gebhart/patrepeval huggingface dataset:
The function of Ia+ dendritic cells and Ia- dendritic cell precursors in thymocyte mitogenesis to lectin and lectin plus interleukin 1. (1988)

The response of thymocytes to lectin is a standard tissue culture model for identifying cytokines such as IL-1 that are required for thymocyte mitogenesis. To study accessory cell requirements for these responses, it was necessary to deplete endogenous accessory cells with two techniques: anti-Ia and complement, and passage over nylon wool. Proliferation to Con A was then restored with 0.1-0.3% exogenous splenic dendritic cells, or 30-fold higher levels of peritoneal macrophages. The "costimulatory" action of IL-1, whereby responses to lectin were enhanced 3-10-fold, required the presence of dendritic cells. This effect of IL-1 could be reproduced by culturing the dendritic cells for 12 h in 1 U/ml human or murine rIL-1 alpha before addition to the thymocyte proliferation assay. The function of IL-1-treated dendritic cells was not blocked by a neutralizing anti-IL-1 antibody. The endogenous population of thymic accessory cells was partially characterized. A trace (0.1-0.3%) fraction of Ia+, Ig-, plastic nonadherent dendritic cells was visualized and enriched to a level of 1-10% by depleting CD4+,CD8+, and Ig+ lymphocytes. When this double-negative population was cultured with IL-1 and washed, the treated thymic dendritic cells were 10-fold more active as accessory cells. When the CD4-,CD8-, Ig- populations were depleted of dendritic cells with anti-Ia and complement, the subsequent addition of IL-1 had a second effect. Ia+ dendritic cells redeveloped over a 2-d interval, and they exhibited the same properties as resident dendritic cells in thymus and spleen. The majority were lysed by 33D1 anti-dendritic cell mAb and complement, lacked Fc receptors, and acted as powerful stimulators of the MLR and Con A mitogenesis. The development of dendritic cells did not occur with IL-2, -3, -4 or granulocyte/macrophage colony-stimulating factor or in nylon-nonadherent populations. The IL-1-dependent, Ia- precursor was not detectable in bone marrow. These results begin to analyze the endogenous accessory function of the thymus in culture. Dendritic cells actively stimulate thymocyte mitogenesis. The mitogenic action of IL-1 involves effects on resident Ia+ dendritic cells as well as a new population of thymic, Ia- precursors.
Polymeric micelles for delivery of poorly soluble drugs: Preparation and anticancer activityin vitroof paclitaxel incorporated into mixed micelles based on poly(ethylene glycol)-lipid conjugate and positively charged lipids (2005)

Paclitaxel-loaded mixed polymeric micelles consisting of poly(ethylene glycol)-distearoyl phosphoethanolamine conjugates (PEG-PE), solid triglycerides (ST), and cationic Lipofectin lipids (LL) have been prepared. Micelles with the optimized composition (PEG-PE/ST/LL/paclitaxel = 12/12/2/1 by weight) had an average micelle size of about 100 nm, and zeta-potential of about -6 mV. Micelles were stable and did not release paclitaxel when stored at 4 degree C in the darkness (just 2.9% of paclitaxel have been lost after 4 months with the particle size remaining unchanged). The release of paclitaxel from such micelles at room temperature was also insignificant. However, at 37 degree C, approx. 16% of paclitaxel was released from PEG-PE/ST/LL/paclitaxel micelles in 72 h, probably, because of phase transition in the ST-containing micelle core. In vitro anticancer effects of PEG-PE/ST/LL/paclitaxel and control micelles were evaluated using human mammary adenocarcinoma (BT-20) and human ovarian carcinoma (A2780) cell lines. Paclitaxel in PEG-PE/ST/LL micelles demonstrated the maximum anti-cancer activity. Cellular uptake of fluorescently-labeled paclitaxel-containing micelles by BT-20 cells was investigated using a fluorescence microscopy. It seems that PEG-PE/ST/LL micelles, unlike micelles without the LL component, could escape from endosomes and enter the cytoplasm of BT-20 cancer cells thus increasing the anticancer efficiency of the micellar paclitaxel.
Constant normal‐moveout (CNMO) correction: a technique and test results (2000)

We introduce a processing technique which minimizes the ‘stretching effects’ of conventional NMO correction. Unlike conventional NMO, the technique implies constant normal moveout (CNMO) for a finite time interval of a seismic trace. The benefits of the proposed method include preservation of higher frequencies and reduction of spectral distortions at far offsets. The need for severe muting after the correction is reduced, allowing longer spreads for stack, velocity and AVO analysis. The proposed technique has been tested on model and real data. The method may improve the resolution of CMP stack and AVO attribute analysis. The only assumptions for this stretch‐free NMO correction are (i) all time samples of a digital reflected wavelet at a particular offset have the same normal moveout, and (ii) reflection records have an interference nature.
Low temperature plasma biomedicine: A tutorial review (2014)

Gas discharge plasmas formed at atmospheric pressure and near room temperature have recently been shown to be potentially useful for surface and wound sterilization, antisepsis, bleeding cessation, wound healing, and cancer treatment, among other biomedical applications. This tutorial review summarizes the field, stressing the likely role of reactive oxygen and nitrogen species created in these plasmas as the biologically and therapeutically active agents. Reactive species, including radicals and non-radical compounds, are generated naturally within the body and are now understood to be essential for normal biological functions. These species are known to be active agents in existing therapies for wound healing, infection control, and cancer treatment. But they are also observed at elevated levels in persons with many diseases and are associated with aging. The physical and chemical complexity of plasma medical devices and their associated biochemical effects makes the development of safe, effective plasma medical devices and procedures a challenge, but encouragingly rapid progress has been reported around the world in the last several years.
Induction of macrophage migration inhibitory factor by lysophosphatidic acid: Relevance to tumor growth and angiogenesis (2003)

Macrophage migration inhibitory factor (MIF) plays an important role not only in the immune system, but also in tumorigenesis. Lysophosphatidic acid (LPA), a unique lipid mediator, shares several biological functions with MIF, including promotion of tumor cell growth and associated angiogenesis. In this study, we investigated the signaling cross-talk between these two molecules during tumorigenesis and angiogenesis. We first examined the expression of MIF mRNA on a murine colon cancer cell line, colon 26, by LPA. We found that LPA enhanced the expression of MIF mRNA in a dose-dependent manner in vitro. In parallel, LPA stimulated cell growth and up-regulated the vascular endothelial growth factor (VEGF). These effects were dramatically blocked by 21 base double strand (ds) RNA specific for mouse MIF mRNA (RNAi). In vivo, colon 26 cells treated with MIF dsRNA were injected into the backs of mice. The size of tumor volumes became significantly smaller than that of controls. Angiogenesis examined by a Millipore chamber method was also suppressed by the MIF dsRNA. Next, we evaluated the signal transduction pathway relevant to the mitogen-activated protein kinase (MAPK) and Akt/PI3K pathways in response to LPA by RNAi. Ras activation and phosphorylation of Akt and ERK1/2 were strongly suppressed by the dsRNA. On the other hand, tyrosine phosphorylation was minimally changed by the treatment. Taken together, these results suggest that MIF could promote both tumor cell growth and angiogenesis induced by LPA via both the Ras-MAPK and Ras-Akt/PI3K signaling pathways.
Lysyl oxidase-like-2 promotes tumour angiogenesis and is a potential therapeutic target in angiogenic tumours (2013)

Lysyl oxidase-like 2 (LOXL2), a secreted enzyme that catalyzes the cross-linking of collagen, plays an essential role in developmental angiogenesis. We found that administration of the LOXL2-neutralizing antibody AB0023 inhibited bFGF-induced angiogenesis in Matrigel plug assays and suppressed recruitment of angiogenesis promoting bone marrow cells. Small hairpin RNA-mediated inhibition of LOXL2 expression or inhibition of LOXL2 using AB0023 reduced the migration and network-forming ability of endothelial cells, suggesting that the inhibition of angiogenesis results from a direct effect on endothelial cells. To examine the effects of AB0023 on tumour angiogenesis, AB0023 was administered to mice bearing tumours derived from SKOV-3 ovarian carcinoma or Lewis lung carcinoma (LLC) cells. AB0023 treatment significantly reduced the microvascular density in these tumours but did not inhibit tumour growth. However, treatment of mice bearing SKOV-3-derived tumours with AB0023 also promoted increased coverage of tumour vessels with pericytes and reduced tumour hypoxia, providing evidence that anti-LOXL2 therapy results in the normalization of tumour blood vessels. In agreement with these data, treatment of mice bearing LLC-derived tumours with AB0023 improved the perfusion of the tumour-associated vessels as determined by ultrasonography. Improved perfusion and normalization of tumour vessels after treatment with anti-angiogenic agents were previously found to improve the delivery of chemotherapeutic agents into tumours and to result in an enhancement of chemotherapeutic efficiency. Indeed, treatment with AB0023 significantly enhanced the anti-tumourigenic effects of taxol. Our results suggest that inhibition of LOXL2 may prove beneficial for the treatment of angiogenic tumours.
Ustekinumab in the treatment of psoriatic arthritis: latest findings and clinical potential (2013)

Ustekinumab (UST) is a fully human immunoglobulin G1κ (IgG1κ) monoclonal antibody against common sub-unit p40 of interleukin-12 (IL-12) and interleukin-23 (IL-23). IL-12 and IL-23 are essential components of the Th1 and Th17 inflammatory pathways, respectively, and are the key mediators of psoriasis. Psoriatic arthritis (PsA), an important systemic inflammatory disorder, has similar pathogenesis to psoriasis. Many of PsA patients do not respond to tumor necrosis factor (TNF) inhibitor therapy, highlighting the need for additional treatment modalities with distinct mechanisms of action. Also, many patients stop responding to these agents after a certain period of use. A significant number of patients have a recurrent course or a persistent disease process. To meet these challenges a new agent working on different inflammatory aspect of PsA is needed. UST has been demonstrated to be effective, safe on short-term use and convenient in the treatment of plaque psoriasis and PsA. Long-term safety is still a concern. Until recently, the exact role of UST in the management of PsA had not been very clear. This article reviews the mechanism of action, pharmacokinetics, efficacy, safety profile and the clinical potential of UST in patients with PsA. We also discuss the three major trials conducted to show the efficacy and safety of UST in PsA.
A Statistical Framework to Predict Functional Non-Coding Regions in the Human Genome Through Integrated Analysis of Annotation Data (2015)

Identifying functional regions in the human genome is a major goal in human genetics. Great efforts have been made to functionally annotate the human genome either through computational predictions, such as genomic conservation, or high-throughput experiments, such as the ENCODE project. These efforts have resulted in a rich collection of functional annotation data of diverse types that need to be jointly analyzed for integrated interpretation and annotation. Here we present GenoCanyon, a whole-genome annotation method that performs unsupervised statistical learning using 22 computational and experimental annotations thereby inferring the functional potential of each position in the human genome. With GenoCanyon, we are able to predict many of the known functional regions. The ability of predicting functional regions as well as its generalizable statistical framework makes GenoCanyon a unique and powerful tool for whole-genome annotation. The GenoCanyon web server is available at http://genocanyon.med.yale.edu.
Mouse mammary tumor virus gene expression is suppressed by oligomeric ellagitannins, novel inhibitors of poly(ADP-ribose) glycohydrolase. (1992)

Oligomeric ellagitannins (nobotanins B, E, and K) were found to be potent inhibitors of poly(ADP-ribose) glycohydrolase purified from mouse mammary tumor 34I cells. Kinetic analysis revealed that the inhibition of nobotanin B (dimer) was competitive with respect to the substrate poly(ADP-ribose), whereas nobotanin E (trimer) and nobotanin K (tetramer) exhibited mixed-type inhibition. These results suggest that the dimeric structure of ellagitannin may have a functional domain that competes with poly(ADP-ribose) on the poly(ADP-ribose) glycohydrolase molecule. To determine the inhibitory effects of oligomeric ellagitannins on poly(ADP-ribose) glycohydrolase in vivo, we examined their effects on de-poly(ADP-ribosyl)ation of some chromosomal proteins in intact 34I cells that was induced by glucocorticoid treatment. Nobotanin B caused concentration-dependent inhibition of glucocorticoid-induced de-poly(ADP-ribosyl)ation of HMG 14 and 17 and histone H1 in intact 34I cells. Interestingly, this inhibition was associated with suppression of the glucocorticoid-sensitive mouse mammary tumor virus (MMTV) mRNA synthesis. In contrast, nobotanin E and K had little inhibitory effect on either de-poly(ADP-ribosyl)ation of these proteins or induction of MMTV transcription after glucocorticoid treatment. Nobotanin B but not E and K was taken into 34I cells. These results may suggest that the suppression of glucocorticoid-sensitive MMTV transcription results from in vivo inhibition of poly(ADP-ribose) glycohydrolase by nobotanin B. These results also indicate the importance of de-poly(ADP-ribosyl)ation of HMG 14 and 17 and histone H1 in regulation of transcription of the glucocorticoid-sensitive MMTV gene.
The role of complement in glucan-induced protection against septic shock. (1988)

Previous studies from our laboratory have shown that glucan will significantly enhance survival, decrease bacteremia, maintain reticuloendothelial function, and reduce histopathology in a murine model of gram-negative septic shock [1]. The present study was undertaken to evaluate the role of complement in glucan-enhanced protection against septic shock. AKR/J mice, which are congenitally C5-deficient, and ICR/HSD mice that were complement-depleted by treatment with purified cobra venom factor (CVF), were injected IP with glucan (50 mg/kg) on days 5 and 3 prior to IP challenge with 1 X 10(8) E. coli. Survival data indicated that glucan (p less than 0.05) increased survival in both C5-deficient and complement-depleted mice. Glucan prophylaxis resulted in a neutrophilic leukocytosis 8 h following E. coli challenge. However, glucan did not alter bone marrow proliferation. We conclude that, 1) glucan's protective effect on survival is not dependent on complement, 2) complement is not required for glucan-induced neutrophilic leukocytosis in this model, and 3) glucan does not enhance bone marrow proliferation in complement-deficient mice.
Traceable Self‐Assembly of Laser‐Triggered Cyanine‐Based Micelle for Synergistic Therapeutic Effect (2015)

To track nanocarriers, many researches adopt nanocarriers labeled with radiotracers or encapsulating near-infrared fluorescence (NIRF) dye. In this study, novel amphiphilic copolymers, methoxy poly(ethylene glycol) (mPEG)-cyanine-poly(ε-caprolactone) (PCL) (mPEG-Cy-PCL) are synthesized. mPEG-Cy-PCL are capable of performing NIRF imaging, photothermal therapy (PTT) on cancer cells and self-assembly nanocarriers. Cy-based micelles can encapsulate doxorubicin (Doxo@Cy-micelle) and achieve NIRF image-guided drug delivery. Doxo@Cy-micelles are nanosized micelles enhancing the accumulation of Doxo in tumor sites and decreasing side effects. Doxo@Cy-micelles exhibit an excellent PTT and synergistic chemotherapy of cancer via laser-triggered release of Doxo from micelles, eventually resulting in decreased cancer recurrence rates. The results show that Cy-based micelles are excellent nanocarriers for NIRF imaging and synergistic photothermal-chemotherapy of cancer.
Extinction of Oct-3/4 gene expression in embryonal carcinoma x fibroblast somatic cell hybrids is accompanied by changes in the methylation status, chromatin structure, and transcriptional activity of the Oct-3/4 upstream region. (1993)

In this study we evaluate, for the first time, the molecular mechanism that underlies the extinction of a tissue-specific transcription factor, Oct-3/4, in somatic cell hybrids and compared it with its down-regulation in retinoic acid (RA)-treated embryonal carcinoma (EC) cells. The Oct-3/4 gene, which belongs to the POU family of transcription factors and is abundantly expressed in EC (OTF9-63) cells, provides an excellent model system with which to study the extinction phenomenon. Unlike other genes whose expression has been repressed in hybrid cells but not during in vivo differentiation, Oct-3/4 expression is dramatically repressed in OTF9-63 x fibroblast hybrids and also during embryogenesis. The ectopic expression of Oct-3/4 in hybrid cells under a constitutive promoter is sufficient for transcriptional activation of an octamer-dependent promoter. These results argue against the possibility that fibroblasts contain a direct repressor which binds directly to the octamer sequence and prevents Oct-3/4 protein from binding. The extinction of Oct-3/4 binding activity in the hybrid cells occurs at the level of mRNA transcription, similarly to the repression of Oct-3/4 transcription during in vivo differentiation. This shutdown of Oct-3/4 transcription in hybrid cells and in RA-treated EC cells is accompanied by de novo methylation of its 1.3-kb upstream region. In contrast to EC cells, in which this region is sensitive to MspI digestion, in hybrid cells and in RA-treated EC cells, the Oct-3/4 upstream region is resistant to MspI digestion, which suggests a change in its chromatin structure. Furthermore, extinction is not restricted to the endogenous Oct-3/4 gene but is also exerted upon a transiently transfected reporter gene driven by the Oct-3/4 upstream region. Thus, changes in the cellular activity of trans-acting factors acting on the upstream region also contribute to the inability of the hybrid and RA-treated EC cells to generate Oct-3/4 transcripts. In conclusion, this study draws a connection between the shutdown of Oct-3/4 expression in RA-differentiated EC cells and its extinction in hybrid cells. In both systems, repression of Oct-3/4 expression is achieved through changes in the methylation status, chromatin structure, and transcriptional activity of the Oct-3/4 upstream regulatory region.
TheDrosophilainsulin/IGF receptor controls growth and size by modulating PtdInsP3 levels (2002)

Understanding the control of size is of fundamental biological and clinical importance. Insulin/IGF signaling during development controls growth and size, possibly by coordinating the activities of the Ras and PI 3-kinase signaling pathways. We show that in Drosophila mutating the consensus binding site for the Ras pathway adaptor Drk/Grb2 in Chico/IRS does not interfere with growth whereas mutating the binding sites of the PI 3-kinase adaptor p60 completely abrogates Chico function. Furthermore, we present biochemical and genetic evidence that loss of the homolog of the tumor suppressor gene, Pten, results in increased PtdInsP(3) levels and that these increased levels are sufficient to compensate for the complete loss of the Insulin/insulin-like growth factor receptor function. This reduction of Pten activity is also sufficient to vastly increase organism size. These results suggest that PtdInsP(3) is a second messenger for growth and that levels of PtdInsP(3) during development regulate organismal size.
Gdev: first-class GPU resource management in the operating system (2012)

Graphics processing units (GPUs) have become a very powerful platform embracing a concept of heterogeneous many-core computing. However, application domains of GPUs are currently limited to specific systems, largely due to a lack of “first-class ” GPU resource management for general-purpose multi-tasking systems. We present Gdev, a new ecosystem of GPU resource management in the operating system (OS). It allows the user space as well as the OS itself to use GPUs as firstclass computing resources. Specifically, Gdev’s virtual memory manager supports data swapping for excessive memory resource demands, and also provides a shared device memory functionality that allows GPU contexts to communicate with other contexts. Gdev further provides a GPU scheduling scheme to virtualize a physical GPU into multiple logical GPUs, enhancing isolation among working sets of multi-tasking systems. Our evaluation conducted on Linux and the NVIDIA GPU shows that the basic performance of our prototype implementation is reliable even compared to proprietary software. Further detailed experiments demonstrate that Gdev achieves a 2x speedup for an encrypted file system using the GPU in the OS. Gdev can also improve the makespan of dataflow programs by up to 49 % exploiting shared device memory, while an error in the utilization of virtualized GPUs can be limited within only 7%. 1
Rho and ROCK Signaling in VEGF‐Induced Microvascular Endothelial Hyperpermeability (2006)

ABSTRACT Objectives: Vascular endothelial growth factor (VEGF) plays an important role in the regulation of microvascular permeability under various physiological and pathological conditions. The authors tested the hypothesis that the small GTPase Rho and its downstream effector ROCK (Rho‐associated coiled‐coil‐containing protein kinase) mediate VEGF‐induced increases in venular permeability. They also investigated myosin light chain (MLC) phosphorylation and actin polymerization, two well‐characterized targets of the Rho‐ROCK pathway that are implicated in the regulation of endothelial barrier function. Methods: The apparent permeability coefficient of albumin ( P a ) was measured in intact isolated porcine coronary venules and in cultured coronary venular endothelial cell (CVEC) monolayers. RhoA activation was determined using a Rhotekin‐agarose pull down assay. MLC phosphorylation was evaluated by immunoblotting with phospho‐specific antibodies, and endothelial cellular F‐actin was viewed using fluorescence microscopy. Results: VEGF increased P a in both isolated coronary venules and CVEC monolayers. The hyperpermeability response occurred in a similar time course to that of Rho activation, MLC phosphorylation, and actin stress fiber formation. Selective blockage of ROCK with Y27632 dose‐dependently inhibited VEGF‐induced venular hyperpermeability. Moreover, inhibition of either Rho with exoenzyme C3 or ROCK with Y‐27632 attenuated VEGF‐induced increases in permeability, MLC phosphorylation, and actin‐stress fiber formation in CVEC monolayers. Conclusions: Collectively, these findings suggest that the Rho–ROCK signal pathway contributes to VEGF‐induced hyperpermeability. Myosin light‐chain phosphorylation and actin stress fiber formation occur concomitantly with the increase in permeability upon VEGF stimulation.