590 research outputs found

    Характеристика экономических отношений на финансовом рынке Украины

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    Розглянуто проблеми, особливості функціонування та взаємодії учасників фінансового ринку України. Обґрунтовано наявність внутрішніх фінансових джерел формування ресурсного потенціалу вітчизняних банків, доведено їх пріоритетність для країни порівняно із зовнішніми джерелами. Окреслено причини, що зумовлюють дефіцит ресурсного потенціалу в банківській системі України. Ключові слова: заощадження, нагромадження, банки, економічне зростання, посередники, фінансовий ринок, ресурси, трансформація, інвестиційний потенціал.Рассмотрены проблемы, особенности функционирования и взаимодействия участников финансового рынка Украины. Обосновано наличие внутренних финансовых источников формирования ресурсного потенциала отечественных банков, доказана их приоритетность для страны по сравнению с внешними источниками. Очерчены причины, которые предопределяют дефицит ресурсного потенциала в банковской системе Украины. Ключевые слова: сбережения, накопления, банки, экономический рост, посредники, финансовый рынок, ресурсы, трансформация, инвестиционный потенциал.The present paper examines topical problems related to the specific aspects of economic relations in the financial market of Ukraine. The relevance and selection of the theme stem from the fact that financial market as a specific organization form of cash flows takes a leading place in the economic mechanism of market economy. Agents of this market are engaged in a whole range of complex economic relations which in their turn play a key role in securing a dynamic and sustainable economic growth of a country. Development of the financial market and creation of adequate flexible and adaptive economic relations between its players are critical for Ukraine. This is explained by specific aspects of the economic system formation and reforming, which are related to undergoing an intersystem transformation stage. The indicated circumstances predetermined the goal and objectives of the study pursued, which come to examination of economic relations in the financial market of Ukraine, identification of the interaction specificity of various financial intermediaries in the accumulation process of idle cash and its transformation into the investment capital of national economy. Based on the results of the analysis conducted, it is established that unlike countries with developed financial systems, where the majority of institutional participants of the capital market are proportionally developed, it is the banking sector that dominates in Ukraine and has a determinant role in financing the economic development of the state. The availability of domestic financial resources for forming the resource potential of banks is substantiated, and their priority versus external resources for Ukraine is proved. The comparison of gross savings and gross capital formation allowed identifying certain problems as to transformation of the former into investment resources in Ukraine. The paper outlines some causes of a poor resource potential of national banking institutions. Keywords: savings, accumulation, banks, economic growth, intermediaries, financial market, resources, transformation, investment potential

    A Polymerase-chain-reaction Assay for the Specific Identification of Transcripts Encoded by Individual Carcinoembryonic Antigen (CEA)-gene-family Members

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    Carcinoembryonic antigen (CEA) is a tumor marker that belongs to a family of closely related molecules with variable expression patterns. We have developed sets of oligonucleotide primers for the specific amplification of transcripts from individual CEA-family members using the reverse transcriptase/ polymerase chain reaction (RT/PCR). Specific primer sets were designed for CEA, non-specific cross-reacting antigen (NCA), biliary glycoprotein (BGP), carcinoembryonic antigen gene-family members 1, 6 and 7 (CGMI, CGM6 and CGM7), and one set for all pregnancy-specific glycoprotein (PSG) transcripts. Primers were first tested for their specificity against individual cDNA clones and product-hybridization with internal, transcript-specific oligonucleotides. Total RNA from 12 brain and 63 gynecological tumors were then tested for expression of CEA-related transcripts. None were found in tumors located in the brain, including various mesenchymal and neuro-epithelial tumors. CEA and NCA transcripts were, however, present in an adenocarcinoma located in the nasal sinuses. In ovarian mucinous adenocarcinomas, we always found co-expression of CEA and NCA transcripts, and occasionally BGP mRNA. CEA-related transcripts were also found in some serous, endometrioid and clear-cell ovarian carcinomas. CEA, NCA and BGP transcripts were present in endometrial carcinomas of the uterus and cervical carcinomas, whereas uterine leiomyomas were completely negative. No transcripts were found from CGM 1, CGM6, CGM7 or from PSG genes in any of the tumors tested. The PCR data were compared with immunohistochemical investigations of ovarian tumors at the protein level using CEA (26/3/13)-, NCA-50/90 (9A6FR) and NCA-95 (80H3)-specific monoclonal antibodies

    The electric dipole response of 76^{76}Se above 4 MeV

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    The dipole response of 3476^{76}_{34}Se in the energy range 4 to 9 MeV has been analyzed using a (γ,γ)(\vec\gamma,{\gamma}') polarized photon scattering technique, performed at the High Intensity γ\gamma-Ray Source facility, to complement previous work performed using unpolarized photons. The results of this work offer both an enhanced sensitivity scan of the dipole response and an unambiguous determination of the parities of the observed J=1 states. The dipole response is found to be dominated by E1E1 excitations, and can reasonably be attributed to a pygmy dipole resonance. Evidence is presented to suggest that a significant amount of directly unobserved excitation strength is present in the region, due to unobserved branching transitions in the decays of resonantly excited states. The dipole response of the region is underestimated when considering only ground state decay branches. We investigate the electric dipole response theoretically, performing calculations in a 3D cartesian-basis time-dependent Skyrme-Hartree-Fock framework.Comment: 20 pages, 18 figures, to be submitted to PR

    Influence of demagnetization in remanence curves of magnetic thin films

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    Remanent magnetization curves of perpendicular magnetic thin films are simulated and measured. The simulations are used to investigate the theoretical influence of the strong demagnetizing field present in these films. Conclusions are drawn from this on how remanence curves should be measured and how they should be corrected for the demagnetizing influence. The experimental part consists of measurements on Fe‐Alumite, Co‐Pt–based multilayers, and Co‐Cr. In addition the latter material is also artificially patterned into microstrips in order to investigate the influence of demagnetization on remanence curves experimentally

    Dipole Strength Distributions from HIGS Experiments

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    A series of photon scattering experiments has been performed on the double-beta decay partners 76Ge and 76Se, in order to investigate their dipole response up to the neutron separation threshold. Gamma-ray beams from bremsstrahlung at the S-DALINAC and from Compton-backscattering at HIGS have been used to measure absolute cross sections and parities of dipole excited states, respectively. The HIGS data allows for indirect measurement of averaged branching ratios, which leads to significant corrections in the observed excitation cross sections. Results are compared to statistical calculations, to test photon strength functions and the Axel-Brink hypothesi

    Estrogen receptor variants in ER-positive basal-type breast cancers responding to therapy like ER-negative breast cancers

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    Immunohistochemically ER-positive HER2-negative (ER+HER2−) breast cancers are classified clinically as Luminal-type. We showed previously that molecular subtyping using the 80-gene signature (80-GS) reclassified a subset of ER+HER2− tumors to molecular Basal-type. We report here that molecular reclassification is associated with expression of dominant-negative ER variants and evaluate response to neoadjuvant therapy and outcome in the prospective neoadjuvant NBRST study (NCT01479101). The 80-GS reclassified 91 of 694 (13.1%) immunohistochemically Luminal-type tumors to molecular Basal-type. Importantly, all 91 discordant tumors were classified as high-risk, whereas only 66.9% of ER+/Luminal-type tumors were classified at high-risk for disease recurrence (i.e., Luminal B) (P < 0.001). ER variant mRNA (ERΔ3, ERΔ7, and ERα-36) analysis performed on 84 ER+/Basal tumors and 48 ER+/Luminal B control tumors revealed that total ER mRNA was significantly lower in ER+/Basal tumors. The relative expression of ERΔ7/total ER was significantly higher in ER+/Basal tumors compared to ER+/Luminal B tumors (P < 0.001). ER+/Basal patients had similar pathological complete response (pCR) rates following neoadjuvant chemotherapy as ER−/Basal patients (34.3 vs. 37.6%), and much higher than ER+/Luminal A or B patients (2.3 and 5.8%, respectively). Furthermore, 3-year distant metastasis-free interval (DMFI) for ER+/Basal patients was 65.8%, significantly lower than 96.3 and 88.9% for ER+/Luminal A and B patients, respectively, (log-rank P < 0.001). Significantly lower total ER mRNA and increased relative ERΔ7 dominant-negative variant expression provides a rationale why ER+/Basal breast cancers are molecularly ER-negative. Identification of this substantial subset of patients is clinically relevant because of the higher pCR rate to neoadjuvant chemotherapy and correlation with clinical outcome

    Registration of ‘NH03614 CL’ Wheat

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    ‘NH03614 CL’ (Reg. No. CV-1051, PI 653833) hard red winter wheat (Triticum aestivum L.) was developed cooperatively by the Nebraska Agricultural Experiment Station and the USDA-ARS and released in 2008 by the developing institutions and the South Dakota Agricultural Experiment Station and the Wyoming Agricultural Experiment Station. In addition to researchers at the releasing institutions, USDA-ARS researchers at Manhattan, KS and St. Paul, MN participated in the development of NH03614 CL. NH03614 CL was selected from the cross ‘Wesley’ sib//‘Millennium’ sib/‘Above’ sib that was made in the spring of 1997 to develop new herbicide-tolerant cultivars. NH03614 CL was selected using the bulk breeding method as an F3:4 line (F3–derived line in the F4 generation) in 2001, and in 2003 was assigned experimental line number NH03164. NH03614 CL was released primarily for its herbicide tolerance to imadazolinone compounds which control many previously diffi cult-to-control weeds in wheat production systems, and for its superior adaptation to rainfed wheat production systems in Nebraska, Wyoming, South Dakota, and counties in adjacent states

    Kinome capture sequencing of high-grade serous ovarian carcinoma reveals novel mutations in theJAK3gene

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    High-grade serous ovarian carcinoma (HGSOC) remains the deadliest form of epithelial ovarian cancer and despite major efforts little improvement in overall survival has been achieved. Identification of recurring "driver" genetic lesions has the potential to enable design of novel therapies for cancer. Here, we report on a study to find such new therapeutic targets for HGSOC using exome-capture sequencing approach targeting all kinase genes in 127 patient samples. Consistent with previous reports, the most frequently mutated gene wasTP53(97% mutation frequency) followed byBRCA1(10% mutation frequency). The average mutation frequency of the kinase genes mutated from our panel was 1.5%. Intriguingly, afterBRCA1,JAK3was the most frequently mutated gene (4% mutation frequency). We tested the transforming properties of JAK3 mutants using the Ba/F3 cell-basedin vitrofunctional assay and identified a novel gain-of-function mutation in the kinase domain ofJAK3(p.T1022I). Importantly, p.T1022IJAK3mutants displayed higher sensitivity to the JAK3-selective inhibitor Tofacitinib compared to controls. For independent validation, we re-sequenced the entireJAK3coding sequence using tagged amplicon sequencing (TAm-Seq) in 463 HGSOCs resulting in an overall somatic mutation frequency of 1%. TAm-Seq screening ofCDK12in the same population revealed a 7% mutation frequency. Our data confirms that the frequency of mutations in kinase genes in HGSOC is low and provides accurate estimates for the frequency ofJAK3andCDK12mutations in a large well characterized cohort. Although p.T1022IJAK3mutations are rare, our functional validation shows that if detected they should be considered as potentially actionable for therapy. The observation ofCDK12mutations in 7% of HGSOC cases provides a strong rationale for routine somatic testing, although more functional and clinical characterization is required to understand which nonsynonymous mutations alterations are associated with homologous recombination deficiency.ISSN:1932-620

    A Large Scale shRNA Barcode Screen Identifies the Circadian Clock Component ARNTL as Putative Regulator of the p53 Tumor Suppressor Pathway

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    BACKGROUND: The p53 tumor suppressor gene is mutated in about half of human cancers, but the p53 pathway is thought to be functionally inactivated in the vast majority of cancer. Understanding how tumor cells can become insensitive to p53 activation is therefore of major importance. Using an RNAi-based genetic screen, we have identified three novel genes that regulate p53 function. RESULTS: We have screened the NKI shRNA library targeting 8,000 human genes to identify modulators of p53 function. Using the shRNA barcode technique we were able to quickly identify active shRNA vectors from a complex mixture. Validation of the screening results indicates that the shRNA barcode technique can reliable identify active shRNA vectors from a complex pool. Using this approach we have identified three genes, ARNTL, RBCK1 and TNIP1, previously unknown to regulate p53 function. Importantly, ARNTL (BMAL1) is an established component of the circadian regulatory network. The latter finding adds to recent observations that link circadian rhythm to the cell cycle and cancer. We show that cells having suppressed ARNTL are unable to arrest upon p53 activation associated with an inability to activate the p53 target gene p21(CIP1). CONCLUSIONS: We identified three new regulators of the p53 pathway through a functional genetic screen. The identification of the circadian core component ARNTL strengthens the link between circadian rhythm and cancer

    Understanding pharmacokinetics using realistic computational models of fluid dynamics: biosimulation of drug distribution within the CSF space for intrathecal drugs

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    We introduce how biophysical modeling in pharmaceutical research and development, combining physiological observations at the tissue, organ and system level with selected drug physiochemical properties, may contribute to a greater and non-intuitive understanding of drug pharmacokinetics and therapeutic design. Based on rich first-principle knowledge combined with experimental data at both conception and calibration stages, and leveraging our insights on disease processes and drug pharmacology, biophysical modeling may provide a novel and unique opportunity to interactively characterize detailed drug transport, distribution, and subsequent therapeutic effects. This innovative approach is exemplified through a three-dimensional (3D) computational fluid dynamics model of the spinal canal motivated by questions arising during pharmaceutical development of one molecular therapy for spinal cord injury. The model was based on actual geometry reconstructed from magnetic resonance imaging data subsequently transformed in a parametric 3D geometry and a corresponding finite-volume representation. With dynamics controlled by transient Navier–Stokes equations, the model was implemented in a commercial multi-physics software environment established in the automotive and aerospace industries. While predictions were performed in silico, the underlying biophysical models relied on multiple sources of experimental data and knowledge from scientific literature. The results have provided insights into the primary factors that can influence the intrathecal distribution of drug after lumbar administration. This example illustrates how the approach connects the causal chain underlying drug distribution, starting with the technical aspect of drug delivery systems, through physiology-driven drug transport, then eventually linking to tissue penetration, binding, residence, and ultimately clearance. Currently supporting our drug development projects with an improved understanding of systems physiology, biophysical models are being increasingly used to characterize drug transport and distribution in human tissues where pharmacokinetic measurements are difficult or impossible to perform. Importantly, biophysical models can describe emergent properties of a system, i.e. properties not identifiable through the study of the system’s components taken in isolation
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