gebhart/patrepeval huggingface dataset:
Tumor Accumulation of NIR Fluorescent PEG–PLA Nanoparticles: Impact of Particle Size and Human Xenograft Tumor Model (2011)

Cancer therapies are often terminated due to serious side effects of the drugs. The cause is the nonspecific distribution of chemotherapeutic agents to both cancerous and normal cells. Therefore, drug carriers which deliver their toxic cargo specific to cancer cells are needed. Size is one key parameter for the nanoparticle accumulation in tumor tissues. In the present study the influence of the size of biodegradable nanoparticles was investigated in detail, combining in vivo and ex vivo analysis with comprehensive particle size characterizations. Polyethylene glycol-polyesters poly(lactide) block polymers were synthesized and used for the production of three defined, stable, and nontoxic near-infrared (NIR) dye-loaded nanoparticle batches. Size analysis based on asymmetrical field flow field fractionation coupled with multiangle laser light scattering and photon correlation spectroscopy (PCS) revealed narrow size distribution and permitted accurate size evaluations. Furthermore, this study demonstrates the constraints of particle size data only obtained by PCS. By the multispectral analysis of the Maestro in vivo imaging system the in vivo fate of the nanoparticles next to their accumulation in special red fluorescent DsRed2 expressing HT29 xenografts could be followed. This simultaneous imaging in addition to confocal microscopy studies revealed information about the accumulation characteristics of nanoparticles inside the tumor tissues. This knowledge was further combined with extended size-dependent fluorescence imaging studies at two different xenograft tumor types, the HT29 (colorectal carcinoma) and the A2780 (ovarian carcinoma) cell lines. The combination of two different size measurement methods allowed the characterization of the dependence of nanoparticle accumulation in the tumor on even rather small differences in the nanoparticle size. While two nanoparticle batches (111 and 141 nm in diameter) accumulated efficiently in the human xenograft tumor tissue, the slightly bigger nanoparticles (diameter 166 nm) were rapidly eliminated by the liver.
Treatment of rheumatoid arthritis with an anti‐CD4 monoclonal antibody (1991)

The effect of treatment with a monoclonal antibody against the CD4 antigen present on T helper cells was studied in 10 patients with severe intractable rheumatoid arthritis. In an open trial, monoclonal antibody 16H5 was infused at a dosage of 0.3 mg/kg of body weight on 7 consecutive days. Studies of the kinetics demonstrated a drastic depletion of CD4+ cells, to as low as 25 cells/microliters, 1 hour after the first infusion. The subsequent recovery of the CD4+ cell numbers 24 hours after infusion did not reach initial levels, and after the full 7-day treatment cycle there was a significant reduction of the number of CD4+ cells (mean +/- SD 51 +/- 28%; P less than 0.02). There was a reduced or even inverse CD4:CD8 ratio, which generally persisted 3-4 weeks. Lymphocyte transformation assays demonstrated significantly reduced reactivity in 5 of the 9 patients who completed the 7-day course, whereas 4 individuals exhibited an unexpected elevation in the T cell response to mitogens and common antigens. Parallel laboratory studies showed a significant decrease in the erythrocyte sedimentation rate (P less than 0.05), rheumatoid factor titer (P less than 0.04), and total immunoglobulin values (P less than 0.01), as well as a reduction in C-reactive protein levels, in 7 of the 9 patients. Clinically, there was a significant reduction in the Ritchie articular index (P less than 0.05) and in the number of swollen joints (P less than 0.04). Adverse effects were urticaria in 2 patients, which led to withdrawal of therapy in 1 of them, and chills with fever, suggestive of a lymphokine release syndrome, in another 2 patients. Only low levels of human anti-mouse immunoglobulin antibodies developed (not exceeding 1.7 mg/liter). It was therefore possible to repeat the treatment cycle, achieving still better efficacy, in 4 of the patients (reductions in the Ritchie index and the number of swollen joints P less than 0.02). Our findings indicate that treatment with monoclonal antibodies against the CD4 antigen leads to immunomodulation which results in clinical benefits, at least during initial observation periods (up to 6 months postinfusion). However, it remains to be determined whether long-term remission can be induced with this therapeutic approach. The use of immunosuppressive therapies or repeated antibody treatments will have to be considered.
Epileptic seizure prediction and control (2003)

Epileptic seizures are manifestations of epilepsy, a serious brain dynamical disorder second only to strokes. Of the world's approximately 50 million people with epilepsy, fully 1/3 have seizures that are not controlled by anti-convulsant medication. The field of seizure prediction, in which engineering technologies are used to decode brain signals and search for precursors of impending epileptic seizures, holds great promise to elucidate the dynamical mechanisms underlying the disorder, as well as to enable implantable devices to intervene in time to treat epilepsy. There is currently an explosion of interest in this field in academic centers and medical industry with clinical trials underway to test potential prediction and intervention methodology and devices for Food and Drug Administration (FDA) approval. This invited paper presents an overview of the application of signal processing methodologies based upon the theory of nonlinear dynamics to the problem of seizure prediction. Broader application of these developments to a variety of systems requiring monitoring, forecasting and control is a natural outgrowth of this field.
Computer translation of IUPAC systematic organic chemical nomenclature. 1. Introduction and background to a grammar-based approach (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTComputer translation of IUPAC systematic organic chemical nomenclature. 1. Introduction and background to a grammar-based approachD. I. Cooke-Fox, G. H. Kirby, and J. D. RaynerCite this: J. Chem. Inf. Comput. Sci. 1989, 29, 2, 101–105Publication Date (Print):May 1, 1989Publication History Published online1 May 2002Published inissue 1 May 1989https://pubs.acs.org/doi/10.1021/ci00062a009https://doi.org/10.1021/ci00062a009research-articleACS PublicationsRequest reuse permissionsArticle Views208Altmetric-Citations26LEARN 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 Get e-Alerts
Dose-intensification of MVAC with recombinant granulocyte colony-stimulating factor as initial therapy in advanced urothelial cancer. (1993)

These findings demonstrate the feasibility and limitations of dose intensification of M-VAC with rhG-CSF. While the overall impact of the increased drug administration can only be assessed in randomized comparisons, the results of the present trial suggest that escalations of the components of the four-drug regimen are unlikely to improve significantly the outcome for patients with advanced urothelial tract tumors.
Passive matrix addressing of electrophoretic image display (2002)

This paper presents a novel technique for passive matrix addressing of electrophoretic displays.The addressing scheme is successfully applied in a working demonstrator with 5x7 pixels.To our knowledge, this is the first time a working electrophoretic display with passive matrix addressing is presented.
Design, synthesis, and structure&ndash;activity relationships of 2-benzylidene-1-indanone derivatives as anti-inflammatory agents for treatment of acute lung injury (2018)

The simple synthetic preparation and biological properties of these derivatives make these 2-benzylidene-indanone scaffolds promising new entities for the development of anti-inflammatory therapeutics for the treatment of acute lung injury.
Nonlinear Blending: A Useful General Concept for the Assessment of Combination Drug Synergy (2007)

Human diseases may involve cellular signaling networks that contain redundant pathways, so that blocking a single pathway in the system cannot achieve the desired effect. As such, the use of drugs in combination are particularly effective interventions in networked systems. However, common synergy measures are often inadequate to quantify the effect of two different drugs in complex cellular systems. This article proposes a general approach to quantifying the synergy of two drugs in combination. This approach is called strong nonlinear blending. Drugs with different relative potencies, different effect maxima, or situations of potentiation or coalism pose no problem for strong nonlinear blending as a way to assess the increased response benefit to be gained by combining two drugs. This is important as testing drug combinations in complex biological systems are likely to produce a wide variety of possible response surfaces. It is also shown that for monotone increasing (or decreasing) dose response surfaces that strong nonlinear blending is equivalent to improved potency along a ray of constant dose ratio. This is important because fixed dose ratios form the basis for many preclinical and clinical combination drug experiments. Two examples are given involving HIV and cancer chemotherapy combination drug experiments.
Introduction to beetle luciferases and their applications (1989)

All beetle luciferases have evolved from a common ancestor: they all use ATP, O2, and a common luciferin as substrates. The most studied of these luciferases is that derived from the firefly Photinus pyralis, a beetle in the superfamily of Cantharoidea. The sensitivity with which the activity of this enzyme can be assayed has made it useful in the measurement of minute concentrations of ATP. With the cloning of the cDNA coding this luciferase, it has also found wide application in molecular biology as a reporter gene. We have recently cloned other cDNAs that code for luciferases from the bioluminescent click beetle, Pyrophorus plagiophthalamus, in the superfamily Elateroidea. These newly acquired luciferases are of at least four different types, distinguishable by their ability to emit different colours of bioluminescence ranging from green to orange. Unique properties of these luciferases, especially their emission of multiple colours, may make them additionally useful in applications.
3-D reconstruction of coronary arterial tree to optimize angiographic visualization (2000)

Due to vessel overlap and foreshortening, multiple projections are necessary to adequately evaluate the coronary tree with arteriography. Catheter-based interventions can only be optimally performed when these visualization problems are successfully solved. The traditional method provides multiple selected views in which overlap and foreshortening are subjectively minimized based on two dimensional (2-D) projections. A pair of images acquired from routine angiographic study at arbitrary orientation using a single-plane imaging system were chosen for three-dimensional (3-D) reconstruction. After the arterial segment of interest (e.g., a single coronary stenosis or bifurcation lesion) was selected, a set of gantry angulations minimizing segment foreshortening was calculated. Multiple computer-generated projection images with minimized segment foreshortening were then used to choose views with minimal overlapped vessels relative to the segment of interest. The optimized views could then be utilized to guide subsequent angiographic acquisition and interpretation. Over 800 cases of coronary arterial trees have been reconstructed, in which more than 40 cases were performed in room during cardiac catheterization. The accuracy of 3-D length measurement was confirmed to be within an average root-mean-square (rms) 3.5% error using eight different pairs of angiograms of an intracoronary guidewire of 105-mm length with eight radiopaque markers of 15-mm interdistance. The accuracy of similarity between the additional computer-generated projections versus the actual acquired views was demonstrated with the average rms errors of 3.09 mm and 3.13 mm in 20 LCA and 20 RCA cases, respectively. The projections of the reconstructed patient-specific 3-D coronary tree model can be utilized for planning optimal clinical views: minimal overlap and foreshortening. The assessment of lesion length and diameter narrowing can be optimized in both interventional cases and studies of disease progression and regression.
Microchip Device for Cell Lysis, Multiplex PCR Amplification, and Electrophoretic Sizing (1998)

The steps of cell lysis, multiplex PCR amplification, and electrophoretic analysis are executed sequentially on a monolithic microchip device. The entire microchip is thermally cycled to lyse cells and to amplify DNA, and the products are then analyzed using a sieving medium for size separation and an intercalating dye for fluorescence detection. Using a standard PCR protocol, a 500-base pair (bp) region of bacteriophage lambda DNA and 154-, 264-, 346-, 410-, and 550-bp regions of E. coli genomic and plasmid DNAs are amplified. The electrophoretic analysis of the products is executed in <3 min following amplification using hydroxyethyl cellulose or poly(dimethylacrylamide) sieving gels. Product sizing is demonstrated by proportioning the amplified product with a DNA sizing ladder.
Chain End Effects and Dewetting in Thin Polymer Films (1996)

The dewetting of thin films of end-functionalized polymers, ω- and α,ω-barium sulfonato polystyrenes, on a silicon substrate has been investigated as a function of initial film thickness, molecular weight, and functionality of the chains. The lower molecular weight monofunctional chains are found to dewet the substrate analogously to normal polystyrene but display an anomalous flow behavior at the surface. Moreover, after dewetting, the entire silicon surface still remains covered by a monolayer of monofunctional chains. The monolayer consists of a polymer brush of densely packed tethered chains, adsorbed via their ionic end groups. The dense packing and special conformations of the chains in the brush prevent interpenetration with other polymer chains, and the unadsorbed macromolecules dewet the brush. When the molecular weight of the monofunctional chains is increased, entanglements between the adsorbed polymer brush and the unadsorbed chains can occur and the dewetting process is retarded. Thin films of the difunctional chains do not dewet regardless of the molecular weight of the chains. The difference between mono- and difunctional materials is attributed to ionic aggregation, which is responsible for thermoreversible cross-linking and stabilization of thicker films by interaction of aggregates with dangling ends. It is suggested to use high molecular weight end-functionalized chains as polymeric additives to retard thin polymer film dewetting.
GeneticFPGA: evolving stable circuits on mainstream FPGA devices (2003)

GeneticFPGA is a Java-based tool for evolving digital circuits on Xilinx XC4000EX/sup TM/ and XC4000XL/sup TM/ devices. Unlike other FPGA architectures popular with evolutionary hardware researchers, the XC4000 series architectures cannot accept arbitrary configuration data. Only a small subset of configuration bit patterns will produce operational circuits; other configuration bit patterns produce circuits which are unreliable and may even permanently damage the FPGA device. GeneticFPGA uses novel software techniques to produce legal circuit configurations for these devices, permitting experimentation with evolvable hardware on the larger, faster more mainstream devices. In addition, these techniques have led to methods for evolving circuits which are neither temperature, voltage, nor silicon dependent. An 8-bit counter and several digital frequency dividers have been successfully evolved using this approach. GeneticFPGA uses Xilinx's JBits/sup TM/ interface to control the generation of bitstream configuration data and the XHWIF portable hardware interface to communicate with a variety of commercially available FPGA-based hardware. GeneticFPGA, JBits, and XHWIF are currently being ported to the Xilinx Virtex/sup TM/ family of devices, which will provide greatly increased reconfiguration speed and circuit density.
Transgenic mice which overproduce Th2 cytokines develop spontaneous atopic dermatitis and asthma (2004)

We have investigated the role of Th2 cytokines in the development of atopic diseases using transgenic mice carrying large genomic segments containing IL4, IL13 and IL5 genes and overexpressing these Th2 cytokines. In vitro stimulated, but not unstimulated, Th2 cells from the transgenic mice expressed high levels of IL4, IL13 and IL5 compared to those from non-transgenic mice. The transgenic mice developed spontaneous atopic dermatitis and airway inflammation against environmental allergens. The affected regions for atopic dermatitis covered the entire body including skin in the face, ear, eye-lid, neck, hind region and tail. Histological features showed thickened epidermis and dermis and infiltration of large numbers of inflammatory cells in the affected regions. The transgenic mice also showed airway inflammation characteristic of asthma, including infiltration of inflammatory cells and hypertrophy of airway epithelial cells. These mice also expressed high level of serum IgE, which is a hallmark of atopic diseases. In summary, this study provides additional evidence that Th2 cytokines play key roles in atopic diseases.
Identification of the Calcium Binding Site and a Novel Ytterbium Site in Blood Coagulation Factor XIII by X-ray Crystallography (1999)

The presence or absence of calcium determines the activation, activity, oligomerization, and stability of blood coagulation factor XIII. To explore these observed effects, we have determined the x-ray crystal structure of recombinant factor XIII A2 in the presence of calcium, strontium, and ytterbium. The main calcium binding site within each monomer involves the main chain oxygen atom of Ala-457, and also the side chains from residues Asn-436, Asp-438, Glu-485, and Glu-490. Calcium and strontium bind in the same location, while ytterbium binds several angstroms removed. A novel ytterbium binding site is also found at the dimer two-fold axis, near residues Asp-270 and Glu-272, and this site may be related to the reported inhibition by lanthanide metals (Achyuthan, K. E., Mary, A., and Greenberg, C. S. (1989) Biochem. J. 257, 331-338). The overall structure of ion-bound factor XIII is very similar to the previously determined crystal structures of factor XIII zymogen, likely due to the constraints of this monoclinic crystal form. We have merged the three independent sets of water molecules in the structures to determine which water molecules are conserved and possibly structurally significant.
MicroRNA expression detected by oligonucleotide microarrays: System establishment and expression profiling in human tissues (2004)

MicroRNAs (MIRs) are a novel group of conserved short approximately 22 nucleotide-long RNAs with important roles in regulating gene expression. We have established a MIR-specific oligonucleotide microarray system that enables efficient analysis of the expression of the human MIRs identified so far. We show that the 60-mer oligonucleotide probes on the microarrays hybridize with labeled cRNA of MIRs, but not with their precursor hairpin RNAs, derived from amplified, size-fractionated, total RNA of human origin. Signal intensity is related to the location of the MIR sequences within the 60-mer probes, with location at the 5' region giving the highest signals, and at the 3' end, giving the lowest signals. Accordingly, 60-mer probes harboring one MIR copy at the 5' end gave signals of similar intensity to probes containing two or three MIR copies. Mismatch analysis shows that mutations within the MIR sequence significantly reduce or eliminate the signal, suggesting that the observed signals faithfully reflect the abundance of matching MIRs in the labeled cRNA. Expression profiling of 150 MIRs in five human tissues and in HeLa cells revealed a good overall concordance with previously published results, but also with some differences. We present novel data on MIR expression in thymus, testes, and placenta, and have identified MIRs highly enriched in these tissues. Taken together, these results highlight the increased sensitivity of the DNA microarray over other methods for the detection and study of MIRs, and the immense potential in applying such microarrays for the study of MIRs in health and disease.
How I treat symptomatic splenomegaly in patients with myelofibrosis (2009)

Managing patients with myelofibrosis (MF), either those with primary MF or those whose MF has evolved from antecedent polycythemia vera or essential thrombocythemia, presents many challenges to the hematologist. MF patients have a range of debilitating disease manifestations (eg, massive splenomegaly, cytopenias, constitutional symptoms, and transformation to a treatment-refractory blast phase). Cure is potentially achievable through allogeneic stem cell transplantation; however, this therapy is either inappropriate or not feasible for the majority of patients. Therefore, remaining therapies are palliative but can be of significant value to some MF patients. In particular, management of symptomatic splenomegaly remains one of the most perplexing aspects of MF clinical care. Using medications is the simplest approach for reducing splenomegaly, yet achieving symptomatic response without undue myelosuppression is challenging. Splenectomy or radiotherapy offers benefit, but careful patient selection and close monitoring are required because both have the potential for dangerous adverse effects. Experimental medical therapies, such as JAK2 inhibitors, show promise and may soon play an important role in the management of symptomatic splenomegaly in MF patients. Future care of MF patients, including splenomegaly management, will continue to require the hematologist to select therapeutic options carefully in the context of realistic, achievable goals.
A reference bacterial genome dataset generated on the MinION™ portable single-molecule nanopore sequencer (2014)

Base-called sequence data are provided to demonstrate the nature of data produced by the MinION™ platform and to encourage the development of customised methods for alignment, consensus and variant calling, de novo assembly and scaffolding. FAST5 files containing event data within the HDF5 container format are provided to assist with the development of improved base-calling methods.
New Insights to Vascular Smooth Muscle Cell and Pericyte Differentiation of Mouse Embryonic Stem Cells In Vitro (2006)

We conclude that OP9 stroma cells induce pericyte differentiation of cocultured mouse ES cells. The induction of pericyte marker genes is temporally separated from the induction of SMC genes and does not require platelet-derived growth factor B or TGFbeta1 signaling.