gebhart/patrepeval huggingface dataset:
Enhancer sequences of the DF3 gene regulate expression of the herpes simplex virus thymidine kinase gene and confer sensitivity of human breast cancer cells to ganciclovir. (1994)

A potentially novel therapeutic strategy for breast cancer treatment involves sensitization of tumor cells to chemotherapy through gene transfer. Clinical application of this approach, however, may be limited by the lack of target cell specificity of currently available gene delivery techniques. Development of vectors with tumor-selective gene expression could overcome this problem. The DF3/MUC1 gene encodes a high molecular weight mucin-like glycoprotein which is overexpressed at the transcriptional level in the majority of human breast cancers. To develop a breast tumor-selective enhancer, we cloned the upstream region of the DF3 gene and have identified a 114-base pair enhancer region that can modulate transcription from heterologous promoters. The present studies demonstrate that the DF3 enhancer sequences can direct selective gene expression in DF3-positive breast carcinoma cells. DF3-positive breast carcinoma cell lines transfected with herpes simplex virus thymidine kinase gene expression cassettes modified by the DF3 enhancer were markedly more sensitive to killing by ganciclovir than were the same cells transfected with the expression cassettes lacking the DF3 enhancer. DF3-negative cell lines transfected with the DF3 enhancer constructs, however, were no more sensitive to ganciclovir than were cells treated with the unmodified expression plasmids. Consistent with an innocent bystander effect, nontransfected human breast carcinoma cells were susceptible in a cell density-dependent manner to ganciclovir-induced cell killing when adjacent to transfected cells. The results also demonstrate that the DF3 enhancer sequences can be effectively incorporated into a retroviral vector to mediate selective gene expression following retroviral infection. These findings suggest that the DF3 promoter/enhancer may be useful for incorporation into vectors designed for gene therapy of breast cancer.
Grouping Web page references into transactions for mining World Wide Web browsing patterns (2002)

Web-based organizations often generate and collect large volumes of data in their daily operations. Analyzing such data involves the discovery of meaningful relationships from a large collection of primarily unstructured data, often stored in Web server access logs. While traditional domains for data mining, such as point of sale databases, have naturally defined transactions, there is no convenient method of clustering web references into transactions. This paper identifies a model of user browsing behavior that separates web page references into those made for navigation purposes and those for information content purposes. A transaction identification method based on the browsing model is defined and successfully tested against other methods, such as the maximal forward reference algorithm proposed in (Chen et al., 1996). Transactions identified by the proposed methods are used to discover association rules from real world data using the WEBMINER system.
Risks to the public in computers and related systems (2004)

Edited by Peter G. Neumann (Risks Forum Moderator and Chairman of the ACM Committee on Computers and Public Policy), plus personal contributions by others, as indicated. Opinions expressed are individual rather than organizational, and all of the usual disclaimers apply. We address problems relating to software, hardware, people, and other circumstances that affect computer systems. To economize on space, we tersify most items and include pointers to items in the online Risks Forum: (R i j) denotes RISKS vol i number j. Cited RISKS items generally identify contributors and sources, together with URLs. Official RISKS archives are available at www.risks.org (which redirects to Newcastle and gets you nice html formatting and a search engine courtesy of Lindsay Marshall; http://catless.ncl.ac.uk/Risks/i.j.html gets you (R i j); and at ftp://www.sri.com/risks.A cumulative summary of RISKS and SEN items is available at http://www.CSL.sri.com/neumann/illustrative.html as well as ftp://ftp.csl.sri.com/illustrative.ps and pdf. Please send RISKS-related items to risks@CSL.sri.com. Read RISKS as a newsgroup (comp.risks), or subscribe via the automated list server at risks-request@CSL.sri.com. "Inside Risks" columns from the Communications of the ACM are also online (http://www.csl.sri.com/neumann/insiderisks.html).
Anti-HER2 vaccines: new prospects for breast cancer therapy (2010)

Each year, breast cancer accounts for more than 400,000 new cancer cases and more than 130,000 cancer deaths in Europe. Prognosis of nonmetastatic breast cancer patients is directly related to the extent of the disease, mainly nodal spreading and tumor size, and to the molecular profile, particularly HER2 over-expression. In patients with HER2-over-expressing tumors, different studies have shown cellular and/or humoral immune responses against HER2 associated with a lower tumor development at early stages of the disease. These findings have led to the hypothesis that the generation of an anti-HER2 immune response should protect patients from HER2-over-expressing tumor growth. Taken together with the clinical efficiency of trastuzumab-based anti-HER2 passive immunotherapy, these observations allowed to envisage various vaccine strategies against HER2. The induction of a stable and strong immunity by cancer vaccines is expected to lead to establishment of immune memory, thereby preventing tumor recurrence. However, an immunological tolerance against HER2 antigen exists representing a barrier to effective vaccination against this oncoprotein. As a consequence, the current challenge for vaccines is to find the best conditions to break this immunological tolerance. In this review, we will discuss the different anti-HER2 vaccine strategies currently developed; considering the strategies having reached the clinical phases as well as those still in preclinical development. The used antigen can be either composed of tumoral allogenic cells or autologous cells, or specific to HER2. It can be delivered by dendritic cells or in a DNA, peptidic or proteic form. Another area of research concerns the use of anti-idiotypic antibodies mimicking HER2.
Oligodendrocyte Precursor Cells Reprogrammed to Become Multipotential CNS Stem Cells (2000)

During animal development, cells become progressively more restricted in the cell types to which they can give rise. In the central nervous system (CNS), for example, multipotential stem cells produce various kinds of specified precursors that divide a limited number of times before they terminally differentiate into either neurons or glial cells. We show here that certain extracellular signals can induce oligodendrocyte precursor cells to revert to multipotential neural stem cells, which can self-renew and give rise to neurons and astrocytes, as well as to oligodendrocytes. Thus, these precursor cells have greater developmental potential than previously thought.
Early effects of renal denervation in the anaesthetised rat: natriuresis and increased cortical blood flow (2001)

A novel method of renal denervation was developed based on electro-coagulation of tissue containing most of the sympathetic fibres travelling towards the kidney. Kidney tissue noradrenaline was decreased to 4.7 % of the content measured in the contralateral innervated kidney when studied 3 days postdenervation. The method was utilised in anaesthetised rats to examine the effects of denervation within the heretofore unexplored first 75 min period postdenervation. Sodium excretion (UNaV) increased significantly (+82 %, P < 0.03) over the 25-50 min after denervation. In a parallel group, with a lower baseline UNaV, there was also a significant increase in UNaV (+54 %, P < 0.03) within the first 25 min. The renal perfusion pressure was maintained at a constant value and the glomerular filtration rate did not change after denervation. Renal cortical and medullary blood flows (CBF, MBF) were estimated as laser Doppler flux and medullary tissue ion concentration was estimated as electrical admittance (Y). Following denervation, in both groups CBF increased significantly within the first 25 min (+12 %, P < 0.01 and +8 %, P < 0.05, respectively) while MBF did not change or decreased slightly; Y did not change. The data document the development of natriuresis within the first 25-50 min after denervation. The increase in CBF indicated that, prior to denervation, the cortical, but not medullary, circulation was under a tonic vasoconstrictor influence of the renal nerves. Such a dissociation of neural effects on the renal cortical vs. medullary vasculature has not been previously described.
High efficiency white organic light emitting diodes employing blue and red platinum emitters (2014)

Platinum-based blue and red emitters were used to make stacked organic light-emitting diodes devices for potential use in solid-state lighting. The electroluminescence (EL) spectra were strongly dependent on the red layer thickness and relative position of the red and blue emissive layers. Although all devices had very little EL in the green region, a color rendering index (CRI) as high as 65 was achieved. Addition of a suitable phosphorescent green emissive layer should produce higher CRI values. All devices tested exhibited external quantum efficiencies greater than 20%, indicating that the Pt-based emitters reported here are potentially useful for solid-state lighting applications.
Single-Cell Enzyme Concentrations, Kinetics, and Inhibition Analysis Using High-Density Hydrodynamic Cell Isolation Arrays (2006)

High-quality single-cell data are required for a quantitative systems biology description of cellular function. However, data of this type are difficult and time-consuming to collect using traditional techniques. We present a robust and simple microfluidic method for trapping single cells in large arrays to address this problem. Ordered single-cell isolation arrays allow for high-density microscopic analysis with simplified image processing. Moreover, for fluorescent assays, on-chip sample preparation (e.g., fluorescent labeling, washing) can be performed, as opposed to manual intensive operations of incubation, centrifugation, and resuspension in previous techniques-saving time and reagents. This technology was applied to determine novel single-cell enzyme kinetics for three different cell types (HeLa, 293T, Jurkat). A kinetic model of this process predicted this varied response was due to variation in the concentration of carboxylesterase between cell types. Nordihydroguaiaretic acid (NDGA) was also characterized as an inhibitor of carboxylesterases. For HeLa cells, 20 nM of the 50 nM total carboxylesterases was unaffected by NDGA. This type of analysis could be directly applied to quantify a variety of intracellular enzymes with available fluorogenic substrates.
High-Resolution NMR Structure of the Chemically-Synthesized Melanocortin Receptor Binding Domain AGRP(87−132) of the Agouti-Related Protein, (2001)

The agouti-related protein (AGRP) is an endogenous antagonist of the melanocortin receptors MC3R and MC4R found in the hypothalamus and exhibits potent orexigenic (appetite-stimulating) activity. The cysteine-rich C-terminal domain of this protein, corresponding to AGRP(87-132), contains five disulfide bonds and exhibits receptor binding affinity and antagonism equivalent to that of the full-length protein. The three-dimensional structure of this domain has been determined by 1H NMR at 800 MHz. The first 34 residues of AGRP(87-132) are well-ordered and contain a three-stranded antiparallel beta sheet, where the last two strands form a beta hairpin. The relative spatial positioning of the disulfide cross-links demonstrates that the ordered region of AGRP(87-132) adopts the inhibitor cystine knot (ICK) fold previously identified for numerous invertebrate toxins. Interestingly, this may be the first example of a mammalian protein assigned to the ICK superfamily. The hairpin's turn region presents a triplet of residues (Arg-Phe-Phe) known to be essential for melanocortin receptor binding. The structure also suggests that AGRP possesses an additional melanocortin-receptor contact region within a loop formed by the first 16 residues of its C-terminal domain. This specific region shows little sequence homology to the corresponding region of the agouti protein, which is an MC1R antagonist involved in pigmentation. Consideration of these sequence differences, along with recent experiments on mutant and chimeric melanocortin receptors, allows us to postulate that this loop in the first 16 residues of its C-terminal domain confers AGRP's distinct selectivity for MC3R and MC4R.
Electron Transfer Control in Soluble Methane Monooxygenase (2014)

The hydroxylation or epoxidation of hydrocarbons by bacterial multicomponent monooxygenases (BMMs) requires the interplay of three or four protein components. How component protein interactions control catalysis, however, is not well understood. In particular, the binding sites of the reductase components on the surface of their cognate hydroxylases and the role(s) that the regulatory proteins play during intermolecular electron transfer leading to the hydroxylase reduction have been enigmatic. Here we determine the reductase binding site on the hydroxylase of a BMM enzyme, soluble methane monooxygenase (sMMO) from Methylococcus capsulatus (Bath). We present evidence that the ferredoxin domain of the reductase binds to the canyon region of the hydroxylase, previously determined to be the regulatory protein binding site as well. The latter thus inhibits reductase binding to the hydroxylase and, consequently, intermolecular electron transfer from the reductase to the hydroxylase diiron active site. The binding competition between the regulatory protein and the reductase may serve as a control mechanism for regulating electron transfer, and other BMM enzymes are likely to adopt the same mechanism.
Enzyme replacement therapy for Gaucher disease (1991)

Four patients with moderately severe type I Gaucher disease were treated with commercially available mannose terminated glucocerebrosidase (Ceredase; Genzyme, Boston, MA) for up to 13 months. The enzyme was administered at the rate of three to four times weekly at one fourth the total recommended dosage, greatly decreasing the cost. Marked regression of hepatomegaly and improvement in liver function tests, peripheral blood counts, and serum angiotensin-converting enzyme levels were documented. The two patients with pulmonary involvement manifested improvement in pulmonary function tests. Skeletal disease remained unchanged.
Regulation of the Cyanide-resistant Alternative Oxidase of Plant Mitochondria (1998)

The cyanide-resistant alternative oxidase of plant mitochondria is a homodimeric protein whose activity can be regulated by a redox-sensitive intersubunit sulfhydryl/disulfide system and by alpha-keto acids. After determining that the Arabidopsis alternative oxidase possesses the redox-sensitive sulfhydryl/disulfide system, site-directed mutagenesis of an Arabidopsis cDNA clone was used to individually change the two conserved Cys residues, Cys-128 and Cys-78, to Ala. Using diamide oxidation and chemical cross-linking of the protein expressed in Escherichia coli, Cys-78 was shown to be: 1) the Cys residue involved in the sulfhydryl/disulfide system; and 2) not required for subunit dimerization. The C128A mutant was stimulated by pyruvate, while the C78A mutant protein had little activity and displayed no stimulation by pyruvate. Mutating Cys-78 to Glu produced an active enzyme which was insensitive to pyruvate, consistent with alpha-keto acid activation occurring through a thiohemiacetal. These results indicate that Cys-78 serves as both the regulatory sulfhydryl/disulfide and the site of activation by alpha-keto acids. In light of these results, the previously observed effects of sulfhydryl reagents on the alternative oxidase of isolated soybean mitochondria were re-examined and were found to be in agreement with a single sulfhydryl residue being the site both of alpha-keto acid activation and of the regulatory sulfhydryl/disulfide system.
Chinese Herbal Medicine (1975)

Background/Aim: Previous reports have associated the KMT2A-ELL fusion gene, generated by t(11;19)(q23;p13.1), with acute myeloid leukemia (AML). We herein report a KMT2A-ELL and a novel ZNF56-KMT2A fusion genes in a pediatric T-lineage acute lymphoblastic leukemia (T-ALL). Materials and Methods: Genetic investigations were performed on bone marrow of a 13-year-old boy diagnosed with T-ALL. Results: A KMT2A-ELL and a novel ZNF56-KMT2A fusion genes were generated on der(11)t(11;19)(q23;p13.1) and der(19)t(11;19)(q23;p13.1), respectively. Exon 20 of KMT2A fused to exon 2 of ELL in KMT2A-ELL chimeric transcript whereas exon 1 of ZNF56 fused to exon 21 of KMT2A in ZNF56-KMT2A transcript. A literature search revealed four more T-ALL patients carrying a KMT2A-ELL fusion. All of them were males aged 11, 11, 17, and 20 years. Conclusion: KMT2A-ELL fusion is a rare recurrent genetic event in T-ALL with uncertain prognostic implications. The frequency and impact of ZNF56-KMT2A in T-ALL are unknown.
Stochastic Algorithms for Maximizing Molecular Diversity (1997)

A common problem in the emerging field of combinatorial drug design is the selection of an appropriate subset of compounds for chemical synthesis and biological evaluation. In this paper, we introduce a new family of selection algorithms that combine a stochastic search engine with a user-defined objective function that encodes any desirable selection criterion. The method is applied to the problem of maximizing molecular diversity, and the results are visualized using Sammon's nonlinear mapping algorithm. By separating the search method from the performance metric, the method can be easily extended to perform complex multi-objective selections in advanced decision-support systems.
Mitogen-Activated Protein Kinase Cascades as Regulators of Stress Responses (1998)

Mitogen-activated protein kinase (MAPK) cascades play an important role in transducting environmental stimuli to the transcriptional machinery in the nucleus by virtue of their ability to phosphorylate and regulate the activity of various transcription factors. Originally found to be activated in response to occupancy of cell surface receptors for polypeptide hormones, cytokines, and growth factors, MAPK cascades were recently found to be activated by a variety of stresses including ischemia reperfusion, neuronal injury, osmotic shock, and exposure to UV irradiation. Therefore, MAPK cascades are likely to be important regulatory elements in a variety of stress responses.
Annihilation assisted upconversion: all-organic, flexible and transparent multicolour display (2008)

In this paper, we demonstrate the first all-organic, transparent, flexible, versatile colour displays based upon triplet–triplet annihilation assisted photon energy upconversion in viscous polymeric matrix. The devices work with ultra-low excitation intensities down to 20 mW cm−2 red or near-IR light. The displays are based on metallated-porphyrin sensitizers in combination with emitters dispersed in a transparent polymeric matrix and are driven by galvo-scanned laser diodes. The displays have external quantum yield as high as 3.2%. The response time can be adjusted to specific application requirements—up to 80 μs allowing kHz-refreshment rate of the displayed information. It is possible to easily tune the optical density of the screens in order to obtain a desired transmittance for the excitation beam. We demonstrate the ability to achieve multicolour emission, using only one excitation source. There are practically no display size limitations.
Two Chromatin Remodeling Activities Cooperate during Activation of Hormone Responsive Promoters (2009)

Steroid hormones regulate gene expression by interaction of their receptors with hormone responsive elements (HREs) and recruitment of kinases, chromatin remodeling complexes, and coregulators to their target promoters. Here we show that in breast cancer cells the BAF, but not the closely related PBAF complex, is required for progesterone induction of several target genes including MMTV, where it catalyzes localized displacement of histones H2A and H2B and subsequent NF1 binding. PCAF is also needed for induction of progesterone target genes and acetylates histone H3 at K14, an epigenetic mark that interacts with the BAF subunits by anchoring the complex to chromatin. In the absence of PCAF, full loading of target promoters with hormone receptors and BAF is precluded, and induction is compromised. Thus, activation of hormone-responsive promoters requires cooperation of at least two chromatin remodeling activities, BAF and PCAF.
Synthesis and Biological Evaluation of 3‐Ethylidene‐1,3‐dihydro‐indol‐2‐ones as Novel Checkpoint 1 Inhibitors. (2006)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Analysis of IL6 and IL1A gene polymorphisms in UK and Dutch patients with sarcoidosis. (2003)

Although the investigated polymorphisms are unlikely to contribute to sarcoidosis susceptibility, the IL6-174C allele might have a role in the genetics underlying sarcoidosis severity or the progression towards pulmonary fibrosis in a particular subgroup.
S-100 protein in soft-tissue tumors derived from Schwann cells and melanocytes. (1982)

In soft tissues outside the central nervous system, S-100 protein is found normally only in Schwann cells. Using the peroxidase-antiperoxidase immunohistochemical method S-100 was also found in tumors derived from Schwann cells and melanocytes, including neurofibromas, neurilemomas, granular cell myoblastomas, cutaneous nevi, and malignant melanomas. S-100 was not detected in malignant Schwannomas, neuroblastomas, oat cell carcinomas, medullary carcinomas of the thyroid, paragangliomas, or meningiomas. S-100 was also absent from neoplasms of soft tissues not usually considered to arise from cells of neural crest origin. S-100 appears to be a useful marker for identifying neoplasms derived from Schwann cells and melanocytes.
Anti-angiogenesis Effects of Borrelidin are Mediated through Distinct Pathways: Threonyl-tRNA Synthetase and Caspases are Independently Involved in Suppression of Proliferation and Induction of Apoptosis in Endothelial Cells (2003)

Borrelidin, an antibiotic with anti-angiogenic activity, not only suppresses new capillary tube formation, but also collapses formed capillary tubes in a rat aorta culture model. Since it selectively inhibits threonyl-tRNA synthetase, we examined the effect of threonine on its anti-angiogenic activity. We found that a high concentration of threonine (1 mM) attenuated the ability of borrelidin to inhibit both capillary tube formation in the rat aorta culture model and human umbilical vein endothelial cells (HUVEC) proliferation, yet did not affect the ability of borrelidin to collapse formed capillary tubes or to induce apoptosis in HUVEC. Borrelidin activated caspase-3 and -8, and inhibitors of both caspase-3 and -8 suppressed borrelidin-induced apoptosis in HUVEC. Taken together, these data suggest that the anti-angiogenic effects of borrelidin are mediated through at least two mechanisms, i.e. one threonine-dependent and the other threonine-independent, and borrelidin induces apoptosis in endothelial cells via the caspase-8/-3 pathway.