gebhart/patrepeval huggingface dataset:
Monozygotic Twinning in Rhesus Monkeys by Manipulation of In Vitro-Derived Embryos1 (2002)

The nonhuman primate is a relevant model for human disease that can be used for diverse biomedical investigations. The ability to propagate a founder animal by application of assisted reproductive technologies is pressing, but an even greater need in many studies is access to genetically identical animals. In an effort to create genetically identical monkeys, we evaluated two approaches to monozygotic twinning; blastomere separation, and blastocyst bisection. Embryos were produced by intracytoplasmic sperm injection of oocytes recovered following controlled ovarian stimulation. The quality of demiembryos produced in these efforts was evaluated by quantitating the efficiency of creating identical pairs for embryo transfer, by morphological assessment, by the allocation of cells to the inner cell mass (ICM) and trophectoderm (TE) in the blastocyst, and by the outcome of embryo transfer to synchronized host animals. Pairs were produced in high yield (85%-95%) by both twinning methods. Demiembryos resulting from blastomere separations at the 2- or 4-cell stage grew to blastocysts at the control frequency. Demiblastocysts contained, on average, half the number of cells of the intact controls while maintaining the same ICM:TE or ICM:total cell ratio. The equivalency of demiblastocysts within a set was also evaluated by differential cell counting. Embryo transfers of identical sets led to a 33% clinical pregnancy rate, with two twin pregnancies initiated. Neither pregnancy resulted in term birth of monozygotic twins, but our results are sufficiently encouraging to justify a large-scale twinning trial in the rhesus macaque.
Influence of Amine Substituents on 5-HT2A versus 5-HT2C Binding of Phenylalkyl- and Indolylalkylamines (1994)

The effect of 15 different amine substituents on 5-HT2A and 5-HT2C serotonin receptor binding was investigated for two series of compounds (i.e., phenylalkylamine and indolylalkylamine derivatives). In general, amine substitution decreases receptor affinity; however, N-(4-bromobenzyl) substitution results in compounds that bind at 5-HT2A receptors with high affinity (Ki < 1 nM) and with > 100-fold selectivity. Although parallel structural modification in the two series result in parallel shifts in 5-HT2C binding, these same modifications alter 5-HT2A binding in a less consistent manner.
Tissue-independent and tissue-specific patterns of DNA methylation alteration in cancer (2016)

Our data show that a considerable fraction of the aberrant cancer DNA methylation landscape results from a mechanism that is largely tissue specific. Histone marks as specified in the normal cell of origin provide highly predictive models of aberrant cancer DNA methylation and outperform those derived from the same marks in hESCs.
Quality of Care for Hospitalized Medicare Patients at Risk for Pressure Ulcers (2001)

These results suggest that US hospitals and physicians have numerous opportunities to improve care related to pressure ulcer prediction and prevention.
A Monte Carlo Program Converting Activity Distributions to Absorbed Dose Distributions in a Radionuclide Treatment Planning System (1996)

In systemic radiation therapy, the absorbed dose distribution must be calculated from the individual activity distribution. A computer code has been developed for the conversion of an arbitrary activity distribution to a 3-D absorbed dose distribution. The activity distribution can be described either analytically or as a voxel based distribution, which comes from a SPECT acquisition. Decay points are sampled according to the activity map, and particles (photons and electrons) from the decay are followed through the tissue until they either escape the patient or drop below a cut off energy. To verify the calculated results, the mathematically defined MIRD phantom and unity density spheres have been included in the code. Also other published dosimetry data were used for verification. Absorbed fractions and S-values were calculated. A comparison with simulated data from the code with MIRD data shows good agreement. The S values are within 10-20% of published MIRD S values for most organs. Absorbed fractions for photons and electrons in spheres (masses between 1 g and 200 kg) are within 10-15% of those published. Radial absorbed dose distributions in a necrotic tumor show good agreement with published data. The application of the code in a radionuclide therapy dose planning system, based on quantitative SPECT, is discussed.
Up‐Regulation of Endothelial Cell Adhesion Molecules Characterizes Disease Activity in Systemic Lupus Erythematosus (1994)

Our findings demonstrate up-regulation of the surface expression of 3 distinct adhesion molecules, E-selectin, VCAM-1, and ICAM-1, in patients with SLE. The abnormal expression of these endothelial cell adhesion molecules is most marked in patients with active disease characterized by significant elevations of the complement split product C3a desArg. We suggest that in certain SLE patients, excessive complement activation in association with primed endothelial cells induces leukocyte-endothelial cell adhesion and leuko-occlusive vasculopathy.
Preparation and characterization of macroporous poly(N‐isopropylacrylamide) hydrogels for the controlled release of proteins (2002)

Abstract Macroporous, temperature‐sensitive poly( N ‐isopropylacrylamide) (PNIPAAm) hydrogels were synthesized with poly(ethylene glycol)s (PEGs; molecular weight = 2000–6000) as the pore‐forming agents. The influence of the molecular weight and PEG content on the responsive kinetics of these macroporous hydrogels was investigated. The PEG‐modified PNIPAAm hydrogels were characterized by the swelling ratio, deswelling–reswelling kinetics, Fourier transform infrared, and differential scanning calorimetry. The morphology of these hydrogels was analyzed with scanning electron microscopy. The prepared macroporous hydrogels exhibited some unique properties in comparison with the gels with low molecular weight PEGs (molecular weight &lt; 2000) as the pore‐forming agents. In addition, a preliminary study on the controlled release of bovine serum albumin from these macroporous hydrogels was carried out. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 152–159, 2003
Specific loss of chondromodulin‐I gene expression in chondrosarcoma and the suppression of tumor angiogenesis and growth by its recombinant protein in vivo (1999)

Chondromodulin-I (ChM-I) was previously identified as an angiogenesis inhibitor in cartilage. Here, we demonstrated that the level of ChM-I transcripts was substantially reduced to 100 or even less in the lower-grade chondrosarcomas, in articular cartilage or other benign cartilage tumors. We implanted human chondrosarcoma OUMS-27 cells into nude mice that reproducibly produced tumors with cartilaginous matrix. Tumor-induced angiogenesis was evident when the tumors were excised 30 days after implantation. However, the local administration of recombinant human ChM-I almost completely blocked vascular invasion and tumor growth in vivo. Moreover, ChM-I also inhibited the growth of HT-29 colon adenocarcinoma in vivo, implying its therapeutic potential for solid tumors.
Estrogen-Specific 17 -Hydroxysteroid Oxidoreductase Type 1 (E.C. 1.1.1.62) as a Possible Target for the Action of Phytoestrogens (1995)

Several plant estrogens, especially coumestrol and genistein, were found to reduce the conversion of [3H]estrone to [3H] 17 beta-estradiol catalyzed by estrogen-specific 17 beta-hydroxysteroid oxidoreductase Type 1 (E.C. 1.1.1.62) in vitro. Coumestrol, the most potent inhibitor in our experiments, is the best inhibitor of the enzyme known to date. All compounds with inhibitory effects were also estrogenic. However, structural demands for 17 beta-HSOR Type 1 inhibition and estrogenicity of tested compounds in breast cancer cells (judged by increased cell proliferation) were not identical. Zearalenone and diethylstilbestrol, both potent estrogens, did not inhibit 17 beta-HSOR Type 1. Thus, changes in the estrogen molecule may discriminate between active sites of 17 beta-HSOR Type 1 and estrogen binding sites of the ER. The effects of these compounds in vivo cannot be predicted on the basis of these results. Inhibition of 17 beta-HSOR Type 1 enzyme could lead to a decrease in the availability of the highly active endogenous estrogen. However, these compounds are estrogenic per se, and they may thus replace endogenous estrogens. Additional studies are needed to further understand the role of these plant estrogens in the etiology of hormone-dependent cancers. It is not easily conceivable how the chemopreventive action of Asian diets, possibly mediated by phytoestrogens in soya products, can be based on the inhibition of estrone reduction at the target cells by phytoestrogens or related compounds, unless they are "incomplete estrogens" (i.e., unable to induce all effects typical of endogenous estrogens).
Cloning, sequencing, and expression of a Thermomonospora fusca protease gene in Streptomyces lividans (1996)

The major Thermomonospora fusca YX extracellular protease gene (tfpA) was cloned into Escherichia coli and Streptomyces lividans and was sequenced. The open reading frame encoded 375 residues, including a 31-residue potential signal sequence, an N-terminal prosequence containing 150 residues, and the 194-residue mature protease that belongs to the chymotrypsin family. The protease was secreted by S. lividans, but evidence suggested that it was bound to an extracellular protease inhibitor. An inhibitor-deficient mutant was selected to produce protease for purification.
T cells from the tumor microenvironment of patients with progressive myeloma can generate strong, tumor-specific cytolytic responses to autologous, tumor-loaded dendritic cells (2002)

Most untreated cancer patients develop progressive tumors. We tested the capacity of T lymphocytes from patients with clinically progressive, multiple myeloma to develop killer function against fresh autologous tumor. In this malignancy, it is feasible to reproducibly evaluate freshly isolated tumor cells and T cells from the marrow tumor environment. When we did this with seven consecutive patients, with all clinical stages of disease, we did not detect reactivity to autologous cancer cells. However, both cytolytic and IFN-gamma-producing responses to autologous myeloma were generated in six of seven patients after stimulation ex vivo with dendritic cells that had processed autologous tumor cells. The antitumor effectors recognized fresh autologous tumor but not nontumor cells in the bone marrow, myeloma cell lines, dendritic cells loaded with tumor-derived Ig, or allogeneic tumor. Importantly, these CD8(+) effectors developed with similar efficiency by using T cells from both the blood and the bone marrow tumor environment. Therefore, even in the setting of clinical tumor progression, the tumor bed of myeloma patients contains T cells that can be activated readily by dendritic cells to kill primary autologous tumor.
Functional Definition of a B Cell Epitope, KGEQGEPGA, on C1q the Fc‐Binding Subunit of the First Component of Complement (1999)

A synthetic peptide representing the C1q epitope KGEQGEPGA has been shown to suppress or delay the onset of CII-induced arthritis when applied intravenously (i.v.) prior to an intradermal (i.d.) challenge, in a mouse model; the phenomenon being associated with the development of immunoglobulin (Ig)M antibodies specific for the KGEQGEPGA epitope. Here we show that this amino acid sequence provides an immunodominant B cell epitope that is recognised by autoantibodies present in the sera of patients with chronic inflammatory diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis, two diseases associated with an immune response to C1q. The peptide's ability to produce peptide specific IgM when applied i.v. in both normal and athymic mice but not in mice exhibiting the x-linked B-cell associated Bruton's tyrosine kinase defect permits classification of the KGEQGEPGA peptide as a T-cell independent antigen type-2 (TI-2). IgM monoclonal antibodies raised against the peptide are able to functionally block activation of the complement cascade by C1q, via a mechanism that inhibits the C4 consumption. Antibodies to this immunodominant epitope may therefore modulate inflammatory processes by interfering with the activation of the classical pathway of the complement.
Cross-Presentation of Adeno-Associated Virus Serotype 2 Capsids Activates Cytotoxic T Cells But Does Not Render Hepatocytes Effective Cytolytic Targets (2007)

Liver toxicity observed in a clinical trial of adeno-associated virus serotype 2 (AAV2) delivered systemically to patients with hemophilia was ascribed to killing of vector-transduced hepatocytes by capsid-specific T cells. This study evaluated the biology of T cell activation in response to AAV capsids in murine models. CD8(+) T cell epitopes were mapped to capsids from AAV2, AAV7, and AAV8. A tetramer generated in response to a dominant capsid epitope in BALB/c mice was shared between these AAV serotypes. Administration of AAV2 vector resulted in the activation of capsid-specific CD8(+) T cells as evidenced by binding to tetramer and production of capsid-induced interferon-gamma expression this was not observed with the AAV7 and AAV8 vectors. CD8(+) T cells specific to AAV2 capsids demonstrate functional cytolytic activity in vivo to peptide-loaded target cells. The frequency of capsid-specific T cells was much higher in liver than in blood or spleen. The performance of liver-directed AAV-mediated gene transfer was not diminished in animals with high levels of pre-existing capsid-specific T cells. We conclude that cross-presentation of AAV capsids does result in activation of cytotoxic T lymphocytes (CTLs) in a serotype-specific manner; however, there is no evidence that vector-transduced hepatocytes are targets for CTL effector activity.
Fiber optic flexural disk microphone (1988)

An interferometric fiber optic microphone consisting of a 10-m-long, 4-cm-diam, flat-wound (spiral) single mode optical fiber bonded to a simply supported, 8-cm-diam, 3-mm-thick aluminum disk will be described. In the presence of a pressure difference across the plate or an acceleration of the plate, the surface strain induced in the plate is transmitted to the optical fiber. The optical phase shift induced by the strain is detected in an all-fiber Michelson interferometer. The calculated strain [A. E. H. Love, A Treatise on the Mathematical Theory of Elasticity (Dover, New York, 1944), 4th ed., Sec. ♯309] and optical strain measured using static pressure, acoustic pressure, and a calibrated aecelerometer, are in good agreement (± 10%) and yield a sensitivity of 30 milliradians per Pascal per meter of optical fiber below the plate resonance frequency of 3 kHz. [Work supported by the Office of Naval Research and Office of Naval Technology.]
Computerized transverse axial scanning (tomography): Part 1. Description of system (1973)

This article describes a technique in which X-ray transmission readings are taken through the head at a multitude of angles: from these data, absorption values of the material contained within the head are calculated on a computer and presented as a series of pictures of slices of the cranium. The system is approximately 100 times more sensitive than conventional X-ray systems to such an extent that variations in soft tissues of nearly similar density can be displayed.
Determination of high-order lens aberration using phase/amplitude linear algebra (1999)

New approaches to measuring lens aberration of optical exposure tools in semiconductor manufacturing environment are discussed. First, plural image quantities are measured and expressed by linear combinations of contributions from several Zernike aberration terms. Then, the linear problem is solved to find the best combination of each term to explain the experimental results. Using side-lobe intensity near octagonal aperture edges in an attenuated phase-shifting mask as a detector, third-order Coma and trifoil aberrations were successfully measured.
Optical raster-scanning displays based on surface-micromachined polysilicon mirrors (1999)

We demonstrate high-resolution, raster-scanning display systems based on pairs of orthogonally scanning, surface-micromachined mirrors. The first mirror of the raster-scanning pair determines the line-scan rate of the display and is driven at its resonant frequency which is on the order of 4.7 kHz. The second mirror, driven at a frequency below its resonance and scanning orthogonally to the first mirror, determines the image refresh rate. Both mirrors have a maximum optical scanning angle of 15/spl deg/. Single-chip and two-chip scanners are demonstrated. The resolution of the single-chip display, based on average pixel size, is 102/spl times/119 pixels. The curvature of the mirror surfaces are characterized and optically compensated to achieve this resolution.
Structure−function studies of an engineered scaffold protein derived from Stefin A. II: Development and applications of the SQT variant (2011)

Constrained binding peptides (peptide aptamers) may serve as tools to explore protein conformations and disrupt protein-protein interactions. The quality of the protein scaffold, by which the binding peptide is constrained and presented, is of crucial importance. SQT (Stefin A Quadruple Mutant-Tracy) is our most recent development in the Stefin A-derived scaffold series. Stefin A naturally uses three surfaces to interact with its targets. SQT tolerates peptide insertions at all three positions. Peptide aptamers in the SQT scaffold can be expressed in bacterial, yeast and human cells, and displayed as a fusion to truncated pIII on phage. Peptides that bind to CDK2 can show improved binding in protein microarrays when presented by the SQT scaffold. Yeast two-hybrid libraries have been screened for binders to the POZ domain of BCL-6 and to a peptide derived from PBP2', specific to methicillin-resistant Staphylococcus aureus. Presentation of the Noxa BH3 helix by SQT allows specific interaction with Mcl-1 in human cells. Together, our results show that Stefin A-derived scaffolds, including SQT, can be used for a variety of applications in cellular and molecular biology. We will henceforth refer to Stefin A-derived engineered proteins as Scannins.
Liposomal malaria vaccine in humans: a safe and potent adjuvant strategy. (1992)

This study describes the safety and immunogenicity of a liposome-based vaccine injected into human subjects. Thirty healthy adult male volunteers were immunized with a liposome-encapsulated recombinant protein (R32NS181) containing epitopes from the repeat region of the circumsporozoite protein of Plasmodium falciparum. This antigen had previously been found to be poorly immunogenic in humans when it was adsorbed with Al(OH)3. In the present study, R32NS181 was encapsulated in liposomes containing monophosphoryl lipid A that were subsequently adsorbed to Al(OH)3. Increasing doses of liposomes containing antigen and monophosphoryl lipid A were used, but the liposomes were always adsorbed to the same dose of Al(OH)3. R32-specific serum IgG antibody responses to liposome-encapsulated R32NS181 were much higher than levels attained previously in humans with R32NS181 adsorbed to Al(OH)3. Geometric mean specific IgG levels after three doses ranged from 14 to 33 micrograms/ml. Sera from volunteers receiving the two highest doses inhibited P. falciparum sporozoite invasion of cultured hepatoma cells by an average of 92%, a result that was again superior to previously reported vaccines. Moderate but acceptable transient local reactogenicity was noted at high doses of the vaccine formulation, but little or no systemic toxicity was seen despite liposomal monophosphoryl lipid A doses up to 2200 micrograms. We conclude that encapsulation of poorly immunogenic circumsporozoite protein repeat peptides in monophosphoryl lipid A-containing liposomes is a successful adjuvant strategy in humans for inducing high levels of specific antibody production.
Band-gap variation and a self-redox effect induced by compositional deviation in ZnxGa2O3+x:Cr3+ persistent phosphors (2014)

We made a systematic investigation on the optical properties of non-doped and Cr-doped ZnxGa2O3+x (0.98 ≤ x ≤ 1.02) spinel crystals. Absorption, photoluminescence excitation, and persistent luminescence excitation spectra indicated that the bottom of the conduction band (CB) was affected (i) by compositional deviation from stoichiometry or (ii) by atmosphere control in a similar way. By constructing an energy level diagram, a broad distribution of trap depth in a Cr3+-doped ZnxGa2O3+x sample with a composition of excess Zn or in one prepared in an O2 atmosphere was attributed to lowering of the CB bottom, which resulted in faster decay of persistent luminescence in these two samples. Defect chemical reactions revealed that the anti-site species of Zn′Ga may be the reason for lowering of the CB bottom. A self-redox effect of Cr ions induced by the compositional deviation was found and explained by the defect reactions. The investigation indicated that the composition with slight Zn deficiency is important to obtain a narrow distribution of trap depths and longer persistent luminescence, however the self-reduction effect of Cr ions in the Zn deficient composition also needs to be considered.
Blockade of B7-H1 Suppresses the Development of Chronic Intestinal Inflammation (2003)

A newly identified costimulatory molecule, programmed death-1 (PD-1), provides a negative signal that is essential for immune homeostasis. However, it has been suggested that its ligands, B7-H1 (PD-L1) and B7-dendritic cells (B7-DC; PD-L2), could also costimulate T cell proliferation and cytokine secretion. Here we demonstrate the involvement of PD-1/B7-H1 and B7-DC interaction in the development of colitis. We first examined the expression profiles of PD-1 and its ligands in both human inflammatory bowel disease and a murine chronic colitis model induced by adoptive transfer of CD4(+)CD45RB(high) T cells to SCID mice. Second, we assessed the therapeutic potential of neutralizing anti-B7-H1 and/or B7-DC mAbs using this colitis model. We found significantly increased expression of PD-1 on T cells and of B7-H1 on T, B, and macrophage/DCs in inflamed colon from both inflammatory bowel disease patients and colitic mice. Unexpectedly, the administration of anti-B7-H1, but not anti-B7-DC, mAb after transfer of CD4(+)CD45RB(high) T cells suppressed wasting disease with colitis, abrogated leukocyte infiltration, and reduced the production of IFN-gamma, IL-2, and TNF-alpha, but not IL-4 or IL-10, by lamina propria CD4(+) T cells. These data suggest that the interaction of PD-1/B7-H1, but not PD-1/B7-DC, might be involved in intestinal mucosal inflammation and also show a possible role of interaction between B7-H1 and an as yet unidentified receptor for B7-H1 in inducing T cell activation.