gebhart/patrepeval huggingface dataset:
Heme triggers TLR4 signaling leading to endothelial cell activation and vaso-occlusion in murine sickle cell disease (2013)

Treatment of sickle cell disease (SCD) is hampered by incomplete understanding of pathways linking hemolysis to vaso-occlusion. We investigated these pathways in transgenic sickle mice. Infusion of hemoglobin or heme triggered vaso-occlusion in sickle, but not normal, mice. Methemoglobin, but not heme-stabilized cyanomethemoglobin, induced vaso-occlusion, indicating heme liberation is necessary. In corroboration, hemoglobin-induced vaso-occlusion was blocked by the methemoglobin reducing agent methylene blue, haptoglobin, or the heme-binding protein hemopexin. Untreated HbSS mice, but not HbAA mice, exhibited ∼10% vaso-occlusion in steady state that was inhibited by haptoglobin or hemopexin infusion. Antibody blockade of adhesion molecules P-selectin, von Willebrand factor (VWF), E-selectin, vascular cell adhesion molecule 1, intercellular adhesion molecule 1, platelet endothelial cell (EC) adhesion molecule 1, α4β1, or αVβ3 integrin prevented vaso-occlusion. Heme rapidly (5 minutes) mobilized Weibel-Palade body (WPB) P-selectin and VWF onto EC and vessel wall surfaces and activated EC nuclear factor κB (NF-κB). This was mediated by TLR4 as TAK-242 blocked WPB degranulation, NF-κB activation, vaso-occlusion, leukocyte rolling/adhesion, and heme lethality. TLR4(-/-) mice transplanted with TLR4(+/+) sickle bone marrow exhibited no heme-induced vaso-occlusion. The TLR4 agonist lipopolysaccharide (LPS) activated ECs and triggered vaso-occlusion that was inhibited by TAK-242, linking hemolysis- and infection-induced vaso-occlusive crises to TLR4 signaling. Heme and LPS failed to activate VWF and NF-κB in TLR4(-/-) ECs. Anti-LPS immunoglobulin G blocked LPS-induced, but not heme-induced, vaso-occlusion, illustrating LPS-independent TLR4 signaling by heme. Inhibition of protein kinase C, NADPH oxidase, or antioxidant treatment blocked heme-mediated stasis, WPB degranulation, and oxidant production. We conclude that intravascular hemolysis in SCD releases heme that activates endothelial TLR4 signaling leading to WPB degranulation, NF-κB activation, and vaso-occlusion.
Sol–Gel Fabrication and Photoluminescence Properties of SiO<SUB>2</SUB> @ Gd<SUB>2</SUB>O<SUB>3</SUB>: Eu<SUP>3+</SUP> Core–Shell Particles (2006)

A uniform nanolayer of europium-doped Gd2O3 was coated on the surface of preformed submicron silica spheres by a Pechini sol-gel process. The resulted SiO2 @ Gd2O3:Eu3+ core-shell structured phosphors were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), photoluminescence (PL) spectra as well as kinetic decays. The XRD results show that the Gd2O3:Eu3+ layers start to crystallize on the SiO2 spheres after annealing at 400 degrees C and the crystallinity increases with raising the annealing temperature. The core-shell phosphors possess perfect spherical shape with narrow size distribution (average size: 640 nm) and non-agglomeration. The thickness of the Gd2O3:Eu3+ shells on the SiO2 cores can be adjusted by changing the deposition cycles (70 nm for three deposition cycles). Under short UV excitation, the obtained SiO2@Gd2O3:Eu3+ particles show a strong red emission with 5D0-7F2 (610 nm) of Eu3+ as the most prominent group. The PL intensity of Eu3+ increases with increasing the annealing temperature and the number of coating cycles.
THE ATP-SENSITIVE POTASSIUM-CHANNEL INHIBITOR GLIBENCLAMIDE IMPROVES OUTCOME IN AN OVINE MODEL OF HEMORRHAGIC SHOCK (2004)

This study was designed as a prospective laboratory experiment to evaluate the effects of the ATP-sensitive potassium-channel inhibitor glibenclamide on hemodynamics and end-organ function in an ovine model of hemorrhagic shock. Twenty-four adult sheep were anesthetized and surgically prepared to measure hemodynamics of the systemic and pulmonary circulation. The anterior surface of the abdominal aorta was exposed at a location 6 cm superior to the iliac bifurcation. After a 60-min period of stabilization, this location was punctured with a 14-G needle. To induce a hemorrhagic hypotension (mean arterial pressure [MAP] less than 50 mmHg) via bleeding, the needle was left in place for 15 s to insure good blood flow. Thereafter, it was removed, and the abdomen closed. The animals were then randomized to receive either glibenclamide (4 mg/kg over 15 min) or an equal volume of the vehicle, started 1 h postinjury. Hemodynamic variables were measured every 30 min. Compared with the control group, MAP and systemic vascular resistance index (SVRI) were significantly higher in the intervention group throughout the entire 6-h study period. Ileal pH and urine output were higher in treated than in control animals (4 h, ileal pH 7.29 +/- 0.31 vs. 7.17 +/- 0.6; 6 h, urine output 36 +/- 9 vs. 7.5 +/- 2 mL; P value less than 0.05 each). Because glibenclamide improved both hemodynamics and organ function, it may be a beneficial component in the acute treatment of hemorrhagic shock.
Free Volume Study on Three Types of Shape Memory Polymers by Positron Annihilation (1999)

Temperature dependence of nanoscopic environment of shape memory polymers such as polynorbornene (Tg=313 K), polyurethane (T g=321 K = dynamic viscoelasticity, destruction of hydrogen bond 353 K) and styrene-butadiene copolymer (Tm= 333 K) is observed in terms of free volume parameters -average size, numerical concentration and size distribution -estimated from positronium lifetime measurement, and mechanisms of their shape recoveries are discussed at a molecular level.
Trastuzumab-Resistant Cells Rely on a HER2-PI3K-FoxO-Survivin Axis and Are Sensitive to PI3K Inhibitors (2012)

The antibody trastuzumab is approved for treatment of patients with HER2 (ERBB2)-overexpressing breast cancer. A significant fraction of these tumors are either intrinsically resistant or acquire resistance rendering the drug ineffective. The development of resistance has been attributed to failure of the antibody to inhibit phosphoinositide 3-kinase (PI3K), which is activated by the HER2 network. Herein, we examined the effects of PI3K blockade in trastuzumab-resistant breast cancer cell lines. Treatment with the pan-PI3K inhibitor XL147 and trastuzumab reduced proliferation and pAKT levels, triggering apoptosis of trastuzumab-resistant cells. Compared with XL147 alone, the combination exhibited a superior antitumor effect against trastuzumab-resistant tumor xenografts. Furthermore, treatment with XL147 and trastuzumab reduced the cancer stem-cell (CSC) fraction within trastuzumab-resistant cells both in vitro and in vivo. These effects were associated with FoxO-mediated inhibition of transcription of the antiapoptosis gene survivin (BIRC5) and the CSC-associated cytokine interleukin-8. RNA interference-mediated or pharmacologic inhibition of survivin restored sensitivity to trastuzumab in resistant cells. In a cohort of patients with HER2-overexpressing breast cancer treated with trastuzumab, higher pretreatment tumor levels of survivin RNA correlated with poor response to therapy. Together, our results suggest that survivin blockade is required for therapeutic responses to trastuzumab and that by combining trastuzumab and PI3K inhibitors, CSCs can be reduced within HER2(+) tumors, potentially preventing acquired resistance to anti-HER2 therapy.
Deep Architectures for Learning Context-dependent Ranking Functions (2018)

Object ranking is an important problem in the realm of preference learning. On the basis of training data in the form of a set of rankings of objects, which are typically represented as feature vectors, the goal is to learn a ranking function that predicts a linear order of any new set of objects. Current approaches commonly focus on ranking by scoring, i.e., on learning an underlying latent utility function that seeks to capture the inherent utility of each object. These approaches, however, are not able to take possible effects of context-dependence into account, where context-dependence means that the utility or usefulness of an object may also depend on what other objects are available as alternatives. In this paper, we formalize the problem of context-dependent ranking and present two general approaches based on two natural representations of context-dependent ranking functions. Both approaches are instantiated by means of appropriate neural network architectures, which are evaluated on suitable benchmark task.
Trichosanthin-monoclonal antibody conjugate specifically cytotoxic to human hepatoma cells in vitro. (1991)

A plant single-chain ribosome-inactivating protein derived from the root tuber of Trichosanthes kirilowii, termed trichosanthin (TCS), was modified with 2-iminothiolane. It was not like trichokirin, a ribosome-inactivating protein derived from the seeds of the same plant, in that TCS retained full activity when 1.5 sulfhydryl groups were introduced into each TCS molecule by 2-iminothiolane modification. The 2-iminothiolane-TCS was conjugated to Hepama-1, a monoclonal antibody directed against human hepatoma with a cross-linking reagent, N-succinimidyl-3-(2-pyridyl)-dithiopropionate. The hepatoma cytotoxicity of the immunotoxin, TCS-Hepama-1, was 500-fold higher than that of free TCS and only 1 log lower than that of free ricin. However, the immunotoxin was approximately 600-fold less cytotoxic to HeLa cells. The results suggested that the immunotoxin was a potent and quite specific antihepatoma agent and might have considerable potential in hepatoma therapy.
Diamonds in the rough: Social media visual analytics for journalistic inquiry (2010)

Journalists increasingly turn to social media sources such as Facebook or Twitter to support their coverage of various news events. For large-scale events such as televised debates and speeches, the amount of content on social media can easily become overwhelming, yet still contain information that may aid and augment reporting via individual content items as well as via aggregate information from the crowd's response. In this work we present a visual analytic tool, Vox Civitas, designed to help journalists and media professionals extract news value from large-scale aggregations of social media content around broadcast events. We discuss the design of the tool, present the text analysis techniques used to enable the presentation, and provide details on the visual and interaction design. We provide an exploratory evaluation based on a user study in which journalists interacted with the system to explore and report on a dataset of over one hundred thousand twitter messages collected during the U.S. State of the Union presidential address in 2010.
Oxidative Stress in Keratoconus? (2011)

The increased levels of oxidative stress markers and the decreased antioxidant capacity and antioxidant defenses in KC corneas, as well as in the post-LASIK ectatic corneas, indicate that oxidative stress might be involved in the development of this disease and may provide new insights for its prevention and treatment in the future.
Idiopathic Feline Hepatic Lipidosis (1987)

Idiopathic hepatic lipidosis (IHL) of cats is a disease causing severe liver dysfunction; cats afflicted with the disease have a guarded to poor prognosis for recovery. Hepatic lipidosis or fatty liver also occurs in most domestic species including the dog, the chicken, and ruminants. A variety of etiologies for hepatic lipidosis are known and may be classified as either metabolic, nutritional, toxic or hypoxic conditions. The cause of IHL is unknown.
Polysaccharides from Ganoderma lucidum Promote Cognitive Function and Neural Progenitor Proliferation in Mouse Model of Alzheimer's Disease (2017)

Promoting neurogenesis is a promising strategy for the treatment of cognition impairment associated with Alzheimer's disease (AD). Ganoderma lucidum is a revered medicinal mushroom for health-promoting benefits in the Orient. Here, we found that oral administration of the polysaccharides and water extract from G. lucidum promoted neural progenitor cell (NPC) proliferation to enhance neurogenesis and alleviated cognitive deficits in transgenic AD mice. G. lucidum polysaccharides (GLP) also promoted self-renewal of NPC in cell culture. Further mechanistic study revealed that GLP potentiated activation of fibroblast growth factor receptor 1 (FGFR1) and downstream extracellular signal-regulated kinase (ERK) and AKT cascades. Consistently, inhibition of FGFR1 effectively blocked the GLP-promoted NPC proliferation and activation of the downstream cascades. Our findings suggest that GLP could serve as a regenerative therapeutic agent for the treatment of cognitive decline associated with neurodegenerative diseases.
Effects of trace nickel on the growth kinetics and the electrical characteristics of metal‐induced laterally crystallized polycrystalline silicon and devices (2005)

Abstract— An increase in the rate of nickel‐based metal‐induced lateral crystallization (MILC) of amorphous‐silicon (a‐Si) was observed when the length of an a‐Si island was decreased or, for a given island length, when an extra crystallization‐inducing window was added. With phosphorus implanted in a localized region offset from the MILC front on the a‐Si side, a slight reduction in the MILC rate was also observed. Nickel incorporated in a‐Si beyond the MILC front is believed to be responsible for these effects. A diffusion coefficient of ∼4 × 10 −8 cm 2 /sec was estimated for nickel in a‐Si at 600°C. An extended low‐temperature anneal performed subsequent to the formation of MILC polycrystalline silicon led to a higher effective mobility and a lower off‐state leakage current. If the anneal was performed in the presence of a phosphorus‐implanted region, the leakage current could be further reduced but the activation of subsequently implanted phosphorus was hindered. The same was not observed for the activation of subsequently implanted boron.
Friction transfer deposition of ordered conjugated polymer nanowires and transistor fabrication (2005)

Monodisperse, ordered conjugated polymer nanowires were deposited by friction-transfer technique. Films that comprise such ordered polymer nanowires show a strong optical and electronic anisotropy due to the high compaction of molecule chains in the individual nanowires. Field-effect transistors that were fabricated using poly[9,9-dioctylfluorene-co-bithiophene(F8T2)] nanowires exhibit a field-effect mobility of 3.5×10−2cm2V−1s−1 along the wire direction, which is much higher than the mobility value (5×10−3cm2V−1s−1) obtained in transistors with spin-coated F8T2.
Foundations of Classical Electrodynamics: Charge, Flux, and Metric (2003)

This book presents a fresh and original exposition of the foundations of classical electrodynamics in the tradition of the so-called metric-free approach.
Alzheimer's β-Amyloid, Human Islet Amylin, and Prion Protein Fragment Evoke Intracellular Free Calcium Elevations by a Common Mechanism in a Hypothalamic GnRH Neuronal Cell Line (2000)

A growing number of reports suggest that elevated levels of extracellular Alzheimer's beta-amyloid protein alter the homeostasis of free [Ca(2+)](i) in different cell types of the mammalian brain. In line with these results, we have previously shown that AbetaP[1-40] forms cation-selective channels (Ca(2+) included) across artificial planar bilayers formed from acidic phospholipids and across excised membrane patches from immortalized hypothalamic GnRH neurons (GT1-7 cells), suggesting that the nonregulated Ca(2+)-influx through these spontaneously formed "amyloid channels" may provide a mechanism to explain its toxicity (1). We have now found and report here that the application of AbetaP[1-40] to GT1-7 neurons consistently elevates [Ca(2+)](i) levels. We also found that human islet amylin and the prion protein fragment (PrP106-126), peptides that acquire beta-pleated sheet conformation in water solutions and have been reported to form ion channels across planar bilayer membranes, also increase cytosolic free calcium in GT1-7 neurons. Searching for protective agents, we found that soluble cholesterol, known to decrease the fluidity of the cell membrane, inhibits AbetaP[1-40]-evoked [Ca(2+)](i) rise. These results suggest that unregulated Ca(2+) entry across amyloid channels may be a common mechanism causing cell death, not only in diseases of the third age, including Alzheimer's disease and type 2 diabetes mellitus, but also in prion-induced diseases.
Monoclonal antibodies to human sarcoma and connective tissue differentiation antigens. (1984)

The use of monoclonal antibodies to distinguish human sarcoma from carcinoma cells has been explored. Spleen cells from a BALB/c mouse immunized with a human malignant fibrohistiocytoma were fused with cells of the mouse P3U1 plasmacytoma cell line. Antibodies were then screened for reactivity against human sarcoma and carcinoma cells growing in culture. This work has yielded 2 immunoglobulin G monoclonal antibodies VIE4 and VIF3 which, respectively, reacted with 85% (17 of 20) and 90% (18 of 20) of sarcoma lines tested but with none of eight carcinoma cell line preparations. Reactivity against normal fibroblasts was also demonstrated. By immunofluorescence, the antigens detected by the two antibodies appear to have distinctive intracellular distributions. Immunoprecipitation with VIF3 has shown that it is detecting a protein with a molecular weight of 70,000. When tested against pathological frozen tissue sections, VIF3 reacted with four of 11 and VIE4 with three of 11 human sarcomas but with none of ten carcinomas tested. VIF3 occasionally bound to normal adult connective tissues, whereas no such reactivity was seen with VIE4. These antibodies appear to be directed to fibroblastic markers associated with sarcomas and connective tissue differentiation antigens.
Removal of zinc is required for processing of the mature nucleocapsid protein of human immunodeficiency virus, type 1, by the viral protease. (1994)

In human immunodeficiency virus, RNA selection and packaging during assembly involve the two retroviral-type fingers of the nucleocapsid protein that are held in a constrained configuration by coordinated zinc ions. In this report, we demonstrate that the nucleocapsid protein in a metal bound state is resistant to cleavage by the viral protease, but upon removal of zinc ions by chelating agents, it is hydrolyzed within the first zinc finger between Phe-16 and Asn-17. However, 3-nitrosobenzamide and cupric ions, which release zinc through oxidation of the cysteine residues of the finger, render the nucleocapsid protein resistant to cleavage. Since protease inhibitors and 3-nitrosobenzamide restrict processes relating to steps early in infection, the cleavage of the nucleocapsid protein may represent an essential event that can be exploited for the design of novel antiviral agents.
Autocrine Production of IGF-I Increases Stem Cell-Mediated Neuroprotection (2014)

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder resulting in motor neuron (MN) loss. There are currently no effective therapies; however, cellular therapies using neural progenitor cells protect MNs and attenuate disease progression in G93A-SOD1 ALS rats. Recently, we completed a phase I clinical trial examining intraspinal human spinal stem cell (HSSC) transplantation in ALS patients which demonstrated our approach was safe and feasible, supporting the phase II trial currently in progress. In parallel, efforts focused on understanding the mechanisms underlying the preclinical benefit of HSSCs in vitro and in animal models of ALS led us to investigate how insulin-like growth factor-I (IGF-I) production contributes to cellular therapy neuroprotection. IGF-I is a potent growth factor with proven efficacy in preclinical ALS studies, and we contend that autocrine IGF-I production may enhance the salutary effects of HSSCs. By comparing the biological properties of HSSCs to HSSCs expressing sixfold higher levels of IGF-I, we demonstrate that IGF-I production augments the production of glial-derived neurotrophic factor and accelerates neurite outgrowth without adversely affecting HSSC proliferation or terminal differentiation. Furthermore, we demonstrate that increased IGF-I induces more potent MN protection from excitotoxicity via both indirect and direct mechanisms, as demonstrated using hanging inserts with primary MNs or by culturing with organotypic spinal cord slices, respectively. These findings support our theory that combining autocrine growth factor production with HSSC transplantation may offer a novel means to achieve additive neuroprotection in ALS.
Vascular smooth muscle cell in atherosclerosis (2015)

Vascular smooth muscle cells (VSMCs) exhibit phenotypic and functional plasticity in order to respond to vascular injury. In case of the vessel damage, VSMCs are able to switch from the quiescent 'contractile' phenotype to the 'proinflammatory' phenotype. This change is accompanied by decrease in expression of smooth muscle (SM)-specific markers responsible for SM contraction and production of proinflammatory mediators that modulate induction of proliferation and chemotaxis. Indeed, activated VSMCs could efficiently proliferate and migrate contributing to the vascular wall repair. However, in chronic inflammation that occurs in atherosclerosis, arterial VSMCs become aberrantly regulated and this leads to increased VSMC dedifferentiation and extracellular matrix formation in plaque areas. Proatherosclerotic switch in VSMC phenotype is a complex and multistep mechanism that may be induced by a variety of proinflammatory stimuli and hemodynamic alterations. Disturbances in hemodynamic forces could initiate the proinflammatory switch in VSMC phenotype even in pre-clinical stages of atherosclerosis. Proinflammatory signals play a crucial role in further dedifferentiation of VSMCs in affected vessels and propagation of pathological vascular remodelling.
Model-based tracking with stereovision for AR (2003)

This demo shows a robust model-based tracker using stereovision. The combined use of a 3D model with stereoscopic analysis allows accurate pose estimation in the presence of partial occlusions by non rigid objects like the hands of the user. Furthermore, using a second camera improves the stability of tracking and also simplifies the algorithm.