gebhart/patrepeval huggingface dataset:
A Novel ALK Secondary Mutation and EGFR Signaling Cause Resistance to ALK Kinase Inhibitors (2011)

Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI), including crizotinib, are effective treatments in preclinical models and in cancer patients with ALK-translocated cancers. However, their efficacy will ultimately be limited by the development of acquired drug resistance. Here we report two mechanisms of ALK TKI resistance identified from a crizotinib-treated non-small cell lung cancer (NSCLC) patient and in a cell line generated from the resistant tumor (DFCI076) as well as from studying a resistant version of the ALK TKI (TAE684)-sensitive H3122 cell line. The crizotinib-resistant DFCI076 cell line harbored a unique L1152R ALK secondary mutation and was also resistant to the structurally unrelated ALK TKI TAE684. Although the DFCI076 cell line was still partially dependent on ALK for survival, it also contained concurrent coactivation of epidermal growth factor receptor (EGFR) signaling. In contrast, the TAE684-resistant (TR3) H3122 cell line did not contain an ALK secondary mutation but instead harbored coactivation of EGFR signaling. Dual inhibition of both ALK and EGFR was the most effective therapeutic strategy for the DFCI076 and H3122 TR3 cell lines. We further identified a subset (3/50; 6%) of treatment naive NSCLC patients with ALK rearrangements that also had concurrent EGFR activating mutations. Our studies identify resistance mechanisms to ALK TKIs mediated by both ALK and by a bypass signaling pathway mediated by EGFR. These mechanisms can occur independently, or in the same cancer, suggesting that the combination of both ALK and EGFR inhibitors may represent an effective therapy for these subsets of NSCLC patients.
Vitrectomy in Intraocular Trauma (1972)

Fibrosis is an essential factor in the natural healing of intraocular injuries, but when it goes on to overgrowth, this originally benign process becomes destructive and gives rise to complications that may eventually result in loss of the eye. Vitrectomy is recommended for the correction of this situation in selected cases in which salvage of some vision is a possibility. The background of this paper is the 11 vitrectomies performed in 119 recently observed surgical cases of intraocular trauma. Such trauma presents a challenge which ophthalmic surgeons have not yet fully faced.
Mediators of inflammation: production and implication in inflammatory bowel disease. (1999)

Ulcerative colitis and Crohn's disease, regardless of the initiating events, share common immunologically mediated pathways of tissue injury and repair. Although their etiology remains unknown, increasing evidence suggests that activated immunological effector mechanisms within the intestinal mucosa are responsible for the pathogenesis of the diseases. Activation of immune, mesenchymal and epithelial cells; transmigration of leukocytes from the circulation to the sites of inflammation; tissue damage; and healing phase are mediated by a number of soluble mediators released by activated intestinal cells. These mediators are involved in a network of cell communication, affecting immune response, synthesis and release of enzymes, and cell proliferation. In the last decades, the identification of potential mediators in intestinal inflammation has expanded to include eicosanoids, platelet activating factor, biogenic amines, kinins, proteases, reactive oxygen species, complement components, cytokines, chemokines, nitric oxide, and neuropeptides. An increasing understanding suggests that in inflammatory bowel disease, regardless of the predisposing and trigger factors, a disruption of certain regulatory mechanisms, mediated by these soluble molecules, results in pathological immune responses to antigens and in chronic inflammation.
The Rationale for Aerosolized Antibiotics (2002)

In order for an antimicrobial agent to be effective, it must fulfill two requirements. First, the agent must reach the site of infection and remain in the vicinity for an adequate length of time. Second, it must bind to a target site and remain bound for a length of time sufficient to disrupt the life cycle of the cell. Once these requirements are met, the drug is able to exert its antimicrobial activity against the cell. In an effort to better understand and predict the killing activity of antibiotics, we have attempted to develop parameters that describe the accumulation and diffusion of drug to and from body sites (pharmacokinetics) and quantify how much of a compound is needed at the site of infection to yield the desired effect (minimum inhibitory concentration). Furthermore, integration of these parameters allows us to evaluate host, drug, and microbial factors and formulate criteria to assess and predict drug activity in patients (pharmacodynamics). Knowledge and application of pharmacodynamic principles can assist clinicians in optimizing antimicrobial therapy by allowing them to maximize the antimicrobial activity of an agent while minimizing patient exposure and thus reducing the likelihood of toxicity.
Graphene Nanoribbon Field Effect Transistor Based Ultra-Low Energy SRAM Design (2016)

Silicon-based Static Random Access Memory (SRAM) has not been keeping pace with technology trends due to the limited improvements in power, performance and density. This paper explores graphene based SRAM as a potential replacement of silicon SRAM for future digital electronics. Due to its higher current on-to-off ratio, the graphene nanoribbon field effect transistor (GNRFET) has been considered in this paper. In the nanometer regime, process variation is not only inevitable but also very pronounced. To mitigate its effects as much as possible, the Schottky-Barrier type GNRFET is considered which presents lower variation in its characteristics due to doping variation. The results show that graphene nanoribbon has a great potential in digital circuit design. The GNRFET based SRAM design presented in this paper leads to significantly lower power consumption, approximately 93% compared to 45 nm silicon technology. This upper bound can be quite achievable as the fabrication technology of graphene reaches maturity.
Synthesis of Difficult Cyclic Peptides by Inclusion of a Novel Photolabile Auxiliary in a Ring Contraction Strategy (1999)

Cyclic peptides comprise a large and important class of biologically active molecules. They are generally synthesized through amide bond-forming reactions of the C- and N- termini under high dilution conditions. Yields of such processes are highly dependent on the size of the ring being formed and on the particular amino acids of the linear precursor, giving rise to the well-known sequence-dependent effect of cyclization. To overcome this problem, we have developed a peptide cyclization strategy that proceeds through a ring closure/ring contraction process. The linear peptide Ala-Phe-Leu-Pro-Ala, which does not generate monocyclic product under conventional cyclization conditions, was used as a model to probe a range of auxiliaries. This has led to the development of a new photolabile peptide cyclization auxiliary. The 6-nitro-2-hydroxybenzyl group is readily and quantitatively introduced at the N-terminus via a reductive alkylation. Cyclization of the auxiliary-peptide initially proceeds through a cyclic nitrophenyl ester that preorganizes the peptide for lactamization. As the C- and N- termini are in close proximity, lactamization is achieved via an intramolecular O−N acyl transfer step to produce the N-substituted target cycle. The auxiliary is then removed by mild photolysis to produce the target cyclic peptide, cyclo-[Ala-Phe-Leu-Pro-Ala], in good yield. This strategy should find further useful applications in the assembly of libraries of small cyclic peptides.
CD133 positive endothelial progenitor cells contribute to the tumour vasculature in non-small cell lung cancer (2004)

A significant increase in CD133 positive cells was documented in patients with NSCLC, suggesting an involvement of endothelial progenitor cells in tumour vasculogenesis and tumour growth in these patients.
A mutational analysis of phosphatidylinositol-3-kinase activation by human colony-stimulating factor-1 receptor (1991)

Colony-stimulating factor-1 (CSF1) is a cell lineage-specific hemopoietin required for the growth, differentiation, and survival of macrophages and their precursors. The human CSF1 receptor (CSF1R) is a 150-kDa transmembrane glycoprotein whose cytoplasmic tyrosine kinase domain is split by a kinase insert (KI) region of approximately 70 amino acids. We tested the ability of CSF1R KI domain deletion mutants to stimulate phosphatidylinositol-3-kinase (PtdIns-3-kinase), an enzyme whose activity is augmented by tyrosine kinase oncogenes and receptor tyrosine kinases, and to support mitogenesis in transfected cells. Receptor immunoprecipitates from CSF1-stimulated cells contained greater than 5-fold more PtdIns-3-kinase activity compared to nonstimulated cells. High performance liquid chromatography analysis of the PtdIns-3-kinase product scraped from thin layer chromatography plates indicated that PtdIns-3-P was produced. CSF1R KI domain deletion mutants retained tyrosine kinase activity in vitro. Receptor immunoprecipitates of two partially overlapping 28 and 30 amino acid KI deletion mutants of CSF1R retained some PtdIns-3-kinase activity, in contrast to immunoprecipitates of CSF1R lacking 67 amino acids of the KI domain. Each deletion mutant stimulated CSF1-dependent DNA synthesis in transfected cells at much reduced levels compared to wild-type receptor expressing cells. These data suggest a role for the CSF1R KI domain in PtdIns-3-kinase association and for CSF1-induced thymidine incorporation into DNA.
Gold nanocages covered with thermally-responsive polymers for controlled release by high-intensity focused ultrasound (2011)

This paper describes the use of Au nanocages covered with smart, thermally-responsive polymers for controlled release with high-intensity focused ultrasound (HIFU). HIFU is a highly precise medical procedure that uses focused ultrasound to heat and destroy pathogenic tissue rapidly and locally in a non-invasive or minimally invasive manner. The released dosage could be remotely controlled by manipulating the power of HIFU and/or the duration of exposure. We demonstrated localized release within the focal volume of HIFU by using gelatin phantom samples containing dye-loaded Au nanocages. By placing chicken breast tissues on top of the phantoms, we further demonstrated the feasibility of this system for controlled release at depths up to 30 mm. Because it can penetrate more deeply into soft tissues than near-infrared light, HIFU is a potentially more effective external stimulus for rapid, on-demand drug release.
The Politics of Nature and Nurture (2002)

Scientists' explanations of group differences are based as much on their political values and unconscious needs as on objective data. It is argued that explanations of black-white differences on intelligence tests, deviant patterns of emotional and social behavior, sex differences, and attitudes toward social change and political action as primary prevention, all are influenced by underlying ideologies.
Physiological activities of 3,3',4,5'-tetrahydroxystilbene isolated from the heartwood of Cassia garrettiana CRAIB. (1984)

3, 3', 4, 5'-Tetrahydroxystilbene (1) isolated from the heartwood of Cassia garrettiana CRAIB. showed a broad spectrum of physiological activities, including antifungal, phytogrowthinhibitory and ichthyotoxic activities. Firstly. 1 showed antifungal activity ; the minimal growthinhibitory concentration (MIC) was 25 μg/ml against Penicillium citrinum and Rhizopus nigricans. Secondly, 1 showed rather strong inhibitory activity on the growth of five plant species at a concentration of 500ppm. Thirdly. 1 had ichthyotoxic activity. The median tolerance limit (TLm) at 48h was 26.5ppm in Oryzias latipes TEMMINCK et SCHLEGEL and 31.5 ppm in Carassius auratus LINNE. Studies were made on the activities of derivatives of 1, i.e., 3, 3', 4, 5'-tetrahydroxystilbenetetraacetate (2), 3, 3', 4, 5'-tetrahydroxystilbene-tetramethyl ether (3), and 3, 3', 4, 5'-tetrahydroxybibenzyl (4). The activities of these derivatives, however, were lower than those of 1, except for the phytogrowth-inhibitory and ichthyotoxic activities of 4. It is clear that for antifungal activity, both the hydroxyl groups attached to the benzene rings and the trans-olefin structure are necessary, while for the phytogrowth-inhibitory and ichthyotoxic activities, only the hydroxyl groups attached to the benzene rings are necessary.
Phase I Study of Paclitaxel (Taxol) and Pegylated Liposomal Doxorubicin (Caelyx) Administered Every 2 Weeks in Patients with Advanced Solid Tumors (2002)

The administration of Caelyx and paclitaxel every 2 weeks is a feasible regimen and is associated with acceptable toxicity.
Hoechst makes plans to integrate polyester business (1998)

RETURN TO ISSUEPREVNewsNEXTHoechst makes plans to integrate polyester businessMICHAEL MCCOYCite this: Chem. Eng. News 1998, 76, 34, 13Publication Date (Print):August 24, 1998Publication History Published online16 November 2010Published inissue 24 August 1998https://pubs.acs.org/doi/10.1021/cen-v076n034.p013https://doi.org/10.1021/cen-v076n034.p013newsACS PublicationsCopyright © 1998 AMERICAN CHEMICAL SOCIETYArticle Views3Altmetric-Citations4LEARN 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 options SUBJECTS:Organic polymers Get e-Alerts
Signaling through ERK1/2 Controls Myelin Thickness during Myelin Repair in the Adult Central Nervous System (2013)

Oligodendrocytes, the myelin-forming cells of the CNS, exquisitely tailor the thickness of individual myelin sheaths to the diameter of their target axons to maximize the speed of action potential propagation, thus ensuring proper neuronal connectivity and function. Following demyelinating injuries to the adult CNS, newly formed oligodendrocytes frequently generate new myelin sheaths. Following episodes of demyelination such as those that occur in patients with multiple sclerosis, however, the matching of myelin thickness to axon diameter fails leaving remyelinated axons with thin myelin sheaths potentially compromising function and leaving axons vulnerable to damage. How oligodendrocytes determine the appropriate thickness of myelin for an axon of defined size during repair is unknown and identifying the signals that regulate myelin thickness has obvious therapeutic implications. Here, we show that sustained activation of extracellular-regulated kinases 1 and 2 (ERK1/2) in oligodendrocyte lineage cells results in accelerated myelin repair after injury, and is sufficient for the generation of thick myelin sheaths around remyelinated axons in the adult mouse spinal cord. Our findings suggest a model where ERK1/2 MAP kinase signaling acts as a myelin thickness rheostat that instructs oligodendrocytes to generate axon-appropriate quantities of myelin.
HIV-1 core promoter lacks a simple initiator element but contains a bipartite activator at the transcription start site (1993)

The human immunodeficiency virus type 1 (HIV-1) core promoter region, extending approximately from nucleotides -40 to +80 relative to the transcription start site, contains a complex array of putative regulatory elements, including a TATA box, an initiator element, an element between the TATA box and start site, binding sites for LBP/UBP, the TAR element, and others. However, because of this elaborate architecture, the precise boundaries and functional roles for the individual regulatory elements have not been defined. To facilitate a detailed analysis of the HIV-1 core promoter, we employed in vitro transcription assays to identify the simplest control elements that activate RNA synthesis in the context of a synthetic, heterologous promoter. Because mutations at the start site previously were shown to diminish transcription, we anticipated finding an initiator as a basic regulator. However, we have demonstrated that the HIV-1 core promoter lacks an initiator that is functionally analogous to those found in the terminal transferase and adenovirus major late promoters. In its place, we identified two elements between -6 and +30, both of which appear to be necessary for significant transcriptional activation. Unlike a strong initiator, the activity of these elements was dependent on the presence of a TATA box and on their position relative to TATA. We have called the region containing these two elements the HIV-1 SSR to distinguish it from the simple transcriptional initiator elements found in other genes.
CRC handbook of chemistry and physics on DVD (2012)

Augmented by a series of practical utilities, the CRC Handbook of Chemistry and Physics on DVD, Version 2013 contains all of the information found in the 93rd print edition-in a conveniently searchable electronic format. A mainstay for scientists around the world for more than 90 years, the handbook continues to evolve with major updates, expansions, and new tables. New tables reflect the reorganization of the Analytical Chemistry section: Section 8: Analytical Chemistry * Introduction * Analytical Standardization and Calibration * Mass- and Volume-Based Concentration Units * Properties of Common Cross-Linked Silicone Stationary Phases * Detectors for Gas Chromatography * Solid-Phase Microextraction Sorbents * Eluotropic Values of Solvents on Octadecylsilane and Octylsilane * Wavelength-Wavenumber Conversion Table * Middle Range Infrared Absorption Correlation Charts * Common Spurious Infrared Absorption Bands * Properties of Important NMR Nuclei * Proton NMR Absorption of Major Chemical Families *15N NMR Chemical Shifts of Major Chemical Families * Natural Abundance of Important Isotopes * Common Mass Spectral Fragmentation Patterns of Organic Compound Families * Common Mass Spectral Fragments Lost * Major Reference Masses in the Spectrum of Heptacosafluorotributylamine (Perfluorotributylamine) * Common Spurious Signals Observed in Mass Spectrometers * Standards for Laboratory Weights * Organic Analytical Reagents for the Determination of Inorganic Cations Updated and Expanded Tables: Section 1: Basic Constants, Units, and Conversion Factors * Major update of CODATA Recommended Values of the Fundamental Physical Constants: 2010 * Update of Atomic Masses and Abundances Section 8: Analytical Chemistry * Major expansion of Abbreviations and Symbols Used in Analytical Chemistry * Major update of 13C NMR Absorptions of Major Functional Groups * Major update of Indicators for Acids and Bases * Major update of Preparation of Special Analytical Reagents Section 9: Molecular Structure and Spectroscopy * Update of Bond Dissociation Energies Section 10: Atomic, Molecular, and Optical Physics * Update of Electronic Affinities * Update of Atomic and Molecular Polarizabilities Section 14: Geophysics, Astronomy, and Acoustics * Update of Solar Irradiance at the Earth * Update of the Global Temperature Trend table to include 2011 data from NASA Section 16: Health and Safety Information * Major update of Chemical Carcinogens to include data from the 2011 National Toxicology Program report System Requirements: Computer: PC meeting the system requirements to run Microsoft(R) Windows(R) version below. Operating System: Microsoft(R) Windows(R) 7, Vista or XP. Hard disk space: 400MB for full install Adobe Acrobat Reader version 8 or later ( Acrobat Reader version 8 is available to install from the CD).
Synthesis of CMOS analog cells using AMIGO (2005)

In this paper, a simulation-based synthesis tool, AMIGO, for analog cell sizing, is presented. AMIGO is based upon genetic optimization techniques adapted to circuit sizing. A framework has been developed using the TCL/TK language that allows the designer to set the optimization problem, define complex constraint functions, watch the progress of optimization, and finally view the results. To increase design reliability, a sizing-rule pre-processor is incorporated in the tool to automatically generate topology related constraints specific to analog building blocks. Different approaches of using circuit optimizers are demonstrated through the synthesis of three different analog cells: a latched-type comparator, a folded cascode opamp and a switched-capacitor integrator. AMIGO showed to be a successful synthesis tool that can be part of a more general synthesis/migration flow.
Global cancer statistics, 2012 (2015)

Cancer constitutes an enormous burden on society in more and less economically developed countries alike. The occurrence of cancer is increasing because of the growth and aging of the population, as well as an increasing prevalence of established risk factors such as smoking, overweight, physical inactivity, and changing reproductive patterns associated with urbanization and economic development. Based on GLOBOCAN estimates, about 14.1 million new cancer cases and 8.2 million deaths occurred in 2012 worldwide. Over the years, the burden has shifted to less developed countries, which currently account for about 57% of cases and 65% of cancer deaths worldwide. Lung cancer is the leading cause of cancer death among males in both more and less developed countries, and has surpassed breast cancer as the leading cause of cancer death among females in more developed countries; breast cancer remains the leading cause of cancer death among females in less developed countries. Other leading causes of cancer death in more developed countries include colorectal cancer among males and females and prostate cancer among males. In less developed countries, liver and stomach cancer among males and cervical cancer among females are also leading causes of cancer death. Although incidence rates for all cancers combined are nearly twice as high in more developed than in less developed countries in both males and females, mortality rates are only 8% to 15% higher in more developed countries. This disparity reflects regional differences in the mix of cancers, which is affected by risk factors and detection practices, and/or the availability of treatment. Risk factors associated with the leading causes of cancer death include tobacco use (lung, colorectal, stomach, and liver cancer), overweight/obesity and physical inactivity (breast and colorectal cancer), and infection (liver, stomach, and cervical cancer). A substantial portion of cancer cases and deaths could be prevented by broadly applying effective prevention measures, such as tobacco control, vaccination, and the use of early detection tests.