gebhart/patrepeval huggingface dataset:
PEG-OligoRNA Hybridization of mRNA for Developing Sterically Stable Lipid Nanoparticles toward In Vivo Administration (2019)

Lipid nanoparticles (LNPs) exhibit high potential as carriers of messenger RNA (mRNA). However, the arduous preparation process of mRNA-loaded LNPs remains a huge obstacle for their widespread clinical application. Herein, we tackled this issue by mRNA PEGylation through hybridization with polyethylene glycol (PEG)-conjugated RNA oligonucleotides (PEG-OligoRNAs). Importantly, mRNA translational activity was preserved even after hybridization of 20 PEG-OligoRNAs per mRNA. The straightforward mixing of the PEGylated mRNA with lipofectamine LTX, a commercial lipid-based carrier, just by pipetting in aqueous solution, allowed the successful preparation of mRNA-loaded LNPs with a diameter below 100 nm, whereas the use of non-PEGylated mRNA provided large aggregates above 100- and 1000-nm. In vivo, LNPs prepared from PEG-OligoRNA-hybridized mRNA exhibited high structural stability in biological milieu, without forming detectable aggregates in mouse blood after intravenous injection. In contrast, LNPs from non-PEGylated mRNA formed several micrometer-sized aggregates in blood, leading to rapid clearance from blood circulation and deposition of the aggregates in lung capillaries. Our strategy of mRNA PEGylation was also versatile to prevent aggregation of another type of mRNA-loaded LNP, DOTAP/Chol liposomes. Together, our approach provides a simple and robust preparation method to LNPs for in vivo application.
B cell-deficient mice do not develop type II collagen-induced arthritis (CIA) (1998)

To investigate the role of B cells in the development of CIA, a model for rheumatoid arthritis, we investigated susceptibility to CIA in mice lacking B cells due to the deletion of the IgM heavy chain gene (muMT). The muMT deletion was backcrossed into two different CIA-susceptible strains, B10.Q and B10.RIII. Two different variants of the CIA model are inducible in these strains: in B10.Q with rat type II collagen (CII) and in B10.RIII with bovine CII. Homozygous deletion of the IgM gene led to the absence of B cells and dramatically reduced immunoglobulin levels compared with wild-type mice. The deletion of IgM totally abrogated development of CIA in both strains, although the anti-CII T cell response did not differ between the muMT and wild-type controls. We conclude that B cells play a crucial role in the development of CIA.
Effect of combined supplementation with alpha-tocopherol, ascorbate, and beta carotene on low-density lipoprotein oxidation. (1993)

Combined supplementation with ascorbate, beta carotene, and alpha-tocopherol is not superior to high-dose alpha-tocopherol alone in inhibiting LDL oxidation. Hence, alpha-tocopherol therapy should be favored in future coronary prevention trials involving antioxidants.
Bright object protection for the ACS MAMA detector (1998)

Bright object protection for the ACS MAMA is similar in concept to that for the STIS FUV MAMA, but several mechanisms provide better protection for the ACS MAMA. A fold mirror blocks all light from reaching the MAMA when the CCDs are being used and the SBC filter wheel has shuttered positions. Protection mechanisms include, hardware, and software tests plus manual screening of proposals. The stellar magnitude limits are tabulated for the ACS filter set. The worst case is for a 19th magnitude O star exposed through the F115LP or F125LP filters or either of the two prisms. Such stars exceed the bright object protection limits and will require careful manual screening. 1.
Mass Spectrometric Sequencing of Proteins from Silver-Stained Polyacrylamide Gels (1996)

Proteins from silver-stained gels can be digested enzymatically and the resulting peptide analyzed and sequenced by mass spectrometry. Standard proteins yield the same peptide maps when extracted from Coomassie- and silver-stained gels, as judged by electrospray and MALDI mass spectrometry. The low nanogram range can be reached by the protocols described here, and the method is robust. A silver-stained one-dimensional gel of a fraction from yeast proteins was analyzed by nano-electrospray tandem mass spectrometry. In the sequencing, more than 1000 amino acids were covered, resulting in no evidence of chemical modifications due to the silver staining procedure. Silver staining allows a substantial shortening of sample preparation time and may, therefore, be preferable over Coomassie staining. This work removes a major obstacle to the low-level sequence analysis of proteins separated on polyacrylamide gels.
Augmentation of postswelling surgical sealant potential of adhesive hydrogels (2010)

Two-component hydrogels formed with star polyethylene glycol amine and linear dextran aldehyde polymers (PEG:dextran) show promise as tissue-specific surgical sealants. However, there is a significant loss of adhesion strength to soft tissues following PEG:dextran swelling, which may limit material ability to appose disjoined tissues and prevent leakage from surgical sites. We covalently incorporated the modified amino acid L-3,4-dihydroxyphenylalanine (L-DOPA) into PEG:dextran to enhance postswelling sealant performance. L-DOPA is an essential component of marine animal adhesive plaques and has been used to confer wet adhesion in synthetic materials. As both PEG:dextran cohesion and adhesion are mediated by aldehyde-amine interactions, L-DOPA side-groups make it a potent network modulator with potential to affect multiple material properties. Following 1-h submersion in aqueous media, PEG:dextran doped with 3 mM L-DOPA/M aldehyde on average swelled 50.3% less, had 287.4% greater stiffness, and had 53.6% greater functional adhesion strength compared to the neat hydrogel. Increased concentrations of L-DOPA up to 11 mM L-DOPA/M aldehyde similarly curtailed swelling and mitigated property loss with hydration, but sacrificed initial functional adhesion strength, material modulus, and biocompatibility. Taken together, these data support tailored L-DOPA conjugation as a promising approach to enhance the clinical performance of PEG:dextran sealants.
Residues in the WD Repeats of Tup1 Required for Interaction with α2 (1997)

The yeast transcriptional repressor Tup1 contains seven WD repeats which interact with the DNA-binding protein alpha2. We have identified mutations in Tup1 that disrupt this interaction. The positions of the amino acids changed by these mutations are consistent with Tup1 being folded into a seven-bladed propeller like that formed by another WD repeat-containing protein, the beta subunit of the heterotrimeric G protein used in signal transduction. Our results also indicate that the interaction between Tup1 and alpha2 resembles the interaction between Gbeta and G alpha, suggesting that a similar structural interface is formed by WD repeat proteins that are used in both transcriptional regulation and signal transduction.
Properties of a new intravenous immunoglobulin (IGIV‐C, 10%) produced by virus inactivation with caprylate and column chromatography (2003)

Compared with the current commercial process, the new IGIV-C manufacturing process produces a more highly purified preparation that contains slightly higher levels of IgG4 and retains antibody activities required for clinical efficacy.
Production of Tissue-Engineered Small Intestine in Rats with Different Ages of Cell Donors (2018)

This study compared side-by-side the impact of donor age on the production of tissue-engineered small intestine (TESI). Each age represents a specific period of life: E18 for fetuses, 5-day-old pups for neonates, 21-day-old rats for weanlings, and 6-week-old rats for adults. The TESI produced was compared macroscopically and microscopically. The mechanism(s) contributing to the differences observed was explored by detecting proliferating cells in the TESI and by analyzing intestinal stem cell gene expression in donor cells. These data may provide valuable information for future application of TESI clinically.
Derivation of 0-g structural control models from analysis and 1-G experimentation (1995)

The Middeck Active Control Experiment (MACE) is a space shuttle flight experiment, manifest for launch on STS-67 on March 2, 1995, intended to demonstrate high authority active structural control in zero gravity conditions. Since no experimental on-orbit data is available before flight, the model used to derive these controllers must be obtained from a combination of analysis and openand closed-loop ground testing. A general modeling approach to obtain this 0-g model is presented along with its application to the MACE test article. This modeling approach starts with a 1-g model, which includes gravity and suspension effects on the structure. This 1-g model is improved using ground test results in a process called updating. Once the model has been updated, it is verified through a combination of structural perturbation and closed-loop control. Finally, after the model has been verified, the gravity and suspension effects are removed to arrive at a prediction of the 0-g behavior of the structure.
Genetic and Neutralization Properties of Subtype C Human Immunodeficiency Virus Type 1 Molecular env Clones from Acute and Early Heterosexually Acquired Infections in Southern Africa (2006)

A standard panel of subtype C human immunodeficiency virus type 1 (HIV-1) Env-pseudotyped viruses was created by cloning, sequencing, and characterizing functional gp160 genes from 18 acute and early heterosexually acquired infections in South Africa and Zambia. In general, the gp120 region of these clones was shorter (most evident in V1 and V4) and less glycosylated compared to newly transmitted subtype B viruses, and it was underglycosylated but no different in length compared to chronic subtype C viruses. The gp120s also exhibited low amino acid sequence variability (12%) in V3 and high variability (39%) immediately downstream of V3, a feature shared with newly transmitted subtype B viruses and chronic viruses of both subtypes. When tested as Env-pseudotyped viruses in a luciferase reporter gene assay, all clones possessed an R5 phenotype and resembled primary isolates in their sensitivity to neutralization by HIV-1-positive plasmas. Results obtained with a multisubtype plasma panel suggested partial subtype preference in the neutralizing antibody response to infection. The clones were typical of subtype C in that all were resistant to 2G12 (associated with loss of N-glycosylation at position 295) and most were resistant to 2F5, but all were sensitive to 4E10 and many were sensitive to immunoglobulin G1b12. Finally, conserved neutralization epitopes in the CD4-induced coreceptor binding domain of gp120 were poorly accessible and were difficult to induce and stabilize with soluble CD4 on Env-pseudotyped viruses. These results illustrate key genetic and antigenic properties of subtype C HIV-1 that might impact the design and testing of candidate vaccines. A subset of these gp160 clones are suitable for use as reference reagents to facilitate standardized assessments of vaccine-elicited neutralizing antibody responses.
Immunologic reactions in amyotrophic lateral sclerosis brain and spinal cord tissue. (1992)

Expression of proteins associated with immune function was investigated immunohistochemically in postmortem brain and spinal cord of patients with amyotrophic lateral sclerosis (ALS). Reactive microglia/macrophages displaying high levels of leukocyte common antigen (LCA), the immunoglobulin receptor Fc gamma R1, lymphocyte function associated molecule-1 (LFA-1), the complement receptors CR3 and CR4, the class II major histocompatibility complex molecules HLA-DR, HLA-DP and HLA-DQ and common determinants of the class I HLA-A,B,C complex were abundant in affected areas in ALS. These areas included the primary motor cortex, motor nuclei of the brain stem, the anterior horn of the spinal cord, and the full extent of the corticospinal tract. A significant number of T lymphocytes of the helper/inducer (CD4+) and cytotoxic/suppressor (CD8+) subtypes were observed marginating along the walls of capillaries and venules and extending into the parenchyma of affected areas. Clusters of complement activated oligodendroglia as well as degenerating neurites positive for C3d and C4d were frequently detected in ALS-affected areas. These data provide evidence of immune-effector changes in ALS. They are consistent with an autoimmune or slow virus theory of the disorder, but may reflect only secondary changes.
Techniques for depth-resolved imaging through turbid media including coherence-gated imaging (2003)

This article aims to review the panoply of techniques for realising optical imaging through turbid media such as biological tissue. It begins by briefly discussing optical scattering and outlines the various approaches that have been developed to image through scattering media including spatial filtering, time-gated imaging and coherence-based techniques. The discussion includes scanning and wide-field techniques and concentrates on techniques to discriminate in favour of unscattered ballistic light although imaging with scattered light is briefly reviewed. Wide-field coherence-gated imaging techniques are discussed in some detail with particular emphasis placed on techniques to achieve real-time high-resolution three-dimensional imaging including through turbid media, providing rapid whole-field acquisition and high depth and transverse spatial resolution images.
A Requirement for Sodium in the Growth of Rhodopseudomonas spheroides (1960)

It was shown by MacLeod and his co-workers that among bacteria only the true marine forms have a specific sodium requirement. These all require this ion in concentrations of the order of a few tenths of 1 %. The non-marine bacteria studied by MacLeod were distinguished from marine forms by their lack of any requirement for sodium (MacLeod, Onofrey &amp; Norris, 1954; MacLeod &amp; Onofrey, 1956). In view of these facts, the following observation, which I made in the course of studying the amino acid nutrition of Rhodopseudomonas spheroides, seemed significant. This bacterium can grow very well in media of ordinary ionic strength and thus is not obviously marine. I observed that it did not grow in a medium in which an artificial mixture of amino acids had replaced an acid hydrolysate of casein. Since almost 40 % of the hydrolysate used was sodium chloride, I added a little NaCl to the medium containing the artificial mixture of amino acids. I then found that the growth was as rapid as in the medium made with casein hydrolysate. It was easily shown that a very much simpler mixture of amino acids permitted rapid growth in the presence of as little as 100 μg. NaCl/ml. This requirement for a low concentration of sodium seemed to set this organism apart both from marine and from terrestrial bacteria and thus to merit a more detailed analysis, the first results of which are reported here.
Data acquisition for an intelligent bedside monitoring system (2002)

The authors have developed a software architecture for intelligent monitoring tasks at the bedside in critical care environments (SIMON). This architecture includes a data acquisition module. The authors have modeled their design of this component on the concepts proposed by the IEEE P1073 standardization committee. It should be seen as a bridge towards an environment based on that standard. The authors have designed their system to be able to acquire all data available from all bedside instruments to allow signal analysis at the lowest level. The authors are using SIMON on-line in the Cardiac Care Unit at Vanderbilt University Medical Center.
An immunotoxin with greatly reduced immunogenicity by identification and removal of B cell epitopes (2008)

Recombinant immunotoxins are hybrid proteins composed of an Fv that binds to a tumor antigen fused to a bacterial or plant toxin. Immunotoxin BL22 targets CD22 positive malignancies and is composed of an anti-CD22 Fv fused to a 38-kDa fragment of Pseudomonas exotoxin A (PE38). BL22 has produced many complete remissions in drug-resistant Hairy cell leukemia, where many treatment cycles can be given, because neutralizing antibodies do not form. In marked contrast, only minor responses have been observed in trials with immunotoxins targeting solid tumors, because only a single treatment cycle can be given before antibodies develop. To allow more treatment cycles and increase efficacy, we have produced a less immunogenic immunotoxin by identifying and eliminating most of the B cell epitopes on PE38. This was accomplished by mutation of specific large hydrophilic amino acids (Arg, Gln, Glu, Lys) to Ala, Ser, or Gly. The new immunotoxin (HA22-8X) is significantly less immunogenic in three strains of mice, yet retains full cytotoxic and anti-tumor activities. Elimination of B-cell epitopes is a promising approach to the production of less immunogenic proteins for therapeutic purposes.
Human Glioma-Induced Immunosuppression Involves Soluble Factor(s) That Alters Monocyte Cytokine Profile and Surface Markers (1999)

Patients with gliomas exhibit deficient in vitro and in vivo T cell immune activity, and human glioblastoma culture supernatants (GCS) inhibit in vitro T lymphocyte responses. Because APC are essential for initiating and regulating T cell responses, we investigated whether GCS would affect cytokines produced by monocytes and T cells from healthy donors of PBMC. Incubation of PBMC with GCS decreased production of IL-12, IFN-gamma, and TNF-alpha, and increased production of IL-6 and IL-10. The GCS-induced changes in IL-12 and IL-10 occurred in monocytes, and involved changes in IL-12 p40 and IL-10 mRNA expression. Incubation with GCS also resulted in reduced expression of MHC class II and of CD80/86 costimulatory molecules on monocytes. The immunosuppressive effects were not the result of IL-6 or TGF-beta1 that was detected in GCS. However, it was due to a factor(s) that is resistant to pH extremes, differentially susceptible to temperature, susceptible to trypsin, and has a minimum molecular mass of 40 kDa. Our findings show that glioblastoma-generated factors that are known to suppress T cell responses alter the cytokine profiles of monocytic APC that, in turn, inhibit T cell function. This model indicates that monocytes can serve as an intermediate between tumor-generated immune-suppressive factors and the T cell responses that are suppressed in gliomas.
Immunochemistry of Salmonella O-Antigens: Preparation of an Octasaccharide-Bovine Serum Albumin Immunogen Representative of Salmonella Serogroup B O-Antigen and Characterization of the Antibody Response (1978)

The O-antigenic polysaccharide of phenol-water extracted Salmonella typhimurium (O antigens 4, 12) lipopolysaccharide was enzymatically cleaved by phage P22 endorhamnosidase. An octasaccharide with the (formula: see text) structure Gal-Man-Rha-Gal-Man-Rha was isolated and shown to retain the O-antigen 4 specificity of the native polysaccharide. After oxidation of the terminal reducing rhamnose residue to the corresponding aldonic acid, the octasaccharide was covalently linked to bovine serum albumin (OLS-BSA) by use of a water-soluble carbodimide. The resulting conjugate showed O-antigen 4 specificity in enzyme-linked immunosorbent assay (ELISA) ans passive hemagglutination inhibition tests. Immunization of rabbits with the OLS-BSA conjugate gave rise to antibodies directed toward both the octasaccharide and the carrier protein. ELISA titration with synthetic disaccharide-protein conjugates as antigens revealed that the antibody titer against the mannose-rhamnose structure was higher than against the abequose-mannose structure. In rabbits immunized with heat-killed whole bacteria the titers against the two disaccharides were equal. The reason for this difference is not obvious. It is evident, however, that the OLS-BSA conjugate elicited in rabbits O-antibodies with the same specificity as whole bacteria.
Anisotropy and Ising-type transition of the S=5/2 two-dimensional Heisenberg antiferromagnet Mn-formate di-Urea (2003)

Recently reported measurements of specific heat on the compound Mn-formate di-Urea by Takeda et al. [Phys. Rev. B 63, 024425 (2001)] are considered. As a model to describe the overall thermodynamic behavior of such a compound, the easy-axis two-dimensional Heisenberg antiferromagnet is proposed and studied by means of the pure quantum self-consistent harmonic approximation. In particular, it is shown that when the temperature decreases, the compound exhibits a crossover from two-dimensional (2D) Heisenberg to 2D-Ising behavior, followed by a 2D-Ising-type phase transition, whose location allows one to get a reliable estimate of the easy-axis anisotropy driving the transition itself. Below the critical temperature TN=3.77 K, the specific heat is well described by the two-dimensional easy-axis model down to a temperature T*=1.57 K, where a T3 law sets in, possibly marking a low-temperature crossover of magnetic fluctuations from two to three dimensions.
The susceptibility to natural killer cell-mediated lysis of HLA class I-positive melanomas reflects the expression of insufficient amounts of different HLA class I alleles (1998)

NK cells selectively lyse tumor cells which do not express one or more MHC class I alleles. The ability to discriminate between self normal or tumor cells is due to the expression of MHC class I-specific killer inhibitory receptors (KIR). In the present study we analyzed melanoma cell lines which were highly susceptible to NK cell-mediated lysis in spite of the expression of a complete set of HLA class I alleles. Quantitative analysis of the HLA class I expression using allele-specific monoclonal antibodies (mAb) revealed a down-regulation of all HLA class I molecules. Treatment of melanoma cells with IFN-gamma resulted in up-regulation of all HLA class I alleles that was paralleled by the acquisition of resistance to lysis. That resistance to lysis reflected the up-regulation of HLA class I molecules was revealed by the finding that mAb-mediated masking of either KIR or their HLA class I ligands completely restored the melanoma cell lysis. These results were obtained by the use of selected NK cell clones derived either from allogeneic or autologous donors. In addition, similar results were obtained using in vitro expanded autologous NK cell populations. Our data indicate that NK cells can lyse not only melanoma cells which have lost the expression of one or more HLA class I alleles but also cells expressing a decreased amount of class I molecules.