Showing papers by "Martin Luther University of Halle-Wittenberg published in 2007"

SOM fractionation methods: Relevance to functional pools and to stabilization mechanisms

Abstract: Soil organic matter (SOM) consists of various functional pools that are stabilized by specific mechanisms and have certain turnover rates. For the development of mechanistic models that predict changes in SOM storage, these pools have to be quantified and characterized. In the past, numerous fractionation schemes have been developed to separate and analyse such SOM fractions. In this review, the SOM fractions obtained with such operational fractionation procedures are described in terms of their pool sizes, chemical properties, and turnover rates. The main objective of this review is to evaluate these operationally defined fractions with respect to their suitability to describe functional SOM pools that could be used to parameterize SOM turnover models. Fractionation procedures include (1) physical separation of SOM into aggregate, particle size, and density fractions and fractions according to their magnetic susceptibility, and (2) various wet chemical procedures that fractionate SOM according to solubility, hydrolysability, and resistance to oxidation or by destruction of the mineral phase. Furthermore, combinations of fractionation methods are evaluated. The active SOM pool with turnover rates

Intrinsic motions along an enzymatic reaction trajectory

Abstract: The mechanisms by which enzymes achieve extraordinary rate acceleration and specificity have long been of key interest in biochemistry. It is generally recognized that substrate binding coupled to conformational changes of the substrate-enzyme complex aligns the reactive groups in an optimal environment for efficient chemistry. Although chemical mechanisms have been elucidated for many enzymes, the question of how enzymes achieve the catalytically competent state has only recently become approachable by experiment and computation. Here we show crystallographic evidence for conformational substates along the trajectory towards the catalytically competent 'closed' state in the ligand-free form of the enzyme adenylate kinase. Molecular dynamics simulations indicate that these partially closed conformations are sampled in nanoseconds, whereas nuclear magnetic resonance and single-molecule fluorescence resonance energy transfer reveal rare sampling of a fully closed conformation occurring on the microsecond-to-millisecond timescale. Thus, the larger-scale motions in substrate-free adenylate kinase are not random, but preferentially follow the pathways that create the configuration capable of proficient chemistry. Such preferred directionality, encoded in the fold, may contribute to catalysis in many enzymes.

Comparison of quantification methods to measure fire-derived (black/elemental) carbon in soils and sediments using reference materials from soil, water, sediment and the atmosphere

Abstract: Black carbon (BC), the product of incomplete combustion of fossil fuels and biomass (called elemental carbon (EC) in atmospheric sciences), was quantified in 12 different materials by 17 laboratories from different disciplines, using seven different methods. The materials were divided into three classes: (1) potentially interfering materials, (2) laboratory-produced BC-rich materials, and (3) BC-containing environmental matrices (from soil, water, sediment, and atmosphere). This is the first comprehensive intercomparison of this type (multimethod, multilab, and multisample), focusing mainly on methods used for soil and sediment BC studies. Results for the potentially interfering materials (which by definition contained no fire-derived organic carbon) highlighted situations where individual methods may overestimate BC concentrations. Results for the BC-rich materials (one soot and two chars) showed that some of the methods identified most of the carbon in all three materials as BC, whereas other methods identified only soot carbon as BC. The different methods also gave widely different BC contents for the environmental matrices. However, these variations could be understood in the light of the findings for the other two groups of materials, i.e., that some methods incorrectly identify non-BC carbon as BC, and that the detection efficiency of each technique varies across the BC continuum. We found that atmospheric BC quantification methods are not ideal for soil and sediment studies as in their methodology these incorporate the definition of BC as light-absorbing material irrespective of its origin, leading to biases when applied to terrestrial and sedimentary materials. This study shows that any attempt to merge data generated via different methods must consider the different, operationally defined analytical windows of the BC continuum detected by each technique, as well as the limitations and potential biases of each technique. A major goal of this ring trial was to provide a basis on which to choose between the different BC quantification methods in soil and sediment studies. In this paper we summarize the advantages and disadvantages of each method. In future studies, we strongly recommend the evaluation of all methods analyzing for BC in soils and sediments against the set of BC reference materials analyzed here.

Cyclic adenosine monophosphate is a key component of regulatory T cell–mediated suppression

Abstract: Naturally occurring regulatory T cells (T reg cells) are a thymus-derived subset of T cells, which are crucial for the maintenance of peripheral tolerance by controlling potentially autoreactive T cells. However, the underlying molecular mechanisms of this strictly cell contact–dependent process are still elusive. Here we show that naturally occurring T reg cells harbor high levels of cyclic adenosine monophosphate (cAMP). This second messenger is known to be a potent inhibitor of proliferation and interleukin 2 synthesis in T cells. Upon coactivation with naturally occurring T reg cells the cAMP content of responder T cells is also strongly increased. Furthermore, we demonstrate that naturally occurring T reg cells and conventional T cells communicate via cell contact–dependent gap junction formation. The suppressive activity of naturally occurring T reg cells is abolished by a cAMP antagonist as well as by a gap junction inhibitor, which blocks the cell contact–dependent transfer of cAMP to responder T cells. Accordingly, our results suggest that cAMP is crucial for naturally occurring T reg cell–mediated suppression and traverses membranes via gap junctions. Hence, naturally occurring T reg cells unexpectedly may control the immune regulatory network by a well-known mechanism based on the intercellular transport of cAMP via gap junctions.

A bacterial effector acts as a plant transcription factor and induces a cell size regulator.

Abstract: Pathogenicity of many Gram-negative bacteria relies on the injection of effector proteins by type III secretion into eukaryotic cells, where they modulate host signaling pathways to the pathogen's benefit. One such effector protein injected by Xanthomonas into plants is AvrBs3, which localizes to the plant cell nucleus and causes hypertrophy of plant mesophyll cells. We show that AvrBs3 induces the expression of a master regulator of cell size, upa20, which encodes a transcription factor containing a basic helix-loop-helix domain. AvrBs3 binds to a conserved element in the upa20 promoter via its central repeat region and induces gene expression through its activation domain. Thus, AvrBs3 and likely other members of this family provoke developmental reprogramming of host cells by mimicking eukaryotic transcription factors.

Epidemiology of sepsis in Germany: results from a national prospective multicenter study

Abstract: To determine the prevalence and mortality of ICU patients with severe sepsis in Germany, with consideration of hospital size. Prospective, observational, cross-sectional 1-day point-prevalence study. 454 ICUs from a representative nationwide sample of 310 hospitals stratified by size. Data were collected via 1-day on-site audits by trained external study physicians. Visits were randomly distributed over 1 year (2003). Inflammatory response of all ICU patients was assessed using the ACCP/SCCM consensus conference criteria. Patients with severe sepsis were followed up after 3 months for hospital mortality and length of ICU stay. Main outcome measures were prevalence and mortality. A total of 3,877 patients were screened. Prevalence was 12.4% (95% CI, 10.9–13.8%) for sepsis and 11.0% (95% CI, 9.7–12.2%) for severe sepsis including septic shock. The ICU and hospital mortality of patients with severe sepsis was 48.4 and 55.2%, respectively, without significant differences between hospital size. Prevalence and mean length of ICU stay of patients with severe sepsis were significantly higher in larger hospitals and universities (≤ 200 beds: 6% and 11.5 days, universities: 19% and 19.2 days, respectively). The expected number of newly diagnosed cases with severe sepsis in Germany amounts to 76–110 per 100,000 adult inhabitants. To allow better comparison between countries, future epidemiological studies should use standardized study methodologies with respect to sepsis definitions, hospital size, and daily and monthly variability.

Plant pathogen recognition mediated by promoter activation of the pepper Bs3 resistance gene.

Abstract: Plant disease resistance (R) proteins recognize matching pathogen avirulence proteins. Alleles of the pepper R gene Bs3 mediate recognition of the Xanthomonas campestris pv. vesicatoria (Xcv) type III effector protein AvrBs3 and its deletion derivative AvrBs3Deltarep16. Pepper Bs3 and its allelic variant Bs3-E encode flavin monooxygenases with a previously unknown structure and are transcriptionally activated by the Xcv effector proteins AvrBs3 and AvrBs3Deltarep16, respectively. We found that recognition specificity resides in the Bs3 and Bs3-E promoters and is determined by binding of AvrBs3 or AvrBs3Deltarep16 to a defined promoter region. Our data suggest a recognition mechanism in which the Avr protein binds and activates the promoter of the cognate R gene.

Liquid crystal engineering – new complex mesophase structures and their relations to polymer morphologies, nanoscale patterning and crystal engineering

Abstract: This critical review focuses on recent progress in the field of T-shaped ternary amphiphiles. These molecules can self-assemble into a series of new liquid crystalline (LC) phases with polygonal cylinder structures, new lamellar phases and LC phases combining columns and layers. These structures are analyzed on the basis of symmetry, net topology and tiling pattern (Laves and Archimedean tilings) and discussed in relation to morphologies of multiblock copolymers, self organized DNA super-lattices, metal–organic frameworks, crystal-engineering and self-assembled periodic superstructures on surfaces (210 references).

The ribosomal protein genes and Minute loci of Drosophila melanogaster

Abstract: Mutations in genes encoding ribosomal proteins (RPs) have been shown to cause an array of cellular and developmental defects in a variety of organisms. In Drosophila melanogaster, disruption of RP genes can result in the 'Minute' syndrome of dominant, haploinsufficient phenotypes, which include prolonged development, short and thin bristles, and poor fertility and viability. While more than 50 Minute loci have been defined genetically, only 15 have so far been characterized molecularly and shown to correspond to RP genes. We combined bioinformatic and genetic approaches to conduct a systematic analysis of the relationship between RP genes and Minute loci. First, we identified 88 genes encoding 79 different cytoplasmic RPs (CRPs) and 75 genes encoding distinct mitochondrial RPs (MRPs). Interestingly, nine CRP genes are present as duplicates and, while all appear to be functional, one member of each gene pair has relatively limited expression. Next, we defined 65 discrete Minute loci by genetic criteria. Of these, 64 correspond to, or very likely correspond to, CRP genes; the single non-CRP-encoding Minute gene encodes a translation initiation factor subunit. Significantly, MRP genes and more than 20 CRP genes do not correspond to Minute loci. This work answers a longstanding question about the molecular nature of Minute loci and suggests that Minute phenotypes arise from suboptimal protein synthesis resulting from reduced levels of cytoribosomes. Furthermore, by identifying the majority of haplolethal and haplosterile loci at the molecular level, our data will directly benefit efforts to attain complete deletion coverage of the D. melanogaster genome.

Effect of Core Twisting on Self-Assembly and Optical Properties of Perylene Bisimide Dyes in Solution and Columnar Liquid Crystalline Phases

Abstract: A series of highly soluble and fluorescent core-twisted perylene bisimide dyes (PBIs) 3 a-f with different substituents at the bay area (1,6,7,12 positions of the perylene core) were synthesized and fully characterized by (1)H NMR, UV/Vis spectroscopy, MS spectrometry, and elemental analysis. The pi-pi aggregation properties of these new functional dyes were investigated in detail both in solution and in condensed phase by UV/Vis and fluorescence spectroscopy, vapor pressure osmometry (VPO), differential scanning calorimetry (DSC), polarizing optical microscopy (POM), and X-ray diffraction. Concentration-dependent UV/Vis measurements and VPO analysis revealed that these core-twisted pi-conjugated systems show distinct self-dimerization equilibria in apolar solvent methylcyclohexane (MCH) with dimerization constants between 1.3x10(4) and 30 M(-1). The photoluminescence spectra of the dimers of PBIs 3 a-f exhibit bathochromic shifts of quite different magnitude which could be attributed to different longitudinal or rotational offsets between the dyes as well as differences in the respective pi-pi stacking distance. In condensed state, quite a few of these PBIs form luminescent rectangular or hexagonal columnar liquid crystalline phases with low isotropization temperatures. The effects of the distortion of the pi systems on their pi-pi stacking and the optical properties of the resultant stacks in solution and in LC phases have been explored in detail. In one case (3 a) a particularly interesting phase change from crystalline into liquid crystalline could be observed upon annealing that was accompanied by a transformation from non-fluorescent H-type into strongly fluorescent J-type packing of the dyes.

Endpoints in Adjuvant Treatment Trials: A Systematic Review of the Literature in Colon Cancer and Proposed Definitions for Future Trials

Abstract: Disease-free survival is increasingly being used as the primary endpoint of most trials testing adjuvant treatments in cancer. Other frequently used endpoints include overall survival, recurrence-free survival, and time to recurrence. These endpoints are often defined differently in different trials in the same type of cancer, leading to a lack of comparability among trials. In this Commentary, we used adjuvant studies in colon cancer as a model to address this issue. In a systematic review of the literature, we identified 52 studies of adjuvant treatment in colon cancer published in 1997-2006 that used eight other endpoints in addition to overall survival. Both the definition of these endpoints and the starting point for measuring time to the events that constituted these endpoints varied widely. A panel of experts on clinical research on colorectal cancer then reached consensus on the definition of each endpoint. Disease-free survival--defined as the time from randomization to any event, irrespective of cause--was considered to be the most informative endpoint for assessing the effect of treatment and therefore the most relevant to clinical practice. The proposed guidelines may add to the quality and cross-comparability of future studies of adjuvant treatments for cancer.

Functional integration of hepatocytes derived from human mesenchymal stem cells into mouse livers

Abstract: Aims: At present, clinical success of hepatocyte transplantation as an alternative to whole liver transplantation is hampered by the limited availability of suitable donor organs for the isolation of transplantable hepatocytes. Hence, novel cell sources are required to deliver hepatocytes of adequate quality for clinical use. Mesenchymal stem cells (MSCs) from human bone marrow may have the potential to differentiate into hepatocytes in vitro and in vivo. Methods: Isolated MSCs were selected by density gradient centrifugation and plastic adherence, differentiated in the presence of human hepatocyte growth medium and transplanted in immunodeficient Pfp/Rag2 mice. Results: Here, we demonstrate that human MSCs gain in vitro the characteristic morphology and function of hepatocytes in response to specified growth factors. Specifically, preconditioned MSCs store glycogen, synthesise urea and feature the active hepatocyte-specific gene promoter of phosphoenolpyruvate carboxykinase (PCK1). After transplantation into livers of immunodeficient mice, preconditioned MSCs engraft predominantly in the periportal portion of the liver lobule. In situ, the cells continue to store glycogen and express PCK1, connexin32, albumin and the human hepatocyte-specific antigen HepPar1, indicating that the transplanted cells retain prominent qualities of hepatocytes after their regional integration. Conclusion: MSCs derived from human bone marrow may serve as a novel source for the propagation of hepatocyte-like cells suitable for cell therapy in liver diseases.

New Aspects of Microbial Nitrogen Transformations in the Context of Wastewater Treatment – A Review

Abstract: Over the past few years, new technologies for nitrogen removal have been developed mainly because of the increasing financial costs of the traditional wastewater treatment technologies. Newly discovered pathways, like the anaerobic oxidation of ammonium (ANAMMOX), and uses for nitrogen removal technologies are under discussion. Processes and technologies such as: Partial nitrification; Single reactor systems for High Ammonium Removal Over Nitrite (SHARON); Anammox; Aerobic/anoxic deammonification; Oxygen Limited Autotrophic Nitrification-Denitrification (OLAND); Completely Autotrophic Nitrogen Removal Over Nitrite (CANON); wetland based systems, all have a high potential for nitrogen removal. However, the pathways of nitrogen transformation processes are very complex. An understanding of how various environmental factors affect these processes and a sound knowledge of existing, worldwide experience pertaining to these novel technologies are the key if the nitrogen removal rates are to be improved and success is to be realized in full-scale applications. This review describes the present knowledge of the new treatment technologies for wastewater with high nitrogen loads. Special emphasis is given to the influence of environmental factors and the reactor configuration on the nitrogen transformation process and microbial activity.

Optimal L p - L q -estimates for parabolic boundary value problems with inhomogeneous data

Abstract: In this paper we investigate vector-valued parabolic initial boundary value problems \({(\mathcal A(t,x,D)}\) , \({\mathcal B_j(t,x,D))}\) subject to general boundary conditions in domains G in \({\mathbb R^n}\) with compact C 2m -boundary. The top-order coefficients of \({\mathcal A}\) are assumed to be continuous. We characterize optimal L p -L q -regularity for the solution of such problems in terms of the data. We also prove that the normal ellipticity condition on \({\mathcal A}\) and the Lopatinskii–Shapiro condition on \({(\mathcal A, \mathcal B_1,\dots, \mathcal B_m)}\) are necessary for these L p -L q -estimates. As a byproduct of the techniques being introduced we obtain new trace and extension results for Sobolev spaces of mixed order and a characterization of Triebel-Lizorkin spaces by boundary data.

Convergence of the generalized- α scheme for constrained mechanical systems

Abstract: A variant of the generalized-α scheme is proposed for constrained mechanical systems represented by index-3 DAEs. Based on the analogy with linear multistep methods, an elegant convergence analysis is developed for this algorithm. Second-order convergence is demonstrated both for the generalized coordinates and the Lagrange multipliers, and those theoretical results are illustrated by numerical tests.

Melatonin, endocrine pancreas and diabetes.

Abstract: Melatonin influences insulin secretion both in vivo and in vitro (i) The effects are MT(1)-and MT(2)-receptor-mediated (ii) They are specific, high-affinity, pertussis-toxin-sensitive, G(i)-protein-coupled, leading to inhibition of the cAMP-pathway and decrease of insulin release [Correction added after online publication 4 December 2007: in the preceding sentence, 'increase of insulin release' was changed to 'decrease of insulin release'] Furthermore, melatonin inhibits the cGMP-pathway, possibly mediated by MT(2) receptors In this way, melatonin likely inhibits insulin release A third system, the IP(3)-pathway, is mediated by G(q)-proteins, phospholipase C and IP(3), which mobilize Ca(2+) from intracellular stores, with a resultant increase in insulin (iii) Insulin secretion in vivo, as well as from isolated islets, exhibits a circadian rhythm This rhythm, which is apparently generated within the islets, is influenced by melatonin, which induces a phase shift in insulin secretion (iv) Observation of the circadian expression of clock genes in the pancreas could possibly be an indication of the generation of circadian rhythms in the pancreatic islets themselves (v) Melatonin influences diabetes and associated metabolic disturbances The diabetogens, alloxan and streptozotocin, lead to selective destruction of beta-cells through their accumulation in these cells, where they induce the generation of ROS Beta-cells are very susceptible to oxidative stress because they possess only low-antioxidative capacity Results suggest that melatonin in pharmacological doses provides protection against ROS (vi) Finally, melatonin levels in plasma, as well as the arylalkylamine-N-acetyltransferase (AANAT) activity, are lower in diabetic than in nondiabetic rats and humans In contrast, in the pineal gland, the AANAT mRNA is increased and the insulin receptor mRNA is decreased, which indicates a close interrelationship between insulin and melatonin

Sorptive stabilization of organic matter by microporous goethite: sorption into small pores vs. surface complexation

Abstract: Summary Stabilization of organic matter (OM) by sorption to minerals is thought to be due to (i) sorption into small pores (O < 50 nm) that prevents hydrolytic enzymes approaching and decomposing the organic substrate or (ii) reduced availability of organic molecules after formation of strong multiple bonds by complexation of organic ligands at mineral surfaces. We tested these two potential mechanisms by studying the binding of dissolved OM to microporous goethite (α-FeOOH). The size of organic molecules dissolved prior to and after equilibration with goethite was determined using atomic force microscopy (AFM). The goethite–OM complexes were analysed for bulk and surface elemental composition (by X-ray photoelectron spectroscopy, XPS), specific surface area (SSA) and mesopore and micropore volumes (by N2 adsorption/desorption), by scanning electron microscopy (SEM), and by diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy. The absolute density of goethite–OM complexes was determined by gas pycnometry and the sorbed OM’s apparent density was calculated by assuming no major changes in the volumes of the goethite upon sorption of OM. The stability of the OM–mineral interactions was tested in desorption experiments and by treatment with NaOCl. Surface accumulation of OM by sorption decreased the N2-accessible SSA of the goethite, mostly because micropores (O < 2 nm) were rendered inaccessible to N2. The decrease in accessibility of micropores was most pronounced at small surface OM concentrations. The majority of dissolved organic molecules detected with AFM prior to interaction with goethite were globular with a diameter of 4–10 nm, the rest were mainly linear, 20–100 nm long and 4–8 nm thick. After contact with goethite, the latter type of molecules dominated, which suggests preferential sorption of globular molecules. Their size exceeded or equalled the size of micropores and small mesopores (O < 10 nm) and so sorption therein is unlikely. Also, the changes in volumes of pores with a size of 2–50 nm were smaller than the estimated volume of the OM sorbed. The apparent density of sorbed OM always exceeded that of the freeze-dried OM and was largest at small surface concentrations. DRIFT spectroscopy showed that most carboxyl groups at the goethite surface were in their complexed form. The proportion of complexed carboxyl groups dropped at larger surface concentrations, parallel to the decrease in micropore volume. Thus, micropores seem to favour the formation of multiple complex bonds per molecule. Scanning electron microscopy showed that at small surface concentrations, OM coated the goethite crystals and crystallites tightly, while at larger surface concentrations bulky accumulations of OM were more abundant. Even strongly desorbing reagents such as NaOH and Na pyrophosphate released only part of the sorbed OM. Treatment with NaOCl removed mainly bulky accumulations of OM; the OM tightly bound to goethite crystals was hardly affected by NaOCl. We conclude that molecules tightly bound via multiple complex bonds, probably at the mouths of small pores, are barely desorbable and resist the attack of chemical reagents and probably also of enzymes.

IL-13 induces disease-promoting type 2 cytokines, alternatively activated macrophages and allergic inflammation during pulmonary infection of mice with Cryptococcus neoformans.

Abstract: In the murine model of Cryptococcus neoformans infection Th1 (IL-12/IFN-gamma) and Th17 (IL-23/IL-17) responses are associated with protection, whereas an IL-4-dependent Th2 response exacerbates disease. To investigate the role of the Th2 cytokine IL-13 during pulmonary infection with C. neoformans, IL-13-overexpressing transgenic (IL-13Tg(+)), IL-13-deficient (IL-13(-/-)), and wild-type (WT) mice were infected intranasally. Susceptibility to C. neoformans infection was found when IL-13 was induced in WT mice or overproduced in IL-13Tg(+) mice. Infected IL-13Tg(+) mice had a reduced survival time and higher pulmonary fungal load as compared with WT mice. In contrast, infected IL-13(-/-) mice were resistant and 89% of these mice survived the entire period of the experiment. Ag-specific production of IL-13 by susceptible WT and IL-13Tg(+) mice was associated with a significant type 2 cytokine shift but only minor changes in IFN-gamma production. Consistent with enhanced type 2 cytokine production, high levels of serum IgE and low ratios of serum IgG2a/IgG1 were detected in susceptible WT and IL-13Tg(+) mice. Interestingly, expression of IL-13 by susceptible WT and IL-13Tg(+) mice was associated with reduced IL-17 production. IL-13 was found to induce formation of alternatively activated macrophages expressing arginase-1, macrophage mannose receptor (CD206), and YM1. In addition, IL-13 production led to lung eosinophilia, goblet cell metaplasia and elevated mucus production, and enhanced airway hyperreactivity. This indicates that IL-13 contributes to fatal allergic inflammation during C. neoformans infection.

Germline CDKN1B/p27Kip1 mutation in multiple endocrine neoplasia.

Abstract: Context: Germline mutations in the MEN1 gene predispose to multiple endocrine neoplasia type 1 (MEN1) syndrome, but in up to 20–25% of clinical MEN1 cases, no MEN1 mutations can be found. Recently, a germline mutation in the CDKN1B gene, encoding p27Kip1, was reported in one suspected MEN1 family with two acromegalic patients. Objective: Our objective was to evaluate the role of CDKN1B/p27Kip1 in human tumor predisposition in patients clinically suspected of MEN1 but testing negative for MEN1 germline mutation as well as in familial and sporadic acromegaly/pituitary adenoma patients. Design: Genomic DNA was analyzed for germline mutations in the CDKN1B/p27Kip1 gene by PCR amplification and direct sequencing. Setting: The study was conducted at nonprofit academic research and medical centers. Patients: Thirty-six Dutch and one German suspected MEN1 patient, who previously tested negative for germline MEN1 gene mutations, were analyzed. In addition, 19 familial and 50 sporadic acromegaly/pituitary adenoma p...

Neurological Symptoms in Type A Aortic Dissections

Abstract: Background and Purpose— Aortic dissection typically presents with severe chest or back pain. Neurological symptoms may occur because of occlusion of supplying vessels or general hypotension. Especi...

DENCLUE 2.0: fast clustering based on kernel density estimation

Abstract: The Denclue algorithm employs a cluster model based on kernel density estimation A cluster is defined by a local maximum of the estimated density function Data points are assigned to clusters by hill climbing, ie points going to the same local maximum are put into the same cluster A disadvantage of Denclue 10 is, that the used hill climbing may make unnecessary small steps in the beginning and never converges exactly to the maximum, it just comes close We introduce a new hill climbing procedure for Gaussian kernels, which adjusts the step size automatically at no extra costs We prove that the procedure converges exactly towards a local maximum by reducing it to a special case of the expectation maximization algorithm We show experimentally that the new procedure needs much less iterations and can be accelerated by sampling based methods with sacrificing only a small amount of accuracy

Biosorption of metals by a waste biomass

Abstract: The binding of several metals by waste biomass of Streptomyces noursei was investigated. With respect to the binding capacity, the following order was observed: Ag > Cr > Pb > Cu > Zn > Cd > Co > =Ni. The sorption of metal ions increased with the increasing initial concentration of metal. The adsorption equilibrium of copper, lead and chromium sorption, and silver sorption at low concentration can be described by the Freundlich and Langmuir models. The possibilities for desorbing the metals from loaded biomass and the repeated use of biomass were investigated. The influence of various ions in water on metal sorption was tested. The metal capacity and selectivity of metal binding by biomass are important qualities for practical use.

Crystal structure of the incretin-bound extracellular domain of a G protein-coupled receptor

Abstract: Incretins, endogenous polypeptide hormones released in response to food intake, potentiate insulin secretion from pancreatic β cells after oral glucose ingestion (the incretin effect). This response is signaled by the two peptide hormones glucose-dependent insulinotropic polypeptide (GIP) (also known as gastric inhibitory polypeptide) and glucagon-like peptide 1 through binding and activation of their cognate class 2 G protein-coupled receptors (GPCRs). Because the incretin effect is lost or significantly reduced in patients with type 2 diabetes mellitus, glucagon-like peptide 1 and GIP have attracted considerable attention for their potential in antidiabetic therapy. A paucity of structural information precludes a detailed understanding of the processes of hormone binding and receptor activation, hampering efforts to develop novel pharmaceuticals. Here we report the crystal structure of the complex of human GIP receptor extracellular domain (ECD) with its agonist, the incretin GIP1–42. The hormone binds in an α-helical conformation in a surface groove of the ECD largely through hydrophobic interactions. The N-terminal ligand residues would remain free to interact with other parts of the receptor. Thermodynamic data suggest that binding is concomitant with structural organization of the hormone, resulting in a complex mode of receptor–ligand recognition. The presentation of a well structured, α-helical ligand by the ECD is expected to be conserved among other hormone receptors of this class.