gebhart/patrepeval huggingface dataset:
Novel mutant‐enriched sequencing identified high frequency of PIK3CA mutations in pharyngeal cancer (2007)

We previously reported 4 PIK3CA mutations in 38 head and neck cancer samples, 3 of which were identified in 6 pharyngeal cancer samples. To determine the mutation frequency of PIK3CA in pharyngeal cancer, we studied 24 additional cases of pharyngeal squamous cell carcinoma in this study. Using both direct genomic DNA sequencing and novel mutant-enriched sequencing methods developed specifically for the 3 hot-spot mutations (H1047R, E545K and E452K) of PIK3CA, we detected 5 mutations of PIK3CA in the 24 pharyngeal cancers (20.8%). Three of the 5 mutations had been missed by the conventional sequencing method and were subsequently detected by novel mutant-enriched sequencing methods. We showed that the mutant-enriched sequencing method for the H1047R hot-spot mutation can identify the mutation in a mixed population of mutant and wild-type DNA sequences at 1:360 ratios. These novel mutant-enriched sequencing methods allow the detection of the PIK3CA hot-spot mutations in clinical specimens which often contain limited tumor tissues (i.e., biopsy specimens). The data further support that oncogenic PIK3CA may play a critical role in pharyngeal carcinogenesis, and the mutant-enriched sequencing methods for PIK3CA are sensitive and reliable ways to detect PIK3CA mutations in clinical samples. Because PIK3CA and its pathway are potential targets for chemotherapy and radiation therapy, and frequent somatic mutation of PIK3CA has been identified in many human cancer types (e.g., breast cancer, colorectal cancer), the abilities to detect PIK3CA mutations with enhanced sensitivities have great potential impacts on target therapies for many cancer types.
Adapting Drug Approval Pathways for Bacteriophage-Based Therapeutics (2016)

The global rise of multi-drug resistant bacteria has resulted in the notion that an "antibiotic apocalypse" is fast approaching. This has led to a number of well publicized calls for global funding initiatives to develop new antibacterial agents. The long clinical history of phage therapy in Eastern Europe, combined with more recent in vitro and in vivo success, demonstrates the potential for whole phage or phage based antibacterial agents. To date, no whole phage or phage derived products are approved for human therapeutic use in the EU or USA. There are at least three reasons for this: (i) phages possess different biological, physical, and pharmacological properties compared to conventional antibiotics. Phages need to replicate in order to achieve a viable antibacterial effect, resulting in complex pharmacodynamics/pharmacokinetics. (ii) The specificity of individual phages requires multiple phages to treat single species infections, often as part of complex cocktails. (iii) The current approval process for antibacterial agents has evolved with the development of chemically based drugs at its core, and is not suitable for phages. Due to similarities with conventional antibiotics, phage derived products such as endolysins are suitable for approval under current processes as biological therapeutic proteins. These criteria render the approval of phages for clinical use theoretically possible but not economically viable. In this review, pitfalls of the current approval process will be discussed for whole phage and phage derived products, in addition to the utilization of alternative approval pathways including adaptive licensing and "Right to try" legislation.
Toward a standard benchmark for computer security research (2011)

Unlike benchmarks that focus on performance or reliability evaluations, a benchmark for computer security must necessarily include sensitive code and data. Because these artifacts could damage systems or reveal personally identifiable information about the users affected by cyber attacks, publicly disseminating such a benchmark raises several scientific, ethical and legal challenges. We propose the Worldwide Intelligence Network Environment (WINE), a security-benchmarking approach based on rigorous experimental methods. WINE includes representative field data, collected worldwide from 240,000 sensors, for new empirical studies, and it will enable the validation of research on all the phases in the lifecycle of security threats. We tackle the key challenges for security benchmarking by designing a platform for repeatable experimentation on the WINE data sets and by collecting the metadata required for understanding the results. In this paper, we review the unique characteristics of the WINE data, we discuss why rigorous benchmarking will provide fresh insights on the security arms race and we propose a research agenda for this area.
Adoptive Immunotherapy for Hematological Malignancies Using T Cells Gene-Modified to Express Tumor Antigen-Specific Receptors (2014)

Accumulating clinical evidence suggests that adoptive T-cell immunotherapy could be a promising option for control of cancer; evident examples include the graft-vs-leukemia effect mediated by donor lymphocyte infusion (DLI) and therapeutic infusion of ex vivo-expanded tumor-infiltrating lymphocytes (TIL) for melanoma. Currently, along with advances in synthetic immunology, gene-modified T cells retargeted to defined tumor antigens have been introduced as "cellular drugs". As the functional properties of the adoptive immune response mediated by T lymphocytes are decisively regulated by their T-cell receptors (TCRs), transfer of genes encoding target antigen-specific receptors should enable polyclonal T cells to be uniformly redirected toward cancer cells. Clinically, anticancer adoptive immunotherapy using genetically engineered T cells has an impressive track record. Notable examples include the dramatic benefit of chimeric antigen receptor (CAR) gene-modified T cells redirected towards CD19 in patients with B-cell malignancy, and the encouraging results obtained with TCR gene-modified T cells redirected towards NY-ESO-1, a cancer-testis antigen, in patients with advanced melanoma and synovial cell sarcoma. This article overviews the current status of this treatment option, and discusses challenging issues that still restrain the full effectiveness of this strategy, especially in the context of hematological malignancy.
Human osteoclast-like cells in primary culture (1996)

We describe a method for the isolation and culture of osteoclast-like cells from cancellous bone chips of iliac crests from patients undergoing reconstructive maxillofacial surgery. Under aseptic conditions, bone chips were cut into small pieces, incubated briefly with collagenase, and the isolated bone cells were separated from the bone chips by filtration using a nylon mesh. Bone cells were then cultured on a variety of surfaces for up to 10 days. Cell motility and fusion, together with the development of tartrate-resistant acid phosphatase activity, were seen in many cells soon after culture. The large osteoclast-like cells adhered to human cortical bone slices and produced resorption pits. These morphological and functional characteristics suggest that the cells we isolated and cultured were human osteoclasts and their precursors. Thus this method may provide a reliable means of obtaining human osteoclasts from normal tissue for short-term studies of their metabolism or from various skeletal diseases to study pathological aberrations and mechanisms.
Allopurinol in der Behandlung der Gicht und der Harnsäure-Nephrolithiasis (1967)

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study
Ionizing Radiation-Mediated Protein Kinase C Activation and Gene Expression (1991)

Ionizing radiation-induced neoplastic transformation is postulated to occur as a consequence of an initial common event followed by a rare second event. Genes encoding transcription factors are expressed immediately after x-ray exposure in the absence of de novo protein synthesis. c-jun, c-fos and Egr-1 are expressed following irradiation of human normal tissue cells and tumor cell lines. Radiation-mediated expression of these immediate early genes is attenuated by protein kinase inhibitors and abrogated when protein kinase C (PKC) is down regulated or when PKC-mediated signal transduction is deficient. PKC is the target for the tumor promoter phorbol esters. This enzyme has been implicated to play a role in neoplastic transformation and in cellular proliferation following mitogenic stimulation. PKC is also, activated rapidly following ionizing radiation exposure. Radiation-mediated PKC activation and immediate early gene induction may represent initial common events which are then followed by rare presumably mutational processes which result in neoplastic transformation. The potential importance of this finding is demonstrated by the recent report that PKC inhibitors partially suppress neoplastic transformation following x-irradiation. The production of growth factors and cytokines within irradiated tissues may also contribute to tumor promotion or progression. This discussion addresses the molecular processes that occur within a cell following x-irradiation and their potential role in neoplastic transformation.
Ethical Dimensions of Nigerian Journalists and Their Newspapers (1990)

As media in developing countries confront the problems of development, they encounter a number of ethical issues emerging from conflicts between development needs and traditional journalistic considerations. This study samples journalists on 9 Nigerian national newspapers for their perceptions of ethics applications in newspaper editorials in that country. Government appears to influence editorial ethics in ways that are not ownership sensitive and personal ethics conflict with the ethics of the media for which reporters work.
Measured CMOS Switched High-Quality Capacitors in a Reconfigurable Matching Network (2007)

Switched capacitors are here investigated for use in reconfigurable matching networks, particularly for digital video broadcasting-handheld (DVB-H) frequencies. A 0.13-μm CMOS circuit is evaluated through both simulations and measurements. Source grounded nMOS transistors are used to switch high-quality metal capacitors located above metal layer 8. The quality factor and tuning range depend on frequency, switch voltage, capacitor size, and transistor width. There is a clear tradeoff between quality factor and tuning range, and measurements show quality factors above 50, 100, and 150 at tuning ranges of 3.9, 2.4, and 1.6, respectively. A reconfigurable matching network with the switched capacitors has been realized using external inductors and the measured matching domain for the DVB-H frequency band is shown. The total loss of the network is 1.0 dB, a result of the high-quality switched capacitors.
The Antioxidant and Biological Properties of the Carotenoidsa (1998)

Much effort has been expended in evaluating the relative antioxidant potency of carotenoid pigments in both in vitro and in vivo experiments. It is quite clear that in vitro, carotenoids can inhibit the propagation of radical-initiated lipid peroxidation, and thus fulfill the definition of antioxidants. When it comes to in vivo systems, it has been much more difficult to obtain solid experimental evidence that carotenoids are acting directly as biological antioxidants. In fact, under nonphysiological circumstances, carotenoids may act as prooxidants. These results can be modified by altering the oxidant stress, the cellular or subcellular system, the type of animal, and environmental conditions, such as oxygen tension. Results of this type raise the question as to whether it is still appropriate to group the carotenoids with such antioxidant vitamins as vitamin E and vitamin C. Thus, the biological properties of the carotenoids may be much more related to the products of the interaction of carotenoids with oxidant stress, that is, such breakdown products as apocarotenoids and retinoids.
Imaging of malignant liver masses: characterization and detection. (2006)

Noninvasive characterization of focal liver lesions is largely based on their enhancement patterns on contrast-enhanced imaging. The use of microbubble contrast agents combined with specialized ultrasound (US) techniques has significantly expanded the role of US in the diagnosis of focal liver lesions based on their vascularity and specific enhancement features. With the advantage of real-time scanning, contrast-enhanced ultrasound (CEUS) can evaluate small lesions that are indeterminate on computed tomography (CT) or magnetic resonance imaging (MR), because CEUS is far less affected by timing issues. Hepatocellular carcinoma is typically characterized by increased arterial flow with frequent dysmorphic tumor vessels and decreased portal venous flow. However, negative enhancement in the portal phase is often not obvious until late (>2 minutes). On the other hand, metastasis shows prompt brief arterial hypervascularity, with either a rim or diffuse pattern and rapid washout, seen as perfusion defects during the portal venous phase. This pattern of complete rapid washout of metastases within the homogeneously enhanced background liver parenchyma can improve their detection and also improve differentiation from hepatocellular carcinoma or benign focal lesions. All malignant lesions generally show negative enhancement or washout during the extended portal venous phase, and this pattern is useful to differentiate them from benign lesions. Microbubble agents, confined to the intravascular space, may infrequently characterize malignancy by showing washout whereas CT or MR shows persistent enhancement due to interstitial distribution.
Robust Online Time Series Prediction with Recurrent Neural Networks (2016)

Time series forecasting for streaming data plays an important role in many real applications, ranging from IoT systems, cyber-networks, to industrial systems and healthcare. However the real data is often complicated with anomalies and change points, which can lead the learned models deviating from the underlying patterns of the time series, especially in the context of online learning mode. In this paper we present an adaptive gradient learning method for recurrent neural networks (RNN) to forecast streaming time series in the presence of anomalies and change points. We explore the local features of time series to automatically weight the gradients of the loss of the newly available observations with distributional properties of the data in real time. We perform extensive experimental analysis on both synthetic and real datasets to evaluate the performance of the proposed method.
Sugar sensing in higher plants. (1994)

Sugar repression of photosynthetic genes is likely a central control mechanism mediating energy homeostasis in a wide range of algae and higher plants. It overrides light activation and is coupled to developmental and environmental regulations. How sugar signals are sensed and transduced to the nucleus remains unclear. To elucidate sugar-sensing mechanisms, we monitored the effects of a variety of sugars, glucose analogs, and metabolic intermediates on photosynthetic fusion genes in a sensitive and versatile maize protoplast transient expression system. The results show that sugars that are the substrates of hexokinase (HK) cause repression at a low concentration (1 to 10 mM), indicating a low degree of specificity and the irrelevance of osmotic change. Studies with various glucose analogs suggest that glucose transport across the plasma membrane is necessary but not sufficient to trigger repression, whereas subsequent phosphorylation by HK may be required. The effectiveness of 2-deoxyglucose, a nonmetabolizable glucose analog, and the ineffectiveness of various metabolic intermediates in eliciting repression eliminate the involvement of glycolysis and other metabolic pathways. Replenishing intracellular phosphate and ATP diminished by hexoses does not overcome repression. Because mannoheptulose, a specific HK inhibitor, blocks the severe repression triggered by 2-deoxyglucose and yet the phosphorylated products per se do not act as repression signals, we propose that HK may have dual functions and may act as a key sensor and signal transmitter of sugar repression in higher plants.
Making a Robust Interfacial Scaffold: Bijel Rheology and its Link to Processability (2012)

Abstract Confocal microscopy and rheology studies of two bijel systems are presented to elucidate relationships between the physicochemical properties of bijels and their ability to be utilized as soft matter templates for materials synthesis. For the first time, the origins of viscoelasticity in these systems are investigated using conventional rheometry and a direct correspondence between the elastic storage modulus, particle loading, and the departure from criticality is observed. Further, the rheological transitions that accompany fluid re‐mixing in bijels are characterized, providing key insights into the synergistic role of interfacial tension and interparticle interactions in mediating their mechanical robustness. Bijels that are predominantly stabilized by interfacial tension are also highly sensitive to gradients in chemical composition and more easily prone to mechanical failure during processing. Despite this increased sensitivity, a modified strategy for processing these more delicate systems is developed and its efficacy is demonstrated by synthesizing a bicontinuous macroporous hydrogel scaffold.
Preclinical Development of a Vaccine ‘Against Smoking’ (2002)

These data provide credible evidence that a vaccine can break the vicious circle between smoking and instant gratification by intercepting the nicotine molecule. Astonishingly, there is no sign of exhaustion of specific antibodies even under extreme conditions, which makes it highly unlikely that a smoker can overcome the protective effect of the vaccine by smoking more. Finally, the high titers of specific antibodies after 1 year let us hope that booster vaccinations are probably only necessary in intervals of years.
The Key Step in Chlorophyll Breakdown in Higher Plants (1998)

Chlorophyll breakdown in green plants is a long-standing biological enigma. Recent work has shown that pheophorbide a (Pheide a) derived from chlorophyll (Chl) is converted oxygenolytically into a primary fluorescent catabolite (pFCC-1) via a red Chl catabolite (RCC) intermediate. RCC, the product of the ring cleavage reaction catalyzed by Pheide a oxygenase, which is suggested to be the key enzyme in Chl breakdown in green plants, is converted into pFCC-1 by a reductase. In the present study, an in vitro assay comprising 18O2 Pheide a oxygenase and RCC reductase yielded labeled pFCC-1. Fast atom bombardment-mass spectrometric analysis of the purified pFCC-1 product revealed that only one of the two oxygen atoms newly introduced into Pheide a in the course of the cleavage reaction is derived from molecular oxygen. Analysis of the fragment ions located the oxygen atom derived from molecular oxygen on the formyl group of pyrrole B. This finding demonstrates that the cleavage of Pheide a in vascular plants is catalyzed by a monooxygenase. Chlorophyll breakdown is therefore indicated to be mechanistically related in higher plants and in the green alga Chlorella protothecoides.
Charge Recombination in Dye-Sensitized Nanocrystalline TiO2Solar Cells (1997)

Charge recombination between dye-sensitized nanocrystalline TiO2 electrodes and the I3-/I- couple in nonaqueous solution is described. The sensitizer was [RuL2(NCS)2] (L = 2,2‘-bipyridyl-4,4‘-dicarboxylic acid). An apparent inequality between the dark current and the recombination current is ascribed to a voltage shift caused by a potential drop at the SnO2/TiO2 interface, ohmic losses in the SnO2 and TiO2, and an overpotential for the redox reaction at the Pt counter electrode. Treating the dye-coated TiO2 electrodes with pyridine derivatives (4-tert-butylpyridine, 2-vinylpyridine, or poly(2-vinylpyridine)) improves significantly both the open-circuit photovoltage Voc (from 0.57 to 0.73 V) and the cell conversion efficiency (from 5.8 to 7.5%) at a radiant power of 100 mW/cm2 (AM 1.5) with respect to the untreated electrode. An analytical expression relating Voc to the interfacial recombination kinetics is derived, and its limitations are discussed. Analysis of Voc vs radiant power data with this expression indicates that the pyridine compounds may lower the back-electron-transfer rate constant by 1−2 orders of magnitude. The pyridines are found to have no significant effect on the recombination mechanism and kinetics of electron injection from excited dye molecules to TiO2. Studies of the dye-covered electrodes show that the rate of recombination is second order in I3- concentration, which is attributed to the dismutation reaction 2I2- → I3- + I- with I2 as the electron acceptor in the back-reaction. Mass-transport theory is applied to understand the dependence of the short-circuit photocurrent on the radiant power at low I3- concentration and to calculate the diffusion coefficient of I3- ions (7.6 × 10-6 cm2/s) in the porous TiO2 structure. The dependence of other cell parameters on the I3- concentration is also investigated.
A Non-surfactant Templating Route to Mesoporous Silica Materials (1998)

The templated synthesis of mesoporous materials using surfactant templates has been known since 1992. The discovery reported here, that non-surfactant organic molecules, e.g., optically active organic compounds such as D-glucose, also act as templates for the formation of mesoporous silica materials with large surface areas and pore volumes and narrow pore size distribution, opens new opportunities for the preparation of mesostructural materials because of the vast diversity of organic compounds that may function as templates.
Pathways for carboxylic acid decomposition on titania (1988)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPathways for carboxylic acid decomposition on titaniaK. S. Kim and M. A. BarteauCite this: Langmuir 1988, 4, 4, 945–953Publication Date (Print):July 1, 1988Publication History Published online1 May 2002Published inissue 1 July 1988https://pubs.acs.org/doi/10.1021/la00082a028https://doi.org/10.1021/la00082a028research-articleACS PublicationsRequest reuse permissionsArticle Views809Altmetric-Citations91LEARN 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