gebhart/patrepeval huggingface dataset:
Hypermethylation of calcitonin gene regulatory sequences in human breast cancer as revealed by genomic sequencing (1996)

DNA methylation has been studied intensively during the past years in order to elucidate its role in the regulation of gene expression, gene imprinting and cancer progression. Earlier studies have shown that a general genomic under-methylation is associated with chronic lymphocytic leukemia and metastatic prostate cancer. Site-specific methylation changes, as revealed by the use of methylation-sensitive restriction enzymes, have been reported to occur in the promotor region of the calcitonin gene in chronic myeloid leukemia as it progresses from the chronic phase to blast crisis, in non-Hodgkin's lymphoid neoplasms and in non-lymphocytic leukemia. We have now explored possible methylation changes associated with benign and malignant breast tumors. Two approaches were employed: (i) chemical determination of general genomic methylation status and (ii) base-specific analysis of the methylation changes in the promoter of the calcitonin gene with the aid of genomic sequencing. The results did not reveal any changes of total DNA 5-methylcytosine content in ductal carcinoma of breast in comparison with benign tumors. There was a small, yet significant, increase in 5-methylcytosine content in lobular carcinoma. Genomic sequencing of the promoter region of the calcitonin gene, however, revealed a striking hypermethylation at or around the transcription start site of the gene in ductal carcinomas. In benign tumors and lobular carcinomas, this region was either entirely unmethylated or only slightly methylated. The latter changes may reflect a regional hypermethylation of the short arm of chromosome 11, which harbors, in addition to the calcitonin gene, a number of putative or established tumor-suppressor genes. Our results demonstrate that genomic sequencing in its present form can be used for a reliable and precise DNA methylation analysis of primary human tumors.
전통식혜제조 - 제 1 보 엿기름과 효소를 이용한 제조 (1999)

전통 식혜제조 방법을 과학화 체계화시키기 위하여 엿기름과 시판 아밀라아제를 단독 또는 혼합 사용하여 식혜를 제조하였다. 엿기름의 아밀라아제 활성(환원력)은 9,725unit/g이었다. 엿기름 식혜는 엿기름 4%, 쌀 20%를 사용하여 60℃에서 5시간 반응시키는 것이 가장 효과적이었다. 시판 β-아밀라아제(Biozyme ML, Hamilton GL), α-아밀라아제(복합효소 5000, Teramyl, Fungamyl), pullulanase(Enzyme CK-20)는 단독, 또는 엿기름과 함께 사용하면 초기에는 엿기름을 단독 사용한 것보다 당화율을 증가시켰으나 5시간 후에는 엿기름 단독 사용한 것보다 큰 차이가 없었다.
Endogene Lektine in Tumoren und ihre mögliche Bedeutung für Diagnose und Therapie von Krebserkrankungen (1989)

The oncological application of knowledge of biological recognition processes offers opportunities to favorably translate results from basic science into clinical procedures within tumor diagnosis and therapy. Based on the attractive assumption that biological information can be stored in a glycobiological code within the sugar chains of cellular glycoconjugates, the specific interaction of proteins and carbohydrates warrants special attention. Lectins form a particular class of carbohydrate-binding proteins, separated from sugar-specific enzymes as well as antibodies. They are expressed by normal cells, but also, remarkably, by tumor cells. The pattern of lectin expression can be recorded by routine histopathological procedures using labelled carriers that have been chemically modified by defined coupling of the histochemically crucial carbohydrate moieties. The tumor-associated differences, documented by application of these neoglycoproteins, serve as guidelines for consequently following biochemical studies and for lectin-mediated drug targeting. Increased selectivity of drug delivery by using tailor-made neoglycoproteins as transport vehicles may result from specifically aiming at lectins as cellular targets for binding of the 'Trojan horse'. Besides these aspects of tumor lectinology the assumption of the noteworthy significance of protein-carbohydrate recognition may also contribute to progress in a challenging as well as complex problem in tumor research, the formation of metastases. Joint approaches with chemical, biochemical, cell biological, histochemical and oncological techniques will allow to critically assess the value of tumor lectinology for oncology.
Break-induced replication: What is it and what is it for? (2008)

Homologous recombination (HR) is considered to be an error-free mechanism for the repair of DNA double-strand breaks (DSBs). Indeed, most DSB repair events occur by a non-crossover mechanism limiting loss of heterozygosity (LOH) for markers downstream of the site of repair and preventing chromosome rearrangements. However, DSBs that arise by replication fork collapse or by erosion of uncapped telomeres have only one free end and are thought to repair by strand invasion into a homologous duplex DNA followed by replication to the chromosome end (break-induced replication, BIR). As BIR from one of the two ends of a DSB would result in a long tract of LOH it suggests BIR is suppressed when DSBs have two ends in order for repair to occur by a more conservative HR mechanism. Recent studies showed that BIR can occur by several rounds of strand invasion, DNA synthesis and dissociation resulting in chromosome rearrangements when dissociation and reinvasion occur within dispersed repeated sequences. Thus template switching BIR can be highly mutagenic and this process could be important for genome evolution and disease development.
Mechanism of All- Trans Retinoic Acid Effect on Tumor-Associated Myeloid-Derived Suppressor Cells (2007)

Myeloid-derived suppressor cells (MDSC) play an important role in tumor escape by suppressing T-cell responses. MDSC represent a group of cells of myeloid lineage at different stages of differentiation. Increased arginase activity and production of reactive oxygen species (ROS) are among the main functional characteristics of these cells. Recent studies have shown that all-trans retinoic acid (ATRA) had a potent activity in eliminating MDSC in cancer patients and in tumor-bearing mice. ATRA differentiates these cells into mature myeloid cells. However, the mechanism of this effect is unclear. Here, we have shown that ATRA dramatically and specifically up-regulated gene expression and protein level of glutathione synthase (GSS) in MDSC. This resulted in accumulation of glutathione (GSH) in these cells, observed in both mice and cancer patients. Blockade of GSH synthesis cancelled the effect of ATRA on MDSC. Accumulation of GSH in these cells using N-acetyl-L-cysteine mimicked the effect of ATRA on MDSC differentiation. Analysis of potential mechanisms of ATRA effect on GSS revealed that ATRA regulates its expression not by directly binding to the promoter but primarily via activation of extracellular signal-regulated kinase 1/2. Thus, ATRA induced differentiation of MDSC primarily via neutralization of high ROS production in these cells. This novel mechanism involves specific up-regulation of GSS and accumulation of GSH and could be used in developing and monitoring therapeutic application of ATRA.
Therapeutic implications of microglia activation by lipopolysaccharide and reactive oxygen species generation in septic shock and central nervous system pathologies: a review. (1998)

The pathophysiology of organ system failure in sepsis, in particular the effects of septic shock on the central nervous system, are still incompletely understood. Lipopolysaccharide (LPS) from Gram-negative bacteria affects the permeability of the blood-brain barrier and causes the activation of brain microglia. A growing body of research supports involvement of activated brain microglia in brain pathologies caused by infectious diseases, trauma, tumors, ischemia, Alzheimer's disease, Parkinson's disease, Down's syndrome, multiple sclerosis and AIDS. Those seminal studies that have contributed to the characterization of the in vivo and in vitro effects of LPS on microglia function, mediator generation and receptor expression are presented within a historical perspective. In particular, all those in vitro studies on O2-, H2O2 and NO. generation by either unprimed or primed microglia have been extensively reviewed. The apparent controversial effect of LPS on microglia O2- is discussed. Because treatment modalities for septic shock have not significantly affected the current high mortality, alternative strategies with antioxidants are currently being investigated. Reduction of microglia O2- generation is proposed as a possible complementary strategy to antioxidative therapy for septic shock and CNS pathologies that involve activated microglia.
Cationic Lipid-Mediated Gene Delivery to Murine Lung:  Correlation of Lipid Hydration with in Vivo Transfection Activity (1997)

A panel of lipidic tetraalkylammonium chlorides has been prepared and screened in studies of both lipid hydration and in vivo mouse transfection. The effect of cationic lipid structure on liposome surface hydration was determined using differential scanning calorimetry. Increases in headgroup steric bulk and the inclusion of cis-unsaturation in the hydrophobic domain led to greater lipid hydration, indicative of a decrease in lipid polar domain associations. Cationic lipids containing hydrogen-bonding functionality in the polar domain exhibited a corresponding decrease in observed lipid hydration, indicative of an increase in lipid polar domain associations. To explore a potential correlation of the hydration data with transfection activity, we examined the in vivo transfection activity of the lipid panel by direct intratracheal instillation of cationic liposome-DNA complexes into BALB/c mice. The more active transfection agents were the lipids that featured headgroup structures promoting close polar domain association in combination with fatty acyl cis-unsaturation. The hydration data suggest that the more effective transfection lipids for mouse lung delivery are those possessing the greatest imbalance between the cross-sectional areas occupied by the polar and hydrophobic domains.
Agonistic monoclonal antibodies against the Met receptor dissect the biological responses to HGF (1998)

Hepatocyte growth factor, also known as scatter factor, is a pleiotropic cytokine, which stimulates cell motility, invasion, proliferation, survival and morphogenesis, and induces the expression of specific genes by activating its receptor tyrosine kinase. In this work we have isolated, characterized and used as agonists two monoclonal antibodies (mAbs) directed against the extracellular domain of HGF receptor to investigate the requirements for receptor activation and for the different biological responses. The two mAbs display similar affinities, react with epitopes different from the hepatocyte growth factor binding site, and behave as either full or partial agonists. The full agonist mAb (DO-24) triggers all the biological effects elicited by hepatocyte growth factor, namely motility, proliferation, cell survival, invasion, tubulogenesis and angiogenesis. The partial agonist mAb (DN-30) induces only motility. Only the full agonist mAb is able to induce and sustain the expression of urokinase-type plasminogen activator receptor for prolonged periods of time, while both mAbs up-regulate the constitutive expression of urokinase-type plasminogen activator. Both mAbs activate receptor phosphorylation, which, being strictly dependent on mAb bivalence, requires receptor dimerization. Since simple receptor dimerization is not sufficient to trigger full biological responses, we propose that the region on the ss chain of the receptor recognized by the full agonist mAb is crucial for optimal receptor activation.
Clinical performance of posterior compomer restorations over 4 years. (2006)

Twenty restorations were not investigated at the 4-year recall (drop-out). After 48 months, 11 restorations (Hytac: n = 8, Dyract AP: n = 3) had to be replaced due to tooth fracture (n = 4), gap formation (n = 5), and adhesive failure (n = 2). Forty restorations were still in function after 4 years (overall failure rate 16%; Hytac: 21%; Dyract: 9%). Between the recalls, statistically significant differences were detected for the criteria marginal integrity (Alpha dropping from 76% at baseline to 32% after 4 years), restoration integrity (Alpha ratings at baseline 99% vs. 40% after 4 years), and occlusion (100% vs. 24%). For the criteria surface roughness (from the 6-month recall) and anatomical shape (after 4 years), a significant difference between the materials was evident in favor of Dyract AP. Except gap-free margins, the predominant criterion in the microscopic analysis at baseline was marginal overhang (24%) and 30% negative step formation after 4 years.
Triiodothyronine Stimulation of in Vitro Growth and Maturation of Embryonic Chick Cartilage* (1982)

We studied the direct effect of T3 on cartilage growth and maturation in vitro. Pelvic cartilages from 9-day-old chick embryos were incubated in a serum-free organ culture system which supported cartilage growth over a 5-day interval. The addition of T3 (15 nM) to the medium increased cartilage wet weight (approximately 100%), dry weight (77%), length (35%), and total soluble protein (67%) over 3 days compared to cartilage incubated in medium alone. The DNA content was only slightly increased (2%) by T3 over the interval. T3 stimulated the same parameters of growth similarly after 5 days of incubation. In addition, T3 increased the incorporation of [14C]leucine into protein (82%) and 35SO4 into proteoglycan (53%). A dose-dependent increase in cartilage wet weight was seen with T3 (0.0015-15 nM) over 3 days of incubation. Cartilage incubated with T3 demonstrated microscopic changes in maturation, with development of large numbers of hypertrophied chondrocytes, and biochemical evidence of maturation, with increased alkaline phosphatase activity (130%). The dose-response range for T3 stimulation of alkaline phosphatase activity (0.015-0.15 nM) was considerably more restricted than that for stimulation of growth (0.0015-15 nM). These studies demonstrate that T3 in physiological concentrations directly affects cartilage growth and maturation, primarily through stimulating chondrocyte hypertrophy.
Query-level learning to rank using isotonic regression (2008)

Ranking functions determine the relevance of search results of search engines, and learning ranking functions has become an active research area at the interface between Web search, information retrieval and machine learning. Generally, the training data for learning to rank come in two different forms: (1) absolute relevance judgments assessing the degree of relevance of a document with respect to a query. This type of judgments is also called labeled data and are usually obtained through human editorial efforts; and (2) relative relevance judgments indicating that a document is more relevant than another with respect to a query. This type of judgments is also called preference data and can usually be extracted from the abundantly available user click-through data recording users' interactions with the search results. Most existing learning to rank methods ignore the query boundaries, treating the labeled data or preference data equally across queries. In this paper, we propose a minimum effort optimization method that takes into account the entire training data within a query at each iteration. We tackle this optimization problem using functional iterative methods where the update at each iteration is computed by solving an isotonic regression problem. This more global approach results in faster convergency and signficantly improved performance of the learned ranking functions over existing state-of-the-art methods. We demonstrate the effectiveness of the proposed method using data sets obtained from a commercial search engine as well as publicly available data.
Inactivation of Ca2+/calmodulin-dependent protein kinase II by basal autophosphorylation. (1993)

Incubation of either purified rat forebrain Ca2+/calmodulin-dependent protein kinase II (CaMKII) or the purified recombinant, baculovirus-expressed mouse alpha subunit of CaMKII (Brickey, D. A., Colbran, R. J., Fong, Y.-L., and Soderling, T. R. (1990) Biochem. Biophys. Res. Commun. 173, 578-584) with EGTA, magnesium acetate, and [gamma-32P]ATP resulted in the incorporation of up to 1.0 mol of 32PO4/mol of subunit within 60 min at 30 degrees C; both serine and threonine residues became autophosphorylated. The Vmax for this basal autophosphorylation was 0.051 +/- 0.005 mol of 32PO4/mol of subunit/min, and the Km(ATP) was 145 +/- 8 microM. Vmax and Km(ATP) values for Ca2+/calmodulin-dependent autophosphorylation were determined to be 1.3 +/- 0.4 mol/mol/min and 19 +/- 2 microM, respectively. Basal autophosphorylation resulted in inactivation of Ca2+/calmodulin-dependent kinase activity toward exogenous peptide substrate; there was no measurable increase in Ca(2+)-independent CaMKII activity. Inactivation was not observed following preincubation with non-hydrolyzable ATP analogs in place of ATP. CaMKII that had been inactivated by basal autophosphorylation could be fully re-activated by incubation with the purified catalytic subunit of protein phosphatase 2A. Following basal autophosphorylation, the calmodulin-binding ability of CaMKII was also reduced, presumably accounting for the observed inactivation. Both the inactivation and the decrease in calmodulin-binding that resulted from basal autophosphorylation were abrogated by mutation of threonine 306 to alanine, but not by mutation of threonine 305 to alanine. Furthermore, mutation of threonine 306, but not threonine 305, to alanine reduced the extent of basal autophosphorylation at threonine residues. Thus, basal autophosphorylation at threonine 306 blocks calmodulin binding, resulting in inactivation of CaMKII.
Chondrogenic differentiation of induced pluripotent stem cells from osteoarthritic chondrocytes in alginate matrix (2012)

Induced pluripotent stem cells (iPSCs) have the potential to revolutionise cell therapy; however, it remains unclear whether iPSCs can be generated from human osteoarthritic chondrocytes (OCs) and subsequently induced to differentiate into chondrocytes. In the present study, we investigated the differentiation potential of OCs into iPSCs using defined transcription factors and explored the possibility of using these OC-derived iPSCs for chondrogenesis. Our study demonstrates that iPSCs can be generated from OCs and that these iPSCs are indistinguishable from human embryonic stem cells (hESCs). To promote chondrogenic differentiation, we used lentivirus to transduce iPSCs seeded in alginate matrix with transforming growth factor-β1 (TGF-β1) and then in vitro co-cultured these iPSCs with chondrocytes. Gene expression analysis showed that this combinational strategy promotes the differentiation of the established iPSCs into chondrocytes in alginate matrix. Increased expression of cartilage-related genes, including collagen II, aggrecan, and cartilage oligomeric matrix protein (COMP), and decreased gene expression of the degenerative cartilage marker, vascular endothelial growth factor (VEGF), were observed. The histological results revealed a dense sulphated extracellular matrix in the co-culture of TGF-β1-transfected iPSCs with chondrocytes in alginate matrix. Additionally, in vivo chondroinductive activity was also evaluated. Histological examination revealed that more new cartilage was formed in the co-culture of TGF-β1-transfected iPSCs with chondrocytes in alginate matrix. Taken together, our data indicate that iPSCs can be generated from OCs by defined factors and the combinational strategy results in significantly improved chondrogenesis of OC-derived iPSCs. This work adds to our understanding of potential solutions to osteoarthritic cell replacement problem.
Characterization and expression of a cloned tetracycline resistance determinant from the chromosome of Streptococcus mutans (1984)

A chromosomal tetracycline resistance (Tcr) determinant previously cloned from Streptococcus mutans into Streptococcus sanguis (Tobian and Macrina, J. Bacteriol. 152:215-222, 1982) was characterized by using restriction endonuclease mapping, deletion analysis, and Southern blot hybridization. Deletion analysis allowed localization of the Tcr determinant to a 2.8-kilobase region of the originally cloned 10.4-kilobase sequence. This cloned determinant hybridized to a representative of the tetM class of streptococcal Tcr determinants but not to representatives of the tetL and tetN classes and, like other tetM determinants, mediated high-level resistance to tetracycline and low-level resistance to minocycline. A portion (approximately 3 kilobases) of the isolated streptococcal fragment was subcloned into Escherichia coli, where it conferred resistance to tetracycline and minocycline. Two proteins with apparent molecular weights of 33,000 and 35,000, encoded by the S. mutans DNA, were synthesized in E. coli minicells. Insertion of DNA into a unique SstI site of the cloned S. mutans fragment resulted in inactivation of Tcr expression in E. coli and S. sanguis, as well as loss of production of both the 33,000- and 35,000-dalton proteins in E. coli minicells. Incubation of minicells in subinhibitory concentrations of tetracycline did not result in changes in the levels of synthesis of either protein. Our data suggest that at least one of these proteins is involved in the expression of Tcr.
Characterization of a broadband pulse for phase controlled multiphoton microscopy by single beam SPIDER (2007)

We present what we believe to be a new version of spectral phase interferometry for direct electric field reconstruction (SPIDER) using only a single-phase and polarization controlled laser beam. Two narrow pulses and one broadband pulse are selected out of an ultrafast laser pulse by a polarization and phase control technique to generate second harmonic generation (SHG) signals, which are equivalent to a spectral shear interferogram in the conventional SPIDER method. The spectral phase of the broadband laser pulse is extracted analytically with double quadrature spectral interferometry (DQSI). An arbitrary spectral phase can be retrieved with great precision and compensated in situ at the sample position of a microscope. This new method requires no separate reference beam and is suitable for nonlinear optical microscopy with a phase controlled laser pulse.
Enhanced Named Entity Extraction via Error-Driven Aggregation (2010)

Despite recent advances in named entity extraction technologies, state-of-the-art extraction tools achieve insufficient accuracy rates for practical use in many operational settings. However, they are not generally prone to the same types of error, suggesting that substantial improvements may be achieved via appropriate combinations of existing tools, provided their behavior can be accurately characterized and quantified. In this paper, we present an inference methodology for the aggregation of named entity extraction technologies that is founded upon a black-box analysis of their respective error processes. This method has been shown to produce statistically significant improvements in extraction relative to standard performance metrics and to mitigate the weak performance of entity extractors operating under suboptimal conditions. Moreover, this approach provides a framework for quantifying uncertainty and has demonstrated the ability to reconstruct the truth when majority voting fails.
High Density Lipoprotein Cholesterol Subfractions in Older People (1994)

The slight increase in HDL-C with age appears to be due to an increase in the HDL2-C subfraction. HDL-C subfractions are independently related to triglyceride levels, body weight, and insulin concentrations in older people, all potentially modifiable risk factors. Both HDL2-C and HDL3-C are lower in older people with prevalent cardiovascular disease, although only HDL3-C was correlated with carotid atherosclerosis. These findings are consistent with the hypothesis that HDL subfractions are important risk factors for atherosclerotic cardiovascular disease in the elderly.