1,674 research outputs found

    Comparison of the ultrafast to slow time scale dynamics of three liquid crystals in the isotropic phase

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    The dynamics of three liquid crystals, 4'(pentyloxy)-4-biphenylcarbonitrile (5-OCB), 4'-pentyl-4-biphenylcarbonitrile (5-CB), and 1-isothiocyanato-(4-propylcyclohexyl)benzene (3-CHBT), are investigated from very short time (~1 ps) to very long time (>100 ns) as a function of temperature using optical heterodyne detected optical Kerr effect experiments. For all three liquid crystals, the data decay exponentially only on the longest time scale (>several ns). The temperature dependence of the long time scale exponential decays is described well by the Landau-de Gennes theory of the randomization of pseudonematic domains that exist in the isotropic phase of liquid crystals near the isotropic to nematic phase transition. At short time, all three liquid crystals display power law decays. Over the full range of times, the data for all three liquid crystals are fit with a model function that contains a short time power law. The power law exponents for the three liquid crystals range between 0.63 and 0.76, and the power law exponents are temperature independent over a wide range of temperatures. Integration of the fitting function gives the empirical polarizability-polarizability (orientational) correlation function. A preliminary theoretical treatment of collective motions yields a correlation function that indicates that the data can decay as a power law at short times. The power law component of the decay reflects intradomain dynamics

    Absolute differential positronium-formation cross sections

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    The first absolute experimental determinations of the differential cross-sections for the formation of ground-state positronium are presented for He, Ar, H2 and CO2 near 0○. Results are compared with available theories. The ratio of the differential and integrated cross-sections for the targets exposes the higher propensity for forward-emission of positronium formed from He and H2

    Liquid crystal dynamics in the isotropic phase

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    The dynamics in the isotropic phase of the liquid crystal 1-isothiocyanato-(4-propylcyclohexyl) benzene (3-CHBT) are investigated from very short time (~1 ps) to very long time (>100 ns) as function of temperature. The data decay exponentially only on the longest time scale (>10 ns). The temperature dependence of the long time scale exponential decays is described well by the Landau-de Gennes theory of the randomization of pseudo-nematic domains that exist in the isotropic phase of liquid crystals near the isotropic to nematic phase transition. Over the full range of times, the data are fit with a model function that contains a short time power law. The power law exponent is temperature independent over a wide range of temperatures. Integration of the function gives the empirical polarizability-polarizability (orientational) correlation function. A preliminary theoretical treatment of collective motions yields a correlation function that indicates that the data can decay as a power law at short times. The power law component of the decay reflects intradomain dynamics

    DeepSRE: Identification of sterol responsive elements and nuclear transcription factors Y proximity in human DNA by Convolutional Neural Network analysis

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    SREBP1 and 2, are cholesterol sensors able to modulate cholesterol-related gene expression responses. SREBPs binding sites are characterized by the presence of multiple target sequences as SRE, NFY and SP1, that can be arranged differently in different genes, so that it is not easy to identify the binding site on the basis of direct DNA sequence analysis. This paper presents a complete workflow based on a one-dimensional Convolutional Neural Network (CNN) model able to detect putative SREBPs binding sites irrespective of target elements arrangements. The strategy is based on the recognition of SRE linked (less than 250 bp) to NFY sequences according to chromosomal localization derived from TF Immunoprecipitation (TF ChIP) experiments. The CNN is trained with several 100 bp sequences containing both SRE and NF-Y. Once trained, the model is used to predict the presence of SRE-NFY in the first 500 bp of all the known gene promoters. Finally, genes are grouped according to biological process and the processes enriched in genes containing SRE-NFY in their promoters are analyzed in details. This workflow allowed to identify biological processes enriched in SRE containing genes not directly linked to cholesterol metabolism and possible novel DNA patterns able to fill in for missing classical SRE sequences

    RT-PCR and in situ hybridization analysis of apolipoprotein H expression in rat normal tissues

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    In this study, by using different techniques (i.e. Northern blot hybridization, RT-PCR and Southern blot hybridization) on various normal rat tissues, we were able to identify liver, kidney, heart, small intestine, brain, spleen, stomach and prostate as tissues in which the ApoH gene is transcribed. Moreover, for some of these tissues, by in situ hybridization, we found a specific localization of apoH transcripts. For instance epithelial cells of the bile ducts in liver and of the proximal tubules in kidney are the major sites of apoH synthesis. Our data suggest that some of the different physiological roles proposed for apoH could correlate with its direct expression, while others could correlate with its absorption from bloodstream or adjacent cells

    Orientational Dynamics of the Ionic Organic Liquid 1-Ethyl-3-Methylimidazolium Nitrate

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    Optical heterodyne-detected optical Kerr effect ͑OHD-OKE͒ experiments are used to study the orientational dynamics of the ionic organic liquid 1-ethyl-3-methylimidazolium nitrate (EMIM ϩ NO 3 Ϫ ) over time scales from ϳ1 ps to ϳ2 ns, and the temperatures range from 410 to 295 K. The temperatures cover the normal liquid state and the weakly supercooled state. The orientational dynamics exhibit characteristics typical of normal organic glass-forming liquids. The longest time scale portion of the data decays as a single exponential and obeys the Debye-StokesEinstein relation. The decay of the OHD-OKE signal begins (ϳ1 ps) with a temperature independent power law, t Ϫz , zϭ1.02Ϯ0.05, the ''intermediate power law.'' The power law decay is followed by a crossover region, modeled as a second power law, the von Schweidler power law. The longest time scale decay is the exponential ␣ relaxation. The intermediate power law decay has been observed in van der Waals supercooled liquids previously. These are the first such observations on an ionic organic liquid. The observation of the dynamical signatures observed in other liquids demonstrates that the orientational dynamics of ionic organic liquids are fundamentally the same as van der Waals liquids and supports the universality of the intermediate power law decay in the dynamics of complex liquids. Within the mode-coupling theory ͑MCT͒ framework, the MCT critical temperature T C is estimated to be T C Х255 K

    Frequency and clinical aspects of neurological and psychiatric symptoms in patients with non-celiac wheat sensitivity

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    Background: Non-Celiac Wheat Sensitivity (NCWS) is characterized by both intestinal and extra-intestinal symptoms. The study aims to investigate the frequency of neuropsychiatric manifestations in NCWS patients and identify their clinical and demographic characteristics. Methods: 278 clinical records of NCWS patients, diagnosed by a double-blind placebo-controlled wheat challenge between 2006 and 2020, were retrospectively revised. Fifty-two patients with Celiac Disease (CD) and 54 patients with Irritable Bowel Syndrome (IBS) served as controls. Results: 87% of the NCWS patients had an IBS-like clinical presentation. The NCWS group showed a longer duration of symptoms, a higher frequency of positive serum anti-nuclear antibodies than CD and IBS patients, and a higher frequency of DQ2/DQ8 haplotypes and duodenal mucosa lymphocytosis than IBS controls. In addition, 50% of NCWS patients showed neuropsychiatric manifestations, while lower percentages were observed in CD (25%) and IBS (28%) controls. Neuropsychiatric symptoms in NCWS were more frequently associated with the male sex, longer duration of symptoms, and IBS-diarrhea-like clinical presentation. Conclusions: Our data suggest that in patients with IBS-like symptoms and neuropsychiatric manifestations of unknown cause, it could be useful to investigate a correlation of these symptoms with wheat ingestion to identify NCWS patients with this ‘atypical’ manifestation

    PCSK9-D374Y mediated LDL-R degradation can be functionally inhibited by EGF-A and truncated EGF-A peptides: An in vitro study

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    Background and aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to low density lipoprotein receptor (LDLR) through the LDLR epidermal growth factor-like repeat A (EGF-A) domain and induces receptor internalization and degradation. PCSK9 has emerged as a novel therapeutic target for hypercholesterolemia. Clinical studies with PCSK9 inhibiting antibodies have demonstrated strong LDL-c lowering effects, but other therapeutic approaches using small molecule inhibitors for targeting PCSK9 functions may offer supplementary therapeutic options. The aim of our study was to evaluate the effect of synthetic EGF-A analogs on mutated (D374Y) PCSK9-D374Y mediated LDLR degradation in vitro. Methods: Huh7 human hepatoma cells were transiently transfected to overexpress the gain-of-function D374Y PCSK9 mutation, which has been associated with severe hypercholesterolemia in humans. Results: Transient transfection of cells with PCSK9-D374Y expression vector very effectively enhanced degradation of mature LDLR in Huh7. Treatment with both EGF-A and EGF-A truncated peptides inhibited this effect and showed increased LDLR protein in Huh7 cells transfected with PCSK9-D374Y in a clear concentration dependent manner. Huh7 transfected cells treated with increasing concentration of EGF-A analogs also showed an increase internalization of labeled Dil-LDL. Conclusions: The result of our study shows that EGF-A analogs are able to effectively hamper the enhanced degradation of LDLR in liver cells expressing PCSK9-D374Y

    Hydrogen bond dissociation and reformation in methanol oligomers following hydroxyl stretch relaxation

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    Vibrational relaxation and hydrogen bond dynamics in methanol-d dissolved in CCl 4 have been measured with ultrafast infrared pump-probe spectroscopy. We excited the subensemble of methanol-d molecules both accepting and donating hydrogen bonds at ∼2500 cm -1 . Following vibrational relaxation with a ∼500 fs lifetime, the signal does not decay to zero. Rather, the signal increases to a second maximum at ∼4 ps. The decay from the second maximum occurs on two time scales. We propose a model in which hydrogen bond dissociation, following vibrational relaxation, decreases the concentration of methanol-d molecules that accept and donate hydrogen bonds and produce the observed long-lived bleach of the absorption signal. Using a set of coupled kinetic equations, the time constants for hydrogen bond dissociation and reformation have been determined. Hydrogen bond breaking occurs with ∼200 fs and ∼2 ps time constants. We attribute the fast rate to a direct breaking mechanism wherein the excited hydroxyl stretch decays into modes that directly lead to the hydrogen bond dissociation. The slower rate of breaking is attributed to an indirect mechanism wherein the dissociation of hydrogen bonds follows vibrational energy flow from the initially excited molecule to other components of the same oligomer. The final stage of relaxation, after the second maximum, involves reformation of transiently broken hydrogen bonds. The bonds that break directly recover with ∼7 ps and .10 ns time constants, while the bonds that break indirectly recover with ∼20 ps and .10 ns time constants. Experiments conducted on ethanol-d solutions in CCl 4 demonstrate that the same vibrational relaxation and hydrogen bond dynamic events occur with very similar amplitudes and rate constants. Measurements of the rates of spectral diffusion and polarization anisotropy decay via vibrational excitation transfer and orientational relaxation verify that the initial fast decay of the signal is dominated by vibrational relaxation
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