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Library Buildings around the World" is a survey based on researches of several years. The objective was to gather library buildings on an international level starting with 1990.
The parts Germany, France, United Kingdom, United States have been thoroughly revised, supplemented and completed for this 2nd edition. A revision of the other countries is planned for the next edition.
Noise-induced hearing loss is one of the most common auditory pathologies, resulting from overstimulation of the human cochlea, an exquisitely sensitive micromechanical device. At very low frequencies (less than 250 Hz), however, the sensitivity of human hearing, and therefore the perceived loudness is poor. The perceived loudness is mediated by the inner hair cells of the cochlea which are driven very inadequately at low frequencies. To assess the impact of low-frequency (LF) sound, we exploited a by-product of the active amplification of sound outer hair cells (OHCs) perform, so-called spontaneous otoacoustic emissions. These are faint sounds produced by the inner ear that can be used to detect changes of cochlear physiology. We show that a short exposure to perceptually unobtrusive, LF sounds significantly affects OHCs: a 90 s, 80 dB(A) LF sound induced slow, concordant and positively correlated frequency and level oscillations of spontaneous otoacoustic emissions that lasted for about 2 min after LF sound offset. LF sounds, contrary to their unobtrusive perception, strongly stimulate the human cochlea and affect amplification processes in the most sensitive and important frequency range of human hearing.
This article reviews the most recent results concerning second harmonic generation (SHG) experiments of non-phase matchable and phase matchable powder samples at high pressures and explains the pressure dependence of the intensity of the SHG signal by correlating it to the ratio between the average coherence length and the average particle size. The examples discussed here include pressure-induced structural changes in quartz, ZnO, ice VII and KIO3. It is shown that the second harmonic generation technique is a unique tool for the detection of pressure-induced structural phase transitions. It is laboratory based and allows fast measurements. It is complementary to X-ray diffraction and provides additional information about the presence of an inversion center for unknown or controversially discussed structures at high pressure.
The question of whether most gliomas are infected with human cytomegalovirus (HCMV) has been under dispute for more than 10 years. We recently reported our failure to detect HCMV in gliomas in Neuro-Oncology.1 Our article was accompanied by 2 related editorials,2,3 one of which boldly criticized our approach.3 Instead of fighting a petty, ivory tower dispute, we would like to lobby for a serious collaborative approach to providing conclusive evidence on the presence of HCMV in glioma (and other cancers). Since we developed the concept of oncomodulation (ie, that HCMV …
Biodiversity is unevenly distributed on Earth and hotspots of biodiversity are often associated with areas that have undergone orogenic activity during recent geological history (i.e. tens of millions of years). Understanding the underlying processes that have driven the accumulation of species in some areas and not in others may help guide prioritization in conservation and may facilitate forecasts on ecosystem services under future climate conditions. Consequently, the study of the origin and evolution of biodiversity in mountain systems has motivated growing scientific interest. Despite an increasing number of studies, the origin and evolution of diversity hotspots associated with the Qinghai-Tibetan Plateau (QTP) remains poorly understood. We review literature related to the diversification of organisms linked to the uplift of the QTP. To promote hypothesis-based research, we provide a geological and palaeoclimatic scenario for the region of the QTP and argue that further studies would benefit from providing a complete set of complementary analyses (molecular dating, biogeographic, and diversification rates analyses) to test for a link between organismic diversification and past geological and climatic changes in this region. In general, we found that the contribution of biological interchange between the QTP and other hotspots of biodiversity has not been sufficiently studied to date. Finally, we suggest that the biological consequences of the uplift of the QTP would be best understood using a meta-analysis approach, encompassing studies on a variety of organisms (plants and animals) from diverse habitats (forests, meadows, rivers), and thermal belts (montane, subalpine, alpine, nival). Since the species diversity in the QTP region is better documented for some organismic groups than for others, we suggest that baseline taxonomic work should be promoted.
Telecommunications companies traditionally offer several tariffs from which their customers can choose the tariff that best suits their preferences. Yet, customers sometimes make choices that are not optimal for them because they do not minimize their bill for a certain usage amount. We show in this paper that companies should be very concerned about choices in which customers pick tariffs that are too small for them because they lead to a significant increase in customers churn. In contrast, this is not the case if customers choose tariffs that are too big for them. The reason is that in particular flat-rates provide customers with the additional benefit that they guarantee a constant bill amount that consumption can be enjoyed more freely because all costs are already accounted for.
Surface disinfectants are part of broader preventive strategies preventing the transmission of bacteria, fungi and viruses in medical institutions. To evaluate their virucidal efficacy, these products must be tested with appropriate model viruses with different physico-chemical properties under conditions representing practical application in hospitals.
The aim of this study was to evaluate a quantitative carrier assay. Furthermore, different putative model viruses like adenovirus type 5 (AdV-5) and different animal parvoviruses were evaluated with respect to their tenacity and practicability in laboratory handling. To evaluate the robustness of the method, some of the viruses were tested in parallel in different laboratories in a multi-center study. Different biocides, which are common active ingredients of surface disinfectants, were used in the test. After drying on stainless steel discs as the carrier, model viruses were exposed to different concentrations of three alcohols, peracetic acid (PAA) or glutaraldehyde (GDA), with a fixed exposure time of 5 minutes. Residual virus was determined after treatment by endpoint titration.
All parvoviruses exhibited a similar stability with respect to GDA, while AdV-5 was more susceptible. For PAA, the porcine parvovirus was more sensitive than the other parvoviruses, and again, AdV-5 presented a higher susceptibility than the parvoviruses. All parvoviruses were resistant to alcohols, while AdV-5 was only stable when treated with 2-propanol. The analysis of the results of the multi-center study showed a high reproducibility of this test system.
In conclusion, two viruses with different physico-chemical properties can be recommended as appropriate model viruses for the evaluation of the virucidal efficacy of surface disinfectants: AdV-5, which has a high clinical impact, and murine parvovirus (MVM) with the highest practicability among the parvoviruses tested.
he predictive likelihood is of particular relevance in a Bayesian setting when the purpose is to rank models in a forecast comparison exercise. This paper discusses how the predictive likelihood can be estimated for any subset of the observable variables in linear Gaussian state-space models with Bayesian methods, and proposes to utilize a missing observations consistent Kalman filter in the process of achieving this objective. As an empirical application, we analyze euro area data and compare the density forecast performance of a DSGE model to DSGE-VARs and reduced-form linear Gaussian models.
At the forefront of those who tenaciously pondered this issue are, I would claim, Walter Benjamin and Ludwig Wittgenstein. Benjamin and Wittgenstein both are philosophers of language who tried to establish in unique ways the doctrine of resemblance respectively: "Lehre vom Ähnlichen" and "[Lehre der] Familienähnlichkeit." What they see and find in language are not communication and mutual understanding but instead one of the weirdest phenomena in/of the world, viz., resemblance (likeness) in/of language. This phenomenon, I would insist, indicates the correlation of appearing and disappearing, of differentiating and integrating, and of dividing and imparting of language as such. For Benjamin and Wittgenstein, to sum up, language is a paradigmatic paradoxical site of (dis)appearance, differentiating integrity, and divisive imparting. For this reason, it is worthwhile to pin down where their thoughts on language converge and where they diverge.
Benjamin's early reception in the United States can be broken into eight phases: 1) a few notices of his work in the 1930s; 2) the appearance of two major works, without translation, in the 'Zeitschrift für Sozialforschung', when it was published in New York and mimeographed in Los Angeles; 3) several reports of his suicide along with the death of other Jewish and left-wing writers who fell victim to Nazi terror; 4) scattered use of his work in the late 1940s and 1950s; 5) a growing realization in the early 1960s that American literary and cultural criticism was missing something of significance by neglecting Benjamin's work; 6) the appearance in the 1960s of competing portraits of Benjamin by four of his surviving friends, including Hannah Arendt, who edited and introduced the first collection of his writings in English; 7) an uncanny repetition of the earlier neglect, as a significant number of Benjamin's texts are published in Great Britain during the 1970s and early 1980s but remain unavailable in the States; 8) the beginning of a sustained critical engagement with Benjamin in the late 1970s.
We use data from the 2009 Internet Survey of the Health and Retirement Study to examine the consumption impact of wealth shocks and unemployment during the Great Recession in the US. We find that many households experienced large capital losses in housing and in their financial portfolios, and that a non-trivial fraction of respondents have lost their job. As a consequence of these shocks, many households reduced substantially their expenditures. We estimate that the marginal propensities to consume with respect to housing and financial wealth are 1 and 3.3 percentage points, respectively. In addition, those who became unemployed reduced spending by 10 percent. We also distinguish the effect of perceived transitory and permanent wealth shocks, splitting the sample between households who think that the stock market is likely to recover in a year’s time, and those who do not. In line with the predictions of standard models of intertemporal choice, we find that the latter group adjusted much more than the former its spending in response to financial wealth shocks.
Using data from the US Health and Retirement Study, we study the causal effect of increased health insurance coverage through Medicare and the associated reduction in health-related background risk on financial risk-taking. Given the onset of Medicare at age 65, we identify our effect of interest using a regression discontinuity approach. We find that getting Medicare coverage induces stockholding for those with at least some college education, but not for their less-educated counterparts. Hence, our results indicate that a reduction in background risk induces financial risk-taking in individuals for whom informational and pecuniary stock market participation costs are relatively low.
In this thesis hard probes are studied in the partonic transport model BAMPS (Boltzmann Approach to MultiParton Scatterings). Employing Monte Carlo techniques, this model describes the 3+1 dimensional evolution of the quark gluon plasma phase in ultra-relativistic heavy-ion collisions by propagating all particles in space and time and carrying out their collisions according to the Boltzmann equation. Since hard probes are produced in hard processes with a large momentum transfer, the value of the running coupling is small and their interactions should be describable within perturbative QCD (pQCD). This work focuses on open heavy flavor, but also addresses the suppression of light parton jets, in particular to highlight differences due to the mass. For light partons, radiative processes are the dominant contribution to their energy loss. For heavy quarks, we show that also binary interactions with a running coupling and an improved Debye screening matched to hard-thermal-loop calculations play an important role. Furthermore, the impact of the mass in radiative interactions, prominently named the dead cone effect, and the interplay with the Landau-Pomeranchuk-Migdal (LPM) effect are studied in great detail. Since the transport model BAMPS has access to all medium properties and the space time information of heavy quarks, it is the ideal tool to study the dissociation and regeneration of J/psi mesons, which is also investigated in this thesis.
Panama is a megadiverse country that together with Costa Rica constitutes Lower Central America (LCA). Western Panama's Cordillera Central accounts for the eastern part of the LCA highlands shared between these countries. The aim of the present study is to compile the most complete and updated picture possible of the taxonomy, diversity, and distribution of reptiles that occur from 500 m asl upwards along the Talamanca and Tabasará ranges. These two continuous mountain ridges account for the western two-thirds of the Cordillera Central between the Costa Rican border and 81°W Including specimens collected four own research travels, I morphologically examined more than 1800 specimens, analyzed 16S and/or COI barcodes of 300 specimens, and performed a thorough search in literature and databases to obtain locality records for specimens and species occurrences. My complete occurrence dataset comprises 14620 georeferenced occurrence records in three quality categories. Conceivable occurrences of species not yet documented from a given area are evaluated on the basis of existing data either as "plausible" or "possible". I provide all datasets which I generated for this study in Appendices. The previously published descriptions of Dactyloa ginaelisae Lotzkat, Hertz, Bienentreu & Köhler 2013, Norops benedikti (Lotzkat, Bienentreu, Hertz & Köhler 2011), Sibon perissostichon Köhler, Lotzkat & Hertz 2010, and Sibon noalamina Lotzkat, Hertz & Köhler 2012 are included in the present work. In the course of integrative taxonomic analyses, I classify 15 genealogical lineages revealed by DNA barcoding within 7 anole species as Deep Conspecific Lineages (DCLs) because they lack consistent morphological differences to their nominal conspecifics. I provisionally classify 18 mitochondrial lineages found within six other anole species as Unconfirmed Genealogical Lineages (UGLs) pending adequate analyses of their morphological variation. I regard the two additional UGLs Celestus sp. and Geophis sp. and the two Confirmed Genealogical Lineages (CGLs) Lepidoblepharis sp. 1 and 2 to represent undescribed species. My taxonomic analyses yield the hitherto most comprehensive survey of the variability exhibited by dozens of reptile species in western Panama. The 16S and/or COI barcodes I provide represent 65 species recognized herein and constitute the first DNA barcode reference library for LCA reptiles. The reptile fauna of Panama comprises 265 species, including the four UGLs and CGLs mentioned above and characterized for the first time in this study, as well as Dendrophidion crybelum Cadle 2012 whose presence in the country I consider plausible. My occurrence dataset reveals that 160 of these species have been documented to occur in my study area. Adding the 20 species whose occurrence therein I consider plausible, I report the total species richness of the Talamanca and Tabasará ranges as comprising 180 species representing 81 genera in 25 families. With 178.8 species per 10 000 km2, the relative species richness of the area is extremely high even in a tropical context. In view of their overall documented distribution, I regard the presence of 27 additional species in my study area as possible. For the 180 species occurring in my study area I provide standardized species accounts that, together with the taxonomic results, for the first time permit the doubtless identification of all 180 species, and illustrate 168 of these with color photographs. Concerning biogeography, my georeferenced dataset yields noteworthy distribution extensions for many species. Moreover, I present the hitherto most comprehensive, detailed, and reproducible assessments of the distribution patterns, historical origins, and conservation as well as of the occurrence among physiographic regions, climatic and altitudinal belts, political subdivisions, and protected areas, for my study area's reptile fauna. With 65 species, more than a third of the fauna is endemic to LCA. Among these, 42 Talamancan highland endemics are restricted to the LCA highlands, in the case of 16 small-scale highland endemics with documented ranges spanning less than 100 km. I assess many of these endemics as endangered. The fact that several of these species do not occur in any protected area renders the establishment of additional conservation areas necessary, especially in the central Serranía de Tabasará. Distributional range boundaries shared among different clades of highland anoles indicate physiographic and climatic barriers that may have effected in situ speciation within these lineages. As the largest study on Panamanian reptile diversity assembled to date, the present dissertation considerably increases our knowledge on the reptiles along the Cordillera Central and beyond, and thus constitutes a solid basis for future studies.
It has long been observed that subjects cross-linguistically have topic properties: they are typically definite, referential and/or generic (Givón 1976). Bantu languages are said to illustrate this generalization: preverbal position for NPs is equated with both subject and topic status and postverbal position with focus (and non-subject). However, there is a growing body of work showing that preverbal subjects are not necessarily syntactically or semantically equivalent to topics. For example, Zerbian’s (2006) careful study of preverbal position in Northern Sotho shows that preverbal subjects meet few of the semantic tests for aboutness topics. The study of restrictions on preverbal subjects in Durban Zulu presented in this paper builds on Zerbian (2006) and Halpert (2012). In particular, we investigate the interpretational properties of preverbal indefinite subjects. These subjects show us that preverbal subjects carry a presupposition of existence. We explore an analysis connecting the "strong reading" of preverbal subjects with how high the verb moves in Zulu (following Tsai’s 2001 work on Mandarin).
Locative inversion in Cuwabo
(2014)
This paper proposes a detailed description of locative inversion (LI) constructions in Cuwabo, in terms of morphosyntactic properties and thematic restrictions. Of particular interest are the use of disjoint verb forms in LI, and the co-existence of formal and semantic LI, which challenges the widespread belief that the two constructions cannot be found in the same language.
Introduction
(2014)
Bantu languages have been at the heart of the research on the interaction between syntax, prosody and information structure. In these predominantly SVO languages, considerable attention has been devoted to postverbal phenomena. By addressing issues related to Subjects, Topics and Object-Verb word orders, the goal of the present papers is to deepen our understanding of the interaction of different grammatical components (syntax, phonology, semantics/pragmatics) both in individual languages and across the Bantu family. Each paper makes a valuable contribution to ongoing discussions on the preverbal domain.
In this thesis, Planck size black holes are discussed. Specifically, new families of black holes are presented. Such black holes exhibit an improved short scale behaviour and can be used to implement gravity self-complete paradigm. Such geometries are also studied within the ADD large extra dimensional scenario. This allows black hole remnant masses to reach the TeV scale. It is shown that the evaporation endpoint for this class of black holes is a cold stable remnant. One family of black holes considered in this thesis features a regular de Sitter core that counters gravitational collapse with a quantum outward pressure. The other family of black holes turns out to nicely fit into the holographic information bound on black holes, and lead to black hole area quantization and applications in the gravitational entropic force. As a result, gravity can be derived as emergent phenomenon from thermodynamics.
The thesis contains an overview about recent quantum gravity black hole approaches and concludes with the derivation of nonlocal operators that modify the Einstein equations to ultraviolet complete field equations.
The Generalized Uncertainty Principle (GUP) arises from Quantum Gravity thought experiments and contains a minimal lenght. In this thesis I calculate Schwarzschild Black Holes that are modified by the GUP. These Black Holes have the property, that their temperature does not diverge for small masses, although they still posses a curvature singularity. I calculate analytically that in more than 3+1 dimensions the temperature diverges again.
In this study, we describe the synthesis of 1,4-disustituted-1,2,3-triazolo-quinazoline ribonucleosides or acyclonucleosides by means of 1,3-dipolar cycloaddition between various O or N-alkylated propargyl-quinazoline and 1'-azido-2',3',5'-tri-O-benzoylribose or activated alkylating agents under microwave conditions. None of the compounds selected showed significant anti-HCV activity in vitro.
The measurement of dielectrons (electron-positron pairs) allows to investigate the properties of strongly interacting matter, in particular the Quark-Gluon Plasma (QGP), which is created in relativistic heavy-ion collisions at the LHC. The evolution of the collision can be probed via dielectrons since electrons do not interact strongly and are created during all stages of the collision. One of the interests in dielectron measurements is motivated by possible modifications of the electromagnetic emission spectrum in the QGP, where pp collisions are used as a medium-free reference. The dielectron spectrum consists of contributions from various processes. In order to estimate contributions of known dielectron sources, simulations of the so-called dielectron cocktail are performed. In this thesis, dielectron cocktails in minimum bias pp collisions at p s = 7 TeV, p–Pb collisions at p sNN = 5.02 TeV and in central (0-10%) and semi-central (20-50%) Pb–Pb collisions at p sNN = 2.76 TeV at the LHC are presented.
A checklist and classification of the species of Elateridae reported from mainland Ecuador are given. Anchastus boulardi Chassain, Cardiorhinus apicalis Golbach, Physorhinus marginatus Candèze, and P. sexnotatus Steinheil are reported from Ecuador for the first time. The recorded elaterid fauna of Ecuador is now represented by 140 species, 38 genera, and 9 subfamilies, which are low taxon richness numbers when compared to those of neighboring countries.
The papers in this volume take up some aspects of the preverbal domain(s) in Bantu languages. They were originally presented at the Workshop BantuSynPhonIS: Preverbal Domain(s), held at the Center for General Linguistics (ZAS), in Berlin, on 14-15 November 2014. This workshop was coorganized by ZAS (Fatima Hamlaoui & Tonjes Veenstra) and the Humboldt University (Tom Güldemann, Yukiko Morimoto and Ines Fiedler).
Noumenal Power
(2014)
In political or social philosophy, we speak about power all the time. Yet the meaning of this important concept is rarely made explicit, especially in the context of normative discussions. But as with many other concepts, once one considers it more closely, fundamental problems arise, such as whether a power relation is necessarily a relation of subordination and domination. In the following, I suggest a novel understanding of what power is and what it means to exercise it.
To overcome poor treatment response of pediatric high-risk acute lymphoblastic leukemia (ALL), novel treatment strategies are required to reactivate programmed cell death in this malignancy. Therefore, we take advantage of using small-molecule antagonists of Inhibitor of apoptosis (IAP) proteins, so called Smac mimetics such as BV6, which are described to overcome apoptosis resistance and thereby sensitize tumor cells for several apoptotic stimuli. To address the question whether redox alterations can sensitize leukemic cells for Smac mimetic-mediated cell death, we interfered with the cellular redox status in different ALL cell lines. Here, we show for the first time that redox alterations, mediated by the glutathione depleting agent Buthioninesulfoximine (BSO), prime ALL cells for BV6-induced apoptosis. Besides ALL cell lines, BV6/BSO cotreatment similarly synergizes in cell death induction in patient-derived primary leukemic samples. In contrast, the combination treatment does not exert any cytotoxicity against peripheral blood lymphocytes (PBLs) or mesenchymal stroma cells (MSCs) from healthy donors, suggesting some tumor selectivity of this treatment. We also identify the underlying molecular mechanism of the novel synergistic drug interaction of BSO and BV6. We demonstrate that both agents act in concert to increase reactive oxygen species (ROS) production, lipid peroxidation and finally apoptotic cell death. Enhanced ROS levels in the combination treatment account for cell death induction, since several ROS scavengers, like NAC, MnTBAP and Trolox attenuate BSO/BV6-induced apoptosis. BSO/BV6-induced ROS can be mainly classified as lipid peroxides, since the vitamin E derivate α-Tocopherol as well as Glutathione peroxidase 4 (GPX4), which both specifically reduce lipid-membrane peroxides, prevent lipid peroxidation, caspase activation and cell death induction. Vice versa, GPX4 knockdown and pharmacological inhibition of GPX4 by RSL3 or Erastin enhance BV6-induced cell death. Importantly, cell death induction critically depends on the formation of a complex consisting of RIP1/FADD/Caspase-8, since all complex components are required for ROS production, lipid peroxidation and cell death induction. Taken together, we demonstrate that BSO and BV6 cooperate to induce ROS production and lipid peroxidation which are eventually required for caspase activation and cell death execution. Collectively, findings of this study indicate that BV6-induced apoptosis is mediated via redox alterations offering promising new treatment strategy to overcome apoptosis resistance in ALL.
Euro area data show a positive connection between sovereign and bank risk, which increases with banks’ and sovereign long run fragility. We build a macro model with banks subject to moral hazard and liquidity risk (sudden deposit withdrawals): banks invest in risky government bonds as a form of capital buffer against liquidity risk. The model can replicate the positive connection between sovereign and bank risk observed in the data. Central bank liquidity policy, through full allotment policy, is successful in stabilizing the spiraling feedback loops between bank and sovereign risk.
Trust in policy makers fluctuates signi
cantly over the cycle and affects the transmission mechanism. Despite this it is absent from the literature. We build a monetary model embedding trust cycles; the latter emerge as an equilibrium phenomenon of a game-theoretic interaction between atomistic agents and the monetary authority. Trust affects agents' stochastic discount factors, namely the price of future risk, and through this it interacts with the monetary transmission mechanism. Using data from the Eurobarometer surveys, we analyze the link between trust and the transmission mechanism of macro and monetary shocks: Empirical results are in line with theoretical ones.
Changes in vitamin D serum levels have been associated with inflammatory diseases, such as inflammatory bowel disease (IBD), rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis (MS), atherosclerosis, or asthma. Genome- and transcriptome-wide studies indicate that vitamin D signaling modulates many inflammatory responses on several levels. This includes (i) the regulation of the expression of genes which generate pro-inflammatory mediators, such as cyclooxygenases or 5-lipoxygenase, (ii) the interference with transcription factors, such as NF-κB, which regulate the expression of inflammatory genes and (iii) the activation of signaling cascades, such as MAP kinases which mediate inflammatory responses. Vitamin D targets various tissues and cell types, a number of which belong to the immune system, such as monocytes/macrophages, dendritic cells (DCs) as well as B- and T cells, leading to individual responses of each cell type. One hallmark of these specific vitamin D effects is the cell-type specific regulation of genes involved in the regulation of inflammatory processes and the interplay between vitamin D signaling and other signaling cascades involved in inflammation. An important task in the near future will be the elucidation of the regulatory mechanisms that are involved in the regulation of inflammatory responses by vitamin D on the molecular level by the use of techniques such as chromatin immunoprecipitation (ChIP), ChIP-seq, and FAIRE-seq.
Immune cells are key players in several physiological and pathophysiological events such as acute and chronic inflammation, atherosclerosis and cancer. Especially in acute inflammation, macrophages are indispensable for the switch from the acute inflammatory phase to the resolution phase. Not only the phagocytosis of apoptotic cells, but especially the surrounding cytokines and mediators are able to switch macrophage polarization from inflammatory- to anti-inflammatory phenotypes. Within this cytokine environment, sphingosine-1-phosphate (S1P) plays an important role for immune cell activation, polarization and migration.
Tumor development usually follows predictable paths where tumor cells acquire common characteristics and features known as the hallmarks of cancer. Recently, additional characteristics have been added to these hallmarks since solid tumors are composed of a very heterogeneous population of transformed, formerly normal tissue cells and stromal cells, e.g. immune cells and fibroblasts. Compelling evidence suggests that stromal cells and tumor cells maintain a symbiotic relationship to build up the tumor microenvironment and to fuel tumor growth. In cancer therapies, common features of tumors such as unrestricted cell growth, suppression of immunological responses, and the ability to form new blood vessels (angiogenesis) have emerged as the main targets of interest. The lipid mediator prostaglandin E2 (PGE2) is known to promote all these features and thus, is connected to cancer progression in general. Its synthesis is triggered in response to stress factors or during inflammation. Inducible PGE2 production relies on the enzymes cyclooxygenase 2 (COX-2) and microsomal prostanglandin E synthase 1 (mPGES-1), which are simultaneously expressed in response to a variety of different stimuli and are functionally coupled. Inhibition of COX-2 with non-steroidal antiinflammatory drugs (NSAIDs) for cancer treatment is, however, limited by cardiovascular risks, since selective COX-2 inhibition disrupts the prostacyclin/thromboxane balance. Therefore targeting mPGES-1 downstream of COX-2 for PGE2 inhibition was evaluated in this work in different steps of carcinogenesis. Knockdown of mPGES-1 in DU145 prostate cancer cells revealed that the mPGES-1 status did not affect growth of monolayer tumor cells, but significantly impaired 3D growth of multi-cellular tumor spheroids (MCTS). Spheroid formation induced COX-2 in DU145 and other prostate cancer spheroids. High levels of PGE2 were detected in supernatants of DU145 MCTS as opposed to monolayer DU145 cells. Pharmacological inhibition of COX-2 and mPGES-1 confirmed the pivotal role of PGE2 for DU145 MCTS growth. Besides promoting spheroid growth, MCTS-derived PGE2 also inhibited cytotoxic T lymphocyte (CTL) activation. When investigating the mechanisms of COX-2 induction during spheroid formation, the typical tumor microenvironmental factors such as glucose deprivation, hypoxia or tumor cell apoptosis failed to enhance COX-2. Interestingly, when interfering with apoptosis in DU145 spheroids, the pan-caspase inhibitor Z-VAD-FMK triggered a Summary 12 shift towards necrosis, thus enhancing COX-2 expression. Coculturing viable DU145 monolayer cells with isolated heat-shocked-treated necrotic DU145 cells, but not with necrotic cell supernatants, induced COX-2 and PGE2, confirming the impact of necrosis for MCTS growth and CTL inhibition. As mentioned, in vivo tumors are very heterogenous mixtures of tumor cells and stromal cells e.g. immune cells. Hence, the interaction of the immune system with tumors was investigated in further experiments. When coculturing MCF-7 breast cancer spheroids with human peripheral blood mononuclear cells (PBMCs), only low levels of PGE2 were detected, since MCF-7 cells did not upregulate COX-2 during spheroid formation and did not induce PGE2 production by PBMCs. Under inflammatory conditions, by adding the toll-like receptor 4 (TLR4) agonist lipopolysaccharide (LPS) to cocultures, PGE2 production was triggered, spheroid sizes were reduced, and numbers of high levels of granzyme B expressing (GrBhi) CTLs were increased, while CD80 expression by tumor-associated phagocytes was also elevated. Inhibition of CD80 but not CD86 diminished numbers of GrBhi CTLs and attenuated spheroid lysis. To determine the role of ctivation-induced PGE2 production, use of the COX-2 inhibitor celecoxib and the experimental mPGES-1 inhibitor C3 further increased CD80 expression. Addition of PGE2, the prostaglandin E2 (EP2) receptor agonist butaprost, and the phosphodiesterase 4 (PDE4) inhibitor rolipram reduced LPS/C3-triggered CD80 expression, confirming the impact of COX- 2/mPGES-1-derived PGE2 on shaping phagocyte phenotypes in an EP2/cAMP-dependent manner. In a spontaneous breast cancer model (MMTV-PyMT), mPGES-1-deficiency significantly delayed tumor growth in mice, confirming an overall protumorigenic role of mPGES-1 in breast cancer development in vivo. However in tumors of mPGES-1-/- mice, tumor-infiltrating phagocytes expressed low levels of CD80 similar to their wildtype counterparts. These data suggest that the immunosuppressive microenvironment does not allow for immunostimulatory effects by mPGES-1 inhibition without an activating stimulus. Evidences in this study recommend the application of mPGES-1 inhibitors for treating cancer diseases, since mPGES-1 promotes tumor growth in multiple steps of carcinogenesis, ranging from well-characterized effects of tumor cell growth to immune suppression of CTL activity and phagocyte polarization. Regarding the latter, blunting PGE2 during immune activation may limit the tumor-favoring features of inflammation and improve the efficiency of TLR4 based immune therapies.
In mitochondria, biogenesis of oxidase is a crucial process involving the participation of an array of assembly factors. Studying the process of biogenesis in eukaryotes is highly complicated due to the presence and partaking of two genetic systems. Employing a bacterial model such as Paracoccus denitrificans that utilizes only one genetic system enables easy studying of the assembly process. The aa3 cytochrome c oxidase of P. denitrificans shows high structural and functional homology to its mitochondrial counterpart despite its simple subunit composition. The assembly of the core subunits I and II that house the active redox centers (heme a, and heme a3.CuB centre in subunit I; and the binuclear CuA centre in subunit II) along with the chaperons responsibly for their incorporation form the crux of this work. This work concentrates particularly on CtaG, a chaperone previously speculated to be involved in the delivery of copper to the CuB center in subunit I. As the full length structure of CtaG or its structural homologues have not been solved, attempts were made to obtain high-diffracting crystals of CtaG by heterologously expressing it in E. coli. Growth media, expression strains and induction parameters were some of the conditions screened in order to obtain optimal yield. Additives, pH and detergent were screened to yield a homogeneous preparation of CtaG. Crystallization trials were conducted by employing the sitting drop, vapour diffusion, method and later the bicelles were employed. Preliminary crystals obtained were further optimized employing seeding, detergent and additives, to improve diffraction. The diffraction improved from 30 Å to 15 Å. BN PAGE (Blue Native Polyacrylamide Gel Electrophoresis) analysis and cross-linking studies were undertaken to decipher the oligomeric condition of CtaG. Both the methods indicate that the protein is a dimer under native conditions. To study the importance of CtaG in the process of oxidase assembly, two deletion mutants were obtained from the lab; one with only ctaG deleted and the other with ctaG and most of the upstream ORF. The effect of the deletion was assayed on the assembly and activity of oxidase. The deletion mutants showed residual activity of approx. 20 %, while displaying a very low heme signal (both in membranes and in purified COX). In order to exclude polar effects arising due to gene manipulation, complementation strains were prepared, reintroducing ctaG alone into both the deletion strains. Complementation strains, where only ctaG was deleted and re-introduced assayed for COX activity showed a restoration in activity to approx. 70 %. Further, calculating the heme:protein ratio, the deletion strains displayed a value of 7 nmol/mg of oxidase which was increased to wild type levels of 16 nmol/mg in the complementation strains. To further confirm the absence of the copper in subunit I, total reflection X-ray fluorescence spectroscopy analysis was carried out, which showed a decrease in the copper content in the deletion strain, restored on complementation. The strain lacking in the ORF and ctaG when complemented with ctaG alone illustrated no increase in activity or heme signal in comparison to that of the deletion strain. These point at a possible role for ORF in the assembly of COX, which is still absent in the complementation strains. To further characterize the ORF, a series of bioinformatical analysis was carried out, the results from which were insufficient to characterize the ORF conclusively. In order to enlist the proteins involved in the biosynthesis of COX, two independent approaches were employed. Two-dimensional gel examinations of solubilised membranes from untreated and cross-linked cells were analyzed by Western blotting. The CtaG-COX interaction was observed in untreated membranes, which was additionally strengthened by cross-linking. To further confirm this association, pull-down assays were done employing protein A coated magnetic beads coated with different antibodies and incubated with solubilised membranes derived from untreated or cross-linked cells. The elutions were assayed by Western blotting and confirmed for the CtaG-COX interaction. These fractions were further analysed by mass spectrometry to identify other chaperons involved in biogenesis of oxidase. Along with CtaG, I also noticed Sco, Surf1c and other factors involved in the recruitment and transport of heme (CtaB, CtaA, and Ccm proteins). Interestingly, protein components of both ribosomal subunits and protein translocation factors were observed, which indicated a co-translational approach for co-factor insertion into COX.
We outline a procedure for consistent estimation of marginal and joint default risk in the euro area financial system. We interpret the latter risk as the intrinsic financial system fragility and derive several systemic fragility indicators for euro area banks and sovereigns, based on CDS prices. Our analysis documents that although the fragility of the euro area banking system had started to deteriorate before Lehman Brothers' file for bankruptcy, investors did not expect the crisis to affect euro area sovereigns' solvency until September 2008. Since then, and especially after November 2009, joint sovereign default risk has outpaced the rise of systemic risk within the banking system.
Irene Heim in unpublished work proposed a new syntax-semantics interface for propositional attitude reports based on an ontology without transworld individuals, but counterpart functions instead. We show that the approach can capture the 'de re'/'de dicto' distinction, but makes different predictions from accounts with transworld individuals. Specifically, the account uses a non-invertible counterpart functions: a single individual in an alternative world can be the counterpart of many individuals of the real world. The directionality of counterpart functions predicts that a 'de dicto' interpreted DP cannot be an argument of a 'de re' interpreted predicate. We show that the predicted restriction is corroborated by existing work on restrictions on 'de re' interpretation. The derivation of constraints on 'de re' interpretation argues empirically for the counterpart ontology and Heim’s implementation thereof.
The late physicist Carl Sagan, whom I quote in the first part of my title, skillfully phrased the common sense view on evidence in the mature sciences. In linguistics, however, evidence has become a controversial issue, especially so when it comes to the investigation of less well studied languages. In this paper, I argue that Sagan's principle should be applied to linguistics. The growing accessibility of a wide array of experimental techniques and computational tools to analyze such data makes it feasible to back up extraordinary claims with evidence from a variety of sources. At the same time, it is in many cases possible to agree on what constitutes an ordinary claim and focus the extra effort on extraordinary claims. For non-controversial claims no more than the minimum effort to establish the claim and properly document the evidence is necessary.
Decomposing coordination
(2014)
Natural languages display a surprising diversity of expression of elementary logical operations. The study of this variation is emerging as an important topic of cross-linguistic semantics. In this paper, we address the expression of coordination from this perspective, especially coordination of individual denoting expressions such as "John and Mary". We argue that there is an underlying universal structure for individual coordination, and that the cross-linguistic variation can be explained by assuming that languages pronounce different morphemes of this universal structure. In particular, we argue that there two main types of system for the expression of individual coordination: the J-type and the μ-type. In μ-type languages the morpheme used for individual coordination also has uses a quantificational or focus particle, while in the J-type languages it doesn't. Instead at least in many J-type languages the same morpheme is used for individual and propositional coordination. The evidence we present for our model comes from two sources: new data from specific data of the J-type and μ-type languages, and from a study of the historical development of the expression of individual coordination in Indo-European which switched from a μ-type to a J-type system.
We study the effect of weakening creditor rights on distress risk premia via a bankruptcy reform that shifts bargaining power in financial distress toward shareholders. We find that the reform reduces risk factor loadings and returns of distressed stocks. The effect is stronger for firms with lower firm-level shareholder bargaining power. An increase in credit spreads of riskier relative to safer firms, in particular for firms with lower firm-level shareholder bargaining power, confirms a shift in bargaining power from bondholders to shareholders. Out-of-sample tests reveal that a reversal of the reform's effects leads to a reversal of factor loadings and returns.
The recent financial crisis highlighted the limits of the "originate to distribute" model of banking, but its nexus with the macroeconomy remains unexplored. I build a business cycle model with banks engaging in credit risk transfer (CRT) under informational externalities. Markets for CRT provide liquidity insurance to banks, but the emergence of a pooling equilibrium can also impair the banks’ monitoring incentives. In normal times and in face of standard macro shocks the insurance benefits of CRT prevail and the business cycle is stabilized. In face of financial/liquidity shocks the extent of informational asymmetries is larger and the business cycle is amplified. The macro model with CRT can also reproduce well a number of macro and banking statistics over the period of rapid growth of this banks’ business model.
We propose a novel approach on how to estimate systemic risk and identify its key determinants. For US financial companies with publicly traded equity options, we extract option-implied value-at-risks and measure the spillover effects between individual company value-at-risks and the option-implied value-at-risk of a financial index. First, we study the spillover effect of increasing company risks on the financial sector. Second, we analyze which companies are mostly affected if the tail risk of the financial sector increases. Key metrics such as size, leverage, market-to-book ratio and earnings have a significant influence on the systemic risk profiles of financial institutions.
We study the effect of weakening creditor rights on distress risk premia via a bankruptcy reform that shifts bargaining power in financial distress toward shareholders. We find that the reform reduces risk factor loadings and returns of distressed stocks. The effect is stronger for firms with lower firm-level shareholder bargaining power. An increase in credit spreads of riskier relative to safer firms, in particular for firms with lower firm-level shareholder bargaining power, confirms a shift in bargaining power from bondholders to shareholders. Out-of-sample tests reveal that a reversal of the reform's effects leads to a reversal of factor loadings and returns.
A selection of duplicates from the collection of Michel Edmond de Selys Longchamps was found at the Übersee-Museum Bremen/Germany (UMB). Selys determined a lot of Odonata in the UMB collection and sent 80 European and 76 exotic species to Bremen on 23 April, 1875. According to the labels 121 specimens could be assigned to this shipment and eleven specimens must have been sent to UMB in later years. This collection includes two paralectotypes (Progomphus gracilis Hagen inSelys, 1853;Palaemnema nathalia Selys, 1886) and seven syntypes (Rhinocypha trifasciata Selys, 1853; Dysphaea dimidiata limbata Selys, 1859; Argia sordida Hagen inSelys, 1865; Oxyagrion dissidens Selys, 1876; Oxyagrion haematinum Selys, 1876; Oxyagrion pavi-dum Hagen in Selys, 1876; Telagrion longum Selys, 1876). In addition, a male specimen of Euphaea tricolor subcostalis Selys, 1873 might also belong to the original syntype series. Altogether three specimens with labeled nomina nuda(Diplax catharina Selys, Diplax fausta Selys, Dythemis bilineata Hagen) and two labeled with manuscript names (Diplax marcellina Selys, Perithemis ovate Bates) are in this collection.
Pseudoperonospora cubensis, an obligate biotrophic oomycete causing devastating foliar disease in species of the Cucurbitaceae family, was never reported in seeds or transmitted by seeds. We now show that P. cubensis occurs in fruits and seeds of downy mildew-infected plants but not in fruits or seeds of healthy plants. About 6.7% of the fruits collected during 2012–2014 have developed downy mildew when homogenized and inoculated onto detached leaves and 0.9% of the seeds collected developed downy mildew when grown to the seedling stage. This is the first report showing that P. cubensis has become seed-transmitted in cucurbits. Species-specific PCR assays showed that P. cubensis occurs in ovaries, fruit seed cavity and seed embryos of cucurbits. We propose that international trade of fruits or seeds of cucurbits might be associated with the recent global change in the population structure of P. cubensis.
Does austerity pay off?
(2014)
Policy makers often implement austerity measures when the sustainability of public finances is in doubt and, hence, sovereign yield spreads are high. Is austerity successful in bringing about a reduction in yield spreads? We employ a new panel data set which contains sovereign yield spreads for 31 emerging and advanced economies and estimate the effects of cuts of government consumption on yield spreads and economic activity. The conditions under which austerity takes place are crucial. During times of fiscal stress, spreads rise in response to the spending cuts, at least in the short-run. In contrast, austerity pays off, if conditions are more benign.
Kempfidris : a new genus of myrmicine ants from the Neotropical region (Hymenoptera: Formicidae)
(2014)
The new genus Kempfidris gen. nov. is described based on the workers of a single species, K. inusualis comb. nov., from Brazil, Ecuador, and Venezuela. Kempfidris inusualis comb. nov. was originally described by Fernández (2007) and provisionally placed in Monomorium awaiting a better understanding of the internal relationships in Myrmicinae. Kempfidris gen. nov. has a series of distinctive morphological characters including the mandibular configuration, vestibulate propodeal spiracle, propodeal carinae, and cylindrical micro-pegs on the posteromedian portion of abdominal tergum VI and anteromedian portion of abdominal tergum VII. This last trait appears to be autapomorphic for the genus.
One of the leading methods of estimating the structural parameters of DSGE models is the VAR-based impulse response matching estimator. The existing asympotic theory for this estimator does not cover situations in which the number of impulse response parameters exceeds the number of VAR model parameters. Situations in which this order condition is violated arise routinely in applied work. We establish the consistency of the impulse response matching estimator in this situation, we derive its asymptotic distribution, and we show how this distribution can be approximated by bootstrap methods. Our methods of inference remain asymptotically valid when the order condition is satisfied, regardless of whether the usual rank condition for the application of the delta method holds. Our analysis sheds new light on the choice of the weighting matrix and covers both weakly and strongly identified DSGE model parameters. We also show that under our assumptions special care is needed to ensure the asymptotic validity of Bayesian methods of inference. A simulation study suggests that the frequentist and Bayesian point and interval estimators we propose are reasonably accurate in finite samples. We also show that using these methods may affect the substantive conclusions in empirical work.
We examine both the degree and the structural stability of inflation persistence at different quantiles of the conditional inflation distribution. Previous research focused exclusively on persistence at the conditional mean of the inflation rate. As economic theory provides reasons for inflation persistence to differ across conditional quantiles, this is a potentially severe constraint. Conventional studies of inflation persistence cannot identify changes in persistence at selected quantiles that leave persistence at the median of the distribution unchanged. Based on post-war US data we indeed find robust evidence for a structural break in persistence at all quantiles of the inflation process in the early 1980s. While prior to the 1980s inflation was not mean reverting, quantile autoregression based unit root tests suggest that since the end of the Volcker disinflation the unit root can be rejected at every quantile of the conditional inflation distribution.
"I Am a Hottentot" : africanist mimicry and green xenophilia in Hans Paasche and Karen Blixen
(2014)
Claims that industrialized western countries must reform their environmental practices have often been made with reference to less-developed non-western societies living in greater "harmony" or "balance" with the natural world. Examples of what I call green xenophilia (from the Greek "xenos", meaning strange, unknown or foreign, and "philia", meaning love or attraction), are myriad, wide-ranging and culturally dispersed. They range from the appearance of the iconic "crying Indian" in anti-pollution TV and newspaper spots in the months leading up to the first Earth Day on April 22 1970 to numerous environmentalist individuals' and groups' use of the fabricated "Chief Seattle's Speech" as an authoritative touchstone of ecological consciousness, and from the British Schumacher College's endorsement of India as a source of simplicity, holism, humility, vegetarianism etc. to leading deep ecologists' advocacy of East Asian religions (especially Buddhism, Jainism and Taoism) as "biocentric" alternatives to "anthropocentric" Christianity (Rolston 1987; Dunaway 2008; Krupat 2011; Corrywright 2010). Invocations of non-western cultures, identities and worldviews have proved potent heuristic devices, enabling greens both to critique the status quo and to gesture (however schematically) towards the possibility of alternatives. Pervasive media-borne ideas and images like "the Green Tibet" (Huber 1997) and "the ecological Indian" (Krech 1999) have given environmentalist ideas about the good life physical incarnation, making them seem less remote and abstract. Yet the prevalence of xenophile dis course has also made environmentalism vulnerable to recurrent accusations of romantic primitivism, orientalism and exoticism, as western greens have sometimes (though not always) appeared to buttress traditional socio-cultural norms in the very act of challenging them (Guha 1989; Lohmann 1993; Bartholomeusz 1998). What is gained and what is risked when western greens speak about, with, for or as "the other"? In this essay I engage with two early-twentieth-century North European writers, the German Hans Paasche (1881-1921) and the Dane Karen Blixen (1885-1962), whose works bring this question to the forefront. Critical of European industrialization, and awkwardly positioned vis-a-vis their upper-class social milieus, Paasche and Blixen wrote as self-made "Africans", testing the limits between colonialism, anti-colonialism and emergent forms of environmentalism and green" lifestyle reform. More precisely, Paasche in "Die Forschungsreise des Afrikaners Lukanga Kukara ins Innerste Deutschland" ("The African Lukanga Mukara's Research Joumey into the Innermost of Germany" (1912-1913) and Blixen in "Out of Africa" (1937) deploy the ambiguous form of mimicry that Susan Gubar labels "racechange", impersonating or appropriating culturally other voices and perspectives on animals, food, physical embodiment and human-natural relations (Gubar 1997). Paasche and Blixen, I argue, used their considerable intercultural insight to construct images of Africa that they hoped would stand in redemptive contrast to the humanly and environmentally ruinous beliefs and practices of European modernity. I am interested in the acts of ethnic and textual self-alienation that these writers perform because they highlight the discursive, ethical and political ambiguities of green xenophilia - ambiguities that can be explored from different positions within the developing field of ecocritical studies.
Modeling the effects of neuronal morphology on dendritic chloride diffusion and GABAergic inhibition
(2014)
Poster presentation at the Twenty Third Annual Computational Neuroscience Meeting: CNS*2014 Québec City, Canada. 26-31 July 2014.
Gamma-aminobutyric acid receptors (GABAARs) are ligand-gated chloride (Cl−) channels which mediate the majority of inhibitory neurotransmission in the CNS. Spatiotemporal changes of intracellular Cl− concentration alter the concentration gradient for Cl− across the neuronal membrane and thus affect the current flow through GABAARs and the efficacy of GABAergic inhibition. However, the impact of complex neuronal morphology on Cl− diffusion and the redistribution of intracellular Cl− is not well understood. Recently, computational models for Cl− diffusion and GABAAR-mediated inhibition in realistic neuronal morphologies became available [1-3]. Here we have used computational models of morphologically complex dendrites to test the effects of spines on Cl− diffusion. In all dendritic morphologies tested, spines slowed down longitudinal Cl− diffusion along dendrites and decreased the amount and spatial spread of synaptically evoked Cl− changes. Spine densities of 2-10 spines/µm decreased the longitudinal diffusion coefficient of Cl− to 80-30% of its value in smooth dendrites, respectively. These results suggest that spines are able to limit short-term ionic plasticity [4] at dendritic GABAergic synapses.