gebhart/patrepeval huggingface dataset:
Cross-Linking 3D Assemblies of Nanoparticles into Mechanically Strong Aerogels by Surface-Initiated Free-Radical Polymerization (2008)

Skeletal nanoparticles of porous low-density materials formally classified as aerogels are cross-linked by surface-initiated polymerization (SIP) using a new surface-confined bidentate free-radical initiator structurally related to azobisisobutyronitrile (AIBN). Methylmethacrylate, styrene, and divinylbenzene are introduced in the mesopores, and upon heating at 70 °C, all mesoporous surfaces throughout the entire skeletal framework are coated conformally with a 10−12 nm thick polymer layer indistinguishable spectroscopically from the respective commercial bulk materials. The amount of polymer incorporated in the structure is controlled by the concentration of the monomer in the mesopores, and albeit an up to a 3-fold increase in bulk density (up to 0.6−0.8 g cm−3) and a decrease in the porosity even down to 40%, the materials remain mesoporous with average pore diameters increasing from 20 nm in the native samples to 41 and 62 nm in PMMA and polystyrene cross-linked samples, respectively. The new materials combine hydrophobicity with vastly improved mechanical properties in terms of strength, modulus, and toughness relative to their native (non-cross-linked) counterparts. The effect of polymer accumulation on the modulus has been also simulated numerically. Being able to use SIP for cross-linking 3D assemblies of nanoparticles comprising the skeletal framework of typical aerogels paves the way for the deconvolution of cross-linking from gelation (a free-radical versus an ionic process, respectively), so that ultimately all gelation and cross-linking reagents can be included together in one pot, leading to great process simplification. The mechanical properties of the new materials render them appropriate for anti-ballistic applications (e.g., armor).
A Peptide Model of Basement Membrane Collagen α 1(IV) 531- 543 Binds the α3β1 Integrin (1995)

Tumor cell adhesion to the triple-helical domain of basement membrane (type IV) collagen occurs at several different regions. Cellular recognition of the sequence spanning alpha 1(IV)531-543 has been proposed to be independent of triple-helical conformation (Miles, A. J., Skubitz, A. P. N., Furcht, L. T., and Fields, G. B. (1994) J. Biol. Chem. 269, 30939-30945). In the present study, integrin interactions with a peptide analog of the alpha 1(IV)-531-543 sequence have been analyzed. Tumor cell adhesion (melanoma, ovarian carcinoma) to the alpha 1(IV)531-543 chemically synthesized peptide was inhibited by a monoclonal antibody against the alpha 3 integrin subunit, and to a lesser extent by monoclonal antibodies against the beta 1 and alpha 2 integrin subunits. An anti-alpha 5 monoclonal antibody and normal mouse IgG were ineffective as inhibitors of tumor cell adhesion to the peptide. Two cell surface proteins of 120 and 150 kDa bound to an alpha 1(IV)531-543 peptide affinity column and were eluted with 20 mM EDTA. When the eluted proteins were incubated with monoclonal antibodies against either the alpha 3 or beta 1 integrin subunit, proteins corresponding in molecular weight to alpha 3 and beta 1 integrin subunits were precipitated. No proteins were immunoprecipated with monoclonal antibodies against the alpha 2 or alpha 5 integrin subunits. Thus, the alpha 3 beta 1 integrin from two tumor cell types has been shown to bind directly to the alpha 1 (IV)531-543 peptide. The alpha 1(IV)531-543 peptide is the first collagen-like sequence that has been shown to bind the alpha 3 beta 1 integrin.
A Retro-Inverso Miniantibody with Anti-HIV Activity (2000)

An HIV-1-specific miniantibody, a peptide representing the third heavy chain complementarity-determining region (CDR) of an HIV-specific mouse antibody, was characterized and modified with unnatural D-isomeric amino acids. The CDR peptide and its parent antibody bound to a similar epitope, located in the V3 region of HIV-1 gp120. A shortened CDR sequence was modified with D-amino acids to create an all-D-amino acid retro-inverso (RI) peptide with a reversed sequence order. The RI CDR was less susceptible to proteolytic degradation than its L-counterpart and had a higher affinity for HIV-1 peptides. The miniantibody and its parent antibody showed neutralization of both primary and laboratory strains of HIV-1. In accordance with the binding studies, the RI CDR showed a stronger HIV-inhibiting capacity than its L-counterpart. We conclude that the anti-HIV retro-inverso CDR identified in this study has the potential to become a future anti-HIV drug. It has a virus-neutralizing capacity in vitro and appears to be stable. Future research should focus on characterizing its antiviral activity in vivo.
Analysis of sample set enrichment scores: assaying the enrichment of sets of genes for individual samples in genome-wide expression profiles (2006)

Versions are available in Octave and Java (with a graphical user interface). Software can be downloaded at http://people.genome.duke.edu/assess.
PEGylation of interleukin‐10 for the mitigation of enhanced pain states (2009)

The anti-inflammatory cytokine interleukin-10 (IL-10) shows promise for the treatment of neuropathic pain, but for IL-10 to be clinically useful as a short-term therapeutic its duration needs to be improved. In this study, IL-10 was covalently modified with polyethylene glycol (PEG) with the goal of stabilizing and increasing protein levels in the CSF to improve the efficacy of IL-10 for treating neuropathic pain. Two different PEGylation methods were explored in vitro to identify suitable PEGylated IL-10 products for subsequent in vivo testing. PEGylation of IL-10 by acylation yielded a highly PEGylated product with a 35-fold in vitro biological activity reduction. PEGylation of IL-10 by reductive amination yielded products with a minimal number of PEG molecules attached and in vitro biological activity reductions of approximately 3-fold. In vivo collections of cerebrospinal fluid after intrathecal administration demonstrated that 20 kDa PEG attachment to IL-10 increased the concentration of IL-10 in the cerebrospinal fluid over time. Relative to unmodified IL-10, the 20 kDa PEG-IL-10 product exhibited an increased therapeutic duration and magnitude in an animal model of neuropathic pain. This suggests that PEGylation is a viable strategy for the short-term treatment or, in conjunction with other approaches, the long-term treatment of enhanced pain states.
Calculating aluminum content in total parenteral nutrition admixtures (2005)

The Food and Drug Administration (FDA) rule for limiting aluminum content in total parenteral nutrition (TPN) preparations continues to cause concerns among health care professionals, especially pharmacists.1 The federal regulation applies to drug manufacturers and not pharmacy practitioners and has three main objectives: (1) that the labels of all large- and small-volume parenterals used to prepare TPN formulations state the maximum aluminum concentration (in micrograms per liter) at expiration, (2) that the data submitted to FDA supporting the label claim must include information that describes a validated assay method for aluminum determination, and (3) that objectives 1 and 2 allow, but not mandate, health care professionals to calculate a patient’s exposure to aluminum when receiving TPN and take actions that limit intake in patients susceptible to aluminum toxicity. The statement on clinical limits for aluminum levels required by FDA for inclusion in the package insert contains this warning: “Levels of aluminum at greater than 4 to 5 μg/kg/ day accumulate aluminum at levels associated with central nervous system and bone toxicity.”2 Although the FDA rule does not require pharmacists to intervene whenever a TPN formulation contains more aluminum than a daily dosage of 5 μg/kg, we believe that practicing pharmacists have a professional responsibility to calculate the daily aluminum load of compounded TPN preparations and that this information should be reported on the label of each admixture dispensed. Such calculations can be performed manually, but ideally the total aluminum content in a TPN preparation should be included in the software programs used for automated compounding devices.
Retinal damage by light in rats. (1966)

The retina of laboratory rats is affected irreversibly by intense light applied for less than 1 hour or for up to 2 days depending upon experimental conditions. Exposure of unanesthetized and unrestrained animals was in chambers surrounded by a green filter and circular fluorescent lamps of a nominal brightness of 2,040 footlamberts. Eyes of anesthetized animals were exposed diffusely to either the light from a 100 to. zirconium arc passing through filters or monochromatic light of various icavelengths. Irreversible reduction in ERG amplitudes and degeneration of visual cells and pigment epithelium indicated the severity of the light damage. The effect was very dependent upon the body (eye) temperature during exposure. Hyperthermia greatly accelerated and intensified the damaging action of light and for this reason most experiments reported in this paper were performed at a high body temperature. At a body temperature around 104° F. severe damage teas produced with exposures to 5 to 10 iiw per square centimeter retina for 1 hour. The minimal damaging dose at a high temperature was estimated to be about 1 ixw per square centimeter. The action spectrum~of the daviaging effect approximated that of visual excitation as measured by the ERG. Hooded (pigmented) animals were no more affected than albinos of different strains. Recovery in the dark from a just subliminally damaging dose of light at a high body temperature required about 24 hours and was preceded by a period of time during ichich the retina was sensitized to an additional dose. During or following exposure to light at a high body temperature visual cell and pigmentepithelial_damage developedTabout simultaneouslu and was first indicated bit pyknosis Trncl cell swelling followed rapidly by the dissolution of nuclei and cytoplasm. The crucial reaction in producing the damage is considered a dark-reaction initiated by light of an -inte7isiiTj_ which bleaches measurably rhodopsin. Hypotheses on the reaction sequence which 'leads to damage are briefly discussed.
Herpes simplex virus glycoprotein D is recognized as antigen by CD4+ and CD8+ T lymphocytes from infected mice. Characterization of T cell clones. (1990)

Several previous reports have described the surprising inability to detect murine CTL specific for glycoprotein D (gD), one of the important protective immunogens of HSV. Using slight variations of published procedures, we were able to show that the immune response to HSV in infected mice includes the generation of CTL specific for gD. C3H/OuJ (H-2k) mice were infected by injection in the hind footpads with purified HSV-1. Lymphocytes from draining lymph nodes were then isolated and shown to proliferate in response to, and to kill, transformed fibroblasts (H-2k) expressing HSV-1 gD. Two gD-specific T cell clones were isolated. One clone, designated CGD1, was shwon to be CD8+. This clone recognizes HSV-1 gD, but not HSV-2 gD, in the context of class I MHC molecules and kills the appropriate MHC-matched fibroblasts expressing HSV-1 gD. Unusual features of this cytolytic clone include augmentation by IL-4 of proliferative responses to Ag, inhibition of its lytic activity by a mAb specific for Thy-1 and recognition of infected fibroblasts in preference to infected lymphoblasts. The other clone, designated CGD3, was shown to be CD4+. This clone recognizes both HSV-1 gD and HSV-2 gD in the context of class II MHC molecules and has cytolytic potential.
Structure-Based Stabilization of HIV-1 gp120 Enhances Humoral Immune Responses to the Induced Co-Receptor Binding Site (2009)

The human immunodeficiency virus type 1 (HIV-1) exterior envelope glycoprotein, gp120, possesses conserved binding sites for interaction with the primary virus receptor, CD4, and also for the co-receptor, generally CCR5. Although gp120 is a major target for virus-specific neutralizing antibodies, the gp120 variable elements and its malleable nature contribute to evasion of effective host-neutralizing antibodies. To understand the conformational character and immunogenicity of the gp120 receptor binding sites as potential vaccine targets, we introduced structure-based modifications to stabilize gp120 core proteins (deleted of the gp120 major variable regions) into the conformation recognized by both receptors. Thermodynamic analysis of the re-engineered core with selected ligands revealed significant stabilization of the receptor-binding regions. Stabilization of the co-receptor-binding region was associated with a marked increase in on-rate of ligand binding to this site as determined by surface plasmon resonance. Rabbit immunization studies showed that the conformational stabilization of core proteins, along with increased ligand affinity, was associated with strikingly enhanced humoral immune responses against the co-receptor-binding site. These results demonstrate that structure-based approaches can be exploited to stabilize a conformational site in a large functional protein to enhance immunogenic responses specific for that region.
Hypersusceptibility to Substrate Analogs Conferred by Mutations in Human Immunodeficiency Virus Type 1 Reverse Transcriptase (2006)

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) contains four structural motifs (A, B, C, and D) that are conserved in polymerases from diverse organisms. Motif B interacts with the incoming nucleotide, the template strand, and key active-site residues from other motifs, suggesting that motif B is an important determinant of substrate specificity. To examine the functional role of this region, we performed “random scanning mutagenesis” of 11 motif B residues and screened replication-competent mutants for altered substrate analog sensitivity in culture. Single amino acid replacements throughout the targeted region conferred resistance to lamivudine and/or hypersusceptibility to zidovudine (AZT). Substitutions at residue Q151 increased the sensitivity of HIV-1 to multiple nucleoside analogs, and a subset of these Q151 variants was also hypersusceptible to the pyrophosphate analog phosphonoformic acid (PFA). Other AZT-hypersusceptible mutants were resistant to PFA and are therefore phenotypically similar to PFA-resistant variants selected in vitro and in infected patients. Collectively, these data show that specific amino acid replacements in motif B confer broad-spectrum hypersusceptibility to substrate analog inhibitors. Our results suggest that motif B influences RT-deoxynucleoside triphosphate interactions at multiple steps in the catalytic cycle of polymerization.
Tethering of proteins to RNAs by bacteriophage proteins (2008)

Many steps in the control of gene expression are dependent on RNA-binding proteins, most of which are bi-functional, in as much as they both bind to RNA and interact with other protein partners in a functional complex. A powerful approach to study the functional properties of these proteins in vivo, independently of their RNA-binding ability, is to attach or tether them to specifically engineered reporter mRNAs whose fate can be easily followed. Two tethering systems have been mainly used in eukaryotic cells, namely the MS2 coat protein system and the lambda N-B box system. In this review, we firstly describe several studies in which these tethering systems have been used and provide an overview of these applications. We next describe the major features of these two systems, and, finally, we highlight a number of points that should be considered when designing experiments using this approach.
Pharmacology of Recombinant Adeno-associated Virus Production (2018)

Recombinant adeno-associated viral (rAAV) vectors have been used in more than 150 clinical trials with a good safety profile and significant clinical benefit in many genetic diseases. In addition, due to their ability to infect non-dividing and dividing cells and to serve as efficient substrate for homologous recombination, rAAVs are being used as a tool for gene-editing approaches. However, manufacturing of these vectors at high quantities and fulfilling current good manufacturing practices (GMP) is still a challenge, and several technological platforms are competing for this niche. Herein, we will describe the most commonly used upstream methods to produce rAAVs, paying particular attention to the starting materials (input) used in each platform and which related impurities can be expected in final products (output). The most commonly found impurities in rAAV stocks include defective particles (i.e., AAV capsids that do contain the therapeutic gene or are not infectious), residual proteins from host cells and helper viruses (adenovirus, herpes simplex virus, or baculoviruses), and illegitimate DNA from plasmids, cells, or helper viruses that may be encapsidated into rAAV particles. Given the role that impurities may play in immunotoxicity, this article reviews the impurities inherently associated with each manufacturing platform.
Promoting hepatocyte spheroid formation and functions by coculture with fibroblasts on micropatterned electrospun fibrous scaffolds (2014)

It remains as a great challenge to maintain the viability and functions of hepatocytes in vitro, and the construction of various scaffold materials and establishment of hepatocyte coculture systems are essential for the reconstruction of engineered liver devices. In our previous study, micropatterned electrospun fibrous mats were developed to control cellular behaviors, indicating that the cell growth and extracellular matrix deposition were confined to patterned regions. In the current study, the coculture of primary rat hepatocytes and fibroblasts was established on micropatterned scaffolds to modulate hepatocyte phenotype and functions. The inoculation of lactosylated poly(dl-lactide) into fiber matrices stimulated hepatocyte spheroid formation, and enhanced the albumin secretion, urea synthesis and cytochrome P-450 expression. The micropatterned coculture of hepatocytes and fibroblasts was constructed through layer-by-layer assembly of cell-loaded patterned fibers. Hepatocyte spheroids were effectively formed in the patterned regions with strong cell-cell contact, and fibroblasts were elongated in a bipolar manner and linked up into a single stretch. Compared with random coculture on fibrous mats and monoculture on patterned fibers, the coculture of hepatocytes with fibroblasts on patterned scaffolds resulted in a significantly higher amount of albumin and urea secretions and P450 expressions. Among the patterning designs, the majority of hepatocytes formed into spheroids with an average diameter of 100 μm after coculture with fibroblasts alternately located in the patterned scaffolds. This coculture system may provide a useful in vitro platform to retain the phenotype of hepatocytes and realize their functions.
CubeSat: A New Generation of Picosatellite for Education and Industry Low-Cost Space Experimentation (2000)

The launch and deployment of picosatellites from the Stanford University OPAL microsatellite in February 2000 demonstrate the feasibility and practicability of a new age of space experimentation. Two of the six picosatellites deployed from OPAL were built by The Aerospace Corporation in El Segundo, CA and demonstrated new space testing of MEMS RF switches and intersatellite and ground communication with low power wireless radios. These picosatellites weighting less than one kilogram with dimensions of 4x3x1 inch were built as test platforms for DARPA and were constructed and delivered for flight in less than nine months. From this experience, a new generation of picosats called CubeSat is being developed by a number of organizations and universities to accelerate opportunities with small, low construction cost, low launch cost space experiment platforms. California Polytechnic State University at San Luis Obispo, CA is developing launcher tubes that can be part of a satellite or attached to any orbiting platform to launch from 1-3 CubeSats per tube. These tubes will contain CubeSats of 1-2 kilograms weight and approximately 4-inch cube shape. This size as compared to the picosatellites launched on OPAL provide better surfaces for practical solar power generation, physical size for components and a shape that provides better space thermal stability. A consortium of potential CubeSat developers is now wide ranging with universities from Japan, New Zealand, the US, amateur radio clubs and industry participants. Potential launch opportunities exist with the Russian Dnepr (SS-18) about twice/year, with the OSP (Minotaur) every 18 months and possible 100 km altitude orbits from the second stage of Delta launches. This paper will review the OPAL picosatellite launch and performance, the launcher being built for the CubeSat, the development and payloads of CubeSat developers and cost and timing of launch opportunities.
Iterative Cluster Analysis of Protein Interaction Data (2004)

The program is available upon request from the authors, free for academic users. Additional information available at http://www.uv.es/genomica/UVCLUSTER.
Master switches of T-cell activation and differentiation (2007)

T-cells play a central role in allergic airway diseases such as bronchial asthma. The imbalance between allergen-specific pro-inflammatory and pro-allergic T-cell responses on one hand and regulatory or suppressive T-cell responses on the other may best explain the development of unwanted immune responses against environmental allergens, which lead to immunoglobulin E production and airway inflammation. A key role in the fine tuning of any T-cell response is provided by the engagement of so-called co-stimulatory molecules that are required for the full activation of T-cells and the recognition of antigens via the antigen-specific T-cell receptor. Many of these co-stimulatory molecules have been identified only recently, leading to a fundamental change in the overall understanding of T-cell regulation. Due to their pivotal impact on T-cell differentiation and control, co-stimulatory molecules are promising targets for therapeutic intervention in T-cell-regulated or -mediated immune disorders, including allergic diseases and asthma. In the present article, an attempt is made to summarise the current knowledge on the basic concept of co-stimulation, the presently known co-stimulatory molecules and their various functions on T-cell activation or suppression. The mini-series will be completed by two more articles describing the recent experimental studies and preliminary clinical findings regarding the role of co-stimulatory molecules in allergic disorders and bronchial asthma, and a discussion regarding the feasibility of co-stimulatory molecules as potential targets for the treatment of allergic airway disease. Although it is too early for any clinical implication or utilisation at this moment, the authors are convinced that a better understanding of co-stimulation in the context of allergic asthma will finally provide novel and promising approaches for treatment and prevention.
Realm Specific IP: Framework (2001)

The IESG notes that the set of documents describing the RSIP technology imply significant host and gateway changes for a complete implementation. In addition, the floating of port numbers can cause problems for some applications, preventing an RSIP-enabled host from interoperating transparently with existing applications in some cases (e.g., IPsec). Finally, there may be significant operational complexities associated with using RSIP. Some of these and other complications are outlined in section 6 of RFC 3102, as well as in the Appendices of RFC 3104. Accordingly, the costs and benefits of using RSIP should be carefully weighed against other means of relieving address shortage.