gebhart/patrepeval huggingface dataset:
Characterization of RT6‐Bearing Rat Lymphocytes. II. Developmental Relationships of RT6‐ and RT6+T Cells (1990)

The derivation of RT6+ T cells from postthymic RT6- T cells in weanling rats was formally demonstrated by the intravenous transfer ("parking") of highly purified populations of RT6- lymph node T cells into thymectomized, irradiated, and bone-marrow-reconstituted (TXBM) RT6 and RT7 alloantigen-disparate recipients. Parallel experiments in irradiated and bone-marrow-reconstituted rats, and in rats whose RT6+ T cells had been depleted by injection of DS4.23 anti-RT6.1 mAb, suggested that the transit time between the pre-RT6+ and the RT6+ T-cell compartments approximated 4-5 days. A more precise estimate of the transit time was made by linear regression analysis of the generation of RT6+ T cells in rats that were treated with DS4.23 mAb at timed intervals after thymectomy. This study indicated that 50% of the pre-RT6+ T cells differentiated into RT6+ cells within 4 days, 75% within 8 days, and more than 90% within 16 days. Despite the apparent absence of pre-RT6- T cells 3 weeks after thymectomy, numerous RT6- T cells persisted for at least 10 weeks in thymectomized rats, even after treatment with DS4.23 mAb. Moreover, these RT6+ T cells failed to generate RT6+ T cells after transfer into adoptive hosts. Quantitative and phenotypic analyses indicated that this population of "true" RT6- T cells: (1) constitutes approximately 50% of the total RT6- T cells normally found in control rats; (2) contains CD4+ and CD8+ subsets; (3) expresses both the CD5 pan-T-cell antigen (which is absent from NK cells) and the R73 alpha/beta TCR constant-region determinant; and (4) lacks sIgM. Hence, the present results indicate that the "true" RT6- and the RT6+ T-cell subsets have stable antigenic phenotypes and represent developmentally discrete populations of postthymic cells in normal rats. This is supported by associated phenotypic and functional studies that suggest that the "true" RT6- T-cell subset contains antigenically naive and/or autoreactive clonotypes, whereas the RT6+ T-cell subset contains memory and/or regulatory cells. It remains to be determined whether the "true" RT6- and the RT6+ subsets represent separate lineages of T cells or a single lineage at different stages of activation or maturation.
Mass Spectrometry of Polymers (2001)

Preface, G. Montaudo and R.P. Lattimer Introduction to Mass Spectromety of Polymers, M.J. Polce and C. Wesdemiotis Polymer Characteriztion Methods, G. Montaudo and M.S. Montaudo Pyrolysis Gas Chromatography/Mass Spectrometry (Py-GC/MS), S. Tsuge and H. Ohtani Electrospray Ionization (ESI-MS) and On-Line Liquid Chromatography/Mass Spectrometry (LC/MS), L. Prokai Direct Pyrolysis into the Ion Source (DPMS), G. Montaudo and C. Puglisi Field Ionization (FI-MS) and Field Desorption (FD-MS), R. P. Lattimer Fast Atom bombardment (FAB-MS), G. Montaudo and F. Samperi Time-of-Flight Secondary Ion Mass Spectrometry (FT-MS), S.J. Pastor and C.L. Wilkins Laser Fourier Transform Mass spectrometry (FT-MS), S.J. Pastor and C.L. Wilkins Matrix-Assisted Laser Desorption/Ionizationi Mass Spectrometry (MALDI-MS), G. Montaudo, M.S. Montaudo, and F. Samperi Two-Step Laser Desorption Mass Spectrometry, M.S. deVries and H.E. Hunziker
Subsurface Raman Spectroscopy and Mapping Using a Globally Illuminated Non-Confocal Fiber-Optic Array Probe in the Presence of Raman Photon Migration (2006)

We report the use of a fiber-optic probe with global illumination and an array of 50 collection fibers (PhAT probe, Kaiser Optical Systems, Inc.) to obtain Raman spectra and 50 spatial element maps of polymers through overlayers of other polymers that are highly scattering. Band target entropy minimization (BTEM) is used to recover the spectra of the subsurface components and generate maps of their distributions. This approach to subsurface mapping is tested with model systems consisting of two or three layers of polyethylene, polytetrafluoroethylene (Teflon), and polyoxymethylene (Delrin) arranged in different geometries. Raman spectra and maps were obtained through overlayer thicknesses of up to 13 mm. Subsurface spatial resolution is achieved because each fiber views an asymmetric distribution of Raman scattered light from surface and subsurface components that depends on the position of the fiber relative to the depth and position of a component and the extent of photon diffusion through the system.
A neural network for Ego-motion estimation for optical flow (1995)

In this work we consider the problem to determine qualitative information about the motion of a viewer moving in a stationary environment. First the optical flow (OF) is computed using a token based approach estimating the 2D velocity vectors only for some interesting points. Then our method estimates the motion of the viewer using only the available sparse OF. A neural network extracts information about stable points useful for the computation of vehicle&amp;apos;s heading and Time-to-Collision (TTC). A number of experiments showing the efficacy and robustness of the method have been performed both on synthetic image sequences and on real images acquired by a CCD camera mounted on a mobile platform. 1
Targeting tumor-initiating cells: Eliminating anabolic cancer stem cells with inhibitors of protein synthesis or by mimicking caloric restriction (2015)

We have used an unbiased proteomic profiling strategy to identify new potential therapeutic targets in tumor-initiating cells (TICs), a.k.a., cancer stem cells (CSCs). Towards this end, the proteomes of mammospheres from two breast cancer cell lines were directly compared to attached monolayer cells. This allowed us to identify proteins that were highly over-expressed in CSCs and/or progenitor cells. We focused on ribosomal proteins and protein folding chaperones, since they were markedly over-expressed in mammospheres. Overall, we identified >80 molecules specifically associated with protein synthesis that were commonly upregulated in mammospheres. Most of these proteins were also transcriptionally upregulated in human breast cancer cells in vivo, providing evidence for their potential clinical relevance. As such, increased mRNA translation could provide a novel mechanism for enhancing the proliferative clonal expansion of TICs. The proteomic findings were functionally validated using known inhibitors of protein synthesis, via three independent approaches. For example, puromycin (which mimics the structure of tRNAs and competitively inhibits protein synthesis) preferentially targeted CSCs in both mammospheres and monolayer cultures, and was ~10-fold more potent for eradicating TICs, than "bulk" cancer cells. In addition, rapamycin, which inhibits mTOR and hence protein synthesis, was very effective at reducing mammosphere formation, at nanomolar concentrations. Finally, mammosphere formation was also markedly inhibited by methionine restriction, which mimics the positive effects of caloric restriction in cultured cells. Remarkably, mammosphere formation was >18-fold more sensitive to methionine restriction and replacement, as directly compared to monolayer cell proliferation. Methionine is absolutely required for protein synthesis, since every protein sequence starts with a methionine residue. Thus, the proliferation and survival of CSCs is very sensitive to the inhibition of protein synthesis, using multiple independent approaches. Our findings have important clinical implications, since they may also explain the positive therapeutic effects of PI3-kinase inhibitors and AKT inhibitors, as they ultimately converge on mTOR signaling and would block protein synthesis. We conclude that inhibition of mRNA translation by pharmacological or protein/methionine restriction may be effective strategies for eliminating TICs. Our data also indicate a novel mechanism by which caloric/protein restriction may reduce tumor growth, by targeting protein synthesis in anabolic tumor-initiating cancer cells.
Factor VIIa for Correction of Traumatic Coagulopathy (2004)

FVIIa therapy lead to an immediate reduction in coagulopathic hemorrhage in most cases, accompanied by a significant improvement in laboratory measures. Application of FVIIa as a therapy of last resort makes the identification of equivalent control patients difficult. Use of FVIIa should be considered for any patient with coagulopathic hemorrhage in which surgically-accessible bleeding has been controlled. Prospective trials of FVIIa in patients with traumatic coagulopathy are strongly indicated, and should focus on appropriate patient selection and the dose and timing of therapy.
Confirmation of the helical structure of the 5'/3' termini of the essential DNA packaging pRNA of phage phi 29. (1995)

Bacteriophage phi 29 is typical of double-stranded DNA viruses in that its genome is packaged into a preformed procapsid during viral assembly. An intriguing feature of phi 29 is the presence of a 120-base virus-encoded RNA (pRNA) that is indispensable for DNA packaging. Phylogenetic comparison of similar RNAs in numerous phages has revealed that the secondary structure of the pRNA is well conserved. Computer analysis predicts the presence of an extensive segment of helix with three single-base bulges generated by the pairing of the 5' and 3' ends. The desire to understand the role played by the pRNA in DNA packaging has led to a mutational analysis of the 5'-/3'-terminal region, which is believed to be important in DNA translocation. Deletion of 3 bases from the 3' end of the RNA, shortening the pRNA from 120 to 117 bases, was tolerated without loss of activity, but additional deletion of the base 117 resulted in 100-fold less activity, and a 115-base pRNA was virtually nonfunctional. Additionally, the three unpaired one-base bulges within the helical stretches of the paired proximate ends were nonessential for pRNA activity, as demonstrated by deletion of the bulge individually. An extensive series of helix disruptions by single- and multiple-base substitution almost invariably led to the loss of DNA packaging activity. Additional mutations that restored predicted base pairings rescued pRNA activity. This second site suppression confirmed that the 5'- and 3'-end region was paired and was indeed a helical stretch. The secondary structure was of greater importance than the primary sequence, with the exception of the requirement of an adenine at either the third or fourth position. The specific requirement of an adenine in phi 29 pRNA at this position, as well as conservation of this position in other phage pRNAs, implicates that this base may play a special role in either the DNA-packaging reaction or the maintenance of the pRNA tertiary structure.
Utilization of the mouse large intestine to select an Escherichia coli F-18 DNA sequence that enhances colonizing ability and stimulates synthesis of type 1 fimbriae (1993)

Escherichia coli F-18, a normal human fecal isolate, is an excellent colonizer of the streptomycin-treated mouse large intestine. E. coli F-18 Col-, a derivative of E. coli F-18 which no longer makes the E. coli F-18 colicin, colonizes the large intestine as well as E. coli F-18 when fed to mice alone but is eliminated when fed together with E. coli F-18. Random sequences of E. coli F-18 DNA were cloned into pRLB2, a par-B-stabilized derivative of pHC79. The entire gene library was transformed into E. coli F-18 Col- and fed to streptomycin-treated mice. The mouse large intestine selected a predominant clone which contained a recombinant plasmid (pRLB7) that enhanced E. coli F-18 Col- colonizing ability 100-fold but did not stimulate colicin synthesis. Moreover, pRLB7 simultaneously improved the survival of E. coli F-18 Col- in stationary phase in vitro, utilizing nutrients derived from mouse cecal mucus, and stimulated synthesis of both type 1 fimbriae and three E. coli F-18 Col- outer membrane proteins (74, 71, and 69 kDa). The 6.5-kb E. coli F-18 DNA sequence in pRLB7 does not contain either the fim operon or pilG (hns), both known to be involved in type 1 fimbrial synthesis. The sequence encodes six proteins, all smaller than the three E. coli F-18 Col- outer membrane proteins whose synthesis it stimulates. Collectively, the results suggest that the cloned E. coli F-18 DNA sequence contains one or more regulators of E. coli F-18 Col- operons expressed in the mouse large intestine in vivo and in isolated mouse cecal mucus in vitro.
Effect of modified glucose uptake using genetic engineering techniques on high‐level recombinant protein production in escherichia coli dense cultures (1994)

Reduction of acetate excretion using a modified cellular glucose uptake rate was examined. An Escherichia coli strain bearing a mutationin ptsG, a gene encoding enzyme II in glucose phosphotransferase system (PTS), was constructed and characterized. The growth rate of the mutant strain was slower than its parent in glucose defined medium, butwas not affected in complex medium. Experimental results using this mutant strain showed a significant improvement in culture performance in simple batch cultivations due to reduced acetate excretion through the modified glucose uptake. Both biomass and recombinant protein productivity were increased by more than 50% with the ptsG mutant when compared to the parent strain. Recombinant protein productivity by the newly constructed strain at a level of more than 1.6 g/L was attained consistently in a simple batch bioreactor. (c) 1994 John Wiley & Sons, Inc.
Induction of vascular leakage through release of bradykinin and a novel kinin by cysteine proteinases from Staphylococcus aureus (2005)

Staphylococcus aureus is a major pathogen of gram-positive septic shock and frequently is associated with consumption of plasma kininogen. We examined the vascular leakage (VL) activity of two cysteine proteinases that are secreted by S. aureus. Proteolytically active staphopain A (ScpA) induced VL in a bradykinin (BK) B(2)-receptor-dependent manner in guinea pig skin. This effect was augmented by staphopain B (SspB), which, by itself, had no VL activity. ScpA also produced VL activity from human plasma, apparently by acting directly on kininogens to release BK, which again was augmented significantly by SspB. Intravenous injection of ScpA into a guinea pig caused BK B(2)-receptor-dependent hypotension. ScpA and SspB together induced the release of leucyl-methionyl-lysyl-BK, a novel kinin with VL and blood pressure-lowering activities that are equivalent to BK. Collectively, these data suggest that production of BK and leucyl-methionyl-lysyl-BK by staphopains is a new mechanism of S. aureus virulence and bacterial shock. Therefore, staphopain-specific inhibitors and kinin-receptor antagonists could be used to treat this disease.
New effective method for the synthesis of oligonucleotides via phosphotriester intermediates (1982)

A rapid and convenient method for the synthesis of deoxyribooligonucleotides has been developed using the phosphotriester approach. The advantage of this methodology for work in solution was successfully demonstrated in synthesis of a number of DNA fragments up to 32-long. Adaptation of the presented method to solid-phase synthesis allows a pentadecamer to be assembled in 4-5 hours using dinucleotides as coupling units.
Specific interaction of lymphocyte function-associated antigen 3 with CD2 can inhibit T cell responses. (1993)

Accessory cell surface molecules, such as T cell antigen CD2 and its ligand lymphocyte function-associated antigen 3 (LFA-3; CD58), are critical costimulatory pathways for optimal T cell activation in response to antigens. Interaction of CD2 with cell surface LFA-3 not only increases T cell/accessory cell adhesion, but also induces signal transduction events involved in the regulation of T cell responses. In this report, we show that specific interactions of LFA-3 with CD2 can result in T cell unresponsiveness to antigenic or mitogenic stimuli in vitro. By deletion of certain regions of the extracellular domain of LFA-3, we localized the CD2 binding site to the first domain of LFA-3. We then demonstrated that a soluble, purified first domain-LFA-3/IgG1 fusion protein (LFA3TIP) interacts with CD2 and binds to the same CD2 epitope as purified multimeric or cell surface-expressed LFA-3. LFA3TIP inhibits tetanus toxoid, hepatitis B surface antigen, anti-CD3 mAb, Con A, and phytohemagglutinin P-induced T cell proliferation, as well as xenogeneic and allogeneic mixed lymphocyte reactions (MLR). Unlike anti-LFA-3 or anti-CD2 monoclonal antibodies (mAbs) which inhibit T cell responses by blocking LFA-3/CD2 binding, LFA3TIP is capable of rendering T cells unresponsive to antigenic stimuli in situations where T cell activation is independent of CD2/LFA-3 interactions. Furthermore, LFA3TIP, but not blocking anti-CD2 mAbs, is capable of inducing T cell unresponsiveness to secondary stimulation in allogeneic MLR. This inhibition of T cell responses by LFA3TIP occurs through a different mechanism from that of mAbs to LFA-3 or CD2.
High-Resolution Waveguide Terahertz Spectroscopy of Partially Oriented Organic Polycrystalline Films (2007)

We have characterized the terahertz (THz) vibrational spectroscopy of organic polycrystalline thin films using the new experimental technique of waveguide terahertz time domain spectroscopy (waveguide THz-TDS). The organic materials used in this study are tetracyanoquinodimethane (TCNQ) and 1,3-dicyanobenzene (13DCB). For each material, a thin film is cast onto one of the inner surfaces of a metal parallel plate waveguide (PPWG), followed by measurement of the low-frequency vibrational spectrum using waveguide THz-TDS. The vibrational spectra of the waveguide films are compared to corresponding vibrational spectra of standard pellet samples made by dispersing the organic solid in transparent polyethylene. We show how the waveguide films produce significantly narrower THz vibrational line shapes and reveal additional spectral lines that are obscured by inhomogeneous broadening effects in the pellet samples. When TCNQ waveguide films are cooled to 77 K, vibrational line widths as sharp as 25-30 gigahertz (0.83-1.0 cm(-1)) at the full width at half-maximum are observed, which are among the narrowest far-infrared line widths measured for this material. The origin of the line-narrowing effect for the waveguide films is the suppression of inhomogeneous broadening due to the planar ordering of the film on the waveguide surface. The TCNQ waveguide films are further characterized using optical microscopic evaluation to understand how film morphology affects the THz vibrational spectrum. X-ray diffraction is used to determine the orientation of the polycrystalline TCNQ films on the PPWG surface and to qualitatively explain the different vibrational line strengths observed for the ordered waveguide film relative to the random pellet.
Immunogenicity and Protection of a Recombinant Human Adenovirus Serotype 35-Based Malaria Vaccine againstPlasmodium yoeliiin Mice (2005)

Given the promise of recombinant adenovirus type 5 (rAd5) as a malaria vaccine carrier in preclinical models, we evaluated the potency of rAd35 coding for Plasmodium yoelii circumsporozoite protein (rAd35PyCS). We chose rAd35 since a survey with serum samples from African subjects demonstrated that human Ad35 has a much lower seroprevalence of 20% and a much lower geometric mean neutralizing antibody titer (GMT) of 48 compared to Ad5 (seroprevalence, 85%; GMT, 1,261) in countries with a high malaria incidence. We also demonstrated that immunization with rAd35PyCS induced a dose-dependent and potent, CS-specific CD8(+) cellular and humoral immune response and conferred significant inhibition (92 to 94%) of liver infection upon high-dose sporozoite challenge. Furthermore, we showed that in mice carrying neutralizing antibody activity against Ad5, mimicking a human situation, CS-specific T- and B-cell responses were significantly dampened after rAd5PyCS vaccination, resulting in loss of inhibition of liver infection upon sporozoite challenge. In contrast, rAd35 vaccine was as potent in naive mice as in Ad5-preimmunized mice. Finally, we showed that heterologous rAd35-rAd5 prime-boost regimens were more potent than rAd35-rAd35 because of induction of anti-Ad35 antibodies after rAd35 priming. The latter data provide a further rationale for developing rAd prime-boost regimens but indicate that priming and boosting Ad vectors must be immunologically distinct and also should be distinct from Ad5. Collectively, the data presented warrant further development of rAd35-based vaccines against human malaria.
Trace polypeptides in cellular extracts and human body fluids detected by two-dimensional electrophoresis and a highly sensitive silver stain. (1979)

Development of a highly sensitive silver stain permits the characterization of trace cellular and body fluid proteins separated by the two-dimensional electrophoresis technique of O'Farrell. Many of the proteins detected by the silver stain in urine, spinal fluid, amniotic fluid, and cells were undetected with the widely used Coomassie blue stain. Trace polypeptides observed in Escherichia coli cell lysates with this silver stain could be detected previously only by growth in radioactive precursors followed by lengthy autoradiography. In situations that do not permit the use of radioactive labeling, as in human clinical studies, the enhanced ability to detect proteins achieved by the silver stain will facilitate metabolic studies and the screening for protein abnormalities in mutational studies and in genetic diseases.
Potential benefits of eicosapentaenoic acid on atherosclerotic plaques (2017)

Residual cardiovascular (CV) risk remains in some patients despite optimized statin therapy and may necessitate add-on therapy to reduce this risk. Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, lowers plasma triglyceride levels without raising low-density lipoprotein cholesterol levels and has potential beneficial effects on atherosclerotic plaques. Animal studies have shown that EPA reduces levels of pro-inflammatory cytokines and chemokines. In clinical trials utilizing a wide spectrum of plaque imaging modalities, EPA has shown beneficial effects on plaque characteristics. Studies of patients with coronary artery disease receiving statin therapy suggest that EPA may decrease plaque vulnerability and prevent plaque progression. EPA also decreased pentraxin-3 and macrophage accumulation. A large, randomized, Japanese study reported that EPA plus a statin resulted in a 19% relative reduction in major coronary events at 5years versus a statin alone in patients with hypercholesterolemia (P=0.011). Icosapent ethyl, a high-purity prescription form of EPA ethyl ester, has been shown to reduce triglyceride levels and markers of atherosclerotic inflammation. Results of an ongoing CV outcomes study will further define the potential clinical benefits of icosapent ethyl in reducing CV risk in high-risk patients receiving statin therapy.