gebhart/patrepeval huggingface dataset:
Protein Formulation and Delivery (2007)

Overview of Protein Formulation and Delivery. Proetin Delivery (General Aspects). Compare and Contrast Small Molecule and Large Molecule Formulation and Delivery. Chemical and Physical Considerations in Protein and Peptide Stability. Analytical Methods and Stability Testing of Biopharmaceuticals. The Importance of a Thorough Preformulation Study. Solution Formulation of Proteins/Peptides. Special Considerations in High Concentration Protein Formulations or Formulation for Implantable Devices. Freeze-Drying Concepts: The Basics. Rational Choice of Excipients for Use in Lyophilized Formulations. Formulation of Proteins for Pulmonary Delivery. Formulation of Proteins for Incorporation into Drug Delivery Systems. Needle Free Delivery Approaches. Single Crystal Formulation Approaches (Altus Approach). High Throughput Screening-Transform Approach. Oral Delivery-Oral Heparin. Formulation of Proteins for Delivery into Liposome Formulations. Expiration Dating and Specification Setting for Biologics
Electron-Beam Surface-Patterned Poly(ethylene glycol) Microhydrogels (2003)

This paper describes research addressing the question of whether microscopic hydrogels can be created from poly(ethylene glycol) [PEG 6800] and poly(ethylene oxide) [PEO 200K] using spatially resolved radiation from a scanning electron microscope with an approach similar to that used in the electron-beam patterning of polymeric photoresists. We demonstrate that, indeed, PEG hydrogels with micrometer and submicrometer feature sizes can be created by this approach, and we call these microhydrogels. Using solvent-free PEG 6800 and PEO 200K films ∼50−100-nm thick, we have identified sets of irradiation conditions where sufficient cross-linking occurs so that the exposed patterned polymer remains while the unexposed polymer dissolves during a post-irradiation solvent rinse. Arbitrary spatial patterns can be made. We have generated patterned dots with diameters below 200 nm. Using atomic force microscopy, in air and water, to study ∼5 × 5 μm PEG and PEO pads on silicon, we show that the patterned features generated by electron-beam cross-linking swell when exposed to water. The extent of swelling depends on the incident electron dose. Maximum swelling ratios of 14−16 have been observed. The swelling ratio decreases with increasing dose toward a limit of unity at the highest doses studied. Because of the significance of PEG in biomaterials applications, we examined the adsorption of fibronectin fragments onto the PEG microhydrogels using immunofluoresence optical microscopy. Undetectable Fn levels are observed on microhydrogels subjected to the lowest radiative exposure conditions where maximum swelling occurs. Fn adsorption increases with increasing dose and reaches a maximum at the highest doses where swelling ratios of unity are observed. This approach opens a new means for arbitrarily patterning the spatial distribution of proteins on surfaces and may be useful for controlling surface bioactivity.
Protective Immune Response to Foot-and-Mouth Disease Virus with VP1 Expressed in Transgenic Plants (1998)

It has been reported recently that genes encoding antigens of bacterial and viral pathogens can be expressed in plants in a form in which they retain native immunogenic properties. The structural protein VP1 of foot-and-mouth disease virus (FMDV), which has frequently been shown to contain critical epitopes, has been expressed in different vectors and shown to induce virus-neutralizing antibodies and protection in experimental and natural hosts. Here we report the production of transformed plants (Arabidopsis thaliana) expressing VP1. Mice immunized with leaf plant extracts elicited specific antibody responses to synthetic peptides representing amino acid residues 135 to 160 of VP1, to VP1 itself, and to intact FMDV particles. Additionally, all of the immunized mice were protected against challenge with virulent FMDV. To our knowledge, this is the first study showing protection against a viral disease by immunization with an antigen expressed in a transgenic plant.
Towards a Metric Suite for Early Software Reliability Assessment (2003)

We are developing a suite of metrics for early assessment of software reliability and to provide feedback to the developer on the quality of their testing effort. The suite consists of easy-to-measure information collected from the source code and test programs. We are studying correlation between these metrics and the reliability of the developed software. The results of an initial case study demonstrate the feasibility of the approach. Metrics will be added to or deleted from the suite based on further validation work.
Phage display of peptide / major histocompatibility class I complexes (2001)

Major histocompatibility complex class I (MHC-I) molecules sample peptides from the intracellular environment and present them to cytotoxic T cells (CTL). To establish a selection system, and, thereby, enable a library approach to identify the specificities involved (that of the MHC-I for peptides and subsequently that ot the T cell receptor for peptide-MHC-I complex), we have fused a single chain peptide-MHC-I complex to the phage minor coat protein, gpIII, and displayed it on filamentous phage. Expression of peptide-MHC-I complexes was shown with relevant conformation-specific monoclonal antibodies and, more importantly, with a unique "T cell receptor-like" (i. e. peptide-specific, MHC-I-restricted) antibody. Thus, properly assembled and folded peptide-MHC-I complexes can be displayed on filamentous phage. Despite the successful display, interaction with T cells could not be demonstrated.
Adrenocorticotropin. 47. Synthesis and biological activity of adrenocorticotropic peptides modified at the tryptophan position (1975)

&lt;p&gt;Friday 26 June 2015, 6.30pm&lt;/p&gt;\n&lt;p&gt;An evening with Bruce Hainley and Wayne Koestenbaum at Tate Modern beginning with a screening of Rosa von Praunheim’s award-winning documentary, &lt;em&gt;Tally Brown&lt;/em&gt;, New York (1979), to be followed by a rousing conversation on demi-mondes, queer vocality and stardom.&lt;/p&gt;\n
Transcriptional Inhibitors Identified in a 160,000-Compound Small-Molecule DUX4 Viability Screen (2016)

Facioscapulohumeral muscular dystrophy is a genetically dominant, currently untreatable muscular dystrophy. It is caused by mutations that enable expression of the normally silent DUX4 gene, which encodes a pathogenic transcription factor. A screen based on Tet-on DUX4-induced mouse myoblast death previously uncovered compounds from a 44,000-compound library that protect against DUX4 toxicity. Many of those compounds acted downstream of DUX4 in an oxidative stress pathway. Here, we extend this screen to an additional 160,000 compounds and, using greater stringency, identify a new set of DUX4-protective compounds. From 640 hits, we performed secondary screens, repurchased 46 of the most desirable, confirmed activity, and tested each for activity against other cell death-inducing insults. The majority of these compounds also protected against oxidative stress. Of the 100 repurchased compounds identified through both screens, only SHC40, 75, and 98 inhibited DUX4 target genes, but they also inhibited dox-mediated DUX4 expression. Using a target gene readout on the 640-compound hit set, we discovered three overlooked compounds, SHC351, 540, and 572, that inhibit DUX4 target gene upregulation without nonspecific effects on the Tet-on system. These novel inhibitors of DUX4 transcriptional activity may thus act on pathways or cofactors needed by DUX4 for transcriptional activation in these cells.
Competition between intercellular adhesion molecule‐1 and a small‐molecule antagonist for a common binding site on the αl subunit of lymphocyte function‐associated antigen‐1 (2005)

The lymphocyte function-associated antigen-1 (LFA-1) binding of a unique class of small-molecule antagonists as represented by compound 3 was analyzed in comparison to that of soluble intercellular adhesion molecule-1 (sICAM-1) and A-286982, which respectively define direct and allosteric competitive binding sites within LFA-1's inserted (I) domain. All three molecules antagonized LFA-1 binding to ICAM-1-Immunoglobulin G fusion (ICAM-1-Ig) in a competition ELISA, but only compound 3 and sICAM-1 inhibited the binding of a fluorescein-labeled analog of compound 3 to LFA-1. Compound 3 and sICAM-1 displayed classical direct competitive binding behavior with ICAM-1. Their antagonism of LFA-1 was surmountable by both ICAM-1-Ig and a fluorescein-labeled compound 3 analog. The competition of both sICAM-1 and compound 3 with ICAM-1-Ig for LFA-1 resulted in equivalent and linear Schild plots with slopes of 1.24 and 1.26, respectively. Cross-linking studies with a photoactivated analog of compound 3 localized the high-affinity small-molecule binding site to the N-terminal 507 amino acid segment of the alpha chain of LFA-1, a region that includes the I domain. In addition, cells transfected with a variant of LFA-1 lacking this I domain showed no significant binding of a fluorescein-labeled analog of compound 3 or ICAM-1-Ig. These results demonstrate that compound 3 inhibits the LFA-1/ICAM-1 binding interaction in a directly competitive manner by binding to a high-affinity site on LFA-1. This binding site overlaps with the ICAM-1 binding site on the alpha subunit of LFA-1, which has previously been localized to the I domain.
Methodology for Discovery of Alzheimer's Disease Blood-Based Biomarkers (2009)

Alzheimer's disease (AD) is a degenerative brain disorder. The disease also affects peripheral tissue such as peripheral blood mononuclear cells (PBMCs). Delineating biochemical alterations in AD blood constituents may possibly allow the identification of accessible footprints that reflect degenerative processes within the central nervous system. Here, we describe an integrated methodology for the generation of a blood-based molecular bio-repository, including the collection of clinical and demographic data for downstream stringent sample selection and stratification for the study of molecular signatures in AD. We report the simultaneous extraction of high quality and yield of DNA, RNA, and protein from PBMCs of individuals with sporadic AD, mild cognitive impairment, and normal elderly controls. We describe experimental designs and present examples for the discovery of underlying etiopathogenetic networks in sporadic AD. We suggest that PBMC-associated biomarkers may provide insights into the pathogenesis of AD and be used to monitor disease diagnosis and progression.
Four-dimensional organization of protein kinase signaling cascades: the roles of diffusion, endocytosis and molecular motors (2003)

Extracellular signals received by membrane receptors are processed, encoded and transferred to the nucleus via phosphorylation and spatial relocation of protein members of multiple component pathways, such as mitogen activated protein kinase (MAPK) cascades. The receptor-induced membrane recruitment of the cytoplasmic protein SOS results in the activation of the Ras/MAPK cascade. It has been suggested that the membrane recruitment of signaling proteins causes an increase in the diffusion-limited rates. We have recently shown that this increase is too small to be responsible for enhanced signal transduction. Instead we demonstrate that the function of membrane localization is to increase the number (or average lifetime) of complexes between signaling partners. A hallmark of signaling pathways is the spatial separation of activation and deactivation mechanisms; e.g. a protein can be phosphorylated at the cell surface by a membrane-bound kinase and dephosphorylated in the cytosol by a cytosolic phosphatase. Given the measured values of protein diffusion coefficients and of phosphatase and kinase activities, the spatial separation is shown to result in precipitous phospho-protein gradients. When information transfer is hampered by slow protein diffusion and rapid dephosphorylation, phospho-protein trafficking within endocytic vesicles may be an efficient way to deliver messages to physiologically relevant locations. The proposed mechanism explains recent observations that various inhibitors of endocytosis can inhibit MAPK activation. Additional mechanisms facilitating the relay of signals from cell-surface receptors to the nucleus can involve the assembly of protein kinases on a scaffolding protein and active transport of signaling complexes by molecular motors. We also discuss long-range signaling within a cell, such as survival signaling in neurons. We hypothesize that ligand-independent waves of receptor activation or/and traveling waves of phosphorylated kinases emerge to spread the signals over long distances.
Algorithms for the study of episodic hormone secretion (1982)

There is no generally accepted procedure for identifying ultradian pulsations in hormonal time series. We suggest an approach based on removing long-term trends, such as diurnal rhythms, from the series of observations; identifying peaks in the residual series; and resolving each peak, if appropriate, into overlapping secretory episodes. The first step uses a robust smoothing technique to generate a smoothed series that omits peaks or trends with time constants less than 6--12 h. The smoothed series is subtracted from the original, and in the second step their difference, the residual series, is examined for the presence of peaks. The standard deviation of the assay is calculated at each point, and the residuals are rescaled in terms of this unit. Peaks are identified as individual subseries elevated above the base line of duration n, all the points in which have magnitude at least G(n), where the values of G are cut-off criteria based on the width of the peak. Thus the algorithm selects both narrow high peaks and broader peaks that may be lower. The user selects the G(n) for each hormone based on theoretical considerations or a set of calibration data series. Points that meet these criteria are identified as belonging to peaks and flagged. To assure that the smoothing process is not influenced by runs of closely spaced peaks, these flagged points are then assigned a reduced weight, and the smoothing is repeated; the revised residuals are then reexamined. After these two steps are iterated until there are no further changes, each peak is examined once more to determine whether it can be resolved into more than one overlapping peak. Finally, the process collects statistics on the average frequency and amplitude of the peaks. We have developed computer programs to carry out these algorithms.
Detection of Tumor Cell-Specific mRNA and Protein in Exosome-Like Microvesicles from Blood and Saliva (2014)

The discovery of disease-specific biomarkers in oral fluids has revealed a new dimension in molecular diagnostics. Recent studies have reported the mechanistic involvement of tumor cells derived mediators, such as exosomes, in the development of saliva-based mRNA biomarkers. To further our understanding of the origins of disease-induced salivary biomarkers, we here evaluated the hypothesis that tumor-shed secretory lipidic vesicles called exosome-like microvesicles (ELMs) that serve as protective carriers of tissue-specific information, mRNAs, and proteins, throughout the vasculature and bodily fluids. RNA content was analyzed in cell free-saliva and ELM-enriched fractions of saliva. Our data confirmed that the majority of extracellular RNAs (exRNAs) in saliva were encapsulated within ELMs. Nude mice implanted with human lung cancer H460 cells expressing hCD63-GFP were used to follow the circulation of tumor cell specific protein and mRNA in the form of ELMs in vivo. We were able to identify human GAPDH mRNA in ELMs of blood and saliva of tumor bearing mice using nested RT-qPCR. ELMs positive for hCD63-GFP were detected in the saliva and blood of tumor bearing mice as well as using electric field-induced release and measurement (EFIRM). Altogether, our results demonstrate that ELMs carry tumor cell-specific mRNA and protein from blood to saliva in a xenografted mouse model of human lung cancer. These results therefore strengthen the link between distal tumor progression and the biomarker discovery of saliva through the ELMs.
Purification of a novel growth inhibitory factor for partially differentiated myeloid leukemic cells. (1988)

A novel factor termed growth inhibitory (GI) factor, which specifically inhibits the growth of mouse monocytic leukemia cells including monocytic cell lines (Mm-A and J774.1) and other partially differentiated myeloid leukemic cells, has been purified from conditioned medium of some clones of mouse myeloblastic leukemia M1 cells. The procedure for purification of the GI factor included ammonium sulfate precipitation, CM-Sepharose CL-6B and Sephadex G-200 chromatographies, reverse-phase high-performance liquid chromatography on a C18 hydrophobic support, and high-performance liquid chromatography on a gel filtration column. The purified factor gave a single band of protein with a molecular weight of 25,000 on sodium dodecyl sulfate-polyacrylamide gel. A concentration of 8 X 10(-10) M GI factor was required for 50% inhibition of growth of Mm-A cells. On chromatofocusing, the GI activity was eluted with Polybuffer 96/acetic acid at pH 8.2-8.4. The purified GI factor markedly inhibited growth of mouse bone marrow cells stimulated by macrophage colony-stimulating factor. The GI factor appeared to be a unique cytokine unrelated to known cytokines such as the tumor necrosis factor, interferons, and oncostatin M.
Pd/Si plasma immersion ion implantation for selective electroless copper plating on SiO2 (1992)

Selective deposition of copper in SiO2 trenches has been carried out using Pd/Si plasma immersion ion implantation and electroless Cu plating. To form the seed layer for electroless Cu plating on SiO2, sputtered Pd and Si atoms were partially ionized by the Ar plasma and then deposited at bottoms of SiO2 trenches; Ar ion beam was then applied to assist the mixing of the deposited Pd/Si films with the SiO2 substrate by recoil implantation. We found a threshold Pd dose of 2×1014/cm2 is required to initiate the electroless plating of Cu. By careful control of the anisotropic etching of the oxide trenches and proper choice of the Pd dose, 1-μm wide Cu filled lines with flat surfaces suitable for planarized multilevel metallization were successfully fabricated.
An imaging fiber-based optical tweezer array for microparticle array assembly (2004)

In this letter, we present a method to generate and regenerate arrays of microspheres by optically trapping through optical imaging fiber bundles. In this method, a laser beam is coupled into the proximal end of an optical fiber bundle, and the light energy is distributed across the face of the fiber. Each illuminated individual fiber in the array propagates light to the distal face of the bundle, where light focusing elements at the end of each fiber focus the laser light and form optical traps. These optical traps are capable of capturing and arraying microspheres in parallel. The number of optical traps is determined by the number of fibers in the optical fiber bundle and is capable of creating a dense array (∼5×104 traps/mm2) of optical tweezers.
Somite subdomains, muscle cell origins, and the four muscle regulatory factor proteins. (1994)

We show by immunohistology that distinct expression patterns of the four muscle regulatory factor (MRF) proteins identify subdomains of mouse somites. Myf-5 and MyoD are, at specific stages, each expressed in both myotome and dermatome cells. Myf-5 expression is initially restricted to dorsal cells in all somites, as is MyoD expression in neck somites. In trunk somites, however, MyoD is initially expressed in ventral cells. Myogenin and MRF4 are restricted to myotome cells, though the MRF4-expressing cells are initially less widely distributed than the myogenin-expressing cells, which are at all stages found throughout the myotome. All somitic myocytes express one or more MRFs. The transiently distinct expression patterns of the four MRF proteins identify dorsal and ventral subdomains of somites, and suggest that skeletal muscle cells in somites originate at multiple sites and via multiple molecular pathways.
Excited state absorption of pump radiation as a loss mechanism in solid-state lasers (1989)

The characteristics of optical pumping dynamics in laser-pumped, rare-earth-doped, solid-state laser materials are investigated by using a tunable alexandrite laser to pump Y/sub 3/Al/sub 5/O/sub 12/:Nd/sup 3+/ in an optical cavity. It is found that the slope efficiency of the Nd laser operation depends strongly on the wavelength of the pump laser. For pump wavelengths resulting in low slope efficiencies, intense fluorescence emission is observed from the sample in the blue-green spectral region. This is attributed to the excited-state absorption of pump photons which occurs during radiationless relaxation from the pump band to the metastable state. This type of process is an important loss mechanism for monochromatic pumping of laser systems at specific pump wavelengths.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
An update on diagnostic and prognostic biomarkers for traumatic brain injury (2018)

Traumatic brain injury (TBI) is a major worldwide neurological disorder of epidemic proportions. To date, there are still no FDA-approved therapies to treat any forms of TBI. Encouragingly, there are emerging data showing that biofluid-based TBI biomarker tests have the potential to diagnose the presence of TBI of different severities including concussion, and to predict outcome. Areas covered: The authors provide an update on the current knowledge of TBI biomarkers, including protein biomarkers for neuronal cell body injury (UCH-L1, NSE), astroglial injury (GFAP, S100B), neuronal cell death (αII-spectrin breakdown products), axonal injury (NF proteins), white matter injury (MBP), post-injury neurodegeneration (total Tau and phospho-Tau), post-injury autoimmune response (brain antigen-targeting autoantibodies), and other emerging non-protein biomarkers. The authors discuss biomarker evidence in TBI diagnosis, outcome prognosis and possible identification of post-TBI neurodegernative diseases (e.g. chronic traumatic encephalopathy and Alzheimer's disease), and as theranostic tools in pre-clinical and clinical settings. Expert commentary: A spectrum of biomarkers is now at or near the stage of formal clinical validation of their diagnostic and prognostic utilities in the management of TBI of varied severities including concussions. TBI biomarkers could serve as a theranostic tool in facilitating drug development and treatment monitoring.
Conclusion (2011)

One of the central messages of this book is that there has been no common political response to the structural transformations – immigration, globalization, post-Fordism – that have characterized all Western European countries over the past several decades. These transformations created opportunities for radical right parties to succeed in the long term, but our cross-national historical analysis has demonstrated that they were able to do so only under certain circumstances. The political effects of sociostructural change and exogenous pressures were refracted through national-level variables. In the case of radical right parties, these were not the variables one might immediately suspect, such as the electoral system or other formal political institutions, and this book has focused on two in particular. First, while radical right parties, like fascist movements, are the product of a distinct historical epoch, their success and failure cannot be understood in isolation from the movements that preceded them. Second, the degree of legitimacy accorded to radical right parties – in part because of historical factors, in part because of tactical calculations by other political actors – created opportunities in some cases and major hurdles in other. Thus both historical legacies and political culture were the critical intervening variables between sociostructural transformation and political outcomes.