Acute kidney injury in three dogs after ingestion of a descaling agent containing maleic acid

Maleic acid (MA) is a common component of descaling products and is widely used in daily life. Accidental ingestion in relevant amounts does not play a major role in human beings; however, it seems to be highly toxic for dogs. It has been commonly used experimentally to induce Fanconi syndrome in dogs or small rodents. Two dogs were presented for acute kidney injury (AKI) after accidental ingestion of a descaling agent containing MA at an estimated amount of 70 mg/kg each. The third dog involved was euthanased by the referring veterinarian, and postmortem pathological analysis revealed severe acute tubular necrosis consistent with toxic nephropathy. The other dogs received symptomatic therapy for AKI including treatment with haemodialysis and showed complete normalisation of serum creatinine at a follow-up after five months. Renal damage can be very severe, but seems to be at least partially reversible and an attempt to treatment is warranted.

Strengths, weaknesses, opportunities and threats: A SWOT analysis of the ecosystem services framework

The ecosystem services concept (ES) is becoming a cornerstone of contemporary sustainability thought. Challenges with this concept and its applications are well documented, but have not yet been systematically assessed alongside strengths and external factors that influence uptake. Such an assessment could form the basis for improving ES thinking, further embedding it into environmental decisions and management. The Young Ecosystem Services Specialists (YESS) completed a Strengths–Weaknesses–Opportunities–Threats (SWOT) analysis of ES through YESS member surveys. Strengths include the approach being interdisciplinary, and a useful communication tool. Weaknesses include an incomplete scientific basis, frameworks being inconsistently applied, and accounting for nature's intrinsic value. Opportunities include alignment with existing policies and established methodologies, and increasing environmental awareness. Threats include resistance to change, and difficulty with interdisciplinary collaboration. Consideration of SWOT themes suggested five strategic areas for developing and implementing ES. The ES concept could improve decision-making related to natural resource use, and interpretation of the complexities of human-nature interactions. It is contradictory – valued as a simple means of communicating the importance of conservation, whilst also considered an oversimplification characterised by ambiguous language. Nonetheless, given sufficient funding and political will, the ES framework could facilitate interdisciplinary research, ensuring decision-making that supports sustainable development.

The palaeoecological history of the Praz-Rodet bog (Swiss Jura) based on pollen, plant macrofossils and testate amoebae (Protozoa)

Stratigraphy, radiocarbon dating and analyses of pollen, plant macrofossils and testate amoebae were used to reconstruct the development and ecology of a small raised bog in a karst-dominated landscape in the Swiss Jura Mountains. Special focus was on past vegetation and on the history of Pinus rotundata in relation to anthropogenic and climatic influences. Testate amoebae were used to reconstruc-t past local soil pH and water-table depth. The inferred development of the Praz-Rodet bog typifies a classic hydroseral tefrestrialization of a small basin. Two features are specific for this site. First, the bog was much wetter than today for a long period; according to our hypothesis, this only changed as a consequence of human activities. Second, two hiatuses are present at the coring location (Younger Dryas--early Preboreal, and 4700-2800 cal. yr BP), the former probably caused by low lake productivity due to cold temperatures and the latter by the erosional activity of the adjacent small river. The date of 2800 cal. yr BP for renewed peat accumulation may be related to climatic change (Subboreal-Subatlantic transition). Pollen indicators failed to show one hiatus: an apparently complete pollen sequence is therefore no guarantee of an uninterrupted sediment accumulation. Evidence of early minor human impact on the vegetation in the Joux Valley dates back to c. 6850 calendar years, congruous with the early Neolithic in the Jura Mountains. The history of Pinuis rotindata appears to be more complex than previously believed. Human activity is clearly responsible for the present abundance of this species, but the tree was naturally present on the bog long before the first evidence of important human disturbance of the site (1500 cal. yr BP). It is suggested that, in karst-dominated landscapes, dense forests growing on mineral soils around raised bogs may significantly reduce summer evapotranspiration by acting as windbreaks. Forest clearance results in increased evapotranspiration, causing a lowering of the water table on the bog and a modification of the vegetation cover. This hypothesis has implications for the management of similar small raised bogs in karst-dominated landscape.

Extreme River Floods in Western Switzerland and the Lake of Constance Region in the Period Prior to Instrumental Measurements

The floods that occurred on the Aare and Rhine rivers in May 2015 and the mostly successful handling of this event in terms of flood protection measures are a good reminder of how important it is to comprehend the causes and processes involved in such natural hazards. While the needed data series of gauge measurements and peak discharge calculations reach back to the 19th century, historical records dating further back in time can provide additional and useful information to help understanding extreme flood events and to evaluate prevention measures such as river dams and corrections undertaken prior to instrumental measurements. In my PhD project I will use a wide range of historical sources to assess and quantify past extreme flood events. It is part of the SNF-funded project “Reconstruction of the Genesis, Process and Impact of Major Pre-instrumental Flood Events of Major Swiss Rivers Including a Peak Discharge Quantification” and will cover the research locations Fribourg (Saane R.), Burgdorf (Emme R.), Thun, Bern (both Aare R.), and the Lake of Constance at the locations Lindau, Constance and Rorschach. My main goals are to provide a long time series of quantitative data for extreme flood events, to discuss the occurring changes in these data, and to evaluate the impact of the aforementioned human influences on the drainage system. Extracting information given in account books from the towns of Basel and Solothurn may also enable me to assess the frequency and seasonality of less severe river floods. Finally, historical information will be used for remodeling the historical hydrological regime to homogenize the historical data series to modern day conditions and thus make it comparable to the data provided by instrumental measurements. The method I will apply for processing all information provided by historical sources such as chronicles, newspapers, institutional records, as well as flood marks, paintings and archeological evidence has been developed and successfully applied to the site of Basel by Wetter et al. (2011). They have also shown that data homogenization is possible by reconstructing previous stream flow conditions using historical river profiles and by carefully observing and re-constructing human changes of the river bed and its surroundings. Taken all information into account, peak discharges for past extreme flood events will be calculated with a one-dimensional hydrological model.

Role of the cyclin dependent kinase-4 in normal and neoplastic proliferation

In the last few years, our laboratory has studied the regulatory mechanisms of proliferation and differentiation in epidermal tissues. Our results showed differences in the roles of cyclin dependent-kinases 4 and 6, and the three D-type cyclins, during normal epidermal proliferation and neoplastic development. Thus, to elucidate the role of the different cell cycle regulators, we developed transgenic mice that overexpress CDK4 (K5-CDK4), or their cognate D-type cyclins, in epithelial tissues. The most severe phenotype was observed in K5-CDK4 animals that developed dermal fibrosis, epidermal hyperplasia and hypertrophy. Forced expression of CDK4 in the epidermal basal cell layer increased the malignant conversion of skin papillomas to squamous cell carcinomas (SCC). Contrastingly, lack of CDK4 completely inhibited tumor development, suggesting that CDK4 is required in this process. Biochemical studies demonstrated that p21 Cip1 and p27Kip1 inhibitors are sequestered by CDK4 resulting in indirect activation of Cyclin E/CDK2, implicating the non-catalytic activity of CDK4 in deregulation of the cell cycle progression. ^ It has been proposed that the proliferative and oncogenic role of Myc is linked to its ability to induce the transcription of CDK4, cyclin D1, and cyclin D2 in vitro. Deregulation of Myc oncogene has been found in several human cancers. Also it has been demonstrated that CDK4 has the ability to functionally inactivate the product of the tumor suppressor gene Rb, providing a link between Myc and the CDK4/cyclin D1/pRb/p16 pathway in some malignant tumors. Here, we sought to determine the role of CDK4 as a mediator of Myc activities by developing a Myc overexpressing mouse nullizygous for CDK4. We demonstrated that lack of CDK4 results in reduced keratinocyte proliferation and epidermal thickness in K5-Myc/CDK4-null mice. In addition, complete reversion of tumor development was observed. All together, this work demonstrates that CDK4 acts as an oncogene independent of the D-type cyclin levels and it is an important mediator of the tumorigenesis induced by Myc. In addition, we showed that the sequestering activity of CDK4 is critical for the development of epidermal hyperplasia during normal proliferation, malignant progression from papillomas to squamous cell carcinomas, and tumorigenesis induced by Myc. ^

Zoning and the built environment: A public health analysis of zoning in Austin, Texas

The built environment is part of the physical environment made by people and for people. Because the built environment is such a ubiquitous component of the environment, it acts as an important pathway in determining health outcomes. Zoning, a type of urban planning policy, is one of the most important mechanisms connecting the built environment to public health. This policy analysis research paper explores how zoning regulations in Austin, Texas promote or prohibit the development of a healthy built environment. A systematic literature review was obtained from Active Living Research, which contained literature published about the relationships between the built environment, physical activity, and health. The results of these studies identified the following four components of the built environment that were associated to health: access to recreational facilities, sprawl and residential density, land use mix, and sidewalks and their walkability. A hierarchy analysis was then performed to demonstrate the association between these aspects of the built environment and health outcomes such as obesity, cardiovascular disease, and general health. Once these associations had been established, the components of the built environment were adapted into the evaluation criteria used to conduct a public health analysis of Austin's zoning ordinance. A total of eighty-eight regulations were identified to be related to these components and their varying associations to human health. Eight regulations were projected to have a negative association to health, three would have both a positive and negative association simultaneously, and nine were indeterminable with the information obtained through the literature review. The remaining sixty-eight regulations were projected to be associated in a beneficial manner to human health. Therefore, it was concluded that Austin's zoning ordinance would have an overwhelmingly positive impact on the public's health based on identified associations between the built environment and health outcomes.^

A novel mechanism of 3-bromopyruvate-induced cell death through targeting hexokinase and ubiquitination

Increased dependence on aerobic glycolysis for energy (ATP) supply has been observed in various human cancer cells. It is plausible to exploit this metabolic alteration for therapeutic benefits by inhibiting glycolysis to preferentially abolish cancer energy metabolism and kill the malignant cells. 3-Bromopyruvate has been shown to be a potent inhibitor of glycolysis capable of inducing severe ATP reduction and cell death in various cancer cell lines, especially cancer cells with mitochondrial defects or under hypoxic conditions. However, the detailed mechanisms of this novel anticancer agent still remain unclear. My study demonstrated that 3-Bromopyruvate caused a covalent modification of hexokinase II, a key glycolytic enzyme, and disrupted its association with mitochondria. This led to mitochondrial permeability transition and a substantial release of apoptosis-inducing faction (AIF) prior to cytochrome c release. Dissociation of HK II from mitochondria using a cell permeable specific peptide also induced the release of AIF and cytochrome c, and caused substantial cell death. HK II-targeted peptide did not cause significant change in mitochondria respiration and glycolysis activity, suggesting that dissociation of this molecule from mitochondria alone can also cause cell death, and that this may be a novel mechanism by which 3-Bromopyruvate exerts its potent cytotoxic action, in addition to its inhibition of the enzyme activity. Another significant new discovery was that 3-Bromopyruvate induced rapid reduction of protein ubiquitination in vivo, which occurred within several hours of drug incubation and before ATP reduction and cell death. Further mechanistic studies showed that this was due to the inhibition the ubiquitin activating enzyme E1 and the conjugating enzyme E2. Knocking down ubiquitin protein expression by siRNA did not suppress mitochondria respiration and glycolysis, but caused significant cell death. Taken together, this study demonstrated that induction of HK II dissociation from mitochondria and inhibition of glycolysis are two newly discovered mechanisms that contribute to the potent anticancer activity of 3-Bromopyruvate, and identified this compound as a valuable chemical tool for research in protein ubiquitination. ^

Aedes aegypti, Aedes albopictus, and Dengue virus in Harris county: An estimate of risk

Recent outbreaks of dengue fever (DF) along the United States/Mexico border, coupled with the high number of reported cases in Mexico suggest that there is the possibility for DF emergence in Houston, Texas1,2. To determine the presence of DF, populations of Aedes aegypti and Aedes albopictus were identified and tested for dengue virus. Maps were created to identify "hot spots" (Figure 1) based on historical data on Ae. aegypti and Ae. albopictus, demographic information, and locations of human cases of dengue fever. BG Sentinel Traps®, in conjunction with BG Lure® attractant, octanol and dry ice, were used to collect mosquitoes, which were then tested for presence of dengue virus using ELISA techniques. All samples tested were negative for dengue virus (DV). Survival of DV ultimately comes down to whether or not it will be vectored by a mosquito to a susceptible human host. The presence of infected humans and contact with the mosquito vectors are two critical factors necessary in the establishment of DF. Historical records indicate the presence of Ae. aegypti and Ae. albopictus in Harris County, which would support localized dengue transmission if infected individuals are present.^ (1) Brunkard JM, Robles-Lopez JL, Ramirez J, Cifuentes E, Rothenberg SJ, Hunsperger EA, Moore CG, Brussolo RM, Villarreal NA, Haddad BM, 2007. Dengue fever seroprevalence and risk factors, Texas-Mexico border, 2004. Emerg Infect Dis 13: 1477-1483. (2) Ramos MM, Mohammed H, Zielinski-Gutierrez E, Hayden MH, Lopez JL, Fournier M, Trujillo AR, Burton R, Brunkard JM, Anaya-Lopez L, Banicki AA, Morales PK, Smith B, Munoz JL, Waterman SH, 2008. Epidemic dengue and dengue hemorrhagic fever at the Texas-Mexico Border: results of a household-based seroepidemiologic survey, December 2005. Am J Trop Med Hyg 78: 364-369.^

A literature review of the use of DDT to fight malaria

Background. First synthesized in 1874, dichlorodiphenyltrichloroethane (DDT) was not used until the second half of World War II after its insecticidal properties were discovered in 1939. For decades DDT has been used globally with the intent of eradicating malaria. This began in 1955 when the eighth World Health Assembly launched a global campaign selecting DDT as the chemical of choice for the eradication of malaria. The United States banned DDT use in 1972 partially due to the publication of “Silent Spring” by Rachel Carson in 1962 which suggested that DDT was harmful to the environment, wildlife and is a carcinogen. ^ Objectives. To critically review the literature on DDT, and evaluate its importance in malaria prevention and control. Methods: The design of this systematic literature review is a narrative summary and evaluation of the papers reviewed. The data came from searches using PubMed and MEDLINE which are free and publicly available databases. Inclusive criteria that were considered during the search are English language peer reviewed journal articles published in the last 20 years. The keywords were: “insecticidal and agricultural use of DDT”, “human impact of malaria”, “economic impact of malaria”, “benefits of DDT”, “effects of DDT”, “importance of malaria control”, and alternatives to DDT for malaria control. ^ Results. Malaria continues to be one of the most common infectious diseases and creates a tremendous global public health problem. WHO recommends DDT for malaria vector control because compared to other pesticides, it is the most persistent in indoor spraying. ^ Conclusion. Indoor spraying of DDT in malaria endemic areas may cause increased exposure of the chemical to humans; however I conclude that the overall benefits outweigh the risks because more lives are saved due to fewer infections with malaria.^

The application of principal component analysis on human development indicators: Temporal approach from 1999 to 2010

Background and Objective. Ever since the human development index was published in 1990 by the United Nations Development Programme (UNDP), many researchers started searching and corporative studying for more effective methods to measure the human development. Published in 1999, Lai’s “Temporal analysis of human development indicators: principal component approach” provided a valuable statistical way on human developmental analysis. This study presented in the thesis is the extension of Lai’s 1999 research. ^ Methods. I used the weighted principal component method on the human development indicators to measure and analyze the progress of human development in about 180 countries around the world from the year 1999 to 2010. The association of the main principal component obtained from the study and the human development index reported by the UNDP was estimated by the Spearman’s rank correlation coefficient. The main principal component was then further applied to quantify the temporal changes of the human development of selected countries by the proposed Z-test. ^ Results. The weighted means of all three human development indicators, health, knowledge, and standard of living, were increased from 1999 to 2010. The weighted standard deviation for GDP per capita was also increased across years indicated the rising inequality of standard of living among countries. The ranking of low development countries by the main principal component (MPC) is very similar to that by the human development index (HDI). Considerable discrepancy between MPC and HDI ranking was found among high development countries with high GDP per capita shifted to higher ranks. The Spearman’s rank correlation coefficient between the main principal component and the human development index were all around 0.99. All the above results were very close to outcomes in Lai’s 1999 report. The Z test result on temporal analysis of main principal components from 1999 to 2010 on Qatar was statistically significant, but not on other selected countries, such as Brazil, Russia, India, China, and U.S.A.^ Conclusion. To synthesize the multi-dimensional measurement of human development into a single index, the weighted principal component method provides a good model by using the statistical tool on a comprehensive ranking and measurement. Since the weighted main principle component index is more objective because of using population of nations as weight, more effective when the analysis is across time and space, and more flexible when the countries reported to the system has been changed year after year. Thus, in conclusion, the index generated by using weighted main principle component has some advantage over the human development index created in UNDP reports.^

Inhibitor of cytochrome c messenger RNA -protein interaction in stimulated rat skeletal muscle

The purpose of this work was to examine the possible mechanisms for the regulation of cytochrome c gene expression in response to increased contractile activity in rat skeletal muscle. The working hypothesis was that increased contractile activity enhances cytochrome c gene expression through a cis-element. A 110% increase in cytochrome c mRNA concentration was observed in tibialis anterior (TA) muscle after 9 days of chronic stimulation. Similar difference (120%) exists between soleus (SO) muscle of higher contractile activity and white vastus lateralis (WV) muscle of lower contractile activity. These results suggest that the endogenous cytochrome c gene expression is regulated by contractile activity. Cytochrome c-reporter genes were injected into skeletal muscles to identify the cis-element that is responsible for the regulation. Although the data was inconclusive, part of it suggested the importance of the 3$\sp\prime$-untranslated region (3$\sp\prime$-UTR) in mediating the response to increased contractile activity.^ RNA gel mobility shift (GMSA) and ultraviolet (UV) cross-linking assays revealed specific RNA-protein interaction in a 50-nucleotide region of the 3$\sp\prime$-UTR in unstimulated TA muscle. Computer analysis predicted a stem-loop structure of 17 nucleotides, which provides a structural basis for RNA-protein interaction. These 17 nucleotides are 100% conserved among rat, mouse and human cytochrome c genes and their 13 pseudogenes, suggesting a functional role for this region. The RNA-protein interaction was significantly less in highly active SO muscle than in inactive WV muscle and was dramatically decreased in stimulated TA muscle due to a protein inhibitor(s) associated with ribosome. It is possible that cytochrome c mRNAs undergoing translation are subject to a compartmentalized regulatory influence.^ The conclusion from these results is that increases in contractile activity induce or activate a protein inhibitor(s) associated with ribosome in rat skeletal muscle. The inhibitor decreases RNA-protein interaction in the 3$\sp\prime$-UTR of cytochrome c mRNA, which may result in increased mRNA stability and/or translation. ^

A novel DNA damage inducible inhibitor of p53

p53 is required for the maintenance of the genomic stability of cells. Mutations in the p53 tumor-suppressor gene occur in more than 50% of human cancers of diverse types. In addition, 70% of families with Li-Fraumeni syndrome have a germline mutation in p53, predisposing these individuals to multiple forms of cancer. In response to DNA damage, p53 becomes stabilized and activated. However the exact mechanism by which DNA damage signals the stabilization and activation of p53 still remains elusive. The biochemical activity of p53 that is required for tumor suppression, and presumably the cellular response to DNA damage, involves the ability of the protein to bind to specific DNA sequences and to function as a transcription factor. For the downstream targets, p53 transactivates many genes involved in growth arrest, apoptosis and DNA repair such as p21, Bax and GADD45, respectively. An open question in the field is how cells can determine the downstream effects of p53. ^ We hypothesize that, through its associated proteins, p53 can differentially transactivate its target genes, which determine its downstream effect. Additionally, p53 interacting proteins may be involved in signaling for the stabilization and activation of p53. Therefore, a key aspect to understanding p53 function is the identification and analysis of proteins that interact with it. We have employed the Sos recruitment system (SRS), a cytoplasmic yeast two-hybrid screen to identify p53 interacting proteins. The SRS is based on the ability of Sos to activate Ras when it becomes localized to the plasma membrane. The system takes advantage of an S. cerevisiae strain, cdc25-2 temperature sensitive mutant, harboring a mutation in Sos. In this strain, fusion proteins containing a truncated Sos will only localize to the membrane by protein-protein interaction, which allows growth at non-permissive temperature. This system allows the use of intact transcriptional activators such as p53. ^ To date, using a modified SRS library screen to identify p53 interacting proteins, I have identified p53 (known to interact with itself) and a novel p53-interacting protein (PIP). PIP is a specific p53 interacting protein in the SRS. The interaction of p53 and PIP was further confirmed by performing in vitro and in vivo binding assays. In the in vivo binding study, the interaction can only be detected in the presence of ionizing radiation suggesting that this interaction might be involved in DNA-damage induced p53-signalling pathway. After screening cDNA and genomic libraries, a full-length PIP-cDNA clone ( ∼ 3kb) was obtained which encodes a protein of 429 amino acids with calculated molecular weight of 46 kDa. The results of genebank search indicated that the PIP is an unidentified gene and contains a conserved ring-finger domain, which is present in a diverse family of regulatory proteins involved in different aspects of cellular function. Northern blot analysis revealed that the size of its messenge is approximately 3 kb preferentially expressed in brain, heart, liver and kidney. The PIP protein is mainly located in the cytoplasm as determined by the cellular localization of a green fluorescence fusion protein. Preliminary functional analysis revealed that PIP downregulated the transactivation activity of p53 on both p21 and mdm2 promoters. Thus, PIP may be a novel negative regulator of p53 subsequent to DNA damage. ^

Pollen records and lithology of profiles from Lobsigensee, Switzerland

Lobsigensee is a small kettle hole lake 15 km north-west of Bern on the Swiss Plateau, at an altitude of 514 m asl. Its surface is 2ha today, its maximum depth 2.7 m; it has no inlet and the overflow functions mainly during snow melting. The area was covered by Rhone ice during the Last Glaciation (map in Fig.2). Local geology, climate and vegetation are summarized in Figure 3A-C, the history of settlement in Figures 5-7. In order to reconstruct the vegetational and environmental history of the lake and its surroundings pollen analysis and other bio- and isotope stratigraphies were applied to twelve profiles cored across the basin with modified Livingstone corers (Fig.3 D). (1) The standard diagram: The central core LQ-90 is described as the standard pollen diagram (Chapter 3) with 10 local pollen assemblage zones of the Late-Glacial (local PAZ Ll to Ll0, from about 16'000(7) to 10'000 years BP) and 20 PAZ of the Holocene (local PAZ L11 to L30), see Figs. 8-10 and 20-24. Local PAZ L 1 to L3 are in the Late-Glacial clay and record the vegetational development after the ice retreat: L1 shows very low pollen concentration and high Pinus percentages due to long-distance transport and reworking; the latter mechanism is corroborated by the findings of thermophilous and pre-Quaternary taxa. Local PAZ L2 has a high di versi ty of non-arboreal pollen (NAP) and reflects the Late-Glacial steppe rich in heliophilous species. Local PAZ L3 is similar but additionally rich in Betula nana and Sal1x, thus reflecting a "shrub tundra". The PAZ L1 to L3 belong to the Oldest Dryas biozone. Local PAZ L4 to L 10 are found in the gyttja of the profundal or in the lake marl of the littoral and record the Late-Glacial forests. L4 is the shrub phase of reforestation with very high Junlperus and rapidly increasing Betula percentages. L5 is the PAZ with a first, L7 with a second dominance of tree-birches, separated by L6 showing a depression in the Betula curve. L4 to L7 can be assigned to the Balling biozone. Possible correlation of the Betula depression to the Older Dryas biozone is discussed. In local PAZ L8 Plnus immigrates and expands. L9 shows a facies difference in that Plnus dominates over Betula in littoral but not in profundal spectra. L8 and L9 belong to the Allerod biozone. In its youngest part the volcanic ash from Laach/Eifel is regularly found (11,000 BP). The local PAZ Ll0 corresponds to the Younger Dryas blozone. The merely slight increase of the NAP indicates that the pine forests of the lowland were not strongly affected by a cooler climate. In order to evaluate the significance of the littoral accumulation of coniferous pollen the littoral profile LQ-150 is compared to the profundal. Radiocarbon stratigraphies derived from different materials are presented in Figures 13 and 14 and in Tables 2 and 3. The hard-water errors in the gyttja samples and the carbonate samples are similar. The samples of terrestrial plant macrofossils are not affected by hard-water errors. Two plateaux of constant age appear in the age-depth relationship; their consequence for biostratigraphy as well as pollen concentration and influx diagrams are discussed. Radiocarbon ages of the Late-Glacial pollen zones are shown in Table 10. The Holocene vegetational history is recorded in the local PAZ L 11 to L30. After a Preboreal (PAZ L11) dominated by pine and birch the expansions of Corylus, Ulmus and Quercus are very rapid. Among these taxa Corylus dominates dur ing the Boreal (PAZ L 12 and L 1 3), whereas the components of the mixed oak forest dominate in the Older Atlantic (PAZ L14 to L16). In the Younger Atlantic (PAZ L 17 to L 19) Fagus and Alnus play an increasing, the mixed oak forest a decreasing role. During the period of local PAZ L19 Neolithic settlers lived on the shore of Lobsigensee. During the Subboreal (PAZ L20 and L21) and the Older Subatlantic (L22 to L25) strong fluctuations of Fagus and often antagonistic peaks of NAP, Alnus, Betula and Corylus can be interpreted as signs of human impact on vegetation. L23 is characterized not only by high values of NAP (especially apophytes and anthropochorous species) but also by the appearance of Juglans, Castanea and Secale which point to the Roman colonization of the area. For a certain period during the Younger Subatlantic (PAZ L26 to L30) the lake was used for retting hemp (Cannabis). Later the dominance of Quercus pollen indicates the importance of wood pastures. The youngest sediments reflect the wide-spread agricultural grass lands and the plantation of Pinus and Picea. Radiocarbon dates for the Holocene are given in Figure 23 and Table 4, the extrapolated ages of the Holocene pollen zones in Table 15. (2) The cross sections: Figures 25 and 26 give a summary of the litho- and palynostratigraphy of the two cross sections. Based on 11 Late-Glacial and 9 Holocene pollen diagrams (in addition to the standard ones), the consistency of the criteria for the definition of the pollen zones is examined in Tables 7 and 8 for the Late-Glacial and in Tables 11 to 14 for the Holocene. Sediment thicknesses across the basin for each pollen zone are presented in these tables as well as in Figures 43 to 45 for the Late-Glacial and in Figures 59 to 65 for the Holocene. Sediment focusing can explain differences between the gyttja cores of the profundal. Focusing is more than compensated for through "stretching" by carbonate precipitation on the littoral terrace. Pollen influx to the cross section are discussed (Chapters 4.1.5. and 4.2.3.). (3) The regional pollen zones: Based on some selected sites between Lake Geneva and Lake Constance regional pollen zones are proposed (Table 16, 17 and 19). (4) Paleoecology: Climatic change in the Late-Glacial can be inferred from Coleoptera, Trichoptera, Chironomidae and d18O of carbonates: a distinct warming is recorded around 12' 600 BP and around 10' 000 BP. The Younger Dryas biozone (10'700-10'000 BP) was the only cooling found in the Late-Glacial. The Betula depression often correlated wi th the Older Dryas biozone was possibl not colder but dryer than the previous period. During the Holocene the lowland site is not very sensitive to the minor climatic changes. Table 22 summarizes climatic and trophic changes before 8'000 BP as deduced from various biostratigraphies studied by a number of authors. Ostracods, Chironomids and fossil pigments indicate that anoxic conditions prevailed during the BoIling (possibly meromixis). Changes in the lake level are illustrated in Figure 74. A first lake-level lowering occurred in the early Holocene (10'000 to 9'000 BP), a second during the Atlantic (about 6'800 to 5'200 BP). The first "shrinking" of the lake volume resulted in a eutrophication recorded by laminations in the profundal and by pigments of Cyanophyceae. The second fall in water level corresponds to an increase of Nymphaeaceae. Human impact can be inferred in three ways: eutrophication of the lake (since the Neolithic), changes of terrestrial vegetation by deforestations (cyclicity of Fagus, see Figures 78 to 80), and enhanced erosion (increasing sedimentation rates by inwashed clay, particularly since the Roman Colonization, see Figures 49 and 81). Summary: This paper was planned as the final report on Lobsigensee. However, a number of issues are not answered but can only be asked more precisely, for example: (1) For the two periods with the highest rates of change, Le. the Bolling and the Preboreal biozones, pollen influx may reflect vegetation dynamics. Detailed investigations of these periods in annually laminated sediments are planned. (2) Biostratigraphies other than palynostratigraphy are needed to estimate the degree of linkage or independence in the development of terrestrial and lacustrine ecosystems. Often our sampling intervals were not identical, thus influencing our temporal resolution. (3) 6180- and 14C-stratigraPhies with high resolution will elucidate the leads and lags of these dynamic periods. Plateaux of constant age in the age-depth relationship have a strong bearing on both biological and geophysical understanding of Late-Glacial and early Holocene developments. (4) Numerical methods applied to the pollen diagrams of the cross section will help to quantify the significance of similari ties and dissimilarities across a single basin (with Prof. Birks). (5) Numerical methods applied to different sites on the Swiss Plateau and on the transect across the Alps will be helpful in evaluating the influence of different environmental factors (with Prof. Birks). (6) A new map 1: 1000 with 50cm-contour lines prov ided by Prof. Zurbuchen will be combined with a grid of cores sampling the transition from lake marl to peat enabling us to calculate paleo-volumes of the lake. This is interesting for the two "shrinking periods" (in Fig. 74A numbers 2-6 and 7-10), both accompanied by eutrophication. The pal eo-volume during the Neoli thic set tlement of the Cortaillod culture linked wi th an est l.mate of trophic change derived from diatoms (Prof. Smol in prep.) could possibly give an indication of the size of the human population of this period. (7) For the period with the antagonism between Fagus peaks and ABC-peaks close collaboration between palynologists, geochemists and archeologists should enable us to determine the influence of prehistoric and historic people on vegetation (collaboration with Prof. Stockli and Prof. Herzig). (8) The core LL-75 taken with a "cold letter box" will be analysed for major and trace elements by Dr. Sturm for 210pb and 137Cs by Prof.von Gunten and for pollen. We will see if our local PAZ L30 really corresponds to the surface sediment and if the small seepage lake reflects modern pollution.

Evaluation of a transplantation algorithm for expressive speech synthesis

When designing human-machine interfaces it is important to consider not only the bare bones functionality but also the ease of use and accessibility it provides. When talking about voice-based inter- faces, it has been proven that imbuing expressiveness into the synthetic voices increases signi?cantly its perceived naturalness, which in the end is very helpful when building user friendly interfaces. This paper proposes an adaptation based expressiveness transplantation system capable of copying the emotions of a source speaker into any desired target speaker with just a few minutes of read speech and without requiring the record- ing of additional expressive data. This system was evaluated through a perceptual test for 3 speakers showing up to an average of 52% emotion recognition rates relative to the natural voice recognition rates, while at the same time keeping good scores in similarity and naturality.

Extending the expressiveness of fuzzy logic languages

En el trabajo que aquí presentamos se incluye la base teórica (sintaxis y semántica) y una implementación de un framework para codificar el razonamiento de la representación difusa o borrosa del mundo (tal y como nosotros, seres humanos, entendemos éste). El interés en la realización de éste trabajo parte de dos fuentes: eliminar la complejidad existente cuando se realiza una implementación con un lenguaje de programación de los llamados de propósito general y proporcionar una herramienta lo suficientemente inteligente para dar respuestas de forma constructiva a consultas difusas o borrosas. El framework, RFuzzy, permite codificar reglas y consultas en una sintaxis muy cercana al lenguaje natural usado por los seres humanos para expresar sus pensamientos, pero es bastante más que eso. Permite representar conceptos muy interesantes, como fuzzificaciones (funciones usadas para convertir conceptos no difusos en difusos), valores por defecto (que se usan para devolver resultados un poco menos válidos que los que devolveríamos si tuviésemos la información necesaria para calcular los más válidos), similaridad entre atributos (característica que utilizamos para buscar aquellos individuos en la base de datos con una característica similar a la buscada), sinónimos o antónimos y, además, nos permite extender el numero de conectivas y modificadores (incluyendo modificadores de negación) que podemos usar en las reglas y consultas. La personalización de la definición de conceptos difusos (muy útil para lidiar con el carácter subjetivo de los conceptos borrosos, donde nos encontramos con que cualificar a alguien de “alto” depende de la altura de la persona que cualifica) es otra de las facilidades incluida. Además, RFuzzy implementa la semántica multi-adjunta. El interés en esta reside en que introduce la posibilidad de obtener la credibilidad de una regla a partir de un conjunto de datos y una regla dada y no solo el grado de satisfacción de una regla a partir de el universo modelado en nuestro programa. De esa forma podemos obtener automáticamente la credibilidad de una regla para una determinada situación. Aún cuando la contribución teórica de la tesis es interesante en si misma, especialmente la inclusión del modificador de negacion, sus multiples usos practicos lo son también. Entre los diferentes usos que se han dado al framework destacamos el reconocimiento de emociones, el control de robots, el control granular en computacion paralela/distribuída y las busquedas difusas o borrosas en bases de datos. ABSTRACT In this work we provide a theoretical basis (syntax and semantics) and a practical implementation of a framework for encoding the reasoning and the fuzzy representation of the world (as human beings understand it). The interest for this work comes from two sources: removing the existing complexity when doing it with a general purpose programming language (one developed without focusing in providing special constructions for representing fuzzy information) and providing a tool intelligent enough to answer, in a constructive way, expressive queries over conventional data. The framework, RFuzzy, allows to encode rules and queries in a syntax very close to the natural language used by human beings to express their thoughts, but it is more than that. It allows to encode very interesting concepts, as fuzzifications (functions to easily fuzzify crisp concepts), default values (used for providing results less adequate but still valid when the information needed to provide results is missing), similarity between attributes (used to search for individuals with a characteristic similar to the one we are looking for), synonyms or antonyms and it allows to extend the number of connectives and modifiers (even negation) we can use in the rules. The personalization of the definition of fuzzy concepts (very useful for dealing with the subjective character of fuzziness, in which a concept like tall depends on the height of the person performing the query) is another of the facilities included. Besides, RFuzzy implements the multi-adjoint semantics. The interest in them is that in addition to obtaining the grade of satisfaction of a consequent from a rule, its credibility and the grade of satisfaction of the antecedents we can determine from a set of data how much credibility we must assign to a rule to model the behaviour of the set of data. So, we can determine automatically the credibility of a rule for a particular situation. Although the theoretical contribution is interesting by itself, specially the inclusion of the negation modifier, the practical usage of it is equally important. Between the different uses given to the framework we highlight emotion recognition, robocup control, granularity control in parallel/distributed computing and flexible searches in databases.