gebhart/patrepeval huggingface dataset:
Apoptosis induction via microtubule disassembly by an antitumour compound, pironetin (1999)

We reported previously that pironetin and its derivatives were potent inhibitors of cell cycle progression at the M-phase and showed antitumour activity against a murine tumour cell line, P388 leukaemia, transplanted in mice. In this paper, we investigated the mechanism of action of pironetins in antitumour activity and cell cycle arrest at the M-phase. As reported previously for murine leukaemia P388 cells, pironetin showed antitumour activity in a dose-dependent manner in the human leukaemia cell line HL-60. Since DNA fragmentation was observed in both P388 and HL-60 cells, the antitumour activity of pironetin is thought to be due to the induction of apoptosis. Pironetin also induced the rapid phosphorylation of Bcl-2 before formation of the DNA ladder in HL-60 cells, as seen with several tubulin binders. These results suggest that the antitumour activity of pironetin is due to apoptosis caused by the phosphorylation of Bcl-2, and that pironetin targets the microtubules. Pironetin and demethylpironetin exhibited reversible disruption of the cellular microtubule network in normal rat fibroblast 3Y1 cells. However, epoxypironetin, which contains epoxide instead of the double bond of pironetin, showed only weak activity. Since the concentrations that inhibit cell cycle progression at the M-phase were the same as those for disruption of the microtubule network, it was suggested that the mitotic arrest induced by pironetin was the result of the loss of the mitotic spindle. These compounds also inhibited the microtubule-associated protein-induced and glutamate-induced tubulin assembly in vitro. Pironetin inhibited the binding of [3H]vinblastine, but not that of [3H]colchicine, to tubulin, and the Kd values revealed that the affinity of pironetin for tubulin is stronger than that of vinblastine. These results suggest that pironetins are novel antitumour agents which inhibit microtubule assembly.
What Is the Clinical Presentation of Adverse Local Tissue Reaction in Metal-on-metal Hip Arthroplasty? An MRI Study (2018)

Level III, diagnostic study.
Total synthesis and membrane modifying properties of the lipopeptaibol trikoningin KB II and its analogues with acyl chains of different length at the N- and C-termini (1999)

Trikoningin KB II, a ten-amino acid residue lipopeptaibol blocked at the N-terminus by the n-octanoyl group and at the C-terminus by the 1,2-amino alcohol l-leucinol, and extracted from the fungus Trichoderma koningii, exhibits membrane-modifying properties. We have synthesized by solution-phase methods trikoningin KB II and several analogues with acyl chains of different length at the N- and C-termini. Permeability measurements showed that an appropriate length of the linear acyl chain is a more important characteristic for the onset of significant membrane-modifying activity than its position in the peptide chain. Copyright © 1999 European Peptide Society and John Wiley & Sons, Ltd.
MineSpider: Extracting Hidden URLs Behind Evasive Drive-by Download Attacks (2016)

Drive-by download attacks force users to automatically download and install malware by redirecting them to malicious URLs that exploit vulnerabilities of the user's web browser. In addition, several evasion techniques, such as code obfuscation and environment-dependent redirection, are used in combination with drive-by download attacks to prevent detection. In environment-dependent redirection, attackers profile the information on the user's environment, such as the name and version of the browser and browser plugins, and launch a drive-by download attack on only certain targets by changing the destination URL. When malicious content detection and collection techniques, such as honeyclients, are used that do not match the specific environment of the attack target, they cannot detect the attack because they are not redirected. Therefore, it is necessary to improve analysis coverage while countering these adversarial evasion techniques. We propose a method for exhaustively analyzing JavaScript code relevant to redirections and extracting the destination URLs in the code. Our method facilitates the detection of attacks by extracting a large number of URLs while controlling the analysis overhead by excluding code not relevant to redirections. We implemented our method in a browser emulator called MineSpider that automatically extracts potential URLs from websites. We validated it by using communication data with malicious websites captured during a three-year period. The experimental results demonstrated that MineSpider extracted 30,000 new URLs from malicious websites in a few seconds that conventional methods missed.
Depth encoding multicrystal detectors for PET (1998)

A detector unit having a depth encoding scheme was designed and an experimental study has been performed to test the new idea for a positron camera detector. The detector unit consists of a multistage rectangular block of scintillation crystals optically coupled at the bottom face to four photomultiplier tubes (PMTs) in a 2/spl times/2 array or to a position sensitive photomultiplier tube. Each stage of the crystal block consists of four elements in a 2/spl times/2 array. Each scintillation event is mapped in a two dimensional (2D) distribution through the relative ratio of the output signals of the PMTs. The three dimensional location in the detector unit projects into the 2D map so that four top crystals correspond to four innermost regions in the map, and the four bottom crystals facing the PMTs correspond to four outermost regions. With appropriate light control in such a crystal block of Gd/sub 2/SiO/sub 5/:Ce coupled to four PMTs, good positioning performance to encode the depth-of-interaction was obtained for Cs-137 gamma-rays incidence.
Infectious etiopathogenesis of extranodal lymphomas (2008)

Several infectious agents are established causes of non-Hodgkin’s lymphoma in humans. They include human immunodeficiency virus (HIV), Epstein–Barr virus, human herpes virus 8, hepatitis C virus (HCV), and Helicobacter pylori. HIV-associated non-Hodgkin’s lymphomas, although histologically heterogeneous, are characterized by an aggressive clinical course. High-grade disease is common and extranodal sites are often involved, with lesions in the central nervous system being virtually unknown except in the immunosuppressed. Serological surveys from many different populations consistently reported that more than 90% adults are positive for Epstein–Barr virus infection. HCV is hepatotropic and causes hepatitis, liver cirrhosis, and hepatocellular carcinoma. Lyme borreliosis is a multiorgan infection caused by tick-borne spirochetes of the Borrelia burgdorferi. Campylobacter jejuni is probably the most prevalent cause of bacteria-mediated diarrheal disease worldwide and is considered an initiating factor in chronic autoimmune diseases, such as the Guillain–Barre syndrome and reactive arthritis.
Laboratory screening evaluation of the safety of low pH oral care rinse products to dental enamel. (2020)

To assess the hard tissue safety of a variety of low pH oral care rinses to dental enamel in a newly developed screening method.Bovine enamel specimens were subjected to a cycling model that consisted of commercial mouthrinse product exposures and artificial saliva soaks based on a previously published screening method. The effect of test products on the surface of treated specimens was measured using surface microhardness (SMH). Results are presented as the change in SMH (between sound enamel baseline and cycling final). An assortment of rinse products were assessed relative to distilled water (positive control) and 1% citric acid (negative control). A priori, a product was considered safe if the change in measured SMH values over the course of six treatment cycles was both significantly greater than the negative control and was not significantly different from the positive control. A non-inferiority statistical test was applied to create a quantitative rule defining product safety.Products tested included two rinses with a pH in excess of 5.5, and eight with a pH less than 5.5. Four of the rinses included fluoride, while six did not. Analyses showed that all of the rinse products tested passed the non-inferiority acceptance criteria. One of the 10 marketed oral care rinses failed to meet the a priori criteria needed to be considered safe as the product was significantly better than the negative control but also significantly lower than the positive control treatment. This product had the lowest pH of all products tested and did not contain fluoride. Application of the non-inferiority statistical test showed the questionable product passing safety criteria. As a proposed method for a screening tool, further testing would be recommended based on these results.An in vitro enamel safety screening method was applied as an assessment of the enamel demineralization safety to a number of oral care rinse products. Surface microhardness, coupled with a non-inferiority statistical evaluation, provided a reasonable approach for detecting potential product issues. Products failing this screening laboratory method may require additional testing to verify their safety on hard tissues.
A New, Improved and Convenient Synthesis of 4H‐Cyclopenta[2,1‐b:3,4‐b′]dithiophen‐4‐one. (2002)

Abstract For Abstract see ChemInform Abstract in Full Text.
VEGF-C signaling pathways through VEGFR-2 and VEGFR-3 in vasculoangiogenesis and hematopoiesis (2000)

Signaling by vascular endothelial growth factors (VEGFs) through VEGF receptors (VEGFRs) plays important roles in vascular development and hematopoiesis. The authors analyzed the function of VEGF-C signaling through both VEGFR-2 and VEGFR-3 in vasculoangiogenesis and hematopoiesis using a coculture of para-aortic splanchnopleural mesoderm (P-Sp) explants from mouse embryos with stromal cells (OP9). Vasculogenesis and angiogenesis were evaluated by the extent of vascular bed and network formation, respectively. Addition of VEGF-C to the P-Sp culture enhanced vascular bed formation and suppressed definitive hematopoiesis. Both vascular bed and network formations were completely suppressed by addition of soluble VEGFR-1-Fc competitor protein. Formation of vascular beds but not networks could be rescued by VEGF-C in the presence of the competitor, while both were rescued by VEGF-A. VEGFR-3-deficient embryos show the abnormal vasculature and severe anemia. Consistent with these in vivo findings, vascular bed formation in the P-Sp from the VEGFR-3-deficient embryos was enhanced to that in wild-type or heterozygous embryos, and hematopoiesis was severely suppressed. When VEGFR-3-Fc chimeric protein was added to trap endogenous VEGF-C in the P-Sp culture of the VEGFR-3-deficient embryos, vascular bed formation was suppressed and hematopoiesis was partially rescued. These results demonstrate that because VEGF-C signaling through VEGFR-2 works synergistically with VEGF-A, the binding of VEGF-C to VEGFR-3 consequently regulates VEGFR-2 signaling. In VEGFR-3-deficient embryos, an excess of VEGF-C signals through VEGFR-2 induced the disturbance of vasculogenesis and hematopoiesis during embryogenesis. This indicates that elaborated control through VEGFR-3 signaling is critical in vasculoangiogenesis and hematopoiesis. (Blood. 2000;96:3793-3800)
Direct Synthesis of Protoberberine Alkaloids by Rh‐Catalyzed C−H Bond Activation as the Key Step (2015)

A one-pot reaction of substituted benzaldehydes with alkyne-amines by a Rh-catalyzed C-H activation and annulation to afford various natural and unnatural protoberberine alkaloids is reported. This reaction provides a convenient route for the generation of a compound library of protoberberine salts, which recently have attracted great attention because of their diverse biological activities. In addition, pyridinium salt derivatives can also be formed in good yields from α,β-unsaturated aldehydes and amino-alkynes. This reaction proceeds with excellent regioselectivity and good functional group compatibility under mild reaction conditions by using O2 as the oxidant.
ALTERED FRAILTY METABOLOME LINKS CHRONIC INFLAMMATION TO FUNCTIONAL DECLINE (2018)

Frailty is a syndrome of accelerated aging-related multisystemic decline that affects a subset of the most vulnerable older adults. While changes in metabolism have been implicated in development of frailty, comprehensive analyses of metabolic products that differentiate frail from resilient individuals and correlate with physical decline have not been investigated. We used LC/MS technology to profile 141 metabolites in a set of community-dwelling (age 20–97, N=120) individuals. After adjusting for age, the kynurenine/tryptophan ratio was the top metabolomic risk factor for frailty status, the top predictor of walking speed, IL-6, TNFαR1 and IFNγ levels. Increased kynurenine/tryptophan ratio was associated with weaker grip strength. Further dissection of the pathway revealed the accumulation of several kynurenine pathway intermediates with aging and frailty, including increased cytotoxic and neurotoxic 3-hydroxykynurenine, in frail patients compared to young. These discoveries may in part explain the link between inflammation and cognitive and physical decline in frailty.
Combinatorial approach to thin-film transistors using multicomponent semiconductor channels: An application to amorphous oxide semiconductors in In–Ga–Zn–O system (2007)

A combinatorial approach was applied to thin-film transistors (TFTs) using amorphous In–Ga–Zn–O semiconductor channels. A large number of TFTs, having n-type channels with different chemical compositions, were fabricated simultaneously on a substrate. A systematic relation was clarified among the compositional ratio of In:Ga:Zn, oxygen partial pressure in film deposition atmosphere, and TFT characteristics. The results provide an experimental basis to understand the roles of each metallic element in the In–Ga–Zn–O system. This information leads to a guideline to tune the metallic compositions for required TFT specifications.
Abstract 3738: A novel mechanism of STAT3 activation by genotoxic chemotherapy (2023)

Abstract CARP-1, a perinuclear phospho-protein, is a biphasic regulator of cell survival and apoptosis signaling induced by genotoxic drugs. We have previously found that apoptosis induced by genotoxic drugs involved elevated levels of CARP-1. Exposure to genotoxic drugs also induced CARP-1 interaction with NF-κB kinase subunit γ (aka, NEMO) to promote NF-κB activation and cell survival. To further elucidate chemotherapy-activated, CARP-1-dependent cell survival mechanisms, we UV cross-linked protein extracts from Adriamycin-treated HeLa cervical cancer cells with a CARP-1 (614-638) peptide, and conducted liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses of the peptide-bound protein complexes. This experiment revealed STAT3 interaction with CARP-1 (614-638) peptide. Our mutagenesis and co-IP-WB experiments revealed CARP-1 (550-650) directly interacts with a 40 amino acid peptide located in the STAT3 DNA binding domain. Overexpression of mutant STAT3 with in-frame-deletion of CARP-1/CCAR1-binding epitope (CE) peptide (Gst-STAT3 (ΔCE) mutant), but not Gst-STAT3 (WT), failed to translocate to nucleus in Adriamycin-treated cells. Disruption of STAT3-CARP-1 interaction or expression of STAT3 (ΔCE) mutant abolished Adriamycin-induced STAT3 Y705 and S727 phosphorylation. Collectively our data demonstrate that CARP-1 interaction with STAT3 regulates genotoxic chemotherapy-activated STAT3 and its nuclear translocation to promote cancer cell survival and growth. Citation Format: Jaganathan Venkatesh, Magesh Muthu, Nuwan C. Acharige, Mary K. Pflum, Arun K. Rishi. A novel mechanism of STAT3 activation by genotoxic chemotherapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3738.
Molecular Imaging of Mesothelin-Expressing Ovarian Cancer with a Human and Mouse Cross-Reactive Nanobody (2018)

Mesothelin is an epithelial marker highly expressed at the cell surface of cancer cells from diverse origins, including ovarian and pancreatic adenocarcinomas and mesotheliomas. Previously, we identified and characterized an antimesothelin nanobody (NbG3a) for in vitro diagnostic applications. The main goal of this research was to establish the potential of NbG3a as a molecular imaging agent. Site-specific biotinylated NbG3a (bNbG3a) was bound to streptavidin-conjugated reagents for in vitro and in vivo assays. Initially, we performed microscale thermophoresis to determine the binding affinity between bNbG3a and human ( K<sub>d</sub> = 46 ± 8 nM) or mouse ( K<sub>d</sub> = 4.8 ± 0.4 nM) mesothelin protein. The human and mouse cross-reactivity was confirmed by in vivo optical imaging using bNbG3a bound to fluorescent streptavidin. We also localized the binding site of nNbG3a on human mesothelin using overlapping peptide scan. NbG3a recognized an epitope within residues 21-65 of the mature membrane bound form of human mesothelin, which is part of the N-terminal region of mesothelin that is important for interactions between mesothelin on peritoneal cells and CA125 on tumor cells. Next, the bNbG3a in vivo half-life after intravenous injection in healthy mice was estimated by ELISA assay to be 5.3 ± 1.3 min. In tumor-bearing animals, fluorescent bNbG3a accumulated in a subcutaneous ovarian xenograft (A1847) and in two syngeneic, orthotopic ovarian tumors (intraovary and intraperitoneal ID8) within an hour of intravenous injection that peaked by 4 h and persisted up to 48 h. MRI analysis of bNbG3a-targeted streptavidin-labeled iron oxides showed that the MRI signal intensity decreased 1 h after injection for a subcutaneous xenograft model of ovarian cancer for bNbG3a-labeled iron oxides compared to unlabeled iron oxides. The signal intensity differences continued up to the final time point at 24 h post injection. Finally, in vivo immunofluorescence 24 or 48 h after bNbG3a intravenous injection showed bNbG3a diffuse distribution of both xenograft and syngeneic ovarian tumors, with local areas of high concentration throughout A1847 human tumor. The data support the use of NbG3a for continued preclinical development and translation to human applications for cancers that overexpress mesothelin.
Nanostructured Integrated Electron Source (1997)

Additive nanolithography with electron-beam induced deposition is applied to generate a nanostructured integrated field emission electron source. The source is built into a lithographically fabricated pattern of connecting lines on a chip. Current stabilizing resistors are integrated in to the connecting lines with the deposition technique. Field emission microscope investigation of deposited supertips proves that a confined emission is delivered from conducting tips into a beam divergence angle of ±7°. The reduced brightness of the deposited supertips is evaluated. A tenfold higher reduced brightness is observed if compared to conventional Schottky field emitters.
Enhancing carrier mobility of IGZO TFT fabricated by non‐vacuum mist CVD with O3 assistance (2013)

Abstract Recently, we succeeded in demonstrating an oxide TFT consisting of a channel layer (IGZO) and gate insulator (AlO x ) continuously fabricated by non‐vacuum mist CVD. In this report, each thin film and the interfaces of the films have been improved with ozone (O 3 ) assistance, as the initial oxide TFT had poor characteristics compared with those of the IGZO TFT fabricated by the conventional vacuum process. A superhydrophilic interface between AlO x and IGZO was obtained by removing the adhered organic matter from the film surface. The breakdown fields ( E BD ) and dielectric constant ( κ ) of the AlO x thin films were improved from 6 to 8 MV/cm and from 6 to 7, respectively, and the carrier concentration of the IGZO thin film decreased from 10 19 to 10 16 cm –3 . The oxide TFT exhibited field effect mobility ( μ lin ) of 8.7 cm 2 /(Vs), sub‐threshold slope ( S ) of around 0.3 V/dec. and hysteresis ( ΔV H ) of around 0.5 V. These values were obtained by improving each thin film and the interfaces of the films with O 3 assistance. This result is an important first step toward non‐vacuum oxide TFT fabrication processes. (© 2013 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)
Band offset determination of mixed As/Sb type-II staggered gap heterostructure for n-channel tunnel field effect transistor application (2013)

The experimental study of the valence band offset (ΔEv) of a mixed As/Sb type-II staggered gap GaAs0.35Sb0.65/In0.7Ga0.3As heterostructure used as source/channel junction of n-channel tunnel field effect transistor (TFET) grown by molecular beam epitaxy was investigated by x-ray photoelectron spectroscopy (XPS). Cross-sectional transmission electron micrograph shows high crystalline quality at the source/channel heterointerface. XPS results demonstrate a ΔEv of 0.39 ± 0.05 eV at the GaAs0.35Sb0.65/In0.7Ga0.3As heterointerface. The conduction band offset was calculated to be ∼0.49 eV using the band gap values of source and channel materials and the measured valence band offset. An effective tunneling barrier height of 0.21 eV was extracted, suggesting a great promise for designing a metamorphic mixed As/Sb type-II staggered gap TFET device structure for low-power logic applications.
Analyses of Synthetic N-Acyl Dopamine Derivatives Revealing Different Structural Requirements for Their Anti-inflammatory and Transient-Receptor-Potential-Channel-of-the-Vanilloid-Receptor-Subfamily-Subtype-1 (TRPV1)-Activating Properties (2018)

We studied the chemical entities within N-octanoyl dopamine (NOD) responsible for the activation of transient-receptor-potential channels of the vanilloid-receptor subtype 1 (TRPV1) and inhibition of inflammation. The potency of NOD in activating TRPV1 was significantly higher compared with those of variants in which the ortho-dihydroxy groups were acetylated, one of the hydroxy groups was omitted ( N-octanoyl tyramine), or the ester functionality consisted of a bulky fatty acid ( N-pivaloyl dopamine). Shortening of the amide linker (ΔNOD) slightly increased its potency, which was further increased when the carbonyl and amide groups (ΔNODR) were interchanged. With the exception of ΔNOD, the presence of an intact catechol structure was obligatory for the inhibition of VCAM-1 and the induction of HO-1 expression. Because TRPV1 activation and the inhibition of inflammation by N-acyl dopamines require different structural entities, our findings provide a framework for the rational design of TRPV1 agonists with improved anti-inflammatory properties.