gebhart/patrepeval huggingface dataset:
Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production. (1988)

The capacity of 12 cytokines to induce NO2- or H2O2 release from murine peritoneal macrophages was tested by using resident macrophages, or macrophages elicited with periodate, casein, or thioglycollate broth. Elevated H2O2 release in response to PMA was observed in resident macrophages after a 48-h incubation with IFN-gamma, TNF-alpha, TNF-beta, or CSF-GM. Of these, only IFN-gamma induced substantial NO2- secretion during the culture period. The cytokines inactive in both assays under the conditions tested were IL-1 beta, IL-2, IL-3, IL-4, IFN-alpha, IFN-beta, CSF-M, and transforming growth factor-beta 1. Incubation of macrophages with IFN-gamma for 48 h in the presence of LPS inhibited H2O2 production but augmented NO2- release, whereas incubation in the presence of the arginine analog NG-monomethylarginine inhibited NO2- release but not H2O2 production. Although neither TNF-alpha nor TNF-beta induced NO2- synthesis on its own, addition of either cytokine together with IFN-gamma increased macrophage NO2- production up to six-fold over that in macrophages treated with IFN-gamma alone. Moreover, IFN-alpha or IFN-beta in combination with LPS could also induce NO2- production in macrophages, as was previously reported for IFN-gamma plus LPS. These data suggest that: 1) tested as a sole agent, IFN-gamma was the only one of the 12 cytokines capable of inducing both NO2- and H2O2 release; 2) the pathways leading to secretion of H2O2 and NO2- are independent; 3) either IFN-gamma and TNF-alpha/beta or IFN-alpha/beta/gamma and LPS can interact synergistically to induce NO2- release.
Induction of cutaneous delayed-type hypersensitivity reactions in VEGF-A transgenic mice results in chronic skin inflammation associated with persistent lymphatic hyperplasia (2004)

Vascular endothelial growth factor-A (VEGF-A) expression is up-regulated in several inflammatory diseases including psoriasis, delayed-type hypersensitivity (DTH) reactions, and rheumatoid arthritis. To directly characterize the biologic function of VEGF-A in inflammation, we evaluated experimental DTH reactions induced in the ear skin of transgenic mice that overexpress VEGF-A specifically in the epidermis. VEGF-A transgenic mice underwent a significantly increased inflammatory response that persisted for more than 1 month, whereas inflammation returned to baseline levels within 7 days in wild-type mice. Inflammatory lesions in VEGF-A transgenic mice closely resembled human psoriasis and were characterized by epidermal hyperplasia, impaired epidermal differentiation, and accumulation of dermal CD4+ T-lymphocytes and epidermal CD8+ lymphocytes. Surprisingly, VEGF-A also promoted lymphatic vessel proliferation and enlargement, which might contribute to the increased inflammatory response, as lymphatic vessel enlargement was also detected in human psoriatic skin lesions. Combined systemic treatment with blocking antibodies against VEGF receptor-1 (VEGFR-1) and VEGFR-2 potently inhibited inflammation and also decreased lymphatic vessel size. Together, these findings reveal a central role of VEGF-A in promoting lymphatic enlargement, vascular hyperpermeability, and leukocyte recruitment, thereby leading to persistent chronic inflammation. They also indicate that inhibition of VEGF-A bioactivity might be a new approach to anti-inflammatory therapy.
Histamine H 2 -Receptor Antagonist Ranitidine Protects Against Neural Death Induced by Oxygen-Glucose Deprivation (2004)

H2-receptor antagonists protected against OGD-induced neuronal death. Ranitidine attenuated cell death even when administered after OGD. These data suggest that this drug, which is currently used for the treatment of gastric ulcers, may be useful in promoting recovery after ischemia.
AN IN VITRO STUDY OF CELLULAR AND MOLECULAR MECHANISMS OF LIGAMENT SCARRING (2005)

When ligaments such as the medial collateral ligament (MCL) are injured, they generally heal but form scar tissue, which is composed of a disorganized collagen matrix that is over-produced by fibroblasts. Scar tissue has inferior structural and mechanical properties, which can lead to joint instability. Excessive fibroblast contraction is thought to contribute to tissue scarring. Previous studies have shown that both TGF-â1 and TGF-â3 increase fibroblast contraction and collagen synthesis. However, TGF-â1 enhances scar tissue formation whereas TGF-â3 actually reduces it. In addition, both TGF-â isoforms have been found to increase the expression of á-SMA, which correlates with increased fibroblast contractility. An increase in tension at the wound site has also been found to increase á-SMA protein levels. Therefore these factors are all important in the wound healing process. The overall objective of this thesis research was to investigate cellular and molecular mechanisms that affect scar tissue formation in healing ligaments. Contraction forces, collagen synthesis, and á-SMA protein expression of healing and normal MCL fibroblasts in response to treatment with TGF-â1, TGF-â3, and collagen gel tension were investigated. A novel culture force monitor (CFM) system was used to quantify forces of fibroblast contraction. It was found that healing MCL fibroblasts produced greater contractile forces and higher levels of collagen synthesis than normal MCL fibroblasts. In addition, treatment with TGF-â1 or TGF-â3 increased contraction forces in healing fibroblasts compared to untreated controls, with TGF-â1 consistently producing greater contraction forces than treatment with TGF-â3. TGF-â1 and TGF-â3 also induced higher levels of á-SMA protein expression compared to untreated fibroblasts. Consistent with the contraction forces, fibroblasts treated with TGF-â1 expressed higher levels of á-SMA protein than those treated with TGF-â3. Further, it was found that when tension in gels embedded with normal MCL fibroblasts was released, expression of á-SMA protein also decreased. Thus, this study showed that healing and normal fibroblasts have differential contractile and collagen synthesis abilities. The results of this study showed that the presence of TGF-â1, TGF-â3, and tension in the matrix should be regulated to improve ligament healing. Decreasing the ratio of TGF-â1 to TGF-â3 in an injured ligament may decrease fibroblast contraction and thus reduce scar formation in healing MCLs. Finally, reducing tension levels in healing ligaments and hence down-regulating á-SMA protein expression may also decrease ligament scarring.
De novo Fatty Acid Biosynthesis Contributes Significantly to Establishment of a Bioenergetically Favorable Environment for Vaccinia Virus Infection (2014)

The poxvirus life cycle, although physically autonomous from the host nucleus, is nevertheless dependent upon cellular functions. A requirement for de novo fatty acid biosynthesis was implied by our previous demonstration that cerulenin, a fatty acid synthase inhibitor, impaired vaccinia virus production. Here we show that additional inhibitors of this pathway, TOFA and C75, reduce viral yield significantly, with partial rescue provided by exogenous palmitate, the pathway's end-product. Palmitate's major role during infection is not for phospholipid synthesis or protein palmitoylation. Instead, the mitochondrial import and β-oxidation of palmitate are essential, as shown by the impact of etomoxir and trimetazidine, which target these two processes respectively. Moreover, the impact of these inhibitors is exacerbated in the absence of exogenous glucose, which is otherwise dispensable for infection. In contrast to glucose, glutamine is essential for productive viral infection, providing intermediates that sustain the TCA cycle (anaplerosis). Cumulatively, these data suggest that productive infection requires the mitochondrial β-oxidation of palmitate which drives the TCA cycle and energy production. Additionally, infection causes a significant rise in the cellular oxygen consumption rate (ATP synthesis) that is ablated by etomoxir. The biochemical progression of the vaccinia life cycle is not impaired in the presence of TOFA, C75, or etomoxir, although the levels of viral DNA and proteins synthesized are somewhat diminished. However, by reversibly arresting infections at the onset of morphogenesis, and then monitoring virus production after release of the block, we determined that virion assembly is highly sensitive to TOFA and C75. Electron microscopic analysis of cells released into C75 revealed fragmented aggregates of viroplasm which failed to be enclosed by developing virion membranes. Taken together, these data indicate that vaccinia infection, and in particular virion assembly, relies on the synthesis and mitochondrial import of fatty acids, where their β-oxidation drives robust ATP production.
<title>Particulate Model For Halftone Noise In Electrophotography I. Theory</title> (1981)

A model is constructed for the noise-density characteristics of electrophotographic half-tone images. The model has components relating to the fluctuations: within the dot; within the background area; and in dot-size. These components are themselves related to the (toner) particulate nature of the image, enabling comparison to be made with the equivalent continuous tone case.
The Stromal Derived Factor–1/CXCL12–CXC Chemokine Receptor 4 Biological Axis in Non–Small Cell Lung Cancer Metastases (2003)

Non-small cell lung cancer is characterized by a specific metastatic pattern. The mechanism for organ-specific metastasis is poorly understood, although evidence has suggested that the chemokine stromal derived factor-1 (CXCL12) and its cognate receptor CXCR4 may regulate breast cancer metastasis. We hypothesized that the CXCL12-CXCR4 biological axis is important in mediating non-small cell lung cancer metastases. Our results indicate that both non-small cell lung cancer tumor specimens resected from patients and non-small cell lung cancer cell lines express CXCR4, but not CXCL12. Non-small cell lung cancer cell lines undergo chemotaxis in response to CXCL12. CXCL12-CXCR4 activation of non-small cell lung cancer cell lines showed intracellular calcium mobilization and mitogen-activated protein kinase activation with enhanced extracellular signal-related kinase-1/2 phosphorylation without change in either proliferation or apoptosis. Target organs in a murine model that are the preferred destination of human non-small cell lung cancer metastases elaborate higher levels of CXCL12 than does the primary tumor, and suggest the generation of chemotactic gradients. The administration of specific neutralizing anti-CXCL12 antibodies to severe combined immunodeficient mice expressing human non-small cell lung cancer abrogated organ metastases, without affecting primary tumor-derived angiogenesis. These data suggest that the CXCL12-CXCR4 biological axis is involved in regulating the metastasis of non-small cell lung cancer.
Synchronization of data streams in distributed realtime multimodal signal processing environments using commodity hardware (2008)

We describe an API built on top of the NIST Data Flow System II, a sensor-net middleware, which allows to synchronize high volume data streams in real-time, using commodity hardware in distributed computation environments. Experiences with synchronization issues arising from working with multiple data streams in applications such as real-time multi-sensor data fusion and ad hoc video processing are addressed.
Double-Stranded RNA Induces Sequence-Specific Antiviral Silencing in Addition to Nonspecific Immunity in a Marine Shrimp: Convergence of RNAInterference and Innate Immunity in the Invertebrate Antiviral Response? (2005)

Double-stranded RNA (dsRNA) is a common by-product of viral infections and a potent inducer of innate antiviral immune responses in vertebrates. In the marine shrimp Litopenaeus vannamei, innate antiviral immunity is also induced by dsRNA in a sequence-independent manner. In this study, the hypothesis that dsRNA can evoke not only innate antiviral immunity but also a sequence-specific antiviral response in shrimp was tested. It was found that viral sequence-specific dsRNA affords potent antiviral immunity in vivo, implying the involvement of RNA interference (RNAi)-like mechanisms in the antiviral response of the shrimp. Consistent with the activation of RNAi by virus-specific dsRNA, endogenous shrimp genes could be silenced in a systemic fashion by the administration of cognate long dsRNA. While innate antiviral immunity, sequence-dependent antiviral protection, and gene silencing could all be induced by injection of long dsRNA molecules, injection of short interfering RNAs failed to induce similar responses, suggesting a size requirement for extracellular dsRNA to engage antiviral mechanisms and gene silencing. We propose a model of antiviral immunity in shrimp by which viral dsRNA engages not only innate immune pathways but also an RNAi-like mechanism to induce potent antiviral responses in vivo.
Excitatory amino acid antagonists (1991)

Historical introduction: key discoveries Excitatory amino acid neurotransmitters: anatomical systems Excitatory amino acid receptor subtypes Physiology and biophysics of the NMDA receptor channel complex Structure/activity relations of competitive NMDA receptor antagonists Non-competitive NMDA antagonists acting on the glycine site Non-competitive NMDA antagonists acting on the polyamine site Channel blocking drugs for the NMDA receptor Inhibitors of kainate and AMPA ionophore receptors The quisqualate metabotropic receptor: characterization and putative role Excitotoxicity Behavioural effects of NMDA antagonists Excitatory amino acid antagonists and therapy of epilepsy Excitatory amino acid antagonists: opportunities for the treatment of ischaemic brain damage in man Future prospects for excitatory amino acid antagonists
Real-time multi-functional optical coherence tomography (2003)

We demonstrate real-time acquisition, processing, and display of tissue structure, birefringence, and blood flow in a multi-functional optical coherence tomography (MF-OCT) system. This is accomplished by efficient data processing of the phase-resolved inteference patterns without dedicated hardware or extensive modification to the high-speed fiber-based OCT system. The system acquires images of 2048 depth scans per second, covering an area of 5 mm in width x 1.2 mm in depth with real-time display updating images in a rolling manner 32 times each second. We present a video of the system display as images from the proximal nail fold of a human volunteer are taken.
Crystal Structure of the Non-heme Iron Dioxygenase PtlH in Pentalenolactone Biosynthesis (2007)

The non-heme iron dioxygenase PtlH from the soil organism Streptomyces avermitilis is a member of the iron(II)/alpha-ketoglutarate-dependent dioxygenase superfamily and catalyzes an essential reaction in the biosynthesis of the sesquiterpenoid antibiotic pentalenolactone. To investigate the structural basis for substrate recognition and catalysis, we have determined the x-ray crystal structure of PtlH in several complexes with the cofactors iron, alpha-ketoglutarate, and the non-reactive enantiomer of the substrate, ent-1-deoxypentalenic acid, in four different crystal forms to up to 1.31 A resolution. The overall structure of PtlH forms a double-stranded barrel helix fold, and the cofactor-binding site for iron and alpha-ketoglutarate is similar to other double-stranded barrel helix fold enzymes. Additional secondary structure elements that contribute to the substrate-binding site in PtlH are not conserved in other double-stranded barrel helix fold enzymes. Binding of the substrate enantiomer induces a reorganization of the monoclinic crystal lattice leading to a disorder-order transition of a C-terminal alpha-helix. The newly formed helix blocks the major access to the active site and effectively traps the bound substrate. Kinetic analysis of wild type and site-directed mutant proteins confirms a critical function of two arginine residues in substrate binding, while simulated docking of the enzymatic reaction product reveals the likely orientation of bound substrate.
N-Channel Germanium MOSFET Fabricated Below 360 <formula formulatype="inline"><tex Notation="TeX">$^{ \circ}\hbox{C}$</tex></formula> by Cobalt-Induced Dopant Activation for Monolithic Three-Dimensional-ICs (2011)

Below 360°C, we demonstrate germanium (Ge) n+/p junction diode and n-channel Ge metal-oxide-semiconductor field-effect transistor (MOSFET) with a low temperature Al/Al <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> O <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sub> /GeO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> gate stack for monolithic 3-D integration using a metal-induced dopant activation (MIDA) technique. In particular, the cobalt (Co) MIDA phenomenon is investigated on Ge damaged by an implantation process. Shallow (~100 nm) source/drain junctions with very low resistivity (5.2 × 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-4</sup> Ω-cm) are then achieved at very low temperature by the Co MIDA technique. Consequently, high diode and transistor current on/off ratios (~10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">4</sup> and ~10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> , respectively) are obtained in this n-channel Ge MOSFET.
Phase II trial of cisplatin as first-line chemotherapy in patients with advanced or recurrent uterine sarcomas: a Gynecologic Oncology Group study. (1991)

Ninety-six assessable patients with advanced or recurrent uterine sarcomas, who were no longer controllable with surgery and radiotherapy, and who had not received prior chemotherapy were treated with cisplatin 50 mg/m2 intravenously every 3 weeks. Of 63 cases with mixed mesodermal tumors, five complete responses (CRs; 8%) and seven partial responses (PRs; 11%) were observed (95% confidence interval [CI], 10.3% to 30.9%). Of 33 patients with leiomyosarcoma, one PR (3%) was observed (95% CI, .1% to 15.8%). Adverse effects included leukopenia (23%), nausea and vomiting (73%), and mild azotemia (42%). No patients experienced life-threatening toxicity. Cisplatin has definite activity when given at the dose and schedule that we tested for patients with mixed mesodermal sarcomas who have not received prior chemotherapy, but has little activity in patients with leiomyosarcoma.
Akkermansia muciniphila Enhances the Antitumor Effect of Cisplatin in Lewis Lung Cancer Mice (2020)

Recently, intestinal flora plays a vital role in the occurrence and development of tumors and there is link between cancer immunotherapy and Akkermansia muciniphila (Akk). However, the therapeutic efficacy of Akk in lung cancer remained unclear. Hence, our study is aimed at investigating the antitumor effects of cisplatin (CDDP) combined with Akk on lung cancer. Using the murine lung cancer model by subcutaneously inoculating Lewis lung cancer model, 50 mice were divided into five groups: normal, model, CDDP, CDDP+Akk, and CDDP+antibiotics. After treatment within 5 weeks, compared with the model group, the administered group improved the changes of tumor pathomorphology. Compared with the CDDP group, CDDP combining with Akk slowed down the growth of tumor volume, downregulated the levels of ki-67, p53, and factor-associated suicide (Fas) ligand proteins and upregulated Fas proteins, increased the levels of interferon-<i>γ</i>, interleukin-6, and tumor necrosis factor-<i>α</i>, and suppressed the expression of CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup> Treg in mouse peripheral blood and spleen. In addition, transcriptome analysis indicated that Akk combining with CDDP increased obviously the levels of IFI27l2 and IGFBP7 and was related to those pathways including the cytokine-cytokine receptor interaction, Th17 cell differentiation, FOXO, JAK-STAT, and PI3K-Akt signaling pathways. These results suggested that the therapeutic efficacy of the combined treatment of Akk and CDDP was superior to the only CDDP treatment, which could enhance immune regulation and would be a promising strategy for the treatment of lung cancer.
Vaccination with Recombinant Herpes Simplex Virus Glycoproteins: Protection Against Initial and Recurrent Genital Herpes (1987)

The natural history of initial and subsequent recurrent herpes simplex virus (HSV) genital infection was studied in guinea pigs immunized with HSV glycoprotein vaccines before vaginal challenge with HSV-2. The vaccines used included HSV-1 glycoprotein B and HSV-1 glycoprotein D, both prepared by recombinant DNA techniques, and mixtures of HSV-1 or HSV-2 glycoproteins, prepared from infected cell monolayers by lectin chromatography. Immunizing guinea pigs with subunit HSV glycoprotein vaccines favorably altered the clinical and virological course of initial infection and substantially reduced the incidence, frequency, and duration of recurrent herpetic infections. The extent of protection was influenced by the nature of the glycoprotein vaccine, the immunizing dose, and the co-administration of adjuvant.
BALANCE (Bioengineering Approaches for Lifestyle Activity and Nutrition Continuous Engagement): Developing New Technology for Monitoring Energy Balance in Real Time (2010)

Methods that measure energy balance accurately in real time represent promising avenues to address the obesity epidemic. We developed an electronic food diary on a mobile phone that includes an energy balance visualization and computes and displays the difference between energy intake from food entries and energy expenditure from a multiple-sensor device that provides objective estimates of energy expenditure in real time. A geographic information system dataset containing locations associated with activity and eating episodes is integrated with an ArcPad mapping application on the phone to provide users with a visual display of food sources and locations associated with physical activity within their proximal environment. This innovative tool captures peoples' movement through space and time under free-living conditions and could potentially have many health-related applications in the future.
Effects of Clustered Epitopes in Multivalent Ligand−Receptor Interactions (2008)

Many biological ligands are composed of clustered binding epitopes. However, the effects of clustered epitopes on the affinity of ligand-receptor interactions in many cases are not well understood. Clustered carbohydrate epitopes are present in naturally occurring multivalent carbohydrates and glycoproteins, which are receptors on the surface of cells. Recent studies have provided evidence that the enhanced affinities of lectins, which are carbohydrate binding proteins, for multivalent carbohydrates and glycoproteins are due to internal diffusion of lectin molecules from epitope to epitope in these multivalent ligands before dissociation. Indeed, binding of lectins to mucins, which are large linear glycoproteins, appears to be similar to the internal diffusion mechanism(s) of protein ligands binding to DNA, which have been termed the "bind and slide" or "bind and hop" mechanisms. The observed increasing negative cooperativity and gradient of decreasing microaffinity constants of a lectin binding to multivalent carbohydrates and glycoproteins result in an initial fraction of lectin molecules that bind with very high affinity and dynamic motion. These findings have important implications for the mechanisms of binding of lectins to mucins, and for other ligand-biopolymer interactions and clustered ligand-receptor systems in general.