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Showing papers by "University of Rijeka published in 2013"


Journal ArticleDOI
B. S. Acharya1, Marcos Daniel Actis2, T. Aghajani3, G. Agnetta4  +979 moreInstitutions (122)
TL;DR: The Cherenkov Telescope Array (CTA) as discussed by the authors is a very high-energy (VHE) gamma ray observatory with an international collaboration with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America.

701 citations


Journal ArticleDOI
TL;DR: It is shown that TIGIT is a powerful inhibitory receptor for mouse NK cells and binds to mPVR with higher affinity than the co‐stimulatory PVR‐binding receptor mouse DNAM1 (mDNAM1).
Abstract: The activity of natural killer (NK) cells is controlled by a balance of signals derived from inhibitory and activating receptors. TIGIT is a novel inhibitory receptor, recently shown in humans to interact with two ligands: PVR and Nectin2 and to inhibit human NK-cell cytotoxicity. Whether mouse TIGIT (mTIGIT) inhibits mouse NK-cell cytotoxicity is unknown. Here we show that mTIGIT is expressed by mouse NK cells and interacts with mouse PVR. Using mouse and human Ig fusion proteins we show that while the human TIGIT (hTIGIT) cross-reacts with mouse PVR (mPVR), the binding of mTIGIT is restricted to mPVR. We further demonstrate using surface plasmon resonance (SPR) and staining with Ig fusion proteins that mTIGIT binds to mPVR with higher affinity than the co-stimulatory PVR-binding receptor mouse DNAM1 (mDNAM1). Functionally, we show that triggering of mTIGIT leads to the inhibition of NK-cell cytotoxicity, that IFN-γ secretion is enhanced when mTIGIT is blocked and that the TIGIT-mediated inhibition is dominant over the signals delivered by the PVR-binding co-stimulatory receptors. Additionally, we identify the inhibitory motif responsible for mTIGIT inhibition. In conclusion, we show that TIGIT is a powerful inhibitory receptor for mouse NK cells.

209 citations


Journal ArticleDOI
TL;DR: It is confirmed that the intercall durations follow a power-law distribution with an exponential cutoff at the population level but found differences when focusing on individual users, which may enable a more detailed analysis of the huge body of data contained in the logs of massive users.
Abstract: Modern technologies not only provide a variety of communication modes (e.g., texting, cell phone conversation, and online instant messaging), but also detailed electronic traces of these communications between individuals. These electronic traces indicate that the interactions occur in temporal bursts. Here, we study intercall duration of communications of the 100,000 most active cell phone users of a Chinese mobile phone operator. We confirm that the intercall durations follow a power-law distribution with an exponential cutoff at the population level but find differences when focusing on individual users. We apply statistical tests at the individual level and find that the intercall durations follow a power-law distribution for only 3,460 individuals (3.46%). The intercall durations for the majority (73.34%) follow a Weibull distribution. We quantify individual users using three measures: out-degree, percentage of outgoing calls, and communication diversity. We find that the cell phone users with a power-law duration distribution fall into three anomalous clusters: robot-based callers, telecom fraud, and telephone sales. This information is of interest to both academics and practitioners, mobile telecom operators in particular. In contrast, the individual users with a Weibull duration distribution form the fourth cluster of ordinary cell phone users. We also discover more information about the calling patterns of these four clusters (e.g., the probability that a user will call the cr-th most contact and the probability distribution of burst sizes). Our findings may enable a more detailed analysis of the huge body of data contained in the logs of massive users.

186 citations


Journal ArticleDOI
TL;DR: Biological and potential therapeutic effects of ortho-silicic acid and ortho, silicaic acid -releasing silicon compounds as its major natural sources are discussed and certain types of zeolites with well described ion(cation)-exchange properties are identified.
Abstract: Silicon (Si) is the most abundant element present in the Earth's crust besides oxygen. However, the exact biological roles of silicon remain unknown. Moreover, the ortho-silicic acid (H4SiO4), as a major form of bioavailable silicon for both humans and animals, has not been given adequate attention so far. Silicon has already been associated with bone mineralization, collagen synthesis, skin, hair and nails health atherosclerosis, Alzheimer disease, immune system enhancement, and with some other disorders or pharmacological effects. Beside the ortho-silicic acid and its stabilized formulations such as choline chloride-stabilized ortho-silicic acid and sodium or potassium silicates (e.g. M2SiO3; M= Na,K), the most important sources that release ortho-silicic acid as a bioavailable form of silicon are: colloidal silicic acid (hydrated silica gel), silica gel (amorphous silicon dioxide), and zeolites. Although all these compounds are characterized by substantial water insolubility, they release small, but significant, equilibrium concentration of ortho-silicic acid (H4SiO4) in contact with water and physiological fluids. Even though certain pharmacological effects of these compounds might be attributed to specific structural characteristics that result in profound adsorption and absorption properties, they all exhibit similar pharmacological profiles readily comparable to ortho-silicic acid effects. The most unusual ortho-silicic acid-releasing agents are certain types of zeolites, a class of aluminosilicates with well described ion(cation)-exchange properties. Numerous biological activities of some types of zeolites documented so far might probably be attributable to the ortho-silicic acid-releasing property. In this review, we therefore discuss biological and potential therapeutic effects of ortho-silicic acid and ortho-silicic acid -releasing silicon compounds as its major natural sources.

172 citations


Journal ArticleDOI
TL;DR: The present review depicts the central function of astrocytes, concentrating on the importance of GS in glutamate/glutamine metabolism and ammonia detoxification in health and disease.
Abstract: The multifunctional properties of astrocytes signify their importance in brain physiology and neurological function. In addition to defining the brain architecture, astrocytes are primary elements of brain ion, pH and neurotransmitter homoeostasis. GS (glutamine synthetase), which catalyses the ATP-dependent condensation of ammonia and glutamate to form glutamine, is an enzyme particularly found in astrocytes. GS plays a pivotal role in glutamate and glutamine homoeostasis, orchestrating astrocyte glutamate uptake/release and the glutamate-glutamine cycle. Furthermore, astrocytes bear the brunt of clearing ammonia in the brain, preventing neurotoxicity. The present review depicts the central function of astrocytes, concentrating on the importance of GS in glutamate/glutamine metabolism and ammonia detoxification in health and disease.

171 citations


Journal ArticleDOI
01 Jun 2013-Carbon
TL;DR: In this paper, Raman spectroscopy analysis showed that the structure of the amorphous phase produced by ball milling is less disordered than that of ion-beam bombarded graphite and sputtered carbon.

163 citations


Journal ArticleDOI
TL;DR: Findings suggest that EGCG regulates ectopic lipid accumulation through a facilitated autophagic flux and further imply that E GCG may be a potential therapeutic reagent to prevent cardiovascular complications.

157 citations


Journal ArticleDOI
TL;DR: The results showed the nephroprotective activity of berberine against CP-induced renal injury, which could be attributed to the inhibition of oxidative/nitrosative stress, inflammation, autophagy and apoptosis.

156 citations


Journal ArticleDOI
27 Jun 2013-Immunity
TL;DR: It is shown that RORγt⁺ ILCs can directly sense the environment by the engagement of the activating receptor NKp44 and are able to switch between IL-22 or TNF production, depending on the triggering stimulus.

155 citations


Journal ArticleDOI
TL;DR: In human oncogene-transformed and cancer cells, ATM suppressed ARF protein levels and activity in a transcription-independent manner and inhibition of ATM stimulated the tumour-suppressive effects of ARF.
Abstract: The DNA damage response (DDR) pathway and ARF function as barriers to cancer development Although commonly regarded as operating independently of each other, some studies proposed that ARF is positively regulated by the DDR Contrary to either scenario, we found that in human oncogene-transformed and cancer cells, ATM suppressed ARF protein levels and activity in a transcription-independent manner Mechanistically, ATM activated protein phosphatase 1, which antagonized Nek2-dependent phosphorylation of nucleophosmin (NPM), thereby liberating ARF from NPM and rendering it susceptible to degradation by the ULF E3-ubiquitin ligase In human clinical samples, loss of ATM expression correlated with increased ARF levels and in xenograft and tissue culture models, inhibition of ATM stimulated the tumour-suppressive effects of ARF These results provide insights into the functional interplay between the DDR and ARF anti-cancer barriers, with implications for tumorigenesis and treatment of advanced tumours

112 citations


Journal ArticleDOI
TL;DR: The results of this study indicates that RA possesses antioxidant, anti-inflammatory, antiapoptotic and antifibrotic activity against acute liver toxicity.

Journal ArticleDOI
Jelena Aleksić1, Stefano Ansoldi2, Louis Antonelli3, P. Antoranz4  +159 moreInstitutions (24)
TL;DR: In this article, the authors present the results of stereoscopic observations of the satellite galaxy Segue 1 with the MAGIC Telescopes, carried out between 2011 and 2013, using the full likelihood analysis method, which provides optimal sensitivity to characteristic gamma-ray spectral features, like those expected from dark matter annihilation or decay.
Abstract: We present the results of stereoscopic observations of the satellite galaxy Segue 1 with the MAGIC Telescopes, carried out between 2011 and 2013. With almost 160 hours of good-quality data, this is the deepest observational campaign on any dwarf galaxy performed so far in the very high energy range of the electromagnetic spectrum. We search this large data sample for signals of dark matter particles in the mass range between 100 GeV and 20 TeV. For this we use the full likelihood analysis method, which provides optimal sensitivity to characteristic gamma-ray spectral features, like those expected from dark matter annihilation or decay. In particular, we focus our search on gamma-rays produced from different final state Standard Model particles, annihilation with internal bremsstrahlung, monochromatic lines and box-shaped signals. Our results represent the most stringent constraints to the annihilation cross-section or decay lifetime obtained from observations of satellite galaxies, for masses above few hundred GeV. In particular, our strongest limit (95% confidence level) corresponds to a ~500 GeV dark matter particle annihilating into tau+tau-, and is of order ~ 1.2x10^{-24} cm^3 s^{-1} - a factor ~40 above the thermal value.

Journal ArticleDOI
TL;DR: NCLX, by meditating astrocytic mitochondrial Na+/Ca2+ exchange, links between mitochondria and plasma membrane Ca2+ signaling, thereby modulating cytoplasmic Ca 2+ transients required to control a diverse array of astroCyte functions.
Abstract: Mitochondria not only provide cells with energy, but are central to Ca(2+) signaling. Powered by the mitochondrial membrane potential, Ca(2+) enters the mitochondria and is released into the cytosol through a mitochondrial Na(+)/Ca(2+) exchanger. We established that NCLX, a newly discovered mitochondrial Na(+)/Ca(2+) exchanger, is expressed in astrocytes isolated from mice of either sex. Immunoblot analysis of organellar fractions showed that the location of NCLX is confined to mitochondria. Using pericam-based mitochondrial Ca(2+) imaging and NCLX inhibition either by siRNA or by the pharmacological blocker CGP37157, we demonstrated that NCLX is responsible for mitochondrial Ca(2+) extrusion. Suppression of NCLX function altered cytosolic Ca(2+) dynamics in astrocytes and this was mediated by a strong effect of NCLX activity on Ca(2+) influx via store-operated entry. Furthermore, Ca(2+) influx through the store-operated Ca(2+) entry triggered strong, whereas ER Ca(2+) release triggered only modest mitochondrial Ca(2+) transients, indicating that the functional cross talk between the plasma membrane and mitochondrial domains is particularly strong in astrocytes. Finally, silencing of NCLX expression significantly reduced Ca(2+)-dependent processes in astrocytes (i.e., exocytotic glutamate release, in vitro wound closure, and proliferation), whereas Ca(2+) wave propagation was not affected. Therefore, NCLX, by meditating astrocytic mitochondrial Na(+)/Ca(2+) exchange, links between mitochondria and plasma membrane Ca(2+) signaling, thereby modulating cytoplasmic Ca(2+) transients required to control a diverse array of astrocyte functions.

Journal ArticleDOI
TL;DR: It is suggested that luteolin is an effective nephroprotective agent, with potential to reduce Pt accumulation in the kidneys and ameliorate CP-induced nephrotoxicity.

Journal ArticleDOI
TL;DR: This paper examined sources and motives for personal meaning in adulthood using a mixed methods approach and found that personal life, referring mainly to self-transcendent values, was the prominent motive underlying sources of meaning.
Abstract: This study examined sources and motives for personal meaning in adulthood using a mixed methods approach. Participants (N = 666) from seven Western countries reported sources of life meaning, and why they were meaningful. They rated their perceived meaningfulness of 10 life domains and completed the Satisfaction with Life Scale. Family and personal life – indicating personal growth, well-being, harmony and self-actualization – emerged as main sources of meaning. Personal life, referring mainly to self-transcendent values, was the prominent motive underlying sources of meaning. Participants grouped according to age and family role revealed life stage differences in meaningfulness across domains. Hierarchical regressions indicated meaningfulness was not a significant predictor of life satisfaction, confirming that hedonic and eudaimonic dimensions are distinct components of well-being. Findings elucidate the importance of self-generated accounts of meaning as these blend personal, self-transcendent and demo...

Journal ArticleDOI
TL;DR: The authors acknowledge support from the Spanish MICYNN projects AYA2010-22111-C03-02 and Consolider-Ingenio 2007-32022, and from the Generalitat Valenciana project Prometeo 2008/132.
Abstract: AFS acknowledges support from the Spanish MICYNN projects AYA2010-22111-C03-02 and Consolider-Ingenio 2007-32022, and from the Generalitat Valenciana project Prometeo 2008/132.

Journal ArticleDOI
TL;DR: Evidence is provided that pUL51 is crucial for HCMV genome cleavage-packaging and may represent a third component of the viral terminase complex, and interference with the interactions between the terminase subunits by antiviral drugs could be a strategy to disrupt the H CMV replication cycle.
Abstract: Cleavage of human cytomegalovirus (HCMV) genomes as well as their packaging into capsids is an enzymatic process mediated by viral proteins and therefore a promising target for antiviral therapy. The HCMV proteins pUL56 and pUL89 form the terminase and play a central role in cleavage-packaging, but several additional viral proteins, including pUL51, had been suggested to contribute to this process, although they remain largely uncharacterized. To study the function of pUL51 in infected cells, we constructed HCMV mutants encoding epitope-tagged versions of pUL51 and used a conditionally replicating virus (HCMV-UL51-ddFKBP), in which pUL51 levels could be regulated by a synthetic ligand. In cells infected with HCMV-UL51-ddFKBP, viral DNA replication was not affected when pUL51 was knocked down. However, no unit-length genomes and no DNA-filled C capsids were found, indicating that cleavage of concatemeric HCMV DNA and genome packaging into capsids did not occur in the absence of pUL51. pUL51 was expressed mainly with late kinetics and was targeted to nuclear replication compartments, where it colocalized with pUL56 and pUL89. Upon pUL51 knockdown, pUL56 and pUL89 were no longer detectable in replication compartments, suggesting that pUL51 is needed for their correct subnuclear localization. Moreover, pUL51 was found in a complex with the terminase subunits pUL56 and pUL89. Our data provide evidence that pUL51 is crucial for HCMV genome cleavage-packaging and may represent a third component of the viral terminase complex. Interference with the interactions between the terminase subunits by antiviral drugs could be a strategy to disrupt the HCMV replication cycle.

Journal ArticleDOI
TL;DR: A dual analysis of Murine Cytomegalovirus and host cell transcriptomes during lytic infection and numerous novel spliced and unspliced transcripts of MCMV is conducted, finding that the most abundant viral transcript, recently identified as a noncoding RNA regulating cellular microRNAs, also codes for a novel protein.
Abstract: Major gaps in our knowledge of pathogen genes and how these gene products interact with host gene products to cause disease represent a major obstacle to progress in vaccine and antiviral drug development for the herpesviruses. To begin to bridge these gaps, we conducted a dual analysis of Murine Cytomegalovirus (MCMV) and host cell transcriptomes during lytic infection. We analyzed the MCMV transcriptome during lytic infection using both classical cDNA cloning and sequencing of viral transcripts and next generation sequencing of transcripts (RNA-Seq). We also investigated the host transcriptome using RNA-Seq combined with differential gene expression analysis, biological pathway analysis, and gene ontology analysis. We identify numerous novel spliced and unspliced transcripts of MCMV. Unexpectedly, the most abundantly transcribed viral genes are of unknown function. We found that the most abundant viral transcript, recently identified as a noncoding RNA regulating cellular microRNAs, also codes for a novel protein. To our knowledge, this is the first viral transcript that functions both as a noncoding RNA and an mRNA. We also report that lytic infection elicits a profound cellular response in fibroblasts. Highly upregulated and induced host genes included those involved in inflammation and immunity, but also many unexpected transcription factors and host genes related to development and differentiation. Many top downregulated and repressed genes are associated with functions whose roles in infection are obscure, including host long intergenic noncoding RNAs, antisense RNAs or small nucleolar RNAs. Correspondingly, many differentially expressed genes cluster in biological pathways that may shed new light on cytomegalovirus pathogenesis. Together, these findings provide new insights into the molecular warfare at the virus-host interface and suggest new areas of research to advance the understanding and treatment of cytomegalovirus-associated diseases.

Posted Content
TL;DR: In this article, the authors examined the relationship between service quality and customer satisfaction in the hotel industry in Croatia and found that hotel service quality is indeed a significant predictor of customer satisfaction.
Abstract: Purpose – The purpose of the present study was to examine the relationship between service quality and customer satisfaction. The main objective was to discuss the impact of perceived service quality dimensions on customer satisfaction in the hotel industry in Croatia. Methodology – The data were collected us in self-administered questionnaire. The questionnaire consisted of three parts. First, perceived service quality was measured using modified SERVQUAL model. Second, customer satisfaction was operationalized with one variable, representing overall satisfaction measure. Third, demographic variables were included. Questionnaires were distributed to domestic and international hotel guests in the Opatija Riviera (Croatia). Descriptive analysis, factor analysis, reliability analysis, correlation analysis, and multiple regression analysis were performed to analyze the data. Findings – Factor analysis identified four dimensions of perceived service quality, namely reliability, empathy and competence of staff, accessibility and tangibles. Multiple regression analysis showed that reliability, accessibility and tangibles had a significant and positive effect on overall customer satisfaction. On the other hand, empathy and competence of staff positively influenced hotel guests’ satisfaction, but this impact was not statistically significant when other dimensions were involved. These results indicate that hotel service quality is indeed a significant predictor of customer satisfaction. Thus, improving hotel service quality, results with higher satisfaction levels of hotel guests. Value/Originality – The present study focuses on determining relative importance of perceived hotel service quality dimensions in relation to customer satisfaction, reporting the findings from Croatia. Therefore, it contributes to the existing literature on service quality and customer satisfaction relationship in hotel industry.

Journal ArticleDOI
TL;DR: This work identifies a new mechanism in astrocytes that could lead to increased levels of extracellular glutamate in HD and thus may contribute to excitotoxicity in this devastating disease.

Journal ArticleDOI
01 Feb 2013-Leukemia
TL;DR: Acute myeloid leukemia with biallelic CEBPA gene mutations and normal karyotype represents a distinct genetic entity associated with a favorable clinical outcome and shows overlapping biologic, pathologic, immunophenotypic, and prognostic features.
Abstract: Acute myeloid leukemia with biallelic CEBPA gene mutations and normal karyotype represents a distinct genetic entity associated with a favorable clinical outcome. J Clin Oncol 2010; 28: 570–577. 11 Döhner K, Tobis K, Ulrich R, Fröhling S, Benner A, Schlenk RF et al. Prognostic significance of partial tandem duplications of the MLL gene in adult patients 16 to 60 years old with acute myeloid leukemia and normal cytogenetics: a study of the Acute Myeloid Leukemia Study Group Ulm. J Clin Oncol 2002; 20: 3254–3261. 12 Schlenk RF, Döhner K, Krauter J, Fröhling S, Corbacioglu A, Bullinger L et al. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med 2008; 358: 1909–1918. 13 Haferlach C, Mecucci C, Schnittger S, Kohlmann A, Mancini M, Cuneo A et al. AML with mutated NPM1 carrying a normal or aberrant karyotype show overlapping biologic, pathologic, immunophenotypic, and prognostic features. Blood 2009; 114: 3024–3032. 14 Grossmann V, Schnittger S, Schindela S, Klein HU, Eder C, Dugas M et al. Strategy for robust detection of insertions, deletions, and point mutations in CEBPA, a GC-rich content gene, using 454 next-generation deep-sequencing technology. J Mol Diagn 2011; 13: 129–136. 15 Schnittger S, Alpermann T, Eder C, Schindela S, Grossmann V, Kern W et al. The role of different genetic subtypes in CEBPA mutated AML. Blood (ASH Ann Meet) 2010; 116: 752 (Abstracts: oral presentation).

Journal ArticleDOI
TL;DR: MCK-2 may play a dual role in MCMV infection, as a chemokine regulating the host response and attracting specific target cells and as part of a glycoprotein complex promoting entry into cells crucial for virus dissemination.
Abstract: Human cytomegalovirus (HCMV) forms two gH/gL glycoprotein complexes, gH/gL/gO and gH/gL/pUL(128,130,131A), which determine the tropism, the entry pathways and the mode of spread of the virus. For murine cytomegalovirus (MCMV), which serves as a model for HCMV, a gH/gL/gO complex functionally homologous to the HCMV gH/gL/gO complex has been described. Knock-out of MCMV gO does impair, but not abolish, virus spread indicating that also MCMV might form an alternative gH/gL complex. Here, we show that the MCMV CC chemokine MCK-2 forms a complex with the glycoprotein gH, a complex which is incorporated into the virion. We could additionally show that mutants lacking both, gO and MCK-2 are not able to produce infectious virus. Trans-complementation of these double mutants with either gO or MCK-2 showed that both proteins can promote infection of host cells, although through different entry pathways. MCK-2 has been extensively studied in vivo by others. It has been shown to be involved in attracting cells for virus dissemination and in regulating antiviral host responses. We now show that MCK-2, by forming a complex with gH, strongly promotes infection of macrophages in vitro and in vivo. Thus, MCK-2 may play a dual role in MCMV infection, as a chemokine regulating the host response and attracting specific target cells and as part of a glycoprotein complex promoting entry into cells crucial for virus dissemination.

Journal ArticleDOI
J.-Y. Choi1, C. Han1, Andrzej Udalski2, Takahiro Sumi3, B. S. Gaudi4, Andrew Gould4, David P. Bennett5, Martin Dominik6, Jean-Philippe Beaulieu7, Yiannis Tsapras8, Valerio Bozza9, Fumio Abe10, Ian A. Bond11, C. S. Botzler12, P. Chote13, M. Freeman12, Akihiko Fukui, K. Furusawa10, Yoshitaka Itow10, C. H. Ling11, Kimiaki Masuda10, Yutaka Matsubara10, N. Miyake10, Yasushi Muraki10, Kouji Ohnishi, Nicholas J. Rattenbury12, T. Saito14, Denis J. Sullivan13, K. Suzuki10, Winston L. Sweatman11, Daisuke Suzuki3, S. Takino10, Paul J. Tristram, K. Wada3, Philip Yock12, Michał K. Szymański2, M. Kubiak2, Grzegorz Pietrzyński2, Igor Soszyński2, Jan Skowron4, Szymon Kozłowski2, Radosław Poleski2, Krzysztof Ulaczyk2, L. Wyrzykowski15, P. Pietrukowicz2, Leonardo A. Almeida16, Darren L. DePoy17, Subo Dong18, Evgeny Gorbikov19, Francisco Jablonski16, Calen B. Henderson4, K.-H. Hwang1, J. Janczak4, Youn Kil Jung1, Shai Kaspi19, C.-U. Lee20, U. Malamud19, D. Maoz19, D. McGregor4, J. A. Muñoz21, Byeong-Gon Park20, H. Park1, R. W. Pogge4, Yossi Shvartzvald19, In-Gu Shin1, Jennifer C. Yee4, Khalid Al-Subai22, P. Browne6, Martin Burgdorf, S. Calchi Novati, Peter N. Dodds6, X.-S. Fang23, F. Finet, M. Glitrup24, Frank Grundahl24, Shenghong Gu23, S. Hardis25, K. B. W. Harpsøe25, Tobias C. Hinse20, Allan Hornstrup26, M. Hundertmark6, Jens Jessen-Hansen24, U. G. Jørgensen10, N. Kains6, Eamonn Kerins27, C. Liebig6, Mikkel N. Lund24, M. Lundkvist24, G. Maier28, Luigi Mancini9, M. Mathiasen25, Matthew T. Penny27, Sohrab Rahvar29, Davide Ricci30, Gaetano Scarpetta, Jesper Skottfelt25, Colin Snodgrass15, John Southworth31, Jean Surdej, J. Tregloan-Reed31, Joachim Wambsganss28, Olivier Wertz, F. Zimmer28, Michael D. Albrow32, Etienne Bachelet33, V. Batista4, S. Brillant34, Arnaud Cassan7, Andrew A. Cole35, C. Coutures7, S. Dieters35, D. Dominis Prester36, J. Donatowicz37, Pascal Fouqué33, J. G. Greenhill35, D. Kubas34, J. B. Marquette7, J. W. Menzies, Kailash C. Sahu38, M. Zub28, D. M. Bramich34, Keith Horne6, Iain A. Steele39, Rachel Street8 
TL;DR: In this article, the authors presented the discovery via gravitational microlensing of two very low mass, very tight binary systems, which have directly and precisely measured total system masses of 0.025 M and 0.034 M, respectively, making them the lowest mass and tightest field brown dwarfs known.
Abstract: Although many models have been proposed, the physical mechanisms responsible for the formation of low-mass brown dwarfs (BDs) are poorly understood. The multiplicity properties and minimum mass of the BD mass function provide critical empirical diagnostics of these mechanisms. We present the discovery via gravitational microlensing of two very low mass, very tight binary systems. These binaries have directly and precisely measured total system masses of 0.025 M ☉ and 0.034 M ☉, and projected separations of 0.31 AU and 0.19 AU, making them the lowest-mass and tightest field BD binaries known. The discovery of a population of such binaries indicates that BD binaries can robustly form at least down to masses of ~0.02 M ☉. Future microlensing surveys will measure a mass-selected sample of BD binary systems, which can then be directly compared to similar samples of stellar binaries.

Journal ArticleDOI
Jelena Aleksić1, L. A. Antonelli2, P. Antoranz3, Ana Babić4  +168 moreInstitutions (23)
TL;DR: In this article, the authors studied the spectral and flux variability of IC 310 from the X-ray band to the VHE gamma-ray regime and confirmed the blazar-like behavior of the radio galaxy IC 310.
Abstract: Context. The radio galaxy IC 310 has recently been identified as a gamma-ray emitter based on observations at GeV energies with Fermi-LAT and at very high energies (VHE, E>100GeV) with the MAGIC telescopes. Originally classified as a head-tail radio galaxy, the nature of this object is subject of controversy since its nucleus shows blazar-like behavior. Aims. In order to understand the nature of IC 310 and the origin of the VHE emission we studied the spectral and flux variability of IC 310 from the X-ray band to the VHE gamma-ray regime. Methods. The light curve of IC 310 above 300GeV has been measured with the MAGIC telescopes from Oct. 2009 to Feb. 2010. Fermi-LAT data (2008-2011) in the 10-500GeV energy range were also analyzed. In X-ray, archival observations from 2003 to 2007 with XMM, Chandra, and Swift-XRT in the 0.5-10keV band were studied. Results. The VHE light curve reveals several high-amplitude and short-duration flares. Day-to-day flux variability is clearly present. The photon index between 120GeV and 8TeV remains at the value $\Gamma\sim2.0$ during both low and high flux states. The VHE spectral shape does not show significant variability, whereas the flux at 1TeV changes by a factor of $\sim7$. Fermi-LAT detected only eight gamma-ray events in the energy range 10GeV-500GeV in three years of observation. The measured photon index of $\Gamma=1.3\pm0.5$ in the Fermi-LAT range is very hard. The X-ray measurements show strong variability in flux and photon index. The latter varied from $1.76\pm0.07$ to $2.55\pm0.07$. Conclusion. The rapid variability measured confirms the blazar-like behavior of IC 310. The TeV emission seems to originate from scales of less than 80 Schwarzschild radii within the compact core of its FRI radio jet with orientation angle 10deg-38deg. The SED resembles that of an extreme blazar, albeit the luminosity is more than two orders of magnitude lower.

Journal ArticleDOI
TL;DR: Salivary levels of proinflammatory tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) cytokines in whole unstimulated saliva in subjects with burning mouth syndrome before and after treatment with low-level laser therapy (LLLT).
Abstract: The aim of this study was to determine the levels of proinflammatory tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) cytokines in whole unstimulated saliva in subjects with burning mouth syndrome (BMS) before and after treatment with low-level laser therapy (LLLT). BMS is characterized by a continuous, painful burning sensation in a clinically normal-appearing oral mucosa. A sample consisting of 40 consecutive subjects was selected on a voluntary basis from the pool of patients who presented for diagnosis and treatment of BMS at the Oral Medicine Unit of the Faculty of Medicine of the University of Rijeka. For determination of salivary levels of TNF-α and IL-6, ELISA (Sigma Immunochemicals, St. Louis, MO, USA) was performed to determine the salivary levels of TNF-α and IL-6. After 4 weeks of LLLT, the salivary levels of TNF-α and IL-6 in the experimental group decreased significantly (p < 0.001). There was no significant difference in the experimental group regarding visual analogue scale.

Journal ArticleDOI
TL;DR: This article presents a practical approach for dealing with manuscripts suspected of salami publication during the submission process and after article publication in Biochemia Medica.
Abstract: Salami publication or segmented publication is a distinct form of redundant publication which is usually characterized by similarity of hypothesis, methodology or results but not text similarity These aspects of publications are not objectively detected by software applications and therefore present a serious threat to publication ethics This article presents a practical approach for dealing with manuscripts suspected of salami publication during the submission process and after article publication in Biochemia Medica

Journal ArticleDOI
Rachel Street1, J.-Y. Choi2, Yiannis Tsapras3, Chang S. Han2, K. Furusawa4, M. Hundertmark5, Andrew Gould6, Takahiro Sumi7, Ian A. Bond8, D. Wouters9, Robert T. Zellem10, Andrzej Udalski11, Colin Snodgrass12, Keith Horne5, Martin Dominik13, P. Browne5, N. Kains14, D. M. Bramich14, D. Bajek5, Iain A. Steele15, Sergei I. Ipatov16, Fumio Abe4, David P. Bennett17, C. S. Botzler18, P. Chote19, M. Freeman18, Akihiko Fukui4, P. Harris19, Yoshitaka Itow4, C. H. Ling8, Kimiaki Masuda4, Yutaka Matsubara4, N. Miyake4, Yasushi Muraki20, Takahiro Nagayama4, S. Nishimaya, Kouji Ohnishi, Nicholas J. Rattenbury18, To. Saito21, Denis J. Sullivan19, Daisuke Suzuki7, Winston L. Sweatman8, Paul J. Tristram, K. Wada7, Philip Yock18, Michał K. Szymański11, M. Kubiak11, Grzegorz Pietrzyński22, Igor Soszyński11, Radosław Poleski11, Krzysztof Ulaczyk11, L. Wyrzykowski23, Jennifer C. Yee6, Subo Dong24, In-Gu Shin2, C.-U. Lee25, Jan Skowron6, L. de Almeida26, Darren L. DePoy27, B. S. Gaudi6, Li-Wei Hung6, Francisco Jablonski, Shai Kaspi28, N. Klein28, K.-H. Hwang2, J.-R. Koo25, D. Maoz28, J. A. Muñoz29, R. W. Pogge6, D. Polishhook28, Avi Shporer27, Jennie McCormick, G. W. Christie, Tim Natusch, Benjamin William Allen, Jack D. Drummond, D. Moorhouse, G. Thornley, M. Knowler, M. Bos, Greg Bolt, J.-P. Beaulieu9, Michael D. Albrow30, V. Batista6, S. Brillant14, J. A. R. Caldwell, Arnaud Cassan9, Andrew A. Cole31, E. Corrales9, Ch. Coutures9, S. Dieters31, D. Dominis Prester32, J. Donatowicz33, P. Fouqué23, Etienne Bachelet23, J. G. Greenhill31, S. R. Kane34, D. Kubas35, J.-B. Marquette9, R. Martin, J. W. Menzies, K. R. Pollard18, Kailash C. Sahu36, Joachim Wambsganss26, Andrew Williams, M. Zub26, Khalid Al-Subai16, Valerio Bozza37, Martin Burgdorf38, S. Calchi Novati, Peter N. Dodds5, Stefan Dreizler39, François Finet, T. Gerner26, S. Hardis40, K. B. W. Harpsøe41, Frederic V. Hessman39, Tobias C. Hinse25, U. G. Jørgensen40, Eamonn Kerins42, C. Liebig5, Luigi Mancini37, M. Mathiasen40, Matthew T. Penny6, S. Proft26, Sohrab Rahvar43, Davide Ricci, Gaetano Scarpetta, S. Schaefer11, F. Schoenebeck11, John Southworth44, Jean Surdej 
TL;DR: In this article, an analysis of the anomalous microlensing event, MOA-2010-BLG-073, announced by the Microlensing Observations in Astrophysics survey on 2010 March 18, is presented.
Abstract: We present an analysis of the anomalous microlensing event, MOA-2010-BLG-073, announced by the Microlensing Observations in Astrophysics survey on 2010 March 18. This event was remarkable because the source was previously known to be photometrically variable. Analyzing the pre-event source light curve, we demonstrate that it is an irregular variable over timescales >200 days. Its dereddened color, (V – I)_(S,0), is 1.221 ± 0.051 mag, and from our lens model we derive a source radius of 14.7 ± 1.3 R_☉, suggesting that it is a red giant star. We initially explored a number of purely microlensing models for the event but found a residual gradient in the data taken prior to and after the event. This is likely to be due to the variability of the source rather than part of the lensing event, so we incorporated a slope parameter in our model in order to derive the true parameters of the lensing system. We find that the lensing system has a mass ratio of q = 0.0654 ± 0.0006. The Einstein crossing time of the event, t_E = 44.3 ± 0.1 days, was sufficiently long that the light curve exhibited parallax effects. In addition, the source trajectory relative to the large caustic structure allowed the orbital motion of the lens system to be detected. Combining the parallax with the Einstein radius, we were able to derive the distance to the lens, D_L = 2.8 ± 0.4 kpc, and the masses of the lensing objects. The primary of the lens is an M-dwarf with M_(L,1) = 0.16 ± 0.03 M_☉, while the companion has M_(L,2) = 11.0 ± 2.0 M_J, putting it in the boundary zone between planets and brown dwarfs.

Journal Article
TL;DR: In this article, the authors compared subjective well-being, life goals and self-control of people with different profiles of orientations to happiness, and found that people who live a full life are the happiest, they value intrinsic life goals, and have good self control.
Abstract: People pursue happiness through different paths: pleasure, engagement and meaning, which are differently related to well-being. The aim of this research was to compare subjective well-being, life goals and self-control of people with different profiles of orientations to happiness. Students (484 females, 278 males; mean age 20.60) rated their life satisfaction, positive and negative affect, orientations to happiness, and self-control. Based on the K-means cluster analysis participants were grouped into four groups: students who highly endorse hedonic and eudaimonic orientation (the "Full life" group), those who do not endorse either of them (the "Empty life" group), those who live eudaimonic and those who live hedonic life. People who live a full life are the happiest, they value intrinsic life goals and have good self-control. Contrary, people who live empty lives have the lowest well-being, they value extrinsic and intrinsic life goals less than other people and have low self-control.

Journal Article
TL;DR: The results suggest that these proinflammatory cytokines are elevated in the saliva of patients with oral squamous cell carcinoma and oral premalignant lesions as compared to controls, which may have diagnostic and/or prognostic significance.
Abstract: The aim of this study was to determine the salivary concentrations of tumour necrosis factor α (TNF-α) and interleukin 6 (IL-6) in patients with premalignant and malignant lesions. The study involved 57 patients who were examined between 2008 and 2010 at the Department of Oral Medicine and Department of Oral and Maxillofacial Surgery of the Medical Faculty, University of Rijeka, Croatia. They were divided into three groups: 19 patients with oral premalignant lesions, 19 with oral squamous cell carcinoma and 19 healthy control volunteers. Whole saliva was collected and investigated for the presence of TNF-α and IL-6 by enzyme immunoassay at the Department of Dentistry and Maxillofacial Surgery, Medical Faculty, University of Graz, Austria. All groups had statistically significant differences in values of TNF-α and IL-6 (P < 0.001). The results suggest that these proinflammatory cytokines are elevated in the saliva of patients with oral squamous cell carcinoma and oral premalignant lesions as compared to controls, which may have diagnostic and/or prognostic significance.

Journal ArticleDOI
TL;DR: A new tumor immune evasion mechanism that is mediated through the interaction between PS and CD300a is demonstrated and it is suggested that CD300c, similarly toCD300a, also interacts with PS.
Abstract: The activity of NK cells is controlled by inhibitory and activating receptors. The inhibitory receptors interact mostly with MHC class I proteins, however, inhibitory receptors such as CD300a, which bind to non-MHC class I ligands, also exist. Recently, it was discovered that phosphatidylserine (PS) is a ligand for CD300a and that the interaction between PS expressed on apoptotic cells and CD300a inhibits the uptake of apoptotic cells by phagocytic cells. Whether PS can inhibit NK-cell activity through CD300a is unknown. Here, we have generated specific antibodies directed against CD300a and we used these mAbs to demonstrate that various NK-cell clones express different levels of CD300a. We further demonstrated that both CD300a and its highly homologous molecule CD300c bind to the tumor cells equally well and that they recognize PS and additional unknown ligand(s) expressed by tumor cells. Finally, we showed that blocking the PS-CD300a interaction resulted in increased NK-cell killing of tumor cells. Collectively, we demonstrate a new tumor immune evasion mechanism that is mediated through the interaction between PS and CD300a and we suggest that CD300c, similarly to CD300a, also interacts with PS.