Firm-level frictions in macroeconomics

This dissertation consists of three essays on firm-level frictions and their aggregate implications. The first two chapters show that inter-firm lending plays an important role in business cycle fluctuations. In Chapter I, I theoretically investigate the role of supplier credit relationships in propagating and amplifying small shocks using a stylized model of inter-firm trade and lending. I build a network model of the economy in which trade in intermediate goods is financed by supplier credit. In the model, a financial shock to one firm affects its ability to make payments to its suppliers. The credit linkages between firms then transmit financial shocks across firms, amplifying their effects on aggregate output. In Chapter II, I embed this mechanism into a more general macroeconomic framework to study empirically the role that inter-firm credit plays in the business cycle. To calibrate the model, I construct a proxy of inter-industry credit flows from firm- and industry-level data. I find that the credit network of the US accounts for 22 percent of the fall in GDP occurring from an aggregate financial shock. Finally, I use a structural factor approach to estimate the shocks which affected US industrial production (IP) industries from 1997-2013. I find that most aggregate volatility in IP was driven by aggregate liquidity shocks and idiosyncratic productivity shocks, and that the credit network of IP industries generated 17 percent of observed aggregate volatility. During the recent recession, three-quarters of the drop in aggregate IP was due to an aggregate financial shock. Chapter III presents a theoretical investigation of the long-run relationship between international trade and unemployment. I develop and analyze a static general equilibrium model with labor market frictions and heterogeneous firms in which firms can engage in cross-border hiring by employing labor domestically or from abroad. This chapter outlines the conditions on the model parameters under which unemployment rises or falls after trade liberalization, and demonstrates that models in the literature which ignore cross-border hiring likely underestimate the upward force of trade liberalization on unemployment

APPROACHING A DYNAMIC URBAN TRANSIT DEMAND MODEL FOR SYDNEY

Urban Australia has seen a continuing movement away from public transit. In 1988 over 95% of all passenger kilometres in the Sydney Metropolitan area were by car and truck. There is now a growing recognition of the costs of increased automobile use both locally in terms of congestion, pollution and accident costs and globally from vehicle greenhouse gas emissions. Strategies to stem the trend must come from a clear understanding of all the factors affecting demand in the long and short term at the micro-economic level. This paper discusses the approach to be used in development of a dynamic model system for transit demand in Sydney using travel survey data from 1971, 1981 and 1991. Use of data spanning 20 years means that the effect of land use on transit demand can be examined. The model system will aim to allow analysis of questions regarding public vs private transport not as “either / or” but rather in terms of providing the most appropriate mode for the context

Limited Government in Nondemocracies (The Role of Capital Owners).

Nondemocratic regimes are marked by the absence of a formal (or effectively functioning) mechanism of political accountability. The present study, however, investigates the seeds of some kind of an informal mechanism of accountability which may ‘restrict’ the policymaking power of autocratic rulers. In that regard, it focuses on the business-state relations in nondemocratic countries. Autocratic rulers may make policies favoring the interests of the capital owners. The main argument of the study is that if that policymaking springs from the bargaining-power of the private sector, then it can be regarded as a form of accountability—indirect accountability. It is indirect, because, the capital owners cannot directly remove the rulers off the office. Nevertheless, by ceasing to invest or produce (exit), they can halt or shrink the size of the economic activities from which the rulers extract their revenue (tax revenue). As a result, by exiting or simply by (credibly) threatening to exit, capital owners can indirectly hold the autocratic rulers accountable for the policies they make. The present study, thus, quantitatively tests whether we indeed observe a policymaking favoring capitalist interests in general, or at least the interests of the capital owners in the leading economic sector of a country, when (1) the incumbents are financially dependent on tax revenue, and (2) the private-sector credibly threatens to exit or actually exits. Credible exit-threat is conceptualized as a function of (a) investment strength and independence of the private sector and (2) existence of sectorally determined viable exit-opportunities. The results of a series of time-series-cross-sectional regression analyses indicate that, controlling for other factors, the joint presence of the conditions of indirect accountability is positively correlated with the level of certain pro-leading-sector policies. The importance of the findings hinges on a possible link to unlimited government, and democratization, in the long run, through transfer of economic power to the private sector due to policy concession made, and also through formalization and spread of habits of interaction between the government and citizens.Ph.D.Political ScienceUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/64586/1/ealtinog_1.pd

Optical imaging in vivo with a focus on paediatric disease: technical progress, current preclinical and clinical applications and future perspectives

To obtain information on the occurrence and location of molecular events as well as to track target-specific probes such as antibodies or peptides, drugs or even cells non-invasively over time, optical imaging (OI) technologies are increasingly applied. Although OI strongly contributes to the advances made in preclinical research, it is so far, with the exception of optical coherence tomography (OCT), only very sparingly applied in clinical settings. Nevertheless, as OI technologies evolve and improve continuously and represent relatively inexpensive and harmful methods, their implementation as clinical tools for the assessment of children disease is increasing. This review focuses on the current preclinical and clinical applications as well as on the future potential of OI in the clinical routine. Herein, we summarize the development of different fluorescence and bioluminescence imaging techniques for microscopic and macroscopic visualization of microstructures and biological processes. In addition, we discuss advantages and limitations of optical probes with distinct mechanisms of target-detection as well as of different bioluminescent reporter systems. Particular attention has been given to the use of near-infrared (NIR) fluorescent probes enabling observation of molecular events in deeper tissue

Organisation du pole cellulaire bactérien

Chez les bactéries, les pôles cellulaires servent de domaines subcellulaires impliqués dans plusieurs processus cellulaires. Chez l’agent pathogène du choléra, Vibrio cholerae, en forme de bâtonnet incurvé, le pole contenant l’unique flagelle est impliqué dans la virulence. La protéine d’ancrage polaire HubP interagit avec plusieurs ATPases telles que ParA1 (ségrégation des chromosomes), ParC (localisation polaire du système de chimiotaxie) et FlhG (biosynthèse des flagelles), organisant ainsi l'identité polaire de V. cholerae. Cependant, les mécanismes moléculaires exacts de cet ancrage polaire doivent encore être élucidés. L’objectif de cette thèse est d’établir une vue d'ensemble de l'organisation de pôle cellulaire ce qui implique le mécanisme d’orchestration des différentes fonctions cellulaires par l’identification de l’ensemble des partenaires d'interaction de HubP ainsi que la cartographie fine du pôle cellulaire par microscopie à super résolution (PALM). Afin d’identifier de nouveaux partenaires d'interaction de HubP, j'ai étudié la différence de composition en protéines polaires entre les contextes HubP+ et HubP-. La composition en protéines polaires a été quantifiée de manière relative et absolue en ajoutant des Tag isobares aux protéines extraites de mini-cellules. Ces mini-cellules correspondent des petits compartiments cellulaires issus d’un évènement de division anormal proche du pole et sont enrichies en protéines polaires. Parmi ~800 protéines identifiées, ~ 80 protéines ont été considérées comme enrichies en contexte HubP+ incluant de nombreuses protéines attendues (FlhG, ParC et en aval des protéines de chimiotaxie). J'ai étudié la localisation de 14 protéines par microscopie à fluorescence et pu révéler 4 nouvelles protéines présentant une localisation polaire dépendant de HubP : VbrX, VbrY, et 2 protéines hypothétiques MotV et MotW. La délétion de motV et motW provoque un défaut significatif de propagation dans une gélose molle suggérant une implication dans la chimiotaxie et/ou la motilité. Alors que la microscopie électronique a montré que les deux mutants ont bien un flagelle polaire unique, le suivi-vidéo de leur déplacement a révélé que les deux mutants présentaient des défauts de nage assez distincts: ∆motV est plutôt affecté dans le changement de direction et ∆motW dans la vitesse de déplacement. Des expériences de microscopie fluorescente ont montré que MotV, MotW et HubP présentaient des dynamiques de localisation polaire distinctes au cours du cycle cellulaire. Pour une observation fine du pôle cellulaire par PALM, de nouveaux outils d’analyse d’image à haut débit étaient exigés. La précision des contours des petites cellules bactériennes faiblement contrastées n’est pas suffisante par l’observation en fond clair, j'ai développé une nouvelle technique de marquage avec des protéines fluorescentes photo-activables pour un tracé précis de la membrane interne ou du périplasme. En outre, nous avons créé un logiciel utilisant Matlab appelé Vibio qui intègre le contour de cellule et la liste des molécules obtenues par microscopie à super résolution. La capacité d’analyse à haut débit du logiciel permet d’étudier la distribution des molécules de l’échelle de la cellule unique à une population en orientant les cellules par leur courbure longitudinale. J’ai pu révéler que HubP est principalement localisé du côté convexe du pôle de la cellule, tandis que ses partenaires se situaient principalement au milieu du pôle. Mon travail de thèse a révélé avec succès de nouveaux partenaires d'interaction de HubP et la fonction de certaines protéines dans la motilité cellulaire. J'ai développé une nouvelle technique de microscopie pour une localisation subpolaire précise qui fonctionne bien pour l'analyse d'images PALM dans Vibio. J’ai ainsi pu faire progresser les connaissances de l’orchestration des fonctions polaires chez V. cholerae.In rod shaped bacteria, cell poles serve as important subcellular domains involved in several cellular processes including motility, chemotaxis, protein secretion, antibiotic resistance, and chromosome segregation. In the cholera pathogen Vibrio cholerae, vibrioid rod shape and single polarized flagellum involve in the virulence. Polar landmark protein HubP was shown to interact with multiple ATPases, such as ParA1 (chromosome segregation), ParC (polar localization of chemotaxis apparatus), and FlhG (flagella biosynthesis), thus organizing the polar identity of V. cholerae by tethering proteins to cell pole. However, the exact molecular mechanisms are yet to be elucidated. In this thesis, I tackled to unveil comprehensive view of the cell pole organization which implies the orchestration of different cellular functions, by identifying further interaction partners of HubP as well as drawing conceivable picture of the cell pole by super-resolution photoactivated localization microscopy. To identify new interaction partners of HubP, I used minicells in which cell poles were enriched as they derived from cell division near the cell pole. Difference in protein composition between HubP+ and HubP- minicells were examined by isobaric tags for relative and absolute quantitation. Among ~800 proteins identified, ~80 proteins were considered to be enriched in HubP+ minicells including many expected proteins (FlhG, ParC and downstream chemotaxis proteins). I chose 14 proteins to investigate their subcellular localization with fluorescent microscopy. In conclusion, I discovered 4 proteins that showed polar localization in a HubP-dependent manner. These proteins are VbrX, VbrY, and 2 hypothetical proteins MotV and MotW. ∆motV and ∆motW showed significant defect in a diameter of travel in soft agar plate that suggesting the possible involvement in chemotaxis and/or motility. Whereas electron microscopy showed that both mutants possess intact monotrichous flagellum, video-tracking revealed that the two mutants showed rather distinct defects during swimming: MotV is rather turning mutant while MotW is a speed mutant. Fluorescent microscopy experiments indicated that MotV, MotW and HubP showed distinct polar dynamics over cell cycle. For fine-scale observation of the cell pole by PALM, it was appreciated that novel tools for high-throughput analysis was demanded. Since brightfield images are not sufficient to have accurate contours of small and low contrast bacterial cells, I developed new labeling technique with photoactivatable fluorescent proteins for precise outlining at either inner membrane or periplasm. Furthermore, we created Matlab-based software called Vibio which integrates cell outline and the list of molecules obtained by super-resolution microscopy. High-throughput capability of the software enabled to analyze distribution of detected molecules from single cell to whole bunch of cells in a manner that cells are oriented by cell curvature. These allowed me to discover that HubP is mostly lopsided at the convex side of the cell pole, while its partners mostly located middle of the pole. Altogether, I successfully unveiled 4 novel interaction partners of HubP. I revealed of the function of hypothetical proteins that are involved in cell motility. I developed new labeling technique for precise polar localization that works well for PALM image analysis in Vibio. Therefore, I observed precise polar localization of HubP and other polar proteins

applying boundary analyzing techniques to gravity data

Defining the location and boundary of the buried features is an important task in earth science. Many filters, known as edge detection methods, are used in potential field data applications. In this study, the filters were firstly applied to a synthetically generated model. The result maps obtained by using the methods to the gravity anomaly of the model were compared and the skill of the methods were discussed. In the real data application, main faults and fault systems in the region have been tried to be determined by applying the boundary detection methods to the Bouguer gravity anomaly data of Elazig province and its surroundings in Eastern Anatolia region. The East Anatolian fault and the South East Anatolian fault, which are the dominant tectonic structures of the region, have been successfully determined. In addition to this, approximately E-W and SW-NE extensional lineaments were determined between Elazig province and Elazig-Pertek-Akpazar in the northern part of the study area.C1 [Altinoglu, Fatma Figen] Pamukkale Univ, Muhendislik Fak, Jeofizik Muhendisligi Bolumu, Denizli, Turkey

gravity data analysis

Detection of the linear features is a useful task to understand the tectonism of a region. Gravity anomaly data was used to investigate the tectonic structures of SE part of Denizli, western Anatolia. This region is a tectonically active transition zone between Aegean extensional and Anatolian Taurides compressional provinces. Lineaments are appearance of the instantaneous change in the density of the subsurface rocks in gravity data. To determine the lineaments, derivative-based edge detection methods, horizontal gradient, analytic signal, tilt angle and hyperbolic tilt angle applied gravity anomaly data. In defining the lineaments, 3D sediment-basement model, elevation, geology and seismicity data were used comparatively. The sediment-basement topography was modelled by 3D inversion of gravity data. The maximum sediment thickness is defined 2.4 km in the northern part of Acipayam basin and 2.3 km in the southern part of Denizli basin. The earthquake distribution map, geology and elevation maps were provided insight the linear features of the region. As a result of the study, the new tectonic map is attained. Besides the known structures, many new lineaments and some buried faults were defined in the study area.C1 [Altinoglu, Fatma Figen] Pamukkale Univ, Fac Engn, Dept Geophys Engn, TR-20017 Denizli, Turkey

New PALM-compatible integration vectors for use in the Gram-positive model bacterium<i>Bacillus subtilis</i>

ABSTRACTImprovements in super-resolution and single-molecule techniques together with the development of new fluorescent proteins and labelling methods have allowed super-resolution microscopy to be applied to bacterial cells. Cloning vectors remain important tools for researchers to perform efficient labelling. Here, we describe the creation of four PhotoActivated Localization Microscopy (PALM)-compatible integration plasmids for the Gram-positive model organismBacillus subtilis. These plasmids carry either the photoswitchable green fluorescent protein dronPA or the photoactivatable red fluorescent protein PAmCherry1, codon-optimized or not forB. subtilis. For fast and interchangeable cloning, we have inserted multi cloning sites at both the C-terminal and the N-terminal end of the fluorophores. The plasmids replicate inEscherichia coliand allow integration at the ectopicamyEorthrCloci ofB. subtilisvia double homologous recombination, for stable chromosomal insertions of dronPA and PAmCherry1 protein fusions respectively. Dual color imaging is accessible with the simultaneous use of the two vectors. Insertion of the gene encoding the LacI repressor under control of a constitutive promoter in each of the four plasmids yielded four derivative vectors that, combined with an array oflacOoperator sites, allow Fluorescent Repressor-Operator System (FROS) localization studies. We demonstrated the successful photoactivation of the LacI-dronPA or PAmCherry1 fusions, and used them to report with nanoscale precision the subcellular localization of bacteriophage SPP1 DNA in infectedB. subtiliscells as proof of concept. Our PALM-compatible integration vectors expand the genetic toolbox for single molecule localization microscopy studies inB. subtilis.</jats:p

Alzheimer’s Disease Targeted Nano-Based Drug Delivery Systems

Alzheimer’s disease (AD) is the most common neurodegenerative disease, and is part of a massive and growing health care burden that is destroying the cognitive function of more than 50 million individuals worldwide. Today, therapeutic options are limited to approaches with mild symptomatic benefits. The failure in developing effective drugs is attributed to, but not limited to the highly heterogeneous nature of AD with multiple underlying hypotheses and multifactorial pathology. In addition, targeted drug delivery to the central nervous system (CNS), for the diagnosis and therapy of neurological diseases like AD, is restricted by the challenges posed by blood-brain interfaces surrounding the CNS, limiting the bioavailability of therapeutics. Research done over the last decade has focused on developing new strategies to overcome these limitations and successfully deliver drugs to the CNS. Nanoparticles, that are capable of encapsulating drugs with sustained drug release profiles and adjustable physiochemical properties, can cross the protective barriers surrounding the CNS. Thus, nanotechnology offers new hope for AD treatment as a strong alternative to conventional drug delivery mechanisms. In this review, the potential application of nanoparticle based approaches in Alzheimer’s disease and their implications in therapy is discussed.</jats:sec