Showing papers by "Martin Luther University of Halle-Wittenberg published in 2001"

On the Surprising Behavior of Distance Metrics in High Dimensional Spaces

Abstract: In recent years, the effect of the curse of high dimensionality has been studied in great detail on several problems such as clustering, nearest neighbor search, and indexing. In high dimensional space the data becomes sparse, and traditional indexing and algorithmic techniques fail from a efficiency and/or effectiveness perspective. Recent research results show that in high dimensional space, the concept of proximity, distance or nearest neighbor may not even be qualitatively meaningful. In this paper, we view the dimensionality curse from the point of view of the distance metrics which are used to measure the similarity between objects. We specifically examine the behavior of the commonly used Lk norm and show that the problem of meaningfulness in high dimensionality is sensitive to the value of k. For example, this means that the Manhattan distance metric (L1 norm) is consistently more preferable than the Euclidean distance metric (L2 norm) for high dimensional data mining applications. Using the intuition derived from our analysis, we introduce and examine a natural extension of the Lk norm to fractional distance metrics. We show that the fractional distance metric provides more meaningful results both from the theoretical and empirical perspective. The results show that fractional distance metrics can significantly improve the effectiveness of standard clustering algorithms such as the k-means algorithm.

Study of Health in Pomerania (SHIP): A health examination survey in an east German region: Objectives and design

Abstract: Objectives The reason for the Study of Health in Pomerania (SHIP) is the lack of epidemiological studies with a broad range of health indicators. Furthermore, in Germany there is a need for studies that take into account the particular situation of life after the reunification. One objective of SHIP is to provide prevalence estimates on a broad range of diseases, risk and health factors for a defined region in the former GDR.

Fluorescent J‐type Aggregates and Thermotropic Columnar Mesophases of Perylene Bisimide Dyes

Abstract: A series of perylene tetracarboxylic acid bisimides 3 a–e bearing 3,4,5-tridodecyloxyphenyl substituents on the imide N atoms and zero, two, or four phenoxy-type substituents in the bay positions of the perylene core were synthesized. From investigations of their spectroscopic properties and aggregation behavior in low-polarity solvents by absorption and fluorescence optical spectroscopy, not only were these compounds found to form fluorescent J-type aggregates, but also binding constants for aggregation could be derived which reflect the number and steric demand of the phenoxy substituents for bisimides 3 a–d. In the pristine state, 3 a–d form thermotropic hexagonal columnar mesophases which exist over a broad temperature range from below −30 °C to over 300 °C. For the tetraphenoxy-substituted compound 3 e, however, a layered crystalline structure was found. This difference in behavior can be explained by the concept of microphase segregation of the aromatic cores of the molecules and the alkyl chains at the periphery. The high stability and bright fluorescence of the mesophase of several of the compounds make them promising for applications as polarizers or components in (opto)electronic devices.

Symptoms during cancer pain treatment following WHO-guidelines: a longitudinal follow-up study of symptom prevalence, severity and etiology.

Abstract: Most patients with advanced cancer develop diverse symptoms that can limit the efficacy of pain treatment and undermine their quality of life. The present study surveys symptom prevalence, etiology and severity in 593 cancer patients treated by a pain service. Non-opioid analgesics, opioids and adjuvants were administered following the WHO-guidelines for cancer pain relief. Other symptoms were systematically treated by appropriate adjuvant drugs. Pain and symptom severity was measured daily by patient self-assessment; the physicians of the pain service assessed symptom etiology and the severity of confusion, coma and gastrointestinal obstruction at each visit. The patients were treated for an average period of 51 days. Efficacy of pain treatment was good in 70%, satisfactory in 16% and inadequate in 14% of patients. The initial treatment caused a significant reduction in the average number of symptoms from four to three. Prevalence and severity of anorexia, impaired activity, confusion, mood changes, insomnia, constipation, dyspepsia, dyspnoea, coughing, dysphagia and urinary symptoms were significantly reduced, those of sedation, other neuropsychiatric symptoms and dry mouth were significantly increased and those of coma, vertigo, diarrhea, nausea, vomiting, intestinal obstruction, erythema, pruritus and sweating remained unchanged. The most frequent symptoms were impaired activity (74% of days), mood changes (22%), constipation (23%), nausea (23%) and dry mouth (20%). The highest severity scores were associated with impaired activity, sedation, coma, intestinal obstruction, dysphagia and urinary symptoms. Of all 23 symptoms, only constipation, erythema and dry mouth were assessed as being most frequently caused by the analgesic regimen. In conclusion, the high prevalence and severity of many symptoms in far advanced cancer can be reduced, if pain treatment is combined with systematic symptom control. Nevertheless, general, neuropsychiatric and gastrointestinal symptoms are experienced during a major part of treatment time and pain relief was inadequate in 14% of patients. Cancer pain management has to be embedded in a frame of palliative care, taking all the possibilities of symptom management into consideration.

NO-independent regulatory site on soluble guanylate cyclase

Abstract: Nitric oxide (NO) is a widespread, potent, biological mediator that has many physiological and pathophysiological roles1. Research in the field of NO appears to have followed a straightforward path, and the findings have been progressive: NO and cyclic GMP are involved in vasodilatation; glycerol trinitrate relaxes vascular smooth muscles by bioconversion to NO; mammalian cells synthesize NO; and last, NO mediates vasodilatation by stimulating the soluble guanylate cyclase (sGC), a heterodimeric (α/β) haem protein that converts GTP to cGMP2–4. Here we report the discovery of a regulatory site on sGC. Using photoaffinity labelling, we have identified the cysteine 238 and cysteine 243 region in the α1-subunit of sGC as the target for a new type of sGC stimulator. Moreover, we present a pyrazolopyridine, BAY 41-2272, that potently stimulates sGC through this site by a mechanism that is independent of NO. This results in antiplatelet activity, a strong decrease in blood pressure and an increase in survival in a low-NO rat model of hypertension, and as such may offer an approach for treating cardiovascular diseases.

Micro-segregation, molecular shape and molecular topology – partners for the design of liquid crystalline materials with complex mesophase morphologies

Abstract: This article gives an overview of recent progress in the design of novel materials, capable of forming liquid crystalline phases with non-conventional mesophase morphologies. The materials include dendritic molecules, ternary block-copolymers, rod–coil molecules and linear as well as non-linear polyphilic low molecular weight block molecules incorporating rigid segments with a specific shape. Changing the shape of the rigid segments from rod-like to disc-like or to a bent shape leads to additional possibilities for the directed design of mesophase forming materials. Many of these molecules are able to form quite unusual mesophase morphologies, distinct from the conventional lamellar (smectic) and columnar mesophases of classical rod-like and disc-like liquid crystals; they include mesophases which combine lamellar and columnar organisation, columnar mesophases incorporating three discrete sets of columns, biaxial smectic phases, such as the SmAb-phase (McMillan Phase), polar smectic phases and non-conventional layer structures in which rigid units are aligned parallel to the layers. These novel mesophase morphologies were realised by increasing the number of incompatible units combined in these molecules, by changing the volume fractions of the incompatible segments, by tailoring the shape of rigid segments and by controlling the molecular topology.

Cyclooxygenase-2: a novel target for cancer chemotherapy?

Abstract: Epidemiologic studies have documented a 40-50% reduction in incidence of colorectal cancer in individuals taking nonsteroidal antiinflammatory drugs (NSAIDs). Since NSAIDs are known to inhibit cyclooxygenases (COX-1, COX-2), the basic mechanism of their antitumor effects is conceivably the altered metabolism of arachidonic acid and, subsequently, prostaglandins (PGs). Although COX-2, the inducible isoform, is regularly expressed at low levels in colonic mucosa, its activity increases dramatically following mutation of the APC (adenomatous polyposis coli) gene suggesting that beta-catenin/T-cell factor mediated Wnt-signaling activity may regulate COX-2 gene expression. In addition, hypoxic conditions and sodium butyrate exposure may also contribute to COX-2 gene transcription in human cancers. The development of selective COX-2 inhibitors has made it possible to further evaluate the role of COX-2 activity in colorectal carcinogenesis. To date, at least five mechanisms by which COX-2 contributes to tumorigenesis and the malignant phenotype of tumor cells have been identified, including: (1) inhibition of apoptosis; (2) increased angiogenesis; (3) increased invasiveness; (4) modulation of inflammation/immuno-suppression; and (5) conversion of procarcinogens to carcinogens. A clear positive correlation between COX-2 expression and inhibition of apoptosis has been established, associated with increased PGE2 levels resulting in modulation of pro- and anti-apoptotic factors (e.g., bcl-2, MAKs/ras, caspase-3, Par-4). In terms of angiogenesis and invasiveness, COX-2 activity was found to increase the expression of growth factors (e.g., VDEG, PDGF, bFGF) and matrix metalloproteinases (MMPs). Since COX-2 inhibitors have been demonstrated to interfere with tumorigenesis and apoptosis, COX-2 and its gene product may be attractive targets for therapeutic and chemoprotective strategies in colorectal cancer patients. This may lead to new perspectives that by controlling the cancer phenotype, rather than attempting to eradicate all affected cells, may provide significant benefits to the cancer patient.

Carving personality description at its joints: Confirmation of three replicable personality prototypes for both children and adults

Abstract: We tested the hypothesis that there are three major prototypic patterns of personality description (resilient, overcontrolled, and undercontrolled) in a series of studies including adults' self-descriptions on the Big Five and parents' Big Five and Q-Sort judgments of their childern, using both replicated cluster analyses and replicated Q-factor analyses. The consistency of the prototypes across ages, judges, and methods was quantitatively measured. The results confirmed the hypothesis in all studies. Personality social relationship, and social interaction correlates of the prototypes indicated externalizing tendencies for undercontrollers and internalizing tendencies for overcontrollers for both childern and adults. The studies provide strong evidence for a three-prototype model of personality description at the highest level of analysis for both childhood and adulthood. Copyright (C) 2001 John Wiley & Sons, Ltd.

Black hole entropy, special geometry and strings

Abstract: We review work done over the last years on the macroscopic and microscopic entropy of supersymmetric black holes in fourdimensional = 2 supergravity and in = 2 compactifications of string theory and M-theory. Particular emphasis is put on the crucial role of higher curvature terms and of modifications of the area law in obtaining agreement between the macroscopic entropy, which is a geometric property of black hole solutions and the microscopic entropy, which is computed by state counting in Calabi-Yau compactifications of string or M-theory. We also discuss invariance properties of the entropy under stringy T-duality and S-duality transformations in = 2,4 compactifications in presence of higher curvature terms. In order to make the paper self-contained we review the laws of black hole mechanics in higher derivative gravity, the definition of entropy as a surface charge, the superconformal off-shell description of = 2 supergravity, special geometry, and = 2 compactifications of heterotic and type II string theory and of M-theory.

The Arabidopsis thaliana genome contains at least 29 active genes encoding SET domain proteins that can be assigned to four evolutionarily conserved classes

Abstract: SET domains are conserved amino acid motifs present in chromosomal proteins that function in epigenetic control of gene expression. These proteins can be divided into four classes as typified by their Drosophila members E(Z), TRX, ASH1 and SU(VAR)3-9. Homologs of all four classes have been identified in yeast and mammals, but not in plants. A BLASTP screening of the Arabidopsis genome identified 37 genes: three E(z) homologs, five trx homologs, four ash1 homologs and 15 genes similar to Su(var)3-9. Seven genes were assigned as trx-related and three as ash1-related. Only four genes have been described previously. Our classification is based on the characteristics of the SET domains, cysteine-rich regions and additional conserved domains, including a novel YGD domain. RT-PCR analysis, cDNA cloning and matching ESTs show that at least 29 of the genes are active in diverse tissues. The high number of SET domain genes, possibly involved in epigenetic control of gene activity during plant development, can partly be explained by extensive genome duplication in Arabidopsis. Additionally, the lack of introns in the coding region of eight SU(VAR)3-9 class genes indicates evolution of new genes by retrotransposition. The identification of putative nuclear localization signals and AT-hooks in many of the proteins supports an anticipated nuclear localization, which was demonstrated for selected proteins.

Individual differences in creativity: personality, story writing, and hobbies

Abstract: This study investigated the relationship between creativity and personality among college students from a variety of major fields of study. Indicators of creativity were ratings of written stories, lists of personal hobbies, and scores on the Creative Personality Scale (CPS; Gough, 1979). Personality was assessed broadly using the NEO-Five Factor Inventory (Costa and McCrae, 1985) as well as measures of depersonalization, intolerance of ambiguity, faith in intuition, and problem-solving styles. The results showed a positive relationship between openness to experience and all creativity measures. Moreover, high scores on intuition and extraversion were the best predictors for creativity as measured by the CPS. Story creativity was predicted by low scores on conscientiousness. Depersonalization was not significantly related to creativity. The results of this investigation confirm and extend previous research in demonstrating a close association between creativity and specific personality traits. Future research should clarify the nature of the creative personality across individuals of differing levels and domains of expertise. Copyright © 2001 John Wiley & Sons, Ltd.

Intergenerational Transmission of Collectivism and Achievement Values in Two Acculturation Contexts The Case of Turkish Families in Germany and Turkish and Moroccan Families in the Netherlands

Abstract: This study examines the impact of parental goals and acculturation contexts on value transmission in immigrant families. Combining cross-national and cross-ethnic comparisons, 400 Turkish parent-child dyads in Germany and 190 Turkish and Moroccan dyads in the Netherlands were asked to report their commitment to family-based collectivism and individualism, their academic aspirations, as well as conformity, autonomy, and achievement goal stresses in their family. First, value transmission was selective. Across cultures, parental collectivism values were transmitted, but not individualism. Only in Germany, parental aspirations were also transmitted. Second, value transmission was mediated by parental goals. Across cultures, more collectivistic parents stressed conformity more, thereby enhancing effective transmission. Third, transmission was significant after controlling for gender and educational status of parents and youngsters. Finally, our transmission model was replicated across acculturation contexts a...

Interleukin-10 targets p38 MAPK to modulate ARE-dependent TNF mRNA translation and limit intestinal pathology

Abstract: Interleukin-10 (IL-10) is a key inhibitory signal of inflammatory responses that regulates the production of potentially pathogenic cytokines like tumor necrosis factor (TNF). We show here that the development of chronic intestinal inflammation in IL-10-deficient mice requires the function of TNF, indicating that the IL-10/TNF axis regulates mucosal immunity. We further show that IL-10 targets the 3′ AU-rich elements (ARE) of TNF mRNA to inhibit its translation. Moreover, IL-10 does not alter TNF mRNA stability, and its action does not require the presence of the stability-regulating ARE binding factor tristetraprolin, indicating a differential assembly of stability and translation determinants on the TNF ARE. Inhibition of TNF translation by IL-10 is exerted mainly by inhibition of the activating p38/MAPK-activated protein kinase-2 pathway. These results demonstrate a physiologically significant cross-talk between the IL-10 receptor and the stress-activated protein kinase modules targeting TNF mRNA translation. This cross-talk is necessary for optimal TNF production and for the maintenance of immune homeostasis in the gut.

Development, standardization, and testing of a lexicon for reporting contrast-enhanced breast magnetic resonance imaging studies.

Abstract: The purpose of this study was to develop, standardize, and test reproducibility of a lexicon for reporting contrast-enhanced breast magnetic resonance imaging (MRI) examinations. To standardize breast MRI lesion description and reporting, seven radiologists with extensive breast MRI experience developed consensus on technical detail, clinical history, and terminology reporting to describe kinetic and architectural features of lesions detected on contrast-enhanced breast MR images. This lexicon adapted American College of Radiology Breast Imaging and Data Reporting System terminology for breast MRI reporting, including recommendations for reporting clinical history, technical parameters for breast MRI, descriptions for general breast composition, morphologic and kinetic characteristics of mass lesions or regions of abnormal enhancement, and overall impression and management recommendations. To test morphology reproducibility, seven radiologists assessed morphology characteristics of 85 contrast-enhanced breast MRI studies. Data from each independent reader were used to compute weighted and unweighted kappa (κ) statistics for interobserver agreement among readers. The MR lexicon differentiates two lesion types, mass and non-mass-like enhancement based on morphology and geographical distribution, with descriptors of shape, margin, and internal enhancement. Lexicon testing showed substantial agreement for breast density (κ = 0.63) and moderate agreement for lesion type (κ = 0.57), mass margins (κ = 0.55), and mass shape (κ = 0.42). Agreement was fair for internal enhancement characteristics. Unweighted kappa statistics showed highest agreement for the terms dense in the breast composition category, mass in lesion type, spiculated and smooth in mass margins, irregular in mass shape, and both dark septations and rim enhancement for internal enhancement characteristics within a mass. The newly developed breast MR lexicon demonstrated moderate interobserver agreement. While breast density and lesion type appear reproducible, other terms require further refinement and testing to lead to a uniform standard language and reporting system for breast MRI. J. Magn. Reson. Imaging 2001;13:889–895. © 2001 Wiley-Liss, Inc.

Surgical Treatment: Evidence-Based and Problem-Oriented

Abstract: "Surgical Treatment – Evidence-Based and Problem-Oriented" is based upon a concept which the editors believe will become increasingly important in the preparation of clinical textbooks in the 21st century, namely the quality of the evidence upon which currently accepted clinical practice is based needs to be assessed frankly and taken into account when recommendations for patient treatment are made. As is apparent in many of the chapters in this volume, the authors are frequently forced to conclude that a higher level of evidence than is currently available would be necessary in order establish the validity of the currently accepted management of a wide variety of common surgical problems. The editors believe this is a fact of which both students and surgical practitioners need to be aware, so that they may be prepared to update and alter their clinical decision making on the basis of higher levels of evidence when these become available. The editors also hope that increasing awareness of the low level of evidence upon which much present day surgical practice is based will prompt surgeons from many countries to plan or at least participate in clinical trials to achieve a higher quality of evidence upon which to base a more rational clinical practice.

Induction of NAD(P)H oxidase by oxidized low-density lipoprotein in human endothelial cells: antioxidative potential of hydroxymethylglutaryl coenzyme A reductase inhibitor therapy.

Abstract: Background Elevated oxidative stress and superoxide anion formation in vascular cells could promote conversion of LDL to atherogenic oxidized LDL (oxLDL), contributing to endothelial dysfunction and atherosclerosis. As a major source of vascular superoxide anion formation, an endothelial NAD(P)H oxidase, similar to the leukocyte enzyme, has been identified. Methods and Results To elucidate functional differences between NAD(P)H oxidases of endothelial cells and leukocytes, DNA sequences of endothelial NAD(P)H oxidase subunits were determined. Gp91phox cDNA sequence showed no difference between the 2 cell types. Endothelial p67phox cDNA sequence revealed 2 known polymorphisms, which do not affect NAD(P)H oxidase function. Next, we analyzed relative mRNA expression of NAD(P)H subunits in human umbilical vein endothelial cells (HUVECs) and leukocytes using a common cRNA standard in competitive reverse transcription–polymerase chain reaction. NAD(P)H oxidase subunits p22phox and p47phox are expressed at a sim...

Saccharomyces cerevisiae Elongator mutations confer resistance to the Kluyveromyces lactis zymocin.

Abstract: Kluyveromyces lactis killer strains secrete a zymocin complex that inhibits proliferation of sensitive yeast genera including Saccharomyces cerevisiae. In search of the putative toxin target (TOT), we used mTn3:: tagging to isolate zymocin-resistant tot mutants from budding yeast. Of these we identified the TOT1, TOT2 and TOT3 genes (isoallelic with ELP1, ELP2 and ELP3, respectively) coding for the histone acetyltransferase (HAT)-associated Elongator complex of RNA polymerase II holoenzyme. Other than the typical elp ts-phenotype, tot phenocopies hypersensitivity towards caffeine and Calcofluor White as well as slow growth and a G(1) cell cycle delay. In addition, TOT4 and TOT5 (isoallelic with KTI12 and IKI1, respectively) code for components that associate with ELONGATOR: Intriguingly, strains lacking non-Elongator HATs (gcn5, hat1, hpa3 and sas3) or non-Elongator transcription elongation factors TFIIS (dst1) and Spt4p (spt4) cannot confer resistance towards the K.lactis zymocin, thus providing evidence that Elongator equals TOT and that Elongator plays an important role in signalling toxicity of the K.lactis zymocin.

Influence of lateral substituents on the mesophase behaviour of banana-shaped mesogens

Abstract: In this paper we present selected members of 7 new series of bent-shaped five-ring resorcinol derivatives which are distinguished by substituents at the central core as well as at the outer rings. Depending on the kind and position of the substituents and depending on the length of the terminal chains not only have new mesophases (the CPA phase or three unidentified B2-like phases) been identified, but also interesting phase sequences have been observed (B2–N; B2–SmA; B2–SmA–SmC; B2–SmA–SmC–N).

Physical and functional association of SU(VAR)3-9 and HDAC1 in Drosophila.

Abstract: Modification of histones can have a dramatic impact on chromatin structure and function. Acetylation of lysines within the N-terminal tail of the histone octamer marks transcriptionally active regions of the genome whereas deacetylation seems to play a role in transcriptional silencing. Recently, the methylation of the histone tails has also been shown to be important for transcriptional regulation and chromosome structure. Here we show by immunoaffinity purification that two activities important for chromatin-mediated gene silencing, the histone methyltransferase SU(VAR)3-9 and the histone deacetylase HDAC1, associate in vivo. The two activities cooperate to methylate pre-acetylated histones. Both enzymes are modifiers of position effect variegation and interact genetically in flies. We suggest a model in which the concerted histone deacetylation and methylation by a SU(VAR)3-9/HDAC1-containing complex leads to a permanent silencing of transcription in particular areas of the genome.

The product of the ybde gene of the escherichia coli chromosome is involved in detoxification of silver ions

Abstract: Transcription of the ybcZ–ylcA ylcBCD–ybdE region of the Escherichia coli K38 chromosome was analysed by Northern RNA–DNA hybridization, RT-PCR and primer extension. Transcription of a dicistronic ybcZ–ylcA mRNA and a tetracistronic ylcBCD–ybdE mRNA was induced by silver and was initiated from the sigma-70 promoters ylcAp and ylcBp. Expression of β-galactosidase activity from a Φ(ylcBp–lacZ) operon fusion was also induced by Ag+ and Cu2+, but not by Zn2+. In-frame deletion of ybdE from the chromosome yielded a silver-sensitive E. coli mutant strain which did not differ in its copper resistance from its wild-type strain. On the other hand, deletion of the copA gene for the copper-exporting P-type ATPase CopA resulted in copper sensitivity, but not in silver sensitivity. A ΔybdE ΔcopA double mutant strain behaved towards copper as the ΔcopA strain and towards silver as the ΔybdE strain. Thus, in E. coli, the YlcBCD–YbdE system may be involved in silver- but not in copper resistance, and CopA may be involved in copper- but not in silver resistance.