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This dissertation consists of three essays, which study the implication of financial frictions in business cycles and monetary policy making. The first essay develops a Dynamic Stochastic General Equilibrium (DSGE) model to study how the instability of the banking sector can amplify and propagate business cycles. Model simulations show that in an economic down turn, in addition to credit demand contraction induced by low firm net worth, low bank capital
position can create strong credit supply contraction, and have a quantitatively significant effect on business cycle dynamics. The second essay studies the optimal Taylor-type monetary policy rules based on the model developed in the first chapter and find that with interest rate smoothing, 'leaning against the wind' can significantly dampen the procyclicality of financial distortions, and increase the welfare of the economy. The third chapter examines the role of households frugality in a financial crisis and finds that higher savings by more frugal households provide an important cushion for the fall in private investment funding.
In this thesis I use effective models to investigate the properties of QCD-like theories at nonzero temperature and baryon chemical potential. First I construct a PNJL model using a lattice spin model with nearestneighbor interactions for the gauge sector and four-fermion interactions for the quarks in (pseudo)real representations of the gauge group. Calculating the phase diagram in the plane of temperature and quark chemical potential in QCD with adjoint quarks, it is qualitatively confirmed that the critical temperature of the chiral phase transition is much higher than the deconfinement transition temperature. At a chemical potential equal to half of the diquark mass in the vacuum, a diquark Bose–Einstein condensation (BEC) phase transition occurs. In the two-color case, a Ginzburg–Landau expansion is used to study the tetracritical behavior around the intersection point of the deconfinement and BEC transition lines which are both of second order. A compact expression for the expectation value of the Polyakov loop in an arbitrary representation of the gauge group is obtained for any number of colors, which allows us to study Casimir scaling at both nonzero temperature and chemical potential. Subsequently I study the thermodynamics of two-color QCD (QC2D) at high temperature and/or density using ZQCD, a dimensionally reduced superrenormalizable effective theory, formulated in terms of a coarse grained Wilson line. In the absence of quarks, the theory is required to respect the Z2 center symmetry, while the effects of quarks of arbitrary masses and chemical potentials are introduced via soft Z2 breaking operators. Perturbative matching of the effective theory parameters to the full theory is carried out explicitly, and it is argued how the new theory can be used to explore the phase diagram of two-color QCD.
The venture capital industry holds relevance for entrepreneurs looking for money to finance an innovative project, investors seeking to make money by investing in entrepreneurial firms and governments trying to promote innovation and entrepreneurship. Venture capital investment could facilitate innovation and thus a better economy.
Venture capital has enabled the U.S. to support its entrepreneurial talent by turning ideas into world-famous products and services, building companies from mere business plans to mature and powerful organizations. Three of the five largest U.S. public companies by market capitalization – Apple, Google and Microsoft – received most of their early external funding from venture capital. Having its ups and downs, venture capital investment in the U.S. expanded from virtually zero in the mid-1970s to $8 billion in 1995 and $49.3 billion in 2014. Venture backed companies have been a prime driver of economic growth in the U.S.Across the pacific, venture capital investment in China has grown out of the transition from a centrally planned economy to a free market economy over the past three decades, becoming an important pillar supporting China’s innovation system. In 2015, a total of 2,824 venture capital investment deals provided an aggregate investment of $36.9 billion. Venture capital has long been a hot topic in China’s capital market, particularly since the government decided to boost “mass entrepreneurship and innovation” in 2014.
In the U.S., most venture capital firms are organized as limited partnerships, with the venture capitalists being general partners and the investors limited partners. Studies have shown that investors choose to invest through venture funds as an intermediary rather than placing their investments directly with the entrepreneurs; because of the high risk nature of the entrepreneur’s business, it is hard for them to get bank loans or direct equity investments. Conflicts may also arise, however, between the venture capitalists acting as agents and the investors as principals.5 This agency problem maybe particularly severe, since venture capital provides money for businesses with high potential and high risk, although the limited partnership has certain merits and is still most commonly chosen as the business form for venture capital funds.6 At the same time, the fact that general partners have total control of the partnership business necessitates that the agency problem is addressed by legal rules, contracts and other mechanisms.
Meanwhile, despite the rapid growth of venture capital investments in China, little attention has been paid to the organizational form of venture capital funds. In contrast to the U.S., most Chinese venture funds have been structured as corporations. One may argue that it was due to legislative reasons: that the limited partnership was not recognized by Chinese law when venture capital first appeared in China. However, after adopted a chapter was adopted in the Partnership Enterprise Law (PEL) governing limited partnerships in 2007, most of the venture funds abided by their choice, while those opting for the limited partnership have encountered difficulties: the limited partners are having trouble trusting the general partners with their money and are therefore interfering with the operation of the partnership business, which may lead to dissolution of the partnership.
This thesis applies transaction cost theory to explain the benefits and costs of choosing the limited partnership as a business form in the special context of venture capital investments, showing that the potential agency conflict between the general partners and the limited partners have been mitigated by legal and other mechanismsin the United States, and that the U.S. investors could therefore exploit the merit of the limited partnership form in venture capital financing. In China, investors have different answers to the agency problem. Similarly to the situation in the U.S., Chinese partners also employ contract terms to deal with agency problems, and the legislators enact laws that aim at regulating the limited partnership form; some legislation was even transplanted from the U.S., such as that part of the PEL which governs limited partnerships. It seems, then, that similar mechanisms that deal with agency problems also exist in China. However, given the unique history of the development of China’s innovation system and venture capital market, the effectiveness of these constraints is questionable. Chinese venture capital investors have therefore characteristically behaved differently to U.S. investors. Rather than relying on these questionable mechanisms, Chinese investors as well as the Chinese government have developed different approaches to addressing these agency problems.
Over the last decade, cryo-EM has developed exponentially due to improvements in both hardware (“machine”-based) and software (“algorithm”-based). These improvements have pushed the best achievable resolutions closer to atomic level, bridging “gaps” not covered by other biophysical techniques, and allowing more difficult biological questions to be addressed. Thus, this PhD project was designed and constructed to apply cryo-EM to answer biological questions, while allowing simultaneous cryo-EM method development.
The biological focus of this research is pentameric ligand-gated ion channels (pLGICs), specifically the serotonin receptor type-3 receptor (5HT3R), which also belongs to the Cys-loop receptor family. 5HT3R plays an important role in fast synaptic signal transduction in response to agonist and antagonist binding. Binding to its native ligand results in opening of the channel at the transmembrane domain, allowing cations to pass through, resulting in membrane depolarization and conversion of the chemical signal into an electrical one.
This work consisted mainly of two specific aims. One was focused on conformational investigation of 5HT3R in its ligand-bound open conformation, using cryo-electron microscopy (cryo-SPA), in order to understand the gating mechanism upon ligand activation. The other one was to combine SPA with cryo-ET and STA to push the resolution limitation of conventional cryo-ET and STA workflows.
In the end, three different cryo-EM conformations of membrane-embedded 5HT3R were resolved using cryo-SPA, two structures in resting closed forms, one C5-symmetric and one C1-asymmetric, and one serotonin-bound open form. These three structures presented a number of novel features related to the transition of the receptor to its ion-conductive state. Specifically, the serotonin-bound receptor shows asymmetric opening, which was speculated to occur via an intermediate asymmetric Apo state. In addition to the cryo-SPA work, application of cryo-ET and STA to the study of 5HT3R in native vesicles is described in this thesis. Additional work on methods development, focused on combining SPA and STA techniques, along with preliminary results on tobacco mosaic virus are also detailed and discussed.
Moreover, previously unreported asymmetric arrangements of the subunits of the homopentameric 5HT3R around the pore axis were revealed. The asymmetric open state is stabilized by phospholipids inserted at the interface between subunits, at a site well-documented for the binding of allosteric pLGIC modulators. These results not only give structural support to a large body of functional data on the effects of lipids on the function of this receptor family, but also provide structural guidance for future studies in this field. Meanwhile, the SPA-STA combined methods developed during the course of this work have the potential to help resolve higher resolution tomography-based structures, which would benefit researchers seeking to do in-situ-based structural studies.
Trace elemental concentrations of bivalve shells content a wealthy of environmental and climatic information of the past, and therefore the studies of trace elemental distributions in bivalve shells gained increasing interest lately. However, after more than half century of research, most of the trace elemental variations are still not well understood and trace elemental proxies are far from being routinely applicable. This dissertation focuses on a better understanding of the trace elemental chemistry of Arctica islandica shells from Iceland, and paving the way for the application of the trace elemental proxies to reconstruct the environmental and climatic changes. Traits of trace elemental concentrations on A. islandica shells were explored and evaluated. Then based the geochemical traits of the shells, four non-environmental/climatic controlling is indentified. (1) Trace elemental concentrations of bivalve shells are effected by early diagenesis by the leach or exchange of elemental ions, especially in shell tip part, even with the protection of periostrucum; (2) The analytical methods also affect the results of trace elemental concentrations, especially for the element, such as Mg, which is highly enriched in organic matrices; (3) Shell organic matrices are found play a dominating role on the concentration of trace elements on A. islandica shells. Most trace elements only occurred in insoluble organic matrices (IOM), although others are only found in the carbonate fraction. IOM of A. islandica shells is significantly enriched in Mg, while Li and Na are more deplete in IOM, but enriched in shell carbonate. Ba is more or less even contented in IOM and shell carbonate. The concentrations of certain elements vary between primary layer and secondary layer; (4) The vital /physiological controlling on trace elemental distributions of bivalve shells is also confirmed. Six elemental (B, Na, Mg, Mn, Sr, and Ba) concentrations show significant correlation (exponential functions) with ontogenetic age and shell grow rates (logarithmic equations). It is worthy to remark that B, Mg, Sr and Ba concentrations are negatively correlated with shell growth rate, positive with ontogenetic age, while the concentrations of Na and Mn show the opposite trends. At last, all the controlling described above can be taken into account and corrected to extract the environmental and climatic signal by a kind of standardization. The derived six exponential functions of the high correlations between six trace elemental concentrations and ontogenetic year are applied to make the standardization of these element-Ca ratios. The gotten standardized indices are compared with the variations of environmental and climatic parameters in this region, and many correlations are found. Standardized indices of Sr/Ca ratios are strongly related to the sun spot number, autumn NAO, autumn Europe surface air temperature (SAT) and Arctic sea surface temperature anomaly (TA), and those of Mg/Ca ratios are strongly associated with Arctic TA, Europe SAT and Solar variation (irradiance). The variations of autumn Europe SAT demonstrated more similarity with standardized indices of B/Ca than other parameters. Except for the SAT index of Arctic, the standardized indices of Na/Ca showed no distinct relation to temperature. European precipitation and the Arctic sea level pressure index compared well the Na/Ca ratios of the shells, and so did the autumn NAO. Standardized indices of Mn/Ca were correlated with the number of hurricanes in the North Atlantic, Northern Europe SAT and sun spot number.
The transporter associated with antigen processing-like (TAPL) acts as a lysosomal ATP-dependent polypeptide transporter with broad length selectivity. To characterize in detail its substrate specificity, a procedure for solubilization, purification and functional reconstitution of human TAPL was developed. TAPL was expressed in Sf9 insect cells with the baculovirus expression system and solubilized from crude membranes. By intensive screening of detergents, the mild non-ionic detergents digitonin and dodecylmaltoside were found to be ideal for solubilization with respect to efficiency, long term stability, and functionality of TAPL. TAPL was isolated in a two-step procedure with a yield of 500 micro g/L cell culture and, subsequently, reconstituted into proteoliposomes. The KM(pep) for the peptide RRYCfKSTEL (f refers to fluorescence label) and KM(ATP) were determined to be 10.5 ± 2.3 micro M and 97.6 ± 27.5 micro M, respectively, which are in the same range as the Michaelis-Menten constants determined in the membranes. The peptide transport activity of the reconstituted TAPL strongly depends on the lipid composition. Interestingly, the E. coli lipids are prefered over other tested natural lipids extracts. Moreover, phosphatidylcholine, the most abundant phospholipid in eukaryotic cells influenced TAPL activity in a dose dependent manner. In addition, some negatively charged lipids like DOPA and DOPS increased peptide transport activity with preference for DOPS. However, DOPE or egg PG which are also negatively charged had no effect. It seems not only the charge but also the specific head group of phospholipids that has impact on the function of TAPL. With the help of combinatorial peptide libraries containing D-amino acid residues at defined positions as well as bulky fluorescein labeled peptides, the key positions of the peptides were localized to the N- and C-terminal residues with respect to peptide transport. The C-terminal position has the strongest selectivity since modification at this position shows strongest impact on peptide transport. Additionally, positions 2 and 3 of the peptide also have weak influence on peptide selectivity. Subsequently, the residue preferences at the key positions were systematically investigated by combinatorial peptide libraries with defined residues at certain positions. At both ends, TAPL favors positively charged, aromatic, or hydrophobic residues and disfavors negatively charged residues as well as asparagine and methionine. The residue preferences at the key positions are valid for peptide substrates with different length, indicating a general rule for TAPL selectivity. Besides specific interactions of both terminal residues, electrostatic interactions are important, since peptides with positive net charge are more efficiently transported than negatively charged ones. By size exclusion chromatography (SEC) and blue native PAGE, TAPL purified in the presence of digitonin or dodecylmaltoside had an apparent molecular weight of 200 kDa which is close to the theoretical molecular mass of the TAPL homodimer (172 kDa). The purified and reconstituted TAPL showed specific ATP hydrolysis activity which can be inhibited by orthovanadate. TAPL in proteoliposomes showed 6-fold higher ATP hydrolysis than digitonin solubilized protein, indicating the phospholipids impact on TAPL function. However, no peptide substrate stimulated ATPase activity was observed. For site-specific labeling of TAPL, eight cysteines in each half transporter were replaced by alanine or valine. The TAPL cys-less mutant showed the same peptide transport activity as TAPL wt. Based on the functional TAPL cys-less mutant, seven single cysteine mutants were introduced into strategic positions. All single cysteine mutants in the TMD did not influence peptide transport, whereas the mutant L701C, which is close to the conserved H-loop motif, displayed impaired transport. TAPL orthologs Haf-4 and Haf-9 from Caenorhabditis elegans possess around 40% sequence identities with TAPL and 50% with each other. Both proteins are putative half transporters and reported to be involved in the intestinal granule formation (Bauer, 2006; Kawai et al., 2009). To further understand the physiological functions of these two proteins, they were expressed in Sf9 insect cells. Haf-4 and Haf-9 showed weak but specific ATP- and peptide-dependent peptide transport activity for the given peptide RRYCfKSTEL. Therefore, it was proposed that the physiological roles for Haf-4 and Haf-9 might be related to their peptide transport activity. Besides forming functional homodimeric complex as estimated by the peptide transport activities, both half transporter could also form heteromers which was confirmed by coimmunoprecipitation. However, the heteromers showed decreased transport activity.
The application of natural products (NPs) as drugs and lead compounds has greatly improved human health over the past few decades. Despite their success, we still need to find new NPs that can be used as drugs to combat increasing drug resistance via new modes of action and to develop safer treatments with less side effects.
Entomopathogenic bacteria of Xenorhabdus and Photorhabdus that live in mutualistic symbiosis with nematodes are considered as promising producers of NPs, since more than 6.5% of their genomes are assigned to biosynthetic gene clusters (BGCs) responsible for production of secondary metabolites. The investigation on NPs from Xenorhabdus and Photorhabdus can not only provide new compounds for drug discovery but also help to understand the biochemical basis involved in mutualistic and pathogenic symbiosis of bacteria, nematode host and insect prey.
Nonribosomal peptides (NRPs) are a large class of NPs that are mainly found in bacteria and fungi. They are biosynthesized by nonribosomal peptide synthetases (NRPSs) and display diverse functions, representing more than 20 clinically used drugs. Although a large number of NRPs have been identified in Xenorhabdus and Photorhabdus, the advanced genome sequencing and bioinformatic analysis indicate that these bacteria still have many unknown NRPS-encoding gene clusters for NRP production that are worth to explore. Therefore, this thesis focuses on the discovery, biosynthesis, structure identification, and biological functions of new NRPs from Xenorhabdus and Photorhabdus.
The first publication describes the isolation and structure elucidation of seven new rhabdopeptide/xenortide-like peptides (RXPs) from X. innexi, incorporating putrescine or ammonia as the C-terminal amines. Bioactivity testing of these RXPs revealed potent antiprotozoal activity against the causative agents of sleeping sickness (Trypanosoma brucei rhodesiense) and malaria (Plasmodium falciparum), making them the most active RXP derivatives known to date. Biosynthetically, the initial NRPS module InxA might act iteratively with a flexible methyltransferase activity to catalyze the incorporation of the first five or six N-methylvaline/valine to these peptides.
The second publication focuses on the structure elucidation of seven unusual methionine-containing RXPs that were found as minor products in E. coli carrying the BGC kj12ABC from Xenorhabdus KJ12.1. To confirm the proposed structures from detailed HPLC-MS analysis, a solid-phase peptide synthesis (SPPS) method was developed for the synthesis of these partially methylated RXPs. These RXPs also exhibited good effects against T. brucei rhodesiense and P. falciparum, suggesting RXPs might play a role in protecting insect cadaver from soil-living protozoa to support the symbiosis with nematodes.
The third publication presents the identification of a new peptide library, named photohexapeptide library, which occurred after the biosynthetic gene phpS was activated in P. asymbiotica PB68.1 via promoter exchange. The chemical diversity of the photohexapeptides results from unusual promiscuous specificity of five out of six adenylation (A) domains being an excellent example of how to create compound libraries in nature. Furthermore, photohexapeptides enrich the family of the rare linear D-/L-peptide NPs.
The fourth publication concentrates on the structure elucidation of a new cyclohexapeptide, termed photoditritide, which was produced by P. temperata Meg1 after the biosynthetic gene pdtS was activated via promoter exchange. Photoditritide so far is the only example of a peptide from entomopathogenic bacteria that contains the uncommon amino acid homoarginine. The potent antimicrobial activity of photoditritide against Micrococcus luteus implies that photoditritide can protect the insect cadaver from food competitor bacteria in the complex life cycle of nematode and bacteria.
The last publication reports a new family of cyclic lipopeptides (CLPs), named phototemtides, which were obtained after the BGC pttABC from P. temperata Meg1 was heterologously expressed in E. coli. The gene pttA encodes an MbtH protein that was required for the biosynthesis of phototemtides in E. coli. To determine the absolute configurations of the hydroxy fatty acids, a total synthesis of the major compound phototemtide A was performed. Although the antimalarial activity of phototemtide A is only weak, it might be a starting point towards a selective P. falciparum compound, as it shows no activity against any other tested organisms.
Unlimited self-renewal is an absolute prerequisite for any malignancy, and is the ultimate arbiter of the continuous growth and metastasis of tumors. It has been suggested that the self-renewal properties of a tumor are exclusively contained within a small population, i.e., the so-called cancer stem cells. Enhanced self-renewal potential plays a pivotal role in the development of leukemia. My data have shown that APL associated translocation products PML/RARalpha and PLZF/RARalpha increased the replating efficiency of mouse lin-/Sca1+ hematopoietic stem cells (HSCs). This effect is partly mediated by induction of gamma–catenin which is an important mediator of the Wnt signaling pathway and has been shown to be up regulated by the AML associated translocation products(AATPs). Suppression of gamma–catenin by siRNA can abrogate the increased replating efficiency induced by AATPs. Transduction of gamma–catenin in lin-/Sca1+ HSCs led to increased replating efficiency and the expression of stem cell markers Sca1 and c-kit. Additionally it induced accelerated cell cycle progression of mouse bone marrow HSCs. Transduction/transplantation mouse models have shown that ectopic expression of gamma–catenin in HSCs led to acute myeloid leukemia without maturation. These data suggest important roles of Wnt signaling pathway in the leukemogenesis induced by PML/RARalpha, PLZF/RARalpha and AML1/ETO. In contrast to AATPs, CML and Ph+-ALL associated translocation products p185(BCR-ABL) and p210(BCR-ABL) did not affect the self-renewal potential of hematopoietic stem/progenitor cells. However my studies indicated that their reciprocal translocation products p40(ABL/BCR) and p96(ABL/BCR) actually increased the replating efficiency of hematopoietic stem/progenitor cells. The effect is stronger when induced by p96(ABL/BCR) than by p40(ABL/BCR). It is very intriguing that p96(ABL/BCR) can activate Wnt signaling and up regulate the expression of HoxB4. Transduction/transplantation mouse model has shown that p40(ABL/BCR) and p96(ABL/BCR) both have their own leukemogenic potential. Given the fact that leukemic stem cells maintain the growth of tumor and are the origin of relapse, the cure of leukemia is dependent on the eradication of the leukemic stem cell and abrogation of aberrantly regulated self-renewal capability. Both t-RA and As2O3 have been shown to induce complete remission in APL patients with PML/RARalpha translocation product. However, t-RA as a single agent achieves completeremission (CR) but not complete molecular remissions (CMR). Therefore, virtually all patients will experience a relapse within a few months. In contrast to t-RA, As2O3 as a single agent is able to induce CR as well as CMR followed by long-term relapse-free survival in about 50% of APL patients even if relapsed after treatment with t-RA-containing chemotherapy regimens. Nothing is known about the mechanisms leading to the complete different clinical outcomes by the two compounds although both have been shown to induce differentiation of blast cells, proliferation arrest, induction of apoptosis and degradation of PML/RARalpha. We investigated the effect of t-RA and arsenic on PML/RARalpha-expressing cell population with stem cell capacity derived from the APL cell line NB4 as well as Sca1+/lin- murine bone marrow cells. We found that t-RA did not reduce the replating efficiency in PML/RARalpha- and PLZF/RARalpha-infected Sca1+/lincells whereas it selected small compact colonies representing very early progenitor cells. T-RA was unable to reduce the capacity to form colony forming units-spleen (CFU-S) of Sca1+/lin-cells expressing PML/RARalpha, additionally t-RA did not impair the capability of engraftment of NB4 cells in NOD/SCID mouse. On the contrary to t-RA, As2O3 abolished the aberrant self-renewal potential of Sca1+/lin- cells expressing PML/RARalpha. As2O3 not only abolished the replating efficiency of PML/RARalpha positive cells but also completely abrogated the ability of PML/RARalpha-positive HSC to produce CFU-S in vivo. On the contrary to As2O3, t-RA increased the absolute cell number and the percentage of cells in the side population with respect to the whole cell population in NB4 cells. Taken together these data suggest that arsenic but not all-trans retinoic acid overcomes the aberrant stem cell capacity of PML/RARalpha positive leukemic stem cells. My data prove for the first time that there is a direct relationship between the capacity of compounds to effectively target the LSC and their capacity to eradicate the leukemia, and, thereby, to induce complete molecular remission and long-term relapse-free survival. Thus, in order to increase the curative potential of leukemia therapies, future studies need to include the effect of given compounds on the stem cell compartment to determine their ability to eradicate the LSC.
Clinical application of transcranial Doppler for detection of cerebral emboli during cardiac surgery
(2010)
Objective: Neurologic injury is one of the most damaging complications for cardiac surgery. How to decrease neurologic impairment by improving perioperative monitoring remains a challenge for both cardiac surgeons and anesthetists. For this reason, transcranial doppler (TCD) has been widely used in cerebral monitoring during cardiac surgery. In this study, two experiments of clinical application of TCD for detection of cerebral emboli during cardiac surgery were to be done. One was “Solid and gaseous cerebral emboli during valvular surgery are significantly reduced with axillary artery cannulation”. The other was “Do intraoperative cerebral embolic signals differ between valvular surgery (VS) and CABG”. Methods: In experiment one, 20 valve and combined procedures with aortic cannulation (AoC group) were compared to 18 procedures with axillary cannulation (AxC group) in a prospective non-randomized study. In experiment two, 18 VS patients and 18 CABG patients were matched by extracorporeal circulation (ECC) time retrospectively. Intraoperative monitoring of both middle cerebral arteries was performed with TCD discriminating between solid and gaseous embolic signals (ES). Results: In experiment one, the AxC group had less solid ES than the AoC group (38±22 vs 55±25, P<0.05), but no significant difference was found in gaseous (501±271 vs 538±333, P>0.05) and total (539 ± 279 vs 593 ± 350, P>0.05) ES. The AxC group had less solid ES during arterial cannulation (2.1±1.5 vs 6.6±3.6, P<0.05) and during aortic cross-clamp time (4.4 ±3.1 vs 10.2 ± 5.1, P<0.05) than the AoC group. During ECC, gaseous ES was not significantly different between groups (398±210 vs 448±291, P>0.05). However, AxC showed less gaseous ES (85±68 vs 187±148, P<0.05) and less gaseous ES per minute (1.8±1.5 vs 4.5±3.2, P<0.05) during weaning off extracorporeal circulation than the AoC group. No significant difference in gaseous ES (313±163 vs 261±189, P>0.05) and gaseous ES per minute (3.1±2.2 vs 2.8±2.2, P>0.05) was found between groups from bypass start to aortic declamping. No neurologic complications occurred. In experiment two, no significant difference was found in solid (38±20 vs 40±26, P>0.05) or gaseous (457±263 vs 412±157, P>0.05) ES between the VS and CABG group during the whole recording time. During ECC, solid ES (20±10 vs 24±19, P>0.05) and gaseous ES (368±230 vs 317±157, P>0.05) were comparable between groups. Specifically, during weaning off ECC, the VS group had more gaseous ES/min (5.6±3.6 vs 3.1±1.2, P<0.05) than the CABG group. But this difference in gaseous ES/min was not significant during the period from bypass start to aortic declamping (2.5±1.8 vs 3.0±1.8, P>0.05). Conclusion: Cerebral embolization does occur during cardiac surgery. Through these two experiments, we demonstrated the feasibility and importance of clinical application of transcranial doppler for detection of cerebral emboli during cardiac surgery. Due to the diversity in clinical application of TCD, it is impossible to compare the number of ES between different research centers. More unified standards should be drawn in order to make wider clinical application possible. Up till now, no robust evidence shows the correlation between intraoperative ES and postoperative neurological impairment. The research on intraoperative ES and postoperative neurological impairment should rely on a complete concept.
Der Schwerpunkt der vorliegenden Arbeit lag in der Synthese und strukturellen Charakterisierung von sandwichartig aufgebauten kupferhaltigen Organosiloxanen. Diese sollten nach Möglichkeit kristalline Eigenschaften aufweisen und ein interessantes magnetisches Verhalten zeigen. Es galt, die Beziehungen zwischen molekularer Struktur und magnetischen Eigenschaften herauszuarbeiten, um auf der Basis experimenteller Daten dem maßgeschneiderten Design neuer molekularer Magnete näher zu kommen. .... Die in der hier vorgelegten Arbeit erzielten Ergebnisse belegen, dass der Weg zur gezielten Erzeugung molekularer Magnete erfolgreich beschritten wurde. Es wird weiteren Arbeiten vorbehalten bleiben, Cluster der nun vorliegenden Art chemisch so zu verknüpfen, dass daraus polymere Ketten oder Netzwerke entstehen. Deren magnetisches Verhalten lässt erwarten, dass damit möglicherweise neue Materialien zugänglich werden, die dem Anspruch eines molekularen Magneten voll gerecht werden.