gebhart/patrepeval huggingface dataset:
Dimethylfumarate Attenuates Renal Fibrosis via NF-E2-Related Factor 2-Mediated Inhibition of Transforming Growth Factor-β/Smad Signaling (2012)

TGF-β plays a key role in the development of renal fibrosis. Suppressing the TGF-β signaling pathway is a possible therapeutic approach for preventing this disease, and reports have suggested that Nrf2 protects against renal fibrosis by inhibiting TGF-β signaling. This study examines whether dimethylfumarate (DMF), which stimulates Nrf2, prevents renal fibrosis via the Nrf2-mediated suppression of TGF-β signaling. Results showed that DMF increased nuclear levels of Nrf2, and both DMF and adenovirus-mediated overexpression of Nrf2 (Ad-Nrf2) decreased PAI-1, alpha-smooth muscle actin (α-SMA), fibronectin and type 1 collagen expression in TGF-β-treated rat mesangial cells (RMCs) and renal fibroblast cells (NRK-49F). Additionally, DMF and Ad-Nrf2 repressed TGF-β-stimulated Smad3 activity by inhibiting Smad3 phosphorylation, which was restored by siRNA-mediated knockdown of Nrf2 expression. However, downregulation of the antioxidant response element (ARE)-driven Nrf2 target genes such as NQO1, HO-1 and glutathione S-transferase (GST) did not reverse the inhibitory effect of DMF on TGF-β-induced upregulation of profibrotic genes or extracellular matrix proteins, suggesting an ARE-independent anti-fibrotic activity of DMF. Finally, DMF suppressed unilateral ureteral obstruction (UUO)-induced renal fibrosis and α-SMA, fibronectin and type 1 collagen expression in the obstructed kidneys from UUO mice, along with increased and decreased expression of Nrf2 and phospho-Smad3, respectively. In summary, DMF attenuated renal fibrosis via the Nrf2-mediated inhibition of TGF-β/Smad3 signaling in an ARE-independent manner, suggesting that DMF could be used to treat renal fibrosis.
Granulocyte-colony stimulating factor promotes lung metastasis through mobilization of Ly6G+Ly6C+ granulocytes (2010)

Priming of the organ-specific premetastatic sites is thought to be an important yet incompletely understood step during metastasis. In this study, we show that the metastatic tumors we examined overexpress granulocyte-colony stimulating factor (G-CSF), which expands and mobilizes Ly6G+Ly6C+ granulocytes and facilitates their subsequent homing at distant organs even before the arrival of tumor cells. Moreover, G-CSF-mobilized Ly6G+Ly6C+ cells produce the Bv8 protein, which has been implicated in angiogenesis and mobilization of myeloid cells. Anti-G-CSF or anti-Bv8 antibodies significantly reduced lung metastasis. Transplantation of Bv8 null fetal liver cells into lethally irradiated hosts also reduced metastasis. We identified an unexpected role for Bv8: the ability to stimulate tumor cell migration through activation of one of the Bv8 receptors, prokineticin receptor (PKR)-1. Finally, we show that administration of recombinant G-CSF is sufficient to increase the numbers of Ly6G+Ly6C+ cells in organ-specific metastatic sites and results in enhanced metastatic ability of several tumors.
Synthesis of a novel phosphatidylcholine conjugated to docosahexaenoic acid and methotrexate that inhibits cell proliferation (2002)

Here we report the synthesis and characterization of a lipophilic phosphatidylcholine containing the omega-3 fatty acid docosahexaenoic acid (DHA) and the cytotoxic drug methotrexate (MTX). This novel phospholipid combines the fatty acid's and the drug's anticancer activities in a molecule amenable to a liposome bilayer for safe, simultaneous delivery of the two agents. Two phosphatidylcholines were synthesized, from 1-stearoyl or 1-docosahexaenoyl, 2-hydroxy-sn-glycero-3-phosphocholine, to contain MTX in the sn-2 position and either stearic acid or DHA in the sn-1 position. The products contain fatty acid, MTX and phosphorus (1:1:1), and the MTX was released by phospholipase A(2), consistent with the proposed phospholipid structure. The predominant product linked MTX to the glycerol moiety through MTX's gamma-carboxyl group. Liposomes composed of 1-stearoyl, 2-oleoyl phosphatidylcholine plus 1-stearoyl, 2-oleoyl phosphatidylethanolamine and various concentrations of the novel phospholipids caused dose-dependent inhibition of murine leukemia cell proliferation in culture. The DHA- and MTX-containing phosphatidylcholine was more effective than that containing stearic acid, and DHA appeared to synergize with MTX when they were added as free agents or covalently linked in the phospholipid. These data show the feasibility of synthesizing, and the inhibitory activity of phosphatidylcholine with DHA in the sn-1 position and MTX in the sn-2 position, and suggest the compound's potential use in cancer chemotherapy.
Two‐dimensional location and shape reconstruction (1994)

A method for reconstructing the location and the shape of a bounded impenetrable object from measured scattered field data is presented. The algorithm is, in principle, the same as that used for reconstructing the conductivity of a penetrable object and uses the fact that for high conductivity the skin depth of the scatterer is small, in which case the only meaningful information produced by the algorithm is the boundary of the scatterer. A striking increase in efficiency is achieved by incorporating into the algorithm the fact that for large conductivity the contrast is dominated by a large positive imaginary part. This fact, together with the knowledge that the scatterer is constrained in some test domain, constitute the only a priori information about the scatterer that is used. There are no other implicit assumptions about the location, connectivity, convexity, or boundary conditions. Some refinements of the algorithm which reduce the number of points at which the unknown function is updated are incorporated to further increase efficiency. Results of a number of numerical examples are presented which demonstrate the effectiveness of the location and shape reconstruction algorithm.
ENDOTOXIN-MEDIATED DELAYED ISLET GRAFT FUNCTION IS ASSOCIATED WITH INCREASED INTRA-ISLET CYTOKINE PRODUCTION AND ISLET CELL APOPTOSIS1 (2001)

We propose that endotoxin contamination is the primum movens of a chain of events that involves intra-islet cytokine production and release and islet cell apoptosis, and endotoxin contamination can ultimately lead to primary nonfunction in vivo. This emphasizes the fact that using endotoxin-free reagents during isolation is a key factor for successful islet transplantation.
Identification of a pathogenicity island, which contains genes for virulence and avirulence, on a large native plasmid in the bean pathogenPseudomonas syringaepathovar phaseolicola (1999)

The 154-kb plasmid was cured from race 7 strain 1449B of the phytopathogen Pseudomonas syringae pv. phaseolicola (Pph). Cured strains lost virulence toward bean, causing the hypersensitive reaction in previously susceptible cultivars. Restoration of virulence was achieved by complementation with cosmid clones spanning a 30-kb region of the plasmid that contained previously identified avirulence (avr) genes avrD, avrPphC, and avrPphF. Single transposon insertions at multiple sites (including one located in avrPphF) abolished restoration of virulence by genomic clones. Sequencing 11 kb of the complementing region identified three potential virulence (vir) genes that were predicted to encode hydrophilic proteins and shared the hrp-box promoter motif indicating regulation by HrpL. One gene achieved partial restoration of virulence when cloned on its own and therefore was designated virPphA as the first (A) gene from Pph to be identified for virulence function. In soybean, virPphA acted as an avr gene controlling expression of a rapid cultivar-specific hypersensitive reaction. Sequencing also revealed the presence of homologs of the insertion sequence IS100 from Yersinia and transposase Tn501 from P. aeruginosa. The proximity of several avr and vir genes together with mobile elements, as well as G+C content significantly lower than that expected for P. syringae, indicates that we have located a plasmid-borne pathogenicity island equivalent to those found in mammalian pathogens.
Metabolic catastrophe as a means to cancer cell death (2007)

During tumorigenesis, normal growth mechanisms are deregulated and safeguards that eliminate abnormal cells by apoptosis are disabled. Tumor cells must also increase nutrient uptake and angiogenesis to support the upregulation of metabolism necessary for unrestricted growth. In addition, they have to rely on inefficient energy production by glycolysis. This glycolytic state can result from mutations that promote cell proliferation, the hypoxic tumor microenvironment and perhaps mitochondrial malfunction. Moreover, the very signals that enable unrestricted cell proliferation inhibit autophagy, which normally sustains cells during nutrient limitation. In tumors, inactivation of the autophagy pathway may enhance necrosis and inflammation and promote genomic instability, which can further enhance tumor growth. Thus, tumor cells cannot adapt efficiently to metabolic stress and could be induced to die by metabolic catastrophe, in which high energy demand is contrasted by insufficient energy production. Efforts to exploit this unique metabolic state clinically previously focused mainly on detecting tissue displaying increased glycolytic metabolism. The challenge now is to induce metabolic catastrophe therapeutically as an approach to killing the unkillable cells.
Emulsion Liquid Membranes for Wastewater Treatment: Equilibrium Models for Some Typical Metal-Extractant Systems (1994)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEmulsion Liquid Membranes for Wastewater Treatment: Equilibrium Models for Some Typical Metal-Extractant SystemsBhavani. Raghuraman, Neena. Tirmizi, and John. WiencekCite this: Environ. Sci. Technol. 1994, 28, 6, 1090–1098Publication Date (Print):June 1, 1994Publication History Published online1 May 2002Published inissue 1 June 1994https://pubs.acs.org/doi/10.1021/es00055a018https://doi.org/10.1021/es00055a018research-articleACS PublicationsRequest reuse permissionsArticle Views535Altmetric-Citations57LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Display of Biologically Functional Insecticidal Toxin on the Surface of λ Phage (2004)

The successful use of Bacillus thuringiensis insecticidal toxins to control agricultural pests could be undermined by the evolution of insect resistance. Under selection pressure in the laboratory, a number of insects have gained resistance to the toxins, and several cases of resistance in the diamondback moth have been reported from the field. The use of protein engineering to develop novel toxins active against resistant insects could offer a solution to this problem. The display of proteins on the surface of phages has been shown to be a powerful technology to search for proteins with new characteristics from combinatorial libraries. However, this potential of phage display to develop Cry toxins with new binding properties and new target specificities has hitherto not been realized because of the failure of displayed Cry toxins to bind their natural receptors. In this work we describe the construction of a display system in which the Cry1Ac toxin is fused to the amino terminus of the capsid protein D of bacteriophage lambda. The resultant phage was viable and infectious, and the displayed toxin interacted successfully with its natural receptor.
Development of a plastic encapsulated multichip technology for high volume, low cost commercial electronics (1995)

Non-military/noncomputer electronics industry segments such as PC's, workstations, portable electronics, the automotive and medical industries, automated test equipment, and high-end consumer goods, are evolving rapidly. They demand higher complexity and higher performance circuits and components. At the same time, many of these industry segments are being driven to shrink size, weight, and power dissipation. Standard low cost packaging approaches such as thru-hole PCB and chip and wire hybrids, can no longer efficiently interconnect these more complex circuits. These industry segments are being forced to turn to new higher performance packaging approaches such as SMT, MCM, and COB. This paper describes an innovative embedded chip MCM technology that eliminates high cost structures, as well as materials and processes in current thin film MCM technologies. A plastic encapsulated multichip technology has been developed in which an epoxy encapsulant is molded around bare die to form the MCM substrate. This new MCM process readily scales-up to high volume production and is inherently high yielding, while maintaining all of the performance advantages of the GE developed overlay HDI process. This paper describes the thermal, mechanical, and chemical stability issues that drove this development, the process used to fabricate the modules, and the cost and yield advantages associated with this structure.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Diagnosing Non-Intermittent Anomalies in Reinforcement Learning Policy Executions (Short Paper) (2017)

Due to the safety risks and training sample inefficiency, it is often preferred to develop controllers in simulation. However, minor differences between the simulation and the real world can cause a significant sim-to-real gap. This gap can reduce the effectiveness of the developed controller. In this paper, we examine a case study of transferring an octorotor reinforcement learning controller from simulation to the real world. First, we quantify the effectiveness of the real-world transfer by examining safety metrics. We find that although there is a noticeable (around 100%) increase in deviation in real flights, this deviation may not be considered unsafe, as it will be within > 2m safety corridors. Then, we estimate the densities of the measurement distributions and compare the Jensen-Shannon divergences of simulated and real measurements. From this, we show that the vehicle’s orientation is significantly different between simulated and real flights. We attribute this to a different flight mode in real flights where the vehicle turns to face the next waypoint. We also find that the reinforcement learning controller actions appear to correctly counteract disturbance forces. Then, we analyze the errors of a measurement autoencoder and state transition model neural network applied to real data. We find that these models further reinforce the difference between the simulated and real attitude control, showing the errors directly on the flight paths. Finally, we discuss important lessons learned in the sim-to-real transfer of our controller.
Color Doppler sonography of the hepatic artery and portal venous system. (1990)

Color Doppler sonography is an important noninvasive diagnostic tool for detecting abnormalities of the hepatic vasculature in patients with diffuse liver disease. To study its usefulness in these cases, we retrospectively reviewed the findings in 147 patients with abnormal portal venous color Doppler sonograms. This group comprised all patients with abnormal portal venous color Doppler sonograms studied from February 1987 to July 1989. Correlative imaging was not available in all cases. The sonographic diagnoses included (1) portal venous thrombosis (50 patients, 93 vessels); (2) portal-systemic or portal-portal collaterals (80 patients, 95 collaterals); (3) reversed, bidirectional, or other abnormal portal venous flow patterns (36 patients); and (4) abnormal hepatic arterial flow (20 patients). Since the results reported derive from a retrospective review without consistent correlation with other imaging studies, no appraisal of the sensitivity or accuracy of portal color Doppler sonography could be made from our data. The ability of color Doppler sonography to visualize flow without altering hemodynamics has led to several novel observations in these patients. These include increased arterial flow in states of low portal blood flow, reversal of portal flow direction postprandially, coincident reversed and hepatopetal flow in different branches of a single portal vein, and normal helical portal venous flow. These and other findings show that color Doppler sonography has enhanced our ability to detect abnormalities of the hepatic and portal venous system.
White pines,Ribes, and blister rust: a review and synthesis (2010)

Summary For over a century, white pine blister rust ( Cronartium ribicola ) has linked white pines ( Strobus ) with currants and gooseberries ( Ribes ) in a complex and serious disease epidemic in Asia, Europe, and North America. Because of ongoing changes in climate, societal demands for forests and their amenities, and scientific advances in genetics and proteomics, our current understanding and management of the white pine blister rust pathosystem has become outdated. Here, we present a review and synthesis of international scope on the biology and management of blister rust, white pines, Ribes , and other hosts. In this article, we provide a geographical and historical background, describe the taxonomy and life cycle of the rust, discuss pathology and ecology, and introduce a series of invited papers. These review articles summarize the literature on white pines, Ribes , and blister rust with respect to their status, threats, and management through genetics and silviculture. Although the principal focus is on North America, the different epidemics in Europe and Asia are also described. In the final article, we discuss several of the key observations and conclusions from the preceding review articles and identify prudent actions for research and management of white pine blister rust.
Clinical implications of chromosomal abnormalities in multiple myeloma (2006)

The adverse prognostic role of cytogenetic abnormalities has recently been established in plasma cell dyscrasias. Modern techniques such as fluorescence in situ hybridization and comparative genomic hybridization have revealed a higher incidence of cytogenetic abnormalities in patients with multiple myeloma (MM) compared to conventional cytogenetics. Hypodiploidy and chromosome 13 abnormalities are found in more than 50% of myeloma patients, representing well known factors with adverse prognosis. Rearrangements involving the switch regions of immunoglobulin heavy chain (IgH) gene at 14q32 with various partner genes represent the most common structural abnormalities, having an incidence of 70% in MM. Structural abnormalities of chromosomes 17 and 8 involving the p53 and c-myc genes are considered to be less frequent events, but carry a poor prognosis. New therapeutic approaches such as non-myeloablative allotransplantation and modern therapeutic agents (thalidomide, lenalidomide, and bortezomib) and their combinations give promise for an improved therapeutic management of patients with MM. The detection of t(4;14), t(14;16), deletion of chromosome 13 on metaphase analysis, or deletion of p53 by FISH will define high-risk prognostic groups that are not generally controlled with high-dose melphalan and autologous stem cell transplantation (ASCT), and should therefore be treated with more investigational therapies. Alternatively, eligible patients who do not have these poor risk factors are more likely to benefit from a high-dose, melphalan-based, regimen followed by ASCT.
Decreased carotid arterial resistance in cats in response to trigeminal stimulation (1984)

Stimulation of the trigeminal nerve or ganglion in the cat caused a frequency-dependent reduction in carotid vascular resistance. Systemic arterial blood pressure (SABP) decreased at low frequencies (0.2 to 5 sec-1) and increased at higher frequencies, thus increasing carotid blood flow at the higher frequencies. The effect on resistance was predominantly ipsilateral and was unaltered by cervical sympathectomy, but was abolished or substantially reduced by section of the trigeminal root proximal to the ganglion. Diminution of carotid vascular resistance was replicated by stimulation of the greater superficial petrosal (GSP) nerve without any change in SABP. Section of the seventh cranial nerve reduced or abolished the response to stimulation of the trigeminal nerve but not that from the GSP nerve. The trigeminal response was prevented by ganglion-blocking drugs in seven out of eight cats. The resistance response was unaffected by noradrenergic, cholinergic, serotonergic, and histamine-2 blocking agents. No neural connection could be demonstrated between the GSP and the trigeminal ganglion, and the vascular response to GSP stimulation persisted after trigeminal section. It is concluded that activation of the trigeminal system increases carotid blood flow by a pathway involving the seventh cranial nerve, the GSP and Vidian nerves, and a parasympathetic synapse employing an unconventional transmitter. A varying proportion of the response (greatest in the third division) may be mediated by antidromic activation of trigeminal nerves. These findings may have clinical implications for the vascular changes of migraine and other facial pain.
PREPARATION AND ASSAY OF THE INTERNATIONAL STANDARDS FOR CLOSTRIDIUM BOTULINUM TYPES A, B, C, D AND E ANTITOXINS. (1963)

The National Institute for Medical Research, London, was authorized in 1962 by the WHO Expert Committee on Biological Standardization to establish the International Standards for Clostridium botulinum Types A, B, C, D and E Antitoxins and to define the International Units. For this purpose use was made of the material accepted in 1954 as the British reference preparations and reconstituted in 1960 for establishment as the first British standards.
New molecular mediators in tumor angiogenesis (2000)

Angiogenesis is essential for tumor growth and progression. It has been demonstrated that tumor growth beyond a size 1 to 2 mm(3) requires the induction of new vessels. Angiogenesis is regulated by several endogenous stimulators and inhibitors of endothelial cell migration, proliferation and tube formation. Under physiological conditions these mediators of endothelial cell growth are in balance and vessel growth is limited. In fact, within the angiogenic balance endothelial cell turnover is sufficient to maintain a functional vascular wall but does not allow vessel growth. Tumor growth an progression has successfully been correlated to the serum concentration of angiogenic mediators. Furthermore, the vascular density of tumor tissues could be correlated to the clinical course of the disease in several tumor entities. Within the last years several new mediators of endothelial cell growth have been isolated e.g. angiopoietin 1, angiopoietin 2, midkine, pleiotropin, leptin and maspin. In this review we discuss the mechanisms leading to tumor angiogenesis and describe some of the newer mediators of endothelial cell stimulation and inhibition.
A Phase I Study of α-Galactosylceramide (KRN7000)–Pulsed Dendritic Cells in Patients with Advanced and Recurrent Non–Small Cell Lung Cancer (2005)

In this clinical trial, alphaGalCer-pulsed DC administration was well tolerated and could be safely done even in patients with advanced disease.