gebhart/patrepeval huggingface dataset:
High HSP90 Expression Is Associated with Decreased Survival in Breast Cancer (2007)

The heat shock protein HSP90 chaperones proteins implicated in breast cancer progression, including Her2/neu. HSP90-targeting agents are in clinical trials for breast cancer. HSP90 expression is high in breast cancer cell lines, yet no large studies have been conducted on expression in human tumors and the association with clinical/pathologic variables. Tissue microarrays containing 10 cell lines and primary specimens from 655 patients with 10-year follow-up were assessed using our automated quantitative analysis (AQUA) method; we used cytokeratin to define pixels as breast cancer (tumor mask) within the array spot and measured HSP90 expression within the mask using Cy5-conjugated antibodies. We similarly assessed estrogen receptor, progesterone receptor, and Her2/neu expression. HSP90 expression was more variable in human tumors than in cell lines (P < 0.0001). High HSP90 expression was associated with decreased survival (P = 0.0024). On multivariable analysis, high HSP90 expression remained an independent prognostic marker. High HSP90 expression was associated with high Her2/neu and estrogen receptor, large tumors, high nuclear grade, and lymph node involvement. Although HSP90 levels were high in all our cell lines, expression in tumors was more variable. High HSP90 expression in primary breast cancer defines a population of patients with decreased survival. Evaluation of HSP90 expression in early-stage breast cancer may identify a subset of patients requiring more aggressive or pathway-targeted treatment. Prospective studies are needed to confirm the prognostic role of HSP90, as well as the predictive role of HSP90 expression in patients treated with HSP90 inhibitors.
Influence of Insoluble Excipients on Film Coating Systems (2002)

Insoluble excipients are added to polymeric film coating solutions and dispersions to improve the physical appearance of dosage forms, enhance the stability of photolytic drugs, and aid in processing. These insoluble additives, however, may significantly affect the physical, mechanical, adhesive, and drug-release properties of the films. In this review, the theories of the interactions between polymer and insoluble excipient are addressed. This article also discusses the influence of the concentration, particle size, morphology, and surface chemistry of insoluble excipients on the various polymer properties.
A Raf-independent Epidermal Growth Factor Receptor Autocrine Loop Is Necessary for Ras Transformation of Rat Intestinal Epithelial Cells (1997)

We recently have shown that activated Ras, but not Raf, causes transformation of intestinal (RIE-1, IEC-6) epithelial cells, whereas both activated Ras and Raf transform NIH 3T3 fibroblasts (Oldham, S. M., Clark, G. J., Gangarosa, L. M., Coffey, R. J., and Der, C. J. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 6924-6928). The observations that conditioned medium from Ras-, but not Raf-, transfected RIE-1 cells, as well as exogenous transforming growth factor alpha (TGFalpha), promoted morphological transformation of parental RIE-1 cells prompted us to identify epidermal growth factor (EGF) receptor (EGFR) ligands produced by Ras-transformed RIE-1 cells responsible for this autocrine effect. Since studies in fibroblasts have shown that v-Src is transforming, we also determined if v-Src could transform RIE-1 cells. H- or K-Ras-transformed cells secreted significant amounts of TGFalpha protein, and mRNA transcripts for TGFalpha, amphiregulin (AR), and heparin-binding EGF-like growth factor (HB-EGF) were induced. Like Ras, v-Src caused morphological and growth transformation of parental RIE-1 cells. However, TGFalpha protein was not secreted by RIE-1 cells stably expressing v-Src or activated Raf, and only minor increases in EGFR ligand mRNA expression were detected in these cells. A selective EGFR tyrosine kinase inhibitor PD153035 attenuated the Ras-, but not Src-, transformed phenotype. Taken together, these observations provide a mechanistic and biochemical basis for the ability of activated Ras, but not activated Raf, to cause transformation of RIE-1 cells. Finally, we suggest that an EGFR-dependent mechanism is necessary for Ras, but not Src, transformation of these intestinal epithelial cells.
Distribution of the magnetization reversal duration in subnanosecond spin-transfer switching (2007)

We study the experimental distribution of switching times in spin-transfer switching induced by sub-ns current pulses in a pillar-shaped spin valve, whose free layer easy axis is parallel to the spin polarization of the current. The pulse durations leading to successful switching events follow a multiply stepped distribution. The step positions reflect the precessional nature of the switching. Modeling indicates that the switching proceeds through an integer number of gradually amplified precession cycles. This number is determined by the initial magnetization state. The switching probability distribution can be modeled considering the thermal variance of the initial magnetization orientation and by analyzing the occurrence of a vanishing total torque condition in the set possible magnetization trajectories. Modeling helps us to understand why switching cannot happen with a reproducible sub-ns duration when the free layer easy axis is parallel to the spin polarization of the current. To circumvent that problem, we propose to bias the spin valve with a hard axis field, which could provide an increased reproducibility of the switching duration.
Isolation and Characterization of Anthramycin, a New Antitumor Antibiotic (1965)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIsolation and Characterization of Anthramycin, a New Antitumor AntibioticW. Leimgruber, V. Stefanović, F. Schenker, A. Karr, and J. BergerCite this: J. Am. Chem. Soc. 1965, 87, 24, 5791–5793Publication Date (Print):December 1, 1965Publication History Published online1 May 2002Published inissue 1 December 1965https://pubs.acs.org/doi/10.1021/ja00952a050https://doi.org/10.1021/ja00952a050research-articleACS PublicationsRequest reuse permissionsArticle Views572Altmetric-Citations143LEARN 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
Conventional and Immunoelectron Microscopy of Mitochondria (2007)

Electron microscopy (EM) has been a central tool in delineating the subcellular organization and function of the eukaryotic cell. It has provided valuable information on the organization of the Golgi complex; the polarized distribution of proteins on the plasma membrane; and fundamental insights into the essential structure and function of mitochondria beginning with the first EM observations of Claude and Fullam on isolated mitochondria in 1944. Most significant for this volume is the contribution immunoelectron microscopy (IEM) has made in the study of mitochondrial dynamics and in demonstrating the localizations of key mitochondrial proteins in yeast, including, though not limited to, Dnm1p, Fiz1p, and Mgm1p. This chapter is not intended to provide a comprehensive review of all EM and IEM methods as there are a number of excellent books and reviews already available on these topics. Rather, this chapter provides detailed protocols of conventional EM and IEM methods successfully utilized in our center for the examination and analysis of mitochondria in yeast and mammalian cells.
CENP-C is required for maintaining proper kinetochore size and for a timely transition to anaphase. (1994)

The human autoantigen CENP-C has been demonstrated by immunoelectron microscopy to be a component of the inner kinetochore plate. Here we have used antibodies raised against various portions of CENP-C to probe its function in mitosis. We show that nuclear microinjection of anti-CENP-C antibodies during interphase causes a transient arrest at the following metaphase. Injection of the same antibodies after the initiation of prophase, however, does not disrupt mitosis. Correspondingly, indirect immunofluorescence using affinity-purified human anti-CENP-C antibodies reveals that levels of CENP-C staining are reduced at centromeres in cells that were injected during interphase, but appear unaffected in cells which were injected during mitosis. Thus, we suggest that the injected antibodies cause metaphase arrest by reducing the amount of CENP-C at centromeres. Examination of kinetochores in metaphase-arrested cells by electron microscopy reveals that the number of trilaminar structures is reduced. More surprisingly, the few remaining kinetochores in these cells retain a normal trilaminar morphology but are significantly reduced in diameter. In cells arrested for extended periods, these small kinetochores become disrupted and apparently no longer bind microtubules. These observations are consistent with an involvement of CENP-C in kinetochore assembly, and suggest that CENP-C plays a critical role in both establishing and/or maintaining proper kinetochore size and stabilizing microtubule attachments. These findings also support the idea that proper assembly of kinetochores may be monitored by the cell cycle checkpoint preceding the transition to anaphase.
Potential Impact of Seawater Uranium Extraction on Marine Life (2016)

A variety of adsorbent materials have been developed to extract uranium from seawater as an alternative traditional terrestrial mining. A large-scale deployment of these adsorbents would be necessary to recover useful quantities of uranium, and this raises a number of concerns regarding potential impacts on the surrounding marine environment. Two concerns are whether or not the adsorbent materials are toxic and any potentially harmful effects that may result from depleting uranium or vanadium (also highly concentrated by the adsorbents) from the local environment. To test the potential toxicity of the adsorbent with or without bound metals, Microtox assays were used to test both direct contact toxicity and the toxicity of any leachate in the seawater. The Microtox assay was chosen because it detected nonspecific mechanisms of toxicity. Toxicity was not observed with leachates from any of the 68 adsorbent materials that were tested, but direct contact with some adsorbents at very high adsorbent concentrations exhibited toxicity. These concentrations are, however, very unlikely to be seen in the actual marine deployment. Adsorbents that accumulated uranium and trace metals were also tested for toxicity, and no toxic effect was observed. Biofouling on the adsorbents and in columns or flumes containing the adsorbents also indicates that the adsorbents are not toxic and that there may not be an obvious deleterious effect resulting from removing uranium and vanadium from seawater. An extensive literature search was also performed to examine the potential impact of uranium and vanadium extraction from seawater on marine life using the Pacific Northwest National Laboratory’s (PNNL’s) document analysis tool, IN-SPIRE. Although other potential environmental effects must also be considered, results from both the Microtox assay and the literature search provide preliminary evidence that uranium extraction from seawater could be performed with minimal impact on marine fauna.
CCL17 and CCL22 chemokines within tumor microenvironment are related to accumulation of Foxp3+ regulatory T cells in gastric cancer (2008)

Abstract It has been reported that an increased population of regulatory T cells (Tregs) is one of the reasons for impaired anti‐tumor immunity. Recently, Foxp3 has been reported as a reliable marker of Tregs. The authors investigated the frequency of Foxp3 + Tregs within CD4 + cells in TILs, regional lymph nodes and PBLs of gastric cancer patients ( n = 45). Furthermore, to elucidate the mechanisms behind Treg accumulation within tumors, they evaluated the relationship between CCL17 or CCL22 expression and the frequency of Foxp3 + Tregs in gastric cancer. CD4 + CD25 + Foxp3 + Tregs as a percentage of CD4 + cells were counted by flow cytometry and evaluated by immunohistochemistry. Moreover, an in vitro migration assay using Tregs derived from gastric cancers was performed in the presence of CCL17 or CCL22. As a result, the frequency of Foxp3 + Tregs in TILs was significantly higher than that in normal gastric mucosa (12.4% ± 7.5% vs . 4.1% ± 5.3%, p &lt; 0.01). Importantly, the increase in Tregs in TILs occurred to the same extent in early and advanced disease. Furthermore, the frequency of CCL17 + or CCL22 + cells among CD14 + cells within tumors was significantly higher than that of normal gastric mucosa, and there was a significant correlation between the frequency of CCL17 + or CCL22 + cells and Foxp3 + Tregs in TILs. In addition, the in vitro migration assay indicated that Tregs were significantly induced to migrate by CCL17 or CCL22. In conclusion, CCL17 and CCL22 within the tumor are related to the increased population of Foxp3 + Tregs, with such an observation occurring in early gastric cancer. © 2008 Wiley‐Liss, Inc.
Joint VM placement and routing for data center traffic engineering (2012)

Today's data centers need efficient traffic management to improve resource utilization in their networks. In this work, we study a joint tenant (e.g., server or virtual machine) placement and routing problem to minimize traffic costs. These two complementary degrees of freedom—placement and routing—are mutually-dependent, however, are often optimized separately in today's data centers. Leveraging and expanding the technique of Markov approximation, we propose an efficient online algorithm in a dynamic environment under changing traffic loads. The algorithm requires a very small number of virtual machine migrations and is easy to implement in practice. Performance evaluation that employs the real data center traffic traces under a spectrum of elephant and mice flows, demonstrates a consistent and significant improvement over the benchmark achieved by common heuristics.
Proposal of a Genome Editing System for Genetic Resistance to Tomato Spotted Wilt Virus (2014)

Viruses provoke considerable economical losses in agriculture. New molecular approaches to develop genetic resistance based on translational genomics and precision genetic modifications are highly expected. The type II Clustered, Regularly Interspaced Palindromic Repeats (CRISPR) system including Cas9 nuclease represent a promising and very powerful tool to specifically modulate the expression and activity of genes involved in biotic stress responses. In this study, we describe an approach to develop a platform system based on CRISPR system for genome editing technology in tomato. Tomato is an excellent plant for this approach considering the high-quality genome sequence, the rapid life cycle, the highly efficient in vitro plant culture and transformation protocols, Genome editing can be used to allow resistance to Tomato Spotted Wilt Virus (TSWV) infections by the successful obtainment of two specific objectives: (1) development of a Genome Editing (GE) system using CRISPR-Cas9 system in tomato (Objective 1) and (2) test the system in inducing genetic resistance to TSWV infections. First, it will be necessary to model the molecular dynamics of key host and pathogen proteins predicting how targeted mutations affect these interactions. Then these host players will be targeted by CRISPR-Cas9 technology. The obtained plants can be evaluated for their phenotypic resistance and deeply analyzed using "omic" platforms to gain insight into gene regulatory networks of plant resistance. Outcomes of the proposed project will be essentially three: (1) Identify host target proteins interacting with pathogenic proteins and model their dynamic interactions; (2) develop a platform technology usable to obtain resistant tomatoes to TSWV inducing targeted genetic modifications in the genome; (3) facilitate the adaption of this platform to the improvement of important traits in other specialty crops.
Enteric Flora in Health and Disease (2006)

The human gut is the natural habitat for a large and dynamic bacterial community. Recently developed molecular biology tools suggest that a substantial part of these bacterial populations are still to be described. However, the relevance and impact of resident bacteria on host's physiology and pathology is well documented. Major functions of the gut microflora include metabolic activities that result in salvage of energy and absorbable nutrients, protection of the colonized host against invasion by alien microbes, and important trophic effects on intestinal epithelia and on immune structure and function. Gut bacteria play an essential role in the development and homeostasis of the immune system. It is important to underscore that the specialised lymphoid follicles of the gut mucosa are the major sites for induction and regulation of the immune system. On the other hand, there is evidence implicating the gut flora in certain pathological conditions, including multisystem organ failure, colon cancer and inflammatory bowel diseases.
A case study on the implementation of the Illinois Scan Architecture (2002)

Scan based test techniques offer a very efficient alternative to achieve high fault coverage when compared to functional pattern testing. As circuit sizes grow ever larger, test data volume and test application time grow unwieldy even in the very efficient scan based designs. The Illinois Scan Architecture is a low cost alternative to conventional scan. In this paper, we present the first ever reported case study of the effectiveness of the Illinois Scan Architecture on an industrial circuit.
Pasteurella haemolytica leukotoxin: chemiluminescent responses of peripheral blood leukocytes from several different mammalian species to leukotoxin- and opsonin-treated living and killed Pasteurella haemolytica and Staphylococcus aureus. (1986)

A luminol-dependent chemiluminescence (LDCL) assay was used to assess the response of polymorphonuclear leukocyte (PMN) preparations from 4 species of ruminants (ie, cattle, sheep, goats, and antelopes) and 6 species of nonruminants (ie, swine, dogs, cats, rabbits, horses, and persons) to both opsonized and nonopsonized preparations of living and heat-killed Pasteurella haemolytica and Staphylococcus aureus and to opsonized and nonopsonized heat-killed strains of each bacterium in the presence of sterile culture supernatant (leukotoxin) from P haemolytica. The LDCL responses of PMN preparations from each of the species studied were greater for living than for heat-killed S aureus. The most efficient LDCL emission was observed with reaction mixtures containing opsonized living S aureus. Regardless whether they contained killed or living bacteria, the opsonized S aureus preparations elicited LDCL emissions more efficiently than did the corresponding nonopsonized preparations. Living P haemolytica cells and their sterile culture supernatant inhibited the LDCL emissions of phagocytically stimulated PMN preparations from ruminants, but not those from nonruminants. The LDCL response of ruminant PMN to nonopsonized living P haemolytica was characterized by the development of a peak response at 10 minutes of incubation followed by a precipitous decrease and a subsequent complete cessation of chemiluminescence. The peak LDCL response was higher for opsonized living P haemolytica than for nonopsonized living bacteria, and the increased response lasted longer. However, opsonization of living P haemolytica with the serum samples tested only temporarily spared the ruminant PMN preparations from the detrimental effects of leukotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)
The synergic antitumor effects of paclitaxel and temozolomide co-loaded in mPEG-PLGA nanoparticles on glioblastoma cells (2016)

To get better chemotherapy efficacy, the optimal synergic effect of Paclitaxel (PTX) and Temozolomide (TMZ) on glioblastoma cells lines was investigated. A dual drug-loaded delivery system based on mPEG-PLGA nanoparticles (NPs) was developed to potentiate chemotherapy efficacy for glioblastoma. PTX/TMZ-NPs were prepared with double emulsification solvent evaporation method and exhibited a relatively uniform diameter of 206.3 ± 14.7 nm. The NPs showed sustained release character. Cytotoxicity assays showed the best synergistic effects were achieved when the weight ratios of PTX to TMZ were 1:5 and 1:100 on U87 and C6 cells, respectively. PTX/TMZ-NPs showed better inhibition effect to U87 and C6 cells than single drug NPs or free drugs mixture. PTX/TMZ-NPs (PTX: TMZ was 1:5(w/w)) significantly inhibited the tumor growth in the subcutaneous U87 mice model. These results indicate that coordinate administration of PTX and TMZ combined with NPs is an efficient method for glioblastoma.
Glycosidase Inhibition by Multivalent Presentation of Heparan Sulfate Saccharides on Bottlebrush Polymers (2017)

We report herein the first-time exploration of the attachment of well-defined saccharide units onto a synthetic polymer backbone for the inhibition of a glycosidase. More specifically, glycopolymers endowed with heparan sulfate (HS) disaccharides were established to inhibit the glycosidase, heparanase, with an IC<sub>50</sub> value in the low nanomolar range (1.05 ± 0.02 nm), a thousand-fold amplification over its monovalent counterpart. The monomeric moieties of these glycopolymers were designed in silico to manipulate the well-established glycotope of heparanase into an inhitope. Studies concluded that (1) the glycopolymers are hydrolytic stable toward heparanase, (2) longer polymer length provides greater inhibition, and (3) increased local saccharide density (monoantennary vs diantennary) is negligible due to hindered active site of heparanase. Furthermore, HS oligosaccharide and polysaccharide controls illustrate the enhanced potency of a multivalent scaffold. Overall, the results on these studies of the multivalent presentation of saccharides on bottlebrush polymers serve as the platform for the design of potent glycosidase inhibitors and have potential to be applied to other HS-degrading proteins.