2,295 research outputs found

    Sign-changing blowing-up solutions for the critical nonlinear heat equation

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    Let Ω\Omega be a smooth bounded domain in Rn\mathbb{R}^n and denote the regular part of the Green's function on Ω\Omega with Dirichlet boundary condition as H(x,y)H(x,y). Assuming the integer k0k_0 is sufficiently large, q∈Ωq \in \Omega and n≥5n\geq 5. For k≥k0k\geq k_0, we prove that there exist initial data u0u_0 and smooth parameter functions ξ(t)→q\xi(t)\to q, 0<\mu(t)\to 0 (t→+∞t\to +\infty) such that the solution uqu_q of the critical nonlinear heat equation\begin{equation*}\begin{cases}u_t = \Delta u + |u|^{\frac{4}{n-2}}u\text{ in } \Omega\times (0, \infty),\\u = 0\text{ on } \partial \Omega\times (0, \infty),\\u(\cdot, 0) = u_0 \text{ in }\Omega,\end{cases}\end{equation*}has form\begin{equation*}u_q(x, t) \approx \mu(t)^{-\frac{n-2}{2}}\left(Q_k\left(\frac{x-\xi(t)}{\mu(t)}\right) - H(x, q)\right),\end{equation*}where the profile QkQ_k is the non-radial sign-changing solution of the Yamabe equation\begin{equation*}\Delta Q + |Q|^{\frac{4}{n-2}}Q = 0\text{ in }\mathbb{R}^n,\end{equation*}constructed in \cite{delpinomussofrankpistoiajde2011}. In dimension 5 and 6, we also investigate the stability of uq(x,t)u_q(x, t)

    Thermal donors formation via isothermal annealing in magnetic Czochralski high resistivity silicon

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    A quantitative study about the thermal activation of oxygen related thermal donors in high resistivity p-type magnetic Czochralski silicon has been carried out. Thermal donor formation has been performed through isothermal annealing at 430°C up to a total time of 120min. Space charge density after each annealing step has been measured by transient current technique. The localized energy levels related to thermal double donors (TD) have been observed and studied in details by thermally stimulated currents (TSCs) in the range of 10–70K, and activation energies E and effective cross sections σ have been determined for both the emissions TD0∕+ (E=75±5meV, σ=4×10−14cm2) and TD+∕+ (E=170±5meV, σ=2×10−12cm2). The evolution of the space charge density caused by annealing has been unambiguously related to the activation of TDs by means of current deep level transient spectroscopy TSC, and current transients at constant temperature i(t,T). Our results show that TDs compensate the initial boron doping, eventually provoking the sign inversion of the space charge density. TD's generation rate has been found to be linear with the annealing time and to depend critically on the initial interstitial oxygen concentration, in agreement with previous models developed on low resistivity silicon

    Filamin B represses chondrocyte hypertrophy in a Runx2/Smad3-dependent manner

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    FILAMIN B, which encodes a cytoplasmic actin binding protein, is mutated in several skeletal dysplasias. To further investigate how an actin binding protein influences skeletogenesis, we generated mice lacking intact Filamin B. As observed in spondylocarpotarsal synostosis syndrome patients, Filamin B mutant mice display ectopic mineralization in many cartilaginous elements. This aberrant mineralization is due to ectopic chondrocyte hypertrophy similar to that seen in mice expressing Runx2 in chondrocytes. Accordingly, removing one copy of Runx2 rescues the Filamin B mutant phenotype, indicating that Filamin B is a regulator of Runx2 function during chondrocyte differentiation. Filamin B binds Smad3, which is known to interact with Runx2. Smad3 phosphorylation is increased in the mutant mice. Thus, Filamin B inhibits Runx2 activity, at least in part, through the Smad3 pathway. Our results uncover the involvement of actin binding proteins during chondrogenesis and provide a molecular basis to a human genetic disease

    A proteomic analysis of Psychrobacter articus 273-4 adaptation to low temperature and salinity using a 2-D liquid mapping approach

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    Psychrobacter 273-4 was isolated from a 20 000–40 000–year-old Siberian permafrost core, which is characterized by low temperature, low water activity, and high salinity. To explore how 273-4 survives in the permafrost environment, proteins in four 273-4 samples cultured at 4 and 22°C in media with and without 5% 14sodium chloride were profiled and comparatively studied using 2-D HPLC and MS. The method used herein involved fractionation via a pH gradient using chromatofocusing followed by nonporous silica 14(NPS) RP-HPLC and on-line electrospray mass mapping. It was observed that 33 14proteins were involved in the adaptation to low temperature in the cells grown in the nonsaline media while there were only 14 proteins involved in the saline media. There were 45 14proteins observed differentially expressed in response to salt at 22°C while there were 22 14proteins at 4°C. In addition, 5% 14NaCl and 4°C showed a combination effect on protein expression. A total of 56 14proteins involved in the adaptation to low temperature and salt were identified using MS and database searching. The differentially expressed proteins were classified into different functional categories where the response of the regulation system to stress appears to be very elaborate. The evidence shows that the adaptation of 273-4 is based primarily on the control of translation and transcription, the synthesis of proteins (chaperones) to facilitate RNA and protein folding, and the regulation of metabolic pathways.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55939/1/467_ftp.pd

    Streptococcus suis serotype 2 strains isolated in Argentina (South America) are different from those recovered in North America and present a higher risk for humans

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    Introduction: Streptococcus suis serotype 2 is an important swine pathogen and emerging zoonotic agent causing meningitis and septicemia/septic shock. Strains are usually virulent (Eurasia) or of intermediate/low virulence (North America). Very few data regarding human and swine isolates from South America are available. Case presentation: Seventeen new human S. suis cases in Argentina (16 serotype 2 strains and a serotype 5 strain) are reported. Alongside, 14 isolates from pigs are analyzed: 12 from systemic disease, one from lungs and one from tonsils of a healthy animal. All human serotype 2 strains and most swine isolates are sequence type (ST) 1, as determined by multilocus sequence typing and present a mrp+/epf+/sly + genotype typical of virulent Eurasian ST1 strains. The remaining two strains (recovered from swine lungs and tonsils) are ST28 and possess a mrp+/epf − /sly− genotype typical of low virulence North American strains. Representative human ST1 strains as well as one swine ST28 strain were analyzed by whole-genome sequencing and compared with genomes from GenBank. ST1 strains clustered together with three strains from Vietnam and this cluster is close to another one composed of 11 strains from the United Kingdom. Conclusion: Close contact with pigs/pork products, a good surveillance system, and the presence of potentially virulent Eurasian-like serotype 2 strains in Argentina may be an important factor contributing to the higher number of human cases observed. In fact, Argentina is now fifth among Western countries regarding the number of reported human cases after the Netherlands, France, the UK and Poland.EEA Marcos JuárezFil: Callejo, Raquel. Instituto Nacional de Enfermedades Infecciosas; ArgentinaFil: Han, Zheng. National Institute for Communicable Disease Control and Prevention. Chinese Center for Disease Control. State Key Laboratory for Infectious Disease Prevention and Control. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases; ChinaFil: Pengcheng, Du. Beijing Ditan Hospital. Institute of Infectious Diseases.Capital Medical University. Beijing Key Laboratory of Emerging Infectious Diseases; ChinaFil: Prieto, Monica. Instituto Nacional de Enfermedades Infecciosas; ArgentinaFil: Jianguo, Xu. National Institute for Communicable Disease Control and Prevention. Chinese Center for Disease Control. State Key Laboratory for Infectious Disease Prevention and Control. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases; ChinaFil: Zielinski, Gustavo Carlos. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Marcos Juárez; ArgentinaFil: Auger, Jean-Philippe. University of Montreal. Faculty of Veterinary Medicine. Swine and Poultry Infectious Disease Center (CRIPA); CanadaFil: Gottschalk, Marcelo. University of Montreal. Faculty of Veterinary Medicine. Swine and Poultry Infectious Disease Center (CRIPA); Canad

    ABO(H) blood group A and B glycosyltransferases recognize substrate via specific conformational changes.

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    The final step in the enzymatic synthesis of the ABO(H) blood group A and B antigens is catalyzed by two closely related glycosyltransferases, an alpha-(1-->3)-N-acetylgalactosaminyltransferase (GTA) and an alpha-(1-->3)-galactosyltransferase (GTB). Of their 354 amino acid residues, GTA and GTB differ by only four "critical" residues. High resolution structures for GTB and the GTA/GTB chimeric enzymes GTB/G176R and GTB/G176R/G235S bound to a panel of donor and acceptor analog substrates reveal "open," "semi-closed," and "closed" conformations as the enzymes go from the unliganded to the liganded states. In the open form the internal polypeptide loop (amino acid residues 177-195) adjacent to the active site in the unliganded or H antigen-bound enzymes is composed of two alpha-helices spanning Arg(180)-Met(186) and Arg(188)-Asp(194), respectively. The semi-closed and closed forms of the enzymes are generated by binding of UDP or of UDP and H antigen analogs, respectively, and show that these helices merge to form a single distorted helical structure with alternating alpha-3(10)-alpha character that partially occludes the active site. The closed form is distinguished from the semi-closed form by the ordering of the final nine C-terminal residues through the formation of hydrogen bonds to both UDP and H antigen analogs. The semi-closed forms for various mutants generally show significantly more disorder than the open forms, whereas the closed forms display little or no disorder depending strongly on the identity of residue 176. Finally, the use of synthetic analogs reveals how H antigen acceptor binding can be critical in stabilizing the closed conformation. These structures demonstrate a delicately balanced substrate recognition mechanism and give insight on critical aspects of donor and acceptor specificity, on the order of substrate binding, and on the requirements for catalysis

    Structural Basis for the Inactivity of Human Blood Group O2 Glycosyltransferase

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    The human ABO(H) blood group antigens are carbohydrate structures generated by glycosyltransferase enzymes. Glycosyltransferase A (GTA) uses UDP-GalNAc as a donor to transfer a monosaccharide residue to Fuc alpha1-2Gal beta-R (H)-terminating acceptors. Similarly, glycosyltransferase B (GTB) catalyzes the transfer of a monosaccharide residue from UDP-Gal to the same acceptors. These are highly homologous enzymes differing in only four of 354 amino acids, Arg/Gly-176, Gly/Ser-235, Leu/Met-266, and Gly/Ala-268. Blood group O usually stems from the expression of truncated inactive forms of GTA or GTB. Recently, an O(2) enzyme was discovered that was a full-length form of GTA with three mutations, P74S, R176G, and G268R. We showed previously that the R176G mutation increased catalytic activity with minor effects on substrate binding. Enzyme kinetics and high resolution structural studies of mutant enzymes based on the O(2) blood group transferase reveal that whereas the P74S mutation in the stem region of the protein does not appear to play a role in enzyme inactivation, the G268R mutation completely blocks the donor GalNAc-binding site leaving the acceptor binding site unaffected

    OR.107. TIM-1 Plays a Crucial Role in the Expansion of Autopathogneic T-Cells and Regulation of Autoimmunity [abstract only]

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    T-cell immunoglobulin and mucin (TIM) family Members are differentially expressed on Th1 and Th2 cells. Polymorphisms of TIM-1 have been associated with susceptibility to asthma; however, its role in regulating autoimmunity has not been studied. Here, we have used an agonistic antiTIM-1 antibody (Ab, Clone 3B3) which has previously been shown to costimulate T-cell activation and expansion, to analyze the role of TIM-1 in the development and regulation of experimental autoimmune encephalomyelitis (EAE). Treatment with 3B3 dramatically enhances the severity of EAE as well as the frequency of encephalitogenic CD4+ T-cells and the production of IFN-g and IL-17 by these cells. Furthermore, administration of 3B3 breaks self-tolerance and induces EAE in the disease resistant B10.S strain. We have utilized another anti-TIM-1 Ab (RMT1-10) that does not costimulate T-cell activation in vitro. In contrast to 3B3, treatment with RMT1-10 inhibits the development of EAE and reduces the frequency of encephalitogenic CD4+ T-cells with a commensurate decrease in the production of IFN-g and IL-17. Treatment with RMT1-10 causes CD4+ T-cells to produce more IL-4 and IL-10. We provide evidence that both 3B3 and RMT1-10 bind to the same epitope in the Ig domain of TIM-1, but the binding affinity of 3B3 is much higher than that of RMT1-10. These data suggest that TIM-1 engagement with the agonistic Ab, along with TcR ligation, costimulates T-cell expansion with pro-inflammatory IFN-g and IL-17 production resulting in the breakdown of self-tolerance and development of autoimmunity, whereas blocking anti-TIM-1 Ab causes a decrease in the autopathogenic Th1/ThIL-17 responses. This study demonstrates that TIM-1 is a key cell surface molecule that regulates effector T-cell response and depending on hopw the molecule is engaged, autoimmune responses can be either enhanced or inhibited in vivo

    Scaling relations of metallicity, stellar mass, and star formation rate in metal-poor starbursts: I. A fundamental plane

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    Most galaxies follow well-defined scaling relations of metallicity (O/H), star formation rate (SFR), and stellar mass. However, low-metallicity starbursts, rare in the Local Universe but more common at high redshift, deviate significantly from these scaling relations. On the "main sequence" of star formation, these galaxies have high SFR for a given M*; and on the mass-metallicity relation, they have excess M* for their low metallicity. In this paper, we characterize O/H, M*, and SFR for these deviant "low-metallicity starbursts", selected from a sample of ~1100 galaxies, spanning almost two orders of magnitude in metal abundance, a factor of ~10^6 in SFR, and of ~10^5 in stellar mass. Our sample includes quiescent star-forming galaxies and blue compact dwarfs at redshift 0, luminous compact galaxies at redshift 0.3, and Lyman Break galaxies at redshifts 1-3.4. Applying a Principal Component Analysis (PCA) to the galaxies in our sample with M*<10^{10} Msun gives a Fundamental Plane (FP) of scaling relations; SFR and stellar mass define the plane itself, and O/H its thickness. The dispersion for our sample in the edge-on view of the plane is 0.17 dex, independently of redshift and including the metal-poor starbursts. The same FP is followed by 55100 galaxies selected from the Sloan Digital Sky Survey, with a dispersion of 0.06dex. In a companion paper, we develop multi-phase chemical evolution models that successfully predict the observed scaling relations and the FP; the deviations from the main scaling relations are caused by a different (starburst or "active") mode of star formation. These scaling relations do not truly evolve, but rather are defined by the different galaxy populations dominant at different cosmological epochs.Comment: 14 pages, 7 figures, accepted for publication by MNRA

    Intakes of culinary herbs and spices from a food frequency questionnaire evaluated against 28-days estimated records

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    <p>Abstract</p> <p>Background</p> <p>Worldwide, herbs and spices are much used food flavourings. However, little data exist regarding actual dietary intake of culinary herbs and spices. We developed a food frequency questionnaire (FFQ) for the assessment of habitual diet the preceding year, with focus on phytochemical rich food, including herbs and spices. The aim of the present study was to evaluate the intakes of herbs and spices from the FFQ with estimates of intake from another dietary assessment method. Thus we compared the intake estimates from the FFQ with 28 days of estimated records of herb and spice consumption as a reference method.</p> <p>Methods</p> <p>The evaluation study was conducted among 146 free living adults, who filled in the FFQ and 2-4 weeks later carried out 28 days recording of herb and spice consumption. The FFQ included a section with questions about 27 individual culinary herbs and spices, while the records were open ended records for recording of herbs and spice consumption exclusively.</p> <p>Results</p> <p>Our study showed that the FFQ obtained slightly higher estimates of total intake of herbs and spices than the total intake assessed by the Herbs and Spice Records (HSR). The correlation between the two assessment methods with regard to total intake was good (r = 0.5), and the cross-classification suggests that the FFQ may be used to classify subjects according to total herb and spice intake. For the 8 most frequently consumed individual herbs and spices, the FFQ obtained good estimates of median frequency of intake for 2 herbs/spices, while good estimates of portion sizes were obtained for 4 out of 8 herbs/spices.</p> <p>Conclusions</p> <p>Our results suggested that the FFQ was able to give good estimates of frequency of intake and portion sizes on group level for several of the most frequently used herbs and spices. The FFQ was only able to fairly rank subjects according to frequency of intake of the 8 most frequently consumed herbs and spices. Other studies are warranted to further explore the intakes of culinary spices and herbs.</p
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