55 research outputs found
AMČR - archeologický záznam C-201900875A
No full textStav: 3Lokalizace/okolnosti: Vítězná, úsek od Všehrdovy k parkovišti Zborovská. Parc. č. 1069, 1073. Inženýrské sítě.Souhrn/upřesnění: Konstrukci zdi Z2 lze interpretovat jako vnější cihelný plášť a zděné jádro kurtiny barokního opevnění (obr. 2, 3), jak lze doložit promítnutím jejího průběhu do výřezu rekonstrukční mapy publikované M. Semerádem a J. Havrdou (Semerád – Havrda 2016, 54, obr. 3).
Zdivo Z5 by mohlo souviset s výstavbou řetězového mostu prolomeného kurtinou v r. 1838 (Semerád – Havrda 2016, 55).
Zdiva Z3 a Z4 nelze prozatím blíže klasifikovat.
Konstrukce identifikovaná v západním profilu v jižním úseku výkopu patrně souvisí se zástavbou 19. stol.
AMČR - archeologický záznam C-9104148A
No full textStav: 3Lokalizace/okolnosti: Pole na JV okraji vsi, mezi silnicí, vodojemem a řekou Metují. Náhodný nález na poli.Souhrn/upřesnění: Dne 30. 1. 2001 přinesl J. Havrda do M Náchod ukázat kamennou vrtanou teslici z amfibolitu. Teslici nalezla sestra pana Havrdy na poli. Nález nepochybně souvisí se zdejším neolitickým sídlištěm
Integration of Notch1 and calcineurin/NFAT signaling pathway in keratinocyte growth and differentiation control.
No full textNoThe Notch and Calcineurin/NFAT pathways have both been implicated in control of keratinocyte differentiation. Induction of the p21WAF1/Cip1 gene by Notch 1 activation in differentiating keratinocytes is associated with direct targeting of the RBP-J¿ protein to the p21 promoter. We show here that Notch 1 activation functions also through a second Calcineurin-dependent mechanism acting on the p21 TATA box-proximal region. Increased Calcineurin/NFAT activity by Notch signaling involves downregulation of Calcipressin, an endogenous Calcineurin inhibitor, through a HES-1-dependent mechanism. Besides control of the p21 gene, Calcineurin contributes significantly to the transcriptional response of keratinocytes to Notch 1 activation, both in vitro and in vivo. In fact, deletion of the Calcineurin B1 gene in the skin results in a cyclic alopecia phenotype, associated with altered expression of Notch-responsive genes involved in hair follicle structure and/or adhesion to the surrounding mesenchyme. Thus, an important interconnection exists between Notch 1 and Calcineurin-NFAT pathways in keratinocyte growth/differentiation control
Abstract 2047: The muscarinic receptor antagonist, benztropine, blocks the expansion of a temozolomide resistant subpopulation of glioma cells
No full textAbstract
Virtually all malignant gliomas become drug-resistant and recur after initial treatment, recurrent tumors are fatal within two-years, and no therapies exist that cure gliomas. The recognition that subpopulations of primitive cells with an oligodendrocyte precursor-like (OPC-like) phenotype capable of resisting standard therapy and contributing to recurrence, frames the question of whether adjuvant therapies designed to modify or eliminate OPC-like cells could slow the progression of glioma. Agents that force the differentiation of treatment-resistant OPC-like glioma cells, a phenomenon that requires cessation of proliferation, are compelling candidates for targeting OPC-like GSCs. Recently, it was observed that OPC proliferation was driven by activation of the M1, M3 and M4 muscarinic receptors. In another report, a large-scale drug screen designed to seek drugs to induce OPC differentiation in the context of multiple sclerosis identified a muscarinic receptor antagonist, benztropine (a.k.a. Cogentin), as a promoter of OPC differentiation and cell cycle exit. We have conducted studies in glioma cell lines supporting a role for benztropine in suppressing the development of drug-resistance to the standard glioma chemo-therapeutic temozolomide (TMZ). Upon treatment with TMZ, we identified the emergence of an OPC-like subpopulation of glioma cells identifiable by the co-expression of CD44, CD15 and PDGFRa. Treatment with pre-inhibitory doses of benztropine significantly reduced the TMZ IC50 in all glioma lines examined in association with blocking emergence of the CD44/CD15/PDGFR-positive subpopulation. Ongoing studies are designed to determine the tumor initiating potential of the CD44/CD15/PDGFR-positive subpopulation and whether benztropine will suppress the development of TMZ resistance in animal models of glioma.
Citation Format: Damian A. Almiron Bonnin, Joseph M. Howard, Alison L. Young, Mark A. Israel, Matthew C. Havrda. The muscarinic receptor antagonist, benztropine, blocks the expansion of a temozolomide resistant subpopulation of glioma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2047. doi:10.1158/1538-7445.AM2017-2047</jats:p
Molecular Mechanisms of Notch Signaling Governing Vascular Smooth Muscle Cell Proliferation
No full textVascular smooth muscle cell (VSMC) proliferation is an important feature of atherosclerotic plaque formation and restenosisl. Notchl, Notch2, Notch3 and Notch4 are up-regulated in adult intimal smooth muscle cells and regenerating endothelial cells following injury using the rat balloon catheter denudation model2. In this study, the objective was to determine the mechanisms by which Notch signaling regulates the proliferation of VSMC. We employed an in vitro VSMC model for Notch gain-offunction experiments. We used this model to assess alterations in VSMC proliferation using growth curve and DNA synthesis analysis following expression of the intracellular -do mains (m)o f Notchl (NlICD) and Notch4 (N4ICD) which act as constitutively active signaling receptors, or expression of the downstream effector HES-related transcript-2 ( H R T ~ )O~v.e r-expression of NlICD, N4ICD and HRT2 was demonstrated to positively regulate S-phase entry in a rat smooth muscle cell line (PAC-1). Expression of NlICD and N4ICD was analyzed by quantitative PCR and shown to up-regulate the VSMC specific Notch target genes HRTl and HRT2. The loss of Go/Glarrest was associated with a reduction in protein levels of the cyclin dependent kinase inhibitors p27 and p21. Over-expression of p27 resulted in a dose dependent rescue of the Notchlinduced loss of cell cycle regulation. Finally, direct repression of the p27 promoter by HRT2 was demonstrated using reporter assays, gel retardation assays and chromatin immunoprecipitation. Transcriptional repression is demonstrated to occur within the minimal p27 promoter region 435 - 774bp upstream of the start codon, and mutational analysis demonstrates that repression is dependent on a conserved class-C domain within the minimal promoter region. In order to assess the relevance of in vitro Notch induced proliferation to other smooth muscle hyperplasias, human smooth muscle neoplasms were examined in order to determine whether Notch receptorslligands were expressed. Using in situ hybridization, expression of Notch receptors, particularly Notch 1 and 2 as well as the Notch ligand Jagged 1 was observed in both gastrointestinal stromal tumors and leiomyosarcomas. Lastly, in order to identify novel targets of Notch signaling in smooth muscle cells microarray analysis of human aortic smooth muscle cells was performed following transduction with HRTl and HRT2 adenovirus. Microarray experiments verified the repression of p27 by HRTl and HRT2 in primary human cells. In addition, several novel targets of HRT transcription factors were identified including Jaggedl, Sprouty2 and Sprouty4, which will be useful for generating hypotheses designed to identify smooth muscle-specific Notch signaling pathways
Laser-assisted synthesis of gold nanoparticles and their in situ functionalisation
No full textV rámci této diplomové práce byl syntetizován 6A-sulfanyl-6A-deoxy-beta-CD, jenž sloužil k in situ funkcionalizaci zlatých nanočástic díky afinitě síry ke zlatu. Dále byla provedena příprava zlatých nanočástic fotochemickou syntézou pomocí pulzního laseru. Částice byly charakterizovány transmisní elektronovou mikroskopií a testovány na odezvu biologicky aktivní látky propamidinu 2-hydroxyethansulfonátu.Literární rešerše je rozdělena do čtyř hlavních kapitol. První z nich se zabývá nanotechnologiemi. Další kapitola je cílena konkrétně na zlaté nanočástice. Třetí část se zaměřuje na možnosti přípravy nanočástic pomocí laseru a závěr literární rešerše je věnován základním informacím o cyklodextrinech.In this diploma thesis, 6A-sulfanyl-6A-deoxy-beta-CD was synthesized and served for in situ functionalization of gold nanoparticles due to the affinity of sulfur to gold. Further, the preparation of gold nanoparticles by photochemical synthesis using a pulsing laser was performed. The particles were characterized by transmission electron microscopy and tested for the response of the biologically active substance propamidine 2-hydroxyethansulfonate.The literary research is divided into four main chapters. The first chapter deals with nanotechnology. The next chapter is aimed specifically at gold nanoparticles. The third part is focused on the possibilities of a preparation of nanoparticles using the laser and the conclusion of the literary research is devoted to basic information about cyclodextrins
Robust similarity registration technique for volumetric shapes represented by characteristic functions
No full textThis paper proposes a novel similarity registration technique for volumetric shapes implicitly represented by their characteristic functions (CFs). Here, the calculation of rotation parameters is considered as a spherical cross-correlation problem and the solution is therefore found using the standard phase correlation technique facilitated by principal components analysis (PCA).Thus, fast Fourier transform (FFT) is employed to vastly improve efficiency and robustness. Geometric moments are then used for shape scale estimation which is independent from rotation and translation parameters. It is numerically demonstrated that our registration method is able to handle shapes with various topologies and robust to noise and initial poses. Further validation of our method is performed by registering a lung database
Generalized distribution based diversity measurement: Survey and unification
No full textSocial and natural sciences employ a number of different measures of diversity. The presents paper surveys those depending on the distribution of abundances among a given set of categories. Characteristic properties of the measures are generalized and a unifying notation is derived. It is argued that such unification enables scientists and decision makers to measure distribution based diversity in a new, more flexible manner, and represents a useful complement to models of generalized feature based diversity, such as Nehring and Puppe’s (2002) theory of diversity.Diversity measurement; Generalization; Non–additivity; Concavity; Numbers equivalence
Influencia da preparação da superficie na aderencia de revestimentos de aluminio depositados por aspersão termica a chama
No full textDissertação (mestrado) - Universidade Federal de Santa Catarina, Centro TecnologicoÉ analisada a influência da preparação da superfície de aço carbono com graus A e C de corrosão na aderência de camadas de alumínio depositadas por aspersão térmica a chama. Desgaste, contaminação e possibilidade de reutilização de dois abrasivos a base de óxido de alumínio em duas granulometrias são discutidos diante de rugosidade, impregnação e textura atingidas em quatro operações controladas de jateamento. A possibilidade de reutilização dos abrasivos foi verificada através de ensaios de aderência por tração das camadas depositadas. O efeito positivo do preaquecimento do substrato a 120 °C, 250 °C e do tratamento térmico a 400 °C é avaliado por ensaios de aderência por tração e dobramento
Osteopontin, a Novel Substrate for Matrix Metalloproteinase-3 (Stromelysin-1) and Matrix Metalloproteinase-7 (Matrilysin)
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