gebhart/patrepeval huggingface dataset:
Abstract LB-17: NKX2-1/TITF1/TTF-1-induced ROR1 is required to sustain EGFR survival signaling in lung adenocarcinoma (2012)

Abstract Emerging evidence, though currently sparse, suggests that “lineage-specific transcription factors” with developmental roles in normal progenitor cells of particular lineages may also confer dependency for survival to certain types of cancer cells. Accumulated evidence indicates that NKX2-1, a lineage-specific transcription factor also known as TITF1 and TTF-1, which is expressed in a major fraction of lung adenocarcinomas, plays essential roles in peripheral lung development. We previously identified NKX2-1 as a lineage-survival oncogene in lung adenocarcinoma, while other investigators reached similar conclusions through genome-wide searches for focal genomic aberrations. Previous findings including ours thus clearly indicate the requirement of sustained NKX2-1 expression for lung adenocarcinoma survival, while it remains elusive how NKX2-1 mediates survival signals. In the present study, we show that NKX2-1 induces the expression of the receptor tyrosine kinase-like orphan receptor 1 (ROR1), which in turn sustains a favorable balance between prosurvival PI3K-AKT and proapoptotic p38 signaling, in part through ROR1 kinase-dependent c-Src activation. Interestingly, ROR1 was also identified as a receptor tyrosine kinase with a “sustainer role” for the interaction of EGFR-ERBB3 and ERBB3 phosphorylation in a ROR1 kinase-independent manner, consequentially leading to PI3K activation. It was also of note that ROR1 knockdown effectively inhibited lung adenocarcinoma cell lines irrespective of their EGFR status, including those with resistance to the EGFR tyrosine kinase inhibitor gefitinib. Secondary EGFR mutation, MET amplification, and HGF overexpression may arise in lung adenocarcinomas in patients undergoing EGFR-TKI treatment, leading to treatment resistance. The existence of such diverse mechanisms makes it difficult to predict which should be targeted to prevent expansion of resistant clones. From a clinical point of view, it is thus of particular interest that ROR1 inhibition appears to be effective for treatment of gefitinib-resistant lung adenocarcinomas with various resistance mechanisms. Taken together, the present findings identify ROR1 as an “Achilles’ heel” in lung adenocarcinomas. Future development of novel therapeutic means including ROR1-specific antibodies and small molecules that inhibit both or either of the two distinct prosurvival signal-sustaining functions is greatly anticipated for attempts to reduce the intolerable death toll from currently “hard-to-cure” lung adenocarcinomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-17. doi:1538-7445.AM2012-LB-17
Detection of point mutations with a modified ligase chain reaction (Gap-LCR) (1995)

DNA amplification systems are powerful technologies with the potential to impact a wide range of diagnostic applications. In this study we explored the feasibility and limitations of a modified ligase chain reaction (Gap-LCR) in detection and discrimination of DNAs that differ by a single base. LCR is a DNA amplification technology based on the ligation of two pairs of synthetic oligonucleotides which hybridize at adjacent positions to complementary strands of a target DNA. Multiple rounds of denaturation, annealing and ligation with a thermostable ligase result in the exponential amplification of the target DNA. A modification of LCR, Gap-LCR was developed to reduce the background generated by target-independent, blunt-end ligation. In Gap-LCR, DNA polymerase fills in a gap between annealed probes which are subsequently joined by DNA ligase. We have designed synthetic DNA targets with single base pair differences and analyzed them in a system where three common probes plus an allele-specific probe were used. A single base mismatch either at the ultimate 3' end or penultimate 3' end of the allele specific probe was sufficient for discrimination, though better discrimination was obtained with a mismatch at the penultimate 3' position. Comparison of Gap-LCR to allele-specific PCR (ASPCR) suggested that Gap-LCR has the advantage of having the additive effect of polymerase and ligase on specificity. As a model system, Gap-LCR was tested on a mutation in the reverse transcriptase gene of HIV, specifically, one of the mutations that confers AZT resistance. Mutant DNA could be detected and discriminated in the presence of up to 10,000-fold excess of wild-type DNA.
Estrogenic effects of physiological concentrations of 5-androstene-3 beta, 17 beta-diol and its metabolism in MCF7 human breast cancer cells. (1981)

5-Androstene-3 beta, 17 beta-diol (ADIOL) has previously been shown to have a high affinity for the estrogen receptor and to translocate it to the nucleus in vitro and in vivo. This compound and related C19 delta 5-steroids of adrenal origin have now been examined for their ability to induce the synthesis in MCF7 cells of an estrogen-dependent secreted glycoprotein (M.W. 46,000). Concentrations required for half-maximum induction were 2 nM for ADIOL and 500 nM for dehydroepiandrosterone (DHEA). Dehydroepiandrosterone sulfate showed weak inducing ability at concentrations of 1 microM or greater. The induction by ADIOL was unaffected by the presence of an aromatase inhibitor, and 5 alpha-androstane-3 beta, 17 beta-diol, which cannot be aromatized, also induced the M.W. 46,000 protein at low concentrations. When cells were exposed to 10 nM [3H]ADIOL, the cytosol and nuclear fractions contained [3H]ADIOL resistant to charcoal adsorption. The bound [3H]ADIOL in the cytosol and nucleus was displaceable by 17 beta-estradiol and tamoxifen, suggesting that it was binding to the estrogen receptor. [3H]ADIOL was metabolized to its 3 beta-sulfate, which was excreted into the medium, and to [3H]DHEA, which was found in the cells and the medium as free DHEA and its 3 beta-sulfate. [3H]DHEA was also metabolized by the cells to its 3 beta-sulfate, to free ADIOL, and to the 3 beta-sulfate of adiol. We conclude that: (a) ADIOL is effective as an estrogen in MCF7 cells at a concentration of 2 nM, which is within the range found in the blood of normal women; and (b) sulfurylation is a major route of inactivation of 3 beta-hydroxy delta 5-steroids in MCF7 cells.
RObust Header Compression (ROHC): A Compression Profile for IP (2004)

The original RObust Header Compression (ROHC) RFC (RFC 3095) defines a
framework for header compression, along with compression protocols
(profiles) for IP/UDP/RTP, IP/ESP (Encapsulating Security Payload),
IP/UDP, and also a profile for uncompressed packet streams. However,
no profile was defined for compression of IP only, which has been
identified as a missing piece in RFC 3095. This document defines a
ROHC compression profile for IP, similar to the IP/UDP profile defined
by RFC 3095, but simplified to exclude UDP, and enhanced to compress
IP header chains of arbitrary length. [STANDARDS-TRACK]
Tumor regression responses in melanoma patients treated with a peptide encoded by gene MAGES‐3 (1995)

SCOPUS: ar.j
Evaluation of a Rapid Whole Blood ELISA for Quantification of Troponin I in Patients with Acute Chest Pain (1999)

The Stratus CS provided better analytical performance and comparable or better prognostic information than the Stratus II.
Effect of docetaxel chemotherapy on the activity of a gonadotropin releasing hormone vaccine in patients with advanced prostate cancer (2005)

The administration of docetaxel with high-dose dexamethasone does not inhibit the ability of patients with advanced prostate cancer to be immunized with GnRH-DT vaccine.
Worldwide investment analysis : the case of aluminum (1983)

This study focuses on the likely long term trends in investment, production and trade patterns in the world aluminum industry. It first introduces the non specialist reader to the technical characteristics of bauxite mining and the production of alumina and aluminum. Special emphasis is placed on the critical importance of energy requirements. Next, a verbal description of the method of analysis is presented. A detailed technical statement of the mathematical programming mmodel, and the associated data input are provided in two annexes to the study. The main conclusion drawn from the analysis is that the emerging pattern of investment, production and trade is very robust in the light of the changes that were made in the main parameters, particularly for bauxite and aluminum.
Neuronal Promoter Analysis byin VitroTranscription Using Nuclear Extracts from Rat Brain (1996)

We present a reliable method for making nuclear extracts from rat brain and for using these extracts in an in vitro transcription assay. Our nuclear extract technique allows for the isolation of nuclear proteins from post mitotic neurons that presumably contain all of the factors required for the transcriptional regulation of neuron-specific genes. The use of brain as a source of nuclear extract is in contrast to the more commonly used cultured cell lines in which expression of neuron-specific genes may be poor or lacking in tissue specificity. In vitro transcription using nuclear extracts from expressing (brain) and nonexpressing (liver) tissues provides a direct assessment of promoter strength and level of tissue specificity apart from the effects of higher order DNA structure (i.e., chromatin). In vitro transcription is also amenable to DNA competitor studies and to the addition of purified or partially purified protein factors and antibodies. In this way, true neuron-specific transcriptional activator or repressor sequences or factors can be characterized. The approach is rapid, reliable, and easily quantifiable. Finally, advancements in the field of nucleosome reconstitution have allowed the coupling of in vitro transcription to nucleosome assembly systems and provide a novel and promising approach to the understanding of neuronal-specific gene expression.
Reward-Related Cortical Inputs Define a Large Striatal Region in Primates That Interface with Associative Cortical Connections, Providing a Substrate for Incentive-Based Learning (2006)

The anterior cingulate and orbital cortices and the ventral striatum process different aspects of reward evaluation, whereas the dorsolateral prefrontal cortex and the dorsal striatum are involved in cognitive function. Collectively, these areas are critical to decision making. We mapped the striatal area that receives information about reward evaluation. We also explored the extent to which terminals from reward-related cortical areas converge in the striatum with those from cognitive regions. Using three-dimensional-rendered reconstructions of corticostriatal projection fields along with two-dimensional chartings, we demonstrate the reward and cognitive territories in the primate striatum and show the convergence between these cortical inputs. The results show two labeling patterns: a focal projection field that consists of densely distributed terminal patches, and a diffuse projection consisting of clusters of fibers, extending throughout a wide area of the striatum. Together, these projection fields demonstrate a remarkably large, rostral, reward-related striatal territory that reaches into the dorsal striatum. Fibers from different reward-processing and cognitive cortical areas occupy both separate and converging territories. Furthermore, the diffuse projection may serve a separate integrative function by broadly disseminating general cortical activity. These findings show that the rostral striatum is in a unique position to mediate different aspects of incentive learning. Furthermore, areas of convergence may be particularly sensitive to dopamine modulation during decision making and habit formation.
Opposing roles for IL‐13 and IL‐13 receptor α2 in health and disease (2004)

Interleukin (IL)-13 is a key inducer of several type-2 cytokine-dependent pathologies. It regulates inflammation, mucus production, tissue remodeling, and fibrosis. Consequently, it has become an important therapeutic target for a number of debilitating illnesses, including asthma, idiopathic pulmonary fibrosis, ulcerative colitis, as well as several other diseases in which IL-13 is believed to be overproduced. In the murine model of schistosomiasis, IL-13 has emerged as a central mediator of chronic infection-induced liver pathology. Although IL-4, IL-5, IL-10, and IL-13 each regulate distinct aspects of the granulomatous inflammatory response, IL-13 was identified as the primary mediator of liver fibrosis. Thus, elucidating the mechanisms that regulate the production and function of IL-13 has become an intensive area of research. IL-13 signaling is mediated by the type-2 IL-4 receptor, which consists of the IL-4R alpha and IL-13R alpha 1 chains. However, another IL-13-binding chain, IL-13R alpha 2, appears to strongly inhibit the activity of IL-13. Animals deficient in IL-13R alpha 2 fail to downmodulate granuloma formation in the chronic phase of infection. They also develop severe IL-13-dependent fibrosis and portal hypertension and quickly succumb to the infection. Here, we summarize findings from the schistosomiasis model, which illustrate opposing activities for IL-13 and IL-13R alpha 2 in health and disease.
Establishment of detailed reference values for luteinizing hormone, follicle stimulating hormone, estradiol, and progesterone during different phases of the menstrual cycle on the Abbott ARCHITECT® analyzer (2006)

During a normal menstrual cycle, serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, and progesterone can vary widely between cycles for the same woman, as well as between different woman. Reliable reference values based on the local population are important for correct interpretation of laboratory results. The purpose of our study was to determine detailed reference values for these hormones throughout the menstrual cycle using the Abbott ARCHITECT system. From 20 volunteers (age 20-36 years) with normal cycles and no use of oral contraceptives, samples were taken every day during their cycle. Volunteers received three vaginal ultrasound examinations (days 10 and 13, and 1 or 2 days after ovulation) to measure follicular and corpus luteum development. Hormone levels were measured using the corresponding ARCHITECT assay and were synchronized to the LH peak. Median, and 5th and 95th percentile values were determined for each day of the cycle, as well as for early follicular (days -15 to -6), late follicular (days -5 to -1), LH peak (day 0), early luteal (+1 to +4), mid-luteal (days +5 to +9), and late luteal (days +10 to +14) phases of the cycle. Based on our data, we were able to establish detailed reference values for LH, FSH, estradiol, and progesterone, which should aid in the interpretation of results for these reproductive hormones in a variety of circumstances.
Dialysis process for the removal of surfactants to form colloidal mesoporous silica nanoparticles (2009)

Colloidal mesoporous silica nanoparticles less than 20 nm in diameter are prepared by dialysis; this simple surfactant removal route can avoid aggregation by sedimentation-redispersion and remove cationic surfactants while retaining the original colloidal state, which is applicable to the preparation of primary nanoparticles carrying a functional organic substance.
Noninvasive Neural Prostheses Using Mobile and Wireless EEG (2008)

<para xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> Neural prosthetic technologies have helped many patients by restoring vision, hearing, or movement and relieving chronic pain or neurological disorders. While most neural prosthetic systems to date have used invasive or implantable devices for patients with inoperative or malfunctioning external body parts or internal organs, a much larger population of “healthy” people who suffer episodic or progressive cognitive impairments in daily life can benefit from noninvasive neural prostheses. For example, reduced alertness, lack of attention, or poor decision-making during monotonous, routine tasks can have catastrophic consequences. This study proposes a noninvasive mobile prosthetic platform for continuously monitoring high-temporal resolution brain dynamics without requiring application of conductive gels on the scalp. The proposed system features dry microelectromechanical system electroencephalography sensors, low-power signal acquisition, amplification and digitization, wireless telemetry, online artifact cancellation, and signal processing. Its implications for neural prostheses are examined in two sample studies: 1) cognitive-state monitoring of participants performing realistic driving tasks in the virtual-reality-based dynamic driving simulator and 2) the neural correlates of motion sickness in driving. The experimental results of these studies provide new insights into the understanding of complex brain functions of participants actively performing ordinary tasks in natural body positions and situations within real operational environments. </para>
Micropatterned supported membranes as tools for quantitative studies of the immunological synapse (2006)

In living cells, membrane receptors transduce ligand binding into signals that initiate proliferation, specialization, and secretion of signaling molecules. Spatial organization of such receptors regulates signaling in several key immune cell interactions. In the most extensively studied of these, a T cell recognizes membrane-bound antigen presented by another cell, and forms a complex junction called the "immunological synapse" (IS). The importance of spatial organization at the IS and the quantification of its effect on signaling remain controversial topics. Researchers have successfully investigated the IS using lipid bilayers supported on solid substrates as model antigen-presenting membranes. Recent technical developments have enabled micron- and nanometre-scale patterning of supported lipid bilayers (SLBs) and their application to immune cell studies with provocative results, including spatial mutation of the IS. In this tutorial review, we introduce the IS; discuss SLB techniques, including micropatterning; and discuss various methods used to perturb and quantify the IS.
Therapeutic targeting of apoptosis pathways in cancer (2008)

There is every reason to be optimistic that the wealth of knowledge about the molecular controls of apoptosis will eventually be translated into new clinical therapies for cancer. It is likely that the optimum utility of these pro-apoptotic therapies will be in combination with other treatment modalities, and careful patient selection will be necessary.
Role of synthetic extracellular matrix in development of engineered dental pulp (1998)

In cases of damaged oral tissues, traditional therapies, such as a root canal, replace the injured tissue with a synthetic material. However, while the materials currently used can offer structural replacement of the lost tissue, they are incapable of completely replacing the function of the original tissue, and often fail over time. This report describes a tissue engineering approach to dental pulp tissue replacement utilizing cultured cells seeded upon synthetic extracellular matrices. Human pulp fibroblasts were obtained and multiplied in culture. These cells were then seeded onto three different synthetic matrices: scaffolds fabricated from polyglycolic acid (PGA) fibers, a type I collagen hydrogel, and alginate in an effort to examine which matrix is most suitable for dental pulp tissue formation. In addition, methods previously developed for seeding and culturing pulp cells on PGA were optimized. Culturing cells on PGA resulted in a very high cell density tissue with significant collagen deposition. No cell proliferation was observed on alginate, and the growth of cells in collagen gels after 45 days was only moderate. These studies indicate dental pulp-like tissues can be engineered, and this may provide the first step to engineering a complete tooth.
Perinatal Autoimmunity in Offspring of Diabetic Parents: The German Multicenter BABY-DIAB Study: Detection of Humoral Immune Responses to Islet Antigens in Early Childhood (1996)

IDDM results from immune-mediated destruction of insulin-producing pancreatic beta-cells in individuals genetically susceptible for the disease. There is evidence that the 65-kDa isoform of GAD plays a critical role in the induction of autoimmune diabetes in NOD mice. In humans, it is still unclear when and to what beta-cell antigens autoreactive lymphocytes become activated during early disease. We conducted a prospective study from birth, BABY-DIAB, among children of mothers with IDDM or gestational diabetes or fathers with IDDM, and we investigated the temporal sequence of antibody responses to islet cells (ICA), insulin (IAA), GAD (GADA), and the protein tyrosine phosphatase IA-2/ICA512 (IA-2A). Of 1,019 children included at birth, we have currently followed 513 to the age of 9 months, 214 to the age of 2 years, and 37 to the age of 5 years. At birth, all antibody specificities were frequent in newborns of diabetic mothers but not fathers and are suggested to be transplacentally acquired because they are strongly correlated with antibody levels in their diabetic mothers. In early childhood, antibody levels were <99th percentile of control subjects in the majority of children. However, 37 children exhibited elevated antibody levels; these were most frequently detected at the age of 2 years. The antibody prevalence at age 2 years was 2.3% for ICA, 7% for IAA, 4.2% for GADA, and 2.8% for IA-2A (8.9% positive for at least one antibody). Children of diabetic fathers were positive for at least one antibody more frequently than were children of diabetic mothers (9 months of age: 8.5 vs. 3.6%; 2 years of age: 16.7 vs. 7.9%). There was no specific sequence in the appearance of positive autoantibodies, but 13 (35%) antibody-positive cases already had more than one ICA before the age of 2 years and 7 (19%) showed reactivity to three islet cell antigens before age 5 years. The presence of multiple antibodies confers high risk for the future development of diabetes; three of six children who exhibited positive antibody responses to all four antibodies tested and another child with two positive antibodies developed clinical diabetes at the ages of 13, 21, and 27 months and 5 years. We conclude that loss of tolerance to beta-cell autoantigens and appearance of autoimmune phenomena occur very early in life in individuals with genetic susceptibility for IDDM. Screening programs to identify candidates for disease-prevention therapies can therefore be focused on this young age-group, in whom the disease process may be less advanced and who may therefore be best suited to such therapies.