Innovation in frastructure in Serbia

National Innovation System in Serbia (NIS) is not functional, and it should be an actuator of transition and development. NIS is shaped by past and current social, cultural, and even political factors as well as the current economic environment in Serbia. The work is a part of a wider research of the factors shaping the national innovation system. The goal of this paper is to point out who are the actuators of innovation infrastructure in Serbia, such as the activity of the participants in the organizing the infrastructure, to check whether commercial enterprises are generators and carriers of innovation activities, and to find out whether small and medium enterprises are interested in using innovation infrastructure. One of the goals of this paper is the review of innovation infrastructure concepts in Serbia and review of strategy for development of science and technology

Co-overexpression of bcl-2 and c-myc in uterine cervix carcinomas and premalignant lesions

To establish the role of co-overexpression of bcl-2 and c-myc protooncogenes in uterine cervix carcinogenesis, we examined 138 tissue samples of low grade cervical squamous intraepithelial lesions (SIL), high grade SIL, portio vaginalis uteri (PVU) carcinoma in situ and PVU invasive carcinoma, stage IA-IIA (study group) and 36 samples without SIL or malignancy (control group). The expression of bcl-2 and c-myc was detected immunohistochemically using a monoclonal antibody. Fisher's exact test (P<0.05) was used to assess statistical significance. Overexpression of bcl-2 was found to increase in direct relation to the grade of the cervical lesions. High sensitivity was of great diagnostic significance for the detection of these types of changes in the uterine cervix. On the basis of high predictive values it can be said that in patients with bcl-2 overexpression there is a great possibility that they have premalignant or malignant changes in the uterine cervix. Co-overexpression of bcl-2 and c-myc oncogenes was found only in patients with PVU invasive carcinoma (6/26-23.0%). Statistically significant difference was not found in the frequency of co-overexpression in patients with PVU invasive carcinoma in relation to the control group (Fisher's test; P=0.064). The method's sensitivity of determining these oncogenes with the aim of detecting PVU invasive carcinoma was 23%, while specificity was 72.2%. On the basis of high predictive values (100%), speaking in statistical terms, it can be concluded that all patients with co-overexpression of bcl-2 and c-myc oncogenes will have PVU invasive carcinoma. We confirmed in our research that co-overexpression of bcl-2 and c-myc oncogenes was increased only in PVU invasive carcinoma. However, a more extensive series of samples and additional tests are required to establish the prognostic significance of bcl-2 and c-myc co-overexpression in cervical carcinogenesis

Galaxies behind the Galactic plane: First results and perspectives from the VVV Survey

Vista Variables in The Via Lactea (VVV) is an ESO variability survey that is performing observations in near infrared bands (ZYJHKs) towards the Galactic bulge and part of the disk with the completeness limits at least 3 mag deeper than 2MASS. In the present work, we searched in the VVV survey data for background galaxies near the Galactic plane using ZYJHKs photometry that covers 1.636 square degrees. We identified 204 new galaxy candidates by analyzing colors, sizes, and visual inspection of multi-band (ZYJHKs) images. The galaxy candidates colors were also compared with the predicted ones by star counts models considering a more realistic extinction model at the same completeness limits observed by VVV. A comparison of the galaxy candidates with the expected one by Milennium simulations is also presented. Our results increase the number density of known galaxies behind the Milky Way by more than one order of magnitude. A catalog with galaxy properties including ellipticity, Petrosian radii and ZYJHKs magnitudes is provided, as well as comparisons of the results with other surveys of galaxies towards Galactic plane.Comment: 27 pages, 10 figures, 2 tables; in press at The Astronomical Journa

Evaluation of tolerance to lentiviral LV-RPE65 gene therapy vector after subretinal delivery in non-human primates.

Several approaches have been developed for gene therapy in RPE65-related Leber congenital amaurosis. To date, strategies that have reached the clinical stages rely on adeno-associated viral vectors and two of them documented limited long-term effect. We have developed a lentiviral-based strategy of RPE65 gene transfer that efficiently restored protein expression and cone function in RPE65-deficient mice. In this study, we evaluated the ocular and systemic tolerances of this lentiviral-based therapy (LV-RPE65) on healthy nonhuman primates (NHPs), without adjuvant systemic anti-inflammatory prophylaxis. For the first time, we describe the early kinetics of retinal detachment at 2, 4, and 7 days after subretinal injection using multimodal imaging in 5 NHPs. We revealed prolonged reattachment times in LV-RPE65-injected eyes compared to vehicle-injected eyes. Low- (n = 2) and high-dose (n = 2) LV-RPE65-injected eyes presented a reduction of the outer nuclear and photoreceptor outer segment layer thickness in the macula, that was more pronounced than in vehicle-injected eyes (n = 4). All LV-RPE65-injected eyes showed an initial perivascular reaction that resolved spontaneously within 14 days. Despite foveal structural changes, full-field electroretinography indicated that the overall retinal function was preserved over time and immunohistochemistry identified no difference in glial, microglial, or leucocyte ocular activation between low-dose, high-dose, and vehicle-injected eyes. Moreover, LV-RPE65-injected animals did not show signs of vector shedding or extraocular targeting, confirming the safe ocular restriction of the vector. Our results evidence a limited ocular tolerance to LV-RPE65 after subretinal injection without adjuvant anti-inflammatory prophylaxis, with complications linked to this route of administration necessitating to block this transient inflammatory event

The Fetal Hypothalamus Has the Potential to Generate Cells with a Gonadotropin Releasing Hormone (GnRH) Phenotype

Neurospheres (NS) are colonies of neural stem and precursor cells capable of differentiating into the central nervous system (CNS) cell lineages upon appropriate culture conditions: neurons, and glial cells. NS were originally derived from the embryonic and adult mouse striatum subventricular zone. More recently, experimental evidence substantiated the isolation of NS from almost any region of the CNS, including the hypothalamus. Here we report a protocol that enables to generate large quantities of NS from both fetal and adult rat hypothalami. We found that either FGF-2 or EGF were capable of inducing NS formation from fetal hypothalamic cultures, but that only FGF-2 is effective in the adult cultures. The hypothalamic-derived NS are capable of differentiating into neurons and glial cells and most notably, as demonstrated by immunocytochemical detection with a specific anti-GnRH antibody, the fetal cultures contain cells that exhibit a GnRH phenotype upon differentiation. This in vitro model should be useful to study the molecular mechanisms involved in GnRH neuronal differentiation

Amyloid Precursor-Like Protein 2 deletion-induced retinal synaptopathy related to congenital stationary night blindness: structural, functional and molecular characteristics.

Amyloid precursor protein knockout mice (APP-KO) have impaired differentiation of amacrine and horizontal cells. APP is part of a gene family and its paralogue amyloid precursor-like protein 2 (APLP2) has both shared as well as distinct expression patterns to APP, including in the retina. Given the impact of APP in the retina we investigated how APLP2 expression affected the retina using APLP2 knockout mice (APLP2-KO). Using histology, morphometric analysis with noninvasive imaging technique and electron microscopy, we showed that APLP2-KO retina displayed abnormal formation of the outer synaptic layer, accompanied with greatly impaired photoreceptor ribbon synapses in adults. Moreover, APLP2-KO displayed a significant decease in ON-bipolar, rod bipolar and type 2 OFF-cone bipolar cells (36, 21 and 63 %, respectively). Reduction of the number of bipolar cells was accompanied with disrupted dendrites, reduced expression of metabotropic glutamate receptor 6 at the dendritic tips and alteration of axon terminals in the OFF laminae of the inner plexiform layer. In contrast, the APP-KO photoreceptor ribbon synapses and bipolar cells were intact. The APLP2-KO retina displayed numerous phenotypic similarities with the congenital stationary night blindness, a non-progressive retinal degeneration disease characterized by the loss of night vision. The pathological phenotypes in the APLP2-KO mouse correlated to altered transcription of genes involved in pre- and postsynatic structure/function, including CACNA1F, GRM6, TRMP1 and Gα0, and a normal scotopic a-wave electroretinogram amplitude, markedly reduced scotopic electroretinogram b-wave and modestly reduced photopic cone response. This confirmed the impaired function of the photoreceptor ribbon synapses and retinal bipolar cells, as is also observed in congenital stationary night blindness. Since congenital stationary night blindness present at birth, we extended our analysis to retinal differentiation and showed impaired differentiation of different bipolar cell subtypes and an altered temporal sequence of development from OFF to ON laminae in the inner plexiform layer. This was associated with the altered expression patterns of bipolar cell generation and differentiation factors, including MATH3, CHX10, VSX1 and OTX2. These findings demonstrate that APLP2 couples retina development and synaptic genes and present the first evidence that APLP2 expression may be linked to synaptic disease

Role of Esrrg in the Fibrate-Mediated Regulation of Lipid Metabolism Genes in Human ApoA-I Transgenic Mice

We have used a new ApoA-I transgenic mouse model to identify by global gene expression profiling, candidate genes that affect lipid and lipoprotein metabolism in response to fenofibrate treatment. Multilevel bioinformatical analysis and stringent selection criteria (2-fold change, 0% false discovery rate) identified 267 significantly changed genes involved in several molecular pathways. The fenofibrate-treated group did not have significantly altered levels of hepatic human APOA-I mRNA and plasma ApoA-I compared with the control group. However, the treatment increased cholesterol levels to 1.95-fold mainly due to the increase in high-density lipoprotein (HDL) cholesterol. The observed changes in HDL are associated with the upregulation of genes involved in phospholipid biosynthesis and lipid hydrolysis, as well as phospholipid transfer protein. Significant upregulation was observed in genes involved in fatty acid transport and β-oxidation, but not in those of fatty acid and cholesterol biosynthesis, Krebs cycle and gluconeogenesis. Fenofibrate changed significantly the expression of seven transcription factors. The estrogen receptor-related gamma gene was upregulated 2.36-fold and had a significant positive correlation with genes of lipid and lipoprotein metabolism and mitochondrial functions, indicating an important role of this orphan receptor in mediating the fenofibrate-induced activation of a specific subset of its target genes.National Institutes of Health (HL48739 and HL68216); European Union (LSHM-CT-2006-0376331, LSHG-CT-2006-037277); the Biomedical Research Foundation of the Academy of Athens; the Hellenic Cardiological Society; the John F Kostopoulos Foundatio

Diversity of supernovae Ia determined using equivalent widths of Si II 4000

Spectroscopic and photometric properties of low and high-z supernovae Ia (SNe Ia) have been analyzed in order to achieve a better understanding of their diversity and to identify possible SN Ia sub-types. We use wavelet transformed spectra in which one can easily measure spectral features. We investigate the \ion{Si}{II} 4000 equivalent width (EW_w\lbrace\ion{Si}{II}\rbrace). The ability and, especially, the ease in extending the method to SNe at high-$z$ is demonstrated. We applied the method to 110 SNe Ia and found correlations between EW_w\lbrace\ion{Si}{II}\rbrace and parameters related to the light-curve shape for 88 supernovae with available photometry. No evidence for evolution of EW_w\lbrace\ion{Si}{II}\rbrace with redshift is seen. Three sub-classes of SNe Ia were confirmed using an independent cluster analysis with only light-curve shape, colour, and EW_w\lbrace\ion{Si}{II}\rbrace. SNe from high-$z$ samples seem to follow a similar grouping to nearby objects. The EW_w\lbrace\ion{Si}{II}\rbrace value measured on a single spectrum may point towards SN Ia sub-classification, avoiding the need for expansion velocity gradient calculations.Comment: 12 pages, 5 figure

Berkeley Supernova Ia Program II: Initial Analysis of Spectra Obtained Near Maximum Brightness

In this second paper in a series we present measurements of spectral features of 432 low-redshift (z < 0.1) optical spectra of 261 Type Ia supernovae (SNe Ia) within 20 d of maximum brightness. The data were obtained from 1989 through the end of 2008 as part of the Berkeley SN Ia Program (BSNIP) and are presented in BSNIP I (Silverman et al. 2012). We describe in detail our method of automated, robust spectral feature definition and measurement which expands upon similar previous studies. Using this procedure, we attempt to measure expansion velocities, pseudo-equivalent widths (pEW), spectral feature depths, and fluxes at the centre and endpoints of each of nine major spectral feature complexes. We investigate how velocity and pEW evolve with time and how they correlate with each other. Various spectral classification schemes are employed and quantitative spectral differences among the subclasses are investigated. Several ratios of pEW values are calculated and studied. The so-called Si II ratio, often used as a luminosity indicator (Nugent et al. 1995), is found to be well correlated with the so-called "SiFe" ratio and anticorrelated with the analogous "SSi ratio," confirming the results of previous studies. Furthermore, SNe Ia that show strong evidence for interaction with circumstellar material or an aspherical explosion are found to have the largest near-maximum expansion velocities and pEWs, possibly linking extreme values of spectral observables with specific progenitor or explosion scenarios. [Abridged]Comment: 73 pages, 18 figures, 15 tables, revised version re-submitted to MNRAS. Measured values of the spectral features (i.e., Appendix B) will be publicly available when the paper is accepte

Topological magnetic order and superconductivity in EuRbFe4As4

We study single crystals of the magnetic superconductor EuRbFe4As4 by magnetization, electron spin resonance ESR , angle resolved photoemission spectroscopy, and electrical resistance in pulsed magnetic fields up to 63 T. The superconducting state below 36.5 K is almost isotropic and is only weakly affected by the development of Eu2 magnetic order at 15 K. On the other hand, for the external magnetic field applied along the c axis the temperature dependence of the ESR linewidth reveals a Berezinskii Kosterlitz Thouless topological transition below 15 K. This indicates that Eu2 planes are a good realization of a two dimensional XY magnet, which reflects the decoupling of the Eu2 magnetic moments from superconducting FeAs layer