gebhart/patrepeval huggingface dataset:
Targeting MDM2-p53 Interaction for Cancer Therapy: Are We There Yet? (2014)

Inactivation of the tumor suppressor p53 and/or overexpression of the oncogene MDM2 frequently occur in human cancers, and are associated with poor prognosis, advanced forms of the disease, and chemoresistance. MDM2, the major negative regulator of p53, induces p53 degradation and inactivates its tumor suppressing activity. In turn, p53 regulates MDM2 expression. This MDM2-p53 negative feedback loop has been widely studied and presents an attractive target for cancer therapy, with a few of the inhibitors of this interaction already having advanced into clinical trials. Additionally, there is an increasing interest in understanding MDM2's p53-independent activities in carcinogenesis and cancer progression, which may also have implications for cancer therapy. This review aims to highlight the various roles that the MDM2-p53 interaction plays in cancer, the p53 independent oncogenic activities of MDM2 and the various strategies that may be used to target MDM2 and the MDM2-p53 interaction. We will summarize the major preclinical and clinical evidences of MDM2 inhibitors for human cancer treatment and make suggestions to further improve efficacy and safety of this interesting class of cancer therapeutics.
Genes associated with hypersensitive response (HR) in the citrus EST database (CitEST) (2007)

Plants are continuously exposed to pathogen attack, but successful infection is rare because they protect themselves against pathogens using a wide range of response mechanisms. One of them is the hypersensitive response (HR), which is a form of cell death often associated with plant resistance to pathogen infection to prevent the spreadsebpg@cnpq.br sebpg@cnpq.br of the potential pathogen from infected to uninfected tissues. Cell death is activated by recognition of pathogen-derived molecules by the resistance (R) gene products, and is associated with the massive accumulation of reactive oxygen species (ROS), salicylic acid (SA), and other pro-death signals such as nitric oxide (NO). The analysis of the citrus EST (CitEST) database revealed the presence of putative genes likely to be involved in HR through their products, like metacaspases, lipoxygenases, phospholipases, pathogenesis-related proteins, glutathione transferases/peroxidases, enzymes involved in the phenylpropanoid pathway and in the formation and detoxification of ROS, as well as those involved in the formation and regulation of ion channels, SA and NO. By analysis of the EST database of Citrus, it was possible to identify several putative genes that code for key enzymes involved in HR triggering and also in plant defense against biotic and abiotic stress.
Improved Immunogenicity of HIV-1 Epitopes in HBsAg Chimeric DNA Vaccine Plasmids by Structural Mutations of HBsAg (1999)

To improve the immunogenicity of epitopes from the envelope protein of HIV-1, we have developed gene gun-delivered subunit DNA vaccines by inserting the sequences encoding the V3 region into the hepatitis B virus (HBV) envelope gene, often called the surface antigen (HBsAg). We have examined the possibility of modifying the immune response to V3 by introducing modifications into the carrier HBsAg in gene gun DNA immunization of mice. In some plasmid constructions, the V3 sequence was introduced into the preS2 region of the HBsAg. Although this region is not present in all protein subunits of the HBsAg particles produced, abolishing the internal translational initiation site for the S protein had no effect on the immune response to V3. Expression of V3 at the N-terminal or C-terminal part of the HBsAg protein resulted in equal anti-V3 antibody and cytotoxic T-lymphocyte (CTL) responses. However, elimination of secretion by single amino-acid mutations in the HBsAg decreased the anti-HBsAg antibody response but enhanced the anti-V3 antibody response. In contrast, the CTL response to V3 was independent of the structural mutations but could be improved by a total deletion of the HBsAg sequence part. Thus, the immune response to heterologous epitopes can be altered by modifications in the carrier HBsAg protein. Modifications of the HBsAg carrier might interfere with the dominant immune response to the HBsAg epitopes, allowing better antibody induction to less immunogenic foreign epitopes. However, for induction of CTL responses, the expression of minimal epitopes may be advantageous.
Nucleic acid aptamers: an emerging frontier in cancer therapy (2012)

The last two decades have witnessed the development and application of nucleic acid aptamers in a variety of fields, including target analysis, disease therapy, and molecular and cellular engineering. The efficient and widely applicable aptamer selection, reproducible chemical synthesis and modification, generally impressive target binding selectivity and affinity, relatively rapid tissue penetration, low immunogenicity, and rapid systemic clearance make aptamers ideal recognition elements for use as therapeutics or for in vivo delivery of therapeutics. In this feature article, we discuss the development and biomedical application of nucleic acid aptamers, with emphasis on cancer cell aptamer isolation, targeted cancer therapy, oncology biomarker identification and drug discovery.
SmI2-Mediated Carbonyl-Alkene Couplings for the Synthesis of Small Carbocyclic Rings (2011)

The electron transfer reducing agent samarium diiodide (SmI2) mediates reductive carbonyl-alkene couplings to give small carbocyclic rings with high diastereocontrol. The substrate scope and mechanism of the reactions is discussed. The application of these versatile reactions in target synthesis is also described.
pygrank: A Python package for graph node ranking (2022)

We introduce pygrank, an open source Python package to define, run and evaluate node ranking algorithms. We provide object-oriented and extensively unit-tested algorithmic components, such as graph filters, post-processors, measures, benchmarks, and online tuning. Computations can be delegated to numpy, tensorflow, or pytorch backends and fit in back-propagation pipelines. Classes can be combined to define interoperable complex algorithms. Within the context of this paper, we compare the package with related alternatives, describe its architecture, demonstrate its flexibility and ease of use with code examples, and discuss its impact.
Identification and validation of FGFR2 peptide for detection of early Barrett's neoplasia (2017)

The incidence of esophageal adenocarcinoma (EAC) is rising rapidly, and early detection within the precursor state of Barrett's esophagus (BE) is challenged by flat premalignant lesions that are difficult detect with conventional endoscopic surveillance. Overexpression of cell surface fibroblast growth factor receptor 2 (FGFR2) is an early event in progression of BE to EAC, and is a promising imaging target. We used phage display to identify the peptide SRRPASFRTARE that binds specifically to the extracellular domain of FGFR2. We labeled this peptide with a near-infrared fluorophore Cy5.5, and validated the specific binding to FGFR2 overexpressed in cells <i>in vitro</i>. We found high affinity k<sub>d</sub> = 68 nM and rapid binding k = 0.16 min<sup>-1</sup> (6.2 min). In human esophageal specimens, we found significantly greater peptide binding to high-grade dysplasia (HGD) versus either BE or normal squamous epithelium, and good correlation with anti-FGFR2 antibody. We also observed significantly greater peptide binding to excised specimens of esophageal squamous cell carcinoma and gastric cancer compared to normal mucosa. These results demonstrate potential for this FGFR2 peptide to be used as a clinical imaging agent to guide tissue biopsy and improve methods for early detection of EAC and potentially other epithelial-derived cancers.
Anatomical Distribution of Prolactin-Like Immunoreactivity in the Rat Brain (1993)

The present study examines prolactin PRL-like immunoreactivity (PRL-LIR) in the rat central nervous system and describes the distribution of labeled perikarya and fibers using a specific antiserum to ovine PRL. This antiserum does not cross-react with molecules of the pro-opiomelanocortin (POMC) family and recognizes rat PRL. PRL-LIR cell bodies are found exclusively in the lateral hypothalamic area surrounding the fornix, especially dorsolateral to it. No labeled cells are detectable in any other part of the brain, including the arcuate nucleus. Labeled fibers are dispersed in almost all parts of the brain. Dense plexuses are observed in the hypothalamus, midline thalamus nuclei, bed nucleus of stria terminalis, raphe dorsalis, and locus coeruleus. There is no apparent decrease in the number of PRL-LIR cell bodies and fibers in hypoprolactinemic mutant rats or after hypophysectomy, suggesting that central PRL is synthesized in such hypothalamic neurons. Comparison of PRL and alpha-melanocyte-stimulating hormone immunostainings provides evidence that the PRL network is independent of those of POMC and melanin-concentrating hormone. The present results support the hypothesis of two independent PRL systems: one peripheral (pituitary gland) and the other cerebral. Concerning the functional role of brain PRL, its widespread projections suggest that PRL is involved in multiple regulations. The presence of PRL-LIR in brain areas involved in sleep-wake control is a strong argument for its role in such a regulation.
Nitrate transport and signalling (2007)

Physiological measurements of nitrate (NO(3)(-)) uptake by roots have defined two systems of high and low affinity uptake. In Arabidopsis, genes encoding both of these two uptake systems have been identified. Most is known about the high affinity transport system (HATS) and its regulation and yet measurements of soil NO(3)(-) show that it is more often available in the low affinity range above 1 mM concentration. Several different regulatory mechanisms have been identified for AtNRT2.1, one of the membrane transporters encoding HATS; these include feedback regulation of expression, a second component protein requirement for membrane targeting and phosphorylation, possibly leading to degradation of the protein. These various changes in the protein may be important for a second function in sensing NO(3)(-) availability at the surface of the root. Another transporter protein, AtNRT1.1 also has a role in NO(3)(-) sensing that, like AtNRT2.1, is independent of their transport function. From the range of concentrations present in the soil it is proposed that the NO(3)(-)-inducible part of HATS functions chiefly as a sensor for root NO(3)(-) availability. Two other key NO(3)(-) transport steps for efficient nitrogen use by crops, efflux across membranes and vacuolar storage and remobilization, are discussed. Genes encoding vacuolar transporters have been isolated and these are important for manipulating storage pools in crops, but the efflux system is yet to be identified. Consideration is given to how well our molecular and physiological knowledge can be integrated as well to some key questions and opportunities for the future.
Combining Pattern Instability and Shape-Memory Hysteresis for Phononic Switching (2009)

We report a fully reversible and robust shape-memory effect in a two-dimensional nanoscale periodic structure composed of three steps, the elastic instability governing the transformation, the plasticity that locks in the transformed pattern as a result of an increase in glass transition temperature (T(g)), and the subsequent elastic recovery due to the vapor-induced decrease in T(g). Solvent swelling of a cross-linked epoxy/air cylinder structure induces an elastic instability that causes a reversible change in the shape of the void regions from circular to oval. The pattern symmetry changes from symmorphic p6mm to nonsymmorphic p2gg brought via the introduction of new glide symmetry elements and leads to a significant change in the phononic band structure, specifically in the opening of a new narrow-band gap due to anticrossing of bands, quite distinct from gaps originating from typical Bragg scattering. We also demonstrate that numerical simulations correctly capture the three steps of the shape-memory cycle observed experimentally.
Laser materials processing systems in 2005 – The world market reaches record volume (2006)

Abstract The market for laser materials processing systems reached a new all time high in 2005. Worldwide sales last year were EUR 4.75 billion (US$ 5.91 billion). This compares to a volume of EUR 4.65 billion (US$ 5.78 billion) in 2004, corresponding to a 2% increase (Fig. 1). These figures are estimated by Optech Consulting based on the market development in the first three quarters of 2005.
Internet Portal for the Environmental Industry (2001)

The Internet revolution has swept the world like no other communication technology before it. Not only has it provided a completely new method of delivering information and services with unprecedented speed, but it also has significantly reduced the importance of distance as a factor in the ability of various parties to collaborate and to exchange and share information with one other. Locus Technologies has attempted to capitalize on this explosion of interest in the Internet and on the advances in tools and technologies in this arena by building a suite of Internet-based applications. This suite, named LocusFocus, includes modules for: (1) operating and controlling groundwater treatment and recovery facilities from a web-based browser; (2) managing environmental data; (3) uploading field data into, and retrieving such data from a centralized database using hand-held, wireless devices; (4) storing and retrieving project documents; and (5) collaborating on-line. LocusFocus is the first comprehensive multi-channel dynamic web portal for the environmental industry.
High pressure infrared xenon laser excited by a UV preionized discharge (1981)

Laser action from neutral Xe transitions has been achieved in an Ar–Xe mixture at 1 atm and in a He–Xe, He–Ar–Xe mixture at 2.5 atm excited by a UV preionized short discharge (Δt?50 ns). In the best mixture, He–Ar–Xe (100–60–1), an overall conversion efficiency of 0.2% was obtained with a 10-mJ output. These nonoptimized results may be improved by decreasing the input energy density and increasing the pressure.
Accident Detection Using Convolutional Neural Networks (2019)

Accidents have been a major cause of deaths in India. More than 80% of accident-related deaths occur not due to the accident itself but the lack of timely help reaching the accident victims. In highways where the traffic is really light and fast-paced an accident victim could be left unattended for a long time. The intent is to create a system which would detect an accident based on the live feed of video from a CCTV camera installed on a highway. The idea is to take each frame of a video and run it through a deep learning convolution neural network model which has been trained to classify frames of a video into accident or non-accident. Convolutional Neural Networks has proven to be a fast and accurate approach to classify images. CNN based image classifiers have given accuracy's of more than 95% for comparatively smaller datasets and require less preprocessing as compared to other image classifying algorithms.
Chemotaxis of human articular chondrocytes and mesenchymal stem cells (2008)

Migration of chondrocytes and mesenchymal stem cells (MSCs) may be important in cartilage development, tissue response to injury, and in tissue engineering. This study analyzed growth factors and cytokines for their ability to induce migration of human articular chondrocytes and bone marrow-derived mesenchymal stem cells in Boyden chamber assays. In human articular chondrocytes serum induced dose- and time-dependent increases in cell migration. Among a series of growth factors and cytokines tested only PDGF induced a significant increase in cell migration. The PDGF isoforms AB and BB were more potent than AA. There was an aging-related decline in the ability of chondrocytes to migrate in response to serum and PDGF. Human bone marrow MSC showed significant chemotaxis responses to several factors, including FBS, PDGF, VEGF, IGF-1, IL-8, BMP-4, and BMP-7. In summary, these results demonstrate that directed cell migration is inducible in human articular chondrocytes and MSC. PDGF is the most potent factor analyzed, and may be useful to promote tissue integration during cartilage repair or tissue engineering.
<i>miR-21</i> as a key regulator of oncogenic processes (2009)

Small non-coding miRNAs (microRNAs) are emerging as key factors involved in cancer at all stages ranging from initiation to metastasis. MIRN21 is an miRNA gene that codes for the miR-21 miRNA which has been found to be overexpressed in many tumour samples where it has been analysed. Whereas consistent overexpression of miR-21 in tumours could be suggestive of functional effects of miR-21 in cancer, more in-depth functional studies with miR-21 are demonstrating that mir-21 displays oncogenic activity and can be classed as an oncomir. Extensive efforts are underway to identify the downstream genes and gene networks regulated by miR-21 and to identify the upstream factors that are regulating expression of miR-21. Even though miR-21 is one of the most intensively studied miRNAs, for all miRNAs, our understanding of miRNA signalling pathways is currently in its early stages. The unravelling of such RNA signalling pathways and networks will be key to understanding the role that dysregulated miRNA functioning can play in oncogenic processes.
Different HLA-B27 subtypes present the same immunodominant Epstein-Barr virus peptide. (1993)

An immunological basis has been postulated for the strong association between at least five subtypes of the HLA-B27 allele (B27.01, .02, .04, .05, and .06) and ankylosing spondylitis, namely that cytotoxic T lymphocyte (CTL) responses are induced against an "arthritogenic" peptide that these different subtypes can all present. This requires a degree of overlap between the peptide binding repertoires of different B27 molecules. The present work, using CTL responses to Epstein-Barr virus (EBV) as a model system in which to identify B27-restricted epitopes, provides the first direct evidence that different disease-related alleles can present the same immunodominant peptide. We first noted that EBV-specific CTL clones, whether from B27.05-, B27.02-, or B27.04-positive donors, were largely subtype-specific in their restriction, recognizing only EBV-transformed B cell lines of the relevant B27 subtype. However, when tested against targets expressing individual EBV proteins from recombinant vaccinia virus vectors, all B27.05-restricted, all B27.02-restricted, and a proportion of B27.04-restricted clones were reactive to the same viral nuclear antigen, Epstein-Barr nuclear antigen (EBNA)3C. In subsequent peptide sensitization assays, all the EBNA3C-specific clones tested and also the EBNA3C-specific component within polyclonal CTL preparations from B27.05-, B27.02-, or B27.04-positive donors recognized the same immunodominant viral peptide RRIYDLIEL (EBNA3C residues 258-266). This sequence accords well with the proposed B27.05 peptide motif and clearly must be accommodated within the different peptide binding grooves of B27.05, B27.02, and B27.04 molecules. Clonal analysis revealed a second component of the B27.04-restricted response that was not shared with other subtypes. This was directed against an EBV latent membrane protein LMP2 epitope whose sequence RRRWRRLTV satisfies some but not all requirements of the B27.05 peptide motif. We conclude that there is indeed a degree of functional overlap between different B27 subtypes in their selection and presentation of CTL epitopes.
Decomposition of 3-Hydroxyanthranilic Acid Under Simulated Physiologic Conditions. (1965)

The stability of 3-hydroxyanthranilic acid (3-HOA) in buffer solutions was investigated as it relates to pH, oxygen tension, and catalytic ion concentrations. The data show that 3-HOA is unstable under certain simulated physiologic conditions, and suggest that the amounts found in some samples of voided urine are not necessarily the true quantities formed, but rather may be the amounts remaining after decomposition of the metabolite in the interim between formation and analysis.
Kinetics of selenate and selenite adsorption/desorption at the goethite/water interface (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTKinetics of selenate and selenite adsorption/desorption at the goethite/water interfacePengchu Zhang and Donald L. SparksCite this: Environ. Sci. Technol. 1990, 24, 12, 1848–1856Publication Date (Print):December 1, 1990Publication History Published online1 May 2002Published inissue 1 December 1990https://pubs.acs.org/doi/10.1021/es00082a010https://doi.org/10.1021/es00082a010research-articleACS PublicationsRequest reuse permissionsArticle Views864Altmetric-Citations223LEARN 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
Synthesis, Physicochemical Characterization, and Biological Evaluation of 2-(1‘-Hydroxyalkyl)-3-hydroxypyridin-4-ones:  Novel Iron Chelators with Enhanced pFe<sup>3+</sup> Values (1999)

The synthesis of a range of 2-(1'-hydroxyalkyl)-3-hydroxypyridin-4-ones as bidentate iron(III) chelators with potential for oral administration is described. The pK(a) values of the ligands and the stability constants of their iron(III) complexes have been determined. Results indicate that the introduction of a 1'-hydroxyalkyl group at the 2-position leads to a significant improvement in the pFe(3+) values. Such an effect was found to be greater with the hydroxyethyl substituent than with the hydroxymethyl substituent, particularly in the cases of 1-ethyl-2-(1'-hydroxyethyl)-3-hydroxypyridin-4-one (pFe(3+) = 21.4) and 1,6-dimethyl-2-(1'-hydroxyethyl)-3-hydroxypyridin-4-one (pFe(3+) = 21.5) where an enhancement on pFe(3+) values in the region of two orders of magnitude is observed, as compared with Deferiprone (1, 2-dimethyl-3-hydroxypyridin-4-one) (pFe(3+) = 19.4). The ability of these novel 3-hydroxypyridin-4-ones to facilitate the iron excretion in bile was investigated using a [(59)Fe]ferritin-loaded rat model. Chelators and prodrug chelators possessing high pFe(3+) values show great promise in their ability to remove iron under in vivo conditions.