Hierarchical Losses and New Resources for Fine-grained Entity Typing and Linking

Extraction from raw text to a knowledge base of entities and fine-grained types is often cast as prediction into a flat set of entity and type labels, neglecting the rich hierarchies over types and entities contained in curated ontologies. Previous attempts to incorporate hierarchical structure have yielded little benefit and are restricted to shallow ontologies. This paper presents new methods using real and complex bilinear mappings for integrating hierarchical information, yielding substantial improvement over flat predictions in entity linking and fine-grained entity typing, and achieving new state-of-the-art results for end-to-end models on the benchmark FIGER dataset. We also present two new human-annotated datasets containing wide and deep hierarchies which we will release to the community to encourage further research in this direction: MedMentions, a collection of PubMed abstracts in which 246k mentions have been mapped to the massive UMLS ontology; and TypeNet, which aligns Freebase types with the WordNet hierarchy to obtain nearly 2k entity types. In experiments on all three datasets we show substantial gains from hierarchy-aware training.Comment: ACL 201

Identification of Loci Controlling Restriction of Parasite Growth in Experimental Taenia crassiceps Cysticercosis

Human neurocysticercosis (NC) caused by Taenia solium is a parasitic disease of the central nervous system that is endemic in many developing countries. In this study, a genetic approach using the murine intraperitoneal cysticercosis caused by the related cestode Taenia crassiceps was employed to identify host factors that regulate the establishment and proliferation of the parasite. A/J mice are permissive to T. crassiceps infection while C57BL/6J mice (B6) are comparatively restrictive, with a 10-fold difference in numbers of peritoneal cysticerci recovered 30 days after infection. The genetic basis of this inter-strain difference was explored using 34 AcB/BcA recombinant congenic strains derived from A/J and B6 progenitors, that were phenotyped for T. crassiceps replication. In agreement with their genetic background, most AcB strains (A/J-derived) were found to be permissive to infection while most BcA strains (B6-derived) were restrictive with the exception of a few discordant strains, together suggesting a possible simple genetic control. Initial haplotype association mapping using >1200 informative SNPs pointed to linkages on chromosomes 2 (proximal) and 6 as controlling parasite replication in the AcB/BcA panel. Additional linkage analysis by genome scan in informative [AcB55xDBA/2]F1 and F2 mice (derived from the discordant AcB55 strain), confirmed the effect of chromosome 2 on parasite replication, and further delineated a major locus (LOD = 4.76, p<0.01; peak marker D2Mit295, 29.7 Mb) that we designate Tccr1 (T. crassiceps cysticercosis restrictive locus 1). Resistance alleles at Tccr1 are derived from AcB55 and are inherited in a dominant fashion. Scrutiny of the minimal genetic interval reveals overlap of Tccr1 with other host resistance loci mapped to this region, most notably the defective Hc/C5 allele which segregates both in the AcB/BcA set and in the AcB55xDBA/2 cross. These results strongly suggest that the complement component 5 (C5) plays a critical role in early protective inflammatory response to infection with T. crassiceps

Genetic Control of Susceptibility to Infection with Candida albicans in Mice

Candida albicans is an opportunistic pathogen that causes acute disseminated infections in immunocompromised hosts, representing an important cause of morbidity and mortality in these patients. To study the genetic control of susceptibility to disseminated C. albicans in mice, we phenotyped a group of 23 phylogenetically distant inbred strains for susceptibility to infection as measured by extent of fungal replication in the kidney 48 hours following infection. Susceptibility was strongly associated with the loss-of-function mutant complement component 5 (C5/Hc) allele, which is known to be inherited by approximately 40% of inbred strains. Our survey identified 2 discordant strains, AKR/J (C5-deficient, resistant) and SM/J (C5-sufficient, susceptible), suggesting that additional genetic effects may control response to systemic candidiasis in these strains. Haplotype association mapping in the 23 strains using high density SNP maps revealed several putative loci regulating the extent of C. albicans replication, amongst which the most significant were C5 (P value = 2.43×10−11) and a novel effect on distal chromosome 11 (P value = 7.63×10−9). Compared to other C5-deficient strains, infected AKR/J strain displays a reduced fungal burden in the brain, heart and kidney, and increased survival, concomitant with uniquely high levels of serum IFNγ. C5-independent genetic effects were further investigated by linkage analysis in an [A/JxAKR/J]F2 cross (n = 158) where the mutant Hc allele is fixed. These studies identified a chromosome 11 locus (Carg4, Candida albicans resistance gene 4; LOD = 4.59), and a chromosome 8 locus (Carg3; LOD = 3.95), both initially detected by haplotype association mapping. Alleles at both loci were inherited in a co-dominant manner. Our results verify the important effect of C5-deficiency in inbred mouse strains, and further identify two novel loci, Carg3 and Carg4, which regulate resistance to C. albicans infection in a C5-independent manner

Comparison of collective investment in the Czech Republic and Serbia

The master thesis deals with collective investment in two European countries, in the Czech Republic and Serbia. The first chapter describes collective investment and its characteristics. It characterizes basic risks, advantages and disadvantages, institutional arrangement of funds and their regulation. The next chapter discusses the characteristics of the Serbian financial system, its institutions and collective investment entities. The chapter discussing Czech collective investment and entities operating on the Czech market is similarly structured. The final part compares the collective investment funds of the two countries based on the fees and taxation methods, with the aim of pointing out the differences between them.Diplomová práce se zabývá kolektivním investováním ve dvou evropských státech, v České republice a Srbsku. První kapitola popisuje kolektivní investování a jeho charakteristiky. Charakterizuje základní rizika, výhody a nevýhody, institucionální uspořádaní fondů a způsob jejich regulace. Další kapitola projednává charakteristiky srbského finančního systému, jeho institucí a subjektů kolektivního investování. Podobným způsobem je členěna i kapitola projednávající české kolektivní investování a subjekty působící na českém trhu. Závěrečná část porovnává fondy kolektivního investování dvou států podle poplatků a způsobů zdanění, s cílem poukázat na rozdíly mezi nimi

Development and realization of optical sources for automated 10 Gbit/s and 40 Gbit/s test systems

Zsfassung in engl. SpracheKurzfassung In den letzten Jahren stieg der Anteil der optischen Kommunikation am weltweiten Datenverkehr stark an. Wir stehen gerade an der Schwelle, dass schon einzelne Haushalte breitbandig mit optischen Medien an das Internet angebunden werden. Um die hohe Anzahl an optischen Verbindungen seitens der Internetanbieter günstig realisieren zu können, wurden in den letzten Jahren diverse Konzepte für eine optische Verbindung der "last-mile" entwickelt. Viele dieser Konzepte erfordern neuartige Datenübertragungskomponenten. Vor allem die optischen Empfänger müssen für neue Modulationsverfahren und Netzwerktopologien optimiert, verbessert oder vollkommen neu entwickelt werden. Im Rahmen dieser Diplomarbeit wurde ein flexibles optisches Testsystem entwickelt, welches ermöglichen soll neuartige übertragungsverfahren und Techniken zu testen und zu erforschen. Es wurden zwei Laserquellen bestehend aus mehreren Modulen entwickelt, die im Zusammenspiel in der Lage sind, komplexe Modulationsarten mit hoher Geschwindigkeit und Qualität in Form von optischen Signalen zu realisieren. Die vorliegende Arbeit beschreibt einerseits die Motivation, die solch einer Entwicklung zu Grunde liegt, als auch die konkrete Realisierung des Testsystems. Die zwei realisierten modularen optischen Quellen arbeiten auf den Telekommunikationswellenlängen von 1310nm und 1550 nm. Die schnellere der beiden Quellen kann bis zu 40 Gbit/s schnelle Signale generieren. Der neuartige Aspekt der Quellen ist dabei die Modulierbarkeit bis hinunter zu DC. Damit ist es möglich Datensignale, welche in geschalteten optischen Netzen existieren, nachzubilden. Diese haben neben der schnellen AC-Modulation auch sprunghaft wechselnde Amplituden und Mittelwerte, es handelt sich dabei um sogenannte Burst-Mode-Signale. Die Realisierung der beiden optischen Quellen erfolgte jeweils in Form von drei Funktionsmodulen: Zum einen das Modul "Laser", welches sowohl die Ansteuerung als auch die Temperaturregelung der eigentlichen Laserdiode beinhaltet. Dabei kann die Laserdiode entweder im Dauerstrichmodus oder direkt moduliert betrieben werden. Die direkte Modulation der Laserdioden wird für niedrige Datenraten genutzt. Für höhere Übertragungsgeschwindigkeiten wird das zweite Modul "Modulation" eingesetzt. Dieses nutzt einen optischen Modulator und ermöglicht somit eine schnelle und präzise Modulation der Lichtleistung mit dem Nachteil, dass keine DC-Signale übertragen werden können. Als drittes Modul "Leistungsanpassung" wurde eine steuerbare optische Abschwächung realisiert, die es ermöglicht, das Gesamtsignal in einem weiten Leistungsbereich auszugeben. Durch Kombination der drei Module, zusammen mit externen elektrischen Signalgeneratoren, ist es möglich hochkomplexe optische Signalformen mit hoher Reproduzierbarkeit zu generieren. In der Arbeit ist nicht nur der Entwurf und der Aufbau beschrieben, sondern auch die Messungen der grundlegenden Parameter der Module, sowie das Zusammenspiel der Module am Beispiel der Generation exemplarischer "Burst-Mode"-Signale. Der Abschluss umfasst eine Zusammenfassung der erreichten Ergebnisse und einen Ausblick auf zukünftige Forschungsmöglichkeiten mit dem Testsystem.Abstract In the last years the share of optical communication in global data networks becomes more and more important. The number of households that are directly connected with optical bers (ber to the home) starts to increase. To allow a huge number of optical endpoints modern concepts of optical communications have been developed. A lot of these new technologies require new network components. Especially optical receivers need to be optimized, improved or even developed newly. The presented work describes the development and the realization of a test system allowing the generation of highly complex optical waveforms which are used in modern optical switched network topologies. Two laser sources were realized. Both consist of different modules, which in combination allow complex modulation schemes with a high modulation rate together with a high quality. The work describes on one hand the motivation to develop such a test system and on the other hand the practical realization as well as measurements of the whole test system. The two realized optical sources are designed for the common telecommunication wavelengths of 1310nm and 1550 nm. The faster one of the two sources is capable of producing signals with a data rate up to 40Gbit/s. The novelty of these sources is the possibility to apply modulation signals down to DC. With this feature it is possible to generate optical data signals which are common in switched optical networks. Such signals usually have a fast AC modulation at the same time with variable amplitudes and optical mean values. Such signals are usually called burst mode signals. The practical realization of the two optical sources is separated in three independent modules for each source. One module is called 'laser' and houses temperature regulation as well as controlling of the laser diode itself. The laser diode can be operated in continuous wave mode or in direct modulated mode. This direct modulated mode can be used for data rates down to DC. For higher transmission speeds a second module was realized for each source. It uses an external modulator which allows fast and precise modulation at high speeds with the drawback that the DC modulation cannot be used for this module. A third module which is called 'power control' has a controllable optical attenuator which allows to vary the optical output power in a wide range. The combination of these three modules together with external signal generators allows generation of highly complex optical signal patterns with good reproducibility. In the presented work not only the development and the realization of the modules are described but also measurements of the basic parameters of each module. Furthermore, the combination of these modules and an exemplary burst mode signal generation setup are presented. In the last chapter a conclusion of the reached performance and a forecast on possible future research scenarios are presented.9

Hyperinflace v Jugoslávii na začátku 90. let

This bachelor thesis is focused on a thorough analysis of the hyperinflation that affected Yugoslavia in the early 1990s. The main aim is to identify the causes and consequences of the hyperinflation. The introductory chapter describes the events in the Socialist Federal Republic of Yugoslavia, as well as the specifics of the economic policy at that time. The second part is devoted to the very course of the hyperinflation, including the war in Croatia, and the sanctions that the United Nations imposed on Yugoslavia. The following part of the thesis is focused on the comparison of the current hyperinflation in Venezuela with the hyperinflation in the former Yugoslavia using the macroeconomic aggregates. The final part is devoted to the current situation in Serbia. Recommendations for the government and the central bank regarding the economic policy have also been established and their main aim is to mitigate the risk of hyperinflation in the future

Complement component 5 (C5)-dependent and independent susceptibility to eukaryotic pathogens in mouse models

The complement system is an intricate immune surveillance system that plays an integrative role in host defense and homeostasis. The dominant protective effect of the fifth complement component (C5) was firmly established in the mouse model of disseminated Candida albicans infection, where C5 deficiency results in increased mortality and high fungal burden. Using a cohort of 23 inbred mouse strains, we have uncovered several putative genetic associations by GWAS, in addition to C5, that control replication of C. albicans in the host, and identified two discordant strains, namely AKR/J and SM/J. C5-deficient AKR/J strain displays a reduced fungal burden in target organs and increased survival, concomitant with high levels of serum IFNγ. Subsequent genetic linkage analysis in informative F2 progeny derived from susceptible A/J and resistant AKR/J mice validated loci on chromosome 8 (Carg3, Candida albicans resistance gene 3; LOD=3.95) and chromosome 11 (Carg4; LOD=4.59) as modulating susceptibility to C. albicans infection in the context of C5-deficiency. Furthermore, we ascribed the genetic basis of increased susceptibility in C5-sufficient SM/J mice to distal chromosome 15 (Carg5; LOD=6.09) by performing genetic linkage analysis in [B6xSM/J]F2 animals fixed for functional C5 alleles. Detailed scrutiny of the innate immune compartment revealed a complex myeloid defect in SM/J mice, regulated in part by Carg5 and exemplified by decreased Ly6G expression, aberrant reactive oxygen species generation, decreased recruitment of inflammatory monocytes, and increased serum CCL2. Finally, by combining haplotype association mapping in 34 AcB/BcA recombinant congenic strains (RCS) and linkage analysis in informative F2 progeny derived from permissive DBA/2J and restrictive AcB55 strains, we demonstrate that C5 underlies the Tccr1 locus on chromosome 2 (Taenia crassiceps cysticercosis restrictive locus 1; LOD=4.76) and modulates the outcome to Taenia crassiceps infection in mice. Therefore, the work in this thesis bona fide identified the complement system in the early protective inflammatory response to infection with diametrically divergent pathogens C. albicans and T. crassiceps, and uncovered novel C5-independent loci involved in the host response to C. albicans.Le système du complément est un système de surveillance immunitaire élaboré qui joue un rôle intégrant dans la défense de l'hôte et de l'homéostasie. L’effet dominant protecteur du cinquième composant du complément (C5) a été fermement établi dans le modèle murin d’infection systémique à Candida albicans, où le déficit en C5 cause une mortalité accrue et une charge fongique élevée. En utilisant une cohorte de 23 lignées pures de souris, nous avons découvert plusieurs associations génétiques putatives, en plus de C5, qui contrôlent la réplication de C. albicans dans l’hôte, et identifié deux lignées discordantes, soit AKR/J et SM/J. La lignée C5-déficiante AKR/J affiche une charge fongique réduite dans les organes cibles et une survie améliorée, concomitamment avec des niveaux élevés d’IFNγ dans le sérum. Une analyse de liaison génétique par balayage du génome entier dans la progéniture F2 dérivée de la lignée susceptible A/J et résistante AKR/J a validé les locus sur le chromosome 8 (Carg3, Candida albicans resistance gene 3; LOD=3.95) et le chromosome 11 (Carg4; LOD=4.59) modulant la susceptibilité à l’infection à C. albicans dans le contexte de déficit en C5. De plus, nous avons attribué la base génétique de la susceptibilité accrue des souris C5-suffisantes SM/J au segment distal sur le chromosome 15 (Carg5; LOD=6.09) en effectuant une analyse de liaison génétique dans les animaux [B6xSM/J]F2 fixés pour les allèles C5 fonctionnels. Une inspection détaillée du compartiment immunitaire inné a révélé un défaut myéloïde complexe chez la lignée SM/J, régulé en partie par Carg5 et caractérisé par l’expression abaissée de Ly6G, la production aberrante d’espèces réactives de l’oxygène, le recrutement réduit des monocytes inflammatoires, et les niveaux circulatoires de CCL2 augmentés. Finalement, en combinant la cartographie de l’association des haplotypes dans 34 lignées de souris AcB/BcA recombinantes et l’analyse de liaison génétique dans la progéniture F2 informative dérivée de la lignée permissive DBA/2J et restrictive AcB55, nous avons démontré que C5 est à la base du locus Tccr1 (Taenia crassiceps cysticercosis restrictive locus 1; LOD=4.76) et module l’issue de l’infection à Taenia crassiceps chez la souris. Donc, le travail dans cette thèse met en évidence le besoin commun pour le système du complément dans la réponse inflammatoire protectrice durant les débuts de l’infection par des pathogènes diamétralement distincts, C. albicans et T. crassiceps, et dévoile des nouveaux locus indépendants du C5 impliqués dans la réponse de l’hôte à C. albicans

Genetic control of susceptibility to candida albicans in SM/J mice

In the immunocompromised host, invasive infection with the fungal pathogen Candida albicans is associated with high morbidity and mortality. Sporadic cases in otherwise normal individuals are rare, and they are thought to be associated with genetic predisposition. Using a mouse model of systemic infection with C. albicans, we identified the SM/J mouse strain as unusually susceptible to infection. Genetic linkage studies in informative [C57BL/6JxSM/J]F2 mice identified a major locus on distal chromosome 15, given the appellation Carg5, that regulates C. albicans replication in SM/J mice. Cellular and molecular immunophenotyping experiments, as well as functional studies in purified cell populations from SM/J and C57BL/6J, and in [C57BL/ 6JxSM/J]F2 mice fixed for homozygous or heterozygous Carg5 alleles, indicate that Carg5-regulated susceptibility in SM/J is associated with a complex defect in the myeloid compartment of these mice. SM/J neutrophils express lower levels of Ly6G, and importantly, they show significantly reduced production of reactive oxygen species in response to stimulation with fMLF and PMA. Likewise, CD11b+Ly6G2Ly6Chi inflammatory monocytes were present at lower levels in the blood of infected SM/J, recruited less efficiently at the site of infection, and displayed blunted oxidative burst. Studies in F2 mice establish strong correlations between Carg5 alleles, Ly6G expression, production of serum CCL2 (MCP-1), and susceptibility to C. albicans. Genomic DNA sequencing of chromatin immunoprecipitated for myeloid proinflammatory transcription factors IRF1, IRF8, STAT1 and NF-kB, as well as RNA sequencing, were used to develop a "myeloid inflammatory score" and systematically analyze and prioritize potential candidate genes in the Carg5 interval.Peer reviewed: YesNRC publication: Ye

Long-Term Trend of Liver Cancer Mortality in Serbia, 1991–2015: An Age-Period-Cohort and Joinpoint Regression Analysis

Background and Objectives: Trends of liver cancer mortality vary widely around the world. The purpose of this study was to assess the trend of liver cancer mortality in Serbia. Material and Methods: Descriptive epidemiological study design was used in this research. The age-standardized rates (ASRs, per 100,000) were calculated using the direct method, according to the World standard population. Temporal trends were assessed using the average annual percent change (AAPC) with 95% confidence interval (95% CI), according to joinpoint regression. An age-period-cohort analysis was used to evaluate the underlying factors for liver cancer mortality trends. Results: In Serbia from 1991 to 2015, over 11,000 men and nearly 8000 women died from liver cancer. The trend in liver cancer mortality significantly decreased both in men (AAPC = &minus;1.3%; 95% CI = &minus;1.7 to &minus;0.9) and women (AAPC = &minus;1.5%; 95% CI = &minus;1.9 to &minus;1.1). For liver cancer mortality, statistically significant cohort and period effects were observed in both genders. Conclusions: The downward trends in liver cancer mortality in Serbia are recorded during the past decades