been localized, allowing the construction of a linear map of the parental dhfr locus. We also show that the 220-kilobase type II amplicons are arranged as inverted repeat structures in the CHOC 400 genome and arose from the type I sequence relatively early in the amplification process. Our data indicate that there are a number of minor amplicon types in the CHOC 400 cell line that were not detected in previous studies; however, the type II amplicons represent ca. 75% of all the amplicons in the CHOC 400 genome. Both the type I and type II amplicons are shown to be composed entirely of sequences that were present in the parental dhfr locus. Studies of less resistant cell lines show that initial amplicons can be larger than those observed in CHOC 400. Once established, a given amplicon type appears to be relatively stable throughout subsequent amplification steps. We also present a modification of an in-gel renaturation method that gives a relatively complete picture of the size and variability of amplicons in the genome.
Modulating AML1-ETO with Signature-Based Small Molecule Library Screening. (2006)

Abstract We sought to develop a strategy to pharmacologically modulate AML1-ETO, the most common gene rearrangement associated with acute myeloblastic leukemia (AML). Like many other oncogenic transcription factors associated with the acute leukemias, AML1-ETO has been considered undruggable. In principle, these well-characterized somatic mutations identified in the acute leukemias represent unique, tumor-specific therapeutic targets. In practice, acute leukemia therapy continues to focus on nonspecific cytotoxic agents. In order to address this challenge, we developed a genomic, signature-based small molecule library screening approach, Gene Expression-based High-throughput Screening (GE-HTS). This approach uses gene expression signatures as surrogates for different biological states in a small molecule library screen. We focused our initial efforts on identifying modulators of AML1-ETO. First, a 25-gene signature for AML1-ETO abrogation was defined by transcriptional profiling of t(8;21) Kasumi-1 cells with and without AML1-ETO-directed RNA interference and with a U937 inducible model of AML1-ETO. The signature was confirmed in microarray data from t(8;21)-containing primary patient leukemias (p &amp;lt; 0.001). Next, the ability of 2,600 FDA-approved drugs and bioactive agents to induce this abrogation signature was evaluated by ligation mediated amplification (LMA) and bead-based fluorescence detection. The screen identified 16 hits confirmed on repeat testing, including seven corticosteroids. Five hits were selected for further study based on their chemical diversity, ability to induce a robust expression signature, and potential for clinical translation: 5-aza-deoxycytidine, floxuridine, methotrexate, methylprednisolone, and pyrimethamine. Next, whole genome effects of these compounds with microarray-based expression profiling were evaluated. Using Gene Set Enrichment Analysis (GSEA), we determined that all five compounds induce both whole genome effects consistent with AML1-ETO knockdown and a whole genome program consistent with neutrophil maturation. In a subset of these compounds, we also see changes in cell surface markers and morphological features consistent with myeloid maturation. Intriguingly, two of the hits are well-characterized DNA methyltransferase inhibitors, and two of the hits are dihydrofolate reductase inhibitors that increase S-adenosylhomocysteine, an inhibitor of methyltransferases. Thus, reversal of AML1-ETO-mediated gene silencing by demethylation may overcome its repressive effects. This application of knockdown-derived expression signatures to small molecule library screening should enable the targeting of nearly any oncogenic transcription factor.
Visualization of blood-brain barrier disruption on MR images of cats with acute cerebral infarction: value of administering a high dose of contrast material. (1994)

Detection of disruption of the blood-brain barrier in acute cerebral infarction in cats is improved when high doses (0.3 mmol/kg) of contrast material are used. Disruption may not be visualized when 0.1 mmol/kg, the currently accepted standard dose, is used.
An Extended Table of Hammett Substitutent Constants Based on the Ionization of Substituted Benzoic Acids (1958)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAn Extended Table of Hammett Substitutent Constants Based on the Ionization of Substituted Benzoic AcidsDARL H. McDANIEL and HERBERT C. BROWNCite this: J. Org. Chem. 1958, 23, 3, 420–427Publication Date (Print):March 1, 1958Publication History Published online1 May 2002Published inissue 1 March 1958https://pubs.acs.org/doi/10.1021/jo01097a026https://doi.org/10.1021/jo01097a026research-articleACS PublicationsRequest reuse permissionsArticle Views10718Altmetric-Citations930LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
CHANGES IN CIRCULATING SOMATOMEDIN‐C LEVELS IN BROMOCRIPTINE‐TREATED ACROMEGALY (1982)

To determine whether the improvement in clinical status of patients with active acromegaly correlates with a reduction of circulating somatomedin-C, serum immunoreactive somatomedin-C was measured in twenty-seven patients before and during bromocriptine therapy. The patients were assessed using a clinical and metabolic score which included both subjective criteria of improved sweating and facial features, and objective criteria of a reduction in ring circumference and the area under the glucose tolerance curve. Using this, together with the change in GH levels before and during bromocriptine therapy, the patients could be divided into three groups. In one group, there was no clinical improvement, a less than 30% decline in somatomedin-C, and in four of six patients no significant decline in GH. In both the other groups there was clinical improvement and a greater than 30% decrease in somatomedin-C. In one of these two groups, however GH did not decline, while in the other it was reduced significantly. The results suggest that during bromocriptine treatment of acromegaly, serum somatomedin-C concentrations correlate better with clinical status that does serum GH. Since some patients have no significant fall in GH but show both clinical improvement and a reduction in somatomedin-C, it seems likely that in some patients bromocriptine may improve acromegaly by a mechanism other than a simple decrease in total immunoreactive GH secretion.
Post-translational Modifications of the Four Conserved Lysine Residues within the Collagenous Domain of Adiponectin Are Required for the Formation of Its High Molecular Weight Oligomeric Complex (2006)

Adiponectin is a multifunctional adipokine that circulates as several oligomeric complexes in the blood stream. However, the molecular basis that regulates the production of the adiponectin oligomers remains largely elusive. We have shown previously that several conserved lysine residues (positions 68, 71, 80, and 104) within the collagenous domain of adiponectin are modified by hydroxylation and glycosylation (Wang, Y., Xu, A., Knight, C., Xu, L. Y., and Cooper, G. J. (2002) J. Biol. Chem. 277, 19521-19529). Here, we investigated the potential roles of these post-translational modifications in oligomeric complex formation of adiponectin. Gel filtration chromatography revealed that adiponectin produced from mammalian cells formed trimeric, hexameric, and high molecular weight (HMW) oligomeric complexes. These three oligomeric forms were differentially glycosylated, with the HMW oligomer having the highest carbohydrate content. Disruption of hydroxylation and glycosylation by substitution of the four conserved lysines with arginines selectively abrogated the intracellular assembly of the HMW oligomers in vitro as well as in vivo. In type 2 diabetic patients, both the ratios of HMW to total adiponectin and the degree of adiponectin glycosylation were significantly decreased compared with healthy controls. Functional studies of adiponectin-null mice revealed that abrogation of lysine hydroxylation/glycosylation markedly decreased the ability of adiponectin to stimulate phosphorylation of AMP-activated protein kinase in liver tissue. Chronic treatment of db/db diabetic mice with wild-type adiponectin alleviated hyperglycemia, hypertriglyceridemia, hepatic steatosis, and insulin resistance, whereas full-length adiponectin without proper post-translational modifications and HMW oligomers showed substantially decreased activities. Taken together, these data suggest that hydroxylation and glycosylation of the lysine residues within the collagenous domain of adiponectin are critically involved in regulating the formation of its HMW oligomeric complex and consequently contribute to the insulin-sensitizing activity of adiponectin in hepatocytes.
New Discovery of the Early Cretaceous Volcanic Rocks on the Barton Peninsula, King George Island,Antarctica and Its Geological Significance (2000)

Ages determined with the 40Ar/39Ar isotopic system affirms the Early Cretaceous volcanic activity in the Barton Peninsula, King George Island, Antarctica. Two specimens of basaltic andesite collected from the lowermost volcanic sequence of the peninsula were irradiated and analyzed in different experiments, yielding an identical age spectrum, and two magmatic thermal events of the Early Cretaceous (120.4±1.6 Ma, 119±1 Ma) and Early Tertiary (5 3.1±1.5 Ma, 52±1 Ma) are distinguished. The former is interpreted to represent the primary cooling age of basaltic andesite, whereas the latter is the thermal reset age caused by the intrusion of granitic pluton. These new ages clearly indicate that volcanism was active during the Early Cretaceous on the Barton Peninsula and that intensive hy-drothermal alteration and mineralization of Mesozoic volcanic rocks resulted from Tertiary magmatism.
Family and Parental influence on the development of children with disabilities (2004)

본 연구는 가족기능, 사회적 지원, 부모양육 스트레스, 그리고 어머니 상호작용 유형이 장애를 가진 어린 아동의 발달에 미치는 영향을 검증하고자 하였다. 연구 참여자는 자폐증/광범위성발달장애(PDD)로 진단되었거나, 또는 일반적인 발달장애를 가진 50명의 아동과 그 어머니들이다. 자료 수집은 어머니와 아동의 상호작용 평가를 위해 비디오 촬영이 이루어졌으며, 가족기능, 사회적 지원, 부모양육 스트레스를 평가하기 위해 어머니에 의한 자기-보고식 질문지가 수행되었다. 상관관계 분석결과는 가족 기능, 사회적 지원, 부모양육 스트레스, 그리고 어머니 상호작용 유형 간에 낮거나 중간정도의 상관관계가 있는 것으로 나타내었다. 위계적 회귀분석(Hierarchical regression analysis)결과는 가족 변인들(가족 응집력, 지원에 대한 만족, 부모의 스트레스)과 어머니의 반응성이 아동발달 수준에 영향력이 있는지를 나타내었다. 특히 어머니의 반응성은 변인의 14%를 설명하면서 아동발달에 대해 가장 유의미한 예측변인으로 나타났다. 이와 같은 위계적 회귀분석 결과는 어머니의 반응성이 아동발달에 미치는 영향력에 대해 가족요인이 중재적 이라는 가설을 지지하였다.
Clinical Effect of Point Mutations in Myelodysplastic Syndromes (2011)

Somatic point mutations are common in myelodysplastic syndromes and are associated with specific clinical features. Mutations in TP53, EZH2, ETV6, RUNX1, and ASXL1 are predictors of poor overall survival in patients with myelodysplastic syndromes, independently of established risk factors. (Funded by the National Institutes of Health and others.).
Basic Concepts in Population Modeling, Simulation, and Model‐Based Drug Development: Part 3—Introduction to Pharmacodynamic Modeling Methods (2014)

Population pharmacodynamic (PD) models describe the time course of drug effects, relating exposure to response, and providing a more robust understanding of drug action than single assessments. PD models can test alternative dose regimens through simulation, allowing for informed assessment of potential dose regimens and study designs. This is the third paper in a three‐part series, providing an introduction into methods for developing and evaluating population PD models. Example files are available in the Supplementary Data . CPT Pharmacometrics Syst. Pharmacol . (2014) 3, e88; doi: 10.1038/psp.2013.71 ; published online 2 January 2014
[Use of a three-component scheme of immunosuppression on morphologic and immunohistochemical changes of transplants in the early postoperative period]. (2002)

Three-component (cyclosporin A, corticosteroids and azathioprine) immunosuppression has been widely introduced in the treatment of recipients of renal transplants because it allows a significant reduction of the components' doses in greater effectiveness. The analysis of the results of 83 puncture biopsies obtained in the immediate postoperative period after kidney transplantation has shown that administration of an imidazole derivative allows raising therapeutic concentration of cyclosporin up to 200-300 ng/ml, thus preventing rejection crises. However, increased blood concentration of cyclosporin does not increase its toxicity as a result of a significant fall in the overall level of the metabolites.
Control of the Heterogeneous Azeotropic n-Butanol/Water Distillation System (2008)

The interest in n-butanol as a biofuel has increased in recent years because of its superior fuel qualities compared to ethanol: higher octane number, lower heat of vaporization, higher energy density (energy/volume), and lower vapor pressure. However, the concentration of n-butanol coming from the fermenter is lower than that achieved in ethanol fermentation. In addition, acetone and ethanol are also produced. Recent studies to improve yield and increase n-butanol concentration have explored fed-batch systems with stripping, adsorption, liquid−liquid extraction, distillation, and/or pervaporation to recover products. The production of n-butanol involves removing the acetone and ethanol and separating the n-butanol from the water. This separation is made difficult by the presence of an azeotrope. Fortunately, unlike the homogeneous azeotrope found in the ethanol/water system, the n-butanol/water azeotrope is heterogeneous; thus, two liquid phases occur in the decanter. Therefore, a simple two-column distillation system can be used. This paper studies the control of the n-butanol/water azeotropic distillation system and develops a simple effective control structure that is capable of handling very large disturbances in throughput and feed composition. The control system is very robust and is demonstrated to be applicable for systems that are designed for a wide range of feed compositions.
Increased accumulation of p53 protein in cisplatin‐resistant ovarian cell lines (1993)

We have examined p53 protein levels in cell lines selected for resistance to the chemotherapeutic drug cis-diamminedichloroplatinum (II), cisplatin. The majority of the independent cisplatin-resistant clones isolated by a single selection with cisplatin from the ovarian tumour cell line A2780 showed increased levels of p53 protein compared to the parental cell line. Elevated p53 protein levels were also observed in cisplatin-resistant ovarian human tumour lines isolated after multiple exposures to cisplatin (A2780/cp70 and OVIP/DDP). Direct PCR sequencing of p53 cDNAs showed that both the A2780/cp70 and the parental A2780 cell lines had a wild-type p53 gene sequence. The OVIP and OVIP/DDP lines both had a heterozygous mutation at codon 126. Cell-cycle analysis after gamma-irradiation or cisplatin treatment showed evidence of a G1/S and G2/M cell-cycle checkpoint in both A2780/cp70 and the sensitive parental cell lines. However, the resistant cell line A2780/cp70 showed less inhibition of DNA synthesis after gamma-irradiation than the sensitive cell line. Transfection of a mutant p53 gene construct (containing a mutation at codon 143, val to ala) into the A2780/cp70 resistant cells conferred a significantly increased sensitivity to cisplatin, suggesting that p53 is a direct determinant of cisplatin resistance in these cells. However, expression of this mutant p53 in the A2780 cells did not affect sensitivity.
Human pharmacokinetic characterization and in vitro study of the interaction between doxorubicin and paclitaxel in patients with breast cancer. (1997)

PTX, as clinically formulated in CEL, is responsible for a nonlinear disposition of DOX and DOL. Nonlinearity is PTX- and DOX-dependent, and possibly caused by competition for biliary excretion of taxanes and anthracyclines mediated by P-gp. Nonlinearity indicates that even minor modifications of dose and infusion duration of DOX and PTX may lead to unpredictable pharmacodynamic consequences. The postulated role of P-gp suggests that CEL is clinically active, and advises caution in designing combinations of PTX with other drugs that are substrate for P-gp.
Enhanced resistive switching performance for bilayer HfO2/TiO2resistive random access memory (2016)

We prepared bilayer HfO2/TiO2 resistive random accessory memory (RRAM) using magnetron sputtering on an ITO/PEN flexible substrate. The switching voltages (VSET and VRESET) were smaller for the Pt/HfO2/TiO2/ITO device than for a Pt/HfO2/ITO memory device. The insertion of a TiO2 layer in the switching layer was inferred to act as an oxygen reservoir to reduce the switching voltages. In addition, greatly improved uniformity was achieved, which showed the coefficient of the variations of VSET and VRESET to be 9.90% and 6.35% for the bilayer structure RRAM. We deduced that occurrence of conductive filament connection/rupture at the interface of the HfO2 and TiO2, in combination with the HfO2 acting as a virtual cathode, led to the improved uniformity. A multilevel storage capability can be obtained by varying the stop voltage in the RESET process for bilayer HfO2/TiO2 RRAM. By analyzing the current conduction mechanism, we demonstrated that the multilevel high resistance state (HRS) was attributable to the increased barrier height when the stop voltage was increased.
Finding the Position and Orientation of a Sensor on a Robot Manipulator Using Quaternions (1991)

The problem of finding the relative position and orientation between the reference frames of a link-mounted sensor and the link has been formulated as a kinematic equation of the form H l H x = H x H c in terms of homogeneous transformation matrices by Shiu and Ahmad (1987). In this article, normal ized quaternions (Euler parameters) are used to transform the kinematic equation into two simple and structured linear systems with rank-deficient coefficient matrices. Closed-form solutions to these systems are derived using the generalized inverse method with singular-value decomposition analysis. To obtain a unique solution, two distinct robot movements are required. This leads to an overdetermined system of equations. A criterion for selecting the independent set of equations is developed. A set of closed-form formulae for the solution of these equations are derived. The selection crite rion and the solution formulae can be easily incorporated in application programs that require the calculation of the rela tive position and orientation of the sensor.
[Prevalence of the most common respiratory allergens generating positive prick-reaction based on the examination of 2124 children suffering from respiratory allergy, between 1992-2000]. (2005)

The authors' findings are similar to those of other investigators.
Mutational analysis of CDKN2 (MTS1/p16ink4) in human breast carcinomas. (1994)

The CDKN2 gene that encodes the cell cycle regulatory protein cyclin-dependent kinase-4 inhibitor (p16) has recently been mapped to chromosome 9p21. Frequent homozygous deletions of this gene have been documented in cell lines derived from different types of tumors, including breast tumors, suggesting that CDKN2 is a tumor suppressor gene involved in a wide variety of human cancers. To determine the frequency of CDKN2 mutations in breast carcinomas, we screened 37 primary tumors and 5 established breast tumor cell lines by single-strand conformation polymorphism analysis. In addition, Southern blot analysis was performed on a set of five primary breast carcinoma samples and five breast tumor cell lines. Two of the five tumor cell lines revealed a homozygous deletion of the CDKN2 gene, but no mutations were observed in any of the primary breast carcinomas. These results suggest that the mutation of the CDKN2 gene may not be a critical genetic change in the formation of primary breast carcinoma.
Treatment of giant cell arteritis: Interleukin-6 as a biologic marker of disease activity (2000)

Plasma IL-6 is more sensitive than ESR for indicating disease activity in untreated and treated GCA patients. Standard corticosteroid regimens only partially suppress vascular inflammation. Smoldering disease activity may expose GCA patients to the risk of progressive vascular disease (e.g., formation of aortic aneurysms) and chronic systemic complications such as IL-6-mediated osteopenia.
Clinical Characteristics of Complex Partial Seizures : a Temporal versus a Frontal Lobe Onset (1998)

Methods : We analysed 129 seizures that occured during video-EEG monitoring in 13 patients with temporal lobe epilepsy(TLE) and in 9 patients with frontal lobe epilepsy(FLE) as well as neuroimaging studies. We compared first the clinical behaviours that occurred in frontal lobe seizures to those of temporal lobe seizures(second stage analysis). To eliminate clinical behaviours that could occur as the discharge propagated another lobe, we compared only clinical seizure events in which we had no evidence of spread to other regions, or that spread only to the homologous contralateral lobe(first stage analysis). The Fisher exact test was used for analysis. Results : Although staring, sitting up, leg movement, and tonic-clonic movement, generalization occurred more frequently in FLE, and oral, alimentary and hand automatisms were more frequent in TLE, no statistically significant difference was found between the two groups. In second stage analysis, sitting up, tonic-clonic movement were seen only in FLE and oral, alimentary and hand automatisms only in TLE. Staring, hand posturing occurred more frequently in FLE. Conclusion : We therefore conclude that the reliability of clinical behaviour alone to predict the site of origin of an epileptic discharge is limited when the surface EEG is equivocal or neuroradiologic evidence of a focus is not clear. (J Korean Pediatr Soc 1998;41:769-774)