gebhart/patrepeval huggingface dataset:
Effects of irradiation on the release of growth factors from cultured bovine, porcine, and human endothelial cells. (1989)

The effects of radiation on the release of mitogenic factors into the media of cultured endothelial cells of bovine, porcine, and human origins were studied. Although unirradiated controls revealed a significant background activity, single doses of irradiation (20-60 Gy) resulted in a dose-related increased release of growth factor activity, measured by the mitogenic effects of the conditioned media on both 3T3 mouse fibroblasts and unirradiated endothelial cells serving as target cells. Receptor binding competition assays for the platelet-derived growth factor receptor revealed that 12-28% of the total mitogenic activity was due to platelet-derived growth factor-like mitogens. Mitogenic assays using endothelial cells and specific antibody mediated inhibition assays suggested that another component of the mitogenic activity was due to a fibroblast growth factor-like factor. Although radiation resulted in a significant increase in cell death, the enhanced growth factor activities did not appear to result from cell lysis-related leakage of intracellular stores of growth factor. Instead, our data suggest that the growth factors were synthesized de novo and secreted at elevated levels by the cells which maintained postradiation a high level of metabolic activity. Time course studies demonstrated that the growth factors accumulation in the conditioned media started within the first 24 h after radiation and reached a plateau within 72 h after treatment. Radiation-induced release of endothelial cell-derived growth factors may be involved in the pathogenesis of both early vascular damage and the late fibrosis which represents a prominent feature of late radiation damage in normal tissues.
Vamorolone, a dissociative steroidal compound, reduces pro-inflammatory cytokine expression in glioma cells and increases activity and survival in a murine model of cortical tumor (2016)

Corticosteroids, such as dexamethasone, are routinely used as palliative care in neuro-oncology for their anti-inflammatory benefits, however many patients experience dose limiting side effects caused by glucocorticoid response element (GRE)-mediated transcription. The purpose of this study was to use a murine model to investigate a new steroid alternative, vamorolone, which promises to reduce side effects through dissociating GRE-mediated transcription and NF-κB -mediated anti-inflammatory actions. To compare vamorolone to dexamethasone in reducing pro-inflammatory signals in vitro, murine glioma cells were treated with dexamethasone, vamorolone or vehicle control. Changes in mRNA expression were assessed using the nanostring inflammatory platform. Furthermore, drug efficacy, post-treatment behavioral activity and side effects were assessed by treating two cohorts of brain tumor bearing mice with dexamethasone, vamorolone, or vehicle control. Our investigation showed that treatment with vamorolone resulted in a reduction of pro-inflammatory signals in tumor cells in vitro similar to treatment with dexamethasone. Treatment with vamorolone resulted in a better safety profile in comparison to dexamethasone treatment. Vamorolone- treated mice showed similar or better activity and survival when compared to dexamethasone-treated mice. Our data indicate vamorolone is a potential steroid-sparing alternative for treating patients with brain tumors.
Multiple Lineages of Human Breast Cancer Stem/Progenitor Cells Identified by Profiling with Stem Cell Markers (2009)

Heterogeneity of cancer stem/progenitor cells that give rise to different forms of cancer has been well demonstrated for leukemia. However, this fundamental concept has yet to be established for solid tumors including breast cancer. In this communication, we analyzed solid tumor cancer stem cell markers in human breast cancer cell lines and primary specimens using flow cytometry. The stem/progenitor cell properties of different marker expressing-cell populations were further assessed by in vitro soft agar colony formation assay and the ability to form tumors in NOD/SCID mice. We found that the expression of stem cell markers varied greatly among breast cancer cell lines. In MDA-MB-231 cells, PROCR and ESA, instead of the widely used breast cancer stem cell markers CD44(+)/CD24(-/low) and ALDH, could be used to highly enrich cancer stem/progenitor cell populations which exhibited the ability to self renew and divide asymmetrically. Furthermore, the PROCR(+)/ESA(+) cells expressed epithelial-mesenchymal transition markers. PROCR could also be used to enrich cells with colony forming ability from MB-361 cells. Moreover, consistent with the marker profiling using cell lines, the expression of stem cell markers differed greatly among primary tumors. There was an association between metastasis status and a high prevalence of certain markers including CD44(+)/CD24(-/low), ESA(+), CD133(+), CXCR4(+) and PROCR(+) in primary tumor cells. Taken together, these results suggest that similar to leukemia, several stem/progenitor cell-like subpopulations can exist in breast cancer.
Asp 46 can substitute for Asp 96 as the Schiff base proton donor in bacteriorhodopsin (1995)

Bacteriorhodopsin functions as a light-driven proton pump in the purple membrane of Halobacterium salinarium. A variety of studies have established that a proton is transferred over an approximately 10 A distance from Asp 96 to the retinylidene Schiff base during the M --> N transition of the bR photocycle. In order to further explore the mechanism of this Schiff base reprotonation, we compared the properties of the double mutant Thr 46 --> Asp/Asp 96 --> Asn (T46D/D96N), the single mutants Asp 96 --> Asn (D96N) and Thr 46 --> Asp (T46D), and wild-type bR. In contrast to D96N, which exhibits a very slow M decay, T46D/D96N has an M decay close to that of wild-type bR. FTIR difference spectroscopy detects bands in the carboxyl and carboxylate stretch region of T46D/D96N consistent with the deprotonation of Asp 46 during the M --> N transition. In addition, bands associated with structural changes of Asn 96 in the mutant D96N are absent in T46D/D96N. Resonance Raman spectroscopy provides evidence that both T46D/D96N and T46D have a long-lived N-like species in their photocycles. These data demonstrate that Asp 46 can substitute for Asp 96 as the proton donor group in the reprotonation pathway of the Schiff base during the M --> N transition. However, N decay is delayed in comparison to wild-type bR. This may be due to a partial block in the proton pathway leading from the cytoplasmic medium to Asp 46.
Mu opiate receptor subtypes. (2004)

The . opiate receptor gene (MOR) has at least 14 exons that can generate 15 different splice variants. Recently, two new human MOR splice variants (hMOR-1O and hMOR-1X) have been identified and characterized. The two variants containing human MOR exons 1, 2, and 3 and a fourth alternative exon O, or exon X, are expressed in human brain tissue, and are selective for mu opioid binding in transfected cells. It is unclear; however, what the biologic role of these two novel human splice variants is in vivo. The mu3 opiate receptor subtype found in various human tissues where it is coupled to constitutive nitric oxide synthase derived nitric oxide release is characterized by its opiate alkaloid selectivity and its insensitivity to opioid peptides. The mu3 clone exhibits 100% identity to the mu1 receptor subtype in the center and conserved region, but with a truncated 5'-end (position 503 of mu1 mRNA) (missing several hundred nucleotides). In addition, the 3'-end of the new clone contains the 3'-end of the mu1 receptor, followed by a new fragment of 263 bases, and then by a 202 bp fragment of the 3'-end of the mu1 gene untranslated region. When mu3 is expressed in a heterologous system, the protein produced from this cDNA exhibits all of the expected biochemical characteristics of the mu3 receptor. The isolation of this novel splice variant adds support to the presence of morphinergic signaling in animals.
Transplantation of Bone Marrow–Derived Mesenchymal Stem Cells Improves Diabetic Polyneuropathy in Rats (2008)

These results suggest that MSC transplantation could have therapeutic effects on DPN through paracrine actions of growth factors secreted by MSCs.
Factor VIII C2 Domain Missense Mutations Exhibit Defective Trafficking of Biologically Functional Proteins (1996)

The half-life of coagulation factor VIII (FVIII) in plasma is prolonged by noncovalent interaction with von Willebrand factor (vWF). Antibody inhibition data indicate that epitopes within the carboxyl terminus of the FVIII light chain play a role in vWF binding. Analysis of hemophilia A patient DNA samples have identified missense mutations within this carboxyl terminus of the FVIII light chain at amino acid 2307 in which arginine is replaced with either glutamine or leucine. Patients with these mutations have reduced FVIII activity proportional to reduced cross-reacting material in their plasma. It was hypothesized that the reduced levels of FVIII in plasma due to these mutations may be related to a defect in vWF binding with resultant plasma instability. Wild-type and mutant FVIII cDNA expression vectors were prepared and expressed in COS-1 monkey cells by transient DNA transfection. FVIII mutants R2307Q and R2307L were synthesized at equal rates compared to FVIII wild-type but had greater than 10-fold reduced accumulation of antigen and activity levels in the conditioned medium. An additional mutation, Y2305F, also displayed a similar defect in protein accumulation, whereas Y2332F was secreted similarly to wild-type. The specific activity of immunoaffinity purified R2307Q was mildly reduced compared to FVIII wild-type, whereas vWF binding properties were retained. Inhibition of intracellular cysteine proteases resulted in intracellular accumulation of R2307Q protein, suggesting that the mechanism leading to hemophilia A is related to a block in secretion and subsequent degradation within the secretory pathway rather than extracellular instability.
THE EFFECT OF INITIAL ACID CONCENTRATION ON THE LIGNIN ISOLATED BY THE ACIDOLYSIS OF ASPEN WOOD (1961)

A further study has been made of the isolation, by acidolysis, of lignin from aspen wood meal (Populustremuloides Michx.) using a dioxane–water (9:1) solvent medium containing hydrogen chloride and a low extraction temperature of 87 ± 2° for a short extraction time of 0.5 hour. Lignins so isolated included those: (a) under different initial acid concentrations of 0.0, 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.8, and 1.7 equivalents of HCl/liter of solvent medium; (b) from successive extractions under increasing initial acid concentrations of 0.2, 0.4, 0.8, and 1.6 equivalents/liter; and (c) from successive extractions under constant initial acid concentrations of 0.2 equivalent/liter.All the lignin fractions so isolated were studied with respect to their yield, methoxyl content, infrared absorption spectra, and the yields of vanillin and syringaldehyde obtained from them by oxidation using alkaline nitrobenzene.Evidence is presented in support of the non-homogeneity of the whole protolignin. This may be the result of the presence of possibly two basic types. One fraction, comprising around 70–85%, is most readily extracted, has a consistently high methoxyl content (ca. 21%), and is capable of being oxidized to give high yields of syringaldehyde and vanillin in a ratio close to 2.5:1. The second fraction is characterized by a greater difficulty of extraction, lower methoxyl content, and significantly lower yields of the aldehydes in a ratio closer to 1:1.
Antibiotic resistance as a global threat: Evidence from China, Kuwait and the United States (2006)

Antimicrobial resistance is a serious and growing problem in all three countries. To date, there is not strong international convergence in the countries' resistance patterns. This finding may change with the greater international travel that will accompany globalization. Future research on the determinants of drug resistance patterns, and their international convergence or divergence, should be a priority.
Photochemical Generation and Reversible Cycloaromatization of a Nine-Membered Ring Cyclic Enediyne (2008)

Irradiation of the nine-membered ring enediyne precursor, which has one of its triple bonds masked as cyclopropenone, efficiently (Phi = 0.34) generates the reactive 4,5-benzocyclonona-2,6-diynol. The latter rapidly equilibrates with the corresponding 1,4-didehydronaphthalene diradical and then undergoes rate-limiting hydrogen abstraction to produce the ultimate product of the Bergman cyclization, benz[f]indanol.
Photodisruption in biological tissues and single cells using femtosecond laser pulses (2001)

Summary form only given. Semi-transparent materials such as biological tissues do not strongly absorb light in the visible range. However, the intensity of a tightly-focused femtosecond laser pulse can be high enough to cause nonlinear absorption of laser energy by the tissue, leading to permanent material change. The nonlinearity of the process ensures the absorption, and therefore material alterations are confined to the extremely small focal volume. In this paper, we show that sub-micrometer sized photodisrupted regions can be produced inside single cells by nonlinear absorption of tightly focused femtosecond laser pulses. Femtosecond pulses deposit very little energy while still causing breakdown, therefore producing surgical photodisruption while minimizing collateral damage (Juhasz et al, 1995; Zysset et al, 1989; Krauss and Puliafito, 1996). This suggests exciting prospects for precise laser surgery.
Differential and synergistic actions of nerve growth factor and cyclic AMP in PC12 cells. (1981)

When a clonal line of rat pheochromocytoma (PC12) was exposed to beta-nerve growth factor (beta NGF), N6, O2-dibutyryl adenosine 3':5' cyclic monophosphate (Bt2cAMP), or a combination of the two, 10, 26, or 70% of the cell clumps, respectively, displayed neurites after 1.d. Increases in the cellular RNA concentration were also found to be additive or greater when both agents were present. Neurites induced by Bt2cAMP alone were not maintained after replacement with beta NGF. The degree of potentiated neurite outgrowth was a function of the time of simultaneous exposure to both agents. The initiation of neurite outgrowth in the presence of Bt2cAMP was independent of RNA synthesis, in contrast to that induced by beta NGF alone. We conclude that beta NGF-induced initiation of morphological differentiation of these cells is not mediated by a cAMP-dependent mechanism. Consideration of Bt2cAMP effects upon other cell lines suggest that Bt2cAMP causes a rapid, but unstable, reorganization of the PC12 cytoskeleton, resulting in the initiation of neurite outgrowth from these cells. In contrast, beta NGF alone achieves a more stable cytoskeleton reorganization by an RNA synthesis-dependent mechanism.
YouTube-8M: A Large-Scale Video Classification Benchmark (2016)

Many recent advancements in Computer Vision are attributed to large datasets. Open-source software packages for Machine Learning and inexpensive commodity hardware have reduced the barrier of entry for exploring novel approaches at scale. It is possible to train models over millions of examples within a few days. Although large-scale datasets exist for image understanding, such as ImageNet, there are no comparable size video classification datasets. In this paper, we introduce YouTube-8M, the largest multi-label video classification dataset, composed of ~8 million videos (500K hours of video), annotated with a vocabulary of 4800 visual entities. To get the videos and their labels, we used a YouTube video annotation system, which labels videos with their main topics. While the labels are machine-generated, they have high-precision and are derived from a variety of human-based signals including metadata and query click signals. We filtered the video labels (Knowledge Graph entities) using both automated and manual curation strategies, including asking human raters if the labels are visually recognizable. Then, we decoded each video at one-frame-per-second, and used a Deep CNN pre-trained on ImageNet to extract the hidden representation immediately prior to the classification layer. Finally, we compressed the frame features and make both the features and video-level labels available for download. We trained various (modest) classification models on the dataset, evaluated them using popular evaluation metrics, and report them as baselines. Despite the size of the dataset, some of our models train to convergence in less than a day on a single machine using TensorFlow. We plan to release code for training a TensorFlow model and for computing metrics.
Compartmentalization of Spermine and Spermidine in the Herpes Simplex Virion (1971)

Enveloped particles of herpes simplex virus produced in human cells in culture contained spermidine and spermine, in a molar ratio of 1.6 +/- 0.2. The spermine present within the nucleocapsid is sufficient to neutralize at least 40% of the viral DNA. Disruption of the envelope with nonionic detergent and urea resulted in the selective loss of spermidine. Exogenous ornithine can function as a precursor to host and viral polyamines only before infection.
Coded Information within the Picture Area (1974)

In years past, the Federal Communications Commission (FCC) has authorized a variety of special signals inserted into or riding “piggyback” with the television program signal. These special or “ancillary” signals were included for a number of purposes, and without in any way adversely affecting the integrity of the program signal. But in 1970 the FCC amended its Rules and Regulations so as to permit transmission of coded patterns in the television picture area, which signals “shall not result in significant degradation of broadcast transmission.”
Correction: Profiling Critical Cancer Gene Mutations in Clinical Tumor Samples (2009)

Background: Detection of critical cancer gene mutations in clinical tumor specimens may predict patient outcomes and inform treatment options; however, high-throughput mutation profiling remains underdeveloped as a diagnostic approach. We report the implementation of a genotyping and validation algorithm that enables robust tumor mutation profiling in the clinical setting.
Development of Vascular Complications in Diabetes (1997)

Chronic complications of diabetes are dominated by disorders of the vascular system. They are a much larger burden on both diabetic patients and overall medical costs than diabetes itself. Large vessel problems are far more frequent than microvascular disorders. Loss of arterial elasticity alters arterial flow patterns and increases microcirculatory peak flow rates. Hyperglycemia may directly disrupt elastin formation. Diabetic leg artery disease may be generated by nerve damage, reversing this interactive contribution sequence. The major anatomic feature of microangiopathy in long-term diabetes is an unevenly distributed thickening of the intima of smaller arterioles. The thickening is primarily due to accumulation of type IV (basement membrane) collagen. Arterioles change local vessel diameter to adjust blood distribution to meet current needs. The thickening compromises the maximum local blood flow that may be achieved by this means. Compromise of maximal arteriolar dilatation does not disrupt exercising muscle but in the kidney, retina, and possibly in nerve, local circumstances can generate serious damage. Each of these system's responses has unique features that mediate its vulnerability, but all these organs show arteriolar hyalinization. The increased arteriolar accumulation of type IV collagen appears to be a response to the tangential force generated by flow over local endothelial cells. An increase in peak arteriolar wall force is mediated by a diabetes-specific doubling of erythrocyte membrane curvature change resistance. Red cell aggregation rate determines the rate of damage. The same nonspecific burden may also predispose to heart disease and stroke. Intensive metabolic control improves red cell deformability and protects against arteriolar damage. Therapies that address the rheologic problem more directly may add to the effectiveness of good diabetes control in the future.
Dihydrolipoic Acid as an Effective Cofactor for Peptide Methionine Sulfoxide Reductase in Enzymatic Repair of Oxidative Damage to Both Lipid-Free and Lipid-Bound Apolipoprotein A-I (2002)

The aim of this study was to examine the possible use of dihydrolipoic acid (DHLA), the reduced form of lipoic acid, in the reduction of oxidized apolipoprotein A-I mediated by peptide methionine sulfoxide reductase (PMSR), and to test the accessibility of methionine sulfoxides in the lipid-bound oxidized apolipoprotein A-I to this reaction. We show that DHLA acts as an effective cofactor for PMSR, mediating restoration of the native secondary structure, tertiary structure, stability, and lipid-binding properties of the native unoxidized protein. Reconstituted high-density lipoproteins were used to demonstrate effective enzymatic reduction of the lipid-bound oxidized protein in the presence of DHLA. These findings suggest that the enzymatic repair of oxidative damage to intact lipoproteins could provide a model of a possible repair mechanism active in vivo during oxidative stress and that the restoration of high-density lipoprotein function could be one of the therapeutic benefits of lipoic acid.
Two Structurally Different Rituximab-Specific CD20 Mimotope Peptides Reveal That Rituximab Recognizes Two Different CD20-Associated Epitopes (2009)

Peptide mimotopes of the CD20 epitope recognized by rituximab are useful tools for studying this therapeutic mAb's functional properties. We previously identified two structurally different peptides that are both effective mimotopes: a 7-mer cyclic peptide (Rp15-C) bearing the antigenic motif (a/sNPS) that matches 170(ANPS)173 of the extracellular loop of CD20, and a 12-mer linear peptide (Rp5-L) containing the antigenic motif (WPxWLE) lacking sequence homology to CD20. In this study, we investigated whether the different structures of Rp15-C and Rp5-L reflect the mimicry of the same or different CD20 epitopes recognized by rituximab. Using immunochemical methods, we found that, like Rp15-C, Rp5-L mimics the raft-associated form of CD20 (by inhibiting rituximab binding to CD20 in vitro). Rp5-L and Rp15-C elicit, in immunized mice, anti-CD20 Abs that stain CD20+ cells with a punctate pattern similar to that of rituximab. However, only anti-Rp5-L Abs recognize denatured CD20. When phage-display peptide libraries were panned with anti-Rp5-L, phage clones were enriched that expressed the consensus qWPxwL, similar to the antigenic motif (WPxWLE), but not matching (a/sNPS). Finally, (WPxWLE) and (ANPS) share some, but not all, contact sites within the rituximab Ag-combining site, indicating that (WPxWLE) is not an exact replica of Rp15-C (or CD20) (ANPS). Altogether, these results indicate that the two structurally different peptides are also conformationally different, and suggest that rituximab recognizes two different CD20-associated epitopes.