scispace - formally typeset
Search or ask a question

Showing papers by "Humboldt University of Berlin published in 2004"


Journal ArticleDOI
TL;DR: In this paper, quantitative real-time PCR was used to determine the mRNA transcription profiles of 13 putative reference genes, comparing their transcription in 16 different tissues and in CCRF-HSB-2 cells stimulated with 12-Otetradecanoylphorbol-13-acetate and ionomycin.

1,582 citations


Journal ArticleDOI
TL;DR: AIEC strains are associated specifically with ileal mucosa in CD, and the abilities of E. coli strains to invade epithelial cells and to survive and replicate within macrophages were assessed using the gentamicin protection assay.

1,400 citations


Journal ArticleDOI
TL;DR: In this article, the behavior of excitable systems driven by Gaussian white noise is reviewed, focusing mainly on those general properties of such systems that are due to noise, and present several applications of their findings in biophysics and lasers.

1,373 citations


Journal ArticleDOI
TL;DR: The application, advancement and future directions of SFF techniques in the design and creation of scaffolds for use in clinically driven tissue engineering are reviewed.

1,067 citations


Journal ArticleDOI
TL;DR: A gene map of the xMHC is presented and its content in relation to paralogy, polymorphism, immune function and disease is reviewed.
Abstract: The major histocompatibility complex (MHC) is the most important region in the vertebrate genome with respect to infection and autoimmunity, and is crucial in adaptive and innate immunity. Decades of biomedical research have revealed many MHC genes that are duplicated, polymorphic and associated with more diseases than any other region of the human genome. The recent completion of several large-scale studies offers the opportunity to assimilate the latest data into an integrated gene map of the extended human MHC. Here, we present this map and review its content in relation to paralogy, polymorphism, immune function and disease.

1,047 citations


Journal ArticleDOI
TL;DR: Four key issues for Web service composition are described, which offer developers reuse possibilities and users seamless access to a variety of complex services.
Abstract: Web service composition lets developers create applications on top of service-oriented computing's native description, discovery, and communication capabilities. Such applications are rapidly deployable and offer developers reuse possibilities and users seamless access to a variety of complex services. There are many existing approaches to service composition, ranging from abstract methods to those aiming to be industry standards. The authors describe four key issues for Web service composition.

770 citations


Journal ArticleDOI
TL;DR: In two kindreds with ARVC, disease was incompletely penetrant in most carriers of PKP2 mutations, and the identified heterozygous mutations inPKP2, which encodes plakophilin-2, an essential armadillo-repeat protein of the cardiac desmosome.
Abstract: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with fibrofatty replacement of cardiac myocytes, ventricular tachyarrhythmias and sudden cardiac death. In 32 of 120 unrelated individuals with ARVC, we identified heterozygous mutations in PKP2, which encodes plakophilin-2, an essential armadillo-repeat protein of the cardiac desmosome. In two kindreds with ARVC, disease was incompletely penetrant in most carriers of PKP2 mutations.

767 citations


Journal ArticleDOI
TL;DR: In this paper, the synthesis and characterization of highly luminescent colloidal nanocrystals consisting of CdSe cores protected with double inorganic shells (core−shell−shell nanocrystal).
Abstract: We report the synthesis and characterization of highly luminescent colloidal nanocrystals consisting of CdSe cores protected with double inorganic shells (core−shell−shell nanocrystals). The outer ZnS shell provides efficient confinement of electron and hole wave functions inside the nanocrystal as well as high photochemical stability. Introducing the middle shell (CdS or ZnSe) sandwiched between CdSe core and ZnS outer shell allows considerable reducing strain inside nanocrystals because CdS and ZnSe have the lattice parameter intermediate to those of CdSe and ZnS. In contrast to CdSe/ZnS core−shells, in the core−shell−shell nanocrystals ZnS shell grows nearly defect free. Due to high quality of the ZnS shell, the core−shell−shell nanocrystals exhibit PL efficiency and photostability exceeding those of CdSe/ZnS nanocrystals. Preferential growth of the middle CdS shell in one crystallographic direction allows engineering the shape and luminescence polarization of the core−shell−shell nanocrystals.

719 citations


Journal ArticleDOI
TL;DR: In this article, a D7-brane probe was introduced into the deformed AdS space to study gravity duals of large N nonsupersymmetric gauge theories with matter in the fundamental representation.
Abstract: We study gravity duals of large N nonsupersymmetric gauge theories with matter in the fundamental representation by introducing a D7-brane probe into deformed AdS backgrounds. In particular, we consider a D7-brane probe in both the AdS Schwarzschild black hole solution and in the background found by Constable and Myers, which involves a nonconstant dilaton and S5 radius. Both these backgrounds exhibit confinement of fundamental matter and a discrete glueball and meson spectrum. We numerically compute the Psi-bar Psi condensate and meson spectrum associated with these backgrounds. In the AdS–black-hole background, a quark-bilinear condensate develops only at a nonzero quark mass. We speculate on the existence of a third order phase transition at a critical quark mass where the D7 embedding undergoes a geometric transition. In the Constable-Myers background, we find a chiral symmetry breaking condensate as well as the associated Goldstone boson in the limit of small quark mass. The existence of the condensate ensures that the D7-brane never reaches the naked singularity at the origin of the deformed AdS space.

677 citations


Journal ArticleDOI
TL;DR: Lumiracoxib showed a three to four-fold reduction in ulcer complications compared with non-steroidal anti-inflammatory drugs without an increase in the rate of serious cardiovascular events, suggesting that lumiracxib is an appropriate treatment for patients with osteoarthritis.

670 citations


Journal ArticleDOI
TL;DR: In this paper, optical, structural, and electrical properties of thin layers made from poly(3-hexylthiophene) (P3HT) samples of different molecular weights are presented.
Abstract: The optical, structural, and electrical properties of thin layers made from poly(3-hexylthiophene) (P3HT) samples of different molecular weights are presented. As reported in a previous paper by Kline et al., Adv. Mater 2003, 15, 1519, the mobilities of these layers are a strong function of the molecular weight, with the largest mobility found for the largest molecular weight. Atomic force microscopy studies reveal a complex polycrystalline morphology which changes considerably upon annealing. X-ray studies show the occurrence of a layered phase for all P3HT fractions, especially after annealing at 1.50 degreesC . However, there is no clear correlation between the differences in the transport properties and the data from structural investigations. In order to reveal the processes limiting the mobility in these layers, the transistor properties were investigated as a function of temperature. The mobility decreases continuously with increasing temperatures; with the same trend pronounced thermochromic effects of the P3HT films occur. Apparently, the polymer chains adopt a more twisted, disordered conformation at higher temperatures, leading to interchain transport barriers. We conclude that the backbone conformation of the majority of the bulk material rather than the crystallinity of the layer is the most crucial parameter controlling the charge transport in these P3HT layers. This interpretation is supported by the significant blue-shift of the solid-state absorption spectra with decreasing molecular weight, which is indicative of a larger distortion of the P3HT backbone in the low-molecular weight P3HT layers

Journal ArticleDOI
TL;DR: 'Function' is the key criterion for determining whether adult neurogenesis is successful and has truly generated new nerve cells and even suggests how they might contribute to cognitive processes.

Journal ArticleDOI
TL;DR: One third of patients presented with mild ALI, but more than half rapidly evolved to acute respiratory distress syndrome (ARDS), confirming the grading of severity between the two forms of the syndrome.
Abstract: Objectives To re-examine the epidemiology of acute lung injury (ALI) in European intensive care units (ICUs).


Journal ArticleDOI
TL;DR: A double mutant lacking both bacillomycin D and fengycin was heavily impaired in its ability to inhibit growth of phytopathogenic fungi, suggesting that both lipopeptides act in a synergistic manner.
Abstract: The environmental strain Bacillus amyloliquefaciens FZB42 promotes plant growth and suppresses plant pathogenic organisms present in the rhizosphere. We sampled sequenced the genome of FZB42 and identified 2,947 genes with >50% identity on the amino acid level to the corresponding genes of Bacillus subtilis 168. Six large gene clusters encoding nonribosomal peptide synthetases (NRPS) and polyketide synthases (PKS) occupied 7.5% of the whole genome. Two of the PKS and one of the NRPS encoding gene clusters were unique insertions in the FZB42 genome and are not present in B. subtilis 168. Matrix-assisted laser desorption ionization-time of flight mass spectrometry analysis revealed expression of the antibiotic lipopeptide products surfactin, fengycin, and bacillomycin D. The fengycin (fen) and the surfactin (srf) operons were organized and located as in B. subtilis 168. A large 37.2-kb antibiotic DNA island containing the bmy gene cluster was attributed to the biosynthesis of bacillomycin D. The bmy island was found inserted close to the fen operon. The responsibility of the bmy, fen, and srf gene clusters for the production of the corresponding secondary metabolites was demonstrated by cassette mutagenesis, which led to the loss of the ability to produce these peptides. Although these single mutants still largely retained their ability to control fungal spread, a double mutant lacking both bacillomycin D and fengycin was heavily impaired in its ability to inhibit growth of phytopathogenic fungi, suggesting that both lipopeptides act in a synergistic manner.

Journal ArticleDOI
Felix Aharonian1, A. G. Akhperjanian2, Klaus-Michael Aye3, A. R. Bazer-Bachi4, M. Beilicke5, Wystan Benbow1, David Berge1, P. Berghaus6, P. Berghaus7, Konrad Bernlöhr8, Konrad Bernlöhr1, O. Bolz1, Catherine Boisson4, C. Borgmeier8, F. Breitling8, A. M. Brown3, J. Bussons Gordo9, P. M. Chadwick3, V. R. Chitnis4, V. R. Chitnis10, L-M. Chounet11, R. Cornils5, Luigi Costamante1, B. Degrange11, A. Djannati-Ataï6, L. O'c. Drury12, Tulun Ergin8, P. Espigat6, F. Feinstein9, P. Fleury11, G. Fontaine11, Stefan Funk1, Y. A. Gallant9, B. Giebels11, Stefan Gillessen1, P. Goret13, Julien Guy7, Julien Guy4, C. Hadjichristidis3, M. Hauser, G. Heinzelmann5, Gilles Henri14, German Hermann1, Jim Hinton1, Werner Hofmann1, M. Holleran15, Dieter Horns1, O. C. de Jager15, I. Jung1, I. Jung16, B. Khélifi1, Nu. Komin8, A. Konopelko8, A. Konopelko1, I. J. Latham3, R. Le Gallou3, M. Lemoine11, A. Lemière6, N. Leroy11, Thomas Lohse8, A. Marcowith4, Conor Masterson1, T. J. L. McComb3, M. de Naurois4, M. de Naurois7, S. J. Nolan3, A. Noutsos3, K. J. Orford3, J. L. Osborne3, M. Ouchrif7, M. Ouchrif4, M. Panter1, Guy Pelletier14, S. Pita6, Martin Pohl17, Martin Pohl18, G. Pühlhofer1, Michael Punch6, B. C. Raubenheimer15, M. Raue5, J. Raux7, J. Raux4, S. M. Rayner3, I. Redondo19, I. Redondo11, A. Reimer18, Olaf Reimer18, J. Ripken5, M. Rivoal4, M. Rivoal7, L. Rob20, L. Rolland7, L. Rolland4, Gavin Rowell1, V. Sahakian2, L. Saugé14, S. Schlenker8, Reinhard Schlickeiser18, C. Schuster18, U. Schwanke8, M. Siewert18, Helene Sol4, R. Steenkamp21, C. Stegmann8, J.-P. Tavernet7, J.-P. Tavernet4, C. G. Théoret6, M. Tluczykont11, D. J. van der Walt15, G. Vasileiadis9, P. Vincent7, P. Vincent4, B. Visser15, Heinrich J. Völk1, Stefan Wagner 
04 Nov 2004-Nature
TL;DR: A TeV γ-ray image of the SNR shows the spatially resolved remnant has a shell morphology similar to that seen in X-rays, which demonstrates that very-high-energy particles are accelerated there, consistent with current ideas of particle acceleration in young SNR shocks.
Abstract: A significant fraction of the energy density of the interstellar medium is in the form of high-energy charged particles (cosmic rays)1. The origin of these particles remains uncertain. Although it is generally accepted that the only sources capable of supplying the energy required to accelerate the bulk of Galactic cosmic rays are supernova explosions, and even though the mechanism of particle acceleration in expanding supernova remnant (SNR) shocks is thought to be well understood theoretically2,3, unequivocal evidence for the production of high-energy particles in supernova shells has proven remarkably hard to find. Here we report on observations of the SNR RX J1713.7 - 3946 (G347.3 - 0.5), which was discovered by ROSAT4 in the X-ray spectrum and later claimed as a source of high-energy γ-rays5,6 of TeV energies (1 TeV = 1012 eV). We present a TeV γ-ray image of the SNR: the spatially resolved remnant has a shell morphology similar to that seen in X-rays, which demonstrates that very-high-energy particles are accelerated there. The energy spectrum indicates efficient acceleration of charged particles to energies beyond 100 TeV, consistent with current ideas of particle acceleration in young SNR shocks.

Journal ArticleDOI
TL;DR: An imaging approach combining DE and T2-weighted CMR accurately differentiates acute from chronic MI.
Abstract: Background— Delayed enhancement (DE) cardiovascular magnetic resonance (CMR) detects acute and chronic myocardial infarction (MI) by visualizing contrast media accumulation in infarcted segments T2-weighted CMR depicts infarct-related myocardial edema as a marker of acute but not chronic myocardial injury We investigated the clinical utility of an approach combining both techniques to differentiate acute from chronic MI Methods and Results— Seventy-three MI patients were studied in 2 groups Group A consisted of 15 acute MI patients who were studied twice, on day 1 and 3 months after MI In group B, 58 patients with acute or chronic MI underwent 1 CMR scan T2-weighted and DE images of matched slices were acquired on a 15-T system In group A, quantitative segmental and region of interest-based analyses were performed to observe signal changes between the acute and chronic phases In group B, T2-weighted and DE images were examined visually by 2 blinded observers for the presence or absence of hyperin

Journal ArticleDOI
TL;DR: The primary endpoint, including incidence of myocardial infarction, did not differ between lumiracoxib and either ibuprofen or naproxen, irrespective of aspirin use, suggesting that lumirACoxib is an appropriate treatment for patients with osteoarthritis, who are often at high cardiovascular risk and taking low-dose aspirin.

Journal ArticleDOI
TL;DR: In this article, the strongest shift in plant development occurred for the very early spring phases and the late spring and summer phases reacted also to the increased temperatures, but they usually show lower trends.

Journal ArticleDOI
26 Feb 2004-Nature
TL;DR: The model shows how the S domain of SRP contacts the large ribosomal subunit at the nascent chain exit site to bind the signal sequence, and that the Alu domain reaches into the elongation-factor-binding site of the ribosome, explaining its elongation arrest activity.
Abstract: Cotranslational translocation of proteins across or into membranes is a vital process in all kingdoms of life. It requires that the translating ribosome be targeted to the membrane by the signal recognition particle (SRP), an evolutionarily conserved ribonucleoprotein particle. SRP recognizes signal sequences of nascent protein chains emerging from the ribosome. Subsequent binding of SRP leads to a pause in peptide elongation and to the ribosome docking to the membrane-bound SRP receptor. Here we present the structure of a targeting complex consisting of mammalian SRP bound to an active 80S ribosome carrying a signal sequence. This structure, solved to 12 A by cryo-electron microscopy, enables us to generate a molecular model of SRP in its functional conformation. The model shows how the S domain of SRP contacts the large ribosomal subunit at the nascent chain exit site to bind the signal sequence, and that the Alu domain reaches into the elongation-factor-binding site of the ribosome, explaining its elongation arrest activity.

Journal ArticleDOI
TL;DR: This early description of MRI-guided focused ultrasound therapy treatment of fibroids shows that, although the volume reduction is moderate, it correlates with treatment volume and the symptomatic response to this treatment is encouraging.
Abstract: OBJECTIVE. The purpose of this study was to explore our hypothesis that MRI-guided focused ultrasound therapy for the treatment of uterine fibroids will lead to a significant reduction in symptoms and improvement in quality of life. We describe focused ultrasound therapy applications and the method for monitoring the thermal energy deposited in the fibroids, including the MRI parameters required, in a prospective review of 108 treatments.MATERIALS AND METHODS. Patients presenting with symptomatic uterine fibroids who attained a minimal symptom severity score and who would otherwise have been offered a hysterectomy were recruited. Thermal lesions were created within target fibroids using an MRI-guided focused ultrasound therapy system. The developing lesion was monitored using real-time MR thermometry, which was used to assess treatment outcome in real time to change treatment parameters and achieve the desired outcome.Fibroid volume, fibroid symptoms, and quality-of-life scores were measured before treatm...

Journal ArticleDOI
TL;DR: An 11.7‐Å‐resolution cryo‐EM map of the yeast 80S·eEF2 complex in the presence of the antibiotic sordarin was interpreted in molecular terms, revealing large conformational changes within eEF2 and the 80S ribosome, including a rearrangement of the functionally important ribosomal intersubunit bridges.
Abstract: An 11.7-A-resolution cryo-EM map of the yeast 80S·eEF2 complex in the presence of the antibiotic sordarin was interpreted in molecular terms, revealing large conformational changes within eEF2 and the 80S ribosome, including a rearrangement of the functionally important ribosomal intersubunit bridges. Sordarin positions domain III of eEF2 so that it can interact with the sarcin–ricin loop of 25S rRNA and protein rpS23 (S12p). This particular conformation explains the inhibitory action of sordarin and suggests that eEF2 is stalled on the 80S ribosome in a conformation that has similarities with the GTPase activation state. A ratchet-like subunit rearrangement (RSR) occurs in the 80S·eEF2·sordarin complex that, in contrast to Escherichia coli 70S ribosomes, is also present in vacant 80S ribosomes. A model is suggested, according to which the RSR is part of a mechanism for moving the tRNAs during the translocation reaction.

Journal ArticleDOI
01 Oct 2004
TL;DR: In this paper, the authors reported the detection of a point-like source of very high energy (VHE) gamma-rays coincident within 1' of Sgr A*, obtained with the H.E.S. array of Cherenkov telescopes.
Abstract: We report the detection of a point-like source of very high energy (VHE) gamma-rays coincident within 1' of Sgr A*, obtained with the H.E.S.S. array of Cherenkov telescopes. The gamma-rays exhibit a power-law energy spectrum with a spectral index of -2.2 +/- 0.09 +/- 0.15 and a flux above the 165 GeV threshold of (1.82 +/- 0.22) \times 10^{-7} m^{-2} s^{-1}. The measured flux and spectrum differ substantially from recent results reported in particular by the CANGAROO collaboration.

Journal ArticleDOI
TL;DR: The present investigation clearly contradicts former hypothesis that the amount of appendages of the total skin surface represents not more than 0.1% and leads to a differential evaluation of skin penetration processes and a completely different understanding of penetration of topically applied drugs and cosmetics.

Journal ArticleDOI
TL;DR: Evidence suggests that tripeptidyl peptidase II (TPPII), a large peptid enzyme with exo-and endo-proteolytic activities, is also involved in antigen processing and may generate a specific set of MHC class I epitopes.

Journal ArticleDOI
TL;DR: VR1 is widely distributed in the skin, suggesting a major role for this receptor, e.g. in nociception and neurogenic inflammation.
Abstract: The vanilloid receptor subtype 1 (VR1)/(TRPV1), binding capsaicin, is a non-selective cation channel that recently has been shown in human keratinocytes in vitro and in vivo. However, a description of VR1 localization in other cutaneous compartments in particular cutaneous nerve fibers is still lacking. We therefore investigated VR1 immunoreactivity as well as mRNA and protein expression in a series (n = 26) of normal (n = 7), diseased (n = 13) [prurigo nodularis (PN) (n = 10), generalized pruritus (n = 1), and mastocytosis (n = 2)], and capsaicin-treated human skin (n = 6). VR1 immunoreactivity could be observed in cutaneous sensory nerve fibers, mast cells, epidermal keratinocytes, dermal blood vessels, the inner root sheet and the infundibulum of hair follicles, differentiated sebocytes, sweat gland ducts, and the secretory portion of eccrine sweat glands. Upon reverse transcriptase-polymerase chain reaction and Western blot analysis, VR1 was detected in mast cells and keratinocytes from human skin. In pruritic skin of PN, VR1 expression was highly increased in epidermal keratinocytes and nerve fibers, which was normalized after capsaicin application. During capsaicin therapy, a reduction of neuropeptides (substance P, calcitonin gene-related peptide) was observed. After cessation of capsaicin therapy, neuropeptides re-accumulated in skin nerves. In conclusion, VR1 is widely distributed in the skin, suggesting a major role for this receptor, e.g. in nociception and neurogenic inflammation.

Journal ArticleDOI
TL;DR: In this paper, a parameter-optimized off-axis setup for digital holographic microscopy is presented for simultaneous, high-resolution, full-field quantitative amplitude and quantitative phase contrast microscopy and the detection of changes in optical path length in transparent objects, such as undyed living cells.
Abstract: A parameter-optimized off-axis setup for digital holographic microscopy is presented for simultaneous, high-resolution, full-field quantitative amplitude and quantitative phase-contrast microscopy and the detection of changes in optical path length in transparent objects, such as undyed living cells. Numerical reconstruction with the described nondiffractive reconstruction method, which suppresses the zero order and the twin image, requires a mathematical model of the phase-difference distribution between the object wave and the reference wave in the hologram plane. Therefore an automated algorithm is explained that determines the parameters of the mathematical model by carrying out the discrete Fresnel transform. Furthermore the relationship between the axial position of the object and the reconstruction distance, which is required for optimization of the lateral resolution of the holographic images, is derived. The lateral and the axial resolutions of the system are discussed and quantified by application to technical objects and to living cells.

Journal ArticleDOI
TL;DR: The data demonstrate that high contact and shear forces are generated during weight bearing combined with knee flexion angles greater than approximately 15° and Clinically, the conditions that produce these larger contact forces should be avoided during post‐operative rehabilitation.

Journal ArticleDOI
TL;DR: There was a significant correlation between capsaicin tussive response and the number of TRPV-1-positive nerves within the patients with cough, indicating that TRPVs may contribute to an enhanced cough reflex and the cough response in chronic persistent cough of diverse causes.
Abstract: Transient receptor potential vanniloid-1 (TRPV-1) mediates the cough response induced by the pepper extract capsaicin and is expressed in sensory nerves that innervate the airway wall. We determined the expression of TRPV-1 in the airways of patients with chronic persistent cough of diverse causes and with an enhanced capsaicin cough response. We obtained airway mucosal biopsies by fiberoptic bronchoscopy in 29 patients with chronic cough and 16 healthy volunteers without a cough. Immunostaining for nerve profiles with anti-protein gene product (PGP)-9.5 antibody showed no increase in nerve profiles in the airway epithelium of patients with chronic cough; however, with an anti-TRPV-1 antibody, there was a fivefold increase of TRPV-1 staining nerve profiles (p < 0.001). There was a significant correlation between capsaicin tussive response and the number of TRPV-1-positive nerves within the patients with cough. Our findings indicate that TRPV-1 receptors may contribute to an enhanced cough reflex and the cough response in chronic persistent cough of diverse causes.

Journal ArticleDOI
TL;DR: The current pathophysiological understanding of stroke is substantially based on experimental studies, and mechanisms of damage and endogenous protection present distinct molecular targets that are the rational basis for the development of neuroprotective drugs.
Abstract: The current pathophysiological understanding of stroke is substantially based on experimental studies. Brain injury after cerebral ischemia develops from a complex signaling cascade that evolves in an at least partially unraveled spatiotemporal pattern. Early excitotoxicity can lead to fast necrotic cell death, which produces the core of the infarction. The ischemic penumbra that surrounds the infarct core suffers milder insults. In this area, both mild excitotoxic and inflammatory mechanisms lead to delayed cell death, which shows biochemical characteristics of apoptosis. While brain cells are challenged by these deleterious mechanisms, they activate innate protective programs of the brain, which can be studied by means of experimentally inducing ischemic tolerance (i.e., ischemic preconditioning). Importantly, cerebral ischemia not only affects the brain parenchyma, but also impacts extracranial systems. For example, stroke induces a dramatic immunosuppression via an overactivation of the sympathetic nervous system. As a result, severe bacterial infections such as pneumonia occur. Complex signaling cascades not only decide about cell survival, but also about the neurological deficit and the mortality after stroke. These mechanisms of damage and endogenous protection present distinct molecular targets that are the rational basis for the development of neuroprotective drugs.