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Showing papers by "Ludwig Maximilian University of Munich published in 2000"


Journal ArticleDOI
16 May 2000
TL;DR: This paper contends that for many scenarios, it is more meaningful to assign to each object a degree of being an outlier, called the local outlier factor (LOF), and gives a detailed formal analysis showing that LOF enjoys many desirable properties.
Abstract: For many KDD applications, such as detecting criminal activities in E-commerce, finding the rare instances or the outliers, can be more interesting than finding the common patterns. Existing work in outlier detection regards being an outlier as a binary property. In this paper, we contend that for many scenarios, it is more meaningful to assign to each object a degree of being an outlier. This degree is called the local outlier factor (LOF) of an object. It is local in that the degree depends on how isolated the object is with respect to the surrounding neighborhood. We give a detailed formal analysis showing that LOF enjoys many desirable properties. Using real-world datasets, we demonstrate that LOF can be used to find outliers which appear to be meaningful, but can otherwise not be identified with existing approaches. Finally, a careful performance evaluation of our algorithm confirms we show that our approach of finding local outliers can be practical.

5,248 citations


Journal ArticleDOI
TL;DR: In the theories considered, the dynamics causes the scalar field to lock automatically into a negative pressure state at the onset of matter domination such that the present epoch is the earliest possible time consistent with nucleosynthesis restrictions when it can start to dominate.
Abstract: Increasing evidence suggests that most of the energy density of the universe consists of a dark energy component with negative pressure that causes the cosmic expansion to accelerate. We address why this component comes to dominate the universe only recently. We present a class of theories based on an evolving scalar field where the explanation is based entirely on internal dynamical properties of the solutions. In the theories we consider, the dynamics causes the scalar field to lock automatically into a negative pressure state at the onset of matter domination such that the present epoch is the earliest possible time consistent with nucleosynthesis restrictions when it can start to dominate.

1,962 citations


Journal ArticleDOI
TL;DR: A positional cloning approach was used to identify the ADHR gene which included the annotation of 37 genes within 4 Mb of genomic sequence, and missense mutations in a gene encoding a new member of the fibroblast growth factor (FGF) family, FGF23 were identified.
Abstract: Proper serum phosphate concentrations are maintained by a complex and poorly understood process. Identification of genes responsible for inherited disorders involving disturbances in phosphate homeostasis may provide insight into the pathways that regulate phosphate balance. Several hereditary disorders of isolated phosphate wasting have been described, including X-linked hypophosphataemic rickets1 (XLH), hypophosphataemic bone disease2 (HBD), hereditary hypophosphataemic rickets with hypercalciuria3 (HHRH) and autosomal dominant hypophosphataemic rickets4,5 (ADHR). Inactivating mutations of the gene PHEX, encoding a member of the neutral endopeptidase family of proteins, are responsible for XLH (refs 6,7). ADHR (MIM 193100) is characterized by low serum phosphorus concentrations, rickets, osteomalacia, lower extremity deformities, short stature, bone pain and dental abscesses4,5. Here we describe a positional cloning approach used to identify the ADHR gene which included the annotation of 37 genes within 4 Mb of genomic sequence. We identified missense mutations in a gene encoding a new member of the fibroblast growth factor (FGF) family, FGF23. These mutations in patients with ADHR represent the first mutations found in a human FGF gene.

1,429 citations


Journal ArticleDOI
TL;DR: This work identifies form-stable coupled excitations of light and matter ("dark-state polaritons") associated with the propagation of quantum fields in electromagnetically induced transparency that can be controlled by an external coherent field as the pulse propagates.
Abstract: We identify form-stable coupled excitations of light and matter ("dark-state polaritons") associated with the propagation of quantum fields in electromagnetically induced transparency. The properties of dark-state polaritons such as the group velocity are determined by the mixing angle between light and matter components and can be controlled by an external coherent field as the pulse propagates. In particular, light pulses can be decelerated and "trapped" in which case their shape and quantum state are mapped onto metastable collective states of matter. Possible applications of this reversible coherent-control technique are discussed.

1,314 citations


Journal ArticleDOI
TL;DR: In this article, a stable all solid-state source for single photons utilizing the fluorescence light from a single nitrogen-vacancy center (N-V center) in diamond is presented.
Abstract: The controlled generation of single photons is mandatory for applications in quantum communication, in particular for secure quantum cryptography, and also for a number of fundamental problems in quantum optics. Here, we present a stable all solid-state source for single photons utilizing the fluorescence light from a single nitrogen-vacancy center (N-V center) in diamond.

1,268 citations


Journal ArticleDOI
25 Feb 2000-Science
TL;DR: Modulation of host cells by bacterial protein translocation adds a new dimension to the chronic Helicobacter infection with yet unknown consequences.
Abstract: The Gram-negative bacterium Helicobacter pylori is a causative agent of gastritis and peptic ulcer disease in humans. Strains producing the CagA antigen (cagA(+)) induce strong gastric inflammation and are strongly associated with gastric adenocarcinoma and MALT lymphoma. We show here that such strains translocate the bacterial protein CagA into gastric epithelial cells by a type IV secretion system, encoded by the cag pathogenicity island. CagA is tyrosine-phosphorylated and induces changes in the tyrosine phosphorylation state of distinct cellular proteins. Modulation of host cells by bacterial protein translocation adds a new dimension to the chronic Helicobacter infection with yet unknown consequences.

1,252 citations


Journal ArticleDOI
01 Jul 2000-Brain
TL;DR: The combination of symptoms, MRI findings and paraneoplastic antibodies established the diagnosis of PLE in 78% of the patients, and treatment of the tumour appeared to have more effect on the neurological outcome than the use of immune modulation.
Abstract: Paraneoplastic limbic encephalitis (PLE) is a rare disorder characterized by personality changes, irritability, depression, seizures, memory loss and sometimes dementia. The diagnosis is difficult because clinical markers are often lacking, and symptoms usually precede the diagnosis of cancer or mimic other complications. The frequency of antineuronal antibodies in patients with PLE has not been investigated. We examined the neurological symptoms and the causal tumours in 50 patients with PLE to determine the utility of paraneoplastic antibodies and other tests. The diagnosis of PLE required neuropathological examination or the presence of the four following criteria: (i) a compatible clinical picture; (ii) an interval of <4 years between the development of neurological symptoms and tumour diagnosis; (iii) exclusion of other neuro-oncological complications; and (iv) at least one of the following: CSF with inflammatory changes but negative cytology; MRI demonstrating temporal lobe abnormalities; EEG showing epileptic activity in the temporal lobes. Of 1047 patients with neurological symptoms, whose sera or CSF were examined for paraneoplastic antibodies, 79 had the presumptive diagnosis of limbic encephalitis, dementia, cognitive dysfunction, or confusion. Fifty of these patients fulfilled our criteria for PLE. Pathological confirmation was obtained in 12 patients. The commonly associated neoplasms were of the lung (50%), testis (20%) and breast (8%). Neurological symptoms preceded the cancer diagnosis in 60% of patients (by a median of 3.5 months). Twenty-five of 44 (57%) patients with MRI studies had signal abnormalities in the limbic system. Thirty (60%) patients had antineuronal antibodies (18 anti-Hu, 10 anti-Ta, 2 anti-Ma), and 20 were antibody-negative or had uncharacterized antibodies (n = 4). The combination of symptoms, MRI findings and paraneoplastic antibodies established the diagnosis of PLE in 78% of the patients. Patients with anti-Hu antibodies usually had small-cell lung cancer (94%), multifocal neurological symptoms (78%) and a poor neurological outcome. Patients with anti-Ta (also called anti-Ma2) antibodies were young men with testicular tumours (100%), frequent hypothalamic involvement (70%) and a poor neurological outcome. In the group of patients without anti-Hu or anti-Ta antibodies, the tumour distribution was diverse, with cancer of the lung the most common (36%); 57% had positive MRI. Fifteen of 34 (44%) patients with a median follow-up of 8 months showed neurological improvement. Treatment of the tumour appeared to have more effect on the neurological outcome than the use of immune modulation. Improvement was observed in 38% of anti-Hu patients, 30% of anti-Ta patients and 64% of patients without these antibodies.

996 citations


Journal ArticleDOI
TL;DR: The presence of occult cytokeratin-positive metastatic cells in bone marrow increases the risk of relapse in patients with stage I, II, or III breast cancer.
Abstract: Background Cytokeratins are specific markers of epithelial cancer cells in bone marrow. We assessed the influence of cytokeratin-positive micrometastases in the bone marrow on the prognosis of women with breast cancer. Methods We obtained bone marrow aspirates from both upper iliac crests of 552 patients with stage I, II, or III breast cancer who underwent complete resection of the tumor and 191 patients with nonmalignant disease. The specimens were stained with the monoclonal antibody A45-B/B3, which binds to an antigen on cytokeratins. The median follow-up was 38 months (range, 10 to 70). The primary end point was survival. Results Cytokeratin-positive cells were detected in the bone marrow specimens of 2 of the 191 control patients with nonmalignant conditions (1 percent) and 199 of the 552 patients with breast cancer (36 percent). The presence of occult metastatic cells in bone marrow was unrelated to the presence or absence of lymph-node metastasis (P=0.13). After four years of follow-up, the presenc...

922 citations


Journal ArticleDOI
03 Feb 2000-Nature
TL;DR: In this article, the results of three specific experiments, involving measurements of polarization correlations between three photons, lead to predictions for a fourth experiment; quantum physical predictions are mutually contradictory with expectations based on local realism.
Abstract: Bell's theorem states that certain statistical correlations predicted by quantum physics for measurements on two-particle systems cannot be understood within a realistic picture based on local properties of each individual particle-even if the two particles are separated by large distances. Einstein, Podolsky and Rosen first recognized the fundamental significance of these quantum correlations (termed 'entanglement' by Schrodinger) and the two-particle quantum predictions have found ever-increasing experimental support. A more striking conflict between quantum mechanical and local realistic predictions (for perfect correlations) has been discovered; but experimental verification has been difficult, as it requires entanglement between at least three particles. Here we report experimental confirmation of this conflict, using our recently developed method to observe three-photon entanglement, or 'Greenberger-Horne-Zeilinger' (GHZ) states. The results of three specific experiments, involving measurements of polarization correlations between three photons, lead to predictions for a fourth experiment; quantum physical predictions are mutually contradictory with expectations based on local realism. We find the results of the fourth experiment to be in agreement with the quantum prediction and in striking conflict with local realism.

917 citations


Journal ArticleDOI
TL;DR: The effect of various drugs affecting the integrity of different components of the cytoskeleton on the elasticity of two fibroblast cell lines was investigated by elasticity measurements with an atomic force microscope (AFM).

912 citations


Journal ArticleDOI
TL;DR: The usefulness of 5-ALA-induced tumor fluorescence for guiding tumor resection on postoperative magnetic resonance (MR) imaging and survival in patients who underwent surgery in the authors' department is indicated.
Abstract: Object It has been established that 5-aminolevulinic acid (5-ALA) induces the accumulation of fluorescent porphyrins in glioblastoma multiforme (GBM), a phenomenon potentially exploitable to guide tumor resection In this study the authors analyze the influence of fluorescence-guided resection on postoperative magnetic resonance (MR) imaging and survival in a series of patients who underwent surgery in the authors' department Methods Fifty-two consecutive patients with GBM received oral doses of 5-ALA (20 mg/kg body weight) 3 hours before induction of anesthesia Intraoperatively, tumor fluorescence was visualized using a modified operating microscope Fluorescing tissue was removed whenever it was considered safely possible Residual enhancement on early postoperative MR imaging was quantified and related to each patient's characteristics to determine which factors influenced resection Survival was analyzed using the Kaplan—Meier method and multivariate analysis was performed in which the Karnofsky P

Journal ArticleDOI
TL;DR: A novel key distribution scheme is implemented using Wigner's inequality to test the security of the quantum channel, and a variant of the BB84 protocol is realized.
Abstract: By realizing a quantum cryptography system based on polarization entangled photon pairs we establish highly secure keys, because a single photon source is approximated and the inherent randomness of quantum measurements is exploited. We implement a novel key distribution scheme using Wigner's inequality to test the security of the quantum channel, and, alternatively, realize a variant of the BB84 protocol. Our system has two completely independent users separated by 360 m, and generates raw keys at rates of 400-800 bits/s with bit error rates around 3%.

Journal ArticleDOI
TL;DR: The present review did not consider cyclic, seasonal, irritable-dysphoric or otherwise impulse-ridden, intermittently explosive or agitated psychiatric conditions for which the bipolar connection is less established.

Journal ArticleDOI

Journal ArticleDOI
22 Jun 2000-Nature
TL;DR: It is found that the emission energy changes abruptly whenever an electron is added to the artificial atom, and that the sizes of the jumps reveal a shell structure.
Abstract: Quantum dots or rings are artificial nanometre-sized clusters that confine electrons in all three directions. They can be fabricated in a semiconductor system by embedding an island of low-bandgap material in a sea of material with a higher bandgap. Quantum dots are often referred to as artificial atoms because, when filled sequentially with electrons, the charging energies are pronounced for particular electron numbers; this is analogous to Hund's rules in atomic physics. But semiconductors also have a valence band with strong optical transitions to the conduction band. These transitions are the basis for the application of quantum dots as laser emitters, storage devices and fluorescence markers. Here we report how the optical emission (photoluminescence) of a single quantum ring changes as electrons are added one-by-one. We find that the emission energy changes abruptly whenever an electron is added to the artificial atom, and that the sizes of the jumps reveal a shell structure.

Journal ArticleDOI
TL;DR: The prevalence of atopic diseases is on the rise and traditional lifestyles may be associated with a reduced risk of atopy.
Abstract: Background The prevalence of atopic diseases is on the rise. Traditional lifestyles may be associated with a reduced risk of atopy. Objectives To test the hypothesis that children living on a farm have lower prevalences of atopic diseases. To identify differences in living conditions between farmers and other families which are associated with the development of atopic conditions. Design Cross-sectional survey among children entering school (aged 5–7 years). A written questionnaire including the ISAAC core questions and asking for exposures on a farm and elsewhere was administered to the parents. Setting: School health entry examination in two Bavarian districts with extensive farming activity. Subjects: 10 163 children. Main outcome measures The prevalence of doctor's diagnoses and symptoms of hay fever, asthma and eczema as assessed by parental report. Results Farmers' children had lower prevalences of hay fever (adjusted odds ratio = 0.52, 95% CI 0.28–0.99), asthma (0.65, 0.39–1.09), and wheeze (0.55, 0.36–0.86) than their peers not living in an agricultural environment. The reduction in risk was stronger for children whose families were running the farm on a full-time basis as compared with families with part-time farming activity. Among farmers' children increasing exposure to livestock was related to a decreasing prevalence of atopic diseases (aOR = 0.41, 95% CI 0.23–0.74). Conclusions Factors related to environmental influences on a farm such as increased exposure to bacterial compounds in stables where livestock is kept prevent the development of allergic disorders in children.

Journal ArticleDOI
TL;DR: In screening over 14,000 mice for a large number of clinically relevant parameters, 182 mouse mutants are recovered and this mutagenesis screen leads to a significant increase in the number of mouse models available to the scientific community.
Abstract: In the post-genome era, the mouse will have a major role as a model system for functional genome analysis. This requires a large number of mutants similar to the collections available from other model organisms such as Drosophila melanogaster and Caenorhabditis elegans. Here we report on a systematic, genome-wide, mutagenesis screen in mice. As part of the German Human Genome Project, we have undertaken a large-scale ENU-mutagenesis screen for dominant mutations and a limited screen for recessive mutations1. In screening over 14,000 mice for a large number of clinically relevant parameters, we recovered 182 mouse mutants for a variety of phenotypes. In addition, 247 variant mouse mutants are currently in genetic confirmation testing and will result in additional new mutant lines. This mutagenesis screen, along with the screen described in the accompanying paper2, leads to a significant increase in the number of mouse models3 available to the scientific community. Our mutant lines are freely accessible to non-commercial users (for information, see http://www.gsf.de/ieg/groups/enu-mouse.html ).

Journal ArticleDOI
07 Apr 2000-Science
TL;DR: Atomic force microscopy and single-molecule force spectroscopy were combined to image and manipulate purple membrane patches from Halobacterium salinarum, revealing the individuality of the unfolding pathways.
Abstract: Atomic force microscopy and single-molecule force spectroscopy were combined to image and manipulate purple membrane patches from Halobacterium salinarum. Individual bacteriorhodopsin molecules were first localized and then extracted from the membrane; the remaining vacancies were imaged again. Anchoring forces between 100 and 200 piconewtons for the different helices were found. Upon extraction, the helices were found to unfold. The force spectra revealed the individuality of the unfolding pathways. Helices G and F as well as helices E and D always unfolded pairwise, whereas helices B and C occasionally unfolded one after the other. Experiments with cleaved loops revealed the origin of the individuality: stabilization of helix B by neighboring helices.

Journal ArticleDOI
TL;DR: The Parkinson's disease-associated human mutant [A30P]αSYN was found to colocalize with βSYN and synaptophysin in synapses of transgenic mouse brain, however, in addition to their normal presynaptic localization, transgenic wild-type and [A 30P] αSYN abnormally accumulated in neuronal cell bodies and neurites throughout the brain.
Abstract: Mutations in the alpha-synuclein (alphaSYN) gene are associated with rare cases of familial Parkinson's disease, and alphaSYN is a major component of Lewy bodies and Lewy neurites. Here we have investigated the localization of wild-type and mutant [A30P]alphaSYN as well as betaSYN at the cellular and subcellular level. Our direct comparative study demonstrates extensive synaptic colocalization of alphaSYN and betaSYN in human and mouse brain. In a sucrose gradient equilibrium centrifugation assay, a portion of betaSYN floated into lower density fractions, which also contained the synaptic vesicle marker synaptophysin. Likewise, wild-type and [A30P]alphaSYN were found in floating fractions. Subcellular fractionation of mouse brain revealed that both alphaSYN and betaSYN were present in synaptosomes. In contrast to synaptophysin, betaSYN and alphaSYN were recovered from the soluble fraction upon lysis of the synaptosomes. Synaptic colocalization of alphaSYN and betaSYN was directly visualized by confocal microscopy of double-stained human brain sections. The Parkinson's disease-associated human mutant [A30P]alphaSYN was found to colocalize with betaSYN and synaptophysin in synapses of transgenic mouse brain. However, in addition to their normal presynaptic localization, transgenic wild-type and [A30P]alphaSYN abnormally accumulated in neuronal cell bodies and neurites throughout the brain. Thus, mutant [A30P]alphaSYN does not fail to be transported to synapses, but its transgenic overexpression apparently leads to abnormal cellular accumulations.

Journal ArticleDOI
TL;DR: In this paper, the relevance of mite and cat allergen exposure for the development of childhood asthma up to age 7 years was assessed in a prospective birth-cohort study.

Journal ArticleDOI
TL;DR: The authors' knowledge of viral gene functions must be integrated into virus–host interaction networks to understand viral pathogenesis, and could lead to new anti-viral strategies and the ability to exploit viral functions as tools in medicine.

Journal ArticleDOI
TL;DR: It is demonstrated that the chemokine receptor CCR5, the principal co-receptor for macrophage-tropic human immunodeficiency virus (HIV)-1, can be released through microparticles from the surface of C CR5+ Chinese hamster ovary cells and peripheral blood mononuclear cells.
Abstract: The release of microparticles from eukaryotic cells is a well-recognized phenomenon. We demonstrate here that the chemokine receptor CCR5, the principal co-receptor for macrophage-tropic human immunodeficiency virus (HIV)-1, can be released through microparticles from the surface of CCR5+ Chinese hamster ovary cells and peripheral blood mononuclear cells. Microparticles containing CCR5 can transfer the receptor to CCR5- cells and render them CCR5+. The CCR5 transfer to CCR5-deficient peripheral blood mononuclear cells homozygous for a 32-base-pair deletion in the CCR5 gene enabled infection of these cells with macrophage-tropic HIV-1. In monocytes, the transfer of CCR5 could be inhibited by cytochalasin D, and transferred CCR5 could be downmodulated by chemokines. A transfer of CCR5 from peripheral blood mononuclear cells to endothelial cells during transendothelial migration could be demonstrated. Thus, the transfer of CCR5 may lead to infection of tissues without endogenous CCR5 expression. Moreover, the intercellular transfer of membrane proteins by microparticles might have broader consequences for intercellular communication beyond the effects seen for HIV-1.

Journal ArticleDOI
TL;DR: Several recent studies have shown that growing up on a farm confers significant protection against the development of atopy, and point particularly towards the importance of exposure to stable dust and farm animals.
Abstract: Background Several recent studies have shown that growing up on a farm confers significant protection against the development of atopy. These findings point particularly towards the importance of exposure to stable dust and farm animals. It has furthermore been reported that endotoxin, an intrinsic part of the outer membrane of gram negative bacteria, is abundant in environments where livestock and poultry is kept. The aim of this study was therefore to measure the level of environmental endotoxin exposure in homes of farmers' children, children with regular contact to livestock and control children with no contact to farm animals. Methods Eighty-four farming and nonfarming families were identified in rural areas in Southern Germany and Switzerland. Samples of settled and airborne dust were collected in stables, and of settled dust indoors from kitchen floors and the children's mattresses. Endotoxin concentrations were determined by a kinetic Limulus assay. Results Endotoxin concentrations were highest in stables of farming families, but were also significantly higher indoors in dust from kitchen floors (143 EU/mg vs 39 EU/mg, P<0.001) and children's mattresses (49479 EU/m 2 vs 9383 EU/m 2 , P<0.001) as compared to control children from nonfarming families. In addition, endotoxin levels were also significantly higher in mattresses and dust from kitchen floors in households where children had regular contact to farm animals (38.6 EU/mg and 23340 EU/m 2 , respectively) as compared to control subjects. Conclusion We propose that the level of environmental exposure to endotoxin and other bacterial wall components is an important protective determinant for the development of atopic diseases in childhood.

Journal ArticleDOI
TL;DR: In this paper, the authors draw implications for technology policy from evidence on the size distribution of returns from eight sets of data on inventions and innovations attributable to private sector firms and universities.

Journal ArticleDOI
TL;DR: Measurements are focused on a glycoprotein, contact site A, as a prototype of cell-adhesion proteins, expressed in aggregating cells of Dictyostelium discoideum, which are engaged in development of a multicellular organism.
Abstract: Cell-cell adhesion mediated by specific cell-surface molecules is essential for multicellular development. Here we quantify de-adhesion forces at the resolution of individual cell-adhesion molecules, by controlling the interactions between single cells and combining single-molecule force spectroscopy with genetic manipulation. Our measurements are focused on a glycoprotein, contact site A (csA), as a prototype of cell-adhesion proteins. csA is expressed in aggregating cells of Dictyostelium discoideum, which are engaged in development of a multicellular organism. Adhesion between two adjacent cell surfaces involves discrete interactions characterized by an unbinding force of 23 +/- 8 pN, measured at a rupture rate of 2.5 +/- 0.5 microm s-1.

Journal ArticleDOI
TL;DR: The identity of the As-induced PCs and of reconstituted metal-peptide complexes has unequivocally been demonstrated by electrospray ionization mass spectroscopy and Gel filtration experiments and inhibitor studies indicate a complexation and detoxification of As by the induced PCs.
Abstract: As is a ubiquitous element present in the atmosphere as well as in the aquatic and terrestrial environments. Arsenite and arsenate are the major forms of As intoxication, and these anions are readily taken up by plants. Both anions efficiently induce the biosynthesis of phytochelatins (PCs) ([gamma-glutamate-cysteine](n)-glycine) in vivo and in vitro. The rapid induction of the metal-binding PCs has been observed in cell suspension cultures of Rauvolfia serpentina, in seedlings of Arabidopsis, and in enzyme preparations of Silene vulgaris upon challenge to arsenicals. The rate of PC formation in enzyme preparations was lower compared with Cd-induced biosynthesis, but was accompanied by a prolonged induction phase that resulted finally in higher peptide levels. An approximately 3:1 ratio of the sulfhydryl groups from PCs to As is compatible with reported As-glutathione complexes. The identity of the As-induced PCs and of reconstituted metal-peptide complexes has unequivocally been demonstrated by electrospray ionization mass spectroscopy. Gel filtration experiments and inhibitor studies also indicate a complexation and detoxification of As by the induced PCs.

Journal ArticleDOI
TL;DR: It is demonstrated that the LOV domains of Avena sativa phototropin undergo a self-contained photocycle characterized by a loss of blue light absorbance in response to light and a spontaneous recovery of the blue light-absorbing form in the dark.
Abstract: The plant photoreceptor phototropin is an autophosphorylating serine-threonine protein kinase activated by UV-A/blue light. Two domains, LOV1 and LOV2, members of the PAS domain superfamily, mediate light sensing by phototropin. Heterologous expression studies have shown that both domains function as FMN-binding sites. Although three plant blue light photoreceptors, cry1, cry2, and phototropin, have been identified to date, the photochemical reactions underlying photoactivation of these light sensors have not been described so far. Herein, we demonstrate that the LOV domains of Avena sativa phototropin undergo a self-contained photocycle characterized by a loss of blue light absorbance in response to light and a spontaneous recovery of the blue light-absorbing form in the dark. Rate constants and quantum efficiencies for the photoreactions indicate that LOV1 exhibits a lower photosensitivity than LOV2. The spectral properties of the photoproduct produced for both LOV domains are unrelated to those found for photoreduced flavins and flavoproteins, but are consistent with those of a flavin-cysteinyl adduct. Flavin-thiol adducts are generally short-lifetime reaction intermediates formed during the flavoprotein-catalyzed reduction of protein disulfides. By site-directed mutagenesis, we have identified several amino acid residues within the putative chromophore binding site of LOV1 and LOV2 that appear to be important for FMN binding and/or the photochemical reactivity. Among those is Cys39, which plays an important role in the photochemical reaction of the LOV domains. Replacement of Cys39 with Ala abolished the photochemical reactions of both LOV domains. We therefore propose that light sensing by the phototropin LOV domains occurs via the formation of a stable adduct between the FMN chromophore and Cys39.

Journal ArticleDOI
TL;DR: In this paper, a formulation of gauge theory on noncommutative spaces based on the notion of covariant coordinates is introduced, and a Seiberg-Witten map is established in all cases.
Abstract: We introduce a formulation of gauge theory on noncommutative spaces based on the notion of covariant coordinates. Some important examples are discussed in detail. A Seiberg-Witten map is established in all cases.

Journal ArticleDOI
TL;DR: For general relativistic spacetimes filled with irrotational ‘dust, a generalized form of Friedmann's equations for an effective expansion factor aD of inhomogeneous cosmologies is derived in this paper.
Abstract: For general relativistic spacetimes filled with irrotational ‘dust’ a generalized form of Friedmann's equations for an ‘effective’ expansion factor aD of inhomogeneous cosmologies is derived. Contrary to the standard Friedmann equations, which hold for homogeneous-isotropic cosmologies, the new equations include the ‘backreaction effect’ of inhomogeneities on the average expansion of the model. A universal relation between ‘backreaction’ and average scalar curvature is also given. For cosmologies whose averaged spatial scalar curvature is proportional to aD-2, the expansion law governing a generic domain can be found. However, as the general equations show, ‘backreaction’ acts as to produce average curvature in the course of structure formation, even when starting with space sections that are spatially flat on average.

Journal ArticleDOI
TL;DR: The authors compared a standard expenditure-based poverty measure with a specifically created composite measure of deprivation using household survey data from South Africa and found that the two measures differ considerably in the impact of race, headship, location (urban, rural), and household size on expenditure poverty versus deprivation.
Abstract: This paper compares a standard expenditure-based poverty measure with a specifically created composite measure of deprivation using household survey data from South Africa. While there is a strong overall correlation between expenditures and levels of deprivation, the correlation is much weaker among the worst-off South Africans. In addition, the two measures differ considerably in the impact of race, headship, location (urban, rural), and household size on expenditure poverty versus deprivation. In general, the deprivation measure finds more Africans, rural dwellers, members of de facto female-headed households, and members of smaller households deprived than expenditure poor. Only the differences in the effect of household size on poverty are sensitive to assumptions about equivalence scales. As a result, the two measures diverge greatly in identifying the poorest and most deprived sections of the population, which may have considerable consequences for targeting.