gebhart/patrepeval huggingface dataset:
Induction of proinflammatory cytokines by a soluble factor of Propionibacterium acnes: implications for chronic inflammatory acne (1995)

Although many cytokines have been implicated in the development and persistence of inflammatory immune responses, it is unknown if any of these are important in inflammatory acne. This study investigated the production of the proinflammatory cytokines interleukin-8 (IL-8), IL-1 beta, and tumor necrosis factor alpha (TNF-alpha) by human monocytic cell lines, ThP-1 and U937, and by freshly isolated peripheral blood mononuclear cells from acne patients. Both Propionibacterium acnes and supernatants obtained from 72-h P. acnes cultures could induce significant concentrations of IL-1 beta, TNF-alpha, and IL-8 by both cell lines and by peripheral blood mononuclear cells as determined by enzyme-linked immunosorbent assay. There was no significant difference between acne and non-acne subjects. Endotoxin quantification and addition of polymyxin B to assays indicated no lipopolysaccharide (LPS) contamination. P. acnes supernatant was fractionated into components with molecular weights of < 3,000, < 10,000, and < 30,000 and assayed for the ability to induce IL-8 and TNF production in ThP-1 cells. Nearly 90% of the original activity was found in the < 30,000-molecular-weight fraction, 50% was in the < 10,000-molecular-weight fraction, and only 15% remained in the < 3,000-molecular-weight fraction. The effluent from the < 3,000-molecular-weight fraction contained about 70% activity, indicating that the inducing factor was not retained in the membrane. Incubation of P. acnes supernatant with various concentrations of mutanolysin or lysozyme resulted in a loss of 60% of the original activity. The addition of jimson lectin, which binds peptidoglycan, resulted in a loss of 70% of the activity in a dose-response manner, whereas peanut lectin had little or no effect on the activity. Heating of the P. acnes supernatant to 65 degrees C also had no effect on the activity. Blocking of CD14, a receptor for both LPS and peptidoglycan, reduced cytokine production by > 50%, suggesting that the soluble stimulating factor may be a secreted form of peptidoglycan-polysaccharide.
Integrated navigation system using camera and gimbaled laser scanner for indoor and outdoor autonomous flight of UAVs (2013)

This paper describes an integrated navigation sensor module, including a camera, a laser scanner, and an inertial sensor, for unmanned aerial vehicles (UAVs) to fly both indoors and outdoors. The camera and the gimbaled laser sensor work in a complementary manner to extract feature points from the environment around the vehicle. The features are processed using an online extended Kalman filter (EKF) in simultaneous localization and mapping (SLAM) algorithm to estimate the navigational states of the vehicle. In this paper, a new method is proposed for calibrating a camera and a gimbaled laser sensor. This calibration method uses a simple visual marker to calibrate the camera and the laser scanner with each other. We also propose a real-time navigation algorithm based on the EKF SLAM algorithm, which is suitable for our camera-laser sensor package. The algorithm merges image features with laser range data for state estimation. Finally, these sensors and algorithms are implemented on our octo-rotor UAV platform and the result shows that our onboard navigation module can provide a real-time three-dimensional navigation solution without any assumptions or prior information on the surroundings.
Effects of niacin-bound chromium and grape seed proanthocyanidin extract on the lipid profile of hypercholesterolemic subjects: a pilot study. (2000)

Hypercholesterolemia, a significant cardiovascular risk factor, is prevalent in the American population. Many drugs lower circulating cholesterol levels, but they are not infrequently associated with severe side effects. Accordingly, natural means to lower cholesterol levels safely would be welcomed. We examined 40 hypercholesterolemic subjects (total cholesterol 210-300 mg/dL) in a randomized, double-blind, placebo-controlled study. The four groups of ten subjects received either placebo bid, chromium polynicotinate (Cr) 200 microg bid, grape seed extract (GSE) 100 mg bid, or a combination of Cr and GSE at the same dosage bid. Over two months, the average percent change +/- SEM in the total cholesterol from baseline among groups was: placebo -3.5% +/- 4, GSE -2.5% +/- 2, Cr -10% +/- 5, and combination -16.5% +/- 3. The decrease in the last group was significantly different from placebo (p < 0.01). The major decrease in cholesterol concentration was in the LDL levels: placebo -3.0% +/- 4, GSE -1.0% +/- 2.0, Cr -14% +/- 4.0, and the combination -20% +/- 6.0. Again, the combination of Cr and GSE significantly decreased LDL when compared to placebo (p<0.01). HDL levels essentially did not change among the groups. Also, there was no significant difference in the triglyceride concentrations among the groups; and no statistically significant differences were seen in the levels of autoantibodies to oxidized LDL (Ox-LDL). However, the trend was for the two groups receiving GSE to have greater decreases in the latter parameter, i.e., -30.7% and -44.0% in the GSE and combined groups in contrast to -17.3% and -10.4% in the placebo and chromium groups. We determined the number of subjects in each group who decreased autoantibodies to oxidized LDL greater than 50% over eight weeks and found these ratios among groups: placebo = 2/9, Cr = 1/10, GSE = 6/10, and combined = 3/8. Thus, 50% of subjects (9/18) receiving GSE had a greater than 50% decrease in autoantibodies compared to 16% (3/19) in the two groups not receiving GSE. No significant changes occurred in the levels of circulating homocysteine and blood pressure among the four groups. We conclude that a combination of Cr and GSE can decrease total cholesterol and LDL levels significantly. Furthermore, there was a trend to decrease the circulating autoantibodies to oxidized LDL in the two groups receiving GSE.
Signaling Pathway Involved in the Activation of Heart 6-Phosphofructo-2-kinase by Insulin (1996)

Incubation of isolated rat cardiomyocytes with insulin increased 2-deoxyglucose uptake, glycogen synthesis, and fructose 2, 6-bisphosphate content. Half-maximal effects were obtained with 1-2 nM insulin. The insulin-induced increase in fructose 2,6-bisphosphate content was preceded by a 2-3-fold activation of 6-phosphofructo-2-kinase, which was independent of glucose transport. Insulin activated phosphatidylinositol 3-kinase and p70 ribosomal S6 kinase (p70 S6 kinase), but had no significant effect on mitogen-activated protein kinase, although phorbol 12-myristate 13-acetate activated the latter. The effect of insulin on fructose 2, 6-bisphosphate, 6-phosphofructo-2-kinase, and phosphatidylinositol 3-kinase was blocked by wortmannin. However, rapamycin, which inhibited p70 S6 kinase activation, and PD 98059, an inhibitor of the mitogen-activated protein kinase pathway, had no effect on the insulin-induced activation of 6-phosphofructo-2-kinase. Heart 6-phosphofructo-2-kinase can therefore be regarded as a glycolytic target of insulin. Its activation by insulin might be mediated by phosphatidylinositol 3-kinase.
Adaptor protein Lnk negatively regulates the mutant MPL, MPLW515L associated with myeloproliferative disorders (2007)

Recently, activating myeloproliferative leukemia virus oncogene (MPL) mutations, MPLW515L/K, were described in myeloproliferative disorder (MPD) patients. MPLW515L leads to activation of downstream signaling pathways and cytokine-independent proliferation in hematopoietic cells. The adaptor protein Lnk is a negative regulator of several cytokine receptors, including MPL. We show that overexpression of Lnk in Ba/F3-MPLW515L cells inhibits cytokine-independent growth, while suppression of Lnk in UT7-MPLW515L cells enhances proliferation. Lnk blocks the activation of Jak2, Stat3, Erk, and Akt in these cells. Furthermore, MPLW515L-expressing cells are more susceptible to Lnk inhibitory functions than their MPL wild-type (MPLWT)-expressing counterparts. Lnk associates with activated MPLWT and MPLW515L and colocalizes with the receptors at the plasma membrane. The SH2 domain of Lnk is essential for its binding and for its down-regulation of MPLWT and MPLW515L. Lnk itself is tyrosine-phosphorylated following thrombopoietin stimulation. Further elucidating the cellular pathways that attenuate MPLW515L will provide insight into the pathogenesis of MPD and could help develop specific therapeutic approaches.
Production of Liquid Alkanes by Aqueous-Phase Processing of Biomass-Derived Carbohydrates (2005)

Liquid alkanes with the number of carbon atoms ranging from C7 to C15 were selectively produced from biomass-derived carbohydrates by acid-catalyzed dehydration, which was followed by aldol condensation over solid base catalysts to form large organic compounds. These molecules were then converted into alkanes by dehydration/hydrogenation over bifunctional catalysts that contained acid and metal sites in a four-phase reactor, in which the aqueous organic reactant becomes more hydrophobic and a hexadecane alkane stream removes hydrophobic species from the catalyst before they go on further to form coke. These liquid alkanes are of the appropriate molecular weight to be used as transportation fuel components, and they contain 90% of the energy of the carbohydrate and H2 feeds.
Protein disulfide isomerase mutant lacking its isomerase activity accelerates protein folding in the cell (1995)

We investigated the effect of protein disulfide isomerase (PDI) on in vivo protein folding of human lysozyme (h-LZM) in a specially constructed yeast coexpression system. Coexpression with PDI increased the amounts of intracellular h-LZM with the native conformation, leading to an increase in h-LZM secretion. The results indicated that PDI is a real catalyst of protein folding in the cell. The secretion of h-LZM increased even when both active sites of PDI were disrupted, suggesting that the effect of PDI resulted from a function other than the formation of disulfide bonds. This is the first finding that PDI without isomerase activity accelerates protein folding in vivo.
Targeting kidney mesangium by nanoparticles of defined size (2011)

Nanoparticles are being investigated for numerous medical applications and are showing potential as an emerging class of carriers for drug delivery. Investigations on how the physicochemical properties (e.g., size, surface charge, shape, and density of targeting ligands) of nanoparticles enable their ability to overcome biological barriers and reach designated cellular destinations in sufficient amounts to elicit biological efficacy are of interest. Despite proven success in nanoparticle accumulation at cellular locations and occurrence of downstream therapeutic effects (e.g., target gene inhibition) in a selected few organs such as tumor and liver, reports on effective delivery of engineered nanoparticles to other organs still remain scarce. Here, we show that nanoparticles of ~75 ± 25-nm diameters target the mesangium of the kidney. These data show the effects of particle diameter on targeting the mesangium of the kidney. Because many diseases originate from this area of the kidney, our findings establish design criteria for constructing nanoparticle-based therapeutics for targeting diseases that involve the mesangium of the kidney.
Bevacizumab (a monoclonal antibody to vascular endothelial growth factor) to prolong progression-free survival in first-line colorectal cancer (CRC) in subjects who are not suitable candidates for first-line CPT-11 (2004)

3516 Background: Bevacizumab [Avastin (BV)] is a recombinant, humanized monoclonal antibody directed against vascular endothelial growth factor. As presented at ASCO 2003, the addition of BV to IFL chemotherapy prolonged median survival from 15.61 months to 20.34 months (p = 0.00004). This was a companion trial that studied the addition of BV to FU/LV chemotherapy in subjects who were not optimal candidates for first-line irinotecan because of age or performance status. Methods: Approximately 200 patients were to be randomized to receive the Roswell Park regimen of FU/LV placebo or FU/LV/BV (5 mg/kg every two weeks). The primary efficacy endpoint was survival; secondary efficacy endpoints included progression free survival (PFS), objective response rate (ORR) and duration of response. Results: 209 patients were randomized between September 7, 2000 and May 6, 2002. For the two groups, FU/LV/Placebo and FU/LV/BV, baseline characteristics were similar. Efficacy and selected safety results are as follows: Conclusions: The addition of BV to FU/LV chemotherapy, in subjects who are not optimal candidates for first-line CPT-11 resulted in a clinically meaningful and statistically significant prolongation of progression-free survival and trends towards improved response rate,duration of response, and survival as compared with FU/LV chemotherapy alone. The addition of BV to FU/LV was well tolerated; Grade 3 hypertension, easily managed with oral medications was increased with BV, The uncommon but life-threatening event of gastrointestinal perforation occurred in 2 patients in the FU/LV/BV arm Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Inc. Genentech, Inc. Genentech, Inc. Genentech, Inc.
Appropriate dose of dexmedetomidine for the prevention of emergence agitation after desflurane anesthesia for tonsillectomy or adenoidectomy in children: up and down sequential allocation (2015)

Clinical Research Information Service KCT0000126 .
Liver‐restricted expression of the canine factor VIII gene facilitates prevention of inhibitor formation in factor VIII‐deficient mice (2009)

These data suggest that AAV8 vector-mediated liver-restricted cFVIII gene expression is sufficient for immune hypo-responsiveness to transgene-derived cFVIII in fviii(-/-) mice.
ChemInform Abstract: Synthon Disconnection Strategy for the Synthesis Design of “Coelenterazine” ‐ A Bioluminescent Marine Natural Product Used in Bioassays (2013)

Abstract Review: 30 refs.
741. Self-Complementary Adeno-Associated Virus Vectors: Packaging Capacity and Purity (2006)

Recombinant adeno-associated virus 2 (AAV) vectors are currently in use in Phase I/II clinical trials for the potential treatment of several diseases. However, the single-stranded nature of the AAV genome impacts on transgene expression from these vectors. Although self- complementary AAV (scAAV) vectors, which contain double- stranded genomes, and therefore bypass the requirement for viral second-strand DNA synthesis, lead to a significant increase in AAV- mediated transduction efficiency, the packaging capacity of these vectors ( 2.4 kb) is significantly smaller than the conventional AAV vectors (4.8 kb). In order to initially determine the maximum packaging capacity of scAAV vectors, we constructed GFP gene expression cassettes of various sizes ranging from 2.2 kb to 4.0 kb. Surprisingly, each of these genomes could be encapsidated into mature progeny virions with very similar titers. The transduction efficiency of vectors containing <3.3 kb genomes was significantly higher than those containing 3.5 kb genomes or larger. When encapsidated genomes from each of the vector stocks were analyzed on alkaline agarose gels, we observed that 45% of viral DNA was double- stranded, and 55% was still single-stranded in vectors containing up to 3.3 kb genomes, and 3.5 kb and larger genomes were packaged only as single-stranded DNA. These data suggest that the maximum packaging capacity of scAAV vectors is 3.3 kb. We also observed that double-stranded AAV genomes larger that 3.5 kb could be encapsidated into virions composed of only two capsid proteins VP1 and VP3. However, the ratio of single-stranded:double-stranded vectors was higher in VP1-VP3 capsids compared with the wild- type capsids. Each of these vectors containing up to 3.3 kb genomes was biologically active, and their transduction efficiencies were very similar. The generation of single-stranded genomes was due to the use of AAV helper plasmid that contains the Rep gene with an ATG start codon, known to lead to higher levels of expression of Rep proteins. We further examined the mechanism of production of single- stranded genomes. Following rescue and replication of AAV genomes and digestion with Msc I restriction endonuclease, we determined that the terminal resolution site (trs) in one of the inverted terminal repeats in the AAV genome was not repaired. We hypothesize that the presence of cryptic ‘trs-like’ sites in recombinant AAV genomes leads to the generation of single-stranded DNA. Taken together, these studies demonstrate that it is feasible to achieve encapsidation of larger genomes into scAAV vectors than was suggested originally, but also underscore the need to exercise caution in using the appropriate helper plasmid in order to generate purified preparations of scAAV stocks that are completely free of single-stranded DNA- containing vectors capable of high-efficiency transduction, which has implications in the optimal use of these vectors in human gene therapy.
Forces acting on the fission yeast anaphase spindle (1996)

The fission yeast mitotic spindle consists of three sets of microtubules: one that extends between the chromosomes and the spindle pole bodies (SPBs); one that extends between the two SPBs forming a region of overlap; and a third, the so-called astral microtubules, that associates laterally with the cytoplasmic face of the SPBs, during anaphase B. The major bundles of the latter can exist with equal probability in two configurations which we have termed parallel and convergent. Mitosis in fission yeast is characterised by an extended anaphase B during which the spindle elongates from 2 mu m (the diameter of the interphase nucleus) to about 14 mu m, spanning the entire length of the cell. Anaphase B spindles viewed by indirect immunofluorescence microscopy frequently appeared bowed but only when the astral microtubules were in the convergent orientation. To investigate the possible significance of this observation, we have examined the situation in the abnormally long spindles that are formed in cells in which cell length has been extended either by overexpression of the weel + gene or by inactivation of the cdc25 + gene. The spindles in these strains were often considerably longer (up to 30 mu m) than in wild type cells but, unlike the latter, did not extend the entire length of the cell. Bowed spindles were again observed but only when the astral microtubules were convergent. We discuss these findings in the context of the astral microtubules either exerting a pulling force on the poles of the anaphase B spindle, or counteracting a pushing force generated by sliding of anti-parallel pole to pole microtubules of the mitotic spindle, or both of the above.
Fetal DNA in uterine vein blood (1993)

Our results argue against the often-stated hypothesis of different ratios of fetal to maternal DNA in the uterine vein versus peripheral blood, and indicate that even delivery does not seem to increase the flow of fetal cells into the maternal circulation.
Allogeneic nonmyeloablative hematopoietic cell transplantation in metastatic colon cancer: tumor-specific T cells directed to a tumor-associated antigen are generated in vivo during GVHD (2006)

A pilot study was conducted to evaluate safety and activity of nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) in colorectal carcinoma (CRC) and to determine whether a T-cell response to a tumor-associated antigen (TAA) was induced. Fifteen patients with metastatic CRC underwent HCT from human leukocyte antigen (HLA)-matched siblings after a nonmyeloablative conditioning regimen. All patients engrafted with a median donor T-cell chimerism of 72% at day +56. Eight patients experienced grades II to IV acute graft-versus-host disease (GVHD). Despite progressive disease before HCT, partial remission and disease stabilization longer than 90 days were observed in 1 and 3 patients, respectively. Induction of TAA-specific T cells was evaluated with a carcinoembryonic antigen (CEA)-specific HLA-A(*)0201 pentamer in 6 patients with CRC. CEA-specific CD8(+) T cells were detected in 3 of 3 patients concomitant with GHVD onset, but not in 3 of 3 patients without GVHD. They were also not detected in 9 of 9 control patients with GVHD who received transplants for diagnoses other than CRC. Antitumor activity of CEA-specific T cells was also validated in vitro. In one patient, the induction of CEA-specific T cells was associated with a decrease of serum CEA levels and a partial response. Thus, graft-versus-host reactions associated with allogeneic HCT can trigger the generation of T cells specific for CEA, and this may be associated with a clinical response.
Deep Laplacian Pyramid Networks for Fast and Accurate Super-Resolution (2017)

Convolutional neural networks have recently demonstrated high-quality reconstruction for single-image super-resolution. In this paper, we propose the Laplacian Pyramid Super-Resolution Network (LapSRN) to progressively reconstruct the sub-band residuals of high-resolution images. At each pyramid level, our model takes coarse-resolution feature maps as input, predicts the high-frequency residuals, and uses transposed convolutions for upsampling to the finer level. Our method does not require the bicubic interpolation as the pre-processing step and thus dramatically reduces the computational complexity. We train the proposed LapSRN with deep supervision using a robust Charbonnier loss function and achieve high-quality reconstruction. Furthermore, our network generates multi-scale predictions in one feed-forward pass through the progressive reconstruction, thereby facilitates resource-aware applications. Extensive quantitative and qualitative evaluations on benchmark datasets show that the proposed algorithm performs favorably against the state-of-the-art methods in terms of speed and accuracy.
Effect of tetracycline on osteogenesis in vitro (1966)

Abstract The effect of tetracycline on developing bones was explored in organotypic tissue culture. Such culture conditions proved to be suitable for certain experiments dealing with the “teratogenic” effect of drugs, and the first part of the paper examines the possibilities, limitations and fallacies of this technique. Embryonic mouse bones cultivated in vitro show rapid incorporation of tetracycline, and after 30 minutes of cultivation a definite fluorescence is seen. The drug is incorporated at least into two fractions: one which is rapidly released after the withdrawal of tetracycline and one which remains in the calcium‐containing zones of the bone. Tetracycline in concentrations of the order of 5 μg/ml completely inhibits the elongation of the calcified zone of the bone rudiments and the increase of their total calcium. However, experiments with labeled calcium still show an incorporation in the presence of tetracycline although no cumulative uptake is seen. The results thus indicate the existence of a rapidly incorporated calcium fraction which is independent of tetracycline. The inhibition of calcification is reversible up to some five days of treatment, whereafter a transfer to normal medium does not lead to a recovery, and the mineralization seems to be irreversibly blocked. It is concluded that the results speak in favor of the theory of a direct action of tetracycline on the formations of the bone salts, rather than interference with enzymatic activity dependent on divalent cations.