Complementary test of the dark matter self-interaction in dark U(1) model by direct and indirect dark matter detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Chian-Shu; Department of Physics, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu, Taiwan, 30010 R.O.C.; Institute of Physics, Academia Sinica, 128 Sec. 2,Academia Rd., Nangang, Taipei, Taiwan, 11529 R.O.C.

2016-01-07

The halo dark matter (DM) can be captured by the Sun if its final velocity after the collision with a nucleus in the Sun is less than the escape velocity. We consider a selfinteracting dark matter (SIDM) model where U(1) gauge symmetry is introduced to account for the DM self-interaction. Such a model naturally leads to isospin violating DM-nucleon interaction, although isospin symmetric interaction is still allowed as a special case. We present the IceCube-PINGU 2σ sensitivity to the parameter range of the above model with 5 years of search for neutrino signature from DM annihilation in the Sun. Thismore » indirect detection complements the direct detection by probing those SIDM parameter ranges which are either the region for very small m{sub χ} or the region opened up due to isospin violations.« less

Complementary test of the dark matter self-interaction in dark U(1) model by direct and indirect dark matter detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Chian-Shu; Lin, Guey-Lin; Lin, Yen-Hsun, E-mail: chianshu@gmail.com, E-mail: glin@cc.nctu.edu.tw, E-mail: chris.py99g@g2.nctu.edu.tw

2016-01-01

The halo dark matter (DM) can be captured by the Sun if its final velocity after the collision with a nucleus in the Sun is less than the escape velocity. We consider a selfinteracting dark matter (SIDM) model where U(1) gauge symmetry is introduced to account for the DM self-interaction. Such a model naturally leads to isospin violating DM-nucleon interaction, although isospin symmetric interaction is still allowed as a special case. We present the IceCube-PINGU 2σ sensitivity to the parameter range of the above model with 5 years of search for neutrino signature from DM annihilation in the Sun. Thismore » indirect detection complements the direct detection by probing those SIDM parameter ranges which are either the region for very small m{sub χ} or the region opened up due to isospin violations.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berger, Joshua; /SLAC; Cui, Yanou

We study novel scenarios where thermal dark matter (DM) can be efficiently captured in the Sun and annihilate into boosted dark matter. In models with semi-annihilating DM, where DM has a non-minimal stabilization symmetry, or in models with a multi-component DM sector, annihilations of DM can give rise to stable dark sector particles with moderate Lorentz boosts. We investigate both of these possibilities, presenting concrete models as proofs of concept. Both scenarios can yield viable thermal relic DM with masses O(1)-O(100) GeV. Taking advantage of the energetic proton recoils that arise when the boosted DM scatters off matter, we proposemore » a detection strategy which uses large volume terrestrial detectors, such as those designed to detect neutrinos or proton decays. In particular, we propose a search for proton tracks pointing towards the Sun. We focus on signals at Cherenkov-radiation-based detectors such as Super-Kamiokande (SK) and its upgrade Hyper-Kamiokande (HK). We find that with spin-dependent scattering as the dominant DM-nucleus interaction at low energies, boosted DM can leave detectable signals at SK or HK, with sensitivity comparable to DM direct detection experiments while being consistent with current constraints. Our study provides a new search path for DM sectors with non-minimal structure.« less

You can hide but you have to run: direct detection with vector mediators

NASA Astrophysics Data System (ADS)

D'Eramo, Francesco; Kavanagh, Bradley J.; Panci, Paolo

2016-08-01

We study direct detection in simplified models of Dark Matter (DM) in which interactions with Standard Model (SM) fermions are mediated by a heavy vector boson. We consider fully general, gauge-invariant couplings between the SM, the mediator and both scalar and fermion DM. We account for the evolution of the couplings between the energy scale of the mediator mass and the nuclear energy scale. This running arises from virtual effects of SM particles and its inclusion is not optional. We compare bounds on the mediator mass from direct detection experiments with and without accounting for the running. In some cases the inclusion of these effects changes the bounds by several orders of magnitude, as a consequence of operator mixing which generates new interactions at low energy. We also highlight the importance of these effects when translating LHC limits on the mediator mass into bounds on the direct detection cross section. For an axial-vector mediator, the running can alter the derived bounds on the spin-dependent DM-nucleon cross section by a factor of two or more. Finally, we provide tools to facilitate the inclusion of these effects in future studies: general approximate expressions for the low energy couplings and a public code runDM to evolve the couplings between arbitrary energy scales.

Direct detection of light ''Ge-phobic'' exothermic dark matter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gelmini, Graciela B.; Georgescu, Andreea; Huh, Ji-Haeng, E-mail: gelmini@physics.ucla.edu, E-mail: a.georgescu@physics.ucla.edu, E-mail: jhhuh@physics.ucla.edu

2014-07-01

We present comparisons of direct dark matter (DM) detection data for light WIMPs with exothermic scattering with nuclei (exoDM), both assuming the Standard Halo Model (SHM) and in a halo model–independent manner. Exothermic interactions favor light targets, thus reducing the importance of upper limits derived from xenon targets, the most restrictive of which is at present the LUX limit. In our SHM analysis the CDMS-II-Si and CoGeNT regions become allowed by these bounds, however the recent SuperCDMS limit rejects both regions for exoDM with isospin-conserving couplings. An isospin-violating coupling of the exoDM, in particular one with a neutron to protonmore » coupling ratio of -0.8 (which we call ''Ge-phobic''), maximally reduces the DM coupling to germanium and allows the CDMS-II-Si region to become compatible with all bounds. This is also clearly shown in our halo-independent analysis.« less

Direct and Indirect Dark Matter Detection in Gauge Theories (in Portuguese)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Queiroz, Farinaldo

The Dark matter (DM) problem constitutes a key question at the interface among Particle Physics, Astrophysics and Cosmology. The observational data which have been accumulated in the last years point to an existence of non baryonic amount of DM. Since the Standard Model (SM) does not provide any candidate for such non-baryonic DM, the evidence of DM is a major indication for new physics beyond the SM. We will study in this work one of the most popular DM candidates, the so called WIMPs (Weakly Interacting Massive Particles) from a direct and indirect detection perspective. In order to approach themore » direct and indirect dection of DM in the context of Particle Physics in a more pedagogic way, we will begin our discussion talking about a minimal extension of the SM. Later we will work on the subject in a 3-3-1 model. Next, we will study the role of WIMPs in the Big Bang Nucleosynthesis. Lastly, we will look for indirect DM signals in the center of our galaxy using the NASA Satellite, called Fermi-LAT. Through a comprehensive analysis of the data events observed by Fermi-LAT and some background models, we will constrain the dark matter annihilation cross section for several annihilation channels and dark matter halo profiles.« less

Light dark matter in the light of CRESST-II

DOE PAGES

Kopp, Joachim; Schwetz, Thomas; Zupan, Jure

2012-03-01

Recently the CRESST collaboration has published the long anticipated results of their direct Dark Matter (DM) detection experiment with a CaWO 4 target. The number of observed events exceeds known backgrounds at more than 4Σ significance, and this excess could potentially be due to DM scattering. We confront this interpretation with null results from other direct detection experiments for a number of theoretical models, and find that consistency is achieved in non-minimal models such as inelastic DM and isospin-violating DM. In both cases mild tension with constraints remain. The CRESST data can, however, not be reconciled with the null resultsmore » and with the positive signals from DAMA and CoGeNT simultaneously in any of the models we study.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Allahverdi, Rouzbeh; Gao, Yu; Knockel, Bradley

In this paper, we study indirect detection signals from solar annihilation of dark matter (DM) particles into light right-handed (RH) neutrinos with a mass in a 1–5 GeV range. These RH neutrinos can have a sufficiently long lifetime to allow them to decay outside the Sun, and their delayed decays can result in a signal in gamma rays from the otherwise “dark” solar direction, and also a neutrino signal that is not suppressed by the interactions with solar medium. We find that the latest Fermi-LAT and IceCube results place limits on the gamma ray and neutrino signals, respectively. Combined photonmore » and neutrino bounds can constrain the spin-independent DM-nucleon elastic scattering cross section better than direct detection experiments for DM masses from 200 GeV up to several TeV. Finally, the bounds on spin-dependent scattering are also much tighter than the strongest limits from direct detection experiments.« less

You can hide but you have to run: Direct detection with vector mediators

DOE PAGES

D’Eramo, Francesco; Kavanagh, Bradley J.; Panci, Paolo

2016-08-18

We study direct detection in simplified models of Dark Matter (DM) in which interactions with Standard Model (SM) fermions are mediated by a heavy vector boson. We consider fully general, gauge-invariant couplings between the SM, the mediator and both scalar and fermion DM. We account for the evolution of the couplings between the energy scale of the mediator mass and the nuclear energy scale. This running arises from virtual effects of SM particles and its inclusion is not optional. We compare bounds on the mediator mass from direct detection experiments with and without accounting for the running. In some casesmore » the inclusion of these effects changes the bounds by several orders of magnitude, as a consequence of operator mixing which generates new interactions at low energy. We also highlight the importance of these effects when translating LHC limits on the mediator mass into bounds on the direct detection cross section. For an axial-vector mediator, the running can alter the derived bounds on the spin-dependent DM-nucleon cross section by a factor of two or more. Lastly, we provide tools to facilitate the inclusion of these effects in future studies: general approximate expressions for the low energy couplings and a public code runDM to evolve the couplings between arbitrary energy scales.« less

You can hide but you have to run: Direct detection with vector mediators

DOE Office of Scientific and Technical Information (OSTI.GOV)

D’Eramo, Francesco; Kavanagh, Bradley J.; Panci, Paolo

We study direct detection in simplified models of Dark Matter (DM) in which interactions with Standard Model (SM) fermions are mediated by a heavy vector boson. We consider fully general, gauge-invariant couplings between the SM, the mediator and both scalar and fermion DM. We account for the evolution of the couplings between the energy scale of the mediator mass and the nuclear energy scale. This running arises from virtual effects of SM particles and its inclusion is not optional. We compare bounds on the mediator mass from direct detection experiments with and without accounting for the running. In some casesmore » the inclusion of these effects changes the bounds by several orders of magnitude, as a consequence of operator mixing which generates new interactions at low energy. We also highlight the importance of these effects when translating LHC limits on the mediator mass into bounds on the direct detection cross section. For an axial-vector mediator, the running can alter the derived bounds on the spin-dependent DM-nucleon cross section by a factor of two or more. Lastly, we provide tools to facilitate the inclusion of these effects in future studies: general approximate expressions for the low energy couplings and a public code runDM to evolve the couplings between arbitrary energy scales.« less

Probing GeV-scale MSSM neutralino dark matter in collider and direct detection experiments

NASA Astrophysics Data System (ADS)

Duan, Guang Hua; Wang, Wenyu; Wu, Lei; Yang, Jin Min; Zhao, Jun

2018-03-01

Given the recent constraints from the dark matter (DM) direct detections, we examine a light GeV-scale (2-30 GeV) neutralino DM in the alignment limit of the Minimal Supersymmetric Standard Model (MSSM). In this limit without decoupling, the heavy CP-even scalar H plays the role of the Standard Model (SM) Higgs boson while the other scalar h can be rather light so that the DM can annihilate through the h resonance or into a pair of h to achieve the observed relic density. With the current collider and cosmological constraints, we find that such a light neutralino DM above 6 GeV can be excluded by the XENON-1T (2017) limits while the survivied parameter space below 6 GeV can be fully tested by the future germanium-based light dark matter detections (such as CDEX), by the Higgs coupling precison measurements or by the production process e+e- → hA at an electron-positron collider (Higgs factory).

Direct detection of exothermic dark matter with light mediator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Geng, Chao-Qiang; Department of Physics, National Tsing Hua University,Hsinchu, Taiwan; Physics Division, National Center for Theoretical Sciences,Hsinchu, Taiwan

2016-08-05

We study the dark matter (DM) direct detection for the models with the effects of the isospin-violating couplings, exothermic scatterings, and/or the lightness of the mediator, proposed to relax the tension between the CDMS-Si signals and null experiments. In the light of the new updates of the LUX and CDMSlite data, we find that many of the previous proposals are now ruled out, including the Ge-phobic exothermic DM model and the Xe-phobic DM one with a light mediator. We also examine the exothermic DM models with a light mediator but without the isospin violation, and we are unable to identifymore » any available parameter space that could simultaneously satisfy all the experiments. The only models that can partially relax the inconsistencies are the Xe-phobic exothermic DM models with or without a light mediator. But even in this case, a large portion of the CDMS-Si regions of interest has been constrained by the LUX and SuperCDMS data.« less

Direct detection of light “Ge-phobic” exothermic dark matter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gelmini, Graciela B.; Georgescu, Andreea; Huh, Ji-Haeng

2014-07-15

We present comparisons of direct dark matter (DM) detection data for light WIMPs with exothermic scattering with nuclei (exoDM), both assuming the Standard Halo Model (SHM) and in a halo model — independent manner. Exothermic interactions favor light targets, thus reducing the importance of upper limits derived from xenon targets, the most restrictive of which is at present the LUX limit. In our SHM analysis the CDMS-II-Si and CoGeNT regions become allowed by these bounds, however the recent SuperCDMS limit rejects both regions for exoDM with isospin-conserving couplings. An isospin-violating coupling of the exoDM, in particular one with a neutronmore » to proton coupling ratio of −0.8 (which we call “Ge-phobic”), maximally reduces the DM coupling to germanium and allows the CDMS-II-Si region to become compatible with all bounds. This is also clearly shown in our halo-independent analysis.« less

On the existence of low-mass dark matter and its direct detection.

PubMed

Bateman, James; McHardy, Ian; Merle, Alexander; Morris, Tim R; Ulbricht, Hendrik

2015-01-27

Dark Matter (DM) is an elusive form of matter which has been postulated to explain astronomical observations through its gravitational effects on stars and galaxies, gravitational lensing of light around these, and through its imprint on the Cosmic Microwave Background (CMB). This indirect evidence implies that DM accounts for as much as 84.5% of all matter in our Universe, yet it has so far evaded all attempts at direct detection, leaving such confirmation and the consequent discovery of its nature as one of the biggest challenges in modern physics. Here we present a novel form of low-mass DM χ that would have been missed by all experiments so far. While its large interaction strength might at first seem unlikely, neither constraints from particle physics nor cosmological/astronomical observations are sufficient to rule out this type of DM, and it motivates our proposal for direct detection by optomechanics technology which should soon be within reach, namely, through the precise position measurement of a levitated mesoscopic particle which will be perturbed by elastic collisions with χ particles. We show that a recently proposed nanoparticle matter-wave interferometer, originally conceived for tests of the quantum superposition principle, is sensitive to these collisions, too.

On the Existence of Low-Mass Dark Matter and its Direct Detection

NASA Astrophysics Data System (ADS)

Bateman, James; McHardy, Ian; Merle, Alexander; Morris, Tim R.; Ulbricht, Hendrik

2015-01-01

Dark Matter (DM) is an elusive form of matter which has been postulated to explain astronomical observations through its gravitational effects on stars and galaxies, gravitational lensing of light around these, and through its imprint on the Cosmic Microwave Background (CMB). This indirect evidence implies that DM accounts for as much as 84.5% of all matter in our Universe, yet it has so far evaded all attempts at direct detection, leaving such confirmation and the consequent discovery of its nature as one of the biggest challenges in modern physics. Here we present a novel form of low-mass DM χ that would have been missed by all experiments so far. While its large interaction strength might at first seem unlikely, neither constraints from particle physics nor cosmological/astronomical observations are sufficient to rule out this type of DM, and it motivates our proposal for direct detection by optomechanics technology which should soon be within reach, namely, through the precise position measurement of a levitated mesoscopic particle which will be perturbed by elastic collisions with χ particles. We show that a recently proposed nanoparticle matter-wave interferometer, originally conceived for tests of the quantum superposition principle, is sensitive to these collisions, too.

Indirect signals from solar dark matter annihilation to long-lived right-handed neutrinos

DOE PAGES

Allahverdi, Rouzbeh; Gao, Yu; Knockel, Bradley; ...

2017-04-04

In this paper, we study indirect detection signals from solar annihilation of dark matter (DM) particles into light right-handed (RH) neutrinos with a mass in a 1–5 GeV range. These RH neutrinos can have a sufficiently long lifetime to allow them to decay outside the Sun, and their delayed decays can result in a signal in gamma rays from the otherwise “dark” solar direction, and also a neutrino signal that is not suppressed by the interactions with solar medium. We find that the latest Fermi-LAT and IceCube results place limits on the gamma ray and neutrino signals, respectively. Combined photonmore » and neutrino bounds can constrain the spin-independent DM-nucleon elastic scattering cross section better than direct detection experiments for DM masses from 200 GeV up to several TeV. Finally, the bounds on spin-dependent scattering are also much tighter than the strongest limits from direct detection experiments.« less

Discretising the velocity distribution for directional dark matter experiments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kavanagh, Bradley J., E-mail: bradley.kavanagh@cea.fr

2015-07-01

Dark matter (DM) direct detection experiments which are directionally-sensitive may be the only method of probing the full velocity distribution function (VDF) of the Galactic DM halo. We present an angular basis for the DM VDF which can be used to parametrise the distribution in order to mitigate astrophysical uncertainties in future directional experiments and extract information about the DM halo. This basis consists of discretising the VDF in a series of angular bins, with the VDF being only a function of the DM speed v within each bin. In contrast to other methods, such as spherical harmonic expansions, themore » use of this basis allows us to guarantee that the resulting VDF is everywhere positive and therefore physical. We present a recipe for calculating the event rates corresponding to the discrete VDF for an arbitrary number of angular bins N and investigate the discretisation error which is introduced in this way. For smooth, Standard Halo Model-like distribution functions, only N=3 angular bins are required to achieve an accuracy of around 01–30% in the number of events in each bin. Shortly after confirmation of the DM origin of the signal with around 50 events, this accuracy should be sufficient to allow the discretised velocity distribution to be employed reliably. For more extreme VDFs (such as streams), the discretisation error is typically much larger, but can be improved with increasing N. This method paves the way towards an astrophysics-independent analysis framework for the directional detection of dark matter.« less

Discretising the velocity distribution for directional dark matter experiments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kavanagh, Bradley J.; School of Physics & Astronomy, University of Nottingham,University Park, Nottingham, NG7 2RD

2015-07-13

Dark matter (DM) direct detection experiments which are directionally-sensitive may be the only method of probing the full velocity distribution function (VDF) of the Galactic DM halo. We present an angular basis for the DM VDF which can be used to parametrise the distribution in order to mitigate astrophysical uncertainties in future directional experiments and extract information about the DM halo. This basis consists of discretising the VDF in a series of angular bins, with the VDF being only a function of the DM speed v within each bin. In contrast to other methods, such as spherical harmonic expansions, themore » use of this basis allows us to guarantee that the resulting VDF is everywhere positive and therefore physical. We present a recipe for calculating the event rates corresponding to the discrete VDF for an arbitrary number of angular bins N and investigate the discretisation error which is introduced in this way. For smooth, Standard Halo Model-like distribution functions, only N=3 angular bins are required to achieve an accuracy of around 10–30% in the number of events in each bin. Shortly after confirmation of the DM origin of the signal with around 50 events, this accuracy should be sufficient to allow the discretised velocity distribution to be employed reliably. For more extreme VDFs (such as streams), the discretisation error is typically much larger, but can be improved with increasing N. This method paves the way towards an astrophysics-independent analysis framework for the directional detection of dark matter.« less

X-ray lines from dark matter: the good, the bad, and the unlikely

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frandsen, Mads T.; Sannino, Francesco; Shoemaker, Ian M.

2014-05-01

We consider three classes of dark matter (DM) models to account for the recently observed 3.5 keV line: metastable excited state DM, annihilating DM, and decaying DM. We study two examples of metastable excited state DM. The first, millicharged composite DM, has both inelasticity and photon emission built in, but with a very constrained parameter space. In the second example, up-scattering and decay come from separate sectors and is thus less constrained. The decay of the excited state can potentially be detectable at direct detection experiments. However we find that CMB constraints are at the border of excluding this asmore » an interpretation of the DAMA signal. The annihilating DM interpretation of the X-ray line is found to be in mild tension with CMB constraints. Lastly, a generalized version of decaying DM can account for the data with a lifetime exceeding the age of the Universe for masses ∼<10{sup 6} GeV.« less

Search for Light Dark Matter Produced in a Proton Beam Dump

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thornton, Remington Tyler

Cosmological observations indicate that our universe contains dark matter (DM), yet we have no measurements of its microscopic properties. Whereas the gravitational interaction of DM is well understood, its interaction with the Standard Model is not. Direct detection experiments, the current standard, search for a nuclear recoil interaction and have a low-mass sensitivity edge of order 1 GeV. A path to detect DM with mass below 1 GeV is the use of accelerators producing boosted low-mass DM. Using neutrino detectors to search for low-mass DM is logical due to the similarity of the DM and neutrino signatures in the detector.more » The MiniBooNE experiment, located at Fermilab on the Booster Neutrino Beamline, has produced the first proton beam-dump light DM search results. Using dark matter scattering from nucleons 90% confidence limits were set over a large parameter space and, to allow tests of other theories, a model independent DM rate was extracted.« less

Search for light dark matter produced in a proton beam dump

NASA Astrophysics Data System (ADS)

Thornton, Remington Tyler

Cosmological observations indicate that our universe contains dark matter (DM), yet we have no measurements of its microscopic properties. Whereas the gravitational interaction of DM is well understood, its interaction with the Standard Model is not. Direct detection experiments, the current standard, search for a nuclear recoil interaction and have a low-mass sensitivity edge of order 1 GeV. A path to detect DM with mass below 1 GeV is the use of accelerators producing boosted low-mass DM. Using neutrino detectors to search for low-mass DM is logical due to the similarity of the DM and neutrino signatures in the detector. The MiniBooNE experiment, located at Fermilab on the Booster Neutrino Beamline, has produced the first proton beam-dump light DM search results. Using dark matter scattering from nucleons 90% confidence limits were set over a large parameter space and, to allow tests of other theories, a model independent DM rate was extracted.

Maximum likelihood sequence estimation for optical complex direct modulation.

PubMed

Che, Di; Yuan, Feng; Shieh, William

2017-04-17

Semiconductor lasers are versatile optical transmitters in nature. Through the direct modulation (DM), the intensity modulation is realized by the linear mapping between the injection current and the light power, while various angle modulations are enabled by the frequency chirp. Limited by the direct detection, DM lasers used to be exploited only as 1-D (intensity or angle) transmitters by suppressing or simply ignoring the other modulation. Nevertheless, through the digital coherent detection, simultaneous intensity and angle modulations (namely, 2-D complex DM, CDM) can be realized by a single laser diode. The crucial technique of CDM is the joint demodulation of intensity and differential phase with the maximum likelihood sequence estimation (MLSE), supported by a closed-form discrete signal approximation of frequency chirp to characterize the MLSE transition probability. This paper proposes a statistical method for the transition probability to significantly enhance the accuracy of the chirp model. Using the statistical estimation, we demonstrate the first single-channel 100-Gb/s PAM-4 transmission over 1600-km fiber with only 10G-class DM lasers.

Interplay between the b →s l l anomalies and dark matter physics

NASA Astrophysics Data System (ADS)

Kawamura, Junichiro; Okawa, Shohei; Omura, Yuji

2017-10-01

Recently, the LHCb Collaboration has reported the excesses in the b →s l l processes. One of the promising candidates for new physics to explain the anomalies is the extended Standard Model (SM) with vectorlike quarks and leptons. In that model, Yukawa couplings between the extra fermions and SM fermions are introduced, adding extra scalars. Then, the box diagrams involving the extra fields achieve the b →s l l anomalies. It has been known that the excesses require the large Yukawa couplings of leptons, so that this kind of model can be tested by studying correlations with other observables. In this paper, we consider the extra scalar to be a dark matter (DM) candidate, and investigate DM physics as well as the flavor physics and the LHC physics. The DM relic density and the direct-detection cross section are also dominantly given by the Yukawa couplings, so that we find some explicit correlations between DM physics and the flavor physics. In particular, we find the predictions of the b →s l l anomalies against the direct detection of DM.

Time-integrated directional detection of dark matter

NASA Astrophysics Data System (ADS)

O'Hare, Ciaran A. J.; Kavanagh, Bradley J.; Green, Anne M.

2017-10-01

The analysis of signals in directional dark matter (DM) detectors typically assumes that the directions of nuclear recoils can be measured in the Galactic rest frame. However, this is not possible with all directional detection technologies. In nuclear emulsions, for example, the recoil events must be detected and measured after the exposure time of the experiment. Unless the entire detector is mounted and rotated with the sidereal day, the recoils cannot be reoriented in the Galactic rest frame. We examine the effect of this "time integration" on the primary goals of directional detection, namely: (1) confirming that the recoils are anisotropic; (2) measuring the median recoil direction to confirm their Galactic origin; and (3) probing below the neutrino floor. We show that after time integration the DM recoil distribution retains a preferred direction and is distinct from that of Solar neutrino-induced recoils. Many of the advantages of directional detection are therefore preserved and it is not crucial to mount and rotate the detector. Rejecting isotropic backgrounds requires a factor of 2 more signal events compared with an experiment with event time information, whereas a factor of 1.5-3 more events are needed to measure a median direction in agreement with the expectation for DM. We also find that there is still effectively no neutrino floor in a time-integrated directional experiment. However to reach a cross section an order of magnitude below the floor, a factor of ˜8 larger exposure is required than with a conventional directional experiment. We also examine how the sensitivity is affected for detectors with only 2D recoil track readout, and/or no head-tail measurement. As for non-time-integrated experiments, 2D readout is not a major disadvantage, though a lack of head-tail sensitivity is.

On the Existence of Low-Mass Dark Matter and its Direct Detection

PubMed Central

Bateman, James; McHardy, Ian; Merle, Alexander; Morris, Tim R.; Ulbricht, Hendrik

2015-01-01

Dark Matter (DM) is an elusive form of matter which has been postulated to explain astronomical observations through its gravitational effects on stars and galaxies, gravitational lensing of light around these, and through its imprint on the Cosmic Microwave Background (CMB). This indirect evidence implies that DM accounts for as much as 84.5% of all matter in our Universe, yet it has so far evaded all attempts at direct detection, leaving such confirmation and the consequent discovery of its nature as one of the biggest challenges in modern physics. Here we present a novel form of low-mass DM χ that would have been missed by all experiments so far. While its large interaction strength might at first seem unlikely, neither constraints from particle physics nor cosmological/astronomical observations are sufficient to rule out this type of DM, and it motivates our proposal for direct detection by optomechanics technology which should soon be within reach, namely, through the precise position measurement of a levitated mesoscopic particle which will be perturbed by elastic collisions with χ particles. We show that a recently proposed nanoparticle matter-wave interferometer, originally conceived for tests of the quantum superposition principle, is sensitive to these collisions, too. PMID:25622565

Probing the coupling of heavy dark matter to nucleons by detecting neutrino signature from the Earth's core

NASA Astrophysics Data System (ADS)

Lin, Guey-Lin; Lin, Yen-Hsun; Lee, Fei-Fan

2015-02-01

We argue that the detection of the neutrino signature from the Earth's core can effectively probe the coupling of heavy dark matter (mχ>104 GeV ) to nucleons. We first note that direct searches for dark matter (DM) in such a mass range provide much less stringent constraint than the constraint provided by such searches for mχ˜100 GeV . Furthermore, the energies of neutrinos arising from DM annihilation inside the Sun cannot exceed a few TeVs at the Sun's surface due to the attenuation effect. Therefore, the sensitivity to the heavy DM coupling is lost. Finally, the detection of the neutrino signature from the Galactic halo can only probe DM annihilation cross sections. We present neutrino event rates in IceCube and KM3NeT arising from the neutrino flux produced by annihilation of Earth-captured DM heavier than 104 GeV . The IceCube and KM3NeT sensitivities to spin-independent DM-proton scattering cross section σχ p in this mass range are presented for both isospin-symmetric and isospin-violating cases.

How light a higgsino or a wino dark matter can become in a compressed scenario of MSSM

NASA Astrophysics Data System (ADS)

Chakraborti, Manimala; Chattopadhyay, Utpal; Poddar, Sujoy

2017-09-01

Higgsinos and Wino have strong motivations for being Dark Matter (DM) candidates in supersymmetry, but their annihilation cross sections are quite large. For thermal generation and a single component DM setup the higgsinos or wino may have masses of around 1 or 2-3 TeV respectively. For such DM candidates, a small amount of slepton coannihilation may decrease the effective DM annihilation cross section. This, in turn reduces the lower limit of the relic density satisfied DM mass by more than 50%. Almost a similar degree of reduction of the same limit is also seen for squark coannihilations. However, on the contrary, for near degeneracy of squarks and higgsino DM, near its generic upper limit, the associated coannihilations may decrease the relic density, thus extending the upper limit towards higher DM masses. We also compute the direct and indirect detection signals. Here, because of the quasi-mass degeneracy of the squarks and the LSP, we come across a situation where squark exchange diagrams may contribute significantly or more strongly than the Higgs exchange contributions in the spin-independent direct detection cross section of DM. For the higgsino-DM scenario, we observe that a DM mass of 600 GeV to be consistent with WMAP/PLANCK and LUX data for sfermion coannihilations. The LUX data itself excludes the region of 450 to 600 GeV, by a half order of magnitude of the cross-section, well below the associated uncertainty. The similar combined lower limit for a wino DM is about 1.1 TeV. There is hardly any collider bound from the LHC for squarks and sleptons in such a compressed scenario where sfermion masses are close to the mass of a higgsino/wino LSP.

Taking Halo-Independent Dark Matter Methods Out of the Bin

DOE PAGES

Fox, Patrick J.; Kahn, Yonatan; McCullough, Matthew

2014-10-30

We develop a new halo-independent strategy for analyzing emerging DM hints, utilizing the method of extended maximum likelihood. This approach does not require the binning of events, making it uniquely suited to the analysis of emerging DM direct detection hints. It determines a preferred envelope, at a given confidence level, for the DM velocity integral which best fits the data using all available information and can be used even in the case of a single anomalous scattering event. All of the halo-independent information from a direct detection result may then be presented in a single plot, allowing simple comparisons betweenmore » multiple experiments. This results in the halo-independent analogue of the usual mass and cross-section plots found in typical direct detection analyses, where limit curves may be compared with best-fit regions in halo-space. The method is straightforward to implement, using already-established techniques, and its utility is demonstrated through the first unbinned halo-independent comparison of the three anomalous events observed in the CDMS-Si detector with recent limits from the LUX experiment.« less

A MiniBooNE Accelerator-Produced (sub)-GeV Dark Matter Search

NASA Astrophysics Data System (ADS)

Thornton, Remington; MiniBooNE-DM Collaboration

2016-09-01

Cosmological observations indicate that our universe contains dark matter (DM), yet we have no measurements of its microscopic properties. Whereas the gravitational interaction of DM is well understood, its interaction with the Standard Model is not. Direct detection experiments search for a nuclear recoil interaction produced by a DM relic particle and have a low-mass sensitivity edge of order 1 GeV. To detect DM with mass below 1 GeV, either the sensitivity of the experiments needs to be improved or use of accelerators producing boosted low-mass DM are needed. Using neutrino detectors to search for low-mass DM is logical due to the similarity of the DM and ν signatures in the detector. The MiniBooNE experiment, located at Fermilab on the Booster Neutrino Beamline, ran for 10 years in ν and ν modes and is already well understood, making it desirable to search for accelerator-produced boosted low-mass DM. A search for DM produced by 8 GeV protons hitting a steel beam-dump has finished, collecting 1 . 86 ×1020 POT . Final analysis containing 90% confidence limits and a model independent fit will be presented.

runDM: Running couplings of Dark Matter to the Standard Model

NASA Astrophysics Data System (ADS)

D'Eramo, Francesco; Kavanagh, Bradley J.; Panci, Paolo

2018-02-01

runDM calculates the running of the couplings of Dark Matter (DM) to the Standard Model (SM) in simplified models with vector mediators. By specifying the mass of the mediator and the couplings of the mediator to SM fields at high energy, the code can calculate the couplings at low energy, taking into account the mixing of all dimension-6 operators. runDM can also extract the operator coefficients relevant for direct detection, namely low energy couplings to up, down and strange quarks and to protons and neutrons.

New probe of dark-matter properties: gravitational waves from an intermediate-mass black hole embedded in a dark-matter minispike.

PubMed

Eda, Kazunari; Itoh, Yousuke; Kuroyanagi, Sachiko; Silk, Joseph

2013-05-31

An intermediate-mass black hole (IMBH) may have a dark-matter (DM) minihalo around it and develop a spiky structure within less than a parsec from the IMBH. When a stellar mass object is captured by the minihalo, it eventually infalls into such an IMBH due to gravitational wave backreaction which in turn could be observed directly by future space-borne gravitational wave experiments such as eLISA and NGO. In this Letter, we show that the gravitational wave (GW) detectability strongly depends on the radial profile of the DM distribution. So if the GW is detected, the power index, that is, the DM density distribution, would be determined very accurately. The DM density distribution obtained would make it clear how the IMBH has evolved from a seed black hole and whether the IMBH has experienced major mergers in the past. Unlike the γ-ray observations of DM annihilation, GW is just sensitive to the radial profile of the DM distribution and even to noninteracting DM. Hence, the effect we demonstrate here can be used as a new and powerful probe into DM properties.

Enhanced direct ambient analysis by differential mobility-filtered desorption electrospray ionization-mass spectrometry.

PubMed

Galhena, Asiri S; Harris, Glenn A; Kwasnik, Mark; Fernández, Facundo M

2010-11-15

Desorption electrospray ionization (DESI) is rapidly becoming established as one of the most powerful ionization techniques allowing direct surface analysis by mass spectrometry (MS) in the ambient environment. DESI provides a significant number of unique analytical capabilities for a broad range of applications, both quantitative and qualitative in nature including biological tissue imaging, pharmaceutical quality control, in vivo analysis, proteomics, metabolomics, forensics, and explosives detection. Despite its growing adoption as a powerful high throughput analysis tool, DESI-MS analysis at trace levels often suffers from background chemical interferences generated during the electrospray ionization processes. In order to improve sensitivity and selectivity, a differential mobility (DM) ion separation cell was successfully interfaced to a custom-built DESI ion source. This new hybrid platform can be operated in two modes: the "DM-off" mode for standard DESI analysis and "DM-on mode" where DESI-generated ions are detected after discrimination by the differential mobility cell. The performance of the DESI-DM-MS platform was tested with several samples typically amenable to DESI analysis, including counterfeit pharmaceuticals and binary mixtures of isobaric chemicals of importance in the pharmaceutical and food industries. In the DM-on mode, DESI-MS signal-to-noise ratios were improved by 70-190% when compared to the DM-off mode. Also, the addition of the DM cell enabled selective in-source ion activation of specific DESI-generated precursor ions, providing tandem MS-like spectra in a single stage mass spectrometer.

The direct detection of boosted dark matter at high energies and PeV events at IceCube

DOE PAGES

Bhattacharya, A.; Gandhi, R.; Gupta, A.

2015-03-13

We study the possibility of detecting dark matter directly via a small but energetic component that is allowed within present-day constraints. Drawing closely upon the fact that neutral current neutrino nucleon interactions are indistinguishable from DM-nucleon interactions at low energies, we extend this feature to high energies for a small, non-thermal but highly energetic population of DM particle χ, created via the decay of a significantly more massive and long-lived non-thermal relic Φ, which forms the bulk of DM. If χ interacts with nucleons, its cross-section, like the neutrino-nucleus coherent cross-section, can rise sharply with energy leading to deep inelasticmore » scattering, similar to neutral current neutrino-nucleon interactions at high energies. Thus, its direct detection may be possible via cascades in very large neutrino detectors. As a specific example, we apply this notion to the recently reported three ultra-high energy PeV cascade events clustered around 1 – 2 PeV at IceCube (IC). We discuss the features which may help discriminate this scenario from one in which only astrophysical neutrinos constitute the event sample in detectors like IC.« less

Active-site-matched fluorescent probes for rapid and direct detection of vicinal-sulfydryl-containing peptides/proteins in living cells.

PubMed

Pan, Xiaohong; Liang, Ziye; Li, Jing; Wang, Shanshan; Kong, Fanpeng; Xu, Kehua; Tang, Bo

2015-01-26

Vicinal-sulfydryl-containing peptides/proteins (VSPPs) play a crucial role in human pathologies. Fluorescent probes that are capable of detecting intracellular VSPPs in vivo would be useful tools to explore the mechanisms of some diseases. In this study, by regulating the spatial separation of two maleimide groups in a fluorescent dye to match that of two active cysteine residues contained in the conserved amino acid sequence (-CGPC-) of human thioredoxin, two active-site-matched fluorescent probes, o-Dm-Ac and m-Dm-Ac, were developed for real-time imaging of VSPPs in living cells. As a result, the two probes can rapidly respond to small peptide models and reduced proteins, such as WCGPCK (W-6), WCGGPCK (W-7), and WCGGGPCK (W-8), reduced bovine serum albumin (rBSA), and reduced thioredoxin (rTrx). Moreover, o-Dm-Ac displays a higher binding sensitivity with the above-mentioned peptides and proteins, especially with W-7 and rTrx. Furthermore, o-Dm-Ac was successfully used to rapidly and directly detect VSPPs both in vitro and in living cells. Thus, a novel probe-design strategy was proposed and the synthesized probe applied successfully in imaging of target proteins in situ. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dark matter and gauged flavor symmetries

DOE PAGES

Bishara, Fady; Greljo, Admir; Kamenik, Jernej F.; ...

2015-12-21

We investigate the phenomenology of flavored dark matter (DM). DM stability is guaranteed by an accidental Z 3 symmetry, a subgroup of the standard model (SM) flavor group that is not broken by the SM Yukawa interactions. We consider an explicit realization where the quark part of the SM flavor group is fully gauged. If the dominant interactions between DM and visible sector are through flavor gauge bosons, as we show for Dirac fermion flavored DM, then the DM mass is bounded between roughly 0.5 TeV and 5 TeV if the DM multiplet mass is split only radiatively. In general,more » however, no such relation exists. We demonstrate this using scalar flavored DM where the main interaction with the SM is through the Higgs portal. For both cases we derive constraints from flavor, cosmology, direct and indirect DM detection, and collider searches.« less

Dark matter and gauged flavor symmetries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bishara, Fady; Greljo, Admir; Kamenik, Jernej F.

We investigate the phenomenology of flavored dark matter (DM). DM stability is guaranteed by an accidental Z 3 symmetry, a subgroup of the standard model (SM) flavor group that is not broken by the SM Yukawa interactions. We consider an explicit realization where the quark part of the SM flavor group is fully gauged. If the dominant interactions between DM and visible sector are through flavor gauge bosons, as we show for Dirac fermion flavored DM, then the DM mass is bounded between roughly 0.5 TeV and 5 TeV if the DM multiplet mass is split only radiatively. In general,more » however, no such relation exists. We demonstrate this using scalar flavored DM where the main interaction with the SM is through the Higgs portal. For both cases we derive constraints from flavor, cosmology, direct and indirect DM detection, and collider searches.« less

NMSSM interpretation of the Galactic Center excess

NASA Astrophysics Data System (ADS)

Cheung, Clifford; Papucci, Michele; Sanford, David; Shah, Nausheen R.; Zurek, Kathryn M.

2014-10-01

We explore models for the GeV Galactic Center excess (GCE) observed by the Fermi Telescope, focusing on χχ→ff ¯ annihilation processes in the Z3 next-to-minimal supersymmetric standard model (NMSSM). We begin by examining the requirements for a simplified model [parametrized by the couplings and masses of dark matter (DM) and mediator particles] to reproduce the GCE via χχ→ff ¯, while simultaneously thermally producing the observed relic abundance. We apply the results of our simplified model to the Z3 NMSSM for singlino/Higgsino (S/H) or bino/Higgsino (B/H) DM. In the case of S/H DM, we find that the DM must be very close to a pseudoscalar resonance to be viable, and large tanβ and positive values of μ are preferred for evading direct detection constraints while simultaneously obtaining the observed Higgs mass. In the case of B/H DM, by contrast, the situation is much less tuned: annihilation generally occurs off resonance, and for large tanβ, direct detection constraints are easily satisfied by choosing μ sufficiently large and negative. The B/H model generally has a light, largely MSSM-like pseudoscalar with no accompanying charged Higgs, which could be searched for at the LHC.

Looking for the WIMP next door

NASA Astrophysics Data System (ADS)

Evans, Jared A.; Gori, Stefania; Shelton, Jessie

2018-02-01

We comprehensively study experimental constraints and prospects for a class of minimal hidden sector dark matter (DM) models, highlighting how the cosmological history of these models informs the experimental signals. We study simple `secluded' models, where the DM freezes out into unstable dark mediator states, and consider the minimal cosmic history of this dark sector, where coupling of the dark mediator to the SM was sufficient to keep the two sectors in thermal equilibrium at early times. In the well-motivated case where the dark mediators couple to the Standard Model (SM) via renormalizable interactions, the requirement of thermal equilibrium provides a minimal, UV-insensitive, and predictive cosmology for hidden sector dark matter. We call DM that freezes out of a dark radiation bath in thermal equilibrium with the SM a WIMP next door, and demonstrate that the parameter space for such WIMPs next door is sharply defined, bounded, and in large part potentially accessible. This parameter space, and the corresponding signals, depend on the leading interaction between the SM and the dark mediator; we establish it for both Higgs and vector portal interactions. In particular, there is a cosmological lower bound on the portal coupling strength necessary to thermalize the two sectors in the early universe. We determine this thermalization floor as a function of equilibration temperature for the first time. We demonstrate that direct detection experiments are currently probing this cosmological lower bound in some regions of parameter space, while indirect detection signals and terrestrial searches for the mediator cut further into the viable parameter space. We present regions of interest for both direct detection and dark mediator searches, including motivated parameter space for the direct detection of sub-GeV DM.

Singlet-triplet fermionic dark matter and LHC phenomenology

NASA Astrophysics Data System (ADS)

Choubey, Sandhya; Khan, Sarif; Mitra, Manimala; Mondal, Subhadeep

2018-04-01

It is well known that for the pure standard model triplet fermionic WIMP-type dark matter (DM), the relic density is satisfied around 2 TeV. For such a heavy mass particle, the production cross-section at 13 TeV run of LHC will be very small. Extending the model further with a singlet fermion and a triplet scalar, DM relic density can be satisfied for even much lower masses. The lower mass DM can be copiously produced at LHC and hence the model can be tested at collider. For the present model we have studied the multi jet (≥ 2 j) + missing energy ([InlineEquation not available: see fulltext.]) signal and show that this can be detected in the near future of the LHC 13 TeV run. We also predict that the present model is testable by the earth based DM direct detection experiments like Xenon-1T and in future by Darwin.

Identifying the theory of dark matter with direct detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gluscevic, Vera; Gresham, Moira I.; McDermott, Samuel D.

2015-12-01

Identifying the true theory of dark matter depends crucially on accurately characterizing interactions of dark matter (DM) with other species. In the context of DM direct detection, we present a study of the prospects for correctly identifying the low-energy effective DM-nucleus scattering operators connected to UV-complete models of DM-quark interactions. We take a census of plausible UV-complete interaction models with different low-energy leading-order DM-nuclear responses. For each model (corresponding to different spin–, momentum–, and velocity-dependent responses), we create a large number of realizations of recoil-energy spectra, and use Bayesian methods to investigate the probability that experiments will be able tomore » select the correct scattering model within a broad set of competing scattering hypotheses. We conclude that agnostic analysis of a strong signal (such as Generation-2 would see if cross sections are just below the current limits) seen on xenon and germanium experiments is likely to correctly identify momentum dependence of the dominant response, ruling out models with either 'heavy' or 'light' mediators, and enabling downselection of allowed models. However, a unique determination of the correct UV completion will critically depend on the availability of measurements from a wider variety of nuclear targets, including iodine or fluorine. We investigate how model-selection prospects depend on the energy window available for the analysis. In addition, we discuss accuracy of the DM particle mass determination under a wide variety of scattering models, and investigate impact of the specific types of particle-physics uncertainties on prospects for model selection.« less

Identifying the theory of dark matter with direct detection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gluscevic, Vera; Gresham, Moira I.; McDermott, Samuel D.

2015-12-29

Identifying the true theory of dark matter depends crucially on accurately characterizing interactions of dark matter (DM) with other species. In the context of DM direct detection, we present a study of the prospects for correctly identifying the low-energy effective DM-nucleus scattering operators connected to UV-complete models of DM-quark interactions. We take a census of plausible UV-complete interaction models with different low-energy leading-order DM-nuclear responses. For each model (corresponding to different spin–, momentum–, and velocity-dependent responses), we create a large number of realizations of recoil-energy spectra, and use Bayesian methods to investigate the probability that experiments will be able tomore » select the correct scattering model within a broad set of competing scattering hypotheses. We conclude that agnostic analysis of a strong signal (such as Generation-2 would see if cross sections are just below the current limits) seen on xenon and germanium experiments is likely to correctly identify momentum dependence of the dominant response, ruling out models with either “heavy” or “light” mediators, and enabling downselection of allowed models. However, a unique determination of the correct UV completion will critically depend on the availability of measurements from a wider variety of nuclear targets, including iodine or fluorine. We investigate how model-selection prospects depend on the energy window available for the analysis. In addition, we discuss accuracy of the DM particle mass determination under a wide variety of scattering models, and investigate impact of the specific types of particle-physics uncertainties on prospects for model selection.« less

Astrophysics-independent bounds on the annual modulation of dark matter signals.

PubMed

Herrero-Garcia, Juan; Schwetz, Thomas; Zupan, Jure

2012-10-05

We show how constraints on the time integrated event rate from a given dark matter (DM) direct detection experiment can be used to bound the amplitude of the annual modulation signal in another experiment. The method requires only mild assumptions about the properties of the local DM distribution: that it is temporally stable on the scale of months and spatially homogeneous on the ecliptic. We apply the method to the annual modulation signal in DAMA/LIBRA, which we compare to the bounds derived from XENON10, XENON100, cryogenic DM search, and SIMPLE data. Assuming a DM mass of 10 GeV, we show that under the above assumptions about the DM halo, a DM interpretation of the DAMA/LIBRA signal is excluded for several classes of models: at 6.3σ (4.6σ) for elastic isospin conserving (violating) spin-independent interactions, and at 4.9σ for elastic spin-dependent interactions on protons.

Theoretical analysis of a method for extracting the phase of a phase-amplitude modulated signal generated by a direct-modulated optical injection-locked semiconductor laser

NASA Astrophysics Data System (ADS)

Lee, Hwan; Cho, Jun-Hyung; Sung, Hyuk-Kee

2017-05-01

The phase modulation (PM) and amplitude modulation (AM) of optical signals can be achieved using a direct-modulated (DM) optical injection-locked (OIL) semiconductor laser. We propose and theoretically analyze a simple method to extract the phase component of a PM signal produced by a DM-OIL semiconductor laser. The pure AM component of the combined PM-AM signal can be isolated by square-law detection in a photodetector and can then be used to compensate for the PM-AM signal based on an optical homodyne method. Using the AM compensation technique, we successfully developed a simple and cost-effective phase extraction method applicable to the PM-AM optical signal of a DM-OIL semiconductor laser.

Exothermic double-disk dark matter

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCullough, Matthew; Randall, Lisa, E-mail: mccull@mit.edu, E-mail: randall@physics.harvard.edu

2013-10-01

If a subdominant component of dark matter (DM) interacts via long-range dark force carriers it may cool and collapse to form complex structures within the Milky Way galaxy, such as a rotating dark disk. This scenario was proposed recently and termed ''Double-Disk Dark Matter'' (DDDM). In this paper we consider the possibility that DDDM remains in a cosmologically long-lived excited state and can scatter exothermically on nuclei (ExoDDDM). We investigate the current status of ExoDDDM direct detection and find that ExoDDDM can readily explain the recently announced ∼ 3σ excess observed at CDMS-Si, with almost all of the 90% best-fitmore » parameter space in complete consistency with limits from other experiments, including XENON10 and XENON100. In the absence of isospin-dependent couplings, this consistency requires light DM with mass typically in the 5-15 GeV range. The hypothesis of ExoDDDM can be tested in direct detection experiments through its peaked recoil spectra, reduced annual modulation amplitude, and, in some cases, its novel time-dependence. We also discuss future direct detection prospects and additional indirect constraints from colliders and solar capture of ExoDDDM. As theoretical proof-of-principle, we combine the features of exothermic DM models and DDDM models to construct a complete model of ExoDDDM, exhibiting all the required properties.« less

Supersymmetric Dark Matter after LHC Run 1

DOE PAGES

Bagnaschi, E. A.; Buchmueller, O.; Cavanaugh, R.; ...

2015-10-23

Different mechanisms operate in various regions of the MSSM parameter space to bring the relic density of the lightest neutralino, χ ~0 1, assumed here to be the lightest SUSY particle (LSP) and thus the dark matter (DM) particle, into the range allowed by astrophysics and cosmology. These mechanisms include coannihilation with some nearly degenerate next-to-lightest supersymmetric particle such as the lighter stau τ ~ 1, stop t ~ 1 or chargino χ ~± 1, resonant annihilation via direct-channel heavy Higgs bosons H / A, the light Higgs boson h or the Z boson, and enhanced annihilation via a largermore » Higgsino component of the LSP in the focus-point region. These mechanisms typically select lower-dimensional subspaces in MSSM scenarios such as the CMSSM, NUHM1, NUHM2, and pMSSM10. We analyze how future LHC and direct DM searches can complement each other in the exploration of the different DM mechanisms within these scenarios. We find that the τ~1 coannihilation regions of the CMSSM, NUHM1, NUHM2 can largely be explored at the LHC via searches for /E T events and long-lived charged particles, whereas theirH / A funnel, focus-point and χ ~± 1 coannihilation regions can largely be explored by the LZ and Darwin DM direct detection experiments. Furthermore, we find that the dominant DM mechanism in our pMSSM10 analysis is χ ~ ±1 coannihilation: parts of its parameter space can be explored by the LHC, and a larger portion by future direct DM searches.« less

Supersymmetric dark matter after LHC run 1

NASA Astrophysics Data System (ADS)

Bagnaschi, E. A.; Buchmueller, O.; Cavanaugh, R.; Citron, M.; De Roeck, A.; Dolan, M. J.; Ellis, J. R.; Flächer, H.; Heinemeyer, S.; Isidori, G.; Malik, S.; Martínez Santos, D.; Olive, K. A.; Sakurai, K.; de Vries, K. J.; Weiglein, G.

2015-10-01

Different mechanisms operate in various regions of the MSSM parameter space to bring the relic density of the lightest neutralino, tilde{χ }^01, assumed here to be the lightest SUSY particle (LSP) and thus the dark matter (DM) particle, into the range allowed by astrophysics and cosmology. These mechanisms include coannihilation with some nearly degenerate next-to-lightest supersymmetric particle such as the lighter stau tilde{τ }1, stop tilde{t}1 or chargino tilde{χ }^± 1, resonant annihilation via direct-channel heavy Higgs bosons H / A, the light Higgs boson h or the Z boson, and enhanced annihilation via a larger Higgsino component of the LSP in the focus-point region. These mechanisms typically select lower-dimensional subspaces in MSSM scenarios such as the CMSSM, NUHM1, NUHM2, and pMSSM10. We analyze how future LHC and direct DM searches can complement each other in the exploration of the different DM mechanisms within these scenarios. We find that the {tilde{τ }_1} coannihilation regions of the CMSSM, NUHM1, NUHM2 can largely be explored at the LHC via searches for / E_T events and long-lived charged particles, whereas their H / A funnel, focus-point and tilde{χ }^± 1 coannihilation regions can largely be explored by the LZ and Darwin DM direct detection experiments. We find that the dominant DM mechanism in our pMSSM10 analysis is tilde{χ }^± 1 coannihilation: parts of its parameter space can be explored by the LHC, and a larger portion by future direct DM searches.

Flavoured Dark Matter moving left

NASA Astrophysics Data System (ADS)

Blanke, Monika; Das, Satrajit; Kast, Simon

2018-02-01

We investigate the phenomenology of a simplified model of flavoured Dark Matter (DM), with a dark fermionic flavour triplet coupling to the left-handed SU(2) L quark doublets via a scalar mediator. The DM-quark coupling matrix is assumed to constitute the only new source of flavour and CP violation, following the hypothesis of Dark Minimal Flavour Violation. We analyse the constraints from LHC searches, from meson mixing data in the K, D, and B d,s meson systems, from thermal DM freeze-out, and from direct detection experiments. Our combined analysis shows that while the experimental constraints are similar to the DMFV models with DM coupling to right-handed quarks, the multitude of couplings between DM and the SM quark sector resulting from the SU(2) L structure implies a richer phenomenology and significantly alters the resulting impact on the viable parameter space.

Sensitivity of Atom Interferometry to Ultralight Scalar Field Dark Matter.

PubMed

Geraci, Andrew A; Derevianko, Andrei

2016-12-23

We discuss the use of atom interferometry as a tool to search for dark matter (DM) composed of virialized ultralight fields (VULFs). Previous work on VULF DM detection using accelerometers has considered the possibility of equivalence-principle-violating effects whereby gradients in the dark matter field can directly produce relative accelerations between media of differing composition. In atom interferometers, we find that time-varying phase signals induced by coherent oscillations of DM fields can also arise due to changes in the atom rest mass that can occur between light pulses throughout the interferometer sequence as well as changes in Earth's gravitational field. We estimate that several orders of magnitude of unexplored phase space for VULF DM couplings can be probed due to these new effects.

Electrophilic dark matter with dark photon: From DAMPE to direct detection

NASA Astrophysics Data System (ADS)

Gu, Pei-Hong; He, Xiao-Gang

2018-03-01

The electron-positron excess reported by the DAMPE collaboration recently may be explained by an electrophilic dark matter (DM). A standard model singlet fermion may play the role of such a DM when it is stabilized by some symmetries, such as a dark U(1)X gauge symmetry, and dominantly annihilates into the electron-positron pairs through the exchange of a scalar mediator. The model, with appropriate Yukawa couplings, can well interpret the DAMPE excess. Naively one expects that in this type of models the DM-nucleon cross section should be small since there is no tree-level DM-quark interactions. We however find that at one-loop level, a testable DM-nucleon cross section can be induced for providing ways to test the electrophilic model. We also find that a U (1) kinetic mixing can generate a sizable DM-nucleon cross section although the U(1)X dark photon only has a negligible contribution to the DM annihilation. Depending on the signs of the mixing parameter, the dark photon can enhance/reduce the one-loop induced DM-nucleon cross section.

Implications of the Fermi-LAT Pass 8 Galactic Center excess on supersymmetric dark matter

NASA Astrophysics Data System (ADS)

Achterberg, Abraham; van Beekveld, Melissa; Caron, Sascha; Gómez-Vargas, Germán A.; Hendriks, Luc; Ruiz de Austri, Roberto

2017-12-01

The Fermi Collaboration has recently updated their analysis of gamma rays from the center of the Galaxy. They reconfirm the presence of an unexplained emission feature which is most prominent in the region of 1–10 GeV, known as the Galactic Center GeV excess (GCE). Although the GCE is now firmly detected, an interpretation of this emission as a signal of self-annihilating dark matter (DM) particles is not unambiguously possible due to systematic effects in the gamma-ray modeling estimated in the Galactic Plane. In this paper we build a covariance matrix, collecting different systematic uncertainties investigated in the Fermi Collaboration's paper that affect the GCE spectrum. We show that models where part of the GCE is due to annihilating DM is still consistent with the new data. We also re-evaluate the parameter space regions of the minimal supersymmetric Standard Model (MSSM) that can contribute dominantly to the GCE via neutralino DM annihilation. All recent constraints from DM direct detection experiments such as PICO, LUX, PandaX and Xenon1T, limits on the annihilation cross section from dwarf spheroidal galaxies and the Large Hadron Collider limits are considered in this analysis. Due to a slight shift in the energy spectrum of the GC excess with respect to the previous Fermi analysis, and the recent limits from direct detection experiments, we find a slightly shifted parameter region of the MSSM, compared to our previous analysis, that is consistent with the GCE. Neutralinos with a mass between 85–220 GeV can describe the excess via annihilation into a pair of W-bosons or top quarks. Remarkably, there are models with low fine-tuning among the regions that we have found. The complete set of solutions will be probed by upcoming direct detection experiments and with dedicated searches in the upcoming data of the Large Hadron Collider.

The dark side of electroweak naturalness beyond the MSSM

NASA Astrophysics Data System (ADS)

Bélanger, Geneviève; Delaunay, Cédric; Goudelis, Andreas

2015-04-01

Weak scale supersymmetry (SUSY) remains a prime explanation for the radiative stability of the Higgs field. A natural account of the Higgs boson mass, however, strongly favors extensions of the Minimal Supersymmetric Standard Model (MSSM). A plausible option is to introduce a new supersymmetric sector coupled to the MSSM Higgs fields, whose associated states resolve the little hierarchy problem between the third generation soft parameters and the weak scale. SUSY also accomodates a weakly interacting cold dark matter (DM) candidate in the form of a stable neutralino. In minimal realizations, the thus-far null results of direct DM searches, along with the DM relic abundance constraint, introduce a level of fine-tuning as severe as the one due to the SUSY little hierarchy problem. We analyse the generic implications of new SUSY sectors parametrically heavier than the minimal SUSY spectrum, devised to increase the Higgs boson mass, on this "little neutralino DM problem". We focus on the SUSY operator of smallest scaling dimension in an effective field theory description, which modifies the Higgs and DM sectors in a correlated manner. Within this framework, we show that recent null results from the LUX experiment imply a tree-level fine-tuning for gaugino DM which is parametrically at least a few times larger than that of the MSSM. Higgsino DM whose relic abundance is generated through a thermal freeze-out mechanism remains also severely fine-tuned, unless the DM lies below the weak boson pair-production threshold. As in the MSSM, well-tempered gaugino-Higgsino DM is strongly disfavored by present direct detection results.

Dark matter

PubMed Central

Peebles, P. James E.

2015-01-01

The evidence for the dark matter (DM) of the hot big bang cosmology is about as good as it gets in natural science. The exploration of its nature is now led by direct and indirect detection experiments, to be complemented by advances in the full range of cosmological tests, including judicious consideration of the rich phenomenology of galaxies. The results may confirm ideas about DM already under discussion. If we are lucky, we also will be surprised once again. PMID:24794526

VizieR Online Data Catalog: Dark matter in dSph galaxies (Charbonnier+, 2011)

NASA Astrophysics Data System (ADS)

Charbonnier, A.; Combet, C.; Daniel, M.; Funk, S.; Hinton, J. A.; Maurin, D.; Power, C.; Read, J. I.; Sarkar, S.; Walker, M. G.; Wilkinson, M. I.

2012-07-01

Due to their large dynamical mass-to-light ratios, dwarf spheroidal galaxies (dSphs) are promising targets for the indirect detection of dark matter (DM) in γ-rays. We examine their detectability by present and future γ-ray observatories. The key innovative features of our analysis are as follows: (i) we take into account the angular size of the dSphs; while nearby objects have higher γ-ray flux, their larger angular extent can make them less attractive targets for background-dominated instruments; (ii) we derive DM profiles and the astrophysical J-factor (which parametrizes the expected γ-ray flux, independently of the choice of DM particle model) for the classical dSphs directly from photometric and kinematic data. We assume very little about the DM profile, modelling this as a smooth split-power-law distribution, with and without subclumps; (iii) we use a Markov chain Monte Carlo technique to marginalize over unknown parameters and determine the sensitivity of our derived J-factors to both model and measurement uncertainties; and (iv) we use simulated DM profiles to demonstrate that our J-factor determinations recover the correct solution within our quoted uncertainties. (6 data files).

On dark matter interactions with the Standard Model through an anomalous Z'

NASA Astrophysics Data System (ADS)

Ismail, Ahmed; Katz, Andrey; Racco, Davide

2017-10-01

We study electroweak scale Dark Matter (DM) whose interactions with baryonic matter are mediated by a heavy anomalous Z'. We emphasize that when the DM is a Majorana particle, its low-velocity annihilations are dominated by loop suppressed annihilations into the gauge bosons, rather than by p-wave or chirally suppressed annihilations into the SM fermions. Because the Z ' is anomalous, these kinds of DM models can be realized only as effective field theories (EFTs) with a well-defined cutoff, where heavy spectator fermions restore gauge invariance at high energies. We formulate these EFTs, estimate their cutoff and properly take into account the effect of the Chern-Simons terms one obtains after the spectator fermions are integrated out. We find that, while for light DM collider and direct detection experiments usually provide the strongest bounds, the bounds at higher masses are heavily dominated by indirect detection experiments, due to strong annihilation into W + W -, ZZ, Zγ and possibly into gg and γγ. We emphasize that these annihilation channels are generically significant because of the structure of the EFT, and therefore these models are prone to strong indirect detection constraints. Even though we focus on selected Z' models for illustrative purposes, our setup is completely generic and can be used for analyzing the predictions of any anomalous Z'-mediated DM model with arbitrary charges.

Leptophilic dark matter in gauged U(1)_{L{_e}-L_{μ }} model in light of DAMPE cosmic ray {e{^+}} + {e{^-}} excess

NASA Astrophysics Data System (ADS)

Duan, Guang Hua; He, Xiao-Gang; Wu, Lei; Yang, Jin Min

2018-04-01

Motivated by the very recent cosmic-ray electron+positron excess observed by DAMPE collaboration, we investigate a Dirac fermion dark matter (DM) in the gauged {{L_e} - {L_μ }} model. DM interacts with the electron and muon via the U(1)_{e-μ } gauge boson Z^' . The model can explain the DAMPE data well. Although a non-zero DM-nucleon cross section is only generated at one loop level and there is a partial cancellation between Z^' }ee and Z^' }μ μ couplings, we find that a large portion of Z' mass is ruled out from direct DM detection limit leaving the allowed Z^' } mass to be close to two times of the DM mass. Implications for pp → Z^' } → 2ℓ and pp → 2ℓ + Z^' }, and muon g-2 anomaly are also studied.

Hidden U (1 ) gauge symmetry realizing a neutrinophilic two-Higgs-doublet model with dark matter

NASA Astrophysics Data System (ADS)

Nomura, Takaaki; Okada, Hiroshi

2018-04-01

We propose a neutrinophilic two-Higgs-doublet model with hidden local U (1 ) symmetry, where active neutrinos are Dirac type, and a fermionic dark matter (DM) candidate is naturally induced as a result of remnant symmetry even after the spontaneous symmetry breaking. In addition, a physical Goldstone boson arises as a consequence of two types of gauge singlet bosons and contributes to the DM phenomenologies as well as an additional neutral gauge boson. Then, we analyze the relic density of DM within the safe range of direct detection searches and show the allowed region of dark matter mass.

Collider study on the loop-induced dark matter mediation

NASA Astrophysics Data System (ADS)

Tsai, Yuhsin

2016-06-01

Collider experiments are one of the most promising ways to constrain Dark Matter (DM) interactions. For DM couplings involving light mediators, especially for the loop-mediated interactions, a meaningful interpretation of the results requires to go beyond effective field theory. In this note we discuss the study of the magnetic dipole interacting DM, focusing on a model with anarchic dark flavor structure. By including the momentum-dependent form factors that mediate the coupling - given by the Dark Penguin - in collider processes, we study bounds from monophoton, diphoton, and non-pointing photon searches at the LHC. We also compare our results to constraints from the direct detection experiments.

MadDM: Computation of dark matter relic abundance

NASA Astrophysics Data System (ADS)

Backović, Mihailo; Kong, Kyoungchul; McCaskey, Mathew

2017-12-01

MadDM computes dark matter relic abundance and dark matter nucleus scattering rates in a generic model. The code is based on the existing MadGraph 5 architecture and as such is easily integrable into any MadGraph collider study. A simple Python interface offers a level of user-friendliness characteristic of MadGraph 5 without sacrificing functionality. MadDM is able to calculate the dark matter relic abundance in models which include a multi-component dark sector, resonance annihilation channels and co-annihilations. The direct detection module of MadDM calculates spin independent / spin dependent dark matter-nucleon cross sections and differential recoil rates as a function of recoil energy, angle and time. The code provides a simplified simulation of detector effects for a wide range of target materials and volumes.

Histochemistry and immunolocalisation of glucokinin in antidiabetic plants used in traditional Mexican medicine

PubMed Central

Rio-Zamorano, Carlos A.; Meneses-Ochoa, Itzel G.; Brechu-Franco, Alicia E.

2017-01-01

Mexico is a megadiverse country that has 3600 to 4000 species of medicinal plants, of which approximately 800 are used to treat conditions related to diabetes mellitus (DM). DM is a chronic degenerative disease of energy metabolism that exists as two types: type 1 (DM1) and type 2 (DM2). DM is considered a public health problem that affects 7% of the Mexican population older than 20 years. DM is clinically controlled with hypoglycaemic drugs, alpha-glucosidase inhibitors, insulin secretion stimulants or the direct application of insulin. The hypoglycaemic effectiveness of specific molecules has been determined only for some medicinal plants in Mexico used to treat DM2. The presence of molecules called glucokinins, wich are similar to animal insulin molecules, has been reported in some plant species; glucokinins act as both growth factors and regulators of glucose metabolism in plants. Therefore, we hypothesized that the hypoglycaemic effectiveness of some of the popularly used species for the control of DM could be due to the presence of glucokinin, as reported for Bauhinia variegata. The goal of this work was to use histochemistry to detect, the accumulation of protein that is immunocytochemically compatible with glucokinin in slide sections of hypoglycaemic species used as remedies for DM2. The top fourteen most used medicinal plants in Mexico were selected for study via microscopic sections. Proteins were histochemically detected using naphthol blue black and Johansen’s quadruple stain, and the immunocytochemical correspondence of the proteins with glucokinin was investigated using an insulin antibody. All species studied reacted positively to proteins and glucokinin in the same structures. The presence of glucokinin in these structures and the corresponding hypoglycaemic effects are discussed in the context of the actions of other compounds. PMID:28735523

Sharing but not caring: dark matter and the baryon asymmetry of the universe

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bernal, Nicolás; Institute of High Energy Physics, Austrian Academy of Sciences,Nikolsdorfer Gasse 18, 1050 Vienna; Fong, Chee Sheng

2016-09-02

We consider scenarios where Dark Matter (DM) particles carry baryon and/or lepton numbers, which can be defined if there exist operators connecting the dark to the visible sector. As a result, the DM fields become intimately linked to the Standard Model (SM) ones and can be maximally asymmetric just like the ordinary matter. In particular, we discuss minimal scenarios where the DM is a complex scalar or a Dirac fermion coupled to operators with nonzero baryon and/or lepton numbers, and that consist of only SM fields. We consider an initial asymmetry stored in either the SM or the DM sector;more » the main role of these operators is to properly share the asymmetry between the two sectors, in accordance with observations. After the chemical decoupling, the DM and SM sectors do not care about each other as there is only an ineffective communication between them. Once the DM mass is specified, the Wilson coefficients of these operators are fixed by the requirement of the correct transfer of the asymmetry. We study the phenomenology of this framework at colliders, direct detection and indirect detection experiments. In particular, the LHC phenomenology is very rich and can be tested in different channels such as the two same-sign leptons with two jets, monojet and monojet with a monolepton.« less

The yield and feasibility of integrated screening for TB, diabetes and HIV in four public hospitals in Ethiopia.

PubMed

Jerene, Degu; Hiruy, Nebiyu; Jemal, Ilili; Gebrekiros, Wondimu; Anteneh, Tadesse; Habte, Dereje; Melese, Muluken; Suarez, Pedro; Sangiwa, Gloria

2017-03-01

Our objective was to demonstrate the feasibility of integrated care for TB, HIV and diabetes mellitus (DM) in a pilot project in Ethiopia. Healthcare workers in four hospitals screened patients with TB for HIV and DM; patients with HIV for DM and TB; and patients with DM for TB. Fasting and random plasma glucose (RPG) tests were used to confirm the diagnosis of DM. We used screening checklists for TB and DM, and additional risk scoring criteria to identify patients at risk of DM. Of 3439 study participants, 888 were patients with DM, 439 patients with TB and 2112 from HIV clinics. Six of the patients with DM had TB of whom five were already on treatment; and 141 (32.4%) patients with TB had DM, of whom only five were previously diagnosed with DM. Symptomatic patients and those with a risk score of 5 or more were about three times more likely to have abnormal blood glucose level. Of 2075 HIV patients with RPG determined, only 31 (1.5%) had abnormal RPG. Tri-directional screening was feasible for detecting and managing previously undiagnosed TB and DM. More work is needed to better understand the interaction between HIV and DM. © The Author 2017. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Solving the muon g -2 anomaly in deflected anomaly mediated SUSY breaking with messenger-matter interactions

NASA Astrophysics Data System (ADS)

Wang, Fei; Wang, Wenyu; Yang, Jin Min

2017-10-01

We propose to introduce general messenger-matter interactions in the deflected anomaly mediated supersymmetry (SUSY) breaking (AMSB) scenario to explain the gμ-2 anomaly. Scenarios with complete or incomplete grand unified theory (GUT) multiplet messengers are discussed, respectively. The introduction of incomplete GUT mulitiplets can be advantageous in various aspects. We found that the gμ-2 anomaly can be solved in both scenarios under current constraints including the gluino mass bounds, while the scenarios with incomplete GUT representation messengers are more favored by the gμ-2 data. We also found that the gluino is upper bounded by about 2.5 TeV (2.0 TeV) in scenario A and 3.0 TeV (2.7 TeV) in scenario B if the generalized deflected AMSB scenarios are used to fully account for the gμ-2 anomaly at 3 σ (2 σ ) level. Such a gluino should be accessible in the future LHC searches. Dark matter (DM) constraints, including DM relic density and direct detection bounds, favor scenario B with incomplete GUT multiplets. Much of the allowed parameter space for scenario B could be covered by the future DM direct detection experiments.

Cancellation Mechanism for Dark-Matter-Nucleon Interaction.

PubMed

Gross, Christian; Lebedev, Oleg; Toma, Takashi

2017-11-10

We consider a simple Higgs portal dark-matter model, where the standard model is supplemented with a complex scalar whose imaginary part plays the role of weakly interacting massive particle dark matter (DM). We show that the direct DM detection cross section vanishes at the tree level and zero momentum transfer due to a cancellation by virtue of a softly broken symmetry. This cancellation is operative for any mediator masses. As a result, our electroweak-scale dark matter satisfies all of the phenomenological constraints quite naturally.

Halo-independent direct detection analyses without mass assumptions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anderson, Adam J.; Fox, Patrick J.; Kahn, Yonatan

2015-10-01

Results from direct detection experiments are typically interpreted by employing an assumption about the dark matter velocity distribution, with results presented in the m{sub χ}−σ{sub n} plane. Recently methods which are independent of the DM halo velocity distribution have been developed which present results in the v{sub min}− g-tilde plane, but these in turn require an assumption on the dark matter mass. Here we present an extension of these halo-independent methods for dark matter direct detection which does not require a fiducial choice of the dark matter mass. With a change of variables from v{sub min} to nuclear recoil momentummore » (p{sub R}), the full halo-independent content of an experimental result for any dark matter mass can be condensed into a single plot as a function of a new halo integral variable, which we call h-tilde (p{sub R}). The entire family of conventional halo-independent g-tilde (v{sub min}) plots for all DM masses are directly found from the single h-tilde (p{sub R}) plot through a simple rescaling of axes. By considering results in h-tilde (p{sub R}) space, one can determine if two experiments are inconsistent for all masses and all physically possible halos, or for what range of dark matter masses the results are inconsistent for all halos, without the necessity of multiple g-tilde (v{sub min}) plots for different DM masses. We conduct a sample analysis comparing the CDMS II Si events to the null results from LUX, XENON10, and SuperCDMS using our method and discuss how the results can be strengthened by imposing the physically reasonable requirement of a finite halo escape velocity.« less

Halo-independent direct detection analyses without mass assumptions

DOE PAGES

Anderson, Adam J.; Fox, Patrick J.; Kahn, Yonatan; ...

2015-10-06

Results from direct detection experiments are typically interpreted by employing an assumption about the dark matter velocity distribution, with results presented in the m χ – σ n plane. Recently methods which are independent of the DM halo velocity distribution have been developed which present results in the v min – g ~ plane, but these in turn require an assumption on the dark matter mass. Here we present an extension of these halo-independent methods for dark matter direct detection which does not require a fiducial choice of the dark matter mass. With a change of variables from v minmore » to nuclear recoil momentum (p R), the full halo-independent content of an experimental result for any dark matter mass can be condensed into a single plot as a function of a new halo integral variable, which we call tilde h(p R). The entire family of conventional halo-independent tilde g ~(v min) plots for all DM masses are directly found from the single tilde h ~(p R) plot through a simple rescaling of axes. By considering results in tildeh ~(p R) space, one can determine if two experiments are inconsistent for all masses and all physically possible halos, or for what range of dark matter masses the results are inconsistent for all halos, without the necessity of multiple tilde g ~(v min) plots for different DM masses. As a result, we conduct a sample analysis comparing the CDMS II Si events to the null results from LUX, XENON10, and SuperCDMS using our method and discuss how the results can be strengthened by imposing the physically reasonable requirement of a finite halo escape velocity.« less

Collider study on the loop-induced dark matter mediation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsai, Yuhsin, E-mail: yhtsai@umd.edu

2016-06-21

Collider experiments are one of the most promising ways to constrain Dark Matter (DM) interactions. For DM couplings involving light mediators, especially for the loop-mediated interactions, a meaningful interpretation of the results requires to go beyond effective field theory. In this note we discuss the study of the magnetic dipole interacting DM, focusing on a model with anarchic dark flavor structure. By including the momentum-dependent form factors that mediate the coupling – given by the Dark Penguin – in collider processes, we study bounds from monophoton, diphoton, and non-pointing photon searches at the LHC. We also compare our results tomore » constraints from the direct detection experiments.« less

Signals of leptophilic dark matter at the ILC

NASA Astrophysics Data System (ADS)

Dutta, Sukanta; Rawat, Bharti; Sachdeva, Divya

2017-09-01

Adopting a model independent approach, we constrain the various effective interactions of leptophilic DM particles with the visible world from the WMAP and Planck data. The thermally averaged indirect DM annihilation cross section and the DM-electron direct-detection cross section for such a DM candidate are observed to be consistent with the respective experimental data. We study the production of cosmologically allowed leptophilic DM in association with Z (Z→ f\\bar{f}), f≡ q, e^-, μ ^- at the ILC. We perform the χ ^2 analysis and compute the 99% C.L. acceptance contours in the m_χ and Λ plane from the two-dimensional differential distributions of various kinematic observables obtained after employing parton showering and hadronisation to the simulated data. We observe that the dominant hadronic channel provides the best kinematic reach of 2.62 TeV (m_χ = 25 GeV), which further improves to ˜ 3 TeV for polarised beams at √{s} = 1 TeV and an integrated luminosity of 1 ab^{-1}.

Higgs naturalness and dark matter stability by scale invariance

NASA Astrophysics Data System (ADS)

Guo, Jun; Kang, Zhaofeng

2015-09-01

Extending the spacetime symmetries of standard model (SM) by scale invariance (SI) may address the Higgs naturalness problem. In this article we attempt to embed accidental dark matter (DM) into SISM, requiring that the symmetry protecting DM stability is accidental due to the model structure rather than imposed by hand. In this framework, if the light SM-like Higgs boson is the pseudo Goldstone boson of SI spontaneously breaking, we can even pine down the model, two-Higgs-doublets plus a real singlet: The singlet is the DM candidate and the extra Higgs doublet triggers electroweak symmetry breaking via the Coleman-Weinberg mechanism; Moreover, it dominates DM dynamics. We study spontaneously breaking of SI using the Gillard-Weinberg approach and find that the second doublet should acquire vacuum expectation value near the weak scale. Moreover, its components should acquire masses around 380 GeV except for a light CP-odd Higgs boson. Based on these features, we explore viable ways to achieve the correct relic density of DM, facing stringent constraints from direct detections of DM. For instance, DM annihilates into b b bar near the SM-like Higgs boson pole, or into a pair of CP-odd Higgs boson with mass above that pole.

Probabilistic Inference of Dark Matter Properties in Galaxy Clusters and the Cosmic Web

NASA Astrophysics Data System (ADS)

Ng, Yin-Yee

2016-03-01

"Mass tells spacetime how to curve, spacetime tells mass how to move". This famous quote by physicist John Archibald Wheeler succinctly summarizes General Relativity, the most successful theory that describes our universe at large scale. However, most of the mass that General Relativity describes, namely dark matter (DM), remains a mystery. We have solid evidence of the existence of DM from various observations, but we know little or nothing about the particle nature of DM and how DM particles interact with different particles. Completing this knowledge gap would improve or revolutionize our established cosmological model, the Lambda Cold-Dark Matter (CDM) model, and give directions to theories beyond the standard particle physics model. This work attempts to study DM by examining and extending existing modeling approaches of DM and its visible tracers in a probabilistic way. The single verified form of DM interaction is gravitational. Currently, the only way to infer the properties of DM is through visible tracers. Most of these indirect detections either have low signal-to-noise, sparse coverage, or missing variables. These limitations introduce additional modeling choices and uncertainties. A probabilistic approach allows us to propagate the uncertainties appropriately and marginalize any missing variables. There are two recurring types of visible tracers that my work uses. The first type of tracers are galaxies and observables in the overdense regions of DM. These tracers allow us to infer the macroscopic dynamical properties of DM distribution that we want to study. The second type of tracers, on the hand, are in the background, i.e. further away than the foreground dark matter, from us observers. The gravity of DM can bend spacetime such that the path of light traveling in the vicinity would also curve, leaving distortions in the galaxy images. In the introduction (first chapter) of this thesis, I will lay out the technical history, terminology and the reasons behind choosing the various data sets and give an overview of the analysis methods for my thesis work. In chapter two, I will present the study based on the observational data of El Gordo, one of the most massive, most ancient, merging galaxy clusters. Under the extreme collision speeds during a merger of a galaxy cluster, it is more probable for DM particles in the cluster to manifest effects of self-interaction. Thus, if DM particles can interact with one another, some preliminary simulations have shown that large-scale spatial distribution of DM can show discrepancies from its galaxy-counterparts. This discrepancy is also known as the galaxy-DM offset, with a caveat. The long duration (millions of years) of a merger means that we cannot detect the direction of motions of the components directly to confirm the offset as a lag. My work on El Gordo was the first to show a quantitative method of estimating how likely the DM components of El Gordo are to be moving in a certain direction. To address my concerns from the study of El Gordo, I conducted a second investigation of galaxy clusters in a cosmological simulation, which is described in chapter 3. The dataset I chose was from the Illustris simulation. As this simulation assumes a Cold-Dark-Matter model (CDM) without requiring an SIDM model, any offset between DM and the member galaxies in a galaxy cluster provides an estimate of the variability of the galaxy-DM o. My study shows that the variability in this setting is non-negligible compared to the small observed offsets, it is likely that random variation can account for the galaxy-DM offsets in observations. The result weakens our belief that SIDM is the cause of the offsets. The fourth chapter of my dissertation builds on top of my previous experience with analyzing the weak lensing data for El Gordo. This time, I performed the weak lensing study for a dataset of a much larger spatial scale, such that, galaxy clusters look like parts of a homogeneous and isotropic DM web. At this scale, it is possible to compare the spatial distribution of DM to simulations to give competitive constraints on cosmological parameters. Using weak lensing signals for estimating cosmological parameters is also known as cosmic shear inference. While I used a parametric technique to estimate the mass of El Gordo in chapter 2, my work in chapter 4 introduces a new non-parametric model using a Gaussian Process. As I have built the lensing physics into the very core of the covariance kernel matrix, we can also simultaneously infer the several important lensing observables, such as shear and convergence, given some lensed galaxy shapes. More importantly, this technique relies on fewer assumptions about the photometric redshift than traditional cosmic shear analysis technique. This may reduce the bias towards a ducial cosmology and lead to interesting discoveries. I conclude my work in Chapter 5 and discuss the implications of my work. This includes some future directions for analyzing DM by using simulations with different underlying DM models and real data. (Abstract shortened by ProQuest.).

Very Degenerate Higgsino Dark Matter

DOE PAGES

Chun, Eung Jin; Jung, Sunghoon; Park, Jong-Chul

2017-01-03

In this paper, we present a study of the Very Degenerate Higgsino Dark Matter (DM), whose mass splitting between the lightest neutral and charged components is O(1) MeV, much smaller than radiative splitting of 355 MeV. The scenario is realized in the minimal supersymmetric standard model by small gaugino mixings. In contrast to the pure Higgsino DM with the radiative splitting only, various observable signatures with distinct features are induced. First of all, the very small mass splitting makes (a) sizable Sommerfeld enhancement and Ramsauer-Townsend (RT) suppression relevant to ~1 TeV Higgsino DM, and (b) Sommerfeld-Ramsauer-Townsend effect saturate at lowermore » velocities v/c ≲ 10 -3. As a result, annihilation signals can be large enough to be observed from the galactic center and/or dwarf galaxies, while the relative signal sizes can vary depending on the locations of Sommerfeld peaks and RT dips. In addition, at collider experiments, stable chargino signatures can be searched for to probe the model in the future. Finally, DM direct detection signals, however, depend on the Wino mass; even no detectable signals can be induced if the Wino is heavier than about 10 TeV.« less

QTL mapping for downy mildew resistance in cucumber via bulked segregant analysis using next-generation sequencing and conventional methods.

PubMed

Win, Khin Thanda; Vegas, Juan; Zhang, Chunying; Song, Kihwan; Lee, Sanghyeob

2017-01-01

QTL mapping using NGS-assisted BSA was successfully applied to an F 2 population for downy mildew resistance in cucumber. QTLs detected by NGS-assisted BSA were confirmed by conventional QTL analysis. Downy mildew (DM), caused by Pseudoperonospora cubensis, is one of the most destructive foliar diseases in cucumber. QTL mapping is a fundamental approach for understanding the genetic inheritance of DM resistance in cucumber. Recently, many studies have reported that a combination of bulked segregant analysis (BSA) and next-generation sequencing (NGS) can be a rapid and cost-effective way of mapping QTLs. In this study, we applied NGS-assisted BSA to QTL mapping of DM resistance in cucumber and confirmed the results by conventional QTL analysis. By sequencing two DNA pools each consisting of ten individuals showing high resistance and susceptibility to DM from a F 2 population, we identified single nucleotide polymorphisms (SNPs) between the two pools. We employed a statistical method for QTL mapping based on these SNPs. Five QTLs, dm2.2, dm4.1, dm5.1, dm5.2, and dm6.1, were detected and dm2.2 showed the largest effect on DM resistance. Conventional QTL analysis using the F 2 confirmed dm2.2 (R 2  = 10.8-24 %) and dm5.2 (R 2  = 14-27.2 %) as major QTLs and dm4.1 (R 2  = 8 %) as two minor QTLs, but could not detect dm5.1 and dm6.1. A new QTL on chromosome 2, dm2.1 (R 2  = 28.2 %) was detected by the conventional QTL method using an F 3 population. This study demonstrated the effectiveness of NGS-assisted BSA for mapping QTLs conferring DM resistance in cucumber and revealed the unique genetic inheritance of DM resistance in this population through two distinct major QTLs on chromosome 2 that mainly harbor DM resistance.

New method for analyzing dark matter direct detection data

NASA Astrophysics Data System (ADS)

Davis, Jonathan H.; Enßlin, Torsten; BÅ`hm, Céline

2014-02-01

The experimental situation of dark matter direct detection has reached an exciting crossroads, with potential hints of a discovery of dark matter (DM) from the CDMS, CoGeNT, CRESST-II and DAMA experiments in tension with null results from xenon-based experiments such as XENON100 and LUX. Given the present controversial experimental status, it is important that the analytical method used to search for DM in direct detection experiments is both robust and flexible enough to deal with data for which the distinction between signal and background points is difficult, and hence where the choice between setting a limit or defining a discovery region is debatable. In this article we propose a novel (Bayesian) analytical method, which can be applied to all direct detection experiments and which extracts the maximum amount of information from the data. We apply our method to the XENON100 experiment data as a worked example, and show that firstly our exclusion limit at 90% confidence is in agreement with their own for the 225 live days data, but is several times stronger for the 100 live days data. Secondly we find that, due to the two points at low values of S1 and S2 in the 225 days data set, our analysis points to either weak consistency with low-mass dark matter or the possible presence of an unknown background. Given the null result from LUX, the latter scenario seems the more plausible.

Charged composite scalar dark matter

NASA Astrophysics Data System (ADS)

Balkin, Reuven; Ruhdorfer, Maximilian; Salvioni, Ennio; Weiler, Andreas

2017-11-01

We consider a composite model where both the Higgs and a complex scalar χ, which is the dark matter (DM) candidate, arise as light pseudo Nambu-Goldstone bosons (pNGBs) from a strongly coupled sector with TeV scale confinement. The global symmetry structure is SO(7)/SO(6), and the DM is charged under an exact U(1)DM ⊂ SO(6) that ensures its stability. Depending on whether the χ shift symmetry is respected or broken by the coupling of the top quark to the strong sector, the DM can be much lighter than the Higgs or have a weak-scale mass. Here we focus primarily on the latter possibility. We introduce the lowest-lying composite resonances and impose calculability of the scalar potential via generalized Weinberg sum rules. Compared to previous analyses of pNGB DM, the computation of the relic density is improved by fully accounting for the effects of the fermionic top partners. This plays a crucial role in relaxing the tension with the current DM direct detection constraints. The spectrum of resonances contains exotic top partners charged under the U(1)DM, whose LHC phenomenology is analyzed. We identify a region of parameters with f = 1.4 TeV and 200 GeV ≲ m χ ≲ 400 GeV that satisfies all existing bounds. This DM candidate will be tested by XENON1T in the near future.

Depression, anxiety, and prevalent diabetes in the Chinese population: Findings from the China Kadoorie Biobank of 0.5 million people

PubMed Central

Mezuk, Briana; Chen, Yiping; Yu, Canqing; Guo, Yu; Bian, Zheng; Collins, Rory; Chen, Junshi; Pang, Zengchang; Wang, Huijun; Peto, Richard; Que, Xiangsan; Zhang, Hui; Tan, Zhongwen; Kendler, Kenneth S.; Li, Liming; Chen, Zhengming

2013-01-01

Objective Despite previous investigation, uncertainty remains about the nature of the associations of major depression (MD) with type 2 diabetes mellitus (T2DM), particularly in adult Chinese, and the relevance of generalized anxiety disorder (GAD) for T2DM. Methods Cross-sectional data from the China Kadoorie Biobank Study, a sample of approximately 500,000 adults from 10 geographically defined regions of China, were analyzed. Past year MD and GAD were assessed using the Composite International Diagnostic Inventory. T2DM was defined as either having self-reported physician diagnosis of diabetes at age 30 or later (“clinically-identified” cases) or having a non-fasting blood glucose ≥11.1 mmol/L or fasting blood glucose ≥7.0 mmol/L but no prior diagnosis of diabetes (“screen-detected” cases). Logistic regression was used to assess the relationship between MD and GAD with clinically-identified and screen-detected T2DM, adjusting for demographic characteristics and health behaviors. Results The prevalence of T2DM was 5.3% (3.2% clinically-identified and 2.1% screen-detected). MD was significantly associated with clinically-identified T2DM (Odds ratio [OR]: 1.75, 95% Confidence Interval (CI): 1.47 – 2.08), but not with screen-detected T2DM (OR: 1.18, 95% CI: 0.92 – 1.51). GAD was associated with both clinically-identified (OR: 2.14, 95% CI: 1.60 – 2.88) and screen-detected (OR: 1.44, 95% CI: 0.99 – 2.08) T2DM. The relationship between MD and GAD with T2DM was moderated by obesity. Conclusion MD is associated with clinically-identified, but not screen-detected T2DM. GAD is associated with both clinically-identified and screen-detected T2DM. The relationship between MD and T2DM is strongest among those who are not obese. PMID:24290039

Target-protecting dumbbell molecular probe against exonucleases digestion for sensitive detection of ATP and streptavidin.

PubMed

Chen, Jinyang; Liu, Yucheng; Ji, Xinghu; He, Zhike

2016-09-15

In this work, a versatile dumbbell molecular (DM) probe was designed and employed in the sensitively homogeneous bioassay. In the presence of target molecule, the DM probe was protected from the digestion of exonucleases. Subsequently, the protected DM probe specifically bound to the intercalation dye and resulted in obvious fluorescence signal which was used to determine the target molecule in return. This design allows specific and versatile detection of diverse targets with easy operation and no sophisticated fluorescence labeling. Integrating the idea of target-protecting DM probe with adenosine triphosphate (ATP) involved ligation reaction, the DM probe with 5'-end phosphorylation was successfully constructed for ATP detection, and the limitation of detection was found to be 4.8 pM. Thanks to its excellent selectivity and sensitivity, this sensing strategy was used to detect ATP spiked in human serum as well as cellular ATP. Moreover, the proposed strategy was also applied in the visual detection of ATP in droplet-based microfluidic platform with satisfactory results. Similarly, combining the principle of target-protecting DM probe with streptavidin (SA)-biotin interaction, the DM probe with 3'-end biotinylation was developed for selective and sensitive SA determination, which demonstrated the robustness and versatility of this design. Copyright © 2016 Elsevier B.V. All rights reserved.

Far-infrared properties of flare stars and dM stars

NASA Technical Reports Server (NTRS)

Mullan, D. J.; Stencel, R. E.; Backman, D. E.

1989-01-01

Results are reported from a search of the IRAS data base for flare stars and for a control sample of dM stars. At 12 microns, 70-80 percent of both samples have been detected. The K-12 colors of flare stars are significantly different from those of dM stars: for a given K magnitude, a flare star is about 70 percent brighter at 12 microns than a dM star. At 100 microns, 27 percent of the flare stars which are sources at 12 microns have been detected, while none of the comparable dM stars has been detected. Implications for microflaring are discussed.

Multiwavelength analysis of annihilating dark matter as the origin of the gamma-ray emission from M31

NASA Astrophysics Data System (ADS)

McDaniel, Alex; Jeltema, Tesla; Profumo, Stefano

2018-05-01

Indirect detection of dark matter (DM) by multiwavelength astronomical observations provides a promising avenue for probing the particle nature of DM. In the case of DM consisting of weakly interacting massive particles (WIMPs), self-annihilation ultimately produces various observable products including e± pairs and gamma rays. The gamma rays can be detected directly, while the e± pairs can be detected by radio emission from synchrotron radiation or X rays and soft gamma rays from inverse Compton scattering. An intriguing region to search for astrophysical signs of DM is the Galactic center (GC) of the Milky Way, due in part to an observed excess of gamma rays that could be DM. A recent observation by the Fermi-LAT collaboration of a similar excess in the central region of the Andromeda galaxy (M31) leads us to explore the possibility of a DM-induced signal there as well. We use the RX-DMFIT tool to perform a multifrequency analysis of potential DM annihilation emissions in M31. We consider WIMP particle models consistent with the GC excess and calculate the expected emission across the electromagnetic spectrum in comparison with available observational data from M31. We find that the particle models that best fit the M31 excess favor lower masses than the GC excess. The best-fitting models are for a b b ¯ final state with Mχ=11 GeV and ⟨σ v ⟩ =2.6 ×10-26 cm3 s-1 , as well as an evenly mixed b b ¯ /τ+τ- final state with Mχ=5.8 GeV and ⟨σ v ⟩=2.03 ×10-26 cm3 s-1 . For conservative estimates of the diffusion and magnetic field models the expected radio emissions appear to be in tension with currently available data in the central region of M31, although this constraint has a fairly strong dependence on the values chosen for parameters describing the magnetic field strength and geometry.

First search for a dark matter annual modulation signal with NaI(Tl) in the Southern Hemisphere by DM-Ice17

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barbosa de Souza, E.; Cherwinka, J.; Cole, A.

The first search for a dark matter annual modulation signal with NaI(Tl) target material in the Southern Hemisphere conducted with the DM-Ice17 experiment is presented. DM-Ice17 consists of 17 kg of NaI(Tl) scintillating crystal under 2200 m.w.e. overburden of Antarctic glacial ice. The analysis presented here utilizes a 60.8 kg yr exposure. While unable to exclude the signal reported by DAMA/LIBRA, the DM-Ice17 data are consistent with no modulation in the energy range of 4-20 keV, providing the strongest limits on WIMP candidates from a direct detection experiment located in the Southern Hemisphere. Additionally, the successful deployment and stable operationmore » of 17 kg of NaI(Tl) crystal over 3.5 years establishes the South Pole ice as a viable location for future underground, low-background experiments.« less

First data from DM-Ice17

DOE PAGES

Cherwinka, J.; Grant, D.; Halzen, F.; ...

2014-11-10

We report the first analysis of background data from DM-Ice17, a direct-detection dark matter experiment consisting of 17 kg of NaI(Tl) target material. It was codeployed with IceCube 2457 m deep in the South Pole glacial ice in December 2010 and is the first such detector operating in the Southern Hemisphere. The background rate in the 6.5–8.0 keV ee region is measured to be 7.9 ± 0.4 counts/day/keV/kg. This is consistent with the expected background from the detector assemblies with negligible contributions from the surrounding ice. The successful deployment and operation of DM-Ice17 establishes the South Pole ice as amore » viable location for future underground, low-background experiments in the Southern Hemisphere. Furthermore, the detector assembly and deployment are described here, as well as the analysis of the DM-Ice17 backgrounds based on data from the first two years of operation after commissioning, July 2011–June 2013.« less

Extended Higgs-portal dark matter and the Fermi-LAT Galactic Center Excess

NASA Astrophysics Data System (ADS)

Casas, J. A.; Gómez Vargas, G. A.; Moreno, J. M.; Quilis, J.; Ruiz de Austri, R.

2018-06-01

In the present work, we show that the Galactic Center Excess (GCE) emission, as recently updated by the Fermi-LAT Collaboration, could be explained by a mixture of Fermi-bubbles-like emission plus dark matter (DM) annihilation, in the context of a scalar-singlet Higgs portal scenario (SHP). In fact, the standard SHP, where the DM particle, S, only has renormalizable interactions with the Higgs, is non-operational due to strong constraints, especially from DM direct detection limits. Thus we consider the most economical extension, called ESHP (for extended SHP), which consists solely in the addition of a second (more massive) scalar singlet in the dark sector. The second scalar can be integrated-out, leaving a standard SHP plus a dimension-6 operator. Mainly, this model has only two relevant parameters (the DM mass and the coupling of the dim-6 operator). DM annihilation occurs mainly into two Higgs bosons, SS→ hh. We demonstrate that, despite its economy, the ESHP model provides an excellent fit to the GCE (with p-value ~ 0.6‑0.7) for very reasonable values of the parameters, in particular, mS simeq 130 GeV. This agreement of the DM candidate to the GCE properties does not clash with other observables and keep the S‑particle relic density at the accepted value for the DM content in the universe.

Explaining the DAMPE data with scalar dark matter and gauged U(1)_{L_e-L_μ } interaction

NASA Astrophysics Data System (ADS)

Cao, Junjie; Feng, Lei; Guo, Xiaofei; Shang, Liangliang; Wang, Fei; Wu, Peiwen; Zu, Lei

2018-03-01

Inspired by the peak structure observed by recent DAMPE experiment in e^+e^- cosmic-ray spectrum, we consider a scalar dark matter (DM) model with gauged U(1)_{L_e-L_μ } symmetry, which is the most economical anomaly-free theory to potentially explain the peak by DM annihilation in nearby subhalo. We utilize the process χ χ → Z^' Z^' → l \\bar{l} l^' \\bar{l}^' , where χ , Z^' , l^{(' )} denote the scalar DM, the new gauge boson and l^{(' )} =e, μ , respectively, to generate the e^+e^- spectrum. By fitting the predicted spectrum to the experimental data, we obtain the favored DM mass range m_χ ˜eq 3060^{+80}_{-100} GeV and Δ m ≡ m_χ - m_{Z^' } ≲ 14 GeV at 68% Confidence Level (C.L.). Furthermore, we determine the parameter space of the model which can explain the peak and meanwhile satisfy the constraints from DM relic abundance, DM direct detection and the collider bounds. We conclude that the model we consider can account for the peak, although there exists a tension with the constraints from the LEP-II bound on m_{Z^' } arising from the cross section measurement of e^+e^- → Z^' *} → e^+ e^-.

A model explaining neutrino masses and the DAMPE cosmic ray electron excess

NASA Astrophysics Data System (ADS)

Fan, Yi-Zhong; Huang, Wei-Chih; Spinrath, Martin; Tsai, Yue-Lin Sming; Yuan, Qiang

2018-06-01

We propose a flavored U(1)eμ neutrino mass and dark matter (DM) model to explain the recent DArk Matter Particle Explorer (DAMPE) data, which feature an excess on the cosmic ray electron plus positron flux around 1.4 TeV. Only the first two lepton generations of the Standard Model are charged under the new U(1)eμ gauge symmetry. A vector-like fermion ψ, which is our DM candidate, annihilates into e± and μ± via the new gauge boson Z‧ exchange and accounts for the DAMPE excess. We have found that the data favors a ψ mass around 1.5 TeV and a Z‧ mass around 2.6 TeV, which can potentially be probed by the next generation lepton colliders and DM direct detection experiments.

DaMaSCUS: the impact of underground scatterings on direct detection of light dark matter

NASA Astrophysics Data System (ADS)

Emken, Timon; Kouvaris, Chris

2017-10-01

Conventional dark matter direct detection experiments set stringent constraints on dark matter by looking for elastic scattering events between dark matter particles and nuclei in underground detectors. However these constraints weaken significantly in the sub-GeV mass region, simply because light dark matter does not have enough energy to trigger detectors regardless of the dark matter-nucleon scattering cross section. Even if future experiments lower their energy thresholds, they will still be blind to parameter space where dark matter particles interact with nuclei strongly enough that they lose enough energy and become unable to cause a signal above the experimental threshold by the time they reach the underground detector. Therefore in case dark matter is in the sub-GeV region and strongly interacting, possible underground scatterings of dark matter with terrestrial nuclei must be taken into account because they affect significantly the recoil spectra and event rates, regardless of whether the experiment probes DM via DM-nucleus or DM-electron interaction. To quantify this effect we present the publicly available Dark Matter Simulation Code for Underground Scatterings (DaMaSCUS), a Monte Carlo simulator of DM trajectories through the Earth taking underground scatterings into account. Our simulation allows the precise calculation of the density and velocity distribution of dark matter at any detector of given depth and location on Earth. The simulation can also provide the accurate recoil spectrum in underground detectors as well as the phase and amplitude of the diurnal modulation caused by this shadowing effect of the Earth, ultimately relating the modulations expected in different detectors, which is important to decisively conclude if a diurnal modulation is due to dark matter or an irrelevant background.

DaMaSCUS: the impact of underground scatterings on direct detection of light dark matter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Emken, Timon; Kouvaris, Chris, E-mail: emken@cp3.sdu.dk, E-mail: kouvaris@cp3.sdu.dk

Conventional dark matter direct detection experiments set stringent constraints on dark matter by looking for elastic scattering events between dark matter particles and nuclei in underground detectors. However these constraints weaken significantly in the sub-GeV mass region, simply because light dark matter does not have enough energy to trigger detectors regardless of the dark matter-nucleon scattering cross section. Even if future experiments lower their energy thresholds, they will still be blind to parameter space where dark matter particles interact with nuclei strongly enough that they lose enough energy and become unable to cause a signal above the experimental threshold bymore » the time they reach the underground detector. Therefore in case dark matter is in the sub-GeV region and strongly interacting, possible underground scatterings of dark matter with terrestrial nuclei must be taken into account because they affect significantly the recoil spectra and event rates, regardless of whether the experiment probes DM via DM-nucleus or DM-electron interaction. To quantify this effect we present the publicly available Dark Matter Simulation Code for Underground Scatterings (DaMaSCUS), a Monte Carlo simulator of DM trajectories through the Earth taking underground scatterings into account. Our simulation allows the precise calculation of the density and velocity distribution of dark matter at any detector of given depth and location on Earth. The simulation can also provide the accurate recoil spectrum in underground detectors as well as the phase and amplitude of the diurnal modulation caused by this shadowing effect of the Earth, ultimately relating the modulations expected in different detectors, which is important to decisively conclude if a diurnal modulation is due to dark matter or an irrelevant background.« less

[Cost effectiveness of mass orthoptic screening in kindergarten for early detection of developmental vision disorders].

PubMed

König, H H; Barry, J C; Leidl, R; Zrenner, E

2000-04-01

Orthoptic screening in the kindergarten is one option to improve early detection of amblyopia in children aged 3 years. The purpose of this study was to analyse the cost-effectiveness of such a screening programme in Germany. Based on data from the literature and own experience gained from orthoptic screening in kindergarten a decision-analytic model was developed. According to the model, all children in kindergarten, aged 3 years, who had not been treated for amblyopia before, were subjected to an orthoptic examination. Non-cooperative children were reexamined in kindergarten after one year. Children with positive test results were examined by an ophthalmologist for diagnosis. Effects were measured by the number of newly diagnosed cases of amblyopia, non-obvious strabismus and amblyogenic refractive errors. Direct costs were estimated from a third-party payer perspective. The influence of uncertain model parameters was tested by sensitivity analysis. In the base analysis the cost per orthoptic screening test was DM 15.39. Examination by an ophthalmologist cost DM 71.20. The total cost of the screening programme in all German kindergartens was DM 6.1 million. With a 1.5% age-specific prevalence of undiagnosed cases, a sensitivity of 95% and a specificity of 98%, a total of 4,261 new cases would be detected. The cost-effectiveness ratio was DM 1,421 per case detected. Sensitivity analysis showed considerable influence of prevalence and specificity on the cost-effectiveness ratio. It was more cost-effective to re-screen non-cooperative children in kindergarten than to have them examined by an ophthalmologist straight-away. The decision-analytic model showed stable results which may serve as a basis for discussion on the implementation of orthoptic screening and for planning a field study.

Addressing diabetes mellitus as part of the strategy for ending TB

PubMed Central

Harries, Anthony D.; Kumar, Ajay M.V.; Satyanarayana, Srinath; Lin, Yan; Zachariah, Rony; Lönnroth, Knut; Kapur, Anil

2016-01-01

As we enter the new era of Sustainable Development Goals, the international community has committed to ending the TB epidemic by 2030 through implementation of an ambitious strategy to reduce TB-incidence and TB-related mortality and avoiding catastrophic costs for TB-affected families. Diabetes mellitus (DM) triples the risk of TB and increases the probability of adverse TB treatment outcomes such as failure, death and recurrent TB. The rapidly escalating global epidemic of DM means that DM needs to be addressed if TB-related milestones and targets are to be achieved. WHO and the International Union Against Tuberculosis and Lung Disease's Collaborative Framework for Care and Control of Tuberculosis and Diabetes, launched in 2011, provides a template to guide policy makers and implementers to combat the epidemics of both diseases. However, more evidence is required to answer important questions about bi-directional screening, optimal ways of delivering treatment, integration of DM and TB services, and infection control. This should in turn contribute to better and earlier TB case detection, and improved TB treatment outcomes and prevention. DM and TB collaborative care can also help guide the development of a more effective and integrated public health approach for managing non-communicable diseases. PMID:26884497

Axion cosmology

NASA Astrophysics Data System (ADS)

Marsh, David J. E.

2016-07-01

Axions comprise a broad class of particles that can play a major role in explaining the unknown aspects of cosmology. They are also well-motivated within high energy physics, appearing in theories related to CP-violation in the standard model, supersymmetric theories, and theories with extra-dimensions, including string theory, and so axion cosmology offers us a unique view onto these theories. I review the motivation and models for axions in particle physics and string theory. I then present a comprehensive and pedagogical view on the cosmology and astrophysics of axion-like particles, starting from inflation and progressing via BBN, the CMB, reionization and structure formation, up to the present-day Universe. Topics covered include: axion dark matter (DM); direct and indirect detection of axions, reviewing existing and future experiments; axions as dark radiation; axions and the cosmological constant problem; decays of heavy axions; axions and stellar astrophysics; black hole superradiance; axions and astrophysical magnetic fields; axion inflation, and axion DM as an indirect probe of inflation. A major focus is on the population of ultralight axions created via vacuum realignment, and its role as a DM candidate with distinctive phenomenology. Cosmological observations place robust constraints on the axion mass and relic density in this scenario, and I review where such constraints come from. I next cover aspects of galaxy formation with axion DM, and ways this can be used to further search for evidence of axions. An absolute lower bound on DM particle mass is established. It is ma > 10-24eV from linear observables, extending to ma ≳ 10-22eV from non-linear observables, and has the potential to reach ma ≳ 10-18eV in the future. These bounds are weaker if the axion is not all of the DM, giving rise to limits on the relic density at low mass. This leads to the exciting possibility that the effects of axion DM on structure formation could one day be detected, and the axion mass and relic density measured from cosmological observables.

An electrochemical immunosensor for quantitative detection of ficolin-3

NASA Astrophysics Data System (ADS)

San, Lili; Zeng, Dongdong; Song, Shiping; Zuo, Xiaolei; Zhang, Huan; Wang, Chenguang; Wu, Jiarui; Mi, Xianqiang

2016-06-01

Diabetes mellitus (DM) is one of the most common metabolic disorders in the world, of which more than 90% is type-2 diabetes mellitus (T2DM). There is a rather urgent need for reliable, sensitive and quick detection techniques in clinical application of T2DM. Ficolin-3 is a potential biomarker of T2DM, because serum ficolin-3 levels are associated with insulin resistance and predict the incidence of T2DM. Herein, a sandwich-type electrochemical immunosensor was developed for the detection of ficolin-3 in human serum. Cyclic voltammetry and the amperometric current versus time were used to characterize the performance of the immunosensor. Under optimal conditions, the detection limitation of ficolin-3 was 100 ng ml-1 and the linear dynamic range was between 2 and 50 μg ml-1. The method has ideal accuracy, excellent stability and selectivity and has wide application prospects in clinical research.

A method to directly image exoplanets in multi-star systems such as Alpha-Centauri

NASA Astrophysics Data System (ADS)

Thomas, Sandrine J.; Belikov, Ruslan; Bendek, Eduardo

2015-09-01

Direct imaging of extra-solar planets is now a reality, especially with the deployment and commissioning of the first generation of specialized ground-based instruments such as the Gemini Planet Imager and SPHERE. These systems will allow detection of Jupiter-like planets 107 times fainter than their host star. Obtaining this contrast level and beyond requires the combination of a coronagraph to suppress light coming from the host star and a wavefront control system including a deformable mirror (DM) to remove residual starlight (speckles) created by the imperfections of telescope. However, all these current and future systems focus on detecting faint planets around single host stars, while several targets or planet candidates are located around nearby binary stars such as our neighboring star Alpha Centauri. Here, we present a method to simultaneously correct aberrations and diffraction of light coming from the target star as well as its companion star in order to reveal planets orbiting the target star. This method works even if the companion star is outside the control region of the DM (beyond its half-Nyquist frequency), by taking advantage of aliasing effects.

Direct imaging of exoplanets around multiple star systems

NASA Astrophysics Data System (ADS)

Thomas, Sandrine

2015-01-01

Direct imaging of extra-solar planets is now a reality, especially with the deployment and commissioning of the first generation of specialized ground-based instruments such as the Gemini Planet Imager and SPHERE. These systems will allow detection of Jupiter-like planets 10^7 times fainter than their host star. Obtaining this contrast level and beyond requires the combination of a coronagraph to suppress light coming from the host star and a wavefront control system including a deformable mirror (DM) to remove residual starlight (speckles) created by the imperfections of telescope. However, all these current and future systems focus on detecting faint planets around a single host star or unresolved binaries/multiples, while several targets or planet candidates are located around nearby binary stars such as our neighboring star Alpha Centauri.Here, we present a method to simultaneously correct aberrations and diffraction of light coming from the target star as well as its companion star in order to reveal planets orbiting the target star. This method works even if the companion star is outside the control region of the DM (beyond its half-Nyquist frequency), by taking advantage of aliasing effects.

Mammographic findings of women recalled for diagnostic work-up in digital versus screen-film mammography in a population-based screening program.

PubMed

Lipasti, Seppo; Anttila, Ahti; Pamilo, Martti

2010-06-01

Limited information is available concerning differences in the radiological findings of women recalled for diagnostic work-up in digital mammography (DM) versus screen-film mammography (SFM) screening. To compare the radiological findings, their positive predictive values (PPVs) for cancer and other process indicators of DM screening performed by computed radiography (CR) technology and SFM screening in a population-based program. The material consisted of women, 50-59 years of age, who were invited for screening: 30 153 women with DM in 2007-2008 and 32 939 women with SFM in 1999-2000. The attendance rate was 77.7% (23 440) in the DM arm and 83.8% (27 593) in the SFM arm. In the DM arm, 1.71% of those screened (401) and in the SFM arm 1.59% (438) were recalled for further work-up. The images resulting in the recall were classified as: 1) tumor-like mass, 2) parenchymal distortion/asymmetry, 3) calcifications, and 4) combination of mass and calcifications. The distributions of the various radiological findings and their PPVs for cancer were compared in both study groups. The recall rates, cancer detection rates, test specificities, and PPVs of the DM and SFM groups were also compared. Women were recalled for diagnostic work-up most often due to tumor-like mass. It was more common in SFM (1.08% per woman screened) than in DM (0.93%). The second most common finding was parenchymal distortion and asymmetry, more often in DM (0.58%) than in SFM (0.37%). Calcifications were the third most common finding. DM exposed calcifications more often (0.49%) than SFM (0.26%). The PPVs for cancer of the recalls were higher in DM than in SFM in all subgroups of radiological findings. The test specificities were similar (DM 98.9%, SFM 98.8%). Significantly more cancers were detected by DM (cancer detection rate 0.623% per woman screened, n=146) than by SFM (cancer detection rate 0.406% per woman screened, n=112). The PPVs for cancer of all recalls for diagnostic work-up were significantly higher in DM (36%) than in SFM (26%). In DM women were recalled for diagnostic work-up more often for calcifications, parenchymal distortions, and asymmetries than in SFM. In the case of tumor-like masses, more women were recalled in SFM. DM detected more cancers than SFM, and the PPVs for cancer were higher in DM than in SFM in all subgroups of radiological findings.

Emergence of the mass discrepancy-acceleration relation from dark matter-baryon interactions

NASA Astrophysics Data System (ADS)

Famaey, Benoit; Khoury, Justin; Penco, Riccardo

2018-03-01

The observed tightness of the mass discrepancy-acceleration relation (MDAR) poses a fine-tuning challenge to current models of galaxy formation. We propose that this relation could arise from collisional interactions between baryons and dark matter (DM) particles, without the need for modification of gravity or ad hoc feedback processes. We assume that these interactions satisfy the following three conditions: (i) the relaxation time of DM particles is comparable to the dynamical time in disk galaxies; (ii) DM exchanges energy with baryons due to elastic collisions; (iii) the product between the baryon-DM cross section and the typical energy exchanged in a collision is inversely proportional to the DM number density. As a proof of principle, we present an example of a particle physics model that gives a DM-baryon cross section with the desired density and velocity dependence. For consistency with direct detection constraints, our DM particles must be either very light (m ll mb) or very heavy (mgg mb), corresponding respectively to heating and cooling of DM by baryons. In both cases, our mechanism applies and an equilibrium configuration can in principle be reached. In this exploratory paper, we focus on the heavy DM/cooling case because it is technically simpler, since the average energy exchanged turns out to be approximately constant throughout galaxies. Under these assumptions, we find that rotationally-supported disk galaxies could naturally settle to equilibrium configurations satisfying a MDAR at all radii without invoking finely tuned feedback processes. We also discuss issues related to the small scale clumpiness of baryons, as well as predictions for pressure-supported systems. We argue in particular that galaxy clusters do not follow the MDAR despite being DM-dominated because they have not reached their equilibrium configuration. Finally, we revisit existing phenomenological, astrophysical and cosmological constraints on baryon-DM interactions in light of the unusual density dependence of the cross section of DM particles.

Dark Matter "Collider" from Inelastic Boosted Dark Matter.

PubMed

Kim, Doojin; Park, Jong-Chul; Shin, Seodong

2017-10-20

We propose a novel dark matter (DM) detection strategy for models with a nonminimal dark sector. The main ingredients in the underlying DM scenario are a boosted DM particle and a heavier dark sector state. The relativistic DM impinged on target material scatters off inelastically to the heavier state, which subsequently decays into DM along with lighter states including visible (standard model) particles. The expected signal event, therefore, accompanies a visible signature by the secondary cascade process associated with a recoiling of the target particle, differing from the typical neutrino signal not involving the secondary signature. We then discuss various kinematic features followed by DM detection prospects at large-volume neutrino detectors with a model framework where a dark gauge boson is the mediator between the standard model particles and DM.

Regression and direct methods do not give different estimates of digestible and metabolizable energy values of barley, sorghum, and wheat for pigs.

PubMed

Bolarinwa, O A; Adeola, O

2016-02-01

Direct or indirect methods can be used to determine the DE and ME of feed ingredients for pigs. In situations when only the indirect approach is suitable, the regression method presents a robust indirect approach. Three experiments were conducted to compare the direct and regression methods for determining the DE and ME values of barley, sorghum, and wheat for pigs. In each experiment, 24 barrows with an average initial BW of 31, 32, and 33 kg were assigned to 4 diets in a randomized complete block design. The 4 diets consisted of 969 g barley, sorghum, or wheat/kg plus minerals and vitamins for the direct method; a corn-soybean meal reference diet (RD); the RD + 300 g barley, sorghum, or wheat/kg; and the RD + 600 g barley, sorghum, or wheat/kg. The 3 corn-soybean meal diets were used for the regression method. Each diet was fed to 6 barrows in individual metabolism crates for a 5-d acclimation followed by a 5-d period of total but separate collection of feces and urine in each experiment. Graded substitution of barley or wheat, but not sorghum, into the RD linearly reduced ( < 0.05) dietary DE and ME. The direct method-derived DE and ME for barley were 3,669 and 3,593 kcal/kg DM, respectively. The regressions of barley contribution to DE and ME in kilocalories against the quantity of barley DMI in kilograms generated 3,746 kcal DE/kg DM and 3,647 kcal ME/kg DM. The DE and ME for sorghum by the direct method were 4,097 and 4,042 kcal/kg DM, respectively; the corresponding regression-derived estimates were 4,145 and 4,066 kcal/kg DM. Using the direct method, energy values for wheat were 3,953 kcal DE/kg DM and 3,889 kcal ME/kg DM. The regressions of wheat contribution to DE and ME in kilocalories against the quantity of wheat DMI in kilograms generated 3,960 kcal DE/kg DM and 3,874 kcal ME/kg DM. The DE and ME of barley using the direct method were not different (0.3 < < 0.4) from those obtained using the regression method (3,669 vs. 3,746 and 3,593 vs. 3,647 kcal/kg DM, respectively). The direct method-derived DE and ME of sorghum were not different (0.5 < < 0.7) from those obtained using the regression method (4,097 vs. 4,145 and 4,042 vs. 4,066 kcal/kg DM, respectively). The direct method- and regression method-derived DE (3,953 and 3,960 kcal/kg DM, respectively) and ME (3,889 and 3,874 kcal/kg DM, respectively) of wheat were not different (0.8 < < 0.9). Results of these 3 experiments suggest that regression and direct methods do not give different estimates of DE and ME in barley, sorghum, and wheat for pigs.

The Fermi-LAT gamma-ray excess at the Galactic Center in the singlet-doublet fermion dark matter model

NASA Astrophysics Data System (ADS)

Horiuchi, Shunsaku; Macias, Oscar; Restrepo, Diego; Rivera, Andrés; Zapata, Oscar; Silverwood, Hamish

2016-03-01

The singlet-doublet fermion dark matter model (SDFDM) provides a good DM candidate as well as the possibility of generating neutrino masses radiatively. The search and identification of DM requires the combined effort of both indirect and direct DM detection experiments in addition to the LHC. Remarkably, an excess of GeV gamma rays from the Galactic Center (GCE) has been measured with the Fermi Large Area Telescope (LAT) which appears to be robust with respect to changes in the diffuse galactic background modeling. Although several astrophysical explanations have been proposed, DM remains a simple and well motivated alternative. In this work, we examine the sensitivities of dark matter searches in the SDFDM scenario using Fermi-LAT, CTA, IceCube/DeepCore, LUX, PICO and LHC with an emphasis on exploring the regions of the parameter space that can account for the GCE. We find that DM particles present in this model with masses close to ~ 99 GeV and ~ (173-190) GeV annihilating predominantly into the W+W- channel and tbar t channel respectively, provide an acceptable fit to the GCE while being consistent with different current experimental bounds. We also find that much of the obtained parameter space can be ruled out by future direct search experiments like LZ and XENON-1T, in case of null results by these detectors. Interestingly, we show that the most recent data by LUX is starting to probe the best fit region in the SDFDM model.

CP violating scalar Dark Matter

NASA Astrophysics Data System (ADS)

Cordero-Cid, A.; Hernández-Sánchez, J.; Keus, V.; King, S. F.; Moretti, S.; Rojas, D.; Sokołowska, D.

2016-12-01

We study an extension of the Standard Model (SM) in which two copies of the SM scalar SU(2) doublet which do not acquire a Vacuum Expectation Value (VEV), and hence are inert, are added to the scalar sector. We allow for CP-violation in the inert sector, where the lightest inert state is protected from decaying to SM particles through the conservation of a Z 2 symmetry. The lightest neutral particle from the inert sector, which has a mixed CP-charge due to CP-violation, is hence a Dark Matter (DM) candidate. We discuss the new regions of DM relic density opened up by CP-violation, and compare our results to the CP-conserving limit and the Inert Doublet Model (IDM). We constrain the parameter space of the CP-violating model using recent results from the Large Hadron Collider (LHC) and DM direct and indirect detection experiments.

Renormalization group equation analysis of a pseudoscalar portal dark matter model

NASA Astrophysics Data System (ADS)

Ghorbani, Karim

2017-10-01

We investigate the vacuum stability and perturbativity of a pseudoscalar portal dark matter (DM) model with a Dirac DM candidate, through the renormalization group equation analysis at one-loop order. The model has a particular feature which can evade the direct detection upper bounds measured by XENON100 and even that from planned experiment XENON1T. We first find the viable regions in the parameter space which will give rise to correct DM relic density and comply with the constraints from Higgs physics. We show that for a given mass of the pseudoscalar, the mixing angle plays no significant role in the running of the couplings. Then we study the running of the couplings for various pseudoscalar masses at mixing angle θ =6^\\circ , and find the scale of validity in terms of the dark coupling, {λ }d. Depending on our choice of the cutoff scale, the resulting viable parameter space will be determined.

Top-philic scalar Dark Matter with a vector-like fermionic top partner

NASA Astrophysics Data System (ADS)

Baek, Seungwon; Ko, Pyungwon; Wu, Peiwen

2016-10-01

We consider a simple extension of the Standard Model with a scalar top-philic Dark Matter (DM) S coupling, apart from the Higgs portal, exclusively to the right-handed top quark t R and a colored vector-like top partner T with a Yukawa coupling y ST which we call the topVL portal. When the Higgs portal is closed and y ST is perturbative (≲1), T S → ( W + b, gt), SSto toverline{t} and Toverline{T}to (qoverline{q}, gg) provide the dominant (co) annihilation contributions to obtain ΩDM h 2 ≃ 0 .12 in light, medium and heavy DM mass range, respectively. However, large {y}_{ST}˜ O(10) can make SS → gg dominate via the loop-induced coupling C SSgg in the m S < m t region. In this model it is the C SSgg coupling that generates DM-nucleon scattering in the direct detection, which can be large and simply determined by ΩDM h 2 ≃ 0 .12 when SS → gg dominates the DM annihilation. The current LUX results can exclude the SS → gg dominating scenario and XENON-1T experiment may further test y ST ≳ 1, and 0 .5 ≲ y ST ≲ 1 may be covered in the future LUX-ZP experiment. The current indirect detection results from Fermi gamma-ray observations can also exclude the SS → gg dominating scenario and are sensitive to the heavy DM mass region, of which the improved sensitivity by one order will push DM mass to be above 400, 600, 1000 GeV for y ST = 0 .3 , 0 .5 , 1 .0, respectively. Toverline{T} pair produced at the hadron collider will decay 100% into [InlineMediaObject not available: see fulltext.] signal when kinematically open. The latest ATLAS 13 TeV 13.2 fb-1 data can excluded m T between 300 (650) and 1150 (1100) GeV for m S =40 (400) GeV and the exclusion region can reach up to m S ˜ 500 GeV.

A Novel Approach in the Weakly Interacting Massive Particle Quest: Cross-correlation of Gamma-Ray Anisotropies and Cosmic Shear

NASA Astrophysics Data System (ADS)

Camera, Stefano; Fornasa, Mattia; Fornengo, Nicolao; Regis, Marco

2013-07-01

Both cosmic shear and cosmological gamma-ray emission stem from the presence of dark matter (DM) in the universe: DM structures are responsible for the bending of light in the weak-lensing regime and those same objects can emit gamma rays, either because they host astrophysical sources (active galactic nuclei or star-forming galaxies) or directly by DM annihilations (or decays, depending on the properties of the DM particle). Such gamma rays should therefore exhibit strong correlation with the cosmic shear signal. In this Letter, we compute the cross-correlation angular power spectrum of cosmic shear and gamma rays produced by the annihilation/decay of weakly interacting massive particle DM, as well as by astrophysical sources. We show that this observable provides novel information on the composition of the extragalactic gamma-ray background (EGB), since the amplitude and shape of the cross-correlation signal strongly depend on which class of sources is responsible for the gamma-ray emission. If the DM contribution to the EGB is significant (at least in a definite energy range), although compatible with current observational bounds, its strong correlation with the cosmic shear makes such signal potentially detectable by combining Fermi Large Area Telescope data with forthcoming galaxy surveys, like the Dark Energy Survey and Euclid. At the same time, the same signal would demonstrate that the weak-lensing observables are indeed due to particle DM matter and not to possible modifications of general relativity.

The Ability of Bacterial Cocaine Esterase to Hydrolyze Cocaine Metabolites and Their Simultaneous Quantification Using High-Performance Liquid Chromatography-Tandem Mass Spectrometry

PubMed Central

Brim, Remy L.; Noon, Kathleen R.; Collins, Gregory T.; Nichols, Joseph; Narasimhan, Diwahar; Sunahara, Roger K.

2011-01-01

Cocaine toxicity is a widespread problem in the United States, responsible for more than 500,000 emergency department visits a year. There is currently no U.S. Food and Drug Administration-approved pharmacotherapy to directly treat cocaine toxicity. To this end, we have developed a mutant bacterial cocaine esterase (DM-CocE), which has been previously shown to rapidly hydrolyze cocaine into inert metabolites, preventing and reversing toxicity with limited immunogenic potential. Herein we describe the ability of DM-CocE to hydrolyze the active cocaine metabolites norcocaine and cocaethylene and its inability to hydrolyze benzoylecgonine. DM-CocE hydrolyzes norcocaine and cocaethylene with 58 and 45% of its catalytic efficiency for cocaine in vitro as measured by a spectrophotometric assay. We have developed a mass spectrometry method to simultaneously detect cocaine, benzoylecgonine, norcocaine, and ecgonine methyl ester to quantify the effect of DM-CocE on normal cocaine metabolism in vivo. DM-CocE administered to rats 10 min after a convulsant dose of cocaine alters the normal metabolism of cocaine, rapidly decreasing circulating levels of cocaine and norcocaine while increasing ecgonine methyl ester formation. Benzoylecgonine was not hydrolyzed in vivo, but circulating concentrations were reduced, suggesting that DM-CocE may bind and sequester this metabolite. These findings suggest that DM-CocE may reduce cocaine toxicity by eliminating active and toxic metabolites along with the parent cocaine molecule. PMID:21885621

On the evaporation of solar dark matter: spin-independent effective operators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liang, Zheng-Liang; Wu, Yue-Liang; Yang, Zi-Qing

2016-09-13

As a part of the effort to investigate the implications of dark matter (DM)-nucleon effective interactions on the solar DM detection, in this paper we focus on the evaporation of the solar DM for a set of the DM-nucleon spin-independent (SI) effective operators. In order to put the evaluation of the evaporation rate on a more reliable ground, we calculate the non-thermal distribution of the solar DM using the Monte Carlo methods, rather than adopting the Maxwellian approximation. We then specify relevant signal parameter spaces for the solar DM detection for various SI effective operators. Based on the analysis, wemore » determine the minimum DM masses for which the DM-nucleon coupling strengths can be probed from the solar neutrino observations. As an interesting application, our investigation also shows that evaporation effect can not be neglectd in a recent proposal aiming to solve the solar abundance problem by invoking the momentum-dependent asymmetric DM in the Sun.« less

Toward (finally!) ruling out Z and Higgs mediated dark matter models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Escudero, Miguel; Berlin, Asher; Hooper, Dan

2016-12-01

In recent years, direct detection, indirect detection, and collider experiments have placed increasingly stringent constraints on particle dark matter, exploring much of the parameter space associated with the WIMP paradigm. In this paper, we focus on the subset of WIMP models in which the dark matter annihilates in the early universe through couplings to either the Standard Model Z or the Standard Model Higgs boson. Considering fermionic, scalar, and vector dark matter candidates within a model-independent context, we find that the overwhelming majority of these dark matter candidates are already ruled out by existing experiments. In the case of Zmore » mediated dark matter, the only scenarios that are not currently excluded are those in which the dark matter is a fermion with an axial coupling and with a mass either within a few GeV of the Z resonance ( m {sub DM} ≅ m {sub Z} /2) or greater than 200 GeV, or with a vector coupling and with m {sub DM} > 6 TeV . Several Higgs mediated scenarios are currently viable if the mass of the dark matter is near the Higgs pole ( m {sub DM} ≅ m {sub H} /2). Otherwise, the only scenarios that are not excluded are those in which the dark matter is a scalar (vector) heavier than 400 GeV (1160 GeV) with a Higgs portal coupling, or a fermion with a pseudoscalar (CP violating) coupling to the Standard Model Higgs boson. With the exception of dark matter with a purely pseudoscalar coupling to the Higgs, it is anticipated that planned direct detection experiments will probe nearly the entire range of models considered in this study.« less

Toward (finally!) ruling out Z and Higgs mediated dark matter models

DOE PAGES

Escudero, Miguel; Fermi National Accelerator Lab.; Berlin, Asher; ...

2016-12-15

In recent years, direct detection, indirect detection, and collider experiments have placed increasingly stringent constraints on particle dark matter, exploring much of the parameter space associated with the WIMP paradigm. In this paper, we focus on the subset of WIMP models in which the dark matter annihilates in the early universe through couplings to either the Standard Model Z or the Standard Model Higgs boson. Considering fermionic, scalar, and vector dark matter candidates within a model-independent context, we find that the overwhelming majority of these dark matter candidates are already ruled out by existing experiments. In the case of Zmore » mediated dark matter, the only scenarios that are not currently excluded are those in which the dark matter is a fermion with an axial coupling and with a mass either within a few GeV of the Z resonance (m DM ≃ m Z/2) or greater than 200 GeV, or with a vector coupling and with m DM > 6 TeV . Several Higgs mediated scenarios are currently viable if the mass of the dark matter is near the Higgs pole (m DM ≃ m H/2). Otherwise, the only scenarios that are not excluded are those in which the dark matter is a scalar (vector) heavier than 400 GeV (1160 GeV) with a Higgs portal coupling, or a fermion with a pseudoscalar (CP violating) coupling to the Standard Model Higgs boson. Furthermore, with the exception of dark matter with a purely pseudoscalar coupling to the Higgs, it is anticipated that planned direct detection experiments will probe nearly the entire range of models considered in this study.« less

Toward (finally!) ruling out Z and Higgs mediated dark matter models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Escudero, Miguel; Fermi National Accelerator Lab.; Berlin, Asher

In recent years, direct detection, indirect detection, and collider experiments have placed increasingly stringent constraints on particle dark matter, exploring much of the parameter space associated with the WIMP paradigm. In this paper, we focus on the subset of WIMP models in which the dark matter annihilates in the early universe through couplings to either the Standard Model Z or the Standard Model Higgs boson. Considering fermionic, scalar, and vector dark matter candidates within a model-independent context, we find that the overwhelming majority of these dark matter candidates are already ruled out by existing experiments. In the case of Zmore » mediated dark matter, the only scenarios that are not currently excluded are those in which the dark matter is a fermion with an axial coupling and with a mass either within a few GeV of the Z resonance (m DM ≃ m Z/2) or greater than 200 GeV, or with a vector coupling and with m DM > 6 TeV . Several Higgs mediated scenarios are currently viable if the mass of the dark matter is near the Higgs pole (m DM ≃ m H/2). Otherwise, the only scenarios that are not excluded are those in which the dark matter is a scalar (vector) heavier than 400 GeV (1160 GeV) with a Higgs portal coupling, or a fermion with a pseudoscalar (CP violating) coupling to the Standard Model Higgs boson. Furthermore, with the exception of dark matter with a purely pseudoscalar coupling to the Higgs, it is anticipated that planned direct detection experiments will probe nearly the entire range of models considered in this study.« less

Twin Higgs Asymmetric Dark Matter.

PubMed

García García, Isabel; Lasenby, Robert; March-Russell, John

2015-09-18

We study asymmetric dark matter (ADM) in the context of the minimal (fraternal) twin Higgs solution to the little hierarchy problem, with a twin sector with gauged SU(3)^{'}×SU(2)^{'}, a twin Higgs doublet, and only third-generation twin fermions. Naturalness requires the QCD^{'} scale Λ_{QCD}^{'}≃0.5-20  GeV, and that t^{'} is heavy. We focus on the light b^{'} quark regime, m_{b^{'}}≲Λ_{QCD}^{'}, where QCD^{'} is characterized by a single scale Λ_{QCD}^{'} with no light pions. A twin baryon number asymmetry leads to a successful dark matter (DM) candidate: the spin-3/2 twin baryon, Δ^{'}∼b^{'}b^{'}b^{'}, with a dynamically determined mass (∼5Λ_{QCD}^{'}) in the preferred range for the DM-to-baryon ratio Ω_{DM}/Ω_{baryon}≃5. Gauging the U(1)^{'} group leads to twin atoms (Δ^{'}-τ^{'}[over ¯] bound states) that are successful ADM candidates in significant regions of parameter space, sometimes with observable changes to DM halo properties. Direct detection signatures satisfy current bounds, at times modified by dark form factors.

Stereoselective Behavior of the Chiral Herbicides Diclofop-Methyl and Diclofop During the Soy Sauce Brewing Process.

PubMed

Lu, Yuele; Zhang, Dong; Liao, Yahui; Diao, Jinling; Chen, Xiaolong

2016-01-01

Chiral pesticides are now receiving more and more attention in the food-making process. This experiment studied the enantioselective behavior of diclofop-methyl (DM) and its main metabolite, diclofop (DC), during the soy sauce brewing process. Two kinds of commonly used strains, Aspergillus oryzae and Saccharomyces rouxii, were investigated. However, they showed a different degradation ability to the enantiomers of DM and DC. It was observed that (-)-(S)-DM was degraded much faster than (+)-(R)-DM by Saccharomyces rouxii, while no stereoselective degradation was found by Aspergillus oryzae. DC represented a relatively long residue period in this fermentation process and both strains showed a weak degradation ability to DC, especially Saccharomyces rouxii. There was little DC detected in the final product, while most of the DC residues persisted in the lees, which were usually used as animal feeds or discarded into the environment directly as waste. Therefore, more attention should be paid to the soy sauce brewing process concerning pesticide residues both in the final product and byproducts. © 2015 Wiley Periodicals, Inc.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anderson, Adam J.; Fox, Patrick J.; Kahn, Yonatan

Results from direct detection experiments are typically interpreted by employing an assumption about the dark matter velocity distribution, with results presented in the m{sub χ}−σ{sub n} plane. Recently methods which are independent of the DM halo velocity distribution have been developed which present results in the v{sub min}−g-tilde plane, but these in turn require an assumption on the dark matter mass. Here we present an extension of these halo-independent methods for dark matter direct detection which does not require a fiducial choice of the dark matter mass. With a change of variables from v{sub min} to nuclear recoil momentum (p{submore » R}), the full halo-independent content of an experimental result for any dark matter mass can be condensed into a single plot as a function of a new halo integral variable, which we call h-til-tilde(p{sub R}). The entire family of conventional halo-independent g-tilde(v{sub min}) plots for all DM masses are directly found from the single h-tilde(p{sub R}) plot through a simple rescaling of axes. By considering results in h-tilde(p{sub R}) space, one can determine if two experiments are inconsistent for all masses and all physically possible halos, or for what range of dark matter masses the results are inconsistent for all halos, without the necessity of multiple g-tilde(v{sub min}) plots for different DM masses. We conduct a sample analysis comparing the CDMS II Si events to the null results from LUX, XENON10, and SuperCDMS using our method and discuss how the results can be strengthened by imposing the physically reasonable requirement of a finite halo escape velocity.« less

Torsion as a dark matter candidate from the Higgs portal

NASA Astrophysics Data System (ADS)

Belyaev, Alexander S.; Thomas, Marc C.; Shapiro, Ilya L.

2017-05-01

Torsion is a metric-independent component of gravitation, which may provide a more general geometry than the one taking place within general relativity. On the other hand, torsion could lead to interesting phenomenology in both particle physics and cosmology. In the present work it is shown that a torsion field interacting with the SM Higgs doublet and having a negligible coupling to standard model (SM) fermions is protected from decaying by a Z2 symmetry, and therefore becomes a promising dark matter (DM) candidate. This model provides a good motivation for Higgs portal vector DM scenario. We evaluate the DM relic density and explore direct DM detection and collider constraints on this model to understand its consistency with experimental data and establish the most up-to-date limits on its parameter space. We have found in the model when the Higgs boson is only partly responsible for the generation of torsion mass, there is a region of parameter space where torsion contributes 100% to the DM budget of the Universe. Furthermore, we present the first results on the potential of the LHC to probe the parameter space of minimal scenario with Higgs portal vector DM using mono-jet searches and have found that LHC at high luminosity will be sensitive to the substantial part of model parameter space which cannot be probed by other experiments.

Direct multiplex PCR (dmPCR) for the identification of six Phlebotomine sand fly species (Diptera: Psychodidae), including major Leishmania vectors of the Mediterranean

USDA-ARS?s Scientific Manuscript database

Sand flies (Diptera: Psychodidae, subfamily Phlebotominae) are haematophagous insects that are known to transmit several anthroponotic and zoonotic diseases. Reliable identification of sand flies at species level is crucial for their surveillance, the detection and spread of their pathogens and the ...

A deviation based assessment methodology for multiple machine health patterns classification and fault detection

NASA Astrophysics Data System (ADS)

Jia, Xiaodong; Jin, Chao; Buzza, Matt; Di, Yuan; Siegel, David; Lee, Jay

2018-01-01

Successful applications of Diffusion Map (DM) in machine failure detection and diagnosis have been reported in several recent studies. DM provides an efficient way to visualize the high-dimensional, complex and nonlinear machine data, and thus suggests more knowledge about the machine under monitoring. In this paper, a DM based methodology named as DM-EVD is proposed for machine degradation assessment, abnormality detection and diagnosis in an online fashion. Several limitations and challenges of using DM for machine health monitoring have been analyzed and addressed. Based on the proposed DM-EVD, a deviation based methodology is then proposed to include more dimension reduction methods. In this work, the incorporation of Laplacian Eigen-map and Principal Component Analysis (PCA) are explored, and the latter algorithm is named as PCA-Dev and is validated in the case study. To show the successful application of the proposed methodology, case studies from diverse fields are presented and investigated in this work. Improved results are reported by benchmarking with other machine learning algorithms.

Optical filtering in directly modulated/detected OOFDM systems.

PubMed

Sánchez, C; Ortega, B; Wei, J L; Capmany, J

2013-12-16

This work presents a theoretical investigation on the performance of directly modulated/detected (DM/DD) optical orthogonal frequency division multiplexed (OOFDM) systems subject to optical filtering. The impact of both linear and nonlinear distortion effects are taken into account to calculate the effective signal-to-noise ratio of each subcarrier. These results are then employed to optimize the design parameters of two simple optical filtering structures: a Mach Zehnder interferometer and a uniform fiber Bragg grating, leading to a significant optical power budget improvement given by 3.3 and 3dB, respectively. These can be further increased to 5.5 and 4.2dB respectively when balanced detection configurations are employed. We find as well that this improvement is highly dependent on the clipping ratio.

Low-mass neutralino dark matter in supergravity scenarios: phenomenology and naturalness

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peiró, M.; Robles, S., E-mail: mpeirogarcia@gmail.com, E-mail: sandra.robles@uam.es

2017-05-01

The latest experimental results from the LHC and dark matter (DM) searches suggest that the parameter space allowed in supersymmetric theories is subject to strong reductions. These bounds are especially constraining for scenarios entailing light DM particles. Previous studies have shown that light neutralino DM in the Minimal Supersymmetric Standard Model (MSSM), with parameters defined at the electroweak scale, is still viable when the low energy spectrum of the model features light sleptons, in which case, the relic density constraint can be fulfilled. In view of this, we have investigated the viability of light neutralinos as DM candidates in themore » MSSM, with parameters defined at the grand unification scale. We have analysed the optimal choices of non-universalities in the soft supersymmetry-breaking parameters for both, gauginos and scalars, in order to avoid the stringent experimental constraints. We show that light neutralinos, with a mass as low as 25 GeV, are viable in supergravity scenarios if the gaugino mass parameters at high energy are very non universal, while the scalar masses can remain of the same order. These scenarios typically predict a very small cross section of neutralinos off protons and neutrons, thereby being very challenging for direct detection experiments. However, a potential detection of smuons and selectrons at the LHC, together with a hypothetical discovery of a gamma-ray signal from neutralino annihilations in dwarf spheroidal galaxies could shed light on this kind of solutions. Finally, we have investigated the naturalness of these scenarios, taking into account all the potential sources of tuning. Besides the electroweak fine-tuning, we have found that the tuning to reproduce the correct DM relic abundance and that to match the measured Higgs mass can also be important when estimating the total degree of naturalness.« less

Low-mass neutralino dark matter in supergravity scenarios: phenomenology and naturalness

NASA Astrophysics Data System (ADS)

Peiró, M.; Robles, S.

2017-05-01

The latest experimental results from the LHC and dark matter (DM) searches suggest that the parameter space allowed in supersymmetric theories is subject to strong reductions. These bounds are especially constraining for scenarios entailing light DM particles. Previous studies have shown that light neutralino DM in the Minimal Supersymmetric Standard Model (MSSM), with parameters defined at the electroweak scale, is still viable when the low energy spectrum of the model features light sleptons, in which case, the relic density constraint can be fulfilled. In view of this, we have investigated the viability of light neutralinos as DM candidates in the MSSM, with parameters defined at the grand unification scale. We have analysed the optimal choices of non-universalities in the soft supersymmetry-breaking parameters for both, gauginos and scalars, in order to avoid the stringent experimental constraints. We show that light neutralinos, with a mass as low as 25 GeV, are viable in supergravity scenarios if the gaugino mass parameters at high energy are very non universal, while the scalar masses can remain of the same order. These scenarios typically predict a very small cross section of neutralinos off protons and neutrons, thereby being very challenging for direct detection experiments. However, a potential detection of smuons and selectrons at the LHC, together with a hypothetical discovery of a gamma-ray signal from neutralino annihilations in dwarf spheroidal galaxies could shed light on this kind of solutions. Finally, we have investigated the naturalness of these scenarios, taking into account all the potential sources of tuning. Besides the electroweak fine-tuning, we have found that the tuning to reproduce the correct DM relic abundance and that to match the measured Higgs mass can also be important when estimating the total degree of naturalness.

Closing in on the Wino LSP via trilepton searches at the LHC

NASA Astrophysics Data System (ADS)

Abdallah, W.; Khalil, S.; Moretti, S.; Munir, S.

2018-01-01

The neutralino dark matter (DM) predicted by the Minimal Supersymmetric Standard Model (MSSM) has been probed in several search modes at the Large Hadron Collider (LHC), one of the leading ones among which is the trilepton plus missing transverse momentum channel. The experimental analysis of this mode has, however, been designed to probe mainly a bino-like DM, originating in the decays of a pair of next-to-lightest neutralino and lightest chargino, both of which are assumed to be wino-like. In this study, we analyse how this trilepton channel can be tuned for probing also the wino-like DM. We note that, while the mentioned standard production mode generally leads to a relatively poor sensitivity for the wino-like DM, there are regions in the MSSM parameter space where the net yield in the trilepton final state can be substantially enhanced at the LHC with √{s}=14 TeV. This is achieved by taking into account also an alternative channel, pair-production of the wino-like DM itself in association with the heavier chargino, and optimisation of the kinematical cuts currently employed by the LHC collaborations. In particular, we find that the cut on the transverse mass of the third lepton highly suppresses both the signal channels and should therefore be discarded in this DM scenario. We perform a detailed detector-level study of some selected parameter space points that are consistent with the most important experimental constraints, including the recent ones from the direct and indirect DM detection facilities. Our analysis demonstrates the high complementarity of the two channels, with their combined significance reaching above 4 σ for a wino-like DM mass around 100 GeV, with an integrated luminosity as low as 100 fb-1.

A novel in chemico method to detect skin sensitizers in highly diluted reaction conditions.

PubMed

Yamamoto, Yusuke; Tahara, Haruna; Usami, Ryota; Kasahara, Toshihiko; Jimbo, Yoshihiro; Hioki, Takanori; Fujita, Masaharu

2015-11-01

The direct peptide reactivity assay (DPRA) is a simple and versatile alternative method for the evaluation of skin sensitization that involves the reaction of test chemicals with two peptides. However, this method requires concentrated solutions of test chemicals, and hydrophobic substances may not dissolve at the concentrations required. Furthermore, hydrophobic test chemicals may precipitate when added to the reaction solution. We previously established a high-sensitivity method, the amino acid derivative reactivity assay (ADRA). This method uses novel cysteine (NAC) and novel lysine derivatives (NAL), which were synthesized by introducing a naphthalene ring to the amine group of cysteine and lysine residues. In this study, we modified the ADRA method by reducing the concentration of the test chemicals 100-fold. We investigated the accuracy of skin sensitization predictions made using the modified method, which was designated the ADRA-dilutional method (ADRA-DM). The predictive accuracy of the ADRA-DM for skin sensitization was 90% for 82 test chemicals which were also evaluated via the ADRA, and the predictive accuracy in the ADRA-DM was higher than that in the ADRA and DPRA. Furthermore, no precipitation of test compounds was observed at the initiation of the ADRA-DM reaction. These results show that the ADRA-DM allowed the use of test chemicals at concentrations two orders of magnitude lower than that possible with the ADRA. In addition, ADRA-DM does not have the restrictions on test compound solubility that were a major problem with the DPRA. Therefore, the ADRA-DM is a versatile and useful method. Copyright © 2015 John Wiley & Sons, Ltd.

Clinical Utility of an Enzyme-Linked Immunosorbent Assay for Detecting Anti-Melanoma Differentiation-Associated Gene 5 Autoantibodies

PubMed Central

Sato, Shinji; Murakami, Akihiro; Kuwajima, Akiko; Takehara, Kazuhiko; Mimori, Tsuneyo; Kawakami, Atsushi; Mishima, Michiaki; Suda, Takafumi; Seishima, Mariko; Fujimoto, Manabu; Kuwana, Masataka

2016-01-01

Objective Autoantibodies to melanoma differentiation-associated gene 5 (MDA5) are specifically expressed in patients with dermatomyositis (DM) and are associated with a subset of DM patients with rapidly progressive interstitial lung disease (RP-ILD). Here, we examined the clinical utility of a newly developed enzyme-linked immunosorbent assay (ELISA) system for detecting these antibodies. Methods Here we developed an improved ELISA for detecting anti-MDA5 antibodies. We then performed a multicenter clinical study involving 8 medical centers and enrolled 242 adult patients with polymyositis (PM)/DM, 190 with non-PM/DM connective tissue disease (CTD), 154 with idiopathic interstitial pneumonia (IIP), and 123 healthy controls. Anti-MDA5 antibodies in the patients’ serum samples were quantified using our newly developed ELISA, and the results were compared to those obtained using the gold-standard immunoprecipitation (IP) assay. In addition, correlations between the ELISA-quantified anti-MDA5 antibodies and clinical characteristics were evaluated. Results In patients with PM/DM, the anti-MDA5 antibody measurements obtained from the ELISA and IP assay were highly concordant; the ELISA exhibited an analytical sensitivity of 98.2%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 99.5% (compared to the IP assay). Anti-MDA5 antibodies were detected in 22.7% of the DM patients, but not in any of the patients with PM, non-PM/DM CTD, or IIP. Clinically amyopathic DM, RP-ILD, arthritis, and fever were more prevalent in DM patients who were anti-MDA5 antibody-positive than in those who were antibody-negative (P ≤ 0.0002 for all comparisons). In addition, anti-MDA5 antibody-positive patients with RP-ILD exhibited higher antibody levels than those without RP-ILD (P = 0.006). Conclusion Our newly developed ELISA can detect anti-MDA5 antibodies as efficiently as the gold standard IP assay and has the potential to facilitate the routine clinical measurement of anti-MDA5 antibodies in patients who suspected to have DM. PMID:27115353

Clinical Utility of an Enzyme-Linked Immunosorbent Assay for Detecting Anti-Melanoma Differentiation-Associated Gene 5 Autoantibodies.

PubMed

Sato, Shinji; Murakami, Akihiro; Kuwajima, Akiko; Takehara, Kazuhiko; Mimori, Tsuneyo; Kawakami, Atsushi; Mishima, Michiaki; Suda, Takafumi; Seishima, Mariko; Fujimoto, Manabu; Kuwana, Masataka

2016-01-01

Autoantibodies to melanoma differentiation-associated gene 5 (MDA5) are specifically expressed in patients with dermatomyositis (DM) and are associated with a subset of DM patients with rapidly progressive interstitial lung disease (RP-ILD). Here, we examined the clinical utility of a newly developed enzyme-linked immunosorbent assay (ELISA) system for detecting these antibodies. Here we developed an improved ELISA for detecting anti-MDA5 antibodies. We then performed a multicenter clinical study involving 8 medical centers and enrolled 242 adult patients with polymyositis (PM)/DM, 190 with non-PM/DM connective tissue disease (CTD), 154 with idiopathic interstitial pneumonia (IIP), and 123 healthy controls. Anti-MDA5 antibodies in the patients' serum samples were quantified using our newly developed ELISA, and the results were compared to those obtained using the gold-standard immunoprecipitation (IP) assay. In addition, correlations between the ELISA-quantified anti-MDA5 antibodies and clinical characteristics were evaluated. In patients with PM/DM, the anti-MDA5 antibody measurements obtained from the ELISA and IP assay were highly concordant; the ELISA exhibited an analytical sensitivity of 98.2%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 99.5% (compared to the IP assay). Anti-MDA5 antibodies were detected in 22.7% of the DM patients, but not in any of the patients with PM, non-PM/DM CTD, or IIP. Clinically amyopathic DM, RP-ILD, arthritis, and fever were more prevalent in DM patients who were anti-MDA5 antibody-positive than in those who were antibody-negative (P ≤ 0.0002 for all comparisons). In addition, anti-MDA5 antibody-positive patients with RP-ILD exhibited higher antibody levels than those without RP-ILD (P = 0.006). Our newly developed ELISA can detect anti-MDA5 antibodies as efficiently as the gold standard IP assay and has the potential to facilitate the routine clinical measurement of anti-MDA5 antibodies in patients who suspected to have DM.

Improved in-plane visibility of tumors using breast tomosynthesis

NASA Astrophysics Data System (ADS)

Ruschin, Mark; Timberg, Pontus; Svahn, Tony; Andersson, Ingvar; Hemdal, Bengt; Mattsson, Sören; Båth, Magnus; Tingberg, Anders

2007-03-01

The purpose of this work was to evaluate and compare the visibility of tumors in digital mammography (DM) and breast tomosynthesis (BT) images. Images of the same women were acquired on both a DM system (Mammomat Novation, Siemens) and a BT prototype system adapted from the same type of DM system. Simulated 3D tumors (average dimension: 8.4 mm x 6.6 mm x 5 mm) were projected and added to each DM image as well as each BT projection image prior to 3D reconstruction. The same beam quality and approximately the same total absorbed dose were used for each breast image acquisition on both systems. Two simulated tumors were added to each of thirty breast scans, yielding sixty cases. A series of 4-alternative forced choice (4-AFC) human observer performance experiments were conducted in order to determine what projected tumor signal intensity in the DM images would be needed to achieve the same detectability as in the reconstructed BT images. Nine observers participated. For the BT experiment, when the tumor signal intensity on the central projection was 0.010 the mean percent of correct responses (PC) was measured to be 81.5%, which converted to a detectability index value (d') of 1.96. For the DM experiments, the same detectability was achieved at a signal intensity determined to be 0.038. Equivalent tumor detection in BT images were thus achieved at around four times less projected signal intensity than in DM images, indicating that the use of BT may lead to earlier detection of breast cancer.

[Study of free radicals in aqueous humor in glaucoma and cataracts: differences in presence or absence of diabetes mellitus and neovascular glaucoma].

PubMed

Oshida, Eiki; Arai, Kiyomi; Sakai, Miki; Chikuda, Makoto

2014-09-01

This study was conducted for the purpose of comparing differences in the types of free radicals in the aqueous humor of glaucoma and cataract patients. Free radicals in the aqueous humor of 44 glaucoma eyes and 15 cataract eyes were measured by electron spin resonance (ESR), followed by comparing the detection rates. In addition, subgroup analyses were also conducted for the presence or absence of complications of diabetes mellitus (DM) and neovascular glaucoma (NVG) in the patients. Three types of free radicals were measured, ascorbate-free radical (AFR), AFR containing a trace amount of superoxide (SO) (AFR +), and SO containing a trace amount of AFR (SO +). Significant differences were observed in the detection rates of each type between the glaucoma group (maximum SO +) and the cataract group (maximum AFR), between the DM group (maximum SO +) and the non-DM group (maximum AFR) in the glaucoma, and between the DM group (maximum AFR +) and the non-DM group (maximum AFR) in the cataract. SO + was detected in all cases of NVG regardless of whether they were DM or non-DM. Glaucoma cases are more susceptible to the generation of SO in the aqueous humor than cataracts, and they are more liable to occur in DM than in non-DM in both glaucoma and cataract cases. This study suggest an evidence for a strong correlation with SO and vascularization in NVG.

Type 1 and type 2 diabetes mellitus: are they mutually exclusive?

PubMed

Fatima, Aziz; Khawaja, Khadija Irfan; Burney, Saira; Minhas, Khushroo; Mumtaz, Usman; Masud, Faisal

2013-07-01

With advancement in the understanding of the pathogenesis underlying diabetes mellitus (DM), the boundary between type 1 and type 2 DM (T1DM and T2DM) does not seem to be as clear cut as previously thought. This study was designed to test the possibility of overlap between the spectra of immune-mediated DM and insulin resistance. To test for the possibility of overlap, we looked for autoantibodies typical of T1DM in patients with classical T2DM, and insulin resistance in patients with T1DM. Autoantibodies against islet cell antigen, glutamic acid decarboxylase-65 and insulinoma-associated antigen-2 were tested in 82 patients with T2DM and 27 patients with T1DM. The patients had been diagnosed on clinical criteria using standard laboratory techniques. Clinical parameters of diagnostic importance were noted, and homeostatic model assessment of insulin resistance (HOMA-IR) was calculated using fasting insulin and fasting blood glucose ratio. Autoantibodies against one or more beta cell antigens were detected in 12.19% of patients clinically diagnosed to have T2DM, and insulin resistance (HOMA-IR > 2.5) was diagnosed in 37.03% of patients with T1DM. It was not possible to identify any combination of clinical or biochemical markers that could predict autoantibody positivity in T2DM patients. T1DM patients with insulin resistance had a significantly higher body mass index than their insulin-sensitive counterparts (p = 0.02). Autoantibodies against beta cell antigens are detectable in insulin-resistant T2DM patients, and insulin resistance may be present in relatively overweight T1DM patients. No differentiating clinical features that might predict autoantibody positivity in T2DM patients were found.

High prevalence of diabetes and anthropometric heterogeneity among tuberculosis patients in Pakistan.

PubMed

Aftab, Huma; Ambreen, Atiqa; Jamil, Mohammad; Garred, Peter; Petersen, Jørgen H; Nielsen, Susanne D; Bygbjerg, Ib C; Christensen, Dirk L

2017-04-01

In Pakistan, the prevalence of diabetes (DM) among adults is 6.9% and expected to double by 2040. DM may facilitate transmission and halter the elimination of tuberculosis (TB). We aimed to determine the prevalence of DM among patients with TB in Pakistan, and to investigate anthropometric biochemical and haemodynamic associations between TB patients with and without DM. We conducted a cross-sectional study at Gulab Devi Chest Hospital in Lahore, Punjab. A total of 3027 newly diagnosed smear-positive TB patients ≥25 years of age were screened for DM by HbA1c regardless of previous DM history. The prevalence of screen-detected DM and known DM among the TB participants was 13.5% and 26.1%, respectively, resulting in a combined DM prevalence of 39.6%. Most participants were male (64.4%). Using bivariate analyses, participants with DM were significantly older (49.8 vs. 40.6 years) with higher haemoglobin (men, 12.1 vs. 11.8 g/dl, women 11.5 vs. 10.7 g/dl), body mass index (21.0 vs. 17.6 kg/m 2 ) and waist-hip ratio (men, 0.87 vs. 0.81, women, 0.87 vs. 0.79) (all P < 0.05) than participants without DM. Stratifying by screen-detected and known DM, these differences remained significant when using multivariate analysis. We report a high prevalence of DM among patients with TB who may be anthropometrically and biochemically distinct from TB patients without DM, and this heterogeneity further transcends the different DM groups. © 2017 John Wiley & Sons Ltd.

Measurement of muon annual modulation and muon-induced phosphorescence in NaI(Tl) crystals with DM-Ice17

DOE PAGES

Cherwinka, J.; Grant, D.; Halzen, F.; ...

2016-02-01

We report the measurement of muons and muon-induced phosphorescence in DM-Ice17, a NaI(Tl) direct detection dark matter experiment at the South Pole. Muon interactions in the crystal are identified by their observed pulse shape and large energy depositions. The measured muon rate in DM-Ice17 is 2.93±0.04 μ/crystal/day with a modulation amplitude of 12.3±1.7%, consistent with expectation. Following muon interactions, we observe long-lived phosphorescence in the NaI(Tl) crystals with a decay time of 5.5±0.5 s. The prompt energy deposited by a muon is correlated to the amount of delayed phosphorescence, the brightest of which consist of tens of millions of photons.more » These photons are distributed over tens of seconds with a rate and arrival timing that do not mimic a scintillation signal above 2 keV ee. Furthermore, while the properties of phosphorescence vary among individual crystals, the annually modulating signal observed by DAMA cannot be accounted for by phosphorescence with the characteristics observed in DM-Ice17.« less

Detection of linkage disequilibrium between the myotonic dystrophy locus and a new polymorphic DNA marker.

PubMed Central

Harley, H G; Brook, J D; Floyd, J; Rundle, S A; Crow, S; Walsh, K V; Thibault, M C; Harper, P S; Shaw, D J

1991-01-01

We have examined the linkage of two new polymorphic DNA markers (D19S62 and D19S63) and a previously unreported polymorphism with an existing DNA marker (ERCC1) to the myotonic dystrophy (DM) locus. In addition, we have used pulsed-field gel electrophoresis to obtain a fine-structure map of this region. The detection of linkage disequilibrium between DM and one of these markers (D19S63) is the first demonstration of this phenomenon in a heterogeneous DM population. The results suggest that at least 58% of DM patients in the British population, as well as those in a French-Canadian subpopulation, are descended from the same ancestral DM mutation. We discuss the implications of this finding in terms of strategies for cloning the DM gene, for a possible role in modification of risk for prenatal and presymptomatic testing, and we speculate on the origin and number of existing mutations which may result in a DM phenotype. PMID:2063878

Supersymmetric model for dark matter and baryogenesis motivated by the recent CDMS result.

PubMed

Allahverdi, Rouzbeh; Dutta, Bhaskar; Mohapatra, Rabindra N; Sinha, Kuver

2013-08-02

We discuss a supersymmetric model for cogenesis of dark and baryonic matter where the dark matter (DM) has mass in the 8-10 GeV range as indicated by several direct detection searches, including most recently the CDMS experiment with the desired cross section. The DM candidate is a real scalar field. Two key distinguishing features of the model are the following: (i) in contrast with the conventional weakly interacting massive particle dark matter scenarios where thermal freeze-out is responsible for the observed relic density, our model uses nonthermal production of dark matter after reheating of the Universe caused by moduli decay at temperatures below the QCD phase transition, a feature which alleviates the relic overabundance problem caused by small annihilation cross section of light DM particles and (ii) baryogenesis occurs also at similar low temperatures from the decay of TeV scale mediator particles arising from moduli decay. A possible test of this model is the existence of colored particles with TeV masses accessible at the LHC.

Simulation of a method to directly image exoplanets around multiple stars systems

NASA Astrophysics Data System (ADS)

Thomas, Sandrine J.; Bendek, Eduardo; Belikov, Ruslan

2014-08-01

Direct imaging of extra-solar planets has now become a reality, especially with the deployment and commissioning of the first generation of specialized ground-based instruments such as the GPI, SPHERE, P1640 and SCExAO. These systems will allow detection of planets 107 times fainter than their host star. For space- based missions, such as EXCEDE, EXO-C, EXO-S, WFIRST/AFTA, different teams have shown in laboratories contrasts reaching 10-10 within a few diffraction limits from the star using a combination of a coronagraph to suppress light coming from the host star and a wavefront control system. These demonstrations use a de- formable mirror (DM) to remove residual starlight (speckles) created by the imperfections of telescope. However, all these current and future systems focus on detecting faint planets around a single host star or unresolved bi- naries/multiples, while several targets or planet candidates are located around nearby binary stars such as our neighbor star Alpha Centauri. Until now, it has been thought that removing the light of a companion star is impossible with current technology, excluding binary star systems from target lists of direct imaging missions. Direct imaging around binaries/multiple systems at a level of contrast allowing Earth-like planet detection is challenging because the region of interest, where a dark zone is essential, is contaminated by the light coming from the hosts star companion. We propose a method to simultaneously correct aberrations and diffraction of light coming from the target star as well as its companion star in order to reveal planets orbiting the target star. This method works even if the companion star is outside the control region of the DM (beyond its half-Nyquist frequency), by taking advantage of aliasing effects.

A Novel Malware Target Recognition Architecture for Enhanced Cyberspace Situation Awareness

DTIC Science & Technology

2011-09-01

71 3.1 Chapter Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 3.2 CRISP - DM Process...71 3.3 Execution of the CRISP - DM Process...64 10. Adaptation of CRISP - DM process (from [13]). . . . . . . . . . . . . . . . . . . . . . . 72 11. Comparison of detection

The Electronics and Data Acquisition System of the DarkSide Dark Matter Search

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agnes, P.; et al.

2014-12-09

It is generally inferred from astronomical measurements that Dark Matter (DM) comprises approximately 27\\% of the energy-density of the universe. If DM is a subatomic particle, a possible candidate is a Weakly Interacting Massive Particle (WIMP), and the DarkSide-50 (DS) experiment is a direct search for evidence of WIMP-nuclear collisions. DS is located underground at the Laboratori Nazionali del Gran Sasso (LNGS) in Italy, and consists of three active, embedded components; an outer water veto (CTF), a liquid scintillator veto (LSV), and a liquid argon (LAr) time projection chamber (TPC). This paper describes the data acquisition and electronic systems ofmore » the DS detectors, designed to detect the residual ionization from such collisions.« less

Tomographic-spectral approach for dark matter detection in the cross-correlation between cosmic shear and diffuse γ-ray emission

NASA Astrophysics Data System (ADS)

Camera, S.; Fornasa, M.; Fornengo, N.; Regis, M.

2015-06-01

We recently proposed to cross-correlate the diffuse extragalactic γ-ray background with the gravitational lensing signal of cosmic shear. This represents a novel and promising strategy to search for annihilating or decaying particle dark matter (DM) candidates. In the present work, we demonstrate the potential of a tomographic-spectral approach: measuring the cross-correlation in separate bins of redshift and energy significantly improves the sensitivity to a DM signal. Indeed, the technique proposed here takes advantage of the different scaling of the astrophysical and DM components with redshift and, simultaneously of their different energy spectra and different angular extensions. The sensitivity to a particle DM signal is extremely promising even when the DM-induced emission is quite faint. We first quantify the prospects of detecting DM by cross-correlating the Fermi Large Area Telescope (LAT) diffuse γ-ray background with the cosmic shear expected from the Dark Energy Survey. Under the hypothesis of a significant subhalo boost, such a measurement can deliver a 5σ detection of DM, if the DM particle is lighter than 300 GeV and has a thermal annihilation rate. We then forecast the capability of the European Space Agency Euclid satellite (whose launch is planned for 2020), in combination with an hypothetical future γ-ray detector with slightly improved specifications compared to current telescopes. We predict that the cross-correlation of their data will allow a measurement of the DM mass with an uncertainty of a factor of 1.5-2, even for moderate subhalo boosts, for DM masses up to few hundreds of GeV and thermal annihilation rates.

Simple non-laboratory- and laboratory-based risk assessment algorithms and nomogram for detecting undiagnosed diabetes mellitus.

PubMed

Wong, Carlos K H; Siu, Shing-Chung; Wan, Eric Y F; Jiao, Fang-Fang; Yu, Esther Y T; Fung, Colman S C; Wong, Ka-Wai; Leung, Angela Y M; Lam, Cindy L K

2016-05-01

The aim of the present study was to develop a simple nomogram that can be used to predict the risk of diabetes mellitus (DM) in the asymptomatic non-diabetic subjects based on non-laboratory- and laboratory-based risk algorithms. Anthropometric data, plasma fasting glucose, full lipid profile, exercise habits, and family history of DM were collected from Chinese non-diabetic subjects aged 18-70 years. Logistic regression analysis was performed on a random sample of 2518 subjects to construct non-laboratory- and laboratory-based risk assessment algorithms for detection of undiagnosed DM; both algorithms were validated on data of the remaining sample (n = 839). The Hosmer-Lemeshow test and area under the receiver operating characteristic (ROC) curve (AUC) were used to assess the calibration and discrimination of the DM risk algorithms. Of 3357 subjects recruited, 271 (8.1%) had undiagnosed DM defined by fasting glucose ≥7.0 mmol/L or 2-h post-load plasma glucose ≥11.1 mmol/L after an oral glucose tolerance test. The non-laboratory-based risk algorithm, with scores ranging from 0 to 33, included age, body mass index, family history of DM, regular exercise, and uncontrolled blood pressure; the laboratory-based risk algorithm, with scores ranging from 0 to 37, added triglyceride level to the risk factors. Both algorithms demonstrated acceptable calibration (Hosmer-Lemeshow test: P = 0.229 and P = 0.483) and discrimination (AUC 0.709 and 0.711) for detection of undiagnosed DM. A simple-to-use nomogram for detecting undiagnosed DM has been developed using validated non-laboratory-based and laboratory-based risk algorithms. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Branched-chain amino acids in metabolic signalling and insulin resistance.

PubMed

Lynch, Christopher J; Adams, Sean H

2014-12-01

Branched-chain amino acids (BCAAs) are important nutrient signals that have direct and indirect effects. Frequently, BCAAs have been reported to mediate antiobesity effects, especially in rodent models. However, circulating levels of BCAAs tend to be increased in individuals with obesity and are associated with worse metabolic health and future insulin resistance or type 2 diabetes mellitus (T2DM). A hypothesized mechanism linking increased levels of BCAAs and T2DM involves leucine-mediated activation of the mammalian target of rapamycin complex 1 (mTORC1), which results in uncoupling of insulin signalling at an early stage. A BCAA dysmetabolism model proposes that the accumulation of mitotoxic metabolites (and not BCAAs per se) promotes β-cell mitochondrial dysfunction, stress signalling and apoptosis associated with T2DM. Alternatively, insulin resistance might promote aminoacidaemia by increasing the protein degradation that insulin normally suppresses, and/or by eliciting an impairment of efficient BCAA oxidative metabolism in some tissues. Whether and how impaired BCAA metabolism might occur in obesity is discussed in this Review. Research on the role of individual and model-dependent differences in BCAA metabolism is needed, as several genes (BCKDHA, PPM1K, IVD and KLF15) have been designated as candidate genes for obesity and/or T2DM in humans, and distinct phenotypes of tissue-specific branched chain ketoacid dehydrogenase complex activity have been detected in animal models of obesity and T2DM.

Measured moisture in buildings and adverse health effects: A review.

PubMed

Mendell, M J; Macher, J M; Kumagai, K

2018-04-23

It has not yet been possible to quantify dose-related health risks attributable to indoor dampness or mold (D/M), to support setting specific health-related limits for D/M. An overlooked target for assessing D/M is moisture in building materials, the critical factor allowing microbial growth. A search for studies of quantified building moisture and occupant health effects identified 3 eligible studies. Two studies assessed associations between measured wall moisture content and respiratory health in the UK. Both reported dose-related increases in asthma exacerbation with higher measured moisture, with 1 study reporting an adjusted odds ratio of 7.0 for night-time asthma symptoms with higher bedroom moisture. The third study assessed relationships between infrared camera-determined wall moisture and atopic dermatitis in South Korea, reporting an adjusted odds ratio of 14.5 for water-damaged homes and moderate or severe atopic dermatitis. Measuring building moisture has, despite extremely limited available findings, potential promise for detecting unhealthy D/M in homes and merits more research attention. Further research to validate these findings should include measured "water activity," which directly assesses moisture availability for microbial growth. Ultimately, evidence-based, health-related thresholds for building moisture, across specific materials and measurement devices, could better guide assessment and remediation of D/M in buildings. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Modelling MEMS deformable mirrors for astronomical adaptive optics

NASA Astrophysics Data System (ADS)

Blain, Celia

As of July 2012, 777 exoplanets have been discovered utilizing mainly indirect detection techniques. The direct imaging of exoplanets is the next goal for astronomers, because it will reveal the diversity of planets and planetary systems, and will give access to the exoplanet's chemical composition via spectroscopy. With this spectroscopic knowledge, astronomers will be able to know, if a planet is terrestrial and, possibly, even find evidence of life. With so much potential, this branch of astronomy has also captivated the general public attention. The direct imaging of exoplanets remains a challenging task, due to (i) the extremely high contrast between the parent star and the orbiting exoplanet and (ii) their small angular separation. For ground-based observatories, this task is made even more difficult, due to the presence of atmospheric turbulence. High Contrast Imaging (HCI) instruments have been designed to meet this challenge. HCI instruments are usually composed of a coronagraph coupled with the full onaxis corrective capability of an Extreme Adaptive Optics (ExAO) system. An efficient coronagraph separates the faint planet's light from the much brighter starlight, but the dynamic boiling speckles, created by the stellar image, make exoplanet detection impossible without the help of a wavefront correction device. The Subaru Coronagraphic Extreme Adaptive Optics (SCExAO) system is a high performance HCI instrument developed at Subaru Telescope. The wavefront control system of SCExAO consists of three wavefront sensors (WFS) coupled with a 1024- actuator Micro-Electro-Mechanical-System (MEMS) deformable mirror (DM). MEMS DMs offer a large actuator density, allowing high count DMs to be deployed in small size beams. Therefore, MEMS DMs are an attractive technology for Adaptive Optics (AO) systems and are particularly well suited for HCI instruments employing ExAO technologies. SCExAO uses coherent light modulation in the focal plane introduced by the DM, for both wavefront sensing and correction. In this scheme, the DM is used to introduce known aberrations (speckles in the focal plane), which interfere with existing speckles. By monitoring the interference between the pre-existing speckles and the speckles added deliberately by the DM, it is possible to reconstruct the complex amplitude (amplitude and phase) of the focal plane speckles. Thus, the DM is used for wavefront sensing, in a scheme akin to phase diversity. For SCExAO and other HCI systems using phase diversity, the wavefront compensation is a mix of closed-loop and open-loop control of the DM. The successful implementation of MEMS DMs open-loop control relies on a thorough modelling of the DM response to the control system commands. The work presented in this thesis, motivated by the need to provide accurate DM control for the wavefront control system of SCExAO, was centred around the development of MEMS DM models. This dissertation reports the characterization of MEMS DMs and the development of two efficient modelling approaches. The open-loop performance of both approaches has been investigated. The model providing the best result has been implemented within the SCExAO wavefront control software. Within SCExAO, the model was used to command the DM to create focal plane speckles. The work is now focused on using the model within a full speckle nulling process and on increasing the execution speed to make the model suitable for on-sky operation.

Microbiological, lipid and immunological profiles in children with gingivitis and type 1 diabetes mellitus.

PubMed

Duque, Cristiane; João, Mariana Ferreira Dib; Camargo, Gabriela Alessandra da Cruz Galhardo; Teixeira, Gláucia Schuindt; Machado, Thamiris Santana; Azevedo, Rebeca de Souza; Mariano, Flávia Sammartino; Colombo, Natália Helena; Vizoto, Natália Leal; Mattos-Graner, Renata de Oliveira

2017-01-01

The aim of this study was to compare the prevalence of periodontal pathogens, systemic inflammatory mediators and lipid profiles in type 1 diabetes children (DM) with those observed in children without diabetes (NDM), both with gingivitis. Twenty-four DM children and twenty-seven NDM controls were evaluated. The periodontal status, glycemic and lipid profiles were determined for both groups. Subgingival samples of periodontal sites were collected to determine the prevalence of periodontal microorganisms by PCR. Blood samples were collected for IL-1-β, TNF-α and IL-6 analysis using ELISA kits. Periodontal conditions of DM and NDM patients were similar, without statistical differences in periodontal indices. When considering patients with gingivitis, all lipid parameters evaluated were highest in the DM group; Capnocytophaga sputigena and Capnocytophaga ochracea were more prevalent in the periodontal sites of DM children. "Red complex" bacteria were detected in few sites of DM and NDM groups. Fusobacterium nucleatum and Campylobacter rectus were frequently found in both groups. Similar levels of IL-1-β, TNF-α and IL-6 were detected in DM and NDM children. Clinical and immunological profiles are similar between DM and NDM children. The presence of Capnocytophaga sputigena and Capnocytophaga ochracea were associated with gingivitis in DM children.

Microbiological, lipid and immunological profiles in children with gingivitis and type 1 diabetes mellitus

PubMed Central

DUQUE, Cristiane; JOÃO, Mariana Ferreira Dib; CAMARGO, Gabriela Alessandra da Cruz Galhardo; TEIXEIRA, Gláucia Schuindt; MACHADO, Thamiris Santana; AZEVEDO, Rebeca de Souza; MARIANO, Flávia Sammartino; COLOMBO, Natália Helena; VIZOTO, Natália Leal; MATTOS-GRANER, Renata de Oliveira

2017-01-01

Abstract Objective The aim of this study was to compare the prevalence of periodontal pathogens, systemic inflammatory mediators and lipid profiles in type 1 diabetes children (DM) with those observed in children without diabetes (NDM), both with gingivitis. Material and methods Twenty-four DM children and twenty-seven NDM controls were evaluated. The periodontal status, glycemic and lipid profiles were determined for both groups. Subgingival samples of periodontal sites were collected to determine the prevalence of periodontal microorganisms by PCR. Blood samples were collected for IL-1-β, TNF-α and IL-6 analysis using ELISA kits. Results Periodontal conditions of DM and NDM patients were similar, without statistical differences in periodontal indices. When considering patients with gingivitis, all lipid parameters evaluated were highest in the DM group; Capnocytophaga sputigena and Capnocytophaga ochracea were more prevalent in the periodontal sites of DM children. “Red complex” bacteria were detected in few sites of DM and NDM groups. Fusobacterium nucleatum and Campylobacter rectus were frequently found in both groups. Similar levels of IL-1-β, TNF-α and IL-6 were detected in DM and NDM children. Conclusion Clinical and immunological profiles are similar between DM and NDM children. The presence of Capnocytophaga sputigena and Capnocytophaga ochracea were associated with gingivitis in DM children. PMID:28403363

Dark matter self-interactions and small scale structure

NASA Astrophysics Data System (ADS)

Tulin, Sean; Yu, Hai-Bo

2018-02-01

We review theories of dark matter (DM) beyond the collisionless paradigm, known as self-interacting dark matter (SIDM), and their observable implications for astrophysical structure in the Universe. Self-interactions are motivated, in part, due to the potential to explain long-standing (and more recent) small scale structure observations that are in tension with collisionless cold DM (CDM) predictions. Simple particle physics models for SIDM can provide a universal explanation for these observations across a wide range of mass scales spanning dwarf galaxies, low and high surface brightness spiral galaxies, and clusters of galaxies. At the same time, SIDM leaves intact the success of ΛCDM cosmology on large scales. This report covers the following topics: (1) small scale structure issues, including the core-cusp problem, the diversity problem for rotation curves, the missing satellites problem, and the too-big-to-fail problem, as well as recent progress in hydrodynamical simulations of galaxy formation; (2) N-body simulations for SIDM, including implications for density profiles, halo shapes, substructure, and the interplay between baryons and self-interactions; (3) semi-analytic Jeans-based methods that provide a complementary approach for connecting particle models with observations; (4) merging systems, such as cluster mergers (e.g., the Bullet Cluster) and minor infalls, along with recent simulation results for mergers; (5) particle physics models, including light mediator models and composite DM models; and (6) complementary probes for SIDM, including indirect and direct detection experiments, particle collider searches, and cosmological observations. We provide a summary and critical look for all current constraints on DM self-interactions and an outline for future directions.

Prenatal molecular diagnosis of inherited neuromuscular diseases: Duchenne/Becker muscular dystrophy, myotonic dystrophy type 1 and spinal muscular atrophy.

PubMed

Esposito, Gabriella; Ruggiero, Raffaella; Savarese, Maria; Savarese, Giovanni; Tremolaterra, Maria Roberta; Salvatore, Francesco; Carsana, Antonella

2013-12-01

Neuromuscular disease is a broad term that encompasses many diseases that either directly, via an intrinsic muscle disorder, or indirectly, via a nerve disorder, impairs muscle function. Here we report the experience of our group in the counselling and molecular prenatal diagnosis of three inherited neuromuscular diseases, i.e., Duchenne/Becker muscular dystrophy (DMD/BMD), myotonic dystrophy type 1 (DM1), spinal muscular atrophy (SMA). We performed a total of 83 DMD/BMD, 15 DM1 and 54 SMA prenatal diagnoses using a combination of technologies for either direct or linkage diagnosis. We identified 16, 5 and 10 affected foetuses, respectively. The improvement of analytical procedures in recent years has increased the mutation detection rate and reduced the analytical time. Due to the complexity of the experimental procedures and the high, specific professional expertise required for both laboratory activities and the related counselling, these types of analyses should be preferentially performed in reference molecular diagnostic centres.

Fermionic minimal dark matter in 5D gauge-Higgs unification

NASA Astrophysics Data System (ADS)

Maru, Nobuhito; Okada, Nobuchika; Okada, Satomi

2017-12-01

We propose a minimal dark matter (MDM) scenario in the context of a simple gauge-Higgs unification (GHU) model based on the gauge group S U (3 )×U (1 )' in five-dimensional Minkowski space with a compactification of the fifth dimension on the 1S/Z2 orbifold. A pair of vectorlike S U (3 ) multiplet fermions in a higher-dimensional representation is introduced in the bulk, and the DM particle is identified with the lightest mass eigenstate among the components in the multiplets. In the original model description, the DM particle communicates with the Standard Model (SM) particles only through the bulk gauge interaction, and hence our model is the GHU version of the MDM scenario. There are two typical realizations of the DM particle in four-dimensional effective theory: (i) the DM particle is mostly composed of the SM S U (2 )L multiplets, or (ii) the DM is mostly composed of the SM S U (2 )L singlets. Since the case (i) is very similar to the original MDM scenario, we focus on the case (ii), which is a realization of the Higgs-portal DM scenario in the context of the GHU model. We identify an allowed parameter region to be consistent with the current experimental constraints, which will be fully covered by the direct dark matter detection experiments in the near future. In the presence of the bulk multiplet fermions in higher-dimensional S U (3 ) representations, we reproduce the 125 GeV Higgs boson mass through the renormalization group evolution of Higgs quartic coupling with the compactification scale of 10-100 TeV.

Effect of autoimmunity risk loci on the honeymoon phase in type 1 diabetes.

PubMed

Moosavi, Mandana; Séguin, Jade; Polychronakos, Constantin

2017-09-01

To analyze the correlation between duration and depth of honeymoon phase in patients with type 1 diabetes (T1DM) and autoimmunity risk loci. From a database of 567 individuals with clinical data, we selected 210 patients for whom we had dense genotyping results of single-nucleotide polymorphisms (SNPs) from our previous genome-wide association studies (GWAS) or targeted genotyping data. Using PLINK software, we analyzed the association between time spent in honeymoon phase as our quantitative trait, and 24 known autoimmunity predisposing SNPs. We found one allele on chromosome 5, rs4613763 mapping to a Prostaglandin Receptor EP4 (PTGER4) to reach statistical significance (P = .0067), in determining a larger proportion of T1DM patients with a detectable honeymoon phase. This polymorphism determines risk for inflammatory bowel disease (IBD) but not T1DM. By showing the role of PTGER4 in autoimmune diseases and its effect on inflammatory responses via its interaction with NF-kB, we hypothesize that PTGER4 modulates honeymoon phase in patients with T1DM without influencing the risk of developing T1DM. We hypothesize that this quantitative trait locus promotes inflammatory suppression of beta cells without directly promoting beta-cell destruction. Understanding SNPs that effect function can provide insight in to pathogenesis of T1DM and the mechanism of the honeymoon phase. Because this is a hypothesis-generating study, it needs to be replicated in an additional larger cohort. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Virgin olive oil ameliorates deltamethrin-induced nephrotoxicity in mice: A biochemical and immunohistochemical assessment.

PubMed

Khalatbary, Ali Reza; Ahmadvand, Hassan; Ghabaee, Davood Nasiry Zarrin; Malekshah, Abbasali Karimpour; Navazesh, Azam

2016-01-01

A major class of synthetic pyrethroid insecticide, deltamethrin (DM), can elicit pathophysiological effects through oxidative stress in non-targeted organisms such as mammals. There is accumulating evidence that virgin olive oil (VOO), a rich source of polyphenolic components, have anti-oxidant, anti-inflammatory, and anti-apoptotic properties. This study aimed to determine the protective and ameliorative effects of VOO against DM-induced nephrotoxicity. Mice were randomly divided into four equal groups: DM group, DM plus VOO group, VOO group, and vehicle group. Five weeks after gavaging, kidney samples were taken for biochemical assessment of malondialdehyde (MDA), glutathione (GSH) and catalase (CAT), and for immunohistochemical assessment of caspase-3, cyclooxygenase-2 (cox-2) and poly (ADP-ribose) polymerase (PARP). The MDA level in kidney was increased in the DM group, which was significantly decreased after VOO administration in the DM plus VOO group. The GSH level and CAT activiy in kidney were decreased in the DM group, which were significantly increased after VOO administration in the DM plus VOO group. Greater expression of caspase-3, cox-2, and PARP could be detected in the DM group, which was significantly attenuated in the DM plus VOO group. Also, the histopathological changes which were detected in the DM group attenuated after VOO consumption. Virgin olive oil exerted protective effects against deltamethrin-induced nephrotoxicity, which might be associated with its anti-apoptotic, anti-inflammatory, and anti-oxidative properties.

Zepto-molar electrochemical detection of Brucella genome based on gold nanoribbons covered by gold nanoblooms

NASA Astrophysics Data System (ADS)

Rahi, Amid; Sattarahmady, Naghmeh; Heli, Hossein

2015-12-01

Gold nanoribbons covered by gold nanoblooms were sonoelectrodeposited on a polycrystalline gold surface at -1800 mV (vs. AgCl) with the assistance of ultrasound and co-occurrence of the hydrogen evolution reaction. The nanostructure, as a transducer, was utilized to immobilize a Brucella-specific probe and fabrication of a genosensor, and the process of immobilization and hybridization was detected by electrochemical methods, using methylene blue as a redox marker. The proposed method for detection of the complementary sequence, sequences with base-mismatched (one-, two- and three-base mismatches), and the sequence of non-complementary sequence was assayed. The fabricated genosensor was evaluated for the assay of the bacteria in the cultured and human samples without polymerase chain reactions (PCR). The genosensor could detect the complementary sequence with a calibration sensitivity of 0.40 μA dm3 mol-1, a linear concentration range of 10 zmol dm-3 to 10 pmol dm-3, and a detection limit of 1.71 zmol dm-3.

A Comparison of Systematic Desensitization and Directed Masturbation in the Treatment of Primary Orgasmic Dysfunction in Females

PubMed Central

Andersen, Barbara L.

2009-01-01

Thirty subjects seeking treatment for primary inorgasmia accompanied by sexual anxiety or aversion were assigned to one of three groups: systematic desensitization (SD), directed masturbation (DM), or waiting list control (WL). Following treatment, subjects were retested, and the WL group then received directed masturbation treatment. A third testing constituted a follow-up for the SD and DM groups and a posttreatment testing for the WL. Both treatments were equally effective in improving subjects’ sexual self-acceptance and increasing sexual pleasure. Changes in anxiety were negligible; however, sexual arousal and orgasm for DM and WL subjects increased. The gains of the WL group not only replicated the findings of the DM group but also were of greater magnitude. PMID:6114968

Direct Dark Matter Detection through the use of a Xenon Based TPC Detector

NASA Astrophysics Data System (ADS)

Daniel, Jonathan; Akerib, Daniel; LZ group at SLAC

2018-01-01

The vast majority of matter in the universe is unaccounted for. Only 15% of the universe's mass density is visible matter, while the other 85% is Dark Matter (DM). The Weakly Interacting Massive Particle (WIMP) is currently the frontrunner of the DM candidates. The Large Underground Xenon (LUX) and next generation LUX-ZEPLIN (LZ) experiments are designed to directly detect WIMPs. Both experiments are xenon-based Time Projection Chambers (TPC) used to observe possible WIMP interactions. These interactions produce photons and electrons with the photons being collected in a set of two photomultiplier tube (PMT) arrays and the electrons drifted upwards in the detector by a strong electric field to create a secondary production of photons in gaseous xenon. These two populations of photons are classified as S1 and S2 signals, respectively. Using these signals we reconstruct the energy and position of the interaction and in doing so we can eliminate background events that would otherwise “light up” the detector. My participation in the experiment, while at SLAC, was the creation of the grids that produce the large electric field, along with additional lab activities aimed at testing the grids. While at Stan State, I work on background modeling in order to distinguish a possible WIMP signal from ambient backgrounds.

Projection of Diabetes Population Size and Associated Economic Burden through 2030 in Iran: Evidence from Micro-Simulation Markov Model and Bayesian Meta-Analysis

PubMed Central

Javanbakht, Mehdi; Mashayekhi, Atefeh; Baradaran, Hamid R.; Haghdoost, AliAkbar; Afshin, Ashkan

2015-01-01

Background The aim of this study was to estimate the economic burden of diabetes mellitus (DM) in Iran from 2009 to 2030. Methods A Markov micro-simulation (MM) model was developed to predict the DM population size and associated economic burden. Age- and sex-specific prevalence and incidence of diagnosed and undiagnosed DM were derived from national health surveys. A systematic review was performed to identify the cost of diabetes in Iran and the mean annual direct and indirect costs of patients with DM were estimated using a random-effect Bayesian meta-analysis. Face, internal, cross and predictive validity of the MM model were assessed by consulting an expert group, performing sensitivity analysis (SA) and comparing model results with published literature and national survey reports. Sensitivity analysis was also performed to explore the effect of uncertainty in the model. Results We estimated 3.78 million cases of DM (2.74 million diagnosed and 1.04 million undiagnosed) in Iran in 2009. This number is expected to rise to 9.24 million cases (6.73 million diagnosed and 2.50 million undiagnosed) by 2030. The mean annual direct and indirect costs of patients with DM in 2009 were US$ 556 (posterior standard deviation, 221) and US$ 689 (619), respectively. Total estimated annual cost of DM was $3.64 (2009 US$) billion (including US$1.71 billion direct and US$1.93 billion indirect costs) in 2009 and is predicted to increase to $9.0 (in 2009 US$) billion (including US$4.2 billion direct and US$4.8 billion indirect costs) by 2030. Conclusions The economic burden of DM in Iran is predicted to increase markedly in the coming decades. Identification and implementation of effective strategies to prevent and manage DM should be considered as a public health priority. PMID:26200913

Projection of Diabetes Population Size and Associated Economic Burden through 2030 in Iran: Evidence from Micro-Simulation Markov Model and Bayesian Meta-Analysis.

PubMed

Javanbakht, Mehdi; Mashayekhi, Atefeh; Baradaran, Hamid R; Haghdoost, AliAkbar; Afshin, Ashkan

2015-01-01

The aim of this study was to estimate the economic burden of diabetes mellitus (DM) in Iran from 2009 to 2030. A Markov micro-simulation (MM) model was developed to predict the DM population size and associated economic burden. Age- and sex-specific prevalence and incidence of diagnosed and undiagnosed DM were derived from national health surveys. A systematic review was performed to identify the cost of diabetes in Iran and the mean annual direct and indirect costs of patients with DM were estimated using a random-effect Bayesian meta-analysis. Face, internal, cross and predictive validity of the MM model were assessed by consulting an expert group, performing sensitivity analysis (SA) and comparing model results with published literature and national survey reports. Sensitivity analysis was also performed to explore the effect of uncertainty in the model. We estimated 3.78 million cases of DM (2.74 million diagnosed and 1.04 million undiagnosed) in Iran in 2009. This number is expected to rise to 9.24 million cases (6.73 million diagnosed and 2.50 million undiagnosed) by 2030. The mean annual direct and indirect costs of patients with DM in 2009 were US$ 556 (posterior standard deviation, 221) and US$ 689 (619), respectively. Total estimated annual cost of DM was $3.64 (2009 US$) billion (including US$1.71 billion direct and US$1.93 billion indirect costs) in 2009 and is predicted to increase to $9.0 (in 2009 US$) billion (including US$4.2 billion direct and US$4.8 billion indirect costs) by 2030. The economic burden of DM in Iran is predicted to increase markedly in the coming decades. Identification and implementation of effective strategies to prevent and manage DM should be considered as a public health priority.

CXCR4-using HIV variants in a cohort of Black men who have sex with men: HIV Prevention Trials Network 061.

PubMed

Chen, Iris; Huang, Wei; Connor, Matthew B; Frantzell, Arne; Cummings, Vanessa; Beauchamp, Geetha G; Griffith, Sam; Fields, Sheldon D; Scott, Hyman M; Shoptaw, Steven; Del Rio, Carlos; Magnus, Manya; Mannheimer, Sharon; Tieu, Hong-Van; Wheeler, Darrell P; Mayer, Kenneth H; Koblin, Beryl A; Eshleman, Susan H

2016-07-01

To evaluate factors associated with HIV tropism among Black men who have sex with men (MSM) in the United States enrolled in a clinical study (HIV Prevention Trials Network 061). HIV tropism was analyzed using a phenotypic assay (Trofile assay, Monogram Biosciences). Samples were analyzed from 43 men who were HIV infected at enrollment and reported either exclusive insertive intercourse or exclusive receptive intercourse; samples were also analyzed from 20 men who were HIV uninfected at enrollment and seroconverted during the study. Clonal analysis of individual viral variants was performed for seroconverters who had dual/mixed (DM) viruses. DM viruses were detected in samples from 11 (26%) of the 43 HIV-infected men analyzed at the enrollment visit; HIV tropism did not differ between those reporting exclusive insertive vs receptive intercourse. DM viruses were also detected in five (25%) of the 20 seroconverters. DM viruses were associated with lower CD4 cell counts. Seroconverters with DM viruses had dual-tropic viruses only or mixed populations of CCR5- and dual-tropic viruses. DM viruses were frequently detected among Black MSM in this study, including seroconverters. Further studies are needed to understand factors driving transmission and selection of CXCR4- and dual-tropic viruses among Black MSM.

Comparing type 1 and type 2 diabetes in pregnancy- similar conditions or is a separate approach required?

PubMed

Owens, Lisa A; Sedar, Jon; Carmody, Louise; Dunne, Fidelma

2015-03-27

Pregnancy in women with type 1 (T1DM) or type 2 diabetes (T2DM) is associated with increased risk. These conditions are managed similarly during pregnancy, and compared directly in analyses, however they affect women of different age, body mass index and ethnicity. We assess if differences exist in pregnancy outcomes between T1DM and T2DM by comparing them directly and with matched controls. We also analyze the effect of glycemic control on pregnancy outcomes and analyze predictive variables for poor outcome. We include 323 women with diabetes and 660 glucose-tolerant controls. T2DM women had higher BMI, age and parity with a shorter duration of diabetes and better glycemic control. Preeclampsia occurred more in women with T1DM only. Rates of elective cesarean section were similar between groups but greater than in controls, emergency cesarean section was increased in women with type 1 diabetes. Maternal morbidity in T1DM was double that of matched controls but T2DM was similar to controls. Babies of mothers with diabetes were more likely to be delivered prematurely. Neonatal hypoglycemia occurred more in T1DM than T2DM and contributed to a higher rate of admission to neonatal intensive care for both groups. Adverse neonatal outcomes including stillbirths and congenital abnormalities were seen in both groups but were more common in T1DM pregnancies. HbA1C values at which these poor outcomes occurred differed between T1 and T2DM. Pregnancy outcomes in T1DM and T2DM are different and occur at different levels of glycemia. This should be considered when planning and managing pregnancy and when counseling women.

Direct and regression methods do not give different estimates of digestible and metabolizable energy of wheat for pigs.

PubMed

Bolarinwa, O A; Adeola, O

2012-12-01

Digestible and metabolizable energy contents of feed ingredients for pigs can be determined by direct or indirect methods. There are situations when only the indirect approach is suitable and the regression method is a robust indirect approach. This study was conducted to compare the direct and regression methods for determining the energy value of wheat for pigs. Twenty-four barrows with an average initial BW of 31 kg were assigned to 4 diets in a randomized complete block design. The 4 diets consisted of 969 g wheat/kg plus minerals and vitamins (sole wheat) for the direct method, corn (Zea mays)-soybean (Glycine max) meal reference diet (RD), RD + 300 g wheat/kg, and RD + 600 g wheat/kg. The 3 corn-soybean meal diets were used for the regression method and wheat replaced the energy-yielding ingredients, corn and soybean meal, so that the same ratio of corn and soybean meal across the experimental diets was maintained. The wheat used was analyzed to contain 883 g DM, 15.2 g N, and 3.94 Mcal GE/kg. Each diet was fed to 6 barrows in individual metabolism crates for a 5-d acclimation followed by a 5-d total but separate collection of feces and urine. The DE and ME for the sole wheat diet were 3.83 and 3.77 Mcal/kg DM, respectively. Because the sole wheat diet contained 969 g wheat/kg, these translate to 3.95 Mcal DE/kg DM and 3.89 Mcal ME/kg DM. The RD used for the regression approach yielded 4.00 Mcal DE and 3.91 Mcal ME/kg DM diet. Increasing levels of wheat in the RD linearly reduced (P < 0.05) DE and ME to 3.88 and 3.79 Mcal/kg DM diet, respectively. The regressions of wheat contribution to DE and ME in megacalories against the quantity of wheat DM intake in kilograms generated 3.96 Mcal DE and 3.88 Mcal ME/kg DM. In conclusion, values obtained for the DE and ME of wheat using the direct method (3.95 and 3.89 Mcal/kg DM) did not differ (0.78 < P < 0.89) from those obtained using the regression method (3.96 and 3.88 Mcal/kg DM).

Probing Models of Dark Matter and the Early Universe

NASA Astrophysics Data System (ADS)

Orlofsky, Nicholas David

This thesis discusses models for dark matter (DM) and their behavior in the early universe. An important question is how phenomenological probes can directly search for signals of DM today. Another topic of investigation is how the DM and other processes in the early universe must evolve. Then, astrophysical bounds on early universe dynamics can constrain DM. We will consider these questions in the context of three classes of DM models--weakly interacting massive particles (WIMPs), axions, and primordial black holes (PBHs). Starting with WIMPs, we consider models where the DM is charged under the electroweak gauge group of the Standard Model. Such WIMPs, if generated by a thermal cosmological history, are constrained by direct detection experiments. To avoid present or near-future bounds, the WIMP model or cosmological history must be altered in some way. This may be accomplished by the inclusion of new states that coannihilate with the WIMP or a period of non-thermal evolution in the early universe. Future experiments are likely to probe some of these altered scenarios, and a non-observation would require a high degree of tuning in some of the model parameters in these scenarios. Next, axions, as light pseudo-Nambu-Goldstone bosons, are susceptible to quantum fluctuations in the early universe that lead to isocurvature perturbations, which are constrained by observations of the cosmic microwave background (CMB). We ask what it would take to allow axion models in the face of these strong CMB bounds. We revisit models where inflationary dynamics modify the axion potential and discuss how isocurvature bounds can be relaxed, elucidating the difficulties in these constructions. Avoiding disruption of inflationary dynamics provides important limits on the parameter space. Finally, PBHs have received interest in part due to observations by LIGO of merging black hole binaries. We ask how these PBHs could arise through inflationary models and investigate the opportunity for corroboration through experimental probes of gravitational waves at pulsar timing arrays. We provide examples of theories that are already ruled out, theories that will soon be probed, and theories that will not be tested in the foreseeable future. The models that are most strongly constrained are those with relatively broad primordial power spectra.

Branched-chain amino acids in metabolic signalling and insulin resistance

PubMed Central

Lynch, Christopher J.; Adams, Sean H.

2015-01-01

Branched-chain amino acids (BCAAs) are important nutrient signals that have direct and indirect effects. Frequently, BCAAs have been reported to mediate antiobesity effects, especially in rodent models. However, circulating levels of BCAAs tend to be increased in individuals with obesity and are associated with worse metabolic health and future insulin resistance or type 2 diabetes mellitus (T2DM). A hypothesized mechanism linking increased levels of BCAAs and T2DM involves leucine-mediated activation of the mammalian target of rapamycin complex 1 (mTORC1), which results in uncoupling of insulin signalling at an early stage. A BCAA dysmetabolism model proposes that the accumulation of mitotoxic metabolites (and not BCAAs per se) promotes β-cell mitochondrial dysfunction, stress signalling and apoptosis associated with T2DM. Alternatively, insulin resistance might promote aminoacidaemia by increasing the protein degradation that insulin normally suppresses, and/or by eliciting an impairment of efficient BCAA oxidative metabolism in some tissues. Whether and how impaired BCAA metabolism might occur in obesity is discussed in this Review. Research on the role of individual and model-dependent differences in BCAA metabolism is needed, as several genes (BCKDHA, PPM1K, IVD and KLF15) have been designated as candidate genes for obesity and/or T2DM in humans, and distinct phenotypes of tissue-specific branched chain ketoacid dehydrogenase complex activity have been detected in animal models of obesity and T2DM. PMID:25287287

The Analysis of Metal Finishing Solutions by Ion Chromatography

DTIC Science & Technology

1987-08-01

Chromatographic Instrumentation ...... 33 2.3 Modes of Separation .................. 35 2.4 Modes of Detection ................... 44 2.5 Method Development...Chromium Plating Solutions a and R with Added HCl ..................... 151 Table 35 . Chromium Plating Solutions a and R with Added NaOH...Dm (20) HETPld= Zd Dm / U (21) HETPsm= Zsm dp dp U / Dm (22) HETPsp= Zs dp dp U / Ds (23) where: dp- Particle diameter. Dm= Solute mobile phase

Occurrence of 4-Nonylphenol in rain and snow

NASA Astrophysics Data System (ADS)

Fries, Elke; Püttmann, Wilhelm

The present technical note reports on the endocrine disruptor 4-nonylphenol (4-NP) in rain and snow. In July 2001, November 2001 and January 2002, rain and snow sampling was conducted at different urban, suburban and rural areas in Germany and Belgium. The mean concentration of 4-NP in rain water and roof run off was 0.253 μg dm -3 ( n=8) with a higher mean concentration in suburban areas at 0.534 μg dm -3 and considerable lower mean concentrations in rural and urban areas at 0.099 and 0.062 μg dm -3, respectively. The mean concentration of 4-NP at 0.099 μg dm -3 ( n=3) was significantly lower in summer rain than in winter rain at 0.346 μg dm -3. In snow samples, 4-NP was detected with a mean value of 0.242 μg dm -3 ( n=8). A higher mean value of 4-NP in snow at 0.478 μg dm -3 ( n=4) was found at urban sites whereas in snow from suburban areas the mean concentration of 4-NP at 0.030 μg dm -3 ( n=2) was much lower. 4-NP was never detected above its determination limit in snow samples from rural areas.

The identification of higher forefoot temperatures associated with peripheral arterial disease in type 2 diabetes mellitus as detected by thermography.

PubMed

Gatt, Alfred; Cassar, Kevin; Falzon, Owen; Ellul, Christian; Camilleri, Kenneth P; Gauci, Jean; Mizzi, Stephen; Mizzi, Anabelle; Sturgeon, Cassandra; Chockalingam, Nachiappan; Formosa, Cynthia

2018-08-01

The purpose of this study was to investigate whether heat emitted from the feet of patients with type 2 diabetes (DM) and peripheral arterial disease (PAD) differed from those with type 2 diabetes without complications (DM). A non-experimental, comparative prospective study design was employed in a tertiary referral hospital. Out of 223 randomly selected participants (430 limbs) who were initially tested, 62 limbs were categorized as DM+PAD and 22 limbs as DM without PAD. Subjects with evidence of peripheral neuropathy were excluded. Participants underwent thermographic imaging. Automatic segmentation of regions of interest extracted the temperature data. A significant difference in temperature in all the toes between the two groups was found (p=0.005, p=0.033, p=0.015, p=0.038 and p=0.02 for toes 1-5 respectively). The mean forefoot temperature in DM+PAD was significantly higher than that in DM (p=.019), with DM+PAD having a higher mean temperature (28.3°C) compared to DM (26.2°C). Similarly, the toes of subjects with DM+PAD were significantly warmer than those of subjects with DM only. Contrary to expectations the mean toe and forefoot temperatures in DM patients with PAD is higher than in those with DM only. This unexpected result could be attributed to disruption of noradrenergic vasoconstrictor thermoregulatory mechanisms with resulting increased flow through cutaneous vessels and subsequent increased heat emissivity. These results demonstrate that thermography may have potential in detecting PAD and associated temperature differences. Copyright © 2018 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

Deltamethrin-Induced Hepatotoxicity and Virgin Olive Oil Consumption: An Experimental Study.

PubMed

Khalatbary, Ali Reza; Ghabaee, Davood Nasiry Zarrin; Ahmadvand, Hassan; Amiri, Fereshteh Talebpour; Lehi, Somaieh Tadayoni

2017-11-01

Deltamethrin (DM) is a synthetic pyrethroid insecticide which can lead to pathological effects in mammals through oxidative stress. On the other hand, virgin olive oil (VOO) is a rich source of phenolic compounds with antioxidants. The aim of the present study was to determine the protective effects of VOO against DM-induced hepatotoxicity. Thirty-six mice were randomly separated into 4 groups: vehicle group, VOO group, DM group, and DM plus VOO group. Immunohistochemistry of PARP, COX-2, and caspase-3 with the biochemical analysis of malondialdehyde and total antioxidant capacity levels were performed in the liver samples 5 weeks after gavaging. Statistical analysis was performed using SPSS, version 15. The data were compared between the groups using the Tukey multiple comparison tests and the analysis of the variance. A P value <0.05 was considered significant. The malondialdehyde level in the liver was increased in the DM group (71.18±0.01), whereas it was significantly (P=0.001) decreased after VOO administration in the DM plus VOO group (39.59±2.43). While the total antioxidant capacity level in the liver was decreased in the DM group (3.05±0.05), it was significantly increased (P=0.03) after VOO administration in the DM plus VOO group (3.95±0.04). A greater expression of caspase-3 (P=0.008), COX-2 (P =0.004), and PARP (P 0.006) could be detected in the DM group, while it was significantly (P=0.009) attenuated in the DM plus VOO group. Also, the degeneration of hepatocytes, which was detected in the DM group, was attenuated after VOO consumption. VOO exerted protective effects against DM-induced hepatotoxicity, which might be associated with its anti-apoptotic, anti-inflammatory, and antioxidative properties.

Associations of Salivary BPIFA1 Protein in Chronic Periodontitis Patients with Type 2 Diabetes Mellitus

PubMed Central

Tang, Chen-Yi

2017-01-01

Aims To explore the differences in salivary BPI fold containing family A, member 1 (BPIFA1) concentration among type 2 diabetes mellitus (T2DM) subjects with various severities of chronic periodontitis and to determine whether BPIFA1 in saliva can be used as a potential biomarker of T2DM. Methods Unstimulated saliva samples were collected from 44 subjects with T2DM and 44 without T2DM (NDM). Additionally, demographic data and general health parameters, including fasting blood glucose (FBG) and body mass index (BMI), were collected. We also detected full-mouth clinical periodontal parameters including probing pocket depth (PPD), clinical attachment level (CAL), bleeding index (BI), and plaque index (PLI). Salivary BPIFA1, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) concentrations were also detected. Results BPIFA1 in saliva was detected at relatively high levels. T2DM subjects had decreased salivary BPIFA1 concentrations (P = 0.031). In T2DM subjects with nonperiodontitis or severe periodontitis, the level of BPIFA1 was significantly lower compared with that of NDM. Salivary TNF-α concentration displayed a similar trend to BPIFA1 in the NDM group. Conclusions BPIFA1 protein is rich in saliva and might be used as a potential predictive biomarker of T2DM, especially in patients with severe periodontitis and nonperiodontitis. This trial is registered with ChiCTR-ROC-17010310. PMID:29109737

Separation and quantification of inulin in selected artichoke (Cynara scolymus L.) cultivars and dandelion (Taraxacum officinale WEB. ex WIGG.) roots by high-performance anion exchange chromatography with pulsed amperometric detection.

PubMed

Schütz, Katrin; Muks, Erna; Carle, Reinhold; Schieber, Andreas

2006-12-01

The profile of fructooligosaccharides and fructopolysaccharides in artichoke heads and dandelion roots was investigated. For this purpose, a suitable method for high-performance anion exchange chromatography with pulsed amperometic detection was developed. The separation of monomers, oligomers and polymers up to a chain length of 79 sugar residues was achieved in one single run. Glucose, fructose, sucrose and individual fructooligosaccharides (kestose, nystose, fructofuranosylnystose) were quantified in six different artichoke cultivars and in dandelion roots. The contents ranged from 12.9 g/kg DM to 71.7 g/kg DM for glucose, from 15.8 g/kg DM to 67.2 g/kg DM for fructose, and from 16.8 g/kg DM to 55.2 g/kg DM for sucrose in the artichoke heads. Kestose was the predominant fructooligosaccharide, followed by nystose and fructofuranosylnystose. In four cultivars fructofuranosylnystose was only detectable in traces and reached its maximum value of 3.6 g/kg DM in the cultivar Le Castel. Furthermore, an average degree of polymerization of 5.3 to 16.7 was calculated for the individual artichoke cultivars, which is noticeably lower than hitherto reported. In contrast, the contents of kestose, nystose and fructofuranosylnystose in dandelion root exceeded that of artichoke, reflecting the short chain characteristic of the inulin, which was confirmed by chromatographic analysis. Copyright (c) 2006 John Wiley & Sons, Ltd.

DM-BLD: differential methylation detection using a hierarchical Bayesian model exploiting local dependency.

PubMed

Wang, Xiao; Gu, Jinghua; Hilakivi-Clarke, Leena; Clarke, Robert; Xuan, Jianhua

2017-01-15

The advent of high-throughput DNA methylation profiling techniques has enabled the possibility of accurate identification of differentially methylated genes for cancer research. The large number of measured loci facilitates whole genome methylation study, yet posing great challenges for differential methylation detection due to the high variability in tumor samples. We have developed a novel probabilistic approach, D: ifferential M: ethylation detection using a hierarchical B: ayesian model exploiting L: ocal D: ependency (DM-BLD), to detect differentially methylated genes based on a Bayesian framework. The DM-BLD approach features a joint model to capture both the local dependency of measured loci and the dependency of methylation change in samples. Specifically, the local dependency is modeled by Leroux conditional autoregressive structure; the dependency of methylation changes is modeled by a discrete Markov random field. A hierarchical Bayesian model is developed to fully take into account the local dependency for differential analysis, in which differential states are embedded as hidden variables. Simulation studies demonstrate that DM-BLD outperforms existing methods for differential methylation detection, particularly when the methylation change is moderate and the variability of methylation in samples is high. DM-BLD has been applied to breast cancer data to identify important methylated genes (such as polycomb target genes and genes involved in transcription factor activity) associated with breast cancer recurrence. A Matlab package of DM-BLD is available at http://www.cbil.ece.vt.edu/software.htm CONTACT: Xuan@vt.eduSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Design of experiments approach to engineer cell-secreted matrices for directing osteogenic differentiation.

PubMed

Decaris, Martin L; Leach, J Kent

2011-04-01

The presentation of extracellular matrix (ECM) proteins provides an opportunity to instruct the phenotype and behavior of responsive cells. Decellularized cell-secreted matrix coatings (DM) represent a biomimetic culture surface that retains the complexity of the natural ECM. Microenvironmental culture conditions alter the composition of these matrices and ultimately the ability of DMs to direct cell fate. We employed a design of experiments (DOE) multivariable analysis approach to determine the effects and interactions of four variables (culture duration, cell seeding density, oxygen tension, and media supplementation) on the capacity of DMs to direct the osteogenic differentiation of human mesenchymal stem cells (hMSCs). DOE analysis revealed that matrices created with extended culture duration, ascorbate-2-phosphate supplementation, and in ambient oxygen tension exhibited significant correlations with enhanced hMSC differentiation. We validated the DOE model results using DMs predicted to have superior (DM1) or lesser (DM2) osteogenic potential for naïve hMSCs. Compared to cells on DM2, hMSCs cultured on DM1 expressed 2-fold higher osterix levels and deposited 3-fold more calcium over 3 weeks. Cells on DM1 coatings also exhibited greater proliferation and viability compared to DM2-coated substrates. This study demonstrates that DOE-based analysis is a powerful tool for optimizing engineered systems by identifying significant variables that have the greatest contribution to the target output.

Dark matter profiles and annihilation in dwarf spheroidal galaxies: prospectives for present and future γ-ray observatories - I. The classical dwarf spheroidal galaxies

NASA Astrophysics Data System (ADS)

Charbonnier, A.; Combet, C.; Daniel, M.; Funk, S.; Hinton, J. A.; Maurin, D.; Power, C.; Read, J. I.; Sarkar, S.; Walker, M. G.; Wilkinson, M. I.

2011-12-01

Due to their large dynamical mass-to-light ratios, dwarf spheroidal galaxies (dSphs) are promising targets for the indirect detection of dark matter (DM) in γ-rays. We examine their detectability by present and future γ-ray observatories. The key innovative features of our analysis are as follows: (i) we take into account the angular size of the dSphs; while nearby objects have higher γ-ray flux, their larger angular extent can make them less attractive targets for background-dominated instruments; (ii) we derive DM profiles and the astrophysical J-factor (which parametrizes the expected γ-ray flux, independently of the choice of DM particle model) for the classical dSphs directly from photometric and kinematic data. We assume very little about the DM profile, modelling this as a smooth split-power-law distribution, with and without subclumps; (iii) we use a Markov chain Monte Carlo technique to marginalize over unknown parameters and determine the sensitivity of our derived J-factors to both model and measurement uncertainties; and (iv) we use simulated DM profiles to demonstrate that our J-factor determinations recover the correct solution within our quoted uncertainties. Our key findings are as follows: (i) subclumps in the dSphs do not usefully boost the signal; (ii) the sensitivity of atmospheric Cherenkov telescopes to dSphs within ˜20 kpc with cored haloes can be up to ˜50 times worse than when estimated assuming them to be point-like. Even for the satellite-borne Fermi-Large Area Telescope (Fermi-LAT), the sensitivity is significantly degraded on the relevant angular scales for long exposures; hence, it is vital to consider the angular extent of the dSphs when selecting targets; (iii) no DM profile has been ruled out by current data, but using a prior on the inner DM cusp slope 0 ≤γprior≤ 1 provides J-factor estimates accurate to a factor of a few if an appropriate angular scale is chosen; (iv) the J-factor is best constrained at a critical integration angle αc= 2rh/d (where rh is the half-light radius and d is the distance from the dwarf) and we estimate the corresponding sensitivity of γ-ray observatories; (v) the 'classical' dSphs can be grouped into three categories: well constrained and promising (Ursa Minor, Sculptor and Draco), well constrained but less promising (Carina, Fornax and Leo I), and poorly constrained (Sextans and Leo II); and (vi) observations of classical dSphs with the Fermi-LAT integrated over the mission lifetime are more promising than observations with the planned Cherenkov Telescope Array for DM particle mass ≲ 700 GeV. However, even the Fermi-LAT will not have sufficient integrated signal from the classical dwarfs to detect DM in the 'vanilla' Minimal Supersymmetric Standard Model. Both the Galactic Centre and the 'ultrafaint' dwarfs are likely to be better targets and will be considered in future work.

A subset of anti-rotavirus antibodies directed against the viral protein VP7 predicts the onset of celiac disease and induces typical features of the disease in the intestinal epithelial cell line T84.

PubMed

Dolcino, Marzia; Zanoni, Giovanna; Bason, Caterina; Tinazzi, Elisa; Boccola, Elisa; Valletta, Enrico; Contreas, Giovanna; Lunardi, Claudio; Puccetti, Antonio

2013-07-01

Celiac disease (CD) is an autoimmune disorder of the small intestine triggered by environmental factors in genetically predisposed individuals. A strong association between type 1 diabetes (T1DM) and CD has been reported. We have previously shown that rotavirus infection may be involved in the pathogenesis of CD through a mechanism of molecular mimicry. Indeed, we identified a subset of anti-transglutaminase IgA antibodies that recognize the rotavirus viral protein VP7. In this study, we aimed at evaluating whether such antibodies may predict the onset of CD in children affected by T1DM. Moreover, to further analyze the link between rotavirus infection and pathogenesis of CD, we analyzed the effect of anti-rotavirus VP7 antibodies on T84 intestinal epithelial cells using the gene-array technique, complemented by the analysis of molecules secreted in the supernatant of stimulated cells. We found that anti-rotavirus VP7 antibodies are present in the vast majority (81%) of T1DM-CD tested sera, but are detectable also in a fraction (27%) of T1DM children without CD. Moreover, we found that anti-rotavirus VP7 antibodies are present before the CD onset, preceding the detection of anti-tTG and anti-endomysium antibodies. The gene-array analysis showed that purified anti-rotavirus VP7 antibodies modulate genes that are involved in apoptosis, inflammation, and alteration of the epithelial barrier integrity in intestinal epithelial cells, all typical features of CD. Taken together, these new data further support the involvement of rotavirus infection in the pathogenesis of CD and suggest a predictive role of anti-rotavirus VP7 antibodies.

Comparison of speckle-tracking echocardiography with invasive hemodynamics for the detection of characteristic cardiac dysfunction in type-1 and type-2 diabetic rat models.

PubMed

Mátyás, Csaba; Kovács, Attila; Németh, Balázs Tamás; Oláh, Attila; Braun, Szilveszter; Tokodi, Márton; Barta, Bálint András; Benke, Kálmán; Ruppert, Mihály; Lakatos, Bálint Károly; Merkely, Béla; Radovits, Tamás

2018-01-16

Measurement of systolic and diastolic function in animal models is challenging by conventional non-invasive methods. Therefore, we aimed at comparing speckle-tracking echocardiography (STE)-derived parameters to the indices of left ventricular (LV) pressure-volume (PV) analysis to detect cardiac dysfunction in rat models of type-1 (T1DM) and type-2 (T2DM) diabetes mellitus. Rat models of T1DM (induced by 60 mg/kg streptozotocin, n = 8) and T2DM (32-week-old Zucker Diabetic Fatty rats, n = 7) and corresponding control animals (n = 5 and n = 8, respectively) were compared. Echocardiography and LV PV analysis were performed. LV short-axis recordings were used for STE analysis. Global circumferential strain, peak strain rate values in systole (SrS), isovolumic relaxation (SrIVR) and early diastole (SrE) were measured. LV contractility, active relaxation and stiffness were measured by PV analysis. In T1DM, contractility and active relaxation were deteriorated to a greater extent compared to T2DM. In contrast, diastolic stiffness was impaired in T2DM. Correspondingly, STE described more severe systolic dysfunction in T1DM. Among diastolic STE parameters, SrIVR was more decreased in T1DM, however, SrE was more reduced in T2DM. In T1DM, SrS correlated with contractility, SrIVR with active relaxation, while in T2DM SrE was related to cardiac stiffness, cardiomyocyte diameter and fibrosis. Strain and strain rate parameters can be valuable and feasible measures to describe the dynamic changes in contractility, active relaxation and LV stiffness in animal models of T1DM and T2DM. STE corresponds to PV analysis and also correlates with markers of histological myocardial remodeling.

Detection of desmoplastic melanoma with dermoscopy and reflectance confocal microscopy.

PubMed

Maher, N G; Solinas, A; Scolyer, R A; Puig, S; Pellacani, G; Guitera, P

2017-12-01

Desmoplastic melanoma (DM) is frequently misdiagnosed clinically and often associated with melanoma in situ (MIS). To improve the detection of DM using dermoscopy and reflectance confocal microscopy (RCM). A descriptive analysis of DM dermoscopy features and a case-control study within a melanoma population for RCM feature evaluation was performed blindly, using data obtained between 2005 and 2015. After retrospectively identifying all DM cases with RCM data over the study period (n = 16), a control group of non-DM melanoma patients with RCM data, in a ratio of at least 3 : 1, was selected. The control group was matched by age and primary tumour site location, divided into non-DM invasive melanomas (n = 27) and MIS (n = 27). Invasive melanomas were selected according to the melanoma subtypes associated with the DM cases. The main outcomes were the frequency of melanoma-specific features on dermoscopy for DM; and the odds ratios of RCM features to distinguish DM from MIS and/or other invasive melanomas; or MIS from the combined invasive melanoma group. At least one of the 14 melanoma-specific features evaluated on dermoscopy was found in 100% of DMs (n = 15 DM with dermoscopy). Known RCM melanoma predictors were commonly found in the DMs, such as pagetoid cells (100%) and cell atypia (100%). The RCM feature of spindle cells in the superficial dermis was more common in DM compared with the entire melanoma control group (OR 3.82, 95% CI 1.01-14.90), and particularly compared to MIS (OR 5.48, 95% CI 1.11-32.36). Nucleated cells in the dermis and the RCM correlate of dermal inflammation were also significant RCM features favouring DM over MIS, as well as invasive melanoma over MIS. Dermoscopy and RCM may be useful tools for the identification of DM. Certain RCM features may help distinguish DM from MIS and other invasive melanomas. Larger studies are warranted. © 2017 European Academy of Dermatology and Venereology.

Can the Direct Medical Cost of Chronic Disease Be Transferred across Different Countries? Using Cost-of-Illness Studies on Type 2 Diabetes, Epilepsy and Schizophrenia as Examples

PubMed Central

Gao, Lan; Hu, Hao; Zhao, Fei-Li; Li, Shu-Chuen

2016-01-01

Objectives To systematically review cost of illness studies for schizophrenia (SC), epilepsy (EP) and type 2 diabetes mellitus (T2DM) and explore the transferability of direct medical cost across countries. Methods A comprehensive literature search was performed to yield studies that estimated direct medical costs. A generalized linear model (GLM) with gamma distribution and log link was utilized to explore the variation in costs that accounted by the included factors. Both parametric (Random-effects model) and non-parametric (Boot-strapping) meta-analyses were performed to pool the converted raw cost data (expressed as percentage of GDP/capita of the country where the study was conducted). Results In total, 93 articles were included (40 studies were for T2DM, 34 studies for EP and 19 studies for SC). Significant variances were detected inter- and intra-disease classes for the direct medical costs. Multivariate analysis identified that GDP/capita (p<0.05) was a significant factor contributing to the large variance in the cost results. Bootstrapping meta-analysis generated more conservative estimations with slightly wider 95% confidence intervals (CI) than the parametric meta-analysis, yielding a mean (95%CI) of 16.43% (11.32, 21.54) for T2DM, 36.17% (22.34, 50.00) for SC and 10.49% (7.86, 13.41) for EP. Conclusions Converting the raw cost data into percentage of GDP/capita of individual country was demonstrated to be a feasible approach to transfer the direct medical cost across countries. The approach from our study to obtain an estimated direct cost value along with the size of specific disease population from each jurisdiction could be used for a quick check on the economic burden of particular disease for countries without such data. PMID:26814959

On the evolution process of two-component dark matter in the Sun

NASA Astrophysics Data System (ADS)

Chen, Chian-Shu; Lin, Yen-Hsun

2018-04-01

We introduce dark matter (DM) evolution process in the Sun under a two-component DM (2DM) scenario. Both DM species χ and ξ with masses heavier than 1 GeV are considered. In this picture, both species could be captured by the Sun through DM-nucleus scattering and DM self-scatterings, e.g. χχ and ξξ collisions. In addition, the heterogeneous self-scattering due to χ and ξ collision is essentially possible in any 2DM models. This new introduced scattering naturally weaves the evolution processes of the two DM species that was assumed to evolve independently. Moreover, the heterogeneous self-scattering enhances the number of DM being captured in the Sun mutually. This effect significantly exists in a broad range of DM mass spectrum. We have studied this phenomena and its implication for the solar-captured DM annihilation rate. It would be crucial to the DM indirect detection when the two masses are close. General formalism of the 2DM evolution in the Sun as well as its kinematics are studied.

Anomaly Detection Techniques for the Condition Monitoring of Tidal Turbines

DTIC Science & Technology

2014-09-29

particularly beneficial to this industry. This paper explores the use of the CRISP - DM data mining process model for identifying key trends within...within tidal turbines with limited historical data. Using the CRISP - DM data mining methodology (Wirth & Hipp, 2000), key relationships between...indicate a change in the response of the system, indicating the possible onset of a fault. 1.2.1. CRISP - DM The CRISP - DM (Cross-Industry Standard

Detecting ultralight bosonic dark matter via absorption in superconductors

DOE PAGES

Hochberg, Yonit; Lin, Tongyan; Zurek, Kathryn M.

2016-07-18

Superconducting targets have recently been proposed for the direct detection of dark matter as light as a keV, via elastic scattering off conduction electrons in Cooper pairs. Detecting such light dark matter requires sensitivity to energies as small as the superconducting gap of O(meV). Here we show that these same superconducting devices can detect much lighter DM, of meV to eV mass, via dark matter absorption on a conduction electron, followed by emission of an athermal phonon. Lastly, we demonstrate the power of this setup for relic kinetically mixed hidden photons, pseudoscalars, and scalars, showing that the reach can exceedmore » current astrophysical and terrestrial constraints with only a moderate exposure.« less

LC-MS/MS method for the simultaneous determination of Lys-MCC-DM1, MCC-DM1 and DM1 as potential intracellular catabolites of the antibody-drug conjugate trastuzumab emtansine (T-DM1).

PubMed

Liu, Yazhong; Zhou, Fang; Sang, Hua; Ye, Hui; Chen, Qianying; Yao, Lan; Ni, Ping; Wang, Guangji; Zhang, Jingwei

2017-04-15

Lysine-MCC-DM1, MCC-DM1 and DM1 are potential catabolites of trastuzumab emtansine (T-DM1). A convenient liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to detect these catabolites simultaneously in in vitro investigations for the first time. Protein precipitation was utilized to prepare the samples. Chromatographic separation was achieved on a Phenomenex Kinetex C18 column (100×2.1mm, 2.6μm) with mobile-phase gradient elution. The calibration curves of each analyte ranging from 1 to 100nM showed good linearity (r 2 >0.995). The method was validated successfully and applied to the intracellular catabolism and regulation of T-DM1. Copyright © 2017 Elsevier B.V. All rights reserved.

Resting-state EEG coupling analysis of amnestic mild cognitive impairment with type 2 diabetes mellitus by using permutation conditional mutual information.

PubMed

Wen, Dong; Bian, Zhijie; Li, Qiuli; Wang, Lei; Lu, Chengbiao; Li, Xiaoli

2016-01-01

This study was meant to explore whether the coupling strength and direction of resting-state electroencephalogram (rsEEG) could be used as an indicator to distinguish the patients of type 2 diabetes mellitus (T2DM) with or without amnestic mild cognitive impairment (aMCI). Permutation conditional mutual information (PCMI) was used to calculate the coupling strength and direction of rsEEG signals between different brain areas of 19 aMCI and 20 normal control (NC) with T2DM on 7 frequency bands: Delta, Theta, Alpha1, Alpha2, Beta1, Beta2 and Gamma. The difference in coupling strength or direction of rsEEG between two groups was calculated. The correlation between coupling strength or direction of rsEEG and score of different neuropsychology scales were also calculated. We have demonstrated that PCMI can calculate effectively the coupling strength and directionality of EEG signals between different brain regions. The significant difference in coupling strength and directionality of EEG signals was found between the patients of aMCI and NC with T2DM on different brain regions. There also existed significant correlation between sex or age and coupling strength or coupling directionality of EEG signals between a few different brain regions from all subjects. The coupling strength or directionality of EEG signals calculated by PCMI are significantly different between aMCI and NC with T2DM. These results showed that the coupling strength or directionality of EEG signals calculated by PCMI might be used as a biomarker in distinguishing the aMCI from NC with T2DM. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Detection of Verticillium wilt of olive trees and downy mildew of opium poppy using hyperspectral and thermal UAV imagery

NASA Astrophysics Data System (ADS)

Calderón Madrid, Rocío; Navas Cortés, Juan Antonio; Montes Borrego, Miguel; Landa del Castillo, Blanca Beatriz; Lucena León, Carlos; Jesús Zarco Tejada, Pablo

2014-05-01

The present study explored the use of high-resolution thermal, multispectral and hyperspectral imagery as indicators of the infections caused by Verticillium wilt (VW) in olive trees and downy mildew (DM) in opium poppy fields. VW, caused by the soil-borne fungus Verticillium dahliae, and DM, caused by the biotrophic obligate oomycete Peronospora arborescens, are the most economically limiting diseases of olive trees and opium poppy, respectively, worldwide. V. dahliae infects the plant by the roots and colonizes its vascular system, blocking water flow and eventually inducing water stress. P. arborescens colonizes the mesophyll, appearing the first symptoms as small chlorotic leaf lesions, which can evolve to curled and thickened tissues and systemic infections that become deformed and necrotic as the disease develops. The work conducted to detect VW and DM infection consisted on the acquisition of time series of airborne thermal, multispectral and hyperspectral imagery using 2-m and 5-m wingspan electric Unmanned Aerial Vehicles (UAVs) in spring and summer of three consecutive years (2009 to 2011) for VW detection and on three dates in spring of 2009 for DM detection. Two 7-ha commercial olive orchards naturally infected with V. dahliae and two opium poppy field plots artificially infected by P. arborescens were flown. Concurrently to the airborne campaigns, olive orchards and opium poppy fields were assessed "in situ" to assess actual VW severity and DM incidence. Furthermore, field measurements were conducted at leaf and crown level. The field results related to VW detection showed a significant increase in crown temperature (Tc) minus air temperature (Ta) and a decrease in leaf stomatal conductance (G) as VW severity increased. This reduction in G was associated with a significant increase in the Photochemical Reflectance Index (PRI570) and a decrease in chlorophyll fluorescence. DM asymptomatic leaves showed significantly higher NDVI and lower green/red index (R550/R670) values than DM symptomatic leaves. The airborne flights enabled the early detection of VW by using canopy-level image-derived airborne Tc-Ta, Crop Water Stress Index (CWSI) calculated from the thermal imagery, blue / green / red ratios (B/BG/BR indices) and chlorophyll fluorescence. The detection of DM infection was achieved by using image-derived Tc-Ta and R550/R670 as a function of aggregated NDVI clusters to compare asymptomatic and symptomatic plants normalized by similar growth levels. These results revealed the potential of high-resolution thermal, multispectral and hyperspectral imagery acquired from UAVs to detect olive trees infected with V. dahliae at early stages of disease development and occurrence of P. arborescens infection in opium poppy fields.

From quarks to nucleons in dark matter direct detection

NASA Astrophysics Data System (ADS)

Bishara, Fady; Brod, Joachim; Grinstein, Benjamin; Zupan, Jure

2017-11-01

We provide expressions for the nonperturbative matching of the effective field theory describing dark matter interactions with quarks and gluons to the effective theory of nonrelativistic dark matter interacting with nonrelativistic nucleons. We give expressions of leading and subleading order in chiral counting. In general, a single partonic operator matches onto several nonrelativistic operators already at leading order in chiral counting. Keeping only one operator at the time in the nonrelativistic effective theory thus does not properly describe the scattering in direct detection. The matching of the axial-axial partonic level operator, as well as the matching of the operators coupling DM to the QCD anomaly term, include naively momentum suppressed terms. However, these are still of leading chiral order due to pion poles and can be numerically important.

Maternal components of RNA-directed DNA methylation are required for seed development in Brassica rapa.

PubMed

Grover, Jeffrey W; Kendall, Timmy; Baten, Abdul; Burgess, Diane; Freeling, Michael; King, Graham J; Mosher, Rebecca A

2018-05-01

Small RNAs trigger repressive DNA methylation at thousands of transposable elements in a process called RNA-directed DNA methylation (RdDM). The molecular mechanism of RdDM is well characterized in Arabidopsis, yet the biological function remains unclear, as loss of RdDM in Arabidopsis causes no overt defects, even after generations of inbreeding. It is known that 24 nucleotide Pol IV-dependent siRNAs, the hallmark of RdDM, are abundant in flowers and developing seeds, indicating that RdDM might be important during reproduction. Here we show that, unlike Arabidopsis, mutations in the Pol IV-dependent small RNA pathway cause severe and specific reproductive defects in Brassica rapa. High rates of abortion occur when seeds have RdDM mutant mothers, but not when they have mutant fathers. Although abortion occurs after fertilization, RdDM function is required in maternal somatic tissue, not in the female gametophyte or the developing zygote, suggesting that siRNAs from the maternal soma might function in filial tissues. We propose that recently outbreeding species such as B. rapa are key to understanding the role of RdDM during plant reproduction. © 2018 The Authors The Plant Journal © 2018 John Wiley & Sons Ltd.

Evaluation of the Finnish Diabetes Risk Score to predict type 2 diabetes mellitus in a Colombian population: A longitudinal observational study.

PubMed

Gomez-Arbelaez, Diego; Alvarado-Jurado, Laura; Ayala-Castillo, Miguel; Forero-Naranjo, Leonardo; Camacho, Paul Anthony; Lopez-Jaramillo, Patricio

2015-12-10

To assess the performance of the Finnish Diabetes Risk Score (FINDRISC) questionnaire for detecting and predicting type 2 diabetes mellitus (DM2) in a Colombian population. This is a longitudinal observational study conducted in Floridablanca, Colombia. Adult subjects (age ≥ 35 years) without known diabetes, were included. A modified version of FINDRISC was completed, and the glycemia values from all the subjects were collected from the hospital's database. Firstly, a cross-sectional analysis was performed and then, the subsample of prediabetic participants was followed for diabetes incidence. A total of 772 subjects were suitable for the study. The overall prevalence of undiagnosed DM2 was 2.59%, and the incidence of DM2 among the prediabetic participants was 7.5 per 100 person-years after a total of 265257 person-years follow-up. The FINDRISC at baseline was significantly associated with undiagnosed and incident DM2. The area under receiver operating characteristics curve of the FINDRISC score for detecting undiagnosed DM2 in both men and women was 0.7477 and 0.7175, respectively; and for predicting the incidence of DM2 among prediabetics was 71.99% in men and 67.74% in women. The FINDRISC questionnaire is a useful screening tool to identify cross-sectionally unknown DM2 and to predict the incidence of DM2 among prediabetics in the Colombian population.

Characterization and photochemistry of 13-desmethyl bacteriorhodopsin.

PubMed

Gillespie, Nathan B; Ren, Lei; Ramos, Lavoisier; Daniell, Heather; Dews, Deborah; Utzat, Karissa A; Stuart, Jeffrey A; Buck, Charles H; Birge, Robert R

2005-08-25

The photochemistry of the 13-desmethyl (DM) analogue of bacteriorhodopsin (BR) is examined by using spectroscopy, molecular orbital theory, and chromophore extraction followed by conformational analysis. The removal of the 13-methyl group permits the direct photochemical formation of a thermally stable, photochemically reversible state, P1(DM) (lambda(max) = 525 nm), which can be generated efficiently by exciting the resting state, bR(DM) with yellow or red light (lambda > 590 nm). Chromophore extraction analysis reveals that the retinal configuration in P1(DM) is 9-cis, identical to that of the retinal configuration in the native BR P1 state. Fourier transform infrared and Raman experiments on P1(DM) indicate an anti configuration around the C15=N bond, as would be expected of an O-state photoproduct. However, low-temperature spectroscopy and ambient, time-resolved studies indicate that the P1(DM) state forms primarily via thermal relaxation from the L(D)(DM) state. Theoretical studies on the BR binding site show that 13-dm retinal is capable of isomerizing into a 9-cis configuration with minimal steric hindrance from surrounding residues, in contrast to the native chromophore in which surrounding residues significantly obstruct the corresponding motion. Analysis of the photokinetic experiments indicates that the Arrhenius activation energy of the bR(DM) --> P1(DM) transition in 13-dm-BR is less than 0.6 kcal/mol (vs 22 +/-5 kcal/mol measured for the bR --> P (P1 and P2) reaction in 85:15 glycerol:water suspensions of wild type). Consequently, the P1(DM) state in 13-dm-BR can form directly from all-trans, 15-anti intermediates (bR(DM) and O(DM)) or all-trans, 15-syn (K(D)(DM)/L(D)(DM)) intermediates. This study demonstrates that the 13-methyl group, and its interactions with nearby binding site residues, is primarily responsible for channeling one-photon photochemical and thermal reactions and is limited to the all-trans and 13-cis species interconversions in the native protein.

Hidden charged dark matter and chiral dark radiation

NASA Astrophysics Data System (ADS)

Ko, P.; Nagata, Natsumi; Tang, Yong

2017-10-01

In the light of recent possible tensions in the Hubble constant H0 and the structure growth rate σ8 between the Planck and other measurements, we investigate a hidden-charged dark matter (DM) model where DM interacts with hidden chiral fermions, which are charged under the hidden SU(N) and U(1) gauge interactions. The symmetries in this model assure these fermions to be massless. The DM in this model, which is a Dirac fermion and singlet under the hidden SU(N), is also assumed to be charged under the U(1) gauge symmetry, through which it can interact with the chiral fermions. Below the confinement scale of SU(N), the hidden quark condensate spontaneously breaks the U(1) gauge symmetry such that there remains a discrete symmetry, which accounts for the stability of DM. This condensate also breaks a flavor symmetry in this model and Nambu-Goldstone bosons associated with this flavor symmetry appear below the confinement scale. The hidden U(1) gauge boson and hidden quarks/Nambu-Goldstone bosons are components of dark radiation (DR) above/below the confinement scale. These light fields increase the effective number of neutrinos by δNeff ≃ 0.59 above the confinement scale for N = 2, resolving the tension in the measurements of the Hubble constant by Planck and Hubble Space Telescope if the confinement scale is ≲1 eV. DM and DR continuously scatter with each other via the hidden U(1) gauge interaction, which suppresses the matter power spectrum and results in a smaller structure growth rate. The DM sector couples to the Standard Model sector through the exchange of a real singlet scalar mixing with the Higgs boson, which makes it possible to probe our model in DM direct detection experiments. Variants of this model are also discussed, which may offer alternative ways to investigate this scenario.

The Role of HLA Class I Gene Variation in Autoimmune Diabetes

PubMed Central

Sia, Charles; Weinem, Michael

2005-01-01

The use of DNA-based genetic typing has enabled the identification of type 1 diabetes mellitus (T1DM) susceptible and protective major histocompatibility complex (MHC) class II alleles and haplotypes. The application of this approach has also progressed to locate MHC class I alleles that contribute to the clinicopathology of T1DM. Recent studies have shown a widespread involvement of genes from the MHC class I gene region in the clinicopathology of T1DM. These genes are shown to be involved in contributing to progression from the preclinical stage of the disease, which is characterized by the occurrence of islet-specific antibodies, to clinical disease and also to the occurrence of autoimmunity. They can either contribute directly to disease development or indirectly in concert with other susceptible MHC class II alleles or haplotypes via linkage disequilibrium. Class I alleles may also be negatively associated with T1DM. These findings are useful for the development of future strategies in designing tolerogenic approaches for the prevention or even reversal of T1DM. In this article, the latest evidence for the different kinds of participation of HLA class I genes in the etiology of T1DM is reviewed. A meta-analysis which included existing association studies was also carried out in order to re-assess the relevance of class I genes in diabetes development. The analysis of an enlarged heterogeneous sample confirmed the involvement of previously detected serotypes in the etiology of T1DM, such as A24, B8 and B18, and revealed hitherto unknown associations with B60 and B62. The analysis points out that much of the conflicting results of previous association studies originate from inadequate sample sizes and accentuate the value of future investigations of larger samples for identifying linkage in multigenic diseases. PMID:17491685

Relationship between Tumor Biomarkers and Efficacy in EMILIA, a Phase III Study of Trastuzumab Emtansine in HER2-Positive Metastatic Breast Cancer.

PubMed

Baselga, José; Lewis Phillips, Gail D; Verma, Sunil; Ro, Jungsil; Huober, Jens; Guardino, Alice E; Samant, Meghna K; Olsen, Steve; de Haas, Sanne L; Pegram, Mark D

2016-08-01

HER2-positive breast cancer is heterogeneous. Some tumors express mutations, like activating PIK3CA mutations or reduced PTEN expression, that negatively correlate with response to HER2-targeted therapies. In this exploratory analysis, we investigated whether the efficacy of trastuzumab emtansine (T-DM1), an antibody-drug conjugate comprised of the cytotoxic agent DM1 linked to the HER2-targeted antibody trastuzumab, was correlated with the expression of specific biomarkers in the phase III EMILIA study. Tumors were evaluated for HER2 (n = 866), EGFR (n = 832), and HER3 (n = 860) mRNA expression by quantitative reverse transcriptase PCR; for PTEN protein expression (n = 271) by IHC; and for PIK3CA mutations (n = 259) using a mutation detection kit. Survival outcomes were analyzed by biomarker subgroups. T-DM1 was also tested on cell lines and in breast cancer xenograft models containing PIK3CA mutations. Longer progression-free survival (PFS) and overall survival (OS) were observed with T-DM1 compared with capecitabine plus lapatinib in all biomarker subgroups. PIK3CA mutations were associated with shorter median PFS (mutant vs. wild type: 4.3 vs. 6.4 months) and OS (17.3 vs. 27.8 months) in capecitabine plus lapatinib-treated patients, but not in T-DM1-treated patients (PFS, 10.9 vs. 9.8 months; OS, not reached in mutant or wild type). T-DM1 showed potent activity in cell lines and xenograft models with PIK3CA mutations. Although other standard HER2-directed therapies are less effective in tumors with PI3KCA mutations, T-DM1 appears to be effective in both PI3KCA-mutated and wild-type tumors. Clin Cancer Res; 22(15); 3755-63. ©2016 AACR. ©2016 American Association for Cancer Research.

Upregulation of Interleukin 21 and Interleukin 21 Receptor in Patients with Dermatomyositis and Polymyositis.

PubMed

Liu, Tao; Hou, Ying; Dai, Ting-Jun; Yan, Chuan-Zhu

2017-09-05

The immunopathologic mechanism underlying dermatomyositis (DM) and polymyositis (PM) remains poorly understood. Many cytokines play a pathogenic role in DM and PM. Interleukin 21 (IL-21) has a pleiotropic effect on inflammation regulation. This study aimed to detect the serum IL-21 level and investigate the expression of IL-21 and IL-21 receptor (IL-21R) in muscle tissues of patients with DM and PM. Biopsied muscle samples were obtained from 11 patients with DM, 12 with PM, and six controls; mRNA levels of IL-21 and IL-21R were analyzed by real-time quantitative reverse transcription-polymerase chain reaction; and immunohistochemical staining was used to evaluate the protein expression of IL-21 and IL-21R. Serum samples were obtained from 36 patients with DM, 19 with PM, and 20 healthy controls. The serum IL-21 level was detected by enzyme-linked immunosorbent assay. The expression of IL-21 was upregulated in patients with DM and PM. The IL-21 mRNA level was significantly increased in muscle tissues of patients with DM and PM (DM vs. control, P= 0.001; PM vs. control, P= 0.001), whereas IL-21R mRNA level in patients with DM/PM was not statistically different from that of healthy controls. Immunohistochemical staining showed both IL-21 and IL-21R were significantly expressed in the inflammatory cells in muscle tissues of patients with DM and PM. The serum IL-21 level was also significantly higher in patients with DM/PM than in controls (DM vs. control, 49.12 [45.28, 60.07] pg/ml vs. 42.54 [38.69, 48.85] pg/ml, P= 0.001; PM vs. control, 50.77 [44.19, 60.62] pg/ml vs. 42.54 [38.69, 48.85] pg/ml, P= 0.005). IL-21 expression is upregulated in patients with DM and PM in both muscle tissue and serum. In addition, IL-21R protein is highly expressed in affected muscle tissues of patients with DM and PM. IL-21 may play a pathogenic role through IL-21R in patients with DM and PM.

Multipartite interacting scalar dark matter in the light of updated LUX data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhattacharya, Subhaditya; Ghosh, Purusottam; Poulose, Poulose, E-mail: subhab@iitg.ernet.in, E-mail: p.ghosh@iitg.ernet.in, E-mail: poulose@iitg.ernet.in

2017-04-01

We explore constraints on multipartite dark matter (DM) framework composed of singlet scalar DM interacting with the Standard Model (SM) through Higgs portal coupling. We compute relic density and direct search constraints including the updated LUX bound for two component scenario with non-zero interactions between two DM components in Z{sub 2} × Z{sub 2}{sup '} framework in comparison with the one having O(2) symmetry. We point out availability of a significantly large region of parameter space of such a multipartite model with DM-DM interactions.

Rationale and design of the ADDITION-Leicester study, a systematic screening programme and Randomised Controlled Trial of multi-factorial cardiovascular risk intervention in people with Type 2 Diabetes Mellitus detected by screening

PubMed Central

2010-01-01

Background Earlier diagnosis followed by multi-factorial cardiovascular risk intervention may improve outcomes in Type 2 Diabetes Mellitus (T2DM). Latent phase identification through screening requires structured, appropriately targeted population-based approaches. Providers responsible for implementing screening policy await evidence of clinical and cost effectiveness from randomised intervention trials in screen-detected T2DM cases. UK South Asians are at particularly high risk of abnormal glucose tolerance and T2DM. To be effective national screening programmes must achieve good coverage across the population by identifying barriers to the detection of disease and adapting to the delivery of earlier care. Here we describe the rationale and methods of a systematic community screening programme and randomised controlled trial of cardiovascular risk management within a UK multiethnic setting (ADDITION-Leicester). Design A single-blind cluster randomised, parallel group trial among people with screen-detected T2DM comparing a protocol driven intensive multi-factorial treatment with conventional care. Methods ADDITION-Leicester consists of community-based screening and intervention phases within 20 general practices coordinated from a single academic research centre. Screening adopts a universal diagnostic approach via repeated 75g-Oral Glucose Tolerance Tests within an eligible non-diabetic population of 66,320 individuals aged 40-75 years (25-75 years South Asian). Volunteers also provide detailed medical and family histories; complete health questionnaires, undergo anthropometric measures, lipid profiling and a proteinuria assessment. Primary outcome is reduction in modelled Coronary Heart Disease (UKPDS CHD) risk at five years. Seven thousand (30% of South Asian ethnic origin) volunteers over three years will be recruited to identify a screen-detected T2DM cohort (n = 285) powered to detected a 6% relative difference (80% power, alpha 0.05) between treatment groups at one year. Randomisation will occur at practice-level with newly diagnosed T2DM cases receiving either conventional (according to current national guidelines) or intensive (algorithmic target-driven multi-factorial cardiovascular risk intervention) treatments. Discussion ADDITION-Leicester is the largest multiethnic (targeting >30% South Asian recruitment) community T2DM and vascular risk screening programme in the UK. By assessing feasibility and efficacy of T2DM screening, it will inform national disease prevention policy and contribute significantly to our understanding of the health care needs of UK South Asians. Trial registration Clinicaltrial.gov (NCT00318032). PMID:20170482

Freeze-in production of sterile neutrino dark matter in U(1){sub B−L} model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Biswas, Anirban; Gupta, Aritra

2016-09-27

With the advent of new and more sensitive direct detection experiments, scope for a thermal WIMP explanation of dark matter (DM) has become extremely constricted. The non-observation of thermal WIMP in these experiments has put a strong upper bound on WIMP-nucleon scattering cross section and within a few years it is likely to overlap with the coherent neutrino-nucleon cross section. Hence in all probability, DM may have some non-thermal origin. In this work we explore in detail this possibility of a non-thermal sterile neutrino DM within the framework of U(1){sub B−L} model. The U(1){sub B−L} model on the other handmore » is a well-motivated and minimal way of extending the standard model so that it can explain the neutrino masses via Type-I see-saw mechanism. We have shown, besides explaining the neutrino mass, it can also accommodate a non-thermal sterile neutrino DM with correct relic density. In contrast with the existing literature, we have found that W{sup ±} decay can also be a dominant production mode of the sterile neutrino DM. To obtain the comoving number density of dark matter, we have solved here a coupled set of Boltzmann equations considering all possible decay as well as annihilation production modes of the sterile neutrino dark matter. The framework developed here though has been done for a U(1){sub B−L} model, can be applied quite generally for any models with an extra neutral gauge boson and a fermionic non-thermal dark matter.« less

Assessment of disease extent on contrast-enhanced MRI in breast cancer detected at digital breast tomosynthesis versus digital mammography alone.

PubMed

Chudgar, A V; Conant, E F; Weinstein, S P; Keller, B M; Synnestvedt, M; Yamartino, P; McDonald, E S

2017-07-01

To compare the utility of breast magnetic resonance imaging (MRI) in determining the extent of disease in patients with newly diagnosed breast cancer detected on combination digital breast tomosynthesis (DBT) versus digital screening mammography (DM). Review of 24,563 DBT-screened patients and 10,751 DM-screened patients was performed. Two hundred and thirty-five DBT patients underwent subsequent MRI examinations; 82 to determine extent of disease after newly diagnosed breast cancer. Eighty-three DM patients underwent subsequent MRI examinations; 23 to determine extent of disease. MRI examinations performed to assess disease extent were considered true positives if additional disease was discovered in the contralateral breast or >2 cm away from the index malignancy. Differences in cancer subtypes and MRI outcomes between the DM and DBT cohorts were compared using chi-squared tests and post-hoc Bonferroni-adjusted tests for equal proportions. No differences in cancer subtype findings were observed between the two cohorts; however, MRI outcomes were found to differ between the DBT and DM cohorts (p=0.024). Specifically, the DBT cohort had significantly (p=0.013) fewer true-positive findings (7/82, 8.5%) than did the DM cohort (7/23; 30%), whereas the false-positive rate was similar between the cohorts (not statistically significant). When stratifying by breast density, this difference in true-positive rates was primarily observed when evaluating women with non-dense breasts (p=0.001). In both the DM- and DBT-screened populations with new cancer diagnoses, MRI is able to detect additional cancer; however, in those patients who have DBT screen-detected cancers the positive impact of preoperative MRI is diminished, particularly in those women with non-dense breasts. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Effects of streptozotocin-induced diabetes on taste buds in rat vallate papillae.

PubMed

Pai, Man-Hui; Ko, Tsui-Ling; Chou, Hsiu-Chu

2007-01-01

Some studies have documented taste changes in patients with diabetes mellitus (DM). In order to understand the relationships between taste disorders caused by DM and the innervation and morphologic changes in the taste buds, we studied the vallate papillae and their taste buds in rats with DM. DM was induced in these rats with streptozotocin (STZ), which causes the death of beta cells of the pancreas. The rats were sacrificed and the vallate papillae were dissected for morphometric and quantitative immunohistochemical analyses. The innervations of the vallate papillae and taste buds in diabetic and control rats were detected using immunohistochemistry employing antibodies directed against protein gene product 9.5 (PGP 9.5) and calcitonin gene-related peptide (CGRP). The results showed that PGP 9.5- and CGRP-immunoreactive nerve fibers in the trench wall of diabetic vallate papillae, as well as taste cells in the taste buds, gradually decreased both intragemmally and intergemmally. The morphometry revealed no significant difference in papilla size between the control and diabetic groups, but there were fewer taste buds per papilla (per animal). The quantification of innervation in taste buds of the diabetic rats supported the visual assessment of immunohistochemical labeling, that the innervation of taste cells was significantly reduced in diabetic animals. These findings suggest that taste impairment in diabetic subjects may be caused by neuropathy defects and/or morphological changes in the taste buds.

Chemical and microbiological hazards associated with recycling of anaerobic digested residue intended for agricultural use

DOE Office of Scientific and Technical Information (OSTI.GOV)

Govasmark, Espen, E-mail: espen.govasmark@bioforsk.no; Staeb, Jessica; Holen, Borge

2011-12-15

In the present study, three full-scale biogas plants (BGP) were investigated for the concentration of heavy metals, organic pollutants, pesticides and the pathogenic bacteria Bacillus cereus and Escherichia coli in the anaerobically digested residues (ADR). The BGPs mainly utilize source-separated organic wastes and industrial food waste as energy sources and separate the ADR into an ADR-liquid and an ADR-solid fraction by centrifugation at the BGP. According to the Norwegian standard for organic fertilizers, the ADR were classified as quality 1 mainly because of high zinc (132-422 mg kg{sup -1} DM) and copper (23-93 mg kg{sup -1} DM) concentrations, but alsomore » because of high cadmium (0.21-0.60 mg kg{sup -1} DM) concentrations in the liquid-ADR. In the screening of organic pollutants, only DEHP (9.7-62.1 mg kg{sup -1}) and {Sigma} PAH 16 (0.2-1.98 mg kg{sup -1} DM) were detected in high concentrations according to international regulations. Of the 250 pesticides analyzed, 11 were detected, but only imazalil (<0.30-5.77 mg kg{sup -1} DM) and thiabendazol (<0.14-0.73 mg kg{sup -1} DM) were frequently detected in the ADR-fiber. Concentrations of imazalil and thiabendazol were highest during the winter months, due to a high consumption of citrus fruits in Norway in this period. Ten percent of the ADR-liquid samples contained cereulide-producing B. cereus, whereas no verotoxigenic E. coli was detected. The authors conclude that the risk of chemical and bacterial contamination of the food chain or the environment from agricultural use of ADR seems low.« less

Chemical and microbiological hazards associated with recycling of anaerobic digested residue intended for agricultural use.

PubMed

Govasmark, Espen; Stäb, Jessica; Holen, Børge; Hoornstra, Douwe; Nesbakk, Tommy; Salkinoja-Salonen, Mirja

2011-12-01

In the present study, three full-scale biogas plants (BGP) were investigated for the concentration of heavy metals, organic pollutants, pesticides and the pathogenic bacteria Bacillus cereus and Escherichia coli in the anaerobically digested residues (ADR). The BGPs mainly utilize source-separated organic wastes and industrial food waste as energy sources and separate the ADR into an ADR-liquid and an ADR-solid fraction by centrifugation at the BGP. According to the Norwegian standard for organic fertilizers, the ADR were classified as quality 1 mainly because of high zinc (132-422 mg kg(-1) DM) and copper (23-93 mg kg(-1) DM) concentrations, but also because of high cadmium (0.21-0.60 mg kg(-1) DM) concentrations in the liquid-ADR. In the screening of organic pollutants, only DEHP (9.7-62.1 mg kg(-1)) and ∑ PAH 16 (0.2-1.98 mg kg(-1) DM) were detected in high concentrations according to international regulations. Of the 250 pesticides analyzed, 11 were detected, but only imazalil (<0.30-5.77 mg kg(-1) DM) and thiabendazol (<0.14-0.73 mg kg(-1) DM) were frequently detected in the ADR-fiber. Concentrations of imazalil and thiabendazol were highest during the winter months, due to a high consumption of citrus fruits in Norway in this period. Ten percent of the ADR-liquid samples contained cereulide-producing B. cereus, whereas no verotoxigenic E. coli was detected. The authors conclude that the risk of chemical and bacterial contamination of the food chain or the environment from agricultural use of ADR seems low. Copyright © 2011 Elsevier Ltd. All rights reserved.

The Initiation of Epigenetic Silencing of Active Transposable Elements Is Triggered by RDR6 and 21-22 Nucleotide Small Interfering RNAs1[W][OA

PubMed Central

Nuthikattu, Saivageethi; McCue, Andrea D.; Panda, Kaushik; Fultz, Dalen; DeFraia, Christopher; Thomas, Erica N.; Slotkin, R. Keith

2013-01-01

Transposable elements (TEs) are mobile fragments of DNA that are repressed in both plant and animal genomes through the epigenetic inheritance of repressed chromatin and expression states. The epigenetic silencing of TEs in plants is mediated by a process of RNA-directed DNA methylation (RdDM). Two pathways of RdDM have been identified: RNA Polymerase IV (Pol IV)-RdDM, which has been shown to be responsible for the de novo initiation, corrective reestablishment, and epigenetic maintenance of TE and/or transgene silencing; and RNA-dependent RNA Polymerase6 (RDR6)-RdDM, which was recently identified as necessary for maintaining repression for a few TEs. We have further characterized RDR6-RdDM using a genome-wide search to identify TEs that generate RDR6-dependent small interfering RNAs. We have determined that TEs only produce RDR6-dependent small interfering RNAs when transcriptionally active, and we have experimentally identified two TE subfamilies as direct targets of RDR6-RdDM. We used these TEs to test the function of RDR6-RdDM in assays for the de novo initiation, corrective reestablishment, and maintenance of TE silencing. We found that RDR6-RdDM plays no role in maintaining TE silencing. Rather, we found that RDR6 and Pol IV are two independent entry points into RdDM and epigenetic silencing that perform distinct functions in the silencing of TEs: Pol IV-RdDM functions to maintain TE silencing and to initiate silencing in an RNA Polymerase II expression-independent manner, while RDR6-RdDM functions to recognize active Polymerase II-derived TE mRNA transcripts to both trigger and correctively reestablish TE methylation and epigenetic silencing. PMID:23542151

The initiation of epigenetic silencing of active transposable elements is triggered by RDR6 and 21-22 nucleotide small interfering RNAs.

PubMed

Nuthikattu, Saivageethi; McCue, Andrea D; Panda, Kaushik; Fultz, Dalen; DeFraia, Christopher; Thomas, Erica N; Slotkin, R Keith

2013-05-01

Transposable elements (TEs) are mobile fragments of DNA that are repressed in both plant and animal genomes through the epigenetic inheritance of repressed chromatin and expression states. The epigenetic silencing of TEs in plants is mediated by a process of RNA-directed DNA methylation (RdDM). Two pathways of RdDM have been identified: RNA Polymerase IV (Pol IV)-RdDM, which has been shown to be responsible for the de novo initiation, corrective reestablishment, and epigenetic maintenance of TE and/or transgene silencing; and RNA-dependent RNA Polymerase6 (RDR6)-RdDM, which was recently identified as necessary for maintaining repression for a few TEs. We have further characterized RDR6-RdDM using a genome-wide search to identify TEs that generate RDR6-dependent small interfering RNAs. We have determined that TEs only produce RDR6-dependent small interfering RNAs when transcriptionally active, and we have experimentally identified two TE subfamilies as direct targets of RDR6-RdDM. We used these TEs to test the function of RDR6-RdDM in assays for the de novo initiation, corrective reestablishment, and maintenance of TE silencing. We found that RDR6-RdDM plays no role in maintaining TE silencing. Rather, we found that RDR6 and Pol IV are two independent entry points into RdDM and epigenetic silencing that perform distinct functions in the silencing of TEs: Pol IV-RdDM functions to maintain TE silencing and to initiate silencing in an RNA Polymerase II expression-independent manner, while RDR6-RdDM functions to recognize active Polymerase II-derived TE mRNA transcripts to both trigger and correctively reestablish TE methylation and epigenetic silencing.

Economic implications of type 2 diabetes management.

PubMed

McAdam Marx, Carrie

2013-06-01

Diabetes mellitus (DM) is a complex and progressive disease associated with significant morbidity and mortality. Both the prevalence and economic burden associated with DM have been steadily increasing and are projected to continue to increase. A series of cost reports published by the American Diabetes Association (ADA) between 1997 and 2012 have suggested that direct medical costs are the primary cost driver in DM. Direct costs have increased over 5-fold during this time frame, from $44 billion to $176 billion annually, likely due to both the increased prevalence of DM and increased costs of providing DM-related care. Trends in anti-diabetic medication usage as reported by Centers for Disease Control data from 1997 to 2011 have found that the proportion of diagnosed patients treated for DM has remained fairly stable. However, there has been an increase in the use of oral agents alone, a decrease in patients on insulin only, and a relatively small increase in the percentage of patients using both insulin and oral agents, suggesting stagnation regarding the uptake of insulin use. In parallel, the ADA cost and utilization data suggest that use of medications to treat DM-related comorbidities and complications has risen, which contributes to the risk of medication errors, avoidable adverse drug events, and noncompliance. These data highlight a few of the challenges involved in managing a population of patients with DM. A comprehensive assessment of unmet needs for the population with DM is essential for effective population management. An approach that strives to identify and reduce barriers to patients receiving optimal care and being active participants in their DM management will facilitate systemwide efforts to improve DM outcomes.

Testing light dark matter coannihilation with fixed-target experiments

DOE PAGES

Izaguirre, Eder; Kahn, Yonatan; Krnjaic, Gordan; ...

2017-09-01

In this paper, we introduce a novel program of fixed-target searches for thermal-origin Dark Matter (DM), which couples inelastically to the Standard Model. Since the DM only interacts by transitioning to a heavier state, freeze-out proceeds via coannihilation and the unstable heavier state is depleted at later times. For sufficiently large mass splittings, direct detection is kinematically forbidden and indirect detection is impossible, so this scenario can only be tested with accelerators. Here we propose new searches at proton and electron beam fixed-target experiments to probe sub-GeV coannihilation, exploiting the distinctive signals of up- and downscattering as well as decaymore » of the excited state inside the detector volume. We focus on a representative model in which DM is a pseudo-Dirac fermion coupled to a hidden gauge field (dark photon), which kinetically mixes with the visible photon. We define theoretical targets in this framework and determine the existing bounds by reanalyzing results from previous experiments. We find that LSND, E137, and BaBar data already place strong constraints on the parameter space consistent with a thermal freeze-out origin, and that future searches at Belle II and MiniBooNE, as well as recently-proposed fixed-target experiments such as LDMX and BDX, can cover nearly all remaining gaps. We also briefly comment on the discovery potential for proposed beam dump and neutrino experiments which operate at much higher beam energies.« less

Testing light dark matter coannihilation with fixed-target experiments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Izaguirre, Eder; Kahn, Yonatan; Krnjaic, Gordan

In this paper, we introduce a novel program of fixed-target searches for thermal-origin Dark Matter (DM), which couples inelastically to the Standard Model. Since the DM only interacts by transitioning to a heavier state, freeze-out proceeds via coannihilation and the unstable heavier state is depleted at later times. For sufficiently large mass splittings, direct detection is kinematically forbidden and indirect detection is impossible, so this scenario can only be tested with accelerators. Here we propose new searches at proton and electron beam fixed-target experiments to probe sub-GeV coannihilation, exploiting the distinctive signals of up- and downscattering as well as decaymore » of the excited state inside the detector volume. We focus on a representative model in which DM is a pseudo-Dirac fermion coupled to a hidden gauge field (dark photon), which kinetically mixes with the visible photon. We define theoretical targets in this framework and determine the existing bounds by reanalyzing results from previous experiments. We find that LSND, E137, and BaBar data already place strong constraints on the parameter space consistent with a thermal freeze-out origin, and that future searches at Belle II and MiniBooNE, as well as recently-proposed fixed-target experiments such as LDMX and BDX, can cover nearly all remaining gaps. We also briefly comment on the discovery potential for proposed beam dump and neutrino experiments which operate at much higher beam energies.« less

Testing light dark matter coannihilation with fixed-target experiments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Izaguirre, Eder; Kahn, Yonatan; Krnjaic, Gordan

In this paper, we introduce a novel program of fixed-target searches for thermal-origin Dark Matter (DM), which couples inelastically to the Standard Model. Since the DM only interacts by transitioning to a heavier state, freeze-out proceeds via coannihilation and the unstable heavier state is depleted at later times. For sufficiently large mass splittings, direct detection is kinematically forbidden and indirect detection is impossible, so this scenario can only be tested with accelerators. Here we propose new searches at proton and electron beam fixed-target experiments to probe sub-GeV coannihilation, exploiting the distinctive signals of up- and down-scattering as well as decaymore » of the excited state inside the detector volume. We focus on a representative model in which DM is a pseudo-Dirac fermion coupled to a hidden gauge field (dark photon), which kinetically mixes with the visible photon. We define theoretical targets in this framework and determine the existing bounds by reanalyzing results from previous experiments. We find that LSND, E137, and BaBar data already place strong constraints on the parameter space consistent with a thermal freeze-out origin, and that future searches at Belle II and MiniBooNE, as well as recently-proposed fixed-target experiments such as LDMX and BDX, can cover nearly all remaining gaps. We also briefly comment on the discovery potential for proposed beam dump and neutrino experiments which operate at much higher beam energies.« less

Dark Influences at the Threshold of Galaxy Formation

NASA Astrophysics Data System (ADS)

Boylan-Kolchin, Michael

As the faintest, lowest-luminosity, and most dark-matter-dominated extremes of the galaxy population, dwarf galaxies present unique opportunities for studying galaxy formation and the properties of dark matter. Accordingly, they have been observed in detail from the ground and (by NASA missions) from space with the hopes of unraveling how dwarf galaxies form, the effects of reionization on galaxy formation, and whether signatures of the particle nature of dark matter (DM) interactions can be observed. Such work has gained in importance as efforts to directly detect DM have so far yielded only upper limits to the interaction between DM and normal matter, leaving astrophysical tests as the primary means of investigating the nature of DM. We propose to undertake an extensive yet focused program of cosmological hydrodynamic simulations aimed at understanding the formation of dwarf galaxies. We will focus on the interplay between galaxy formation and dark matter in these galaxies, pointing toward specific observables to disentangle the effects of galaxy formation physics from the effects of DM physics. Our simulation suite will explore collisionless Cold Dark Matter (CDM) and broad classes of alternatives, where DM has a nonnegligible free-streaming length and / or self-scattering cross section. The novel aspects of the proposed work will include: (1) a modern treatment of baryonic physics using GIZMO, a new code that uses accurate meshless methods for hydrodynamics; (2) Feedback In Realistic Environments (FIRE), a suite of galaxy formation parametrizations with well-tested, explicit implementations of stellar feedback; (3) an exploration of realistic models of DM beyond CDM based on an effective theory of structure formation, with full baryonic physics; and (4) detailed mock observations of the simulations in order to identify specific, distinguishing tests for CDM and its alternatives. Our research will provide a framework within which astrophysical inferences about the nature of DM can be fairly and self-consistently tested. Crucially, we will explore uncertain aspects of galaxy formation and DM physics in a controlled manner, focusing on the halo mass range - 9.5 < log10(M/M_sun) < 10.5 - where current models are most uncertain. This will mark a major effort to systematically study different DM models combined with realistic treatments of galaxy formation physics that are implemented in an identical way for the various DM models. The results of the proposed research will be dramatic improvements in the understanding of how baryonic versus DM physics affect astrophysical observables. Such a study is very timely, as observations of dwarf galaxies in and beyond the Local Group have progressed substantially in recent years, with new revelations about dwarfs' DM content, star formation histories, and stellar metallicities challenging previous interpretations.

Particle Dark Matter Searches Outside the Local Group.

PubMed

Regis, Marco; Xia, Jun-Qing; Cuoco, Alessandro; Branchini, Enzo; Fornengo, Nicolao; Viel, Matteo

2015-06-19

If dark matter (DM) is composed by particles which are nongravitationally coupled to ordinary matter, their annihilations or decays in cosmic structures can result in detectable radiation. We show that the most powerful technique to detect a particle DM signal outside the Local Group is to study the angular cross-correlation of nongravitational signals with low-redshift gravitational probes. This method allows us to enhance the signal to noise from the regions of the Universe where the DM-induced emission is preferentially generated. We demonstrate the power of this approach by focusing on GeV-TeV DM and on the recent cross-correlation analysis between the 2MASS galaxy catalogue and the Fermi-LAT γ-ray maps. We show that this technique is more sensitive than other extragalactic γ-ray probes, such as the energy spectrum and angular autocorrelation of the extragalactic background, and emission from clusters of galaxies. Intriguingly, we find that the measured cross-correlation can be well fitted by a DM component, with a thermal annihilation cross section and mass between 10 and 100 GeV, depending on the small-scale DM properties and γ-ray production mechanism. This solicits further data collection and dedicated analyses.

Particle Dark Matter Searches Outside the Local Group

NASA Astrophysics Data System (ADS)

Regis, Marco; Xia, Jun-Qing; Cuoco, Alessandro; Branchini, Enzo; Fornengo, Nicolao; Viel, Matteo

2015-06-01

If dark matter (DM) is composed by particles which are nongravitationally coupled to ordinary matter, their annihilations or decays in cosmic structures can result in detectable radiation. We show that the most powerful technique to detect a particle DM signal outside the Local Group is to study the angular cross-correlation of nongravitational signals with low-redshift gravitational probes. This method allows us to enhance the signal to noise from the regions of the Universe where the DM-induced emission is preferentially generated. We demonstrate the power of this approach by focusing on GeV-TeV DM and on the recent cross-correlation analysis between the 2MASS galaxy catalogue and the Fermi-LAT γ -ray maps. We show that this technique is more sensitive than other extragalactic γ -ray probes, such as the energy spectrum and angular autocorrelation of the extragalactic background, and emission from clusters of galaxies. Intriguingly, we find that the measured cross-correlation can be well fitted by a DM component, with a thermal annihilation cross section and mass between 10 and 100 GeV, depending on the small-scale DM properties and γ -ray production mechanism. This solicits further data collection and dedicated analyses.

The effect of amorphous selenium detector thickness on dual-energy digital breast imaging

PubMed Central

Hu, Yue-Houng; Zhao, Wei

2014-01-01

Purpose: Contrast enhanced (CE) imaging techniques for both planar digital mammography (DM) and three-dimensional (3D) digital breast tomosynthesis (DBT) applications requires x-ray photon energies higher than the k-edge of iodine (33.2 keV). As a result, x-ray tube potentials much higher (>40 kVp) than those typical for screening mammography must be utilized. Amorphous selenium (a-Se) based direct conversion flat-panel imagers (FPI) have been widely used in DM and DBT imaging systems. The a-Se layer is typically 200 μm thick with quantum detective efficiency (QDE) >87% for x-ray energies below 26 keV. However, QDE decreases substantially above this energy. To improve the object detectability of either CE-DM or CE-DBT, it may be advantageous to increase the thickness (dSe) of the a-Se layer. Increasing the dSe will improve the detective quantum efficiency (DQE) at the higher energies used in CE imaging. However, because most DBT systems are designed with partially isocentric geometries, where the gantry moves about a stationary detector, the oblique entry of x-rays will introduce additional blur to the system. The present investigation quantifies the effect of a-Se thickness on imaging performance for both CE-DM and CE-DBT, discussing the effects of improving photon absorption and blurring from oblique entry of x-rays. Methods: In this paper, a cascaded linear system model (CLSM) was used to investigate the effect of dSe on the imaging performance (i.e., MTF, NPS, and DQE) of FPI in CE-DM and CE-DBT. The results from the model are used to calculate the ideal observer signal-to-noise ratio, d′, which is used as a figure-of-merit to determine the total effect of increasing dSe for CE-DM and CE-DBT. Results: The results of the CLSM show that increasing dSe causes a substantial increase in QDE at the high energies used in CE-DM. However, at the oblique projection angles used in DBT, the increased length of penetration through a-Se introduces additional image blur. The reduced MTF and DQE at high spatial frequencies lead to reduced two-dimensional d′. These losses in projection image resolution may subsequently result in a decrease in the 3D d′, but the degree of which is largely dependent on the DBT reconstruction algorithm. For a filtered backprojection (FBP) algorithm with spectral apodization and slice-thickness filters, which dominate the blur for reconstructed images at oblique angles, the effect of oblique entry of x-rays on 3D d′ is minimal. Thus, increasing dSe results in an improvement in d′ for both CE-DM and CE-DBT with typical FBP reconstruction parameters. Conclusions: Increased dSe improves CE breast imaging performance by increasing QDE of detectors at higher energies, e.g., 49 kVp. Although there is additional blur in the oblique angled projections of a DBT scan, the overall 3D d′ for DBT is not degraded because the dominant source blur at these angles results from the reconstruction filters of the employed FBP algorithm. PMID:25370637

The effect of amorphous selenium detector thickness on dual-energy digital breast imaging.

PubMed

Hu, Yue-Houng; Zhao, Wei

2014-11-01

Contrast enhanced (CE) imaging techniques for both planar digital mammography (DM) and three-dimensional (3D) digital breast tomosynthesis (DBT) applications requires x-ray photon energies higher than the k-edge of iodine (33.2 keV). As a result, x-ray tube potentials much higher (>40 kVp) than those typical for screening mammography must be utilized. Amorphous selenium (a-Se) based direct conversion flat-panel imagers (FPI) have been widely used in DM and DBT imaging systems. The a-Se layer is typically 200 μm thick with quantum detective efficiency (QDE) >87% for x-ray energies below 26 keV. However, QDE decreases substantially above this energy. To improve the object detectability of either CE-DM or CE-DBT, it may be advantageous to increase the thickness (dSe) of the a-Se layer. Increasing the dSe will improve the detective quantum efficiency (DQE) at the higher energies used in CE imaging. However, because most DBT systems are designed with partially isocentric geometries, where the gantry moves about a stationary detector, the oblique entry of x-rays will introduce additional blur to the system. The present investigation quantifies the effect of a-Se thickness on imaging performance for both CE-DM and CE-DBT, discussing the effects of improving photon absorption and blurring from oblique entry of x-rays. In this paper, a cascaded linear system model (CLSM) was used to investigate the effect of dSe on the imaging performance (i.e., MTF, NPS, and DQE) of FPI in CE-DM and CE-DBT. The results from the model are used to calculate the ideal observer signal-to-noise ratio, d', which is used as a figure-of-merit to determine the total effect of increasing dSe for CE-DM and CE-DBT. The results of the CLSM show that increasing dSe causes a substantial increase in QDE at the high energies used in CE-DM. However, at the oblique projection angles used in DBT, the increased length of penetration through a-Se introduces additional image blur. The reduced MTF and DQE at high spatial frequencies lead to reduced two-dimensional d'. These losses in projection image resolution may subsequently result in a decrease in the 3D d', but the degree of which is largely dependent on the DBT reconstruction algorithm. For a filtered backprojection (FBP) algorithm with spectral apodization and slice-thickness filters, which dominate the blur for reconstructed images at oblique angles, the effect of oblique entry of x-rays on 3D d' is minimal. Thus, increasing dSe results in an improvement in d' for both CE-DM and CE-DBT with typical FBP reconstruction parameters. Increased dSe improves CE breast imaging performance by increasing QDE of detectors at higher energies, e.g., 49 kVp. Although there is additional blur in the oblique angled projections of a DBT scan, the overall 3D d' for DBT is not degraded because the dominant source blur at these angles results from the reconstruction filters of the employed FBP algorithm.

IBM1, a JmjC domain-containing histone demethylase, is involved in the regulation of RNA-directed DNA methylation through the epigenetic control of RDR2 and DCL3 expression in Arabidopsis

PubMed Central

Fan, Di; Dai, Yan; Wang, Xuncheng; Wang, Zhenjie; He, Hang; Yang, Hongchun; Cao, Ying; Deng, Xing Wang; Ma, Ligeng

2012-01-01

Small RNA-directed DNA methylation (RdDM) is an important epigenetic pathway in Arabidopsis that controls the expression of multiple genes and several developmental processes. RNA-DEPENDENT RNA POLYMERASE 2 (RDR2) and DICER-LIKE 3 (DCL3) are necessary factors in 24-nt small interfering RNA (siRNA) biogenesis, which is part of the RdDM pathway. Here, we found that Increase in BONSAI Methylation 1 (IBM1), a conserved JmjC family histone demethylase, is directly associated with RDR2 and DCL3 chromatin. The mutation of IBM1 induced the hypermethylation of H3K9 and DNA non-CG sites within RDR2 and DCL3, which repressed their expression. A genome-wide analysis suggested that the reduction in RDR2 and DCL3 expression affected siRNA biogenesis in a locus-specific manner and disrupted RdDM-directed gene repression. Together, our results suggest that IBM1 regulates gene expression through two distinct pathways: direct association to protect genes from silencing by preventing the coupling of histone and DNA methylation, and indirect silencing of gene expression through RdDM-directed repression. PMID:22772985

Laser direct marking applied to rasterizing miniature Data Matrix Code on aluminum alloy

NASA Astrophysics Data System (ADS)

Li, Xia-Shuang; He, Wei-Ping; Lei, Lei; Wang, Jian; Guo, Gai-Fang; Zhang, Teng-Yun; Yue, Ting

2016-03-01

Precise miniaturization of 2D Data Matrix (DM) Codes on Aluminum alloy formed by raster mode laser direct part marking is demonstrated. The characteristic edge over-burn effects, which render vector mode laser direct part marking inadequate for producing precise and readable miniature codes, are minimized with raster mode laser marking. To obtain the control mechanism for the contrast and print growth of miniature DM code by raster laser marking process, the temperature field model of long pulse laser interaction with material is established. From the experimental results, laser average power and Q frequency have an important effect on the contrast and print growth of miniature DM code, and the threshold of laser average power and Q frequency for an identifiable miniature DM code are respectively 3.6 W and 110 kHz, which matches the model well within normal operating conditions. In addition, the empirical model of correlation occurring between laser marking parameters and module size is also obtained, and the optimal processing parameter values for an identifiable miniature DM code of different but certain data size are given. It is also found that an increase of the repeat scanning number effectively improves the surface finish of bore, the appearance consistency of modules, which has benefit to reading. The reading quality of miniature DM code is greatly improved using ultrasonic cleaning in water by avoiding the interference of color speckles surrounding modules.

Effects of corn particle size and source on performance of lactating cows fed direct-cut grass-legume forage.

PubMed

Reis, R B; Emeterio, F S; Combs, D K; Satter, L D; Costa, H N

2001-02-01

We conducted two experiments to evaluate the effects of corn supplementation, source of corn, and corn particle size on performance and nutrient utilization of lactating dairy cows. In experiment 1, treatments were 1) direct-cut grass-legume forage without supplement, 2) direct-cut forage plus 10 kg DM of ground dry shelled corn-based concentrate, and 3) direct-cut forage plus 10 kg DM of coarsely ground high moisture ear corn-based concentrate. In experiment 2, treatments were 1) direct-cut grass-legume forage plus 10 kg DM of ground dry shelled corn-based concentrate, 2) direct-cut forage plus 10 kg DM of coarsely ground high moisture ear corn-based concentrate, and 3) direct-cut forage plus 10 kg of DM finely ground high moisture ear corn-based concentrate. Both experiments were designed as 3 x 3 Latin squares replicated three times. In experiment 1, yields of milk and milk protein increased with concentrate supplementation, but were not affected by source of corn. Solids-corrected milk yield tended to increase with grain supplementation. Dry matter intake increased with concentrate supplementation, but was not affected by source of corn or corn particle size. Corn supplements decreased ruminal pH and acetate to propionate ratio and increased ruminal propionate concentration. Grain supplements reduced ruminal ammonia concentration, increased concentration of urine allantoin, and increased the urinary allantoin to creatinine ratio. In the second study, fine grinding of high moisture corn reduced fecal starch plus free glucose levels and tended to increase its apparent digestibility. In both experiments, starch plus free glucose intake was higher on the diets with dry corn, but its utilization was not affected by source of corn.

Effect of Diabetes Mellitus on Tuberculosis Treatment Outcome and Adverse Reactions in Patients Receiving Directly Observed Treatment Strategy in India: A Prospective Study.

PubMed

Siddiqui, Ali Nasir; Khayyam, Khalid Umer; Sharma, Manju

2016-01-01

Despite successful implementation of directly observed treatment, short course (DOTS) in India, the growing number of diabetes mellitus (DM) patients appears to be a cause in the increasing tuberculosis (TB) incidence, affecting their management. In this regard, a prospective study was conducted on DOTS patients in three primary health care centers in urban slum region of South Delhi, India, to evaluate the effect of DM on sputum conversion, treatment outcome, and adverse drug reactions (ADR) due to anti-TB treatment. Eligible TB patients underwent blood glucose screening at treatment initiation. Disease presentation, clinical outcome, and ADRs were compared between patients of TB with and without DM. Out of 316 patients, the prevalence of DM was found to be 15.8%, in which 19.4% and 9.6% were PTB and EPTB patients, respectively. DM patients have observed higher sputum positivity (OR 1.247 95% CI; 0.539-2.886) at the end of 2-month treatment and poor outcome (OR 1.176 95% CI; 0.310-4.457) at the completion of treatment compared with non DM patients. Presence of DM was significantly associated (OR 3.578 95% CI; 1.114-11.494, p = 0.032) with the development of ADRs. DM influences the treatment outcome of PTB patients in our setting and also on the ADR incidence.

High direct costs of medical care in patients with Type 1 diabetes attending a referral clinic in a government-funded hospital in Northern India.

PubMed

Katam, Kishore K; Bhatia, Vijayalakshmi; Dabadghao, Preeti; Bhatia, Eesh

2016-01-01

There is little information regarding costs of managing type 1 diabetes mellitus (T1DM) from low- and middle-income countries. We estimated direct costs of T1DM in patients attending a referral diabetes clinic in a governmentfunded hospital in northern India. We prospectively enrolled 88 consecutive T1DM patients (mean [SD] age 15.3 [8] years) with age at onset <18 years presenting to the endocrine clinic of our institution. Data on direct costs were collected for a 12 months-6 months retrospectively followed by 6 months prospectively. Patients belonged predominantly (77%) to the middle socioeconomic strata (SES); 81% had no access to government subsidy or health insurance. The mean direct cost per patient-year of T1DM was `27 915 (inter-quartile range [IQR] `19 852-32 856), which was 18.6% (7.1%-30.1%) of the total family income. A greater proportion of income was spent by families of lower compared to middle SES (32.6% v. 6.6%, p<0.001). The mean out-of-pocket payment for diabetes care ranged from 2% to 100% (mean 87%) of the total costs. The largest expenditure was on home blood glucose monitoring (40%) and insulin (39.5%). On multivariate analysis, total direct cost was associated with annual family income (β=0.223, p=0.033), frequency of home blood glucose monitoring (β=0.249, p=0.016) and use of analogue insulin (β=0.225, p=0.016). Direct costs of T1DM were high; in proportion to their income the costs were greater in the lower SES. The largest expenditure was on home blood glucose monitoring and insulin. Support for insulin and glucose testing strips for T1DM care is urgently required.

Evaluation of the Finnish Diabetes Risk Score to predict type 2 diabetes mellitus in a Colombian population: A longitudinal observational study

PubMed Central

Gomez-Arbelaez, Diego; Alvarado-Jurado, Laura; Ayala-Castillo, Miguel; Forero-Naranjo, Leonardo; Camacho, Paul Anthony; Lopez-Jaramillo, Patricio

2015-01-01

AIM: To assess the performance of the Finnish Diabetes Risk Score (FINDRISC) questionnaire for detecting and predicting type 2 diabetes mellitus (DM2) in a Colombian population. METHODS: This is a longitudinal observational study conducted in Floridablanca, Colombia. Adult subjects (age ≥ 35 years) without known diabetes, were included. A modified version of FINDRISC was completed, and the glycemia values from all the subjects were collected from the hospital’s database. Firstly, a cross-sectional analysis was performed and then, the subsample of prediabetic participants was followed for diabetes incidence. RESULTS: A total of 772 subjects were suitable for the study. The overall prevalence of undiagnosed DM2 was 2.59%, and the incidence of DM2 among the prediabetic participants was 7.5 per 100 person-years after a total of 265257 person-years follow-up. The FINDRISC at baseline was significantly associated with undiagnosed and incident DM2. The area under receiver operating characteristics curve of the FINDRISC score for detecting undiagnosed DM2 in both men and women was 0.7477 and 0.7175, respectively; and for predicting the incidence of DM2 among prediabetics was 71.99% in men and 67.74% in women. CONCLUSION: The FINDRISC questionnaire is a useful screening tool to identify cross-sectionally unknown DM2 and to predict the incidence of DM2 among prediabetics in the Colombian population. PMID:26675051

Determination of acetone in saliva by reversed-phase liquid chromatography with fluorescence detection and the monitoring of diabetes mellitus patients with ketoacidosis.

PubMed

Fujii, Shinya; Maeda, Toshio; Noge, Ichiro; Kitagawa, Yutaka; Todoroki, Kenichiro; Inoue, Koichi; Min, Jun Zhe; Toyo'oka, Toshimasa

2014-03-20

In diabetes mellitus (DM) patients with ketoacidosis, ketone bodies, i.e., acetone, acetoacetic acid (AA) and β-hydroxybutyric acid (HA), are increased in the blood and urine. Acetone is also excreted by breathing due to the spontaneous decomposition of AA. Thus, the increase in acetone has been considered as one of the biomarkers for the diagnosis of DM. However, the determination of acetone in one's breath is not recommended because of the sample handling difficulty. We measured acetone in saliva by reversed-phase liquid chromatography (LC) with fluorescence (FL) detection. The proposed method was applied to the determination of acetone in the saliva of healthy volunteers and DM patients with and without ketoacidosis. 3-Pentanone (I.S.) and DBD-H in acetonitrile were added to freshly collected saliva and reacted at room temperature for 20 min in the presence of trifluoroacetic acid. After the reaction, the solution was centrifuged at 10,000 × g and 4 °C for 5 min. The supernatant was separated by reversed-phase LC and the FL detected at 550 nm (excitation at 460 nm). The concentrations of acetone in the DM patients with ketoacidosis were significantly higher than those of the normal subjects and DM patients without ketoacidosis. Furthermore, the total contents of the ketone bodies in the blood correlated with acetone in the saliva of the DM patients. The concentrations of acetone in the saliva of an emergency patient also correlated with the ketone bodies in the blood at each sampling time. The proposed method using LC-FL seems to be useful for the determination of acetone in the saliva of DM patients with ketoacidosis. The method offers a new option for the diagnosis and monitoring of DM patients with ketoacidosis. Copyright © 2014 Elsevier B.V. All rights reserved.

Evaluation of immunogenicity of LY2963016 insulin glargine compared with Lantus® insulin glargine in patients with type 1 or type 2 diabetes mellitus.

PubMed

Ilag, L L; Deeg, M A; Costigan, T; Hollander, P; Blevins, T C; Edelman, S V; Konrad, R J; Ortmann, R A; Pollom, R K; Huster, W J; Zielonka, J S; Prince, M J

2016-02-01

To compare the immunogenicity profiles and the potential effects on clinical outcomes of LY2963016 insulin glargine (LY IGlar) and Lantus® insulin glargine (IGlar), products with identical primary amino acid sequences, in patients with type 1 or type 2 diabetes mellitus (T1DM or T2DM). To assess immunogenicity, anti-insulin glargine antibodies (measured as percent binding) were compared between treatments in 52-week (open-label) and 24-week (double-blind) randomized studies in total study populations of patients with T1DM (N = 535) and T2DM (N = 756), respectively, and two subgroups of patients with T2DM: insulin-naïve patients and those reporting prestudy IGlar treatment (prior IGlar). Relationships between insulin antibody levels and clinical outcomes were assessed using analysis of covariance and partial correlations. Insulin antibody levels were assessed using Wilcoxon rank sum. Treatment comparisons for treatment-emergent antibody response (TEAR) and incidence of detectable antibodies were analysed using Fisher's exact test. No significant treatment differences were observed for insulin antibody levels, incidence of detectable anti-insulin glargine antibodies, or incidence of TEAR [overall and endpoint, by last-observation-carried-forward (LOCF)] in patients with T1DM or patients with T2DM, including the insulin-naïve subgroup. A statistically significant difference was noted in the overall incidence of detectable antibodies but not at endpoint (LOCF) nor in TEAR for the prior IGlar subgroup of patients with T2DM. Insulin antibody levels were low (<5%) in both treatment groups. Insulin antibody levels or developing TEAR was not associated with clinical outcomes. LY IGlar and IGlar have similar immunogenicity profiles; anti-insulin glargine antibody levels were low for both treatments, with no observed effect on efficacy and safety outcomes. © 2015 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

An alternative interpretation for cosmic ray peaks

DOE PAGES

Kim, Doojin; Park, Jong -Chul

2015-10-03

We propose an alternative mechanism based upon dark matter (DM) interpretation for anomalous peak signatures in cosmic ray measurements, assuming an extended dark sector with two DM species. This is contrasted with previous effort to explain various line-like cosmic-ray excesses in the context of DM models where the relevant DM candidate directly annihilates into Standard Model (SM) particles. The heavier DM is assumed to annihilate to an on-shell intermediate state. As the simplest choice, it decays directly into the lighter DM along with an unstable particle which in turn decays to a pair of SM states corresponding to the interestingmore » cosmic anomaly. We show that a sharp continuum energy peak can be readily generated under the proposed DM scenario, depending on dark sector particle mass spectra. Remarkably, such a peak is robustly identified as half the mass of the unstable particle. Furthermore, other underlying mass parameters are analytically related to the shape of energy spectrum. We apply this idea to the two well-known line excesses in the cosmic photon spectrum: 130 GeV γ-ray line and 3.5 keV X-ray line. As a result, each observed peak spectrum is well-reproduced by theoretical expectation predicated upon our suggested mechanism, and moreover, our resulting best fits provide rather improved χ 2 values.« less

Robust constraints and novel gamma-ray signatures of dark matter that interacts strongly with nucleons

NASA Astrophysics Data System (ADS)

Hooper, Dan; McDermott, Samuel D.

2018-06-01

Due to shielding, direct detection experiments are in some cases insensitive to dark matter candidates with very large scattering cross sections with nucleons. In this paper, we revisit this class of models and derive a simple analytic criterion for conservative but robust direct detection limits. While large spin-independent cross sections seem to be ruled out, we identify potentially viable parameter space for dark matter with a spin-dependent cross section with nucleons in the range of 10-27 cm2≲σDM -p≲10-24 cm2 . With these parameters, cosmic-ray scattering with dark matter in the extended halo of the Milky Way could generate a novel and distinctive gamma-ray signal at high galactic latitudes. Such a signal could be observable by Fermi or future space-based gamma-ray telescopes.

Clustering-based Filtering to Detect Isolated and Intermittent Pulses in Radio Astronomy Data

NASA Astrophysics Data System (ADS)

Wagstaff, Kiri; Tang, B.; Lazio, T. J.; Spolaor, S.

2013-01-01

Radio-emitting neutron stars (pulsars) produce a series of periodic pulses at radio frequencies. Dispersion, caused by propagation through the interstellar medium, delays signals at lower frequencies more than higher frequencies. This well understood effect can be reversed though de-dispersion at the appropriate dispersion measure (DM). The periodic nature of a pulsar provides multiple samples of signals at the same DM, increasing the reliability of any candidate detection. However, existing methods for pulsar detection are ineffective for many pulse-emitting phenomena now being discovered. Sources exhibit a wide range of pulse repetition rates, from highly regular canonical pulsars to intermittent and nulling pulsars to rotating radio transients (RRATs) that may emit only a few pulses per hour. Other source types may emit only a few pulses, or even only a single pulse. We seek to broaden the scope of radio signal analysis to enable the detection of isolated and intermittent pulses. Without a requirement that detected sources be periodic, we find that a typical de-dispersion search yields results that are often dominated by spurious detections from radio frequency interference (RFI). These occur across the DM range, so filtering out DM-0 signals is insufficient. We employ DBSCAN data clustering to identify groups within the de-dispersion results, using information for each candidate about time, DM, SNR, and pulse width. DBSCAN is a density-based clustering algorithm that offers two advantages over other clustering methods: 1) the number of clusters need not to be specified, and 2) there is no model of expected cluster shape (such as the Gaussian assumption behind EM clustering). Each data cluster can be selectively masked or investigated to facilitate the process of sifting through hundreds of thousands of detections to focus on those of true interest. Using data obtained by the Byrd Green Bank Telescope (GBT), we show how this approach can help separate RFI from difficult to find single and intermittent pulses.

INTESTINAL PARASITES IN DIABETIC PATIENTS IN SOHAG UNIVERSITY HOSPITALS, EGYPT.

PubMed

Elnadi, Nada A; Hassanien, Hassan A; Ahmad, Amal M; Abd Ellah, Asmaa K

2015-08-01

Intestinal parasites usually create benign diseases, though they may induce complications with high morbidity and mortality to the immunocompromised, including diabetic patients. The study detected the prevalence of intestinal parasitic infections in diabetic patients, comparing to non-diabetic controls and other parameters. A total of 100 fecal samples were collected from diabetic patients at the outpatient clinic of Sohag University Hospitals and another 100 from cross matched controls. The samples were examined macroscopically and microscopically by direct smear and different concentration methods then stained by Modified Ziehl-Neelsen Acid fast stain. Glycated hemoglobin (Hb Alc) was measured to detect DM controlled patients. The data were organized, tabulated, and statistically analyzed. Intestinal parasites were found in 25 (25%) cases out of 100 patients in diabetic group and 7(7%) cases out of 100 controls with high significance (P<0.001)). In the diabetic group, Giardia lamblia was detected in 22 cases (22%) and 5 (5%) among controls, Entamoeba histolytica in 7 cases (7%) and 3 (3%) among controls, Hymenolypis nana in 5 cases (5%) and 3 (3%) among controls, Entamoeba coli in 8 patients (8%), Entamoeba hartmanni in 3 cases (3%), Dientamoeba fragilis in a case (1%), Cryptosporidium parvum in 5 cases (5%) and microsporidia in 3 cases (3%). But, E. coli, E. hartmanni, D. fragilis and C. parvum nor microsporidia were detected in controls. The rate of G. lamblia in DM patients compared to controls was high significant (P<0.001). Hymenolepis nana was 5% (5 cases) in diabetic patients compared to 3% (3 cases) in controls. Residence and sex differences were not significant, while age, >10 years showed the highest prevalence (P< 0.003), type I infection rate was significantly higher than type II (P<0.001). DM control was also significantly affected the infection rates (P<0.007 in type I and P< 0.01 in type II).

Analysis of CTG repeat length variation in the DMPK gene in the general population and the molecular diagnosis of myotonic dystrophy type 1 in Malaysia.

PubMed

Ambrose, Kathlin K; Ishak, Taufik; Lian, Lay-Hoong; Goh, Khean-Jin; Wong, Kum-Thong; Ahmad-Annuar, Azlina; Thong, Meow-Keong

2017-03-31

The lack of epidemiological data and molecular diagnostic services in Malaysia has hampered the setting-up of a comprehensive management plan for patients with myotonic dystrophy type 1 (DM1), leading to delayed diagnosis, treatment and support for patients and families. The aim of this study was to estimate the prevalence of DM1 in the 3 major ethnic groups in Malaysia and evaluate the feasibility of a single tube triplet-primed PCR (TP-PCR) method for diagnosis of DM1 in Malaysia. We used PCR to determine the size of CTG repeats in 377 individuals not known to be affected by DM and 11 DM1 suspected patients, recruited from a tertiary hospital in Kuala Lumpur. TP-PCR was performed on selected samples, followed by Southern blot hybridisation of PCR amplified fragments to confirm and estimate the size of CTG expansion. The number of individuals not known to be affected by DM with (CTG) >18 was determined according to ethnic group and as a whole population. The χ 2 test was performed to compare the distribution of (CTG) >18 with 12 other populations. Additionally, the accuracy of TP-PCR in detecting CTG expansion in 11 patients with DM1 was determined by comparing the results with that from Southern blot hybridisation. Of the 754 chromosomes studied, (CTG) >18 frequency of 3.60%, 1.57% and 4.00% in the Malay, Chinese and Indian subpopulations, respectively, was detected, showing similarities to data from Thai, Taiwanese and Kuwaiti populations. We also successfully detected CTG expansions in 9 patients using the TP-PCR method followed by the estimation of CTG expansion size via Southern blot hybridisation. The results show a low DM1 prevalence in Malaysia with the possibility of underdiagnosis and demonstrates the feasibility of using a clinical and TP-PCR-based approach for rapid and cost-effective DM1 diagnosis in developing countries. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Analysis of CTG repeat length variation in the DMPK gene in the general population and the molecular diagnosis of myotonic dystrophy type 1 in Malaysia

PubMed Central

Ambrose, Kathlin K; Ishak, Taufik; Lian, Lay-Hoong; Goh, Khean-Jin; Wong, Kum-Thong; Ahmad-Annuar, Azlina; Thong, Meow-Keong

2017-01-01

Objective The lack of epidemiological data and molecular diagnostic services in Malaysia has hampered the setting-up of a comprehensive management plan for patients with myotonic dystrophy type 1 (DM1), leading to delayed diagnosis, treatment and support for patients and families. The aim of this study was to estimate the prevalence of DM1 in the 3 major ethnic groups in Malaysia and evaluate the feasibility of a single tube triplet-primed PCR (TP-PCR) method for diagnosis of DM1 in Malaysia. Design, setting and participants We used PCR to determine the size of CTG repeats in 377 individuals not known to be affected by DM and 11 DM1 suspected patients, recruited from a tertiary hospital in Kuala Lumpur. TP-PCR was performed on selected samples, followed by Southern blot hybridisation of PCR amplified fragments to confirm and estimate the size of CTG expansion. Outcome measures The number of individuals not known to be affected by DM with (CTG)>18 was determined according to ethnic group and as a whole population. The χ2 test was performed to compare the distribution of (CTG)>18 with 12 other populations. Additionally, the accuracy of TP-PCR in detecting CTG expansion in 11 patients with DM1 was determined by comparing the results with that from Southern blot hybridisation. Results Of the 754 chromosomes studied, (CTG)>18 frequency of 3.60%, 1.57% and 4.00% in the Malay, Chinese and Indian subpopulations, respectively, was detected, showing similarities to data from Thai, Taiwanese and Kuwaiti populations. We also successfully detected CTG expansions in 9 patients using the TP-PCR method followed by the estimation of CTG expansion size via Southern blot hybridisation. Conclusions The results show a low DM1 prevalence in Malaysia with the possibility of underdiagnosis and demonstrates the feasibility of using a clinical and TP-PCR-based approach for rapid and cost-effective DM1 diagnosis in developing countries. PMID:28363916

Decoherence as a way to measure extremely soft collisions with dark matter

NASA Astrophysics Data System (ADS)

Riedel, C. Jess; Yavin, Itay

2017-07-01

A new frontier in the search for dark matter (DM) is based on the idea of detecting the decoherence caused by DM scattering against a mesoscopic superposition of normal matter. Such superpositions are uniquely sensitive to very small momentum transfers from new particles and forces, especially DM with a mass below 100 MeV. Here we investigate what sorts of dark sectors are inaccessible with existing methods but would induce noticeable decoherence in the next generation of matter interferometers. We show that very soft but medium range (0.1 nm - 1 μ m ) elastic interactions between nuclei and DM are particularly suitable. We construct toy models for such interactions, discuss existing constraints, and delineate the expected sensitivity of forthcoming experiments. The first hints of DM in these devices would appear as small variations in the anomalous decoherence rate with a period of one sidereal day. This is a generic signature of interstellar sources of decoherence, clearly distinguishing it from terrestrial backgrounds. The OTIMA experiment under development in Vienna will begin to probe Earth-thermalizing DM once sidereal variations in the background decoherence rate are pushed below one part in a hundred for superposed 5-nm gold nanoparticles. The proposals by Bateman et al. and Geraci et al. could be similarly sensitive although they would require at least a month of data taking. DM that is absorbed or elastically reflected by the Earth, and so avoids a greenhouse density enhancement, would not be detectable by those three experiments. On the other hand, the aggressive proposals of the MAQRO collaboration and Pino et al. would immediately open up many orders of magnitude in DM mass, interaction range, and coupling strength, regardless of how DM behaves in bulk matter.

Healthcare costs of people with type 2 diabetes mellitus in the Basque Country (Spain).

PubMed

Nuño-Solinís, Roberto; Alonso-Morán, Edurne; Arteagoitia Axpe, Jose M; Ezkurra Loiola, Patxi; Orueta, Juan F; Gaztambide, Sonia

2016-12-01

The aim of the study was to estimate the direct costs of healthcare provided to patients with type 2 diabetes mellitus (T2DM) in the Basque Country and to compare them with those of the population with chronic diseases. A retrospective, cross-sectional, population-based study. Direct healthcare costs for patients aged over 35 years diagnosed with T2DM in the Basque Country (n=126,894) were calculated, stratified by age, sex and deprivation index, and compared to the costs for the population diagnosed with a chronic disease other than T2DM (n=1,347,043). The annual average healthcare cost of a person with T2DM was €3,432. Cost gradually increased with age to €4,313 in patients aged 80 to 84 years. Cost in males were €161 higher as compared to costs in females (P<.001). In the most socioeconomically disadvantaged areas, cost per patient was €468 (14.9%) greater than in the most privileged areas (P<.001). Moreover, cost was 68.5% higher (P<.001) for patients with T2DM than for patients with other chronic diseases. Total annual direct costs amounted to €435.5 million, or 12.78% of total public health expenditure in the region. Direct mean healthcare costs in the Basque Country for patients with T2DM were higher in males, in the most underprivileged areas, in patients with comorbidities, and in older age groups, and represented €3,432 per person per year. Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

Beyond minimal lepton-flavored Dark Matter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Mu-Chun; Huang, Jinrui; Takhistov, Volodymyr

In this paper ,we consider a class of flavored dark matter (DM) theories where dark matter interacts with the Standard Model lepton fields at the renormalizable level. We allow for a general coupling matrix between the dark matter and leptons whose structure is beyond the one permitted by the minimal flavor violation (MFV) assumption. It is assumed that this is the only new source of flavor violation in addition to the Standard Model (SM) Yukawa interactions. The setup can be described by augmenting the SM flavor symmetry by an additional SU(3) χ, under which the dark matter χ transforms. Thismore » framework is especially phenomenologically rich, due to possible novel flavor-changing interactions which are not present within the more restrictive MFV framework. As a representative case study of this setting, which we call “beyond MFV” (BMFV), we consider Dirac fermion dark matter which transforms as a singlet under the SM gauge group and a triplet under SU(3) χ. The DM fermion couples to the SM lepton sector through a scalar mediator Φ. Unlike the case of quark-flavored DM, we show that there is no Z 3 symmetry within either the MFV or BMFV settings which automatically stabilizes the lepton-flavored DM. We discuss constraints on this setup from flavor-changing processes, DM relic abundance as well as direct and indirect detections. We find that relatively large flavor-changing couplings are possible, while the dark matter mass is still within the phenomenologically interesting region below the TeV scale. Collider signatures which can be potentially searched for at the lepton and hadron colliders are discussed. Finally, we discuss the implications for decaying dark matter, which can appear if an additional stabilizing symmetry is not imposed.« less

Beyond minimal lepton-flavored Dark Matter

DOE PAGES

Chen, Mu-Chun; Huang, Jinrui; Takhistov, Volodymyr

2016-02-09

In this paper ,we consider a class of flavored dark matter (DM) theories where dark matter interacts with the Standard Model lepton fields at the renormalizable level. We allow for a general coupling matrix between the dark matter and leptons whose structure is beyond the one permitted by the minimal flavor violation (MFV) assumption. It is assumed that this is the only new source of flavor violation in addition to the Standard Model (SM) Yukawa interactions. The setup can be described by augmenting the SM flavor symmetry by an additional SU(3) χ, under which the dark matter χ transforms. Thismore » framework is especially phenomenologically rich, due to possible novel flavor-changing interactions which are not present within the more restrictive MFV framework. As a representative case study of this setting, which we call “beyond MFV” (BMFV), we consider Dirac fermion dark matter which transforms as a singlet under the SM gauge group and a triplet under SU(3) χ. The DM fermion couples to the SM lepton sector through a scalar mediator Φ. Unlike the case of quark-flavored DM, we show that there is no Z 3 symmetry within either the MFV or BMFV settings which automatically stabilizes the lepton-flavored DM. We discuss constraints on this setup from flavor-changing processes, DM relic abundance as well as direct and indirect detections. We find that relatively large flavor-changing couplings are possible, while the dark matter mass is still within the phenomenologically interesting region below the TeV scale. Collider signatures which can be potentially searched for at the lepton and hadron colliders are discussed. Finally, we discuss the implications for decaying dark matter, which can appear if an additional stabilizing symmetry is not imposed.« less

Dispersion Measure Variation of Repeating Fast Radio Burst Sources

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Yuan-Pei; Zhang, Bing, E-mail: yypspore@gmail.com, E-mail: zhang@physics.unlv.edu

The repeating fast radio burst (FRB) 121102 was recently localized in a dwarf galaxy at a cosmological distance. The dispersion measure (DM) derived for each burst from FRB 121102 so far has not shown significant evolution, even though an apparent increase was recently seen with newly detected VLA bursts. It is expected that more repeating FRB sources may be detected in the future. In this work, we investigate a list of possible astrophysical processes that might cause DM variation of a particular FRB source. The processes include (1) cosmological scale effects such as Hubble expansion and large-scale structure fluctuations; (2)more » FRB local effects such as gas density fluctuation, expansion of a supernova remnant (SNR), a pulsar wind nebula, and an H ii region; and (3) the propagation effect due to plasma lensing. We find that the DM variations contributed by the large-scale structure are extremely small, and any observable DM variation is likely caused by the plasma local to the FRB source. In addition to mechanisms that decrease DM over time, we suggest that an FRB source in an expanding SNR around a nearly neutral ambient medium during the deceleration (Sedov–Taylor and snowplow) phases or in a growing H ii region can increase DM. Some effects (e.g., an FRB source moving in an H ii region or plasma lensing) can produce either positive or negative DM variations. Future observations of DM variations of FRB 121102 and other repeating FRB sources can provide important clues regarding the physical origin of these sources.« less

A High-Performance Deformable Mirror with Integrated Driver ASIC for Space Based Active Optics

NASA Astrophysics Data System (ADS)

Shelton, Chris

Direct imaging of exoplanets is key to fully understanding these systems through spectroscopy and astrometry. The primary impediment to direct imaging of exoplanets is the extremely high brightness ratio between the planet and its parent star. Direct imaging requires a technique for contrast suppression, which include coronagraphs, and nulling interferometers. Deformable mirrors (DMs) are essential to both of these techniques. With space missions in mind, Microscale is developing a novel DM with direct integration of DM and its electronic control functions in a single small envelope. The Application Specific Integrated Circuit (ASIC) is key to the shrinking of the electronic control functions to a size compatible with direct integration with the DM. Through a NASA SBIR project, Microscale, with JPL oversight, has successfully demonstrated a unique deformable mirror (DM) driver ASIC prototype based on an ultra-low power switch architecture. Microscale calls this the Switch-Mode ASIC, or SM-ASIC, and has characterized it for a key set of performance parameters, and has tested its operation with a variety of actuator loads, such as piezo stack and unimorph, and over a wide temperature range. These tests show the SM-ASIC's capability of supporting active optics in correcting aberrations of a telescope in space. Microscale has also developed DMs to go with the SM-ASIC driver. The latest DM version produced uses small piezo stack elements in an 8x8 array, bonded to a novel silicon facesheet structure fabricated monolithically into a polished mirror on one side and mechanical linkage posts that connect to the piezoelectric stack actuators on the other. In this Supporting Technology proposal we propose to further develop the ASIC-DM and have assembled a very capable team to do so. It will be led by JPL, which has considerable expertise with DMs used in Adaptive Optics systems, with high-contrast imaging systems for exoplanet missions, and with designing DM driver electronics. On its part Microscale will continue its design and fabrication of the ASIC-DM combination. Both the SM-ASIC and the DM are currently at a Technology Readiness Level (TRL) of 3; the major goal of the proposed effort is to raise the TRL of the combined system to 4 by scaling up the array formats and by testing, characterizing, and operating multiple generations of the integrated DM-ASIC systems in a laboratory environment. We propose a three year effort, with these tasks: Year 1: Optimize the influence function of an 8x8 DM for active / adaptive optics, by modeling and fabricating different geometric parameters of the facesheet, with its mechanical linkage posts. Fabricate an SM-ASIC and an 8x8 piezo stack DM, and evaluate their performance. Characterize and optimize the integration processes to achieve a driver/DM combination that can support high contrast imaging of exoplanets. Test the control resolution of the ASIC in driving actuators using a commercial interferometer, to ensure the ASIC can command the piezo stack actuator to nanometer levels. The goal, by year three, is control to a small number of picometers; 10-20 pm (surface) may be a practical goal, while 5 pm is the ultimate goal. Year 2: Fabricate 16x16 piezo stack DMs and matching driver ASICS, and repeat Year 1 tasks with the larger format devices. Year 3: Fabricate 32x32 DMs and SM-ASICs, and repeat Year 1 tasks with the larger format devices. Fabricate versions of the 32x32 devices that can be formed into a 2x2 array, to make a composite 64x64 DM/driver. Fabricate such a composite 64x64 DM/ASIC and evaluate its performance.

Ultrasonography screening for hepatocellular carcinoma in Japanese patients with diabetes mellitus.

PubMed

Hiraoka, Atsushi; Ochi, Marie; Matsuda, Rie; Aibiki, Toshihiko; Okudaira, Tomonari; Kawamura, Tomoe; Yamago, Hiroka; Nakahara, Hiromasa; Suga, Yoshifumi; Azemoto, Nobuaki; Miyata, Hideki; Miyamoto, Yasunao; Ninomiya, Tomoyuki; Hirooka, Masashi; Abe, Masanori; Matsuura, Bunzo; Hiasa, Yoichi; Michitaka, Kojiro

2016-09-01

Effective surveillance for hepatocellular carcinoma (HCC) in diabetes mellitus (DM) has not been established. We elucidated the risk factors for HCC in DM patients. From 2000 to 2014, 80 patients diagnosed with HCC for the first time who had concomittant DM but no other etiology of liver disease were enrolled as the DM-HCC group. From 2005 October to 2014, after introduction of the abdominal ultrasonography (US) report database, 2083 DM patients with no viral hepatitis, no known autoimmune hepatic diseases, and/or no evidence of alcohol abuse (>60 g/day) were enrolled as the DM-US group. Findings from the first US screening were evaluated. "Elderly" patients were defined as those aged >65 years. Clinical features of DM-HCC patients were evaluated and compared with those of DM-US patients. In the DM-HCC group (54 men, 26 women), the mean (± SD age was 74.1 ± 8.5 years, and mean HbA1c and fibrosis-4 (FIB-4) index were 7.3 ± 1.3% and 4.50 ± 3.42, respectively. Mean tumor diameter was 5.7 ± 3.5 cm, there were 63/13/2/2 patients classified as Child-Pugh A/B/C/unknown, and 56/24 were single/multiple lesions. In the DM-US group, HCC was detected in three patients (0.14%; 0.3% of those classified as elderly). The mean age and FIB-4 index of these three patients (one man, two women) were 75.6 years (range 67-92 years) and 4.84 (range 2.87-6.98), respectively. Mean tumor diamter was 7.6 cm and there were one and two single and multiple lesions, respectively. In elderly DM-US patients with a high FIB-4 index (≥4), the rate of HCC detection was 5.0%. Being elderly and having a high FIB-4 index are characteristic features of DM-HCC. Similar characteristics were noted for patients with HCC in the DM-US group. HCC surveillance with US is recommended for DM patients, especially those who are elderly (≥65 years) and have a high FIB-4 index. © 2015 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Association between direct measurement of active serum calcium and risk of type 2 diabetes mellitus: A prospective study.

PubMed

Zaccardi, F; Webb, D R; Carter, P; Pitocco, D; Khunti, K; Davies, M J; Kurl, S; Laukkanen, J A

2015-06-01

Previous prospective studies showing a positive association between serum calcium and incidence of type 2 diabetes mellitus (T2DM) have relied on total calcium or an indirect estimate of active, ionized calcium (iCa). We aimed to assess this relationship using a direct measurement of iCa. iCa and cardiometabolic risk factors were measured in a population-based sample of 2350 men without a known history of T2DM at baseline. Associations between iCa levels and incident cases of T2DM (self-reported, ascertained with a glucose tolerance test, or determined by record linkage to national registers) were estimated using Cox regression analyses adjusted for potential confounders. At baseline, mean (standard deviation) age was 53 (5) years and mean iCa 1.18 (0.05) mmol/L. During a median follow-up of 23.1 years, 140 new cases of T2DM were recorded. In a multivariable analysis adjusted for age, body mass index, systolic blood pressure, serum HDL-cholesterol, and family history of T2DM, there was no association comparing second (hazard ratio 0.84; 95% confidence interval 0.59-1.18), third (0.77; 0.52-1.14), or fourth (0.98; 0.69-1.39) vs first quartile of iCa (p for trend 0.538); further adjustment for C-reactive protein, physical activity level, and triglycerides did not change the estimates (p for trend 0.389). In this study, we did not find evidence of an association between direct measurement of active calcium and risk of T2DM. Further studies are needed to confirm our findings and define the relationship between factors influencing indirect calcium estimation and incident T2DM. Copyright © 2015 Elsevier B.V. All rights reserved.

Diabetic retinopathy and its risk factors in patients with type 2 diabetes attending rural primary healthcare facilities in Tamil Nadu.

PubMed

Fredrick, Tony; Kaur, Prabhdeep; Murhekar, Manoj V; Jayaraman, Yuvaraj; Kolandaswamy, K; Rao, Sudha Ramachandra; David, Joseph K

2016-01-01

India has a high burden of diabetic retinopathy ranging from 12.2% to 20.4% among patients with type 2 diabetes mellitus (T2DM). A T2DM management programme was initiated in the public sector in Tamil Nadu. We estimated the prevalence of diabetic retinopathy and its associated risk factors. We did a cross-sectional survey among patients with T2DM attending two primary health centres for treatment and follow-up in Kancheepuram, Tamil Nadu in January- March 2013. We did a questionnaire-based survey, and measured blood pressure and biochemical parameters (serum creatinine, plasma glucose, etc.) of the patients. We examined their eyes by direct and indirect ophthalmoscopy and defined diabetic retinopathy using a modified classification by Klein et al. We calculated the proportion and 95% CI for the prevalence and adjusted odds ratio (AOR) for risk factors associated with diabetic retinopathy. Among the 270 patients, the mean (SD) age was 54.5 (10) years. The median duration of T2DM was 48 months. The prevalence of diabetic retinopathy was 29.6%. Overall, 65.9% of patients had hypertension, 14.4% had nephropathy (eGFR <60 mg/dl) and 67.4% had neuropathy. Among patients with comorbid conditions, 60%, 48%, 32%, and 3% were already diagnosed to have hypertension, neuropathy, retinopathy, and nephropathy, respectively. The risk factors for diabetic retinopathy were hypertension (AOR 3.2, 95% CI 1.7-6.3), duration of T2DM >5 years (AOR 6.5, 95% CI 3.6-11.7), poor glycaemic control (AOR 2.4, 95% CI 1.4-4.4), and nephropathy (AOR 2.3, 95% CI 1.1-4.6). There was a high burden of undetected retinopathy and other comorbid conditions among patients with T2DM. Early detection of comorbid conditions and glycaemic control can be improved by training care-providers and educating patients.

Influences of the current density on the performances of the chrome-plated layer in deterministic electroplating repair

NASA Astrophysics Data System (ADS)

Xia, H.; Shen, X. M.; Yang, X. C.; Xiong, Y.; Jiang, G. L.

2018-01-01

Deterministic electroplating repair is a novel method for rapidly repairing the attrited parts. By the qualitative contrast and quantitative comparison, influences of the current density on performances of the chrome-plated layer were concluded in this study. The chrome-plated layers were fabricated under different current densities when the other parameters were kept constant. Hardnesses, thicknesses and components, surface morphologies and roughnesses, and wearability of the chrome-plated layers were detected by the Vickers hardness tester, scanning electron microscope / energy dispersive X-ray detector, digital microscope in the 3D imaging mode, and the ball-milling instrument with profilograph, respectively. In order to scientifically evaluate each factor, the experimental data was normalized. A comprehensive evaluation model was founded to quantitative analyse influence of the current density based on analytic hierarchy process method and the weighted evaluation method. The calculated comprehensive evaluation indexes corresponding to current density of 40A/dm2, 45A/dm2, 50A/dm2, 55A/dm2, 60A/dm2, and 65A/dm2 were 0.2246, 0.4850, 0.4799, 0.4922, 0.8672, and 0.1381, respectively. Experimental results indicate that final optimal option was 60A/dm2, and the priority orders were 60A/dm2, 55A/dm2, 45A/dm2, 50A/dm2, 40A/dm2, and 65A/dm2.

Compatibility of a dark matter discovery at XENONnT or LZ with the WIMP thermal production mechanism

NASA Astrophysics Data System (ADS)

Catena, Riccardo; Conrad, Jan; Krauss, Martin B.

2018-05-01

The discovery of dark matter (DM) at XENONnT or LZ would place constraints on DM particle mass and coupling constants. It is interesting to ask when these constraints can be compatible with the DM thermal production mechanism. We address this question within the most general set of renormalizable models that preserve Lorentz and gauge symmetry, and that extend the standard model by one DM candidate of mass mDM and one particle of mass Mmed mediating DM-quark interactions. Our analysis divides into two parts. First, we postulate that XENONnT/LZ has detected μS˜O (100 ) signal events, and use this input to calculate the DM relic density, ΩDMh2. Then, we identify the regions in the Mmed-ΩDMh2 plane which are compatible with the observed signal and with current CMB data. We find that for most of the models considered here, O (100 ) signal events at XENONnT/LZ and the DM thermal production are only compatible for resonant DM annihilations, i.e. for Mmed≃2 mDM. In this case, XENONnT/LZ would be able to simultaneously measure mDM and Mmed. We also discuss the dependence of our results on mDM, μS and the DM spin, and provide analytic expressions for annihilation cross sections and mediator decay widths for all models considered in this study.

A Neutrality Test for Detecting Selection on DNA Methylation Using Single Methylation Polymorphism Frequency Spectrum

PubMed Central

Wang, Jun; Fan, Chuanzhu

2015-01-01

Inheritable epigenetic mutations (epimutations) can contribute to transmittable phenotypic variation. Thus, epimutations can be subject to natural selection and impact the fitness and evolution of organisms. Based on the framework of the modified Tajima’s D test for DNA mutations, we developed a neutrality test with the statistic “Dm” to detect selection forces on DNA methylation mutations using single methylation polymorphisms. With computer simulation and empirical data analysis, we compared the Dm test with the original and modified Tajima’s D tests and demonstrated that the Dm test is suitable for detecting selection on epimutations and outperforms original/modified Tajima’s D tests. Due to the higher resetting rate of epimutations, the interpretation of Dm on epimutations and Tajima’s D test on DNA mutations could be different in inferring natural selection. Analyses using simulated and empirical genome-wide polymorphism data suggested that genes under genetic and epigenetic selections behaved differently. We applied the Dm test to recently originated Arabidopsis and human genes, and showed that newly evolved genes contain higher level of rare epialleles, suggesting that epimutation may play a role in origination and evolution of genes and genomes. Overall, we demonstrate the utility of the Dm test to detect whether the loci are under selection regarding DNA methylation. Our analytical metrics and methodology could contribute to our understanding of evolutionary processes of genes and genomes in the field of epigenetics. The Perl script for the “Dm” test is available at http://fanlab.wayne.edu/ (last accessed December 18, 2014). PMID:25539727

Scalar dark matter interpretation of the DAMPE data with U(1) gauge interactions

NASA Astrophysics Data System (ADS)

Cao, Junjie; Feng, Lei; Guo, Xiaofei; Shang, Liangliang; Wang, Fei; Wu, Peiwen

2018-05-01

Recently, the Dark Matter Particle Explorer (DAMPE) experiment released the new measurement of the total cosmic e+e- flux between 25 GeV and 4.6 TeV, which indicates a spectral softening at around 0.9 TeV and a tentative peak at around 1.4 TeV. We utilize a scalar dark matter (DM) model to explain the DAMPE peak by χ χ →Z'Z'→ℓℓ ¯ ℓ'ℓ' ¯ with an additional anomaly-free gauged U (1 ) family symmetry, in which χ , Z', and ℓ(') denote, respectively, the scalar DM, the new gauge boson, and ℓ(')=e , μ , τ with mχ˜mZ'˜2 ×1.5 (TeV ) . We first illustrate that the minimal framework GSM×U (1 )Y' with the above mass choices can explain the DAMPE excess, which, however, be excluded by LHC constraints from the Z' searches. Then, we study a nonminimal framework GSM×U (1 )Y'×U (1 )Y'' in which U (1 )Y'' mixes with U (1)Y'. We show that such a framework can interpret the DAMPE data and at the same time survive all other constraints including the DM relic abundance, DM direct detection, and collider bounds. We also investigate the predicted e+e- spectrum in this framework and find that the mass splitting Δ m =mχ-mZ'' should be less than about 17 GeV to produce the peaklike structure.

MASS MEASUREMENTS IN PROTOPLANETARY DISKS FROM HYDROGEN DEUTERIDE

DOE Office of Scientific and Technical Information (OSTI.GOV)

McClure, M. K.; Bergin, E. A.; Cleeves, L. I., E-mail: mmcclure@eso.org, E-mail: ebergin@umich.edu, E-mail: ilse.cleeves@cfa.harvard.edu

2016-11-10

The total gas mass of a protoplanetary disk is a fundamental, but poorly determined, quantity. A new technique has been demonstrated to assess directly the bulk molecular gas reservoir of molecular hydrogen using the HD J = 1–0 line at 112 μ m. In this work we present a Herschel Space Observatory {sup 10} survey of six additional T Tauri disks in the HD line. Line emission is detected at >3 σ significance in two cases: DM Tau and GM Aur. For the other four disks, we establish upper limits to the line flux. Using detailed disk structure and ray-tracingmore » models, we calculate the temperature structure and dust mass from modeling the observed spectral energy distributions, and we include the effect of UV gas heating to determine the amount of gas required to fit the HD line. The ranges of gas masses are 1.0–4.7 × 10{sup -2} for DM Tau and 2.5–20.4 × 10{sup -2} for GM Aur. These values are larger than those found using CO for GM Aur, while the CO-derived gas mass for DM Tau is consistent with the lower end of our mass range. This suggests a CO chemical depletion from the gas phase of up to a factor of five for DM Tau and up to two orders of magnitude for GM Aur. We discuss how future analysis can narrow the mass ranges further.« less

Cryogenic scintillation properties of n-type GaAs for the direct detection of MeV/c2 dark matter

NASA Astrophysics Data System (ADS)

Derenzo, S.; Bourret, E.; Hanrahan, S.; Bizarri, G.

2018-03-01

This paper is the first report of n-type GaAs as a cryogenic scintillation radiation detector for the detection of electron recoils from interacting dark matter (DM) particles in the poorly explored MeV/c2 mass range. Seven GaAs samples from two commercial suppliers and with different silicon and boron concentrations were studied for their low temperature optical and scintillation properties. All samples are n-type even at low temperatures and exhibit emission between silicon donors and boron acceptors that peaks at 1.33 eV (930 nm). The lowest excitation band peaks at 1.44 eV (860 nm), and the overlap between the emission and excitation bands is small. The X-ray excited luminosities range from 7 to 43 photons/keV. Thermally stimulated luminescence measurements show that n-type GaAs does not accumulate metastable radiative states that could cause afterglow. Further development and use with cryogenic photodetectors promises a remarkable combination of large target size, ultra-low backgrounds, and a sensitivity to electron recoils of a few eV that would be produced by DM particles as light as a few MeV/c2.

Mono-X versus direct searches: simplified models for dark matter at the LHC

DOE PAGES

Liew, Seng Pei; Papucci, Michele; Vichi, Alessandro; ...

2017-06-15

We consider simplified models for dark matter (DM) at the LHC, focused on mono-Higgs, -Z or -b produced in the final state. Our primary purpose is to study the LHC reach of a relatively complete set of simplified models for these final states, while comparing the reach of the mono-X DM search against direct searches for the mediating particle. We find that direct searches for the mediating particle, whether in di-jets, jets+E T, multi-b+E T, or di-boson+E T, are usually stronger. We draw attention to the cases that the mono-X search is strongest, which include regions of parameter space inmore » inelastic DM, two Higgs doublet, and squark mediated production models with a compressed spectrum.« less

Mono-X versus direct searches: simplified models for dark matter at the LHC

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liew, Seng Pei; Papucci, Michele; Vichi, Alessandro

We consider simplified models for dark matter (DM) at the LHC, focused on mono-Higgs, -Z or -b produced in the final state. Our primary purpose is to study the LHC reach of a relatively complete set of simplified models for these final states, while comparing the reach of the mono-X DM search against direct searches for the mediating particle. We find that direct searches for the mediating particle, whether in di-jets, jets+E T, multi-b+E T, or di-boson+E T, are usually stronger. We draw attention to the cases that the mono-X search is strongest, which include regions of parameter space inmore » inelastic DM, two Higgs doublet, and squark mediated production models with a compressed spectrum.« less

Constraints on the dark matter annihilation from Fermi-LAT observation of M31

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Zhengwei; Yuan, Qiang; Huang, Xiaoyuan

2016-12-01

Gamma-ray is a good probe of dark matter (DM) particles in the Universe. We search for the DM annihilation signals in the direction of the Andromeda galaxy (M31) using 7.5 year Fermi-LAT pass 8 data. Similar to Pshirkov et al. (2016), we find that there is residual excess emission from the direction of M31 if only the galactic disk as traced by the far infrared emission is considered. Adding a point-like source will improve the fitting effectively, although additional slight improvements can be found if an extended component such as a uniform disk or two bubbles is added instead. Takingmore » the far infrared disk plus a point source as the background model, we search for the DM annihilation signals in the data. We find that there is strong degeneracy between the emission from the galaxy and that from 10s GeV mass DM annihilation in the main halo with quark final state. However, the required DM annihilation cross section is about 10{sup −25}–10{sup −24} cm{sup 3}s{sup −1}, orders of magnitude larger than the constraints from observations of dwarf spheroidal galaxies, indicating a non-DM origin of the emission. If DM subhalos are taken into account, the degeneracy is broken. When considering the enhancement from DM subhalos, the constraints on DM model parameters are comparable to (or slightly weaker than) those from the population of dwarf spheroidal galaxies. We also discuss the inverse Compton scattering component from DM annihilation induced electrons/positrons. For the first time we include an energy dependent template of the inverse Compton emission (i.e., a template cube) in the data analysis to take into account the effect of diffusion of charged particles. We find a significant improvement of the constraints in the high mass range of DM particles after considering the inverse Compton emission.« less

MicroRNA-134 Contributes to Glucose-Induced Endothelial Cell Dysfunction and This Effect Can Be Reversed by Far-Infrared Irradiation

PubMed Central

Wang, Yen-Li; Chang, Shih-Ting; Liao, Ko-Hsun; Lo, Hung-Hao; Chiu, Ya-Lin; Hsieh, Tsung-Han; Huang, Tse-Shun; Lin, Chin-Sheng; Cheng, Shu-Meng; Cheng, Cheng-Chung

2016-01-01

Diabetes mellitus (DM) is a metabolic disease that is increasing worldwide. Furthermore, it is associated with the deregulation of vascular-related functions, which can develop into major complications among DM patients. Endothelial colony forming cells (ECFCs) have the potential to bring about medical repairs because of their post-natal angiogenic activities; however, such activities are impaired by high glucose- (HG) and the DM-associated conditions. Far-infrared radiation (FIR) transfers energy as heat that is perceived by the thermoreceptors in human skin. Several studies have revealed that FIR improves vascular endothelial functioning and boost angiogenesis. FIR has been used as anti-inflammatory therapy and as a clinical treatment for peripheral circulation improvement. In addition to vascular repair, there is increasing evidence to show that FIR can be applied to a variety of diseases, including cardiovascular disorders, hypertension and arthritis. Yet mechanism of action of FIR and the biomarkers that indicate FIR effects remain unclear. MicroRNA-134 (miR-134-5p) was identified by small RNA sequencing as being increased in high glucose (HG) treated dfECFCs (HG-dfECFCs). Highly expressed miR-134 was also validated in dmECFCs by RT-qPCR and it is associated with impaired angiogenic activities of ECFCs. The functioning of ECFCs is improved by FIR treatment and this occurs via a reduction in the level of miR-134 and an increase in the NRIP1 transcript, a direct target of miR-134. Using a mouse ischemic hindlimb model, the recovery of impaired blood flow in the presence of HG-dfECFCs was improved by FIR pretreatment and this enhanced functionality was decreased when there was miR-134 overexpression in the FIR pretreated HG-dfECFCs. In conclusion, our results reveal that the deregulation of miR-134 is involved in angiogenic defects found in DM patients. FIR treatment improves the angiogenic activity of HG-dfECFCs and dmECFCs and FIR has potential as a treatment for DM. Detection of miR-134 expression in FIR-treated ECFCs should help us to explore further the effectiveness of FIR therapy. PMID:26799933

MicroRNA-134 Contributes to Glucose-Induced Endothelial Cell Dysfunction and This Effect Can Be Reversed by Far-Infrared Irradiation.

PubMed

Wang, Hsei-Wei; Su, Shu-Han; Wang, Yen-Li; Chang, Shih-Ting; Liao, Ko-Hsun; Lo, Hung-Hao; Chiu, Ya-Lin; Hsieh, Tsung-Han; Huang, Tse-Shun; Lin, Chin-Sheng; Cheng, Shu-Meng; Cheng, Cheng-Chung

2016-01-01

Diabetes mellitus (DM) is a metabolic disease that is increasing worldwide. Furthermore, it is associated with the deregulation of vascular-related functions, which can develop into major complications among DM patients. Endothelial colony forming cells (ECFCs) have the potential to bring about medical repairs because of their post-natal angiogenic activities; however, such activities are impaired by high glucose- (HG) and the DM-associated conditions. Far-infrared radiation (FIR) transfers energy as heat that is perceived by the thermoreceptors in human skin. Several studies have revealed that FIR improves vascular endothelial functioning and boost angiogenesis. FIR has been used as anti-inflammatory therapy and as a clinical treatment for peripheral circulation improvement. In addition to vascular repair, there is increasing evidence to show that FIR can be applied to a variety of diseases, including cardiovascular disorders, hypertension and arthritis. Yet mechanism of action of FIR and the biomarkers that indicate FIR effects remain unclear. MicroRNA-134 (miR-134-5p) was identified by small RNA sequencing as being increased in high glucose (HG) treated dfECFCs (HG-dfECFCs). Highly expressed miR-134 was also validated in dmECFCs by RT-qPCR and it is associated with impaired angiogenic activities of ECFCs. The functioning of ECFCs is improved by FIR treatment and this occurs via a reduction in the level of miR-134 and an increase in the NRIP1 transcript, a direct target of miR-134. Using a mouse ischemic hindlimb model, the recovery of impaired blood flow in the presence of HG-dfECFCs was improved by FIR pretreatment and this enhanced functionality was decreased when there was miR-134 overexpression in the FIR pretreated HG-dfECFCs. In conclusion, our results reveal that the deregulation of miR-134 is involved in angiogenic defects found in DM patients. FIR treatment improves the angiogenic activity of HG-dfECFCs and dmECFCs and FIR has potential as a treatment for DM. Detection of miR-134 expression in FIR-treated ECFCs should help us to explore further the effectiveness of FIR therapy.

Ratiometric analysis of optical coherence tomography-measured in vivo retinal layer thicknesses for the detection of early diabetic retinopathy.

PubMed

Bhaduri, Basanta; Shelton, Ryan L; Nolan, Ryan M; Hendren, Lucas; Almasov, Alexandra; Labriola, Leanne T; Boppart, Stephen A

2017-11-01

Influence of diabetes mellitus (DM) and diabetic retinopathy (DR) on parafoveal retinal thicknesses and their ratios was evaluated. Six retinal layer boundaries were segmented from spectral-domain optical coherence tomography images using open-source software. Five study groups: (1) healthy control (HC) subjects, and subjects with (2) controlled DM, (3) uncontrolled DM, (4) controlled DR and (5) uncontrolled DR, were identified. The one-way analyses of variance (ANOVA) between adjacent study groups (i. e. 1 with 2, 2 with 3, etc) indicated differences in retinal thicknesses and ratios. Overall retinal thickness, ganglion cell layer (GCL) thickness, inner plexiform layer (IPL) thickness, and their combination (GCL+ IPL), appeared to be significantly less in the uncontrolled DM group when compared to controlled DM and controlled DR groups. Although the combination of nerve fiber layer (NFL) and GCL, and IPL thicknesses were not different, their ratio, (NFL+GCL)/IPL, was found to be significantly higher in the controlled DM group compared to the HC group. Comparisons of the controlled DR group with the controlled DM group, and with the uncontrolled DR group, do not show any differences in the layer thicknesses, though several significant ratios were obtained. Ratiometric analysis may provide more sensitive parameters for detecting changes in DR. Picture: A representative segmented OCT image of the human retina is shown. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Association of the mu-opioid receptor gene with type 2 diabetes mellitus in an African American population.

PubMed

Gallagher, Carla J; Gordon, Candace J; Langefeld, Carl D; Mychaleckyj, Josyf C; Freedman, Barry I; Rich, Stephen S; Bowden, Donald W; Sale, Michèle M

2006-01-01

African Americans (AA) are at increased risk for developing type 2 diabetes mellitus (T2DM) relative to European Americans. We previously detected linkage of T2DM to 6q24-q27 (LOD 2.26) at 163.5 cM, closest to marker D6S1035, in a genome-wide scan of AA families. The mu-opioid receptor gene (OPRM1) is located within the LOD-1 support interval of this linkage peak. OPRM1 is an attractive positional candidate gene for T2DM susceptibility since agonists of OPRM1 affect glucose-induced insulin release and OPRM1 knockout mice have a more rapid induction of insulin resistance than wild-type. Twenty-two SNPs in this gene, at an average spacing of 3.9 kb, were genotyped in 380 AA T2DM cases and 276 AA controls. In single SNP association analyses, rs648007 demonstrated significant evidence of association with T2DM (P=0.013). Four blocks of high linkage disequilibrium were detected across the OPRM1 gene. Association analyses of haplotypes in each of these blocks revealed two haplotype blocks with significant overall P values (P=0.007 and 0.046). Significant, but rare, risk and protective haplotypes were identified as driving these associations with T2DM (P=0.034-0.047). These associations suggest that the OPRM1 gene plays a role in T2DM susceptibility in African Americans.

Identification of streptococcal proteins reacting with sera from Behçet's disease and rheumatic disorders.

PubMed

Cho, Sung Bin; Lee, Ju Hee; Ahn, Keun Jae; Cho, Suhyun; Park, Yong-Beom; Lee, Soo-Kon; Bang, Dongsik; Lee, Kwang Hoon

2010-01-01

We evaluated the reactivity of sera from Behçet's disease (BD), systemic lupus erythematosus (SLE), dermatomyositis (DM), rheumatoid arthritis (RA), and Takayasu's arteritis (TA) patients against human α-enolase and streptococcal α-enolase, and identified additional streptococcal antigens. Enzyme-linked immunosorbent assay (ELISA) and immunoblotting were performed using sera from patients with BD, SLE, DM, RA, and TA and healthy volunteers (control) against human α-enolase and streptococcal α-enolase. Immunoblot analysis and matrix-assisted laser desorption ionisation-time-of-flight mass spectrometry were used to identify and recombine other streptococcal antigens. Specific positive signals against recombinant human α-enolase were detected by IgM ELISA of serum samples from 50% of BD, 14.3% of SLE, 57.1% of DM, 42.9% of RA, and 57.1% of TA patients. Specific positive signals against streptococcal α-enolase were detected from 42.9% of BD, 14.3% of DM, and 14.3% of TA patients. No SLE and RA sera reacted against streptococcal α-enolase antigen. Streptococcal proteins reacting with sera were identified as hypothetical protein (HP) for SLE and DM patients, acid phosphatase (AP) for RA patients, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) for TA patients. We observed that RA patients did not present serum reactivity against either HP or GAPDH though BD, SLE, DM, and TA patients did. Also, AP reacted with sera from BD, SLE, DM, RA, and TA patients.

TECHNIQUES FOR HIGH-CONTRAST IMAGING IN MULTI-STAR SYSTEMS. I. SUPER-NYQUIST WAVEFRONT CONTROL

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thomas, S.; Belikov, R.; Bendek, E.

2015-09-01

Direct imaging of extra-solar planets is now a reality with the deployment and commissioning of the first generation of specialized ground-based instruments (GPI, SPHERE, P1640, and SCExAO). These systems allow of planets 10{sup 7} times fainter than their host star. For space-based missions (EXCEDE, EXO-C, EXO-S, WFIRST), various teams have demonstrated laboratory contrasts reaching 10{sup −10} within a few diffraction limits from the star. However, all of these current and future systems are designed to detect faint planets around a single host star, while most non-M-dwarf stars such as Alpha Centauri belong to multi-star systems. Direct imaging around binaries/multiple systemsmore » at a level of contrast allowing detection of Earth-like planets is challenging because the region of interest is contaminated by the host star's companion in addition to the host itself. Generally, the light leakage is caused by both diffraction and aberrations in the system. Moreover, the region of interest usually falls outside the correcting zone of the deformable mirror (DM) with respect to the companion. Until now, it has been thought that removing the light of a companion star is too challenging, leading to the exclusion of many binary systems from target lists of direct imaging coronographic missions. In this paper, we will show new techniques for high-contrast imaging of planets around multi-star systems and detail the Super-Nyquist Wavefront Control (SNWC) method, which allows wavefront errors to be controlled beyond the nominal control region of the DM. Our simulations have demonstrated that, with SNWC, raw contrasts of at least 5 × 10{sup −9} in a 10% bandwidth are possible.« less

Nitric oxide levels in patients with diabetes mellitus: A systematic review and meta-analysis.

PubMed

Assmann, Taís S; Brondani, Letícia A; Bouças, Ana P; Rheinheimer, Jakeline; de Souza, Bianca M; Canani, Luís H; Bauer, Andrea C; Crispim, Daisy

2016-12-30

Altered serum nitric oxide (NO) levels in patients with diabetes mellitus (DM) have been reported by different studies; however, results are still controversial. Until this date, no meta-analysis evaluated the association of NO levels with DM. Thus, this paper describes a meta-analysis conducted to evaluate if there is a relationship between NO levels and type 1 DM (T1DM) or type 2 DM (T2DM). A literature search was done to identify all studies that investigated NO levels between T1DM or T2DM patients (cases) and non-diabetic subjects (controls). Measurement of nitrate and nitrite (NOx - the stable NO products) were used to estimate NO concentrations because they closely reflect NO bioavailability. Weighted mean differences (WMD) of NOx levels between case and control samples were calculated for T1DM and T2DM groups. Thirty studies were eligible for inclusion in the meta-analysis (8 in T1DM samples and 22 in T2DM samples). NOx levels were increased in European T1DM patients compared with controls [random effect model (REM) WMD = 8.55, 95% CI 2.88 - 14.21]. No other ethnicity was evaluated in T1DM studies. NOx levels were also increased in both European (REM WMD = 18.76, 95% CI 1.67 - 35.85) and Asian (REM WMD = 18.41, 95% CI 8.01 - 28.81) T2DM patients, but not in Latin American patients compared with controls. This meta-analysis detected a significant increase in NOx levels in European T1DM patients as well as European and Asian T2DM patients. Further studies in other ethnicities are necessary to confirm these data. Copyright © 2016 Elsevier Inc. All rights reserved.

Little composite dark matter

NASA Astrophysics Data System (ADS)

Balkin, Reuven; Perez, Gilad; Weiler, Andreas

2018-02-01

We examine the dark matter phenomenology of a composite electroweak singlet state. This singlet belongs to the Goldstone sector of a well-motivated extension of the Littlest Higgs with T-parity. A viable parameter space, consistent with the observed dark matter relic abundance as well as with the various collider, electroweak precision and dark matter direct detection experimental constraints is found for this scenario. T-parity implies a rich LHC phenomenology, which forms an interesting interplay between conventional natural SUSY type of signals involving third generation quarks and missing energy, from stop-like particle production and decay, and composite Higgs type of signals involving third generation quarks associated with Higgs and electroweak gauge boson, from vector-like top-partners production and decay. The composite features of the dark matter phenomenology allows the composite singlet to produce the correct relic abundance while interacting weakly with the Higgs via the usual Higgs portal coupling λ _{ {DM}}˜ O(1%), thus evading direct detection.

Robust Constraints and Novel Gamma-Ray Signatures of Dark Matter That Interacts Strongly With Nucleons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hooper, Dan; McDermott, Samuel D.

Due to shielding, direct detection experiments are in some cases insensitive to dark matter candidates with very large scattering cross sections with nucleons. In this paper, we revisit this class of models, and derive a simple analytic criterion for conservative but robust direct detection limits. While large spin-independent cross sections seem to be ruled out, we identify potentially viable parameter space for dark matter with a spin-dependent cross section with nucleons in the range ofmore » $$10^{-27} {\\rm cm}^2 < \\sigma_{{\\rm DM}-p} < 10^{-24} \\, {\\rm cm}^{2}$$. With these parameters, cosmic-ray scattering with dark matter in the extended halo of the Milky Way could generate a novel and distinctive gamma-ray signal at high galactic latitudes. Such a signal could be observable by Fermi or future space-based gamma-ray telescopes.« less

Bioactive compounds in cashew nut (Anacardium occidentale L.) kernels: effect of different shelling methods.

PubMed

Trox, Jennifer; Vadivel, Vellingiri; Vetter, Walter; Stuetz, Wolfgang; Scherbaum, Veronika; Gola, Ute; Nohr, Donatus; Biesalski, Hans Konrad

2010-05-12

In the present study, the effects of various conventional shelling methods (oil-bath roasting, direct steam roasting, drying, and open pan roasting) as well as a novel "Flores" hand-cracking method on the levels of bioactive compounds of cashew nut kernels were investigated. The raw cashew nut kernels were found to possess appreciable levels of certain bioactive compounds such as beta-carotene (9.57 microg/100 g of DM), lutein (30.29 microg/100 g of DM), zeaxanthin (0.56 microg/100 g of DM), alpha-tocopherol (0.29 mg/100 g of DM), gamma-tocopherol (1.10 mg/100 g of DM), thiamin (1.08 mg/100 g of DM), stearic acid (4.96 g/100 g of DM), oleic acid (21.87 g/100 g of DM), and linoleic acid (5.55 g/100 g of DM). All of the conventional shelling methods including oil-bath roasting, steam roasting, drying, and open pan roasting revealed a significant reduction, whereas the Flores hand-cracking method exhibited similar levels of carotenoids, thiamin, and unsaturated fatty acids in cashew nuts when compared to raw unprocessed samples.

From direct detection to relic abundance: the case of proton-philic spin-dependent inelastic Dark Matter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scopel, Stefano; Yu, Hyeonhye, E-mail: scopel@sogang.ac.kr, E-mail: skyh2yu@gmail.com

We discuss strategies to make inferences on the thermal relic abundance of a Weakly Interacting Massive Particle (WIMP) when the same effective dimension-six operator that explains an experimental excess in direct detection is assumed to drive decoupling at freeze-out, and apply them to the explicit scenario of WIMP inelastic up-scattering with spin-dependent couplings to protons (proton-philic Spin-dependent Inelastic Dark Matter, pSIDM), a phenomenological set-up containing two Dark Matter (DM) particles χ{sub 1} and χ{sub 2} with masses m {sub χ}= m {sub χ{sub 1}} and m {sub χ{sub 2}}= m {sub χ}+δ that we have shown in a previous papermore » to explain the DAMA effect in compliance with the constraints from other detectors. We also update experimental constraints on pSIDM, extend the analysis to the most general spin-dependent momentum-dependent interactions allowed by non-relativistic Effective Field Theory (EFT), and consider for the WIMP velocity distribution in our Galaxy f ( v ) both a halo-independent approach and a standard Maxwellian. Under these conditions we find that the DAMA effect can be explained in terms of the particle χ{sub 1} in compliance with all the other constraints for all the analyzed EFT couplings and also for a Maxwellian f ( v ). As far as the relic abundance is concerned, we show that the problem of calculating it by using direct detection data to fix the model parameters is affected by a strong sensitivity on f ( v ) and by the degeneracy between the WIMP local density ρ{sub χ} and the WIMP-nucleon scattering cross section, since ρ{sub χ} must be rescaled with respect to the observed DM density in the neighborhood of the Sun when the calculated relic density Ω is smaller than the observed one Ω{sub 0}. As a consequence, a DM direct detection experiment is not directly sensitive to the physical cut-off scale of the EFT, but on some dimensional combination that does not depend on the actual value of Ω. However, such degeneracy can be used to develop a consistency test on the possibility that the WIMP is a thermal relic in the first place. When we apply it to the pSIDM scenario we find that only a WIMP with the standard spin-dependent interaction O=χ-bar {sub 1γ}{sup μ}γ{sup 5χ{sub 2}} q-bar γ{sub μ}γ{sup 5} q + h.c. with quarks can be a thermal relic for, approximately, 10 GeV\\;≲ m {sub χ}≲ 16 GeV, 17 keV\\;≲ δ≲ 28 keV, and a large uncertainty on Ω, 6× 10{sup −7}Ω{sub 0≲} Ω ≲ Ω{sub 0}. In order for the scenario to work the WIMP galactic velocity distribution must depart from a Maxwellian. Moreover, all the χ{sub 2} states must have already decayed today, and this requires some additional mechanism besides that provided by the O operator.« less

Clinical and Laboratory Characteristics of Childhood Diabetes Mellitus: A Single-Center Study from 2000 to 2013

PubMed Central

Park, Tae Hyun; Lee, Dae-Yeol

2016-01-01

We examined the clinical and laboratory characteristics of children newly diagnosed with diabetes mellitus (DM) in a single-center study. We retrospectively reviewed the data of 155 children with DM between January 2000 and December 2013. Of 155 diabetic children, 87 (56.1%) were diagnosed with type 1 DM (T1DM) and 68 (43.9%) with type 2 DM (T2DM). Mean ages at diagnosis were 8.95±3.89 years (T1DM) and 13.76±2.23 years (T2DM), respectively (p<0.001). There were significant differences in HbA1c, C-peptide, and glutamic acid decarboxylase antibody levels between the T1DM and T2DM groups. Annual numbers of children with DM have increased, and since 2011 the number of children with T2DM has surpassed the number with T1DM. The most common clinical symptom in T1DM was polyuria, and 26.4% of children with T1DM presented initially with diabetic ketoacidosis. In contrast, 60.3% of T2DM children showed glucosuria in a school urine screening, and only 19.1% presented with polydipsia. The rate of positivity for at least more than one islet autoantibody was 77.1% in T1DM and 26.3% in T2DM. Serum C-peptide levels in T2DM were increased up to 12 months after onset and remained >3.59 ng/mL for 36 months. However, serum C-peptide levels in T1DM were slightly increased up to 6 months after onset and gradually decreased to 0.32 ng/mL for 36 months. The prevalence of children with DM has increased over the last 14 years, and the proportion of T2DM patients has rapidly increased since 2009. Because childhood DM is associated with several metabolic and cardiovascular complications, children should be screened for early detection of DM, especially asymptomatic T2DM in children and adolescents. PMID:26866002

Healthcare resource use, direct and indirect costs of hypoglycemia in type 1 and type 2 diabetes, and nationwide projections. Results of the HYPOS-1 study.

PubMed

Giorda, C B; Rossi, M C; Ozzello, O; Gentile, S; Aglialoro, A; Chiambretti, A; Baccetti, F; Gentile, F M; Romeo, F; Lucisano, G; Nicolucci, A

2017-03-01

To obtain an accurate picture of the total costs of hypoglycemia, including the indirect costs and comparing the differences between type 1 (T1DM) and type 2 diabetes mellitus (T2DM). HYPOS-1 was a multicenter, retrospective cohort study which analyzed the data of 2229 consecutive patients seen at 18 diabetes clinics. Data on healthcare resource use and indirect costs by diabetes type were collected via a questionnaire. The domains of inpatient admission and hospital stay, work days lost, and third-party assistance were also explored. Resource utilization was reported as estimated incidence rates (IRs) of hypoglycemic episodes per 100 person-years and estimated costs as IRs per person-years. For every 100 patients with T1DM, 9 emergency room (ER) visits and 6 emergency medical service calls for hypoglycemia were required per year; for every 100 patients with T2DM, 3 ER visits and 1 inpatient admission were required, with over 3 nights spent in hospital. Hypoglycemia led to 58 work days per 100 person-years lost by the patient or a family member in T1DM versus 19 in T2DM. The costs in T1DM totaled €90.99 per person-year and €62.04 in T2DM. Direct and indirect costs making up the total differed by type of diabetes (60% indirect costs in T1DM versus 43% in T2DM). The total cost associated with hypoglycemia in Italy is estimated to be €107 million per year. Indirect costs meaningfully contribute to the total costs associated with hypoglycemia. As compared with T1DM, T2DM requires fewer ER visits and incurs lower indirect costs but more frequent hospital use. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Digital breast tomosynthesis (DBT): recommendations from the Italian College of Breast Radiologists (ICBR) by the Italian Society of Medical Radiology (SIRM) and the Italian Group for Mammography Screening (GISMa).

PubMed

Bernardi, Daniela; Belli, Paolo; Benelli, Eva; Brancato, Beniamino; Bucchi, Lauro; Calabrese, Massimo; Carbonaro, Luca A; Caumo, Francesca; Cavallo-Marincola, Beatrice; Clauser, Paola; Fedato, Chiara; Frigerio, Alfonso; Galli, Vania; Giordano, Livia; Giorgi Rossi, Paolo; Golinelli, Paola; Morrone, Doralba; Mariscotti, Giovanna; Martincich, Laura; Montemezzi, Stefania; Naldoni, Carlo; Paduos, Adriana; Panizza, Pietro; Pediconi, Federica; Querci, Fiammetta; Rizzo, Antonio; Saguatti, Gianni; Tagliafico, Alberto; Trimboli, Rubina M; Zappa, Marco; Zuiani, Chiara; Sardanelli, Francesco

2017-10-01

This position paper, issued by ICBR/SIRM and GISMa, summarizes the evidence on DBT and provides recommendations for its use. In the screening setting, DBT in adjunct to digital mammography (DM) increased detection rate by 0.5-2.7‰ and decreased false positives by 0.8-3.6% compared to DM alone in observational and double-testing experimental studies. The reduction in recall rate could be less prominent in those screening programs which already have low recall rates with DM. The increase in radiation exposure associated with DM/DBT protocols has been solved by the introduction of synthetic mammograms (sDM) reconstructed from DBT datasets. Thus, whenever possible, sDM/DBT should be preferred to DM/DBT. However, before introducing DBT as a routine screening tool for average-risk women, we should wait for the results of randomized controlled trials and for a statistically significant and clinically relevant reduction in the interval cancer rate, hopefully associated with a reduction in the advanced cancer rate. Otherwise, a potential for overdiagnosis and overtreatment cannot be excluded. Studies exploring this issue are ongoing. Screening of women at intermediate risk should follow the same recommendations, with particular protocols for women with previous BC history. In high-risk women, if mammography is performed as an adjunct to MRI or in the case of MRI contraindications, sDM/DBT protocols are suggested. Evidence exists in favor of DBT usage in women with clinical symptoms/signs and asymptomatic women with screen-detected findings recalled for work-up. The possibility to perform needle biopsy or localization under DBT guidance should be offered when DBT-only findings need characterization or surgery.

Screening for type 2 diabetes mellitus in overweight and obese subjects made easy by the FINDRISC score.

PubMed

Meijnikman, A S; De Block, C E M; Verrijken, A; Mertens, I; Corthouts, B; Van Gaal, L F

2016-08-01

To evaluate the use of the FINDRISC score in an overweight and obese population to predict glucose status. In 651 overweight/obese subjects (M/F: 193/458, age 43±13 y, BMI 38.2±6.1kg/m(2)) glucose status was tested using OGTT and HbA1c. Furthermore, the FINDRISC questionnaire and CT visceral fat (VAT) and subcutaneous fat (SAT) were examined. Exactly 50.4% were found to have prediabetes and 11.1% were newly diagnosed with type 2 diabetes (T2DM) (M/F=22.2/8.8%). Subjects without T2DM had a FINDRISC score of 11±3, those with pre-DM 13±4, and subjects with de novo T2DM 15±5. The aROC of the FINDRISC for detecting T2DM was 0.76 (95% CI 0.72-0.82), with 13 as cutoff point. The FINDRISC score correlated with VAT (r=0.34, p<0.001) and VAT/SAT ratio (r=0.39, p<0.001). The aROC of the FINDRISC to detect excess VAT was 0.79 (95%CI 0.72-0.84). In a large group of overweight and obese subjects, 50.4% were found to have pre-DM and 11.1% were newly diagnosed with T2DM. The FINDRISC score increased with worsening of glucose tolerance status and proved to be an independent predictor of T2DM status, as did HOMA-B, HOMA-S and VAT. The FINDRISC can also function as a good tool to predict visceral obesity. Copyright © 2016 Elsevier Inc. All rights reserved.

Serum Apelin: A New Marker of Early Atherosclerosis in Children with Type 1 Diabetes Mellitus

PubMed Central

Sabry, Rania N.; El Wakeel, Maged A.; El-Kassas, Ghada M.; Amer, Ahmed F.; El Batal, Wael H.; El-Zayat, Salwa Refat; Abou-El-Asrar, Mohamed

2018-01-01

INTRODUCTION: Type 1 diabetes mellitus (T1DM) is one of the most common chronic diseases in children that may be complicated by micro or macrovascular complications. Measurement of the carotid intima-media thickness (CIMT) allows the early detection of atherosclerotic alterations of blood vessels that may complicate T1DM. SUBJECTS AND METHODS: This study is a case-control study. Participants were classified into two groups. The first group included 40 children with T1DM and the second group included 30 matched healthy controls. The studied cases were recruited from Endocrinology and Diabetology Unit, Pediatric Hospital, Ain Shams University. Serum apelin, cholesterol, TG, LDL were measured for every case. Also, albumin level was analyzed in urine. Measurement of the carotid intima-media thickness (CIMT) was done for all cases. RESULTS: Comparison between T1DM patients and controls revealed that serum apelin, cholesterol, TG, LDL and albuminuria were significantly increased in cases compared to controls. Significant positive correlations were detected between HbA1C, albuminuria and lipid profile with apelin in the diabetic group (p < 0.05). CIMT has significant positive correlation with serum apelin levels (r = 0.36, p = 0.05). Also, this study found positive correlations between CIMT and some variables as LDL, SBP z-score and duration of the illness. CONCLUSION: Increased levels of serum apelin in T1DM patients may be considered as predicting factor for the ongoing development of vascular sequels. This study highlighted the possible validity of apelin assay as an early predictor of atherosclerosis in T1DM children. Evaluating CIMT in these patients is of at most important for early detection of subclinical atherosclerosis. PMID:29731925

Constraints on Dark Matter Interactions with Standard Model Particles from Cosmic Microwave Background Spectral Distortions.

PubMed

Ali-Haïmoud, Yacine; Chluba, Jens; Kamionkowski, Marc

2015-08-14

We propose a new method to constrain elastic scattering between dark matter (DM) and standard model particles in the early Universe. Direct or indirect thermal coupling of nonrelativistic DM with photons leads to a heat sink for the latter. This results in spectral distortions of the cosmic microwave background (CMB), the amplitude of which can be as large as a few times the DM-to-photon-number ratio. We compute CMB spectral distortions due to DM-proton, DM-electron, and DM-photon scattering for generic energy-dependent cross sections and DM mass m_{χ}≳1 keV. Using Far-Infrared Absolute Spectrophotometer measurements, we set constraints on the cross sections for m_{χ}≲0.1 MeV. In particular, for energy-independent scattering we obtain σ_{DM-proton}≲10^{-24} cm^{2} (keV/m_{χ})^{1/2}, σ_{DM-electron}≲10^{-27} cm^{2} (keV/m_{χ})^{1/2}, and σ_{DM-photon}≲10^{-39} cm^{2} (m_{χ}/keV). An experiment with the characteristics of the Primordial Inflation Explorer would extend the regime of sensitivity up to masses m_{χ}~1 GeV.

Dark Matter's secret liaisons: phenomenology of a dark U(1) sector with bound states

NASA Astrophysics Data System (ADS)

Cirelli, Marco; Panci, Paolo; Petraki, Kalliopi; Sala, Filippo; Taoso, Marco

2017-05-01

Dark matter (DM) charged under a dark U(1) force appears in many extensions of the Standard Model, and has been invoked to explain anomalies in cosmic-ray data, as well as a self-interacting DM candidate. In this paper, we perform a comprehensive phenomenological analysis of such a model, assuming that the DM abundance arises from the thermal freeze-out of the dark interactions. We include, for the first time, bound-state effects both in the DM production and in the indirect detection signals, and quantify their importance for FERMI, AMS-02, and CMB experiments. We find that DM in the mass range 1 GeV to 100 TeV, annihilating into dark photons of MeV to GeV mass, is in conflict with observations. Instead, DM annihilation into heavier dark photons is viable. We point out that the late decays of multi-GeV dark photons can produce significant entropy and thus dilute the DM density. This can lower considerably the dark coupling needed to obtain the DM abundance, and in turn relax the existing constraints.

Dark Matter's secret liaisons: phenomenology of a dark U(1) sector with bound states

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cirelli, Marco; Petraki, Kalliopi; Sala, Filippo

Dark matter (DM) charged under a dark U(1) force appears in many extensions of the Standard Model, and has been invoked to explain anomalies in cosmic-ray data, as well as a self-interacting DM candidate. In this paper, we perform a comprehensive phenomenological analysis of such a model, assuming that the DM abundance arises from the thermal freeze-out of the dark interactions. We include, for the first time, bound-state effects both in the DM production and in the indirect detection signals, and quantify their importance for FERMI, AMS-02, and CMB experiments. We find that DM in the mass range 1 GeVmore » to 100 TeV, annihilating into dark photons of MeV to GeV mass, is in conflict with observations. Instead, DM annihilation into heavier dark photons is viable. We point out that the late decays of multi-GeV dark photons can produce significant entropy and thus dilute the DM density. This can lower considerably the dark coupling needed to obtain the DM abundance, and in turn relax the existing constraints.« less

Glycation sites of human plasma proteins are affected to different extents by hyperglycemic conditions in type 2 diabetes mellitus.

PubMed

Frolov, Andrej; Blüher, Matthias; Hoffmann, Ralf

2014-09-01

Glucose can modify proteins in human blood, forming early glycation products (e.g., Amadori compounds), which can slowly degrade to advanced glycation endproducts (AGEs). AGEs contribute significantly to complications of diabetes mellitus and, thus, represent markers of advanced disease stages. They are, however, currently unsuitable for early diagnosis and therapeutic monitoring. Here, we report sensitive strategies to identify and relatively quantify protein glycation sites in human plasma samples obtained from type 2 diabetes mellitus (T2DM) patients and age-matched nondiabetic individuals using a bottom-up approach. Specifically, Amadori peptides were enriched from tryptic digests by boronic acid affinity chromatography, separated by reversed-phase chromatography, and analyzed on-line by high-resolution mass spectrometry. Among the 52 Amadori peptides studied here were 20 peptides resembling 19 glycation sites in six human proteins detected at statistically significantly higher levels in T2DM than in the normoglycemic controls. Four positions appeared to be unique for T2DM within the detection limit. All 19 glycation sites represent promising new biomarker candidates for early diagnosis of T2DM and adequate therapeutic control, as they may indicate early metabolic changes preceding T2DM.

The ArDM experiment

DOE PAGES

Harańczyk, M.; Amsler, C.; Badertscher, A.; ...

2010-08-24

The aim of the ArDM project is the development and operation of a one ton double-phase liquid argon detector for direct Dark Matter searches. The detector measures both the scintillation light and the ionization charge from ionizing radiation using two independent readout systems. This paper briefly describes the detector concept and presents preliminary results from the ArDM R & D program, including a 3 l prototype developed to test the charge readout system.

Unifying leptogenesis, dark matter and high-energy neutrinos with right-handed neutrino mixing via Higgs portal

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bari, Pasquale Di; Ludl, Patrick Otto; Palomares-Ruiz, Sergio

2016-11-21

We revisit a model in which neutrino masses and mixing are described by a two right-handed (RH) neutrino seesaw scenario, implying a strictly hierarchical light neutrino spectrum. A third decoupled RH neutrino, N{sub DM} with mass M{sub DM}, plays the role of cold dark matter (DM) and is produced by the mixing with a source RH neutrino, N{sub S} with mass M{sub S}, induced by Higgs portal interactions. The same interactions are also responsible for N{sub DM} decays. We discuss in detail the constraints coming from DM abundance and stability conditions showing that in the hierarchical case, for M{sub DM}≫M{submore » S}, there is an allowed window on M{sub DM} values necessarily implying a contribution, from DM decays, to the high-energy neutrino flux recently detected by IceCube. We also show how the model can explain the matter-antimatter asymmetry of the Universe via leptogenesis in the quasi-degenerate limit. In this case, the DM mass should be within the range 300 GeV ≲M{sub S}« less

Prevention, Detection, and Management of Diabetes in South Dakota.

PubMed

Hogue, Amy L; Huntington, Mark K

2017-01-01

Diabetes mellitus (DM) is increasing in prevalence nationwide and in South Dakota, with an especially high prevalence in its American Indian population. Screening is not recommended for type 1 DM, but is for type 2 DM and pre-diabetes in certain populations. Fasting glucose, two-hour glucose tolerance test, or hemoglobin A1c are appropriate screening options. Treatment can include diabetic self-management education programs and medications. In addition to glycemic control, other cardiovascular risk factors must be reduced in these patients and specific testing and consultations should be performed to detect complications such as nephropathy or retinopathy. Along with routine age-appropriate immunizations, most diabetic patients should receive the pneumococcal polysaccharide vaccine (PPSV-23), influenza, and the hepatitis B series. Progression from pre-diabetes to type 2 DM can be prevented or delayed in some patients through lifestyle interventions and/or metformin. The South Dakota Diabetes Coalition (www.sddiabetescoalition.org) is an excellent resource for clinicians and patients. Copyright© South Dakota State Medical Association.

Specific autoantibodies in dermatomyositis: a helpful tool to classify different clinical subsets.

PubMed

Merlo, Giulia; Clapasson, Andrea; Cozzani, Emanuele; Sanna, Luigi; Pesce, Giampaola; Bagnasco, Marcello; Burlando, Martina; Parodi, Aurora

2017-03-01

Autoantibodies are important in the diagnosis of dermatomyositis. They can be divided in two different groups: myositis-associated autoantibodies (MAA) prevailing in overlap syndromes, and myositis-specific autoantibodies (MSA), with diagnostic specificity exceeding 90%. Our purpose was to detect retrospectively the prevalence of the most common MSAs in a group of 19 adult DM patients (13 women, 6 men). A severe DM (SDM), with extensive cutaneous and muscular manifestations, dysphagia, and sometimes pneumopathy, was detected in ten cases. Three patients had a mild DM (MDM), with little muscle and skin impairment, and a short course. Four patients suffered from amyopathic DM (ADM), two from paraneoplastic DM (PDM). Each serum was tested for ANA, ENA, MAAs, MSAs. Myositis-specific autoantibodies were detected in 15 cases. The most frequent was anti-TIF1γ, associated with SDM or PDM in four out of seven cases. Anti-MDA5 antibodies were recorded in a SDM and in a ADM with lung fibrosis. Anti-Mi2 and anti-SRP antibodies were both detected in a MDM and in a SDM, whereas anti-SAE1 in a amyopathic form. Other antibodies (anti-NXP2, -Jo1, -PL7, -PL12, -OJ) were found in single patients with SDM. Our series confirmed that specific autoantibodies could be helpful to classify different clinical subsets, particularly in the case of paraneoplastic forms or association with pneumopathy. Moreover, they can help in predicting the disease evolution and influence therapeutic strategies. A greater number of cases should be useful to highlight the clinical and pathogenic role of these antibodies, and develop a homogeneous protocol for diagnosis and treatment.

Distribution and Fate of Tributyltin in the United States Marine Environment

DTIC Science & Technology

Tributyltin ( TBT ) has been measured in water in 12 of 15 harbors studied during U.S. Navy baseline surveys. The highest concentrations of TBT (some...no detectable (5 ng dm-3) TBT . TBT monitoring studies with increased detection limits (l ng dm-3) have documented a high degree of TBT variability...associated with tide, season and intermittent point source discharges. Although yacht harbors were shown to be the principal TBT source in most regions

Focal-plane electric field sensing with pupil-plane holograms

NASA Astrophysics Data System (ADS)

Por, Emiel H.; Keller, Christoph U.

2016-07-01

The direct detection and spectral characterization of exoplanets requires a coronagraph to suppress the diffracted star light. Amplitude and phase aberrations in the optical train fill the dark zone of the coronagraph with quasi-static speckles that limit the achievable contrast. Focal-plane electric field sensing, such as phase diversity introduced by a deformable mirror (DM), is a powerful tool to minimize this residual star light. The residual electric field can be estimated by sequentially applying phase probes on the DM to inject star light with a well-known amplitude and phase into the dark zone and analyzing the resulting intensity images. The DM can then be used to add light with the same amplitude but opposite phase to destructively interfere with this residual star light. Using a static phase-only pupil-plane element we create holographic copies of the point spread function (PSF), each superimposed with a certain pupil-plane phase probe. We therefore obtain all intensity images simultaneously while still retaining a central, unaltered science PSF. The electric field sensing method only makes use of the holographic copies, allowing for correction of the residual electric field while retaining the central PSF for uninterrupted science data collection. In this paper we demonstrate the feasibility of this method with numerical simulations.

Dynamic Membrane Technology for Printing Wastewater Reuse

NASA Astrophysics Data System (ADS)

Liu, Lin; Lu, Xujie; Chen, Jihua

As environmental regulations become rigid and the cost of freshwater increases, wastewater is considered as a major resource in China. The paper presented a study on the implementation of the advanced treatment process using dynamic membrane (DM) in reusing of printing wastewater. The DM was well formed by circulating 1.5g/L of PAC in 20 minutes, the trans-membrane pressure of 200 kPa and the cross-flow velocity of 0.75m/s. The printing effluents were treated in effluent treatment plants comprising a physicochemical option followed by biological process. The treated effluent contained chemical oxygen demand (COD), color and turbidity in the range of 45-60 mg/L, 0.030-0.045 (absorbance at 420 nm) and 3-5 NTU. The results showed that the COD, color and turbidity removal efficiencies of the DM permeate were 84%, 85% and 80%, respectively. The wastewater treated by DM was reused as process water and the final concentrated retentate could be discharged directly into sewage treatment works with no additional treatments. Cleaning and regeneration of DM were very convenient if necessary. The proper process was that the polluted DM was cleaned with tap water at high cross-flow velocity. When irreversible pollutants accumulate, it would be rinsed with chemicals tested and the membrane flux would be restored up to 95%. The result showed that DM was considered as a promising method for purification aimed at reuse of printing wastewater, resulting in direct environmental and economic benefits.

Validation of Indian diabetic risk score in diagnosing type 2 diabetes mellitus against high fasting blood sugar levels among adult population of central India.

PubMed

Bhadoria, Ajeet Singh; Kasar, Pradeep Kumar; Toppo, Neelam Anupama

2015-01-01

Globally the increasing prevalence of diabetes mellitus (DM) is major public health concern. The Indian Diabetes Risk Score (IDRS) was developed by Madras Diabetes Research Foundation (MDRF) as a simple tool to help detect undiagnosed type 2 DM (T2DM) in the community. We conducted a study among 911 adults of Jabalpur District to validate the IDRS score against increased fasting blood sugar levels in diagnosing T2DM. T2DM was confirmed either by history of previously known disease or fasting plasma glucose ≥126 mg/dl on two occasions. Sensitivity, specificity, positive predictive value, negative predictive value, Youden index (sensitivity + specificity -1), likelihood ratio for positive test, and likelihood ratio for negative test were calculated for IDRS cut-offs of ≥20, ≥40, ≥60, and ≥80 against the presence of T2DM (either known diabetic or fasting plasma glucose >126 mg/dl on two occasions). The overall prevalence of T2DM was 9.99% (95% confidence interval, 8.04-11.94%). In the Receiver operating characteristic analysis, IDRS had an area under the curve of 0.736 (P < 0.001). The best cut-off was IDRS 40 with a sensitivity, specificity, and Youden index of 60.4%, 70.7%, and 0.31, respectively. The findings of our study indicate that IDRS has excellent predictive value for detecting undiagnosed diabetes in the community and IDRS is also a much stronger risk indicator than examining individual risk factors like age, family history, obesity, or physical activity.

EZSCAN for undiagnosed type 2 diabetes mellitus: A systematic review and meta-analysis.

PubMed

Bernabe-Ortiz, Antonio; Ruiz-Alejos, Andrea; Miranda, J Jaime; Mathur, Rohini; Perel, Pablo; Smeeth, Liam

2017-01-01

The EZSCAN is a non-invasive device that, by evaluating sweat gland function, may detect subjects with type 2 diabetes mellitus (T2DM). The aim of the study was to conduct a systematic review and meta-analysis including studies assessing the performance of the EZSCAN for detecting cases of undiagnosed T2DM. We searched for observational studies including diagnostic accuracy and performance results assessing EZSCAN for detecting cases of undiagnosed T2DM. OVID (Medline, Embase, Global Health), CINAHL and SCOPUS databases, plus secondary resources, were searched until March 29, 2017. The following keywords were utilized for the systematic searching: type 2 diabetes mellitus, hyperglycemia, EZSCAN, SUDOSCAN, and sudomotor function. Two investigators extracted the information for meta-analysis and assessed the quality of the data using the Revised Version of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) checklist. Pooled estimates were obtained by fitting the logistic-normal random-effects model without covariates but random intercepts and using the Freeman-Tukey Arcsine Transformation to stabilize variances. Heterogeneity was also assessed using the I2 measure. Four studies (n = 7,720) were included, three of them used oral glucose tolerance test as the gold standard. Using Hierarchical Summary Receiver Operating Characteristic model, summary sensitivity was 72.0% (95%CI: 60.0%- 83.0%), whereas specificity was 56.0% (95%CI: 38.0%- 74.0%). Studies were very heterogeneous (I2 for sensitivity: 79.2% and for specificity: 99.1%) regarding the inclusion criteria and bias was present mainly due to participants selection. The sensitivity of EZSCAN for detecting cases of undiagnosed T2DM seems to be acceptable, but evidence of high heterogeneity and participant selection bias was detected in most of the studies included. More studies are needed to evaluate the performance of the EZSCAN for undiagnosed T2DM screening, especially at the population level.

p62/Sequestosome-1, Autophagy-related Gene 8, and Autophagy in Drosophila Are Regulated by Nuclear Factor Erythroid 2-related Factor 2 (NRF2), Independent of Transcription Factor TFEB.

PubMed

Jain, Ashish; Rusten, Tor Erik; Katheder, Nadja; Elvenes, Julianne; Bruun, Jack-Ansgar; Sjøttem, Eva; Lamark, Trond; Johansen, Terje

2015-06-12

The selective autophagy receptor p62/sequestosome 1 (SQSTM1) interacts directly with LC3 and is involved in oxidative stress signaling in two ways in mammals. First, p62 is transcriptionally induced upon oxidative stress by the NF-E2-related factor 2 (NRF2) by direct binding to an antioxidant response element in the p62 promoter. Second, p62 accumulation, occurring when autophagy is impaired, leads to increased p62 binding to the NRF2 inhibitor KEAP1, resulting in reduced proteasomal turnover of NRF2. This gives chronic oxidative stress signaling through a feed forward loop. Here, we show that the Drosophila p62/SQSTM1 orthologue, Ref(2)P, interacts directly with DmAtg8a via an LC3-interacting region motif, supporting a role for Ref(2)P in selective autophagy. The ref(2)P promoter also contains a functional antioxidant response element that is directly bound by the NRF2 orthologue, CncC, which can induce ref(2)P expression along with the oxidative stress-associated gene gstD1. However, distinct from the situation in mammals, Ref(2)P does not interact directly with DmKeap1 via a KEAP1-interacting region motif; nor does ectopically expressed Ref(2)P or autophagy deficiency activate the oxidative stress response. Instead, DmAtg8a interacts directly with DmKeap1, and DmKeap1 is removed upon programmed autophagy in Drosophila gut cells. Strikingly, CncC induced increased Atg8a levels and autophagy independent of TFEB/MitF in fat body and larval gut tissues. Thus, these results extend the intimate relationship between oxidative stress-sensing NRF2/CncC transcription factors and autophagy and suggest that NRF2/CncC may regulate autophagic activity in other organisms too. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

[Direct costs of diabetes mellitus in Germany: first estimation of the differences related to educational level].

PubMed

Korber, K; Teuner, C M; Lampert, T; Mielck, A; Leidl, R

2013-12-01

There are many studies on health inequalities, but these are rarely combined with cost-of-illness analyses. If the cost-of-illness were to be calculated for the individual status groups, it would be possible to assess the economic potential of preventive measures aimed specifically at people from low status groups. The objective of this article is to demonstrate for the first time the preventive potential by taking the example of diabetes mellitus (DM) from an economic perspective. Based on a systematic literature review, the average direct costs per patient with DM were assessed. Then, the prevalence of DM among adults with different educational levels was estimated based on the nationwide survey 'German Health Update' (GEDA), conducted by the Robert Koch-Institute in Germany in 2009. Finally, the cost and prevalence data were used to calculate the direct costs for each educational level. The direct costs of DM amount to about 13.1 billion € per year; about 35% of these costs can be attributed to patients with a low educational level. Thus, their share of the total costs is about 67% higher than their share of the total population. If the prevalence in the group with 'low educational level' (14.8%) could be reduced to the prevalence in the group with 'middle educational level' (7.9%), this would save about 2.2 billion (about 16.5%) € of direct costs. The analysis provides a first estimate of the potential savings from an effective status specific prevention programme. However, the direct costs per patient used were only an average for all people with DM, as a breakdown by educational level was not available. Since education can also affect health behaviour and compliance, which are also determinants of cost, the analyses presented here are probably conservative. © Georg Thieme Verlag KG Stuttgart · New York.

Dark matter candidates and methods for detecting them

NASA Technical Reports Server (NTRS)

Raffelt, G. G.

1992-01-01

A number of experiments employing Ge and Si ionization detectors have excluded large regions in the plane of masses and scattering cross-sections for weakly-interacting dark matter (DM) candidates. It is judged that, before a realistic detection experiment for supersymmetric DM candidates can be conducted, significant development efforts will have to be completed for suitable cryogenic or ionization detectors. Pilot experiments have demonstrated the feasibility of axion searches with microwave cavities, but these are at least two orders of magnitude too low in sensitivity.

Inducible Transposition of a Heat-Activated Retrotransposon in Tissue Culture.

PubMed

Masuta, Yukari; Nozawa, Kosuke; Takagi, Hiroki; Yaegashi, Hiroki; Tanaka, Keisuke; Ito, Tasuku; Saito, Hideyuki; Kobayashi, Hisato; Matsunaga, Wataru; Masuda, Seiji; Kato, Atsushi; Ito, Hidetaka

2017-02-01

A transposition of a heat-activated retrotransposon named ONSEN required compromise of a small RNA-mediated epigenetic regulation that includes RNA-directed DNA methylation (RdDM) machinery after heat treatment. In the current study, we analyzed the transcriptional and transpositional activation of ONSEN to better understand the underlying molecular mechanism involved in the maintenance and/or induction of transposon activation in plant tissue culture. We found the transposition of heat-primed ONSEN during tissue culture independently of RdDM mutation. The heat activation of ONSEN transcripts was not significantly up-regulated in tissue culture compared with that in heat-stressed seedlings, indicating that the transposition of ONSEN was regulated independently of the transcript level. RdDM-related genes were up-regulated by heat stress in both tissue culture and seedlings. The level of DNA methylation of ONSEN did not show any change in tissue culture, and the amount of ONSEN-derived small RNAs was not affected by heat stress. The results indicated that the transposition of ONSEN was regulated by an alternative mechanism in addition to the RdDM-mediated epigenetic regulation in tissue culture. We applied the tissue culture-induced transposition of ONSEN to Japanese radish, an important breeding species of the family Brassicaceae. Several new insertions were detected in a regenerated plant derived from heat-stressed tissues and its self-fertilized progeny, revealing the possibility of molecular breeding without genetic modification. © The Author 2016. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Focal plane based wavefront sensing with random DM probes

NASA Astrophysics Data System (ADS)

Pluzhnik, Eugene; Sirbu, Dan; Belikov, Ruslan; Bendek, Eduardo; Dudinov, Vladimir N.

2017-09-01

An internal coronagraph with an adaptive optical system for wavefront control is being considered for direct imaging of exoplanets with upcoming space missions and concepts, including WFIRST, HabEx, LUVOIR, EXCEDE and ACESat. The main technical challenge associated with direct imaging of exoplanets is to control of both diffracted and scattered light from the star so that even a dim planetary companion can be imaged. For a deformable mirror (DM) to create a dark hole with 10-10 contrast in the image plane, wavefront errors must be accurately measured on the science focal plane detector to ensure a common optical path. We present here a method that uses a set of random phase probes applied to the DM to obtain a high accuracy wavefront estimate even for a dynamically changing optical system. The presented numerical simulations and experimental results show low noise sensitivity, high reliability, and robustness of the proposed approach. The method does not use any additional optics or complex calibration procedures and can be used during the calibration stage of any direct imaging mission. It can also be used in any optical experiment that uses a DM as an active optical element in the layout.

[The attitude of patients with types 1 and 2 diabetes mellitus towards having the disease].

PubMed

Sapozhnikova, I E; Zotina, E N

To analyze the types of attitude towards disease, their relationships to its course in patients with diabetes mellitus (DM). 418 patients with DM, including 318 with type 2 DM (T2DM) and 100 with Type 1 (T1DM), were examined. Clinical and laboratory examinations were performed; the types of attitude towards the disease were studied. The patients with T2DM were more frequently found to have anxious (12.9%) and hypochondriacal (10.7%) types of attitude towards the disease; those with T1DM had euphoric types. The paranoiac type of disease attitude, which was characterized by the presence of peculiar notions about the disease, was detected in 15.1% of the patients with T2DM and in 13% of those with T1DM. Hypernosognosia (overreaction to disease) was more often identified in T2DM (62.3% versus 39% in T1DM (χ2; p < 0.001). In the T2DM group, hypernosognosia was more frequently seen in women, unemployed persons, and obese patients. With the comparable awareness about the disease and degree of self-control, the patients with T2DM with no signs of hypernosognosia had a lower glycated hemoglobin level [7.35 (6.6; 8.6)%] than those with hypernosognosia [7.9 (7; 9.4)%] (p = 0.024). The revealed peculiarities of attitude towards the disease in patients with DM justify the need for increased attention to their psychological characteristics. The situation could be improved if the physicians are be informed, the time of outpatient care is prolonged, and psychotherapists and/or clinical psychologists are widely involved in the management of diabetic patients.

Analysis of MTMR1 expression and correlation with muscle pathological features in juvenile/adult onset myotonic dystrophy type 1 (DM1) and in myotonic dystrophy type 2 (DM2).

PubMed

Santoro, Massimo; Modoni, Anna; Masciullo, Marcella; Gidaro, Teresa; Broccolini, Aldobrando; Ricci, Enzo; Tonali, Pietro Attilio; Silvestri, Gabriella

2010-10-01

Among genes abnormally expressed in myotonic dystrophy type1 (DM1), the myotubularin-related 1 gene (MTMR1) was related to impaired muscle differentiation. Therefore, we analyzed MTMR1 expression in correlation with CUG-binding protein1 (CUG-BP1) and muscleblind-like1 protein (MBNL1) steady-state levels and with morphological features in muscle tissues from DM1 and myotonic dystrophy type 2 (DM2) patients. Semi-quantitative RT-PCR for MTMR1 was done on muscle biopsies and primary muscle cultures. The presence of impaired muscle fiber maturation was evaluated using immunochemistry for neural cell adhesion molecule (NCAM), Vimentin and neonatal myosin heavy chain. CUG-BP1 and MBNL1 steady-state levels were estimated by Western blot. RNA-fluorescence in situ hybridization combined with immunochemistry for CUG-BP1, MBNL1 and NCAM were performed on serial muscle sections. An aberrant splicing of MTMR1 and a significant amount of NCAM-positive myofibers were detected in DM1 and DM2 muscle biopsies; these alterations correlated with DNA repeat expansion size only in DM1. CUG-BP1 levels were increased only in DM1 muscles, while MBNL1 levels were similar among DM1, DM2 and controls. Normal and NCAM-positive myofibers displayed no differences either in the amount of ribonuclear foci and the intracellular distribution of MBNL1 and CUG-BP1. In conclusion, an aberrant MTMR1 expression and signs of altered myofiber maturation were documented in both DM1 and in DM2 muscle tissues. The more severe dysregulation of MTMR1 expression in DM1 versus DM2, along with increased CUG-BP1 levels only in DM1 tissues, suggests that the mutual antagonism between MBNL1 and CUG-BP1 on alternative splicing is more unbalanced in DM1. Copyright © 2010 Elsevier Inc. All rights reserved.

Quantitative Methods to Monitor RNA Biomarkers in Myotonic Dystrophy.

PubMed

Wojciechowska, Marzena; Sobczak, Krzysztof; Kozlowski, Piotr; Sedehizadeh, Saam; Wojtkowiak-Szlachcic, Agnieszka; Czubak, Karol; Markus, Robert; Lusakowska, Anna; Kaminska, Anna; Brook, J David

2018-04-12

Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are human neuromuscular disorders associated with mutations of simple repetitive sequences in affected genes. The abnormal expansion of CTG repeats in the 3'-UTR of the DMPK gene elicits DM1, whereas elongated CCTG repeats in intron 1 of ZNF9/CNBP triggers DM2. Pathogenesis of both disorders is manifested by nuclear retention of expanded repeat-containing RNAs and aberrant alternative splicing. The precise determination of absolute numbers of mutant RNA molecules is important for a better understanding of disease complexity and for accurate evaluation of the efficacy of therapeutic drugs. We present two quantitative methods, Multiplex Ligation-Dependent Probe Amplification and droplet digital PCR, for studying the mutant DMPK transcript (DMPK exp RNA) and the aberrant alternative splicing in DM1 and DM2 human tissues and cells. We demonstrate that in DM1, the DMPK exp RNA is detected in higher copy number than its normal counterpart. Moreover, the absolute number of the mutant transcript indicates its low abundance with only a few copies per cell in DM1 fibroblasts. Most importantly, in conjunction with fluorescence in-situ hybridization experiments, our results suggest that in DM1 fibroblasts, the vast majority of nuclear RNA foci consist of a few molecules of DMPK exp RNA.

Cost-effectiveness of Bariatric Surgery: Increasing the Economic Viability of the Most Effective Treatment for Type II Diabetes Mellitus.

PubMed

Warren, Jeremy A; Ewing, Joseph A; Hale, Allyson L; Blackhurst, Dawn W; Bour, Eric S; Scott, John D

2015-08-01

There has been considerable debate on the cost-effectiveness of bariatric surgery within larger population groups. Despite the recognition that morbid obesity and its comorbidities are best treated surgically, insurance coverage is not universally available. One of the more costly comorbidities of obesity is Type II diabetes mellitus (T2DM). We propose a model that demonstrates the cost-effectiveness of increasing the number of bariatric surgical operations performed on patients with T2DM in the United States. We applied published population cost estimates (2012) for medical care of T2DM to a retrospective cohort of morbidly obese patients in South Carolina. We compared differences in 10-year medical costs between those having bariatric surgery and controls. Resolution of T2DM in the bariatric cohort was assumed to be 40 per cent. Considering only the direct medical costs of T2DM, the 10-year aggregate cost savings compared with a control group is $2.7 million/1000 patients; the total (direct and indirect) cost savings is $5.4 million/1000 patients. When considering resolution of T2DM alone, increasing the number of bariatric operations for a given population leads to a substantial cost savings over a 10-year period. This study adds to the growing body of evidence suggesting that bariatric surgery is a cost-effective means of caring for the obese patient.

Nanostructured zinc oxide platform for mycotoxin detection.

PubMed

Ansari, Anees A; Kaushik, Ajeet; Solanki, Pratima R; Malhotra, B D

2010-02-01

Nanostructured zinc oxide (Nano-ZnO) film has been deposited onto indium-tin-oxide (ITO) glass plate for co-immobilization of rabbit-immunoglubin antibodies (r-IgGs) and bovine serum albumin (BSA) for ochratoxin-A (OTA) detection. The results of X-ray diffraction (XRD) studies reveal the formation of Nano-ZnO with average particle size as ~5.0nm. Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), electrochemical impedance spectroscopy (EIS) techniques have been used to characterize Nano-ZnO/ITO electrode and BSA/r-IgGs/Nano-ZnO/ITO immunoelectrode. Electrochemical impedimetric response of BSA/r-IgGs/Nano-ZnO/ITO immunoelectrode obtained as a function of OTA concentration exhibits linearity as 0.006-0.01nM/dm(3), detection limit of 0.006nM/dm(3), response time as 25s and sensitivity of 189Omega/nM/dm(3)cm(-2) with a regression coefficient of 0.997. 2009 Elsevier B.V. All rights reserved.

Digital breast tomosynthesis for breast cancer screening and diagnosis in women with dense breasts - a systematic review and meta-analysis.

PubMed

Phi, Xuan-Anh; Tagliafico, Alberto; Houssami, Nehmat; Greuter, Marcel J W; de Bock, Geertruida H

2018-04-03

This study aimed to systematically review and to meta-analyse the accuracy of digital breast tomosynthesis (DBT) versus digital mammography (DM) in women with mammographically dense breasts in screening and diagnosis. Two independent reviewers identified screening or diagnostic studies reporting at least one of four outcomes (cancer detection rate-CDR, recall rate, sensitivity and specificity) for DBT and DM in women with mammographically dense breasts. Study quality was assessed using QUADAS-2. Meta-analysis of CDR and recall rate used a random effects model. Summary ROC curve summarized sensitivity and specificity. Sixteen studies were included (five diagnostic; eleven screening). In diagnosis, DBT increased sensitivity (84%-90%) versus DM alone (69%-86%) but not specificity. DBT improved CDR versus DM alone (RR: 1.16, 95% CI 1.02-1.31). In screening, DBT + DM increased CDR versus DM alone (RR: 1.33, 95% CI 1.20-1.47 for retrospective studies; RR: 1.52, 95% CI 1.08-2.11 for prospective studies). Recall rate was significantly reduced by DBT + DM in retrospective studies (RR: 0.72, 95% CI 0.64-0.80) but not in two prospective studies (RR: 1.12, 95% CI 0.76-1.63). In women with mammographically dense breasts, DBT+/-DM increased CDR significantly (versus DM) in screening and diagnosis. In diagnosis, DBT+/-DM increased sensitivity but not specificity. The effect of DBT + DM on recall rate in screening dense breasts varied between studies.

Cosmological implications of Dark Matter bound states

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mitridate, Andrea; Redi, Michele; Smirnov, Juri

2017-05-01

We present generic formulæ for computing how Sommerfeld corrections together with bound-state formation affects the thermal abundance of Dark Matter with non-abelian gauge interactions. We consider DM as a fermion 3plet (wino) or 5plet under SU(2) {sub L} . In the latter case bound states raise to 11.5 TeV the DM mass required to reproduce the cosmological DM abundance and give indirect detection signals such as (for this mass) a dominant γ-line around 70 GeV. Furthermore, we consider DM co-annihilating with a colored particle, such as a squark or a gluino, finding that bound state effects are especially relevant inmore » the latter case.« less

Particle dark matter: A multimessenger endeavour

NASA Astrophysics Data System (ADS)

Regis, M.

2017-01-01

The search for dark matter (DM) as a new, yet undiscovered, particle is explored through a complex host of different signals, from collider to direct and indirect searches. A special focus is dedicated to the latter ones, covering the full electromagnetic spectrum (from radio to gamma-rays), charged cosmic-rays and neutrinos. The expected DM signals are by definition faint, but the possibility to exploit a wide-field investigation offers promising prospects. In this brief review, I summarize the state-of-the-art in the search for particle DM signals, exploring some new ideas that are emerging in the effort of the scientific community to understand the elusive nature of DM.

MALDI-TOF mass spectrometry for the monitoring of she-donkey's milk contamination or adulteration.

PubMed

Cunsolo, Vincenzo; Muccilli, Vera; Saletti, Rosaria; Foti, Salvatore

2013-02-01

Donkey's milk (DM), representing a safe and alternative food in both IgE-mediated and non-IgE-mediated cow's milk protein allergy, can be categorized as precious pharma-food. Moreover, an economically relevant interest for the use of DM in cosmetology is also developing. The detection of adulterations and contaminations of DM is a matter of fundamental importance from both an economic and allergenic standpoint, and, to this aim, fast and efficient analytical approaches to assess the authenticity of this precious nutrient are desirable. Here, a rapid matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS)-based method aimed to the detection of bovine or caprine milk in raw DM is reported. The presence of the extraneous milks was revealed by monitoring the protein profiles of the most abundant whey proteins, α-lactalbumin (α-LA) and β-lactoglobulin, used as molecular markers. The possibility of obtaining a quantitative analysis of the level of cow or goat milk in DM based on the MALDI-TOF peak areas of α-LAs was also explored. The results showed that the experimental quantitative values were in good agreement with the real composition of each mixture. As pretreatment of the milk samples is not required, and owing to the speed and the high sensitivity of MALDI-MS, the protocol here reported could represent a reliable method for routine analyses aimed to assess the absence of contamination in raw fresh DM samples. Copyright © 2013 John Wiley & Sons, Ltd.

Gravitational waves with dark matter minispikes: The combined effect

NASA Astrophysics Data System (ADS)

Yue, Xiao-Jun; Han, Wen-Biao

2018-03-01

It was shown that the dark matter (DM) minihalo around an intermediate mass black hole (IMBH) can be redistributed into a cusp, called the DM minispike. We consider an intermediate-mass-ratio inspiral consisting of an IMBH harbored in a DM minispike with nonannihilating DM particles and a small black hole (BH) orbiting around it. We investigate gravitational waves (GWs) produced by this system and analyze the waveforms with the comprehensive consideration of gravitational pull, dynamical friction and accretion of the minispike and calculate the time difference and phase difference caused by it. We find that for a certain range of frequency, the inspiralling time of the system is dramatically reduced for smaller central IMBH and large density of DM. For the central IMBH with 105 M⊙ , the time of merger is ahead, which can be distinguished by LISA, Taiji and Tianqin. We focus on the effect of accretion and compare it with that of gravitational pull and friction. We find that the accretion mass is a small quantity compared to the initial mass of the small BH and the accretion effect is inconspicuous compared with friction. However, the accumulated phase shift caused by accretion is large enough to be detected by LISA, Taiji, and Tianqin, which indicate that the accretion effect can not be ignored in the detection of GWs.

Screening diabetes in tuberculosis patients in eastern rural China: a community-based cross-sectional study.

PubMed

Zhao, Q; Xiao, X; Lu, W; Qiu, L-X; Zhou, C-M; Jiang, W-L; Xu, B; Diwan, V

2016-10-01

To understand the prevalence of diabetes mellitus (DM) and tuberculosis (TB) comorbidity in rural China and to identify factors associated with TB-DM comorbidity and screening efficacy. A community-based cross-sectional study was carried out in four counties in eastern rural China. All TB patients newly registered from April 2013 to March 2014 were screened for DM using fasting blood glucose (FBG). Screening-positive patients were further examined using glycosylated haemoglobin A1C (HbA1c). Ninety-seven (7.7%) of the 1252 recruited TB patients had DM, 44 (45.4%) of whom were newly diagnosed. The DM-TB patients were significantly older than non-diabetics (mean age 57 ± 13 years vs. 49 ± 19 years, P < 0.001). The risk of DM-TB was higher in patients aged >40 years (OR 3.039) and in overweight patients (OR 2.595). The number needed to screen (NNS) among TB patients to identify one case of DM was 12.97. The NNS to identify one new DM patient (27.4) was lower in participants aged >40 years (20.5), those who were illiterate (19.9), those with a family history of DM (9.3), those with missing bacille Calmette-Guérin vaccination (11.3), current smokers (14.2) and those with body mass index >24 (11.4). Regular DM screening in TB patients is practical in rural China. Better efficacy of DM-TB detection could be obtained by screening high-risk populations, such as overweight TB patients or those with a family history of DM.

Characterization of invisible breast cancers in digital mammography and tomosynthesis: radio-pathological correlation.

PubMed

Aguilar Angulo, P M; Romero Castellano, C; Ruiz Martín, J; Sánchez-Camacho González-Carrato, M P; Cruz Hernández, L M

To review the radio-pathologic features of symptomatic breast cancers not detected at digital mammography (DM) and digital breast tomosynthesis (DBT). Retrospective analysis of 169 lesions from symptomatic patients with breast cancer that were studied with DM, DBT, ultrasound (US) and magnetic resonance (MR). We identified occult lesions (true false negatives) in DM and DBT. Clinical data, density, US and MR findings were analyzed as well as histopathological results. We identified seven occult lesions in DM and DBT. 57% (4/7) of the lesions were identified in high-density breasts (type c and d), and the rest of them in breasts of density type b. Six carcinomas were identified at US and MR (BI-RADS 4 masses); the remaining lesion was only identified at MR. The tumor size was larger than 3cm at MRI in 57% of the lesions. All tumors were ductal infiltrating carcinomas, six of them with high stromal proportion. According to molecular classification, we found only one triple-negative breast cancer, the other lesions were luminal-type. We analyzed the tumor margins of two resected carcinomas that were not treated with neoadjuvant chemotherapy, both lesions presented margins that displaced the adjacent parenchyma without infiltrating it. Occult breast carcinomas in DM and DBT accounted for 4% of lesions detected in patients with symptoms. They were mostly masses, all of them presented the diagnosis of infiltrating ductal carcinoma (with predominance of the luminal immunophenotype) and were detected in breasts of density type b, c and d. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

The impact of diabetes on mobility, balance, and recovery after repositioning maneuvers in individuals with benign paroxysmal positional vertigo.

PubMed

D'Silva, Linda J; Whitney, Susan L; Santos, Marcio; Dai, Hongying; Kluding, Patricia M

2017-06-01

The prevalence of benign paroxysmal positional vertigo (BPPV) is higher in people with type 2 diabetes (DM). The impact of DM on mobility, balance, and management of BPPV is unknown. This prospective study compared symptom severity, mobility and balance before and after the canalith repositioning maneuver (CRM) in people with posterior canal BPPV canalithiasis, with and without DM. Fifty participants, BPPV (n=34) and BPPV+DM (n=16) were examined for symptom severity (dizziness handicap inventory, DHI), mobility (functional gait assessment, FGA), and postural sway (using an accelerometer in five conditions) before and after the CRM. The number of maneuvers required for symptom resolution was recorded. At baseline, no differences in DHI or FGA scores were seen between groups, however, people with BPPV+DM had higher sway velocity in the medio-lateral direction in tandem stance (p<0.01). After treatment, both groups improved in DHI and FGA scores (p<0.01), with no differences between groups. Decrease in sway velocity in the mediolateral direction (p=0.003) were seen in tandem stance in persons with BPPV+DM. There were no differences between the groups in the number of CRMs provided. This pilot study showed no differences in symptom severity, mobility deficits or efficacy of CRM treatments in people with posterior canal BPPV canalithiasis with and without DM. Future studies examining the impact of the severity and duration of diabetes, as well as the influence of diabetic peripheral neuropathy on functional performance are essential. Copyright © 2017 Elsevier Inc. All rights reserved.

Release of Phosphorylated HSP27 (HSPB1) from Platelets Is Accompanied with the Acceleration of Aggregation in Diabetic Patients

PubMed Central

Tokuda, Haruhiko; Kuroyanagi, Gen; Tsujimoto, Masanori; Enomoto, Yukiko; Matsushima-Nishiwaki, Rie; Onuma, Takashi; Kojima, Akiko; Doi, Tomoaki; Tanabe, Kumiko; Akamatsu, Shigeru; Iida, Hiroki; Ogura, Shinji; Otsuka, Takanobu; Iwama, Toru; Tanikawa, Takahisa; Ishikawa, Kei; Kojima, Kumi; Kozawa, Osamu

2015-01-01

We investigated the relationship between HSP27 phosphorylation and collagen-stimulated activation of platelets in patients with diabetes mellitus (DM). Platelet-rich plasma was prepared from blood of type 2 DM patients. The platelet aggregation was analyzed in size of aggregates by an aggregometer using a laser scattering method. The protein phosphorylation was analyzed by Western blotting. Phosphorylated-HSP27 and PDGF-AB released from platelets were measured by ELISA. The phosphorylated-HSP27 levels at Ser-78 and Ser-82 induced by collagen were directly proportional to the platelet aggregation. Total HSP27 levels in platelets were decreased concomitantly with the phosphorylation. The released HSP27 levels were significantly correlated with the phosphorylated levels of HSP27 in the platelets stimulated by 0.3 μg/ml collagen. The low dose collagen-stimulated release of HSP27 was detected but relatively small in healthy donors. The released levels of PDGF-AB were in parallel with the levels of released HSP27. Area under the curve (AUC) of small aggregation (9-25 μm) induced by 0.3 μg/ml collagen was inversely proportional to the levels of released HSP27. AUC of large aggregation (50-70 μm) was directly proportional to the levels of released HSP27. Exogenous recombinant phosphorylated- HSP27 hardly affected the aggregation or the released levels of PDGF-AB induced by collagen. These results strongly suggest that HSP27 is released from human platelets accompanied with its phosphorylation induced by collagen, which is correlated with the acceleration of platelet aggregation in type 2 DM patients. PMID:26046355

Release of Phosphorylated HSP27 (HSPB1) from Platelets Is Accompanied with the Acceleration of Aggregation in Diabetic Patients.

PubMed

Tokuda, Haruhiko; Kuroyanagi, Gen; Tsujimoto, Masanori; Enomoto, Yukiko; Matsushima-Nishiwaki, Rie; Onuma, Takashi; Kojima, Akiko; Doi, Tomoaki; Tanabe, Kumiko; Akamatsu, Shigeru; Iida, Hiroki; Ogura, Shinji; Otsuka, Takanobu; Iwama, Toru; Tanikawa, Takahisa; Ishikawa, Kei; Kojima, Kumi; Kozawa, Osamu

2015-01-01

We investigated the relationship between HSP27 phosphorylation and collagen-stimulated activation of platelets in patients with diabetes mellitus (DM). Platelet-rich plasma was prepared from blood of type 2 DM patients. The platelet aggregation was analyzed in size of aggregates by an aggregometer using a laser scattering method. The protein phosphorylation was analyzed by Western blotting. Phosphorylated-HSP27 and PDGF-AB released from platelets were measured by ELISA. The phosphorylated-HSP27 levels at Ser-78 and Ser-82 induced by collagen were directly proportional to the platelet aggregation. Total HSP27 levels in platelets were decreased concomitantly with the phosphorylation. The released HSP27 levels were significantly correlated with the phosphorylated levels of HSP27 in the platelets stimulated by 0.3 μg/ml collagen. The low dose collagen-stimulated release of HSP27 was detected but relatively small in healthy donors. The released levels of PDGF-AB were in parallel with the levels of released HSP27. Area under the curve (AUC) of small aggregation (9-25 μm) induced by 0.3 μg/ml collagen was inversely proportional to the levels of released HSP27. AUC of large aggregation (50-70 μm) was directly proportional to the levels of released HSP27. Exogenous recombinant phosphorylated- HSP27 hardly affected the aggregation or the released levels of PDGF-AB induced by collagen. These results strongly suggest that HSP27 is released from human platelets accompanied with its phosphorylation induced by collagen, which is correlated with the acceleration of platelet aggregation in type 2 DM patients.

Turn on macrocyclic chemosensor for Al3+ ion with facile synthesis and application in live cell imaging

NASA Astrophysics Data System (ADS)

Ezhumalai, Dhineshkumar; Mathivanan, Iyappan; Chinnadurai, Anbuselvan

2018-06-01

An effort of a new Schiff base macrocyclic chemosensor, 14‑methyl‑2,6,8,12,14,18‑hexaaza‑1,7,13(1,2),4,10,16(1,4)‑hexabenzenacyclooctadecaphane‑2,5,8,11,14,17‑hexaene (me1) and 14,74‑dimethyl‑2,6,8,12,14,18‑hexaaza‑1,7,13(1,2),4,10,16(1,4)‑hexabenzenacyclooctadecadecaphane‑2,5,8,11,14,17‑hexaene (dm2), which enables selective sensing of Al3+ in aqueous DMF were synthesized by a simplistic one-step condensation reaction of macrocyclic compounds. The probe me1 and dm2 characterized by elemental analysis, FT-IR, 1H and 13C NMR, LC-MS spectral techniques. The compounds as mentioned above subjected to FE-SEM with EDS and elemental color mapping. On addition of Al3+, the fluorescent probe me1 and dm2 induces turn-on responses in both absorption and sensing spectra by a PET mechanism. The receptor me1 and dm2 serve highly selective, sensitive and turn-on detection of Al3+. Further, they did not interfere with other cations present in biological or environmental samples. The detection limit is found to be 3 μM and 5 μM. From the view of cytotoxic activity, the ability of these compounds me1 and dm2 to inhibit the growth of KB cell lines examined. The chelating functionality of compounds me1 and dm2 examined for their inhibitory properties of KB cell, live cell images. The compounds me1 and dm2 subjected to theoretical studies by DFT-B3LYP invoking the 6-31G level of theory. The energy of the HOMO and LUMO has been established.

Probing Cold Dark Matter Substructure with Wide Binaries in Dwarf Spheroidal Galaxies

NASA Astrophysics Data System (ADS)

Chaname, Julio

2013-10-01

The mass function of dark matter {DM} halos is a central piece in the current framework of hierarchical structure formation. Although a wealth of information is available on the properties of DM halos with M>1e8 solar masses {Msun}, lower-mass halos remain virtually inaccessible. In particular, we do not know whether there is substructure on scales below dwarf spheroidal {dSph} galaxies, nor whether the DM power spectrum cuts off at some low-mass value. Here we propose an experiment that, using resolved binary systems as gravitational test particles, will probe these unexplored regimes for the first time. We will measure the stellar 2-point correlation function in 370 square arcmin of the Ursa Minor dSph down to separations of 40 mas, corresponding to 3000 AU. If there is no DM substructure on small scales, we will detect a 6-sigma excess due to "wide" binaries at the smallest separations. On the other hand, if DM substructure exists on scales of 1e4 Msun at even 10% of the level predicted by standard theory, then these binaries will have been destroyed and there will be no excess at small separations. Because the wide-binary separation function is identical in the Milky Way disk and halo {despite being radically different dynamical environments}, it is almost certain that dSphs were originally endowed with the same wide-binary distribution. Moreover, the interpretation of the resulting data is free from ambiguities, as there are no known mechanisms for destroying these binaries within dSph environments, other than DM subhalos. Thus this is, to the best of our knowledge, the only current experiment that could detect or rule out DM clustering on M=1e4 Msun scales.

Type 2 Diabetes and Risk of Incident Cancers in China: A Prospective Study among 0.5 Million Chinese Adults.

PubMed

Pan, Xiong-Fei; He, Meian; Yu, Canqing; Lv, Jun; Guo, Yu; Bian, Zheng; Yang, Ling; Chen, Yiping; Wu, Tangchun; Chen, Zhengming; Pan, An; Li, Liming

2018-01-03

Using data from the China Kadoorie Biobank study, we conducted a prospective investigation on the association between type 2 diabetes mellitus (T2DM) and cancer risk in Chinese adults. A total of 508,892 participants (mean (standard deviation) age = 51.5 (10.7) years) without prior cancer diagnosis at baseline (2004-2008) were included. We documented 17,463 incident cancer cases during follow-up until December 31, 2013. Participants with T2DM had increased risks of total and certain site-specific cancers, and the hazard ratio (HR) was 1.13 (95% confidence interval (CI): 1.07, 1.19) for total cancer, 1.51 (1.29, 1.76) for liver cancer, 1.86 (1.43, 2.41) for pancreatic cancer, and 1.21 (1.01, 1.47) for female breast cancer. The associations were largely consistent when doctor-diagnosed and screen-detected T2DM were analyzed separately, except for colorectal cancer (HR = 0.91 (95% CI: 0.73, 1.13) for doctor-diagnosed T2DM, and HR = 1.44 (95% CI: 1.18, 1.77) for screen-detected T2DM). In participants without prior diagnosis of T2DM, higher random blood glucose levels were positively associated with risk of total cancer, liver cancer, and female breast cancer (all P for trend ≤0.02). In conclusion, T2DM is associated with an increased risk of new-onset cancer in China, particularly cancers of the liver, pancreas, and female breast. © The Author(s) 2018. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Higgs boson mass and complex sneutrino dark matter in the supersymmetric inverse seesaw models

NASA Astrophysics Data System (ADS)

Guo, Jun; Kang, Zhaofeng; Li, Tianjun; Liu, Yandong

2014-02-01

The discovery of a relatively heavy Standard Model (SM)-like Higgs boson challenges naturalness of the minimal supersymmetric standard model (MSSM) from both Higgs and dark matter (DM) sectors. We study these two aspects in the MSSM extended by the low-scale inverse seesaw mechanism. Firstly, it admits a sizable radiative contribution to the Higgs boson mass m h , up to ~4 GeV in the case of an IR-fixed point of the coupling Y ν LH u ν c and a large sneutrino mixing. Secondly, the lightest sneutrino, highly complex as expected, is a viable thermal DM candidate. Owing to the correct DM relic density and the XENON100 experimental constraints, two scenarios survive: a Higgs-portal complex DM with mass lying around the Higgs pole or above W threshold, and a coannihilating DM with slim prospect of detection. Given an extra family of sneutrinos, both scenarios naturally work when we attempt to suppress the DM left-handed sneutrino component, confronting with enhancing m h .

Likelihood Analysis of the Minimal AMSB Model

DOE PAGES

Bagnaschi, E.; Borsato, M.; Sakurai, K.; ...

2017-04-27

We perform a likelihood analysis of the minimal Anomaly-Mediated Supersymmetry Breaking (mAMSB) model using constraints from cosmology and accelerator experiments. We find that a wino-like or a Higgsino-like neutralino LSP,more » $$m_{\\tilde \\chi^0_{1}}$$, may provide the cold dark matter (DM) with similar likelihood. The upper limit on the DM density from Planck and other experiments enforces $$m_{\\tilde \\chi^0_{1}} \\lesssim 3~TeV$$ after the inclusion of Sommerfeld enhancement in its annihilations. If most of the cold DM density is provided by the $$\\tilde \\chi_0^1$$, the measured value of the Higgs mass favours a limited range of $$\\tan \\beta \\sim 5$$ (or for $$\\mu > 0$$, $$\\tan \\beta \\sim 45$$) but the scalar mass $$m_0$$ is poorly constrained. In the wino-LSP case, $$m_{3/2}$$ is constrained to about $900~TeV$ and $${m_{\\tilde \\chi^0_{1}}}$$ to $$2.9\\pm0.1~TeV$$, whereas in the Higgsino-LSP case $$m_{3/2}$$ has just a lower limit $$\\gtrsim 650TeV$$ ($$\\gtrsim 480TeV$$) and $$m_{\\tilde \\chi^0_{1}}$$ is constrained to $$1.12 ~(1.13) \\pm0.02~TeV$$ in the $$\\mu>0$$ ($$\\mu<0$$) scenario. In neither case can the anomalous magnetic moment of the muon, $${(g-2)_\\mu}$$, be improved significantly relative to its Standard Model (SM) value, nor do flavour measurements constrain the model significantly, and there are poor prospects for discovering supersymmetric particles at the LHC, {though there} are some prospects for direct DM detection. On the other hand, if the $${m_{\\tilde \\chi^0_{1}}}$$ contributes only a fraction of the cold DM density, {future LHC $$E_T$$-based searches for gluinos, squarks and heavier chargino and neutralino states as well as disappearing track searches in the wino-like LSP region will be relevant}, and interference effects enable $${\\rm BR}(B_{s, d} \\to \\mu^+\\mu^-)$$ to agree with the data better than in the SM in the case of wino-like DM with $$\\mu > 0$$.« less

Dendrobium moniliforme Exerts Inhibitory Effects on Both Receptor Activator of Nuclear Factor Kappa-B Ligand-Mediated Osteoclast Differentiation in Vitro and Lipopolysaccharide-Induced Bone Erosion in Vivo.

PubMed

Baek, Jong Min; Kim, Ju-Young; Ahn, Sung-Jun; Cheon, Yoon-Hee; Yang, Miyoung; Oh, Jaemin; Choi, Min Kyu

2016-03-01

Dendrobium moniliforme (DM) is a well-known plant-derived extract that is widely used in Oriental medicine. DM and its chemical constituents have been reported to have a variety of pharmacological effects, including anti-oxidative, anti-inflammatory, and anti-tumor activities; however, no reports discuss the beneficial effects of DM on bone diseases such as osteoporosis. Thus, we investigated the relationship between DM and osteoclasts, cells that function in bone resorption. We found that DM significantly reduced receptor activator of nuclear factor kappa-B ligand (RANKL)-induced tartrate-resistant acid phosphatase (TRAP)-positive osteoclast formation; DM directly induced the down-regulation of c-Fos and nuclear factor of activated T cells c1 (NFATc1) without affecting other RANKL-dependent transduction pathways. In the later stages of osteoclast maturation, DM negatively regulated the organization of filamentous actin (F-actin), resulting in impaired bone-resorbing activity by the mature osteoclasts. In addition, micro-computed tomography (μ-CT) analysis of the murine model revealed that DM had a beneficial effect on lipopolysaccharide (LPS)-mediated bone erosion. Histological analysis showed that DM attenuated the degradation of trabecular bone matrix and formation of TRAP-positive osteoclasts in bone tissues. These results suggest that DM is a potential candidate for the treatment of metabolic bone disorders such as osteoporosis.

Interpretations of galactic center gamma-ray excess confronting the PandaX-II constraints on dark matter-neutron spin-dependent scatterings in the NMSSM

NASA Astrophysics Data System (ADS)

Shang, Liangliang; He, Yangle; Lian, Jingwei; Pan, Yusi

2018-05-01

The Weakly Interacting Massive Particle (WIMP) has been one of the most attractive candidates for Dark Matter (DM), and the lightest neutralino (\\widetilde{χ }^0_1) in the Next-to-Minimal Supersymmetric Standard Model (NMSSM) is an interesting realization of the WIMP framework. The Galactic Center Excess (GCE) indicated from the analysis of the photon data of the Fermi Large Area Telescope (Fermi-LAT) in the gamma-ray wavelength ≲ 1 fm, can be explained by WIMP DM annihilations in the sky, as shown in many existing works. In this work we consider an interesting scenario in the Z_3-NMSSM where the singlet S and Singlino \\widetilde{S}^0 components play important roles in the Higgs and DM sector. Guided by our analytical arguments, we perform a sophisticated scan over the NMSSM parameter space by considering various observables such as the Standard Model (SM) Higgs data measured by the ATLAS and CMS experiments at the Large Hadron Collider (LHC), and the B-physics observables BR(B_s→ X_sγ ) and BR(B_s→ μ ^+μ ^-). We first collect samples which can explain the GCE well while passing all constraints we consider except for the DM direct detection (DD) bounds from XENON1T and PandaX-II experiments. We analyze the features of these samples suitable for the GCE interpretation and find that \\widetilde{χ }^0_1 DM are mostly Singlino-like and annihilation products are mostly the bottom quark pairs \\bar{b}b through a light singlet-like CP-odd Higgs A_1. Moreover, a good fit to the GCE spectrum generically requires sizable DM annihilation rates < σ _{b\\bar{b}} v > 0 in today's Universe. However, the correlation between the coupling C_{A_1 b\\bar{b}} in < σ _{b\\bar{b}} v > 0 and the coupling C_{Z \\widetilde{χ }^0_1 \\widetilde{χ }^0_1} in DM-neutron Spin Dependent (SD) scattering rate σ ^{SD}_{\\widetilde{χ }^0_1-N} makes all samples we obtain for GCE explanation get excluded by the PandaX-II results. Although the DM resonant annihilation scenarios may be beyond the reach of our analytical approximations and scan strategy, the aforementioned correlation can be a reasonable motivation for future experiments such as PandaX-nT to further test the NMSSM interpretation of GCE.

Dark matter (energy) may be indistinguishable from modified gravity (MOND)

NASA Astrophysics Data System (ADS)

Sivaram, C.

For Newtonian dynamics to hold over galactic scales, large amounts of dark matter (DM) are required which would dominate cosmic structures. Accounting for the strong observational evidence that the universe is accelerating requires the presence of an unknown dark energy (DE) component constituting about 70% of the matter. Several ingenious ongoing experiments to detect the DM particles have so far led to negative results. Moreover, the comparable proportions of the DM and DE at the present epoch appear unnatural and not predicted by any theory. For these reasons, alternative ideas like MOND and modification of gravity or general relativity over cosmic scales have been proposed. It is shown in this paper that these alternate ideas may not be easily distinguishable from the usual DM or DE hypotheses. Specific examples are given to illustrate this point that the modified theories are special cases of a generalized DM paradigm.

[Aerobic methylobacteria as the basis for a biosensor for dichloromethane detection].

PubMed

Plekhanova, Iu V; Firsova, Iu E; Doronina, N V; Trotsenko, Iu A; Reshetilov, A N

2013-01-01

Cells of dichloromethane (DChM) bacteria-destructors were immobilized by sorption on different types of membranes, which were fixed on the measuring surface of a pH-sensitive field transistor. The presence of DChM in the medium (0.6-8.8 mM) led to a change in the transistor's output signal, which was determined by the appearance of H+ ions in the medium due to DChM utilization by methylobateria. Among four strains of methylobacteria--Methylobacterium dichloromethanicum DM4, Methylobacterium extorquens DM 17, Methylopila helvetica DM6, and Ancylobacter dichloromethanicus DM 16--the highest and most stable activity toward DChM degradation was observed in the strain M. dichloromethanicum DM4. Among 11 types of membranes for cell immobilization, Millipore nitrocellulose membranes and chromatographic fiber paper GF/A, which allow one to obtain stable biosensor signals for 2 weeks without a bioreceptor change, were chosen as optimal carriers.

Impact of the Addition of Digital Breast Tomosynthesis (DBT) to Standard 2D Digital Screening Mammography on the Rates of Patient Recall, Cancer Detection, and Recommendations for Short-term Follow-up.

PubMed

Powell, Jaclynn L; Hawley, Jeffrey R; Lipari, Adele M; Yildiz, Vedat O; Erdal, B Selnur; Carkaci, Selin

2017-03-01

The addition of digital breast tomosynthesis (DBT) to digital screening mammography (DM) has been shown to decrease recall rates and improve cancer detection rates, but there is a lack of data regarding the impact of DBT on rates of short-term follow-up. We assessed possible changes in performance measures with the introduction of DBT at our facility. In our observational study, databases were used to compare rates of recall, short-term follow-up, biopsy, and cancer detection between women undergoing DM without (n = 10,477) and women undergoing DM with (n = 2304) the addition of DBT. Regression analysis was performed to determine associations with patient age, breast density, and availability of comparison examinations. The addition of DBT resulted in significantly lower recall rates (16%-14%, P = .017), higher rates of biopsy (12.7%-19.1%, P < .01), and increased detection of ductal carcinoma in situ, with a difference of 2.3 cases per 1000 screens (P = .044). A 33% increase in cancer detection rates was observed with DBT, which did not reach statistical significance. Short-term follow-up of probably benign findings was 80% higher in the DBT group (odds ratio = 1.80, 95% confidence interval = 1.38-2.36, P < .001). To our knowledge, we are the first to study the impact of DBT on rates of short-term follow-up, and observed an 80% increase over the DM group. Further research is needed to determine the malignancy rate of Breast Imaging Reporting and Data System 3 lesions detected with DBT, and establish appropriate follow-up to maximize cancer detection while minimizing expense and patient anxiety. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

[Levels of interlukin-6 and tumor necrosis factor-α in saliva of patients with type 2 diabetes mellitus and oral lichen planus].

PubMed

Liu, Yang; Jin, Jian-qiu; Yuan, Zhen-fang; Liu, Xiao Song; Cao, Jie; Guo, Xiao-hui; Liu, Hong-wei

2011-08-18

To study the relationship between type 2 diabetes mellitus (T2DM) and oral lichen planus (OLP) by detecting the level of salivary tumor necrosis factor (TNF-α) and interlukin-6 (IL-6). Subjects were divided into 4 groups: T2DM/OLP group 29 patients, T2DM group 39 patients, OLP group 21 patients, and control group 43 individuals. The salivary interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) were detected by enzyme-linked immuno sorbent assay (ELISA). (1) The level of salivary IL-6 in patients with T2DM/OLP [(12.30 ± 16.03) ng/L] was significantly higher than those in T2DM [(6.29 ± 5.91) ng/L] and OLP groups [(3.64 ± 4.47) ng/L], P<0.05. The level of salivary IL-6 was significantly lower in OLP group [(3.64 ± 4.47) ng/L] than in control group [(7.91 ± 4.05) ng/L], P<0.001. The level of salivary TNF-α in T2DM group [(8.80 ± 8.41) ng/L] was significantly lower than those in OLP [(14.02 ± 9.65) ng/L] and control groups [(15.02 ± 6.13) ng/L], P<0.05. (2) The level of salivary TNF-α is significantly negative correlated with pH value of saliva in T2DM/OLP group(r=-0.593, P<0.01);The level of salivary TNF-α and IL-6 are significantly positive correlated with waistline in control group(r=0.312,P=0.05).(3) The levels of salivary IL-6 and TNF-α were positively related to OLP clinical type, P<0.05. (4)When OLP played an overlying role on T2DM, the level of TNF-α was weakened and that of IL-6 was strengthened. When T2DM and OLP are in concurrence,there is a synergistic effect,and the secretion of IL-6 increases markedly; The level of salivary TNF-α is associated with local oral environment.

Screening and treatment of childhood type 1 and type 2 diabetes mellitus in Japan.

PubMed

Urakami, Tatsuhiko; Suzuki, Junichi; Mugishima, Hideo; Amemiya, Shin; Sugihara, Shigetaka; Kawamura, Tomoyuki; Kikuchi, Toru; Sasaki, Nozomu; Matsuura, Nobuo; Kitagawa, Teruo

2012-10-01

A large number of children with type 2 diabetes mellitus (T2DM) and a small number with a slowly progressive form of type 1 diabetes mellitus (SPT1DM) have been detected by a urine glucose screening program conducted at Japanese schools since 1974. The incidence of T2DM in children has increased over the last 3 decades and is estimated to be approximately 3.0/100,000/year, which is twice as that of T1DM. In contrast, SPT1DM in children is more prevalent in Asians, particularly Japanese, and exhibits unique clinical features that differ from those of the rapid onset form of T1DM, usually seen in Caucasians. In the first part of this review, we summarize the urine glucose screening program conducted at Japanese schools and clinical characteristics of the 2 diabetic subtypes in Japanese children. In recent years, concerns regarding childhood diabetes in Asian countries, including Japan, have risen, and medical care for the same is exceedingly developing. Intensive insulin therapy such as basal-bolus therapy by multiple daily insulin injections and pump therapy, both using insulin analogs, has been increasing in pediatric patients with T1DM. In addition, various antidiabetic medications have been introduced for children with T2DM. In the second part of this review, we describe treatment of Japanese children with T1DM and T2DM and changes in glycemic control as a result of development of the treatment.

Black hole genesis of dark matter

NASA Astrophysics Data System (ADS)

Lennon, Olivier; March-Russell, John; Petrossian-Byrne, Rudin; Tillim, Hannah

2018-04-01

We present a purely gravitational infra-red-calculable production mechanism for dark matter (DM) . The source of both the DM relic abundance and the hot Standard Model (SM) plasma is a primordial density of micro black holes (BHs), which evaporate via Hawking emission into both the dark and SM sectors. The mechanism has four qualitatively different regimes depending upon whether the BH evaporation is 'fast' or 'slow' relative to the initial Hubble rate, and whether the mass of the DM particle is 'light' or 'heavy' compared to the initial BH temperature. For each of these regimes we calculate the DM yield, Y, as a function of the initial state and DM mass and spin. In the 'slow' regime Y depends on only the initial BH mass over a wide range of initial conditions, including scenarios where the BHs are a small fraction of the initial energy density. The DM is produced with a highly non-thermal energy spectrum, leading in the 'light' DM mass regime (~260 eV and above depending on DM spin) to a strong constraint from free-streaming, but also possible observational signatures in structure formation in the spin 3/2 and 2 cases. The 'heavy' regime (~1.2 × 108 GeV to MPl depending on spin) is free of these constraints and provides new possibilities for DM detection. In all cases there is a dark radiation component predicted.

Natural course of distant metastases following radiotherapy or chemoradiotherapy in HPV-related oropharyngeal cancer.

PubMed

Huang, Shao Hui; Perez-Ordonez, Bayardo; Weinreb, Ilan; Hope, Andrew; Massey, Christine; Waldron, John N; Kim, John; Bayley, Andrew J; Cummings, Bernard; Cho, B C John; Ringash, Jolie; Dawson, Laura A; Siu, Lillian L; Chen, Eric; Irish, Jonathan; Gullane, Patrick; Hui, Angela; Liu, Fei-Fei; Shen, Xiaowei; Xu, Wei; O'Sullivan, Brian

2013-01-01

To describe the natural course of distant metastases (DMs) following radiotherapy (RT) or chemoradiotherapy (CRT) in HPV(+) oropharyngeal carcinoma (OPC). OPC treated with RT/CRT from 1/1/2000 to 5/31/2010 were reviewed. The natural course of DM were compared between HPV(+) and HPV(-) cohorts. Median follow-up was 3.9 years. The DM rate were similar (11% vs. 15% at 3-years, p=0.25) between the HPV(+) (n=457) vs. the HPV(-) (n=167) cases. While almost all (24/25) HPV(-) DM occurred within 2-years following RT (1 was at 2.1 years), 7/54 (13%) of HPV(+) DM were detected beyond 3 years (up to 5.3 years). Disseminating to >2 organs occurred in 18 (33%) HPV(+) vs. none in HPV(-). Post-DM survival rates were 11% vs. 4% at 2-years (p=0.02) for the HPV(+) vs. HPV(-) cases respectively. 5/6 HPV(+) with lung oligo-metastasis were still alive with stable disease beyond 2-years after salvage procedures for DM (chemotherapy: 3; surgical resection: 2; radiotherapy: 1). Although DM rates are similar, the natural course of HPV(+) DM differs from that of HPV(-) patients: it may occur after a longer interval, often with a "disseminating" phenotype, and a small number may have prolonged survival after salvage for DM. Copyright © 2012 Elsevier Ltd. All rights reserved.

Challenges for the functional diffusion map in pediatric brain tumors

PubMed Central

Grech-Sollars, Matthew; Saunders, Dawn E.; Phipps, Kim P.; Kaur, Ramneek; Paine, Simon M.L.; Jacques, Thomas S.; Clayden, Jonathan D.; Clark, Chris A.

2014-01-01

Background The functional diffusion map (fDM) has been suggested as a tool for early detection of tumor treatment efficacy. We aim to study 3 factors that could act as potential confounders in the fDM: areas of necrosis, tumor grade, and change in tumor size. Methods Thirty-four pediatric patients with brain tumors were enrolled in a retrospective study, approved by the local ethics committee, to examine the fDM. Tumors were selected to encompass a range of types and grades. A qualitative analysis was carried out to compare how fDM findings may be affected by each of the 3 confounders by comparing fDM findings to clinical image reports. Results Results show that the fDM in areas of necrosis do not discriminate between treatment response and tumor progression. Furthermore, tumor grade alters the behavior of the fDM: a decrease in apparent diffusion coefficient (ADC) is a sign of tumor progression in high-grade tumors and treatment response in low-grade tumors. Our results also suggest using only tumor area overlap between the 2 time points analyzed for the fDM in tumors of varying size. Conclusions Interpretation of fDM results needs to take into account the underlying biology of both tumor and healthy tissue. Careful interpretation of the results is required with due consideration to areas of necrosis, tumor grade, and change in tumor size. PMID:24305721

System performance enhancement with pre-distorted OOFDM signal waveforms in DM/DD systems.

PubMed

Sánchez, C; Ortega, B; Capmany, J

2014-03-24

In this work we propose a pre-distortion technique for the mitigation of the nonlinear distortion present in directly modulated/detected OOFDM systems and explore the system performance achieved under varying system parameters. Simulation results show that the proposed pre-distortion technique efficiently mitigates the nonlinear distortion, achieving transmission information rates around 40 Gbits/s and 18.5 Gbits/s over 40 km and 100 km of single mode fiber links, respectively, under optimum operating conditions. Moreover, the proposed pre-distortion technique can potentially provide higher system performance to that obtained with nonlinear equalization at the receiver.

Functional and morphological evaluation of hand microcirculation with nailfold capillaroscopy and laser Doppler imaging in Raynaud's and Sjögren's syndrome and poly/dermatomyositis.

PubMed

Szabo, N; Csiki, Z; Szanto, A; Danko, K; Szodoray, P; Zeher, M

2008-01-01

Nailfold capillaroscopy is widely used in autoimmune patients to determine capillary morphology. Laser Doppler imaging (LDI) is a relatively new method for measuring the microcirculation of cutaneous perfusion. The aim of this study was to investigate the capillary morphology and microcirculation among patients with Sjögren's syndrome (SS) and poly/dermatomyositis (PM/DM) with these two non-invasive methods and to detect secondary Raynaud's syndrome (SRS) in these autoimmune diseases. Thirty patients with primary SS, 30 patients with PM/DM, 30 patients with primary Raynaud's syndrome (PRS), and 30 healthy volunteers were included in the study. Nailfold capillaroscopy and LDI were performed on each patient. A comprehensive analysis was performed among the patients and healthy individuals. Among SS patients avascularity and among PM/DM patients avascularity and capillary morphology changes were most often detected by capillaroscopy. With LDI the mean steady-state cutaneous perfusion was 1.25 perfusion units (PU) in region of interest 1 (ROI1), 1.22 in ROI2, and 1.49 at the fingertips in PRS patients; the corresponding values were 1.2, 1.03, and 1.48 PU in SS, 0.91, 0.76, and 1.19 PU in PM/DM, and 1.79, 1.62, and 2.2 PU in the controls. The differences were significant between each autoimmune group compared to the control group (p<0.02, p<0.001, and p<0.001, respectively). By using nailfold capillaroscopy, abnormalities in capillary morphology can be detected, and by using LDI, the reduced blood flow in the capillaries can be detected. These investigations can be useful in the detection of SRS, or in distinguishing whether the reduced blood flow is due to primary/systemic autoimmune diseases.

The role of digital tomosynthesis in reducing the number of equivocal breast reportings

NASA Astrophysics Data System (ADS)

Alakhras, Maram; Mello-Thoms, Claudia; Rickard, Mary; Bourne, Roger; Brennan, Patrick C.

2015-03-01

Purpose To compare radiologists' confidence in assessing breast cancer using combined digital mammography (DM) and digital breast tomosynthesis (DBT) compared with DM alone as a function of previous experience with DBT. Materials and Methods Institutional ethics approval was obtained. Twenty-three experienced breast radiologists reviewed 50 cases in two modes, DM alone and DM+DBT. Twenty-seven cases presented with breast cancer. Each radiologist was asked to detect breast lesions and give a confidence score of 1-5 (1- Normal, 2- Benign, 3- Equivocal, 4- Suspicious, 5- Malignant). Radiologists were divided into three sub-groups according to their prior experience with DBT (none, workshop experience, and clinical experience). Confidence scores using DM+DBT were compared with DM alone for all readers combined and for each DBT experience subgroup. Statistical analyses, using GraphPad Prism 5, were carried out using the Wilcoxon signed-rank test with statistical significance set at p< 0.05. Results Confidence scores were higher for true positive cancer cases using DM+DBT compared with DM alone for all readers (p < 0.0001). Confidence scores for normal cases were lower (indicating greater confidence in the non-cancer diagnosis) with DM+DBT compared with DM alone for all readers (p= 0.018) and readers with no prior DBT experience (p= 0.035). Conclusion Addition of DBT to DM increases the confidence level of radiologists in scoring cancer and normal/benign cases. This finding appears to apply across radiologists with varying levels of DBT experience, however further work involving greater numbers of radiologists is required.

Quantitative analysis of phenolic compounds in Chinese hawthorn (Crataegus spp.) fruits by high performance liquid chromatography-electrospray ionisation mass spectrometry.

PubMed

Liu, Pengzhan; Kallio, Heikki; Lü, Deguo; Zhou, Chuansheng; Yang, Baoru

2011-08-01

Eleven major phenolic compounds (hyperoside, isoquercitrin, chlorogenic acid, ideain, epicatechin, two procyanidin (PA) dimers, three PA trimers and a PA dimer-hexoside) were quantified in the fruits of 22 cultivars/origins of three species of the Chinese hawthorn (Crataegus spp.) by HPLC-ESI-MS-SIR. Hyperoside (0.1-0.8mg/g dry mass [DM]), isoquercitrin (0.1-0.3mg/g DM), chlorogenic acid (0.2-1.6mg/g DM), epicatechin (0.9-11.7mg/g DM), PA B2 (0.7-12.4mg/g DM), PA dimer II (0.1-1.5mg/g DM), PA trimer I (0.1-2.7mg/g DM), PA trimer II (0.7-6.9mg/g DM), PA trimer III (0.01-1.2mg/g DM) and a PA dimer-hexoside (trace-1.1mg/g DM) were detected in all the samples. Ideain (0.0-0.7mg/g DM) was found in all the samples except Crataegus scabrifolia. Significant correlations between the contents of individual PA aglycons were observed (r>0.9, P<0.01). A strong correlation between flavonols was also shown (r=0.71, P<0.01). Fruits of Crataegus pinnatifida var. major had higher contents of PAs but lower contents of flavonols compared with Crataegus brettschneideri. The fruits of C. scabrifolia contained the highest level of PA dimer-hexoside, which was present in trace amounts in the fruits of C. pinnatifida. Copyright © 2011 Elsevier Ltd. All rights reserved.

Exploring fermionic dark matter via Higgs boson precision measurements at the Circular Electron Positron Collider

NASA Astrophysics Data System (ADS)

Xiang, Qian-Fei; Bi, Xiao-Jun; Yin, Peng-Fei; Yu, Zhao-Huan

2018-03-01

We study the impact of fermionic dark matter (DM) on projected Higgs precision measurements at the Circular Electron Positron Collider (CEPC), including the one-loop effects on the e+e-→Z h cross section and the Higgs boson diphoton decay, as well as the tree-level effects on the Higgs boson invisible decay. As illuminating examples, we discuss two UV-complete DM models, whose dark sector contains electroweak multiplets that interact with the Higgs boson via Yukawa couplings. The CEPC sensitivity to these models and current constraints from DM detection and collider experiments are investigated. We find that there exist some parameter regions where the Higgs measurements at the CEPC will be complementary to current DM searches.

PANCREATITIS - DIABETES - PANCREATIC CANCER: Summary of an NIDDK-NCI Workshop

PubMed Central

Andersen, Dana K.; Andren-Sandberg, Åke; Duell, Eric J.; Goggins, Michael; Korc, Murray; Petersen, Gloria M.; Smith, Jill P.; Whitcomb, David C.

2013-01-01

A workshop sponsored by the NIDDK and the NCI on “Pancreatitis-Diabetes-Pancreatic Cancer” focused on the risk factors of chronic pancreatitis (CP) and diabetes mellitus (DM) on the development of pancreatic ductal adenocarcinoma (PDAC). Sessions were held on a) an overview of the problem of PDAC, b) CP as a risk factor for PDAC, c) DM as a risk factor for PDAC, d) pancreatogenic, or type 3c DM (T3cDM), e) genomic associations of CP, DM, and PDAC, f) surveillance of high-risk populations and early detection of PDAC, and g) effects of DM treatment on PDAC. Recent data and current understandings of the mechanisms of CP- and DM-associated factors on PDAC development were discussed, and a detailed review of the possible risks of DM treatment on the development of PDAC was provided by representatives from academia, industry, and the Food and Drug Administration. The current status of possible biomarkers of PDAC and surveillance strategies for high-risk populations were discussed, and the gaps in knowledge and opportunities for further research were elucidated. A broad spectrum of expertise of the speakers and discussants provided an unusually productive workshop, the highlights of which are summarized in the accompanying article. PMID:24152948

Neurofibromin protein loss in desmoplastic melanoma subtypes: implicating NF1 allelic loss as a distinct genetic driver?

PubMed

Kadokura, Alexander; Frydenlund, Noah; Leone, Dominick A; Yang, Shi; Hoang, Mai P; Deng, April; Hernandez-Perez, Marier; Biswas, Asok; Singh, Rajendra; Yaar, Ron; Mahalingam, Meera

2016-07-01

Loss of the NF1 allele, coding for the protein neurofibromin, and polymorphism in the proto-oncogene RET (RETp) are purportedly common in desmoplastic melanoma (DM). DM is categorized into pure (PDM) and mixed (MDM) subtypes, which differ in prognosis. Most NF1 mutations result in a truncated/absent protein, making immunohistochemical screening for neurofibromin an ideal surrogate for NF1 allelic loss. Using antineurofibromin, our aims were to ascertain the incidence of neurofibromin loss in DM subtypes and to evaluate the relationship with RET, perineural invasion (PNI) and established histopathologic prognosticators. A total of 78 archival samples of DM met criteria for inclusion (54 cases of non-DM serving as controls). Immunohistochemistry was performed for neurofibromin, whereas direct DNA sequencing was used for RETp and BRAF mutation status. Statistical analyses included χ(2) test as well as Fisher exact test. Neurofibromin loss was more common in DM than non-DM (69% versus 54%; P=.02). In DM, significant differences in neurofibromin loss were noted in the following: non-head and neck versus head and neck biopsy site (88% versus 55%) and PDM versus MDM variants (80% versus 56%). No significant associations were noted with sex, presence of a junctional component, Breslow depth, ulceration, mitoses, host response, RETp, BRAF status, or PNI. RETp was marginally associated with PNI-positive DM versus PNI-negative DM (36 versus 18%; P=.08). Our findings, the largest to date investigating neurofibromin in DM, validate the incidence of NF1 mutations/allelic loss in DM and suggest that the DM subtypes have distinct genetic drivers. Published by Elsevier Inc.

Cognition and event-related potentials in adult-onset non-demented myotonic dystrophy type 1.

PubMed

Tanaka, H; Arai, M; Harada, M; Hozumi, A; Hirata, K

2012-02-01

To clarify the cognitive and event-related potentials (ERPs) profiles of adult-onset genetically-proven non-demented myotonic dystrophy type 1 (DM1). Fourteen DM1 patients and matched 14 normal controls were enrolled. DM1 patients were compared with normal controls, using a variety of neuropsychological tests; an auditory "oddball" counting paradigm for the ERPs, and low-resolution brain electromagnetic tomography (LORETA). For patients, ERPs and neuropsychological parameters were correlated with CTG repeat size, duration of illness, grip strength, and arterial blood gas analysis. Frontal lobe dysfunction, prolonged N1 latency, and attenuated N2/P3 amplitudes were observed in DM1. Longer CTG repeat size was associated with fewer categories achieved on Wisconsin Card Sorting Test. Greater grip strength was associated with better scores on color-word "interference" of Stroop test. P3 latency was negatively correlated with PaO(2). LORETA revealed significant hypoactivities at the orbitofrontal and medial temporal lobe, cingulate, and insula. There was no correlation between ERPs and CTG expansion. Adult-onset non-demented DM1 presented frontal lobe dysfunction. Absence of correlations between CTG repeat size and objective ERP parameters suggested CTG expansion in lymphocytes does not directly contribute to cognitive dysfunction. CTG expansion in lymphocytes does not directly contribute to cognitive dysfunction of adult-onset non-demented DM1. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Mechanisms of diabetes mellitus-induced bone fragility.

PubMed

Napoli, Nicola; Chandran, Manju; Pierroz, Dominique D; Abrahamsen, Bo; Schwartz, Ann V; Ferrari, Serge L

2017-04-01

The risk of fragility fractures is increased in patients with either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). Although BMD is decreased in T1DM, BMD in T2DM is often normal or even slightly elevated compared with an age-matched control population. However, in both T1DM and T2DM, bone turnover is decreased and the bone material properties and microstructure of bone are altered; the latter particularly so when microvascular complications are present. The pathophysiological mechanisms underlying bone fragility in diabetes mellitus are complex, and include hyperglycaemia, oxidative stress and the accumulation of advanced glycation endproducts that compromise collagen properties, increase marrow adiposity, release inflammatory factors and adipokines from visceral fat, and potentially alter the function of osteocytes. Additional factors including treatment-induced hypoglycaemia, certain antidiabetic medications with a direct effect on bone and mineral metabolism (such as thiazolidinediones), as well as an increased propensity for falls, all contribute to the increased fracture risk in patients with diabetes mellitus.

Direct detection of WIMPs: implications of a self-consistent truncated isothermal model of the Milky Way's dark matter halo

NASA Astrophysics Data System (ADS)

Chaudhury, Soumini; Bhattacharjee, Pijushpani; Cowsik, Ramanath

2010-09-01

Direct detection of Weakly Interacting Massive Particle (WIMP) candidates of Dark Matter (DM) is studied within the context of a self-consistent truncated isothermal model of the finite-size dark halo of the Galaxy. The halo model, based on the ``King model'' of the phase space distribution function of collisionless DM particles, takes into account the modifications of the phase-space structure of the halo due to the gravitational influence of the observed visible matter in a self-consistent manner. The parameters of the halo model are determined by a fit to a recently determined circular rotation curve of the Galaxy that extends up to ~ 60 kpc. Unlike in the Standard Halo Model (SHM) customarily used in the analysis of the results of WIMP direct detection experiments, the velocity distribution of the WIMPs in our model is non-Maxwellian with a cut-off at a maximum velocity that is self-consistently determined by the model itself. For our halo model that provides the best fit to the rotation curve data, the 90% C.L. upper limit on the WIMP-nucleon spin-independent cross section from the recent results of the CDMS-II experiment, for example, is ~ 5.3 × 10-8 pb at a WIMP mass of ~ 71 GeV. We also find, using the original 2-bin annual modulation amplitude data on the nuclear recoil event rate seen in the DAMA experiment, that there exists a range of small WIMP masses, typically ~ 2-16 GeV, within which DAMA collaboration's claimed annual modulation signal purportedly due to WIMPs is compatible with the null results of other experiments. These results, based as they are on a self-consistent model of the dark matter halo of the Galaxy, strengthen the possibility of low-mass (lsim10 GeV) WIMPs as a candidate for dark matter as indicated by several earlier studies performed within the context of the SHM. A more rigorous analysis using DAMA bins over smaller intervals should be able to better constrain the ``DAMA regions'' in the WIMP parameter space within the context of our model.

MicroRNA, Proteins, and Metabolites as Novel Biomarkers for Prediabetes, Diabetes, and Related Complications

PubMed Central

Vaishya, Suniti; Sarwade, Rucha D.; Seshadri, Vasudevan

2018-01-01

Type 2 diabetes mellitus (T2DM) is no more a lifestyle disease of developed countries. It has emerged as a major health problem worldwide including developing countries. However, how diabetes could be detected at an early stage (prediabetes) to prevent the progression of disease is still unclear. Currently used biomarkers like glycated hemoglobin and assessment of blood glucose level have their own limitations. These classical markers can be detected when the disease is already established. Prognosis of disease at early stages and prediction of population at a higher risk require identification of specific markers that are sensitive enough to be detected at early stages of disease. Biomarkers which could predict the risk of disease in people will be useful for developing preventive/proactive therapies to those individuals who are at a higher risk of developing the disease. Recent studies suggested that the expression of biomolecules including microRNAs, proteins, and metabolites specifically change during the progression of T2DM and related complications, suggestive of disease pathology. Owing to their omnipresence in body fluids and their association with onset, progression, and pathogenesis of T2DM, these biomolecules can be potential biomarker for prognosis, diagnosis, and management of disease. In this article, we summarize biomolecules that could be potential biomarkers and their signature changes associated with T2DM and related complications during disease pathogenesis. PMID:29740397

Dark matter annihilation in the circumgalactic medium at high redshifts

NASA Astrophysics Data System (ADS)

Schön, S.; Mack, K. J.; Wyithe, J. S. B.

2018-03-01

Annihilating dark matter (DM) models offer promising avenues for future DM detection, in particular via modification of astrophysical signals. However, when modelling such potential signals at high redshift, the emergence of both DM and baryonic structure, as well as the complexities of the energy transfer process, needs to be taken into account. In the following paper, we present a detailed energy deposition code and use this to examine the energy transfer efficiency of annihilating DM at high redshift, including the effects on baryonic structure. We employ the PYTHIA code to model neutralino-like DM candidates and their subsequent annihilation products for a range of masses and annihilation channels. We also compare different density profiles and mass-concentration relations for 105-107 M⊙ haloes at redshifts 20 and 40. For these DM halo and particle models, we show radially dependent ionization and heating curves and compare the deposited energy to the haloes' gravitational binding energy. We use the `filtered' annihilation spectra escaping the halo to calculate the heating of the circumgalactic medium and show that the mass of the minimal star-forming object is increased by a factor of 2-3 at redshift 20 and 4-5 at redshift 40 for some DM models.

Diabetes and the Esophagus.

PubMed

Monreal-Robles, Roberto; Remes-Troche, José M

2017-12-01

Chronic hyperglycemia is a well-known cause of gastrointestinal motility disorders extending from the esophagus to the anorectum. Even though little attention has been paid to esophageal disorders in the context of DM, its prevalence is higher compared to gastroparesis. Heartburn, as a typical symptom of gastroesophageal reflux disease (GERD), is the most prevalent symptom and has been found in 25 to 41% of patients with DM. Furthermore, DM has recently been established as possible independent factor for the development of Barrett's esophagus. The pathophysiology of esophageal disorders in patients with DM is complex and multifactorial, and the mechanisms described include the following: hyperglycemia, autonomic neuropathy, biomechanical and sensory alterations of the esophagus, presbyesophagus, and psychiatric comorbidity. Opportune detection, together with adequate glycemic control, can delay the onset of esophageal dysfunction and slow its progression in diabetic patients. There is limited evidence on patients with DM and esophageal dysfunction, with respect to medical treatment. Lifestyle modifications, prokinetics, and proton pump inhibitors should be indicated on an individual basis in patients that present with DM and esophageal disorders. A greater number of improved studies are needed to develop new therapeutic strategies. This chapter will review esophageal disorders associated with DM and the currently available treatment options.

Dark Adaptation of Colour Vision in Diabetic Subjects

NASA Astrophysics Data System (ADS)

Márquez-Gamiño, S.; Cortés-Peñaloza, J. L.; Pérez-Hernández, J. U.; Cruz-Rodríguez, E.; Caudillo, C.

2004-09-01

Eye disease, a late complication of diabetes mellitus (DM) occurs even under a careful glicemic control. It includes optic nerve, retina, vitreous humor, crystalline lens and pupillary affection. The physiopathological process could be independent of blood glucose levels or start at initial stages of the disease. Photoreceptors have specific physiological functions. The functional substrate of day light or colour vision in superior primates, the cones have different spectral sensitivity, 455, 530 and 560 nm. The rods, maximal sensitivity at 505 nm, are much more sensitive to light than are cones. Dark adaptation was tested to evaluate functional impairment differences in photoreceptors of diabetic subjects. 14 DM2 (type 2 DM), and 5 DM1 (type 1 DM) patients, as well as 9 healthy subjects were studied. Retinal affected individuals, were excluded. Dark adaptation curves seemed to be different between DM, and healthy subjects. Cones, specially those sensitive to 560 nm type, seems to be more labile to DM, as demonstrated by the lack of sensitivity to low, and medium intensity stimuli. Medical Physics and elementary Biomedical Engineering exhibited to be useful to discern malfunction between different types of photorreceptors. The inexpensive method used could be applied for early color vision alteration detection.

Structural and functional analyses of DM43, a snake venom metalloproteinase inhibitor from Didelphis marsupialis serum.

PubMed

Neves-Ferreira, Ana G C; Perales, Jonas; Fox, Jay W; Shannon, John D; Makino, Débora L; Garratt, Richard C; Domont, Gilberto B

2002-04-12

DM43, an opossum serum protein inhibitor of snake venom metalloproteinases, has been completely sequenced, and its disulfide bond pattern has been experimentally determined. It shows homology to human alpha(1)B-glycoprotein, a plasma protein of unknown function and a member of the immunoglobulin supergene family. Size exclusion and dynamic laser light scattering data indicated that two monomers of DM43, each composed of three immunoglobulin-like domains, associated to form a homodimer in solution. Analysis of its glycan moiety showed the presence of N-acetylglucosamine, mannose, galactose, and sialic acid, most probably forming four biantennary N-linked chains. DM43 inhibited the fibrinogenolytic activities of bothrolysin and jararhagin and formed 1:1 stoichiometric stable complexes with both metalloproteinases. DM43 was ineffective against atrolysin C or A. No complex formation was detected between DM43 and jararhagin C, indicating the essential role of the metalloproteinase domain for interaction. Homology modeling based on the crystal structure of a killer cell inhibitory receptor suggested the existence of an I-type Ig fold, a hydrophobic dimerization surface and six surface loops potentially forming the metalloproteinase-binding surface on DM43.

High Prevalence of Diabetes and Prediabetes and Their Coexistence with Cardiovascular Risk Factors in a Hispanic Community.

PubMed

Pérez, Cynthia M; Soto-Salgado, Marievelisse; Suárez, Erick; Guzmán, Manuel; Ortiz, Ana Patricia

2015-08-01

This study examined the prevalence and association of diabetes mellitus (DM) and prediabetes with cardiovascular risk factors among Puerto Ricans adults. Data from a household survey of 857 adults aged 21-79 years who underwent interviews, physical exams, and blood draws were analyzed. Prevalence of total DM and prediabetes was estimated using American Diabetes Association diagnostic criteria of fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c). Poisson regression models were used to estimate the prevalence ratio for each cardiovascular risk factor under study. Age-standardized prevalence of total DM and prediabetes, detected by FPG and/or HbA1c, was 25.5 and 47.4 %, respectively. Compared with participants with normoglycemia, those with previously diagnosed DM, undiagnosed DM, and prediabetes had more adverse cardiovascular risk factor profiles, characterized by a higher prevalence of general and abdominal obesity, hypertension, low HDL cholesterol, elevated LDL cholesterol, elevated triglycerides, and elevated plasminogen activator inhibitor 1 (p < 0.05). The high prevalence of DM and prediabetes calls for public health actions to plan and implement lifestyle interventions to prevent or delay the onset of DM and cardiovascular disease.

High Prevalence of Diabetes and Prediabetes and Their Coexistence with Cardiovascular Risk Factors in a Hispanic Community

PubMed Central

Soto-Salgado, Marievelisse; Suárez, Erick; Guzmán, Manuel; Ortiz, Ana Patricia

2014-01-01

This study examined the prevalence and association of diabetes mellitus (DM) and prediabetes with cardiovascular risk factors among Puerto Ricans adults. Data from a household survey of 857 adults aged 21–79 years who underwent interviews, physical exams, and blood draws were analyzed. Prevalence of total DM and prediabetes was estimated using American Diabetes Association diagnostic criteria of fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c). Poisson regression models were used to estimate the prevalence ratio for each cardiovascular risk factor under study. Age-standardized prevalence of total DM and prediabetes, detected by FPG and/or HbA1c, was 25.5 and 47.4 %, respectively. Compared with participants with normoglycemia, those with previously diagnosed DM, undiagnosed DM, and prediabetes had more adverse cardiovascular risk factor profiles, characterized by a higher prevalence of general and abdominal obesity, hypertension, low HDL cholesterol, elevated LDL cholesterol, elevated triglycerides, and elevated plasminogen activator inhibitor 1 (p < 0.05). The high prevalence of DM and prediabetes calls for public health actions to plan and implement lifestyle interventions to prevent or delay the onset of DM and cardiovascular disease. PMID:24781780

Use of commercial video games to improve postural balance in patients with multiple sclerosis: A systematic review and meta-analysis of randomised controlled clinical trials.

PubMed

Parra-Moreno, M; Rodríguez-Juan, J J; Ruiz-Cárdenas, J D

2018-03-07

Commercial video games are considered an effective tool to improve postural balance in different populations. However, the effectiveness of these video games for patients with multiple sclerosis (MS) is unclear. To analyse existing evidence on the effects of commercial video games on postural balance in patients with MS. We conducted a systematic literature search on 11 databases (Academic-Search Complete, AMED, CENTRAL, CINAHL, WoS, IBECS, LILACS, Pubmed/Medline, Scielo, SPORTDiscus, and Science Direct) using the following terms: "multiple sclerosis", videogames, "video games", exergam*, "postural balance", posturography, "postural control", balance. Risk of bias was analysed by 2 independent reviewers. We conducted 3 fixed effect meta-analyses and calculated the difference of means (DM) and the 95% confidence interval (95% CI) for the Four Step Square Test, Timed 25-Foot Walk, and Berg Balance Scale. Five randomized controlled trials were included in the qualitative systematic review and 4 in the meta-analysis. We found no significant differences between the video game therapy group and the control group in Four Step Square Test (DM: -.74; 95% CI, -2.79-1.32; P=.48; I 2 =0%) and Timed 25-Foot Walk scores (DM: .15; 95% CI, -1.06-.76; P=.75; I 2 =0%). We did observe intergroup differences in BBS scores in favour of video game therapy (DM: 5.30; 95% CI, 3.39-7.21; P<.001; I 2 =0%), but these were not greater than the minimum detectable change reported in the literature. The effectiveness of commercial video game therapy for improving postural balance in patients with MS is limited. Copyright © 2018 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Role of adipose tissue derived stem cells differentiated into insulin producing cells in the treatment of type I diabetes mellitus.

PubMed

Amer, Mona G; Embaby, Azza S; Karam, Rehab A; Amer, Marwa G

2018-05-15

Generation of new β cells is an important approach in the treatment of type 1 diabetes mellitus (type 1 DM). Adipose tissue-derived stem cells (ADSCs) might be one of the best sources for cell replacement therapy for diabetes. Therefore, this work aimed to test the possible role of transplanted insulin-producing cells (IPCs) differentiated from ADSCs in treatment of streptozotocin (STZ) induced type I DM in rats. Type 1 DM was induced by single intra peritoneal injection with STZ (50 mg/kg BW). Half of the diabetic rats were left without treatment and the other half were injected with differentiated IPCs directly into the pancreas. ADSCs were harvested, cultured and identified by testing their phenotypes through flow cytometry. They were further subjected to differentiation into IPCs using differentiation medium. mRNA expression of pancreatic transcription factors (pdx1), insulin and glucose transporter-2 genes by real time PCR was done to detect the cellular differentiation and confirmed by stimulated insulin secretion. The pancreatic tissues from all groups were examined 2 months after IPC transplantation and were subjected to histological, Immunohistochemical and morphometric study. The differentiated IPCs showed significant expression of pancreatic β cell markers and insulin secretion in glucose dependent manner. Treatment with IPCs induced apparent regeneration, diffused proliferated islet cells and significant increase in C-peptide immune reaction. We concluded that transplantation of differentiated IPCs improved function and morphology of Islet cells in diabetic rats. Consequently, this therapy option may be a promising therapeutic approach to patient with type 1 DM if proven to be effective and safe. Copyright © 2018 Elsevier B.V. All rights reserved.

Gastroesophageal reflux disease in patients with long standing type 1 diabetes mellitus: utility of two self-report questionnaires in a multifactorial disease

PubMed Central

Valdez-Solis, Emmanuel Marin; Ramírez-Rentería, Claudia; Molina-Ayala, Mario; Mendoza-Zubieta, Victoria; Rodríguez-Pérez, Víctor

2017-01-01

Abstract Background: Gastroesophageal pathologies are common and multifactorial in patients with type 1 diabetes (T1DM). The evaluation with endoscopy and 24 h pH esophageal monitoring is expensive and not always available in all medical centers, especially in developing countries so more cost-effective algorithms for diagnosis are required. Clinical questionnaires are easy to apply but its utility for gastroesophageal reflux disease screening in patients with long standing T1DM must be analyzed. Objective: To evaluate the utility of the FSSG and Carlsson-Dent (CDQ) questionnaires to detect the frequency of gastroesophageal reflux disease in patients with T1DM. Methods: Analytic cross-sectional study, included 54 randomly selected patients from the T1DM clinic in our hospital. Before their routine evaluation, were asked to answer FSSG and CDQ questionnaires, classifying them as positive with a score >8 or >4, respectively. we associated and compared the clinical and biochemical characteristics between patients with or without gastroesophageal reflux detected through questionnaires. Results: Median age was 29 years (22-35), 67% were female (median of 16 years from diagnosis). In 39% of the patients FSSG was positive, CDQ was positive in 28%. A total of 71% of patients were taking medications to treat non-specific gastric symptoms. The concordance between questionnaires was 65% (p: <0.001). Those patients with tobacco consumption as well as those with poor glycemic control were more likely to score positive in either questionnaire. Conclusions: Patients T1DM had a high prevalence of gastroesophageal reflux disease. In those patients FSSG questionnaire detected a higher number of patients in comparison with CDQ. PMID:29213156

Gastroesophageal reflux disease in patients with long standing type 1 diabetes mellitus: utility of two self-report questionnaires in a multifactorial disease.

PubMed

Valdez-Solis, Emmanuel Marin; Ramírez-Rentería, Claudia; Ferreira-Hermosillo, Aldo; Molina-Ayala, Mario; Mendoza-Zubieta, Victoria; Rodríguez-Pérez, Víctor

2017-09-30

Gastroesophageal pathologies are common and multifactorial in patients with type 1 diabetes (T1DM). The evaluation with endoscopy and 24 h pH esophageal monitoring is expensive and not always available in all medical centers, especially in developing countries so more cost-effective algorithms for diagnosis are required. Clinical questionnaires are easy to apply but its utility for gastroesophageal reflux disease screening in patients with long standing T1DM must be analyzed. To evaluate the utility of the FSSG and Carlsson-Dent (CDQ) questionnaires to detect the frequency of gastroesophageal reflux disease in patients with T1DM. Analytic cross-sectional study, included 54 randomly selected patients from the T1DM clinic in our hospital. Before their routine evaluation, were asked to answer FSSG and CDQ questionnaires, classifying them as positive with a score >8 or >4, respectively. we associated and compared the clinical and biochemical characteristics between patients with or without gastroesophageal reflux detected through questionnaires. Median age was 29 years (22-35), 67% were female (median of 16 years from diagnosis). In 39% of the patients FSSG was positive, CDQ was positive in 28%. A total of 71% of patients were taking medications to treat non-specific gastric symptoms. The concordance between questionnaires was 65% ( p : <0.001). Those patients with tobacco consumption as well as those with poor glycemic control were more likely to score positive in either questionnaire. Patients T1DM had a high prevalence of gastroesophageal reflux disease. In those patients FSSG questionnaire detected a higher number of patients in comparison with CDQ.

Living with a Red Dwarf: A Chandra Archival Study of dM Star Activity and Habitability

NASA Astrophysics Data System (ADS)

Engle, Scott

2017-09-01

We propose to analyze 6 archival Chandra visits, not pointed at, but serendipitously including 3 dM stars of known age. GJ 669 AB are a common proper motion pair, each are resolved and detected in 3 exposures, and LHS 373 is a much older dM star also detected on 3 exposures. Photometry (by us) of GJ 669 AB began 5 years ago, is ongoing, and has precisely determined rotation rates for both stars and evidence of frequent flaring from GJ 669 B. We will analyze the multiple exposures, derive an accurate mean level of X-ray activity from the targets, and also separate out and individually analyze and model any observed X-ray flares. This proposal will provide highly accurate coronal properties for the targets, but also very useful data for stellar evolution and planetary habitability studies.

A Study of the Patients Suffering from Tuberculosis and Tuberculosis-diabetes Comorbidity in Revised National Tuberculosis Control Program Centers of Northern Madhya Pradesh, India.

PubMed

Agarwal, Anil Kumar; Gupta, Ginisha; Marskole, Priyesh; Agarwal, Anju

2017-01-01

Diabetes mellitus (DM) is recognized as an important risk factor to tuberculosis (TB). India has high TB burden, along with rising DM prevalence. This study was conducted to document the coexistence of DM and TB in persons with established TB under the Revised National Tuberculosis Control Program. This was a cross-sectional, descriptive observational study conducted at selected Directly Observed Therapy center in Gwalior North Central India. A total of 550 patients with confirmed diagnosis of TB and on treatment were recruited. The study participants were screened for DM and diagnoses were made on the basis of the World Health Organization criteria. Clinical parameters were compared between persons with DM and those without DM. DM/TB co-morbidity was noted in 85 individuals and these made up 15.4% of the study population. The mean age was higher in DM patients with TB (43.4 ± 15.4 vs. 33.1 ± 16.2 years, P = 0.000); the mean duration of symptoms of TB with DM was more (124 ± 16.4 vs. 107.49 ± 10.3 days). Multinomial logistic regression analysis showed that increasing age, positive family history of diabetes, sedentary occupation, and presence of pulmonary TB were significantly associated with diabetes among TB patients. Diabetes is an important co-morbid feature to be sought in patients with TB. This study re-echo the need to raise awareness on screening for DM in persons with TB.

High prevalence of undiagnosed diabetes among tuberculosis patients in peripheral health facilities in Kerala

PubMed Central

Kumari, A. K.; Subramonianpillai, J.; Shabna, D. S.; Kumar, S. M.; Balakrishnan, S.; Naik, B.; Kumar, A. M. V.; Isaakidis, P.; Satyanarayana, S.

2013-01-01

Setting: Two tertiary care hospitals and 12 peripheral health institutions (PHIs) in Trivandrum, Kerala, India. Objective: To determine factors associated with the prevalence of diabetes mellitus (DM) among tuberculosis (TB) patients and examine differences in the proportion of new DM cases among TB patients diagnosed at tertiary care centres and PHIs. Design: A descriptive study: TB patients diagnosed during March–September 2012 were screened for known DM. Those with unknown DM status were tested for random blood glucose and fasting blood glucose (FBG); FBG ≥ 126 mg/dl was diagnosed as new DM. Results: Of 920 TB patients, 689 (72%) were male and the mean (standard deviation) age was 47.6 (16.4) years. Of these, 298 (32.4%) were diabetic: 235 (26%) had previously known DM and 63 (7%) were newly diagnosed. During the screening at PHIs and tertiary care hospitals, respectively 30/183 (16.4%) and 33/737 (4.5%) were newly diagnosed with DM (OR 3.71; 95%CI 2.17–6.32). Overall, age >50 years and pulmonary tuberculosis were independently associated with a higher prevalence of diabetes. Conclusion: As nearly one in three TB patients had DM, we recommend that TB patients should be routinely screened for DM in Kerala. As the proportion of new DM was higher among TB patients diagnosed at PHIs, we would recommend that specific attention and investment be directed to PHIs. PMID:26393068

Hepatitis C virus infection and type 1 and type 2 diabetes mellitus.

PubMed

Antonelli, Alessandro; Ferrari, Silvia Martina; Giuggioli, Dilia; Di Domenicantonio, Andrea; Ruffilli, Ilaria; Corrado, Alda; Fabiani, Silvia; Marchi, Santino; Ferri, Clodoveo; Ferrannini, Ele; Fallahi, Poupak

2014-10-15

Hepatitis C virus (HCV) infection and diabetes mellitus are two major public health problems that cause devastating health and financial burdens worldwide. Diabetes can be classified into two major types: type 1 diabetes mellitus (T1DM) and T2DM. T2DM is a common endocrine disorder that encompasses multifactorial mechanisms, and T1DM is an immunologically mediated disease. Many epidemiological studies have shown an association between T2DM and chronic hepatitis C (CHC) infection. The processes through which CHC is associated with T2DM seem to involve direct viral effects, insulin resistance, proinflammatory cytokines, chemokines, and other immune-mediated mechanisms. Few data have been reported on the association of CHC and T1DM and reports on the potential association between T1DM and acute HCV infection are even rarer. A small number of studies indicate that interferon-α therapy can stimulate pancreatic autoimmunity and in certain cases lead to the development of T1DM. Diabetes and CHC have important interactions. Diabetic CHC patients have an increased risk of developing cirrhosis and hepatocellular carcinoma compared with non-diabetic CHC subjects. However, clinical trials on HCV-positive patients have reported improvements in glucose metabolism after antiviral treatment. Further studies are needed to improve prevention policies and to foster adequate and cost-effective programmes for the surveillance and treatment of diabetic CHC patients.

Hepatitis C virus infection and type 1 and type 2 diabetes mellitus

PubMed Central

Antonelli, Alessandro; Ferrari, Silvia Martina; Giuggioli, Dilia; Di Domenicantonio, Andrea; Ruffilli, Ilaria; Corrado, Alda; Fabiani, Silvia; Marchi, Santino; Ferri, Clodoveo; Ferrannini, Ele; Fallahi, Poupak

2014-01-01

Hepatitis C virus (HCV) infection and diabetes mellitus are two major public health problems that cause devastating health and financial burdens worldwide. Diabetes can be classified into two major types: type 1 diabetes mellitus (T1DM) and T2DM. T2DM is a common endocrine disorder that encompasses multifactorial mechanisms, and T1DM is an immunologically mediated disease. Many epidemiological studies have shown an association between T2DM and chronic hepatitis C (CHC) infection. The processes through which CHC is associated with T2DM seem to involve direct viral effects, insulin resistance, proinflammatory cytokines, chemokines, and other immune-mediated mechanisms. Few data have been reported on the association of CHC and T1DM and reports on the potential association between T1DM and acute HCV infection are even rarer. A small number of studies indicate that interferon-α therapy can stimulate pancreatic autoimmunity and in certain cases lead to the development of T1DM. Diabetes and CHC have important interactions. Diabetic CHC patients have an increased risk of developing cirrhosis and hepatocellular carcinoma compared with non-diabetic CHC subjects. However, clinical trials on HCV-positive patients have reported improvements in glucose metabolism after antiviral treatment. Further studies are needed to improve prevention policies and to foster adequate and cost-effective programmes for the surveillance and treatment of diabetic CHC patients. PMID:25317237

Associated autoimmune diseases in children and adolescents with type 1 diabetes mellitus (T1DM).

PubMed

Kakleas, Kostas; Soldatou, Alexandra; Karachaliou, Feneli; Karavanaki, Kyriaki

2015-09-01

Type 1 diabetes (T1DM) is an autoimmune disease with aberrant immune responses to specific β-cell autoantigens, resulting in insulin deficiency. Children and adolescents with T1DM may also develop organ-specific multiple autoimmunity in the context of APS (autoimmune polyendocrine syndrome) type 1, 2 or 3. The most frequently encountered associated autoimmune disorders in T1DM are autoimmune thyroid, followed by celiac, autoimmune gastric disease and other rare autoimmune conditions. There are limited previous studies on the prevalence of associated autoimmunity, especially multiple, in children with T1DM. The present review reports on the classification of autoimmune diabetes, and on the prevalence, pathogenesis, predictive factors and clinical presentation of pancreatic autoimmunity and of all associated autoimmune disorders in children with T1DM. The impact of associated autoimmunity on diabetes control and general health is also discussed, along with suggestions regarding screening strategies and follow-up for early detection and management of the autoimmunity. Copyright © 2015 Elsevier B.V. All rights reserved.

Role of ACE and AGT gene polymorphisms in genetic susceptibility to diabetes mellitus type 2 in a Brazilian sample.

PubMed

Wollinger, L M; Dal Bosco, S M; Rempe, C; Almeida, S E M; Berlese, D B; Castoldi, R P; Arndt, M E; Contini, V; Genro, J P

2015-12-29

The aim of the current study was to investigate the association between the InDel polymorphism in the angiotensin I-converting enzyme gene (ACE) and the rs699 polymorphism in the angiotensinogen gene (AGT) and diabetes mellitus type 2 (DM2) in a sample population from Southern Brazil. A case-control study was conducted with 228 patients with DM2 and 183 controls without DM2. The ACE InDel polymorphism was genotyped by polymerase chain reaction (PCR) with specific primers, followed by electrophoresis on 1.5% agarose gel. The AGT rs699 polymorphism was genotyped using a real-time PCR assay. No significant association between the ACE InDel polymorphism and DM2 was detected (P = 0.97). However, regarding the AGT rs699 polymorphism, DM2 patients had a significantly higher frequency of the AG genotype and lower frequency of the GG genotype when compared to the controls (P = 0.03). Our results suggest that there is an association between the AGT rs699 polymorphism and DM2 in a Brazilian sample.

Search for gamma-ray emission from des dwarf spheroidal galaxy candidates with Fermi LAT data

DOE PAGES

Drlica-Wagner, A.; Albert, A.; Bechtol, K.; ...

2015-08-04

Due to their proximity, high dark-matter (DM) content, and apparent absence of non-thermal processes, Milky Way dwarf spheroidal satellite galaxies (dSphs) are excellent targets for the indirect detection of DM. Recently, eight new dSph candidates were discovered using the first year of data from the Dark Energy Survey (DES). We searched for gamma-ray emission coincident with the positions of these new objects in six years of Fermi Large Area Telescope data. Here, we found no significant excesses of gamma-ray emission. Under the assumption that the DES candidates are dSphs with DM halo properties similar to the known dSphs, we computed individual and combined limits on the velocity-averaged DM annihilation cross section for these new targets. If the estimated DM content of these dSph candidates is confirmed, they will constrain the annihilation cross section to lie below the thermal relic cross section for DM particles with massesmore » $$\\lesssim 20\\;\\mathrm{GeV}$$ annihilating via the $$b\\bar{b}$$ or τ +τ - channels.« less

Search for Gamma-Ray Emission from DES Dwarf Spheroidal Galaxy Candidates with Fermi-LAT Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Drlica-Wagner, A.; et al.

Due to their proximity, high dark-matter (DM) content, and apparent absence of non-thermal processes, Milky Way dwarf spheroidal satellite galaxies (dSphs) are excellent targets for the indirect detection of DM. Recently, eight new dSph candidates were discovered using the first year of data from the Dark Energy Survey (DES). We searched for gamma-ray emission coincident with the positions of these new objects in six years of Fermi Large Area Telescope data. We found no significant excesses of gamma-ray emission. Under the assumption that the DES candidates are dSphs with DM halo properties similar to the known dSphs, we computed individual and combined limits on the velocity-averaged DM annihilation cross section for these new targets. If the estimated DM content of these dSph candidates is confirmed, they will constrain the annihilation cross section to lie below the thermal relic cross section for DM particles with massesmore » $$\\lesssim 20\\,\\mathrm{GeV}$$ annihilating via the $$b\\bar{b}$$ or τ(+)τ(-) channels.« less

Search for gamma-ray emission from des dwarf spheroidal galaxy candidates with Fermi LAT data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Drlica-Wagner, A.; Albert, A.; Bechtol, K.

Due to their proximity, high dark-matter (DM) content, and apparent absence of non-thermal processes, Milky Way dwarf spheroidal satellite galaxies (dSphs) are excellent targets for the indirect detection of DM. Recently, eight new dSph candidates were discovered using the first year of data from the Dark Energy Survey (DES). We searched for gamma-ray emission coincident with the positions of these new objects in six years of Fermi Large Area Telescope data. Here, we found no significant excesses of gamma-ray emission. Under the assumption that the DES candidates are dSphs with DM halo properties similar to the known dSphs, we computed individual and combined limits on the velocity-averaged DM annihilation cross section for these new targets. If the estimated DM content of these dSph candidates is confirmed, they will constrain the annihilation cross section to lie below the thermal relic cross section for DM particles with massesmore » $$\\lesssim 20\\;\\mathrm{GeV}$$ annihilating via the $$b\\bar{b}$$ or τ +τ - channels.« less

Exploring spin-3 /2 dark matter with effective Higgs couplings

NASA Astrophysics Data System (ADS)

Chang, Chia-Feng; He, Xiao-Gang; Tandean, Jusak

2017-10-01

We study an economical model of weakly interacting massive particle dark matter (DM) which has spin 3 /2 and interacts with the 125 GeV Higgs boson via effective scalar and pseudoscalar operators. We apply constraints on the model from the relic density data, LHC measurements of the Higgs boson, and direct and indirect searches for DM, taking into account the effective nature of the DM-Higgs couplings. We show that this DM is currently viable in most of the mass region from about 58 GeV to 2.3 TeV and will be probed more stringently by ongoing and upcoming experiments. Nevertheless, the presence of the DM-Higgs pseudoscalar coupling could make parts of the model parameter space elusive from future tests. We find that important aspects of this scenario are quite similar to those of its more popular spin-1 /2 counterpart.

Ocular complications of diabetes mellitus

PubMed Central

Sayin, Nihat; Kara, Necip; Pekel, Gökhan

2015-01-01

Diabetes mellitus (DM) is a important health problem that induces ernestful complications and it causes significant morbidity owing to specific microvascular complications such as, retinopathy, nephropathy and neuropathy, and macrovascular complications such as, ischaemic heart disease, and peripheral vasculopathy. It can affect children, young people and adults and is becoming more common. Ocular complications associated with DM are progressive and rapidly becoming the world’s most significant cause of morbidity and are preventable with early detection and timely treatment. This review provides an overview of five main ocular complications associated with DM, diabetic retinopathy and papillopathy, cataract, glaucoma, and ocular surface diseases. PMID:25685281

Orally absorbed reactive glycation products (glycotoxins): An environmental risk factor in diabetic nephropathy

PubMed Central

Koschinsky, Theodore; He, Ci-Jiang; Mitsuhashi, Tomoko; Bucala, Richard; Liu, Cecilia; Buenting, Christina; Heitmann, Kirsten; Vlassara, Helen

1997-01-01

Endogenous advanced glycation endproducts (AGEs) include chemically crosslinking species (glycotoxins) that contribute to the vascular and renal complications of diabetes mellitus (DM). Renal excretion of the catabolic products of endogenous AGEs is impaired in patients with diabetic or nondiabetic kidney disease (KD). The aim of this study was to examine the oral absorption and renal clearance kinetics of food AGEs in DM with KD and whether circulating diet-derived AGEs contain active glycotoxins. Thirty-eight diabetics (DM) with or without KD and five healthy subjects (NL) received a single meal of egg white (56 g protein), cooked with (AGE-diet) or without fructose (100 g) (CL-diet). Serum and urine samples, collected for 48 hr, were monitored for AGE immunoreactivity by ELISA and for AGE-specific crosslinking reactivity, based on complex formation with 125I-labeled fibronectin. The AGE-diet, but not the CL-diet, produced distinct elevations in serum AGE levels in direct proportion to amount ingested (r = 0.8, P < 0.05): the area under the curve for serum (≈10% of ingested AGE) correlated directly with severity of KD; renal excretion of dietary AGE, although normally incomplete (only ≈30% of amount absorbed), in DM it correlated inversely with degree of albuminuria, and directly with creatinine clearance (r = 0.8, P < 0.05), reduced to <5% in DM with renal failure. Post-AGE-meal serum exhibited increased AGE-crosslinking activity (two times above baseline serum AGE, three times above negative control), which was inhibited by aminoguanidine. In conclusion, (i) the renal excretion of orally absorbed AGEs is markedly suppressed in diabetic nephropathy patients, (ii) daily influx of dietary AGEs includes glycotoxins that may constitute an added chronic risk for renal-vascular injury in DM, and (iii) dietary restriction of AGE food intake may greatly reduce the burden of AGEs in diabetic patients and possibly improve prognosis. PMID:9177242

Biochemical profile of stone-forming patients with diabetes mellitus.

PubMed

Pak, Charles Y C; Sakhaee, Khashayar; Moe, Orson; Preminger, Glenn M; Poindexter, John R; Peterson, Roy D; Pietrow, Paul; Ekeruo, Wesley

2003-03-01

To test the hypothesis that stone-forming patients with type II diabetes (DM-II) have a high prevalence of uric acid (UA) stones and present with some of the biochemical features of gouty diathesis (GD). The demographic and initial biochemical data from 59 stone-forming patients with DM-II (serum glucose greater than 126 mg/dL, no insulin therapy, older than 35 years of age) from Dallas, Texas and Durham, North Carolina were retrieved and compared with data from 58 patients with GD and 116 with hyperuricosuric calcium oxalate urolithiasis (HUCU) without DM. UA stones were detected in 33.9% of patients with DM-II compared with 6.2% of stone-forming patients without DM (P <0.001). Despite similar ingestion of alkali, the urinary pH in patients with DM-II and UA stones (n = 20) was low (pH = 5.5), as it is in patients with GD, and was significantly lower than in patients with HUCU. The urinary pH in patients with DM-II and calcium stones (n = 39) was intermediate between that in those with DM-II and UA stones and those with HUCU. However, both DM groups had fractional excretion of urate that was not depressed, as it is in those with GD, and was comparable to the value obtained in those with HUCU. The urinary content of undissociated UA was significantly higher, and the saturation of calcium phosphate (brushite) and sodium urate was significantly lower in those with DM-II and UA stones than in those with HUCU. Stone-forming patients with DM-II have a high prevalence of UA stones. Diabetic patients with UA stones share a key feature of those with GD, namely the passage of unusually acid urine, but not the low fractional excretion of urate.

Regulation of DM-20 mRNA expression and intracellular translocation of glutathione-S-transferase pi isoform during oligodendrocyte differentiation in the adult rat spinal cord.

PubMed

Kitada, Masaaki; Takeda, Kazuya; Dezawa, Mari

2016-07-01

We previously demonstrated that NG2-positive oligodendrocyte precursor cells (OPCs) do not express DM-20 mRNA and identified a distinct DM-20 mRNA-positive cell population expressing glutathione-S-transferase pi isoform (GST-pi) in the nucleus (GST-pi(Nuc)) of the adult rat spinal cord. As GST-pi intranuclear localization correlates with progenitor cell properties, we examined the differentiation status of this cell population under the intensive 5-bromo-2'-deoxyuridine (BrdU) administration method, consisting of intraperitoneal BrdU injections every 2 h for 48 h. We observed that a certain population of proliferating/proliferated cells expressed DM-20 mRNA, and sometimes two proliferating/proliferated cells were observed still attached to each other. We performed triple staining for BrdU, DM-20 mRNA, and NG2 and found pairs of neighboring BrdU-positive cells, which were considered to originate from the same progenitor cells and where both cells expressed DM-20 mRNA. Triple staining for BrdU, DM-20 mRNA, and GST-pi detected proliferating/proliferated cells exhibiting the GST-pi(Nuc)/DM-20 mRNA-positive expression pattern. These findings suggested the presence of a GST-pi(Nuc)/DM-20 mRNA-positive oligodendrocyte-lineage progenitor cell population in the adult rat spinal cord. However, we did not find any pair of neighboring BrdU-positive cells with this expression pattern. These observations collectively support the idea that GST-pi(Nuc)/DM-20 mRNA-expressing cells are the progeny of NG2-positive OPCs rather than a novel type of oligodendrocyte-lineage progenitor cells and that DM-20 mRNA expression is dynamically regulated during differentiation of OPCs into oligodendrocytes.

Probing the nature of Dark Matter with the SKA

NASA Astrophysics Data System (ADS)

Colafrancesco, S.; Regis, M.; Marchegiani, P.; Beck, G.; Beck, R.; Zechlin, H.; Lobanov, A.; Horns, D.

2015-04-01

Dark Matter (DM) is a fundamental ingredient of our Universe and of structure formation, and yet its nature is elusive to astrophysical probes. Information on the nature and physical properties of the WIMP (neutralino) DM (the leading candidate for a cosmologically relevant DM) can be obtained by studying the astrophysical signals of their annihilation/decay. Among the various e.m. signals, secondary electrons produced by neutralino annihilation generate synchrotron emission in the magnetized atmosphere of galaxy clusters and galaxies which could be observed as a diffuse radio emission (halo or haze) centered on the DM halo. A deep search for DM radio emission with SKA in local dwarf galaxies, galaxy regions with low star formation and galaxy clusters (with offset DM-baryonic distribution, like e.g. the Bullet cluster) can be very effective in constraining the neutralino mass, composition and annihilation cross-section. For the case of a dwarf galaxy, like e.g. Draco, the constraints on the DM annihilation cross-section obtainable with SKA1-MID will be at least a factor $\\sim 10^3$ more stringent than the limits obtained by Fermi-LAT in the $\\gamma$-rays. These limits scale with the value of the B field, and the SKA will have the capability to determine simultaneously both the magnetic field in the DM-dominated structures and the DM particle properties. The optimal frequency band for detecting the DM-induced radio emission is around $\\sim 1$ GHz, with the SKA1-MID Band 1 and 4 important to probe the synchrotron spectral curvature at low-$\

Facial nerve palsy after reactivation of herpes simplex virus type 1 in diabetic mice.

PubMed

Esaki, Shinichi; Yamano, Koji; Katsumi, Sachiyo; Minakata, Toshiya; Murakami, Shingo

2015-04-01

Bell's palsy is highly associated with diabetes mellitus (DM). Either the reactivation of herpes simplex virus type 1 (HSV-1) or diabetic mononeuropathy has been proposed to cause the facial paralysis observed in DM patients. However, distinguishing whether the facial palsy is caused by herpetic neuritis or diabetic mononeuropathy is difficult. We previously reported that facial paralysis was aggravated in DM mice after HSV-1 inoculation of the murine auricle. In the current study, we induced HSV-1 reactivation by an auricular scratch following DM induction with streptozotocin (STZ). Controlled animal study. Diabetes mellitus was induced with streptozotocin injection in only mice that developed transient facial nerve paralysis with HSV-1. Recurrent facial palsy was induced after HSV-1 reactivation by auricular scratch. After DM induction, the number of cluster of differentiation 3 (CD3)(+) T cells decreased by 70% in the DM mice, and facial nerve palsy recurred in 13% of the DM mice. Herpes simplex virus type 1 deoxyribonucleic acid (DNA) was detected in the facial nerve of all of the DM mice with palsy, and HSV-1 capsids were found in the geniculate ganglion using electron microscopy. Herpes simplex virus type 1 DNA was also found in some of the DM mice without palsy, which suggested the subclinical reactivation of HSV-1. These results suggested that HSV-1 reactivation in the geniculate ganglion may be the main causative factor of the increased incidence of facial paralysis in DM patients. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Identification of novel autoantibodies in type 1 diabetic patients using a high-density protein microarray.

PubMed

Koo, Bo Kyung; Chae, Sehyun; Kim, Kristine M; Kang, Min Jueng; Kim, Eunhee G; Kwak, Soo Heon; Jung, Hye Seung; Cho, Young Min; Choi, Sung Hee; Park, Young Joo; Shin, Choong Ho; Jang, Hak C; Shin, Chan Soo; Hwang, Daehee; Yi, Eugene C; Park, Kyong Soo

2014-09-01

Autoantibodies can facilitate diagnostic and therapeutic means for type 1 diabetes (T1DM). We profiled autoantibodies from serum samples of 16 T1DM patients, 16 type 2 diabetic (T2DM) patients, and 27 healthy control subjects with normal glucose tolerance (NGT) by using protein microarrays containing 9,480 proteins. Two novel autoantibodies, anti-EEF1A1 and anti-UBE2L3, were selected from microarrays followed by immunofluorescence staining of pancreas. We then tested the validity of the candidates by ELISA in two independent test cohorts: 1) 95 adults with T1DM, 49 with T2DM, 11 with latent autoimmune diabetes in adults (LADA), 20 with Graves disease, and 66 with NGT and 2) 33 children with T1DM and 34 healthy children. Concentrations of these autoantibodies were significantly higher in T1DM patients than in NGT and T2DM subjects (P < 0.01), which was also confirmed in the test cohort of children (P < 0.05). Prevalence of anti-EEF1A1 and anti-UBE2L3 antibodies was 29.5% and 35.8% in T1DM, respectively. Of note, 40.9% of T1DM patients who lack anti-GAD antibodies (GADA) had anti-EEF1A1 and/or anti-UBE2L3 antibodies. These were also detected in patients with fulminant T1DM but not LADA. Our approach identified autoantibodies that can provide a new dimension of information indicative of T1DM independent of GADA and new insights into diagnosis and classification of T1DM. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Radiative Natural Supersymmetry with Mixed Axion/Higgsino Cold Dark Matter

NASA Astrophysics Data System (ADS)

Baer, Howard

Models of natural supersymmetry seek to solve the little hierarchy problem by positing a spectrum of light higgsinos ≲ 200 GeV and light top squarks ≲ 500 GeV along with very heavy squarks and TeV-scale gluinos. Such models have low electroweak finetuning and are safe from LHC searches. However, in the context of the MSSM, they predict too low a value of m h and the relic density of thermally produced higgsino-like WIMPs falls well below dark matter (DM) measurements. Allowing for high scale soft SUSY breaking Higgs mass m H u > m 0 leads to natural cancellations during RG running, and to radiatively induced low finetuning at the electroweak scale. This model of radiative natural SUSY (RNS), with large mixing in the top squark sector, allows for finetuning at the 5-10 % level with TeV-scale top squarks and a 125 GeV light Higgs scalar h. If the strong CP problem is solved via the PQ mechanism, then we expect an axion-higgsino admixture of dark matter, where either or both the DM particles might be directly detected.

Radiative natural supersymmetry with mixed axion/higgsino cold dark matter

NASA Astrophysics Data System (ADS)

Baer, Howard

2013-05-01

Models of natural supersymmetry seek to solve the little hierarchy problem by positing a spectrum of light higgsinos <~ 200 GeV and light top squarks <~ 500 GeV along with very heavy squarks and TeV-scale gluinos. Such models have low electroweak finetuning and are safe from LHC searches. However, in the context of the MSSM, they predict too low a value of mh and the relic density of thermally produced higgsino-like WIMPs falls well below dark matter (DM) measurements. Allowing for high scale soft SUSY breaking Higgs mass mHu > m0 leads to natural cancellations during RG running, and to radiatively induced low finetuning at the electroweak scale. This model of radiative natural SUSY (RNS), with large mixing in the top squark sector, allows for finetuning at the 5-10% level with TeV-scale top squarks and a 125 GeV light Higgs scalar h. If the strong CP problem is solved via the PQ mechanism, then we expect an axion-higgsino admixture of dark matter, where either or both the DM particles might be directly detected.

Effective interaction of electroweak-interacting dark matter with Higgs boson and its phenomenology

NASA Astrophysics Data System (ADS)

Hisano, Junji; Kobayashi, Daiki; Mori, Naoya; Senaha, Eibun

2015-03-01

We study phenomenology of electroweak-interacting fermionic dark matter (DM) with a mass of O (100) GeV. Constructing the effective Lagrangian that describes the interactions between the Higgs boson and the SU (2)L isospin multiplet fermion, we evaluate the electric dipole moment (EDM) of electron, the signal strength of Higgs boson decay to two photons and the spin-independent elastic-scattering cross section with proton. As representative cases, we consider the SU (2)L triplet fermions with zero/nonzero hypercharges and SU (2)L doublet fermion. It is found that the electron EDM gives stringent constraints on those model parameter spaces. In the cases of the triplet fermion with zero hypercharge and the doublet fermion, the Higgs signal strength does not deviate from the standard model prediction by more than a few % once the current DM direct detection constraint is taken into account, even if the CP violation is suppressed. On the contrary, O (10- 20)% deviation may occur in the case of the triplet fermion with nonzero hypercharge. Our representative scenarios may be tested by the future experiments.

Dark sector shining through 750 GeV dark Higgs boson at the LHC

NASA Astrophysics Data System (ADS)

Ko, P.; Nomura, Takaaki

2016-07-01

We consider a dark sector with SU(3)C × U(1)Y × U(1)X and three families of dark fermions that are chiral under dark U(1)X gauge symmetry, whereas scalar dark matter X is the SM singlet. U(1)X dark symmetry is spontaneously broken by nonzero VEV of dark Higgs field 〈 Φ 〉, generating the masses of dark fermions and dark photon Z‧. The resulting dark Higgs boson ϕ can be produced at the LHC by dark quark loop (involving 3 generations) and will decay into a pair of photon through charged dark fermion loop. Its decay width can be easily ∼ 45 GeV due to its possible decays into a pair of dark photon, which is not strongly constrained by the current LHC searches pp → ϕ →Z‧Z‧ followed by Z‧ decays into the SM fermion pairs. The scalar DM can achieve thermal relic density without conflict with direct detection bound or the invisible ϕ decay into a pair of DM.

A blind transform based approach for the detection of isolated astrophysical pulses

NASA Astrophysics Data System (ADS)

Alkhweldi, Marwan; Schmid, Natalia A.; Prestage, Richard M.

2017-06-01

This paper presents a blind algorithm for the automatic detection of isolated astrophysical pulses. The detection algorithm is applied to spectrograms (also known as "filter bank data" or "the (t,f) plane"). The detection algorithm comprises a sequence of three steps: (1) a Radon transform is applied to the spectrogram, (2) a Fourier transform is applied to each projection parametrized by an angle, and the total power in each projection is calculated, and (3) the total power of all projections above 90° is compared to the total power of all projections below 90° and a decision in favor of an astrophysical pulse present or absent is made. Once a pulse is detected, its Dispersion Measure (DM) is estimated by fitting an analytically developed expression for a transformed spectrogram containing a pulse, with varying value of DM, to the actual data. The performance of the proposed algorithm is numerically analyzed.

Optimizing diabetes management: managed care strategies.

PubMed

Tzeel, E Albert

2013-06-01

Both the prevalence of type 2 diabetes mellitus (DM) and its associated costs have been rising over time and are projected to continue to escalate. Therefore, type 2 DM (T2DM) management costs represent a potentially untenable strain on the healthcare system unless substantial, systemic changes are made. Managed care organizations (MCOs) are uniquely positioned to attempt to make the changes necessary to reduce the burdens associated with T2DM by developing policies that align with evidence-based DM management guidelines and other resources. For example, MCOs can encourage members to implement healthy lifestyle choices, which have been shown to reduce DM-associated mortality and delay comorbidities. In addition, MCOs are exploring the strengths and weaknesses of several different benefit plan designs. Value-based insurance designs, sometimes referred to as value-based benefit designs, use both direct and indirect data to invest in incentives that change behaviors through health information technologies, communications, and services to improve health, productivity, quality, and financial trends. Provider incentive programs, sometimes referred to as "pay for performance," represent a payment/delivery paradigm that places emphasis on rewarding value instead of volume to align financial incentives and quality of care. Accountable care organizations emphasize an alignment between reimbursement and implementation of best practices through the use of disease management and/ or clinical pathways and health information technologies. Consumer-directed health plans, or high-deductible health plans, combine lower premiums with high annual deductibles to encourage members to seek better value for health expenditures. Studies conducted to date on these different designs have produced mixed results.

Turn on macrocyclic chemosensor for Al3+ ion with facile synthesis and application in live cell imaging.

PubMed

Ezhumalai, Dhineshkumar; Mathivanan, Iyappan; Chinnadurai, Anbuselvan

2018-06-15

An effort of a new Schiff base macrocyclic chemosensor, 1 4 ‑methyl‑2,6,8,12,14,18‑hexaaza‑1,7,13(1,2),4,10,16(1,4)‑hexabenzenacyclooctadecaphane‑2,5,8,11,14,17‑hexaene (me1) and 1 4 ,7 4 ‑dimethyl‑2,6,8,12,14,18‑hexaaza‑1,7,13(1,2),4,10,16(1,4)‑hexabenzenacyclooctadecadecaphane‑2,5,8,11,14,17‑hexaene (dm2), which enables selective sensing of Al 3+ in aqueous DMF were synthesized by a simplistic one-step condensation reaction of macrocyclic compounds. The probe me1 and dm2 characterized by elemental analysis, FT-IR, 1 H and 13 C NMR, LC-MS spectral techniques. The compounds as mentioned above subjected to FE-SEM with EDS and elemental color mapping. On addition of Al 3+ , the fluorescent probe me1 and dm2 induces turn-on responses in both absorption and sensing spectra by a PET mechanism. The receptor me1 and dm2 serve highly selective, sensitive and turn-on detection of Al 3+ . Further, they did not interfere with other cations present in biological or environmental samples. The detection limit is found to be 3μM and 5μM. From the view of cytotoxic activity, the ability of these compounds me1 and dm2 to inhibit the growth of KB cell lines examined. The chelating functionality of compounds me1 and dm2 examined for their inhibitory properties of KB cell, live cell images. The compounds me1 and dm2 subjected to theoretical studies by DFT-B3LYP invoking the 6-31G level of theory. The energy of the HOMO and LUMO has been established. Copyright © 2018 Elsevier B.V. All rights reserved.

Posterior parietal cortex mediates encoding and maintenance processes in change blindness.

PubMed

Tseng, Philip; Hsu, Tzu-Yu; Muggleton, Neil G; Tzeng, Ovid J L; Hung, Daisy L; Juan, Chi-Hung

2010-03-01

It is commonly accepted that right posterior parietal cortex (PPC) plays an important role in updating spatial representations, directing visuospatial attention, and planning actions. However, recent studies suggest that right PPC may also be involved in processes that are more closely associated with our visual awareness as its activation level positively correlates with successful conscious change detection (Beck, D.M., Rees, G., Frith, C.D., & Lavie, N. (2001). Neural correlates of change detection and change blindness. Nature Neuroscience, 4, 645-650.). Furthermore, disruption of its activity increases the occurrences of change blindness, thus suggesting a causal role for right PPC in change detection (Beck, D.M., Muggleton, N., Walsh, V., & Lavie, N. (2006). Right parietal cortex plays a critical role in change blindness. Cerebral Cortex, 16, 712-717.). In the context of a 1-shot change detection paradigm, we applied transcranial magnetic stimulation (TMS) during different time intervals to elucidate the temporally precise involvement of PPC in change detection. While subjects attempted to detect changes between two image sets separated by a brief time interval, TMS was applied either during the presentation of picture 1 when subjects were encoding and maintaining information into visual short-term memory, or picture 2 when subjects were retrieving information relating to picture 1 and comparing it to picture 2. Our results show that change blindness occurred more often when TMS was applied during the viewing of picture 1, which implies that right PPC plays a crucial role in the processes of encoding and maintaining information in visual short-term memory. In addition, since our stimuli did not involve changes in spatial locations, our findings also support previous studies suggesting that PPC may be involved in the processes of encoding non-spatial visual information (Todd, J.J. & Marois, R. (2004). Capacity limit of visual short-term memory in human posterior parietal cortex. Nature, 428, 751-754.). Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Hypoglycemic effect of polysaccharides with different molecular weight of Pseudostellaria heterophylla

PubMed Central

2013-01-01

Abstracts Background The aims of this study were to evaluate the antidiabetic activity and to detect molecular size of Pseudostellaria heterophylla polysaccharide (PHP). Pseudostellaria heterophylla is a medicine extensively used in traditional Chinese medicine formulas to treat diabetes and its complications. Methods Molecular weight of PHP was determined by gel permeation chromatography combined with phenol-sulphuric acid method and the monosaccharides composition was determined by HPLC with a precolumn derivatization. Four polysaccharides with different molecular weight were compared for hypoglycemic active on two animal models both high does alloxan induced type1 diabetic mellitus (T1DM) and high-fat/lower does streptozotocin induced type2 diabetic mellitus (T2DM). Blood sugar, glucose tolerance, and insulin tolerance were detected. Rat serum IL-1β, IL-2, IL-10, Leptin, TNF-α, Acrp30 and CRP were also analyzed by sandwich-ELISA approaches to preliminary probe the hypoglycemic mechanism of PHP. Results The hypoglycemic effects related to molecular size of polysaccharide were more effective against T2DM than T1DM. PHP comprise four monosaccharides of galacturonic acid, glucose, galactose and arabinos. T2DM rats daily receiving oral dose of polysaccharide(100 ~ 400 mg/kg) with 50 ~ 210 kDa molecular weight (PF40) could not only significantly lower blood sugar but also reduce total triglyceride level in serum. PF40 improves in insulin tolerance inhibited the expression of some biomarkers including inflammatory cytokine TNF-α and elevated anti-inflammatory cytokine IL-10, regulated adiponectin Acrp30 and leptin. Conclusions PF40 prevent the cascade of inflammatory events in the treatment of T2DM to block overweight progresses to obesity. PMID:24131482

Comparison of body mass index, waist circumference, and waist to height ratio in the prediction of hypertension and diabetes mellitus: Filipino-American women cardiovascular study.

PubMed

Battie, Cynthia A; Borja-Hart, Nancy; Ancheta, Irma B; Flores, Rene; Rao, Goutham; Palaniappan, Latha

2016-12-01

The relative ability of three obesity indices to predict hypertension (HTN) and diabetes (DM) and the validity of using Asian-specific thresholds of these indices were examined in Filipino-American women (FAW). Filipino-American women ( n  = 382), 40-65 years of age were screened for hypertension (HTN) and diabetes (DM) in four major US cities. Body mass index (BMI), waist circumference (WC) and waist circumference to height ratio (WHtR) were measured. ROC analyses determined that the three obesity measurements were similar in predicting HTN and DM (AUC: 0.6-0.7). The universal WC threshold of ≥ 35 in. missed 13% of the hypertensive patients and 12% of the diabetic patients. The Asian WC threshold of ≥ 31.5 in. increased detection of HTN and DM but with a high rate of false positives. The traditional BMI ≥ 25 kg/m 2 threshold missed 35% of those with hypertension and 24% of those with diabetes. The Asian BMI threshold improved detection but resulted in a high rate of false positives. The suggested WHtR cut-off of ≥ 0.5 missed only 1% of those with HTN and 0% of those with DM. The three obesity measurements had similar but modest ability to predict HTN and DM in FAW. Using Asian-specific thresholds increased accuracy but with a high rate of false positives. Whether FAW, especially at older ages, should be encouraged to reach these lower thresholds needs further investigation because of the high false positive rates.

Comprehensive eye evaluation algorithm

NASA Astrophysics Data System (ADS)

Agurto, C.; Nemeth, S.; Zamora, G.; Vahtel, M.; Soliz, P.; Barriga, S.

2016-03-01

In recent years, several research groups have developed automatic algorithms to detect diabetic retinopathy (DR) in individuals with diabetes (DM), using digital retinal images. Studies have indicated that diabetics have 1.5 times the annual risk of developing primary open angle glaucoma (POAG) as do people without DM. Moreover, DM patients have 1.8 times the risk for age-related macular degeneration (AMD). Although numerous investigators are developing automatic DR detection algorithms, there have been few successful efforts to create an automatic algorithm that can detect other ocular diseases, such as POAG and AMD. Consequently, our aim in the current study was to develop a comprehensive eye evaluation algorithm that not only detects DR in retinal images, but also automatically identifies glaucoma suspects and AMD by integrating other personal medical information with the retinal features. The proposed system is fully automatic and provides the likelihood of each of the three eye disease. The system was evaluated in two datasets of 104 and 88 diabetic cases. For each eye, we used two non-mydriatic digital color fundus photographs (macula and optic disc centered) and, when available, information about age, duration of diabetes, cataracts, hypertension, gender, and laboratory data. Our results show that the combination of multimodal features can increase the AUC by up to 5%, 7%, and 8% in the detection of AMD, DR, and glaucoma respectively. Marked improvement was achieved when laboratory results were combined with retinal image features.

[Relationship between body fat and creatinine clearence in adults with and without diabetes mellitus].

PubMed

Romero-Campos, Sandra; Viveros-Cortés, Ángel; Medina-Escobedo, Martha; Sansores-España, Delia; Villanueva-Jorge, Salha

2015-01-01

Obesity is a risk factor for renal damage. This study aimed to determine the relationship between body fat percent and creatinine clearance in adult patients with and without type 2 diabetes mellitus (T2DM). An observational prospective cross-correlation study was carried out among adults with and without T2DM between 18 and 60 years of age. It was determined the time of evolution with T2DM, as well as fat percentage (FP), body mass index (BMI), creatinine clearance (Cockroft-Gault [CrCCG]), glycemia and micro/macroalbuminuria. The correlation between CrCCG and FP was determined by Spearman's test. 174 subjects were included in this study. Obesity by BMI and FP in subjects with and without T2DM was similar. Of the studied subjects, 12.6 % didn't have kidney damage and 50.7 % had increased risk of renal disease; the frequencies for stages 1-4 of kidney damage were 12.0, 20.1, 4.0 and 0.6 %, respectively. Spearman's test showed a direct relationship between FP and CrCCG, higher in diabetics (r = 0.418, p < 0.0001) than in non-diabetics (p = 0.327, p < 0.0001). The FP was correlated directly with the CrCCG in subjects with and without T2DM; therefore, we can conclude that the greater the kidney damage, the smaller the fat porcentage in the study sample.

INVOLVED IN DE NOVO 2-containing complex involved in RNA-directed DNA methylation in Arabidopsis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ausin, Israel; Greenberg, Maxim V.C.; Simanshu, Dhirendra K.

2012-10-23

At least three pathways control maintenance of DNA cytosine methylation in Arabidopsis thaliana. However, the RNA-directed DNA methylation (RdDM) pathway is solely responsible for establishment of this silencing mark. We previously described INVOLVED IN DE NOVO 2 (IDN2) as being an RNA-binding RdDM component that is required for DNA methylation establishment. In this study, we describe the discovery of two partially redundant proteins that are paralogous to IDN2 and that form a stable complex with IDN2 in vivo. Null mutations in both genes, termed IDN2-LIKE 1 and IDN2-LIKE 2 (IDNL1 and IDNL2), result in a phenotype that mirrors, but doesmore » not further enhance, the idn2 mutant phenotype. Genetic analysis suggests that this complex acts in a step in the downstream portion of the RdDM pathway. We also have performed structural analysis showing that the IDN2 XS domain adopts an RNA recognition motif (RRM) fold. Finally, genome-wide DNA methylation and expression analysis confirms the placement of the IDN proteins in an RdDM pathway that affects DNA methylation and transcriptional control at many sites in the genome. Results from this study identify and describe two unique components of the RdDM machinery, adding to our understanding of DNA methylation control in the Arabidopsis genome.« less

Insulin Resistance-Associated Interhemispheric Functional Connectivity Alterations in T2DM: A Resting-State fMRI Study

PubMed Central

Xia, Wenqing; Wang, Shaohua; Spaeth, Andrea M.; Rao, Hengyi; Wang, Pin; Yang, Yue; Huang, Rong; Cai, Rongrong; Sun, Haixia

2015-01-01

We aim to investigate whether decreased interhemispheric functional connectivity exists in patients with type 2 diabetes mellitus (T2DM) by using resting-state functional magnetic resonance imaging (rs-fMRI). In addition, we sought to determine whether interhemispheric functional connectivity deficits associated with cognition and insulin resistance (IR) among T2DM patients. We compared the interhemispheric resting state functional connectivity of 32 T2DM patients and 30 healthy controls using rs-fMRI. Partial correlation coefficients were used to detect the relationship between rs-fMRI information and cognitive or clinical data. Compared with healthy controls, T2DM patients showed bidirectional alteration of functional connectivity in several brain regions. Functional connectivity values in the middle temporal gyrus (MTG) and in the superior frontal gyrus were inversely correlated with Trail Making Test-B score of patients. Notably, insulin resistance (log homeostasis model assessment-IR) negatively correlated with functional connectivity in the MTG of patients. In conclusion, T2DM patients exhibit abnormal interhemispheric functional connectivity in several default mode network regions, particularly in the MTG, and such alteration is associated with IR. Alterations in interhemispheric functional connectivity might contribute to cognitive dysfunction in T2DM patients. PMID:26064945

Decreasing the roughage:concentrate ratio of a diet to determine the critical roughage part for beef cattle.

PubMed

De Campeneere, S; Fiems, L O; De Boever, J L; Vanacker, J M; De Brabander, D L

2002-02-01

The critical roughage part (CRP) of 2 diet types was determined in a cross-over design with 6 double-muscled and 6 normally conformed Belgian Blue bulls fitted with rumen cannulae. The roughage:concentrate ratio was lowered weekly until signs of a lack of physical structure were observed. For diet 1, consisting of maize silage and concentrates, the initial proportion of maize silage was 25% of DM but it decreased weekly with 5% units of DM. For the second diet, consisting of wheat straw and concentrate, 12% straw (DM basis) was provided during the first week and thereafter the proportion of straw decreased weekly with 3% units of DM. Several directly observable parameters (rumen pH, feed intake, bloat, faecal consistency) were evaluated weekly for each bull. Apart from these direct indicators of acidosis, also other parameters, whose results were only available after the end of the trial, were determined (volatile fatty acid profile, lactic acid concentration, chewing time). The roughage part between the part fed when signs of a lack of physical structure was first observed and the part that was fed the week before, was considered as the CRP. Most animals showed no acute signs of clinical acidosis (directly observable parameters) and finished the trial on a 100% concentrate diet. However, in sacco rumen DM-degradabilities of maize silage, grass silage and wheat grain was depressed considerably when low roughage diets were fed. Based on all observed parameters, the mean CRP was calculated to be 14.7% for diet 1 and 8.1% for diet 2. The beef type (double-muscled or not) had no influence on the CRP.

Thinking about brain insulin resistance.

PubMed

Al Haj Ahmad, Reem M; Al-Domi, Hayder A

2018-05-06

Dementia and type 2 diabetes mellitus (T2DM) are two of the epidemics of our time; in which insulin resistance (IR) is playing the central role. Epidemiological studies found that different types of dementia development may be promoted by the presence of T2DM. We aimed in this review to highlight the role of insulin and the IR in the brain as a pathophysiological factor of dementia development and also to expand our understanding of T2DM as a mediator of IR in the brain and to review the possible mechanisms of action that may explain the association. A critical review of the relevant published English articles up to 2018, using PubMed, Google Scholar, Science Direct, ADI, and WHO database was carried out. Keywords were included insulin resistance, T3DM, T2DM, dementia, brain insulin resistance were used. The rapidly increased prevalence of dementia concurrently with T2DM and obesity need urgent action to illustrate guidelines for prevention, modifying, and treatment based on mechanistic studies. Copyright © 2018 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Dark matter "transporting" mechanism explaining positron excesses

NASA Astrophysics Data System (ADS)

Kim, Doojin; Park, Jong-Chul; Shin, Seodong

2018-04-01

We propose a novel mechanism to explain the positron excesses, which are observed by satellite-based telescopes including PAMELA and AMS-02, in dark matter (DM) scenarios. The novelty behind the proposal is that it makes direct use of DM around the Galactic Center where DM populates most densely, allowing us to avoid tensions from cosmological and astrophysical measurements. The key ingredients of this mechanism include DM annihilation into unstable states with a very long laboratory-frame life time and their "retarded" decay near the Earth to electron-positron pair(s) possibly with other (in)visible particles. We argue that this sort of explanation is not in conflict with relevant constraints from big bang nucleosynthesis and cosmic microwave background. Regarding the resultant positron spectrum, we provide a generalized source term in the associated diffusion equation, which can be readily applicable to any type of two-"stage" DM scenarios wherein production of Standard Model particles occurs at completely different places from those of DM annihilation. We then conduct a data analysis with the recent AMS-02 data to validate our proposal.

Fast Radio Burst/Gamma-Ray Burst Cosmography

NASA Astrophysics Data System (ADS)

Gao, He; Li, Zhuo; Zhang, Bing

2014-06-01

Recently, both theoretical arguments and observational evidence suggested that a small fraction of fast radio bursts (FRBs) could be associated with gamma-ray bursts (GRBs). If such FRB/GRB association systems are commonly detected in the future, the combination of dispersion measures (DM) derived from FRBs and redshifts derived from GRBs makes these systems a plausible tool to conduct cosmography. We quantify uncertainties in deriving the redshift-dependent DM_{IGM} as a function of z and test how well dark energy models can be constrained with Monte Carlo simulations. We show that with several tens of FRB/GRB systems potentially detected in a decade or so, one may reach reasonable constraints on wCDM models. When combined with Type Ia supernova (SN Ia) data, unprecedented constraints on the dark energy equation of state may be achieved, thanks to the prospects of detecting FRB/GRB systems at relatively high redshifts. The ratio between the mean value \\lt {DM_IGM} (z)\\gt and luminosity distance (D L(z)) is insensitive to dark energy models. This gives the prospect of applying SN Ia data to calibrate \\lt {DM_IGM} (z)\\gt using a relatively small sample of FRB/GRB systems, allowing a reliable constraint on the baryon inhomogeneity distribution as a function of redshift. The methodology developed in this paper can also be applied if the FRB redshifts can be measured by other means. Some caveats of putting this method into practice are also discussed.

Role of exercise in the management of diabetes mellitus: the global scenario.

PubMed

Thent, Zar Chi; Das, Srijit; Henry, Leonard Joseph

2013-01-01

Exercise training programs have emerged as a useful therapeutic regimen for the management of type 2 diabetes mellitus (T2DM). Majority of the Western studies highlighted the effective role of exercise in T2DM. Therefore, the main aim was to focus on the extent, type of exercise and its clinical significance in T2DM in order to educate the clinicians from developing countries, especially in Asians. Pubmed, Science Direct, Scopus, ISI Web of Knowledge and Google scholar were searched using the terms "type 2 diabetes mellitus," "type 2 DM," "exercise," and/or "physical activity," and "type 2 diabetes mellitus with exercise." Only clinical or human studies published in English language between 2000 and 2012 were included. Certain criteria were assigned to achieve appropriate results. Twenty five studies met the selected criteria. The majority of the studies were randomized controlled trial study design (65%). Most of the aerobic exercise based studies showed a beneficial effect in T2DM. Resistance exercise also proved to have positive effect on T2DM patients. Minimal studies related to other types of exercises such as yoga classes, joba riding and endurance-type exercise were found. On the other hand, United States of America (USA) showed strong interest of exercise management towards T2DM. Aerobic exercise is more common in clinical practice compared to resistance exercise in managing T2DM. Treatment of T2DM with exercise training showed promising role in USA. A large number of researches are mandatory in the developing countries for incorporating exercise in the effective management of T2DM.

Diabetes mellitus in people with schizophrenia, bipolar disorder and major depressive disorder: a systematic review and large scale meta-analysis.

PubMed

Vancampfort, Davy; Correll, Christoph U; Galling, Britta; Probst, Michel; De Hert, Marc; Ward, Philip B; Rosenbaum, Simon; Gaughran, Fiona; Lally, John; Stubbs, Brendon

2016-06-01

Type 2 diabetes mellitus (T2DM) is highly predictive of cardiovascular diseases and can have particularly deleterious health impacts in people with severe mental illness (SMI), i.e. schizophrenia, bipolar disorder or major depressive disorder. This meta-analysis aimed: a) to describe pooled frequencies of T2DM in people with SMI; b) to analyze the influence of demographic, illness and treatment variables as well as T2DM assessment methods; and c) to describe T2DM prevalence in studies directly comparing persons with each specific SMI diagnosis to general population samples. The trim and fill adjusted pooled T2DM prevalence among 438,245 people with SMI was 11.3% (95% CI: 10.0%-12.6%). In antipsychotic-naïve participants, the prevalence of T2DM was 2.9% (95% CI: 1.7%-4.8%). There were no significant diagnostic subgroup differences. A comparative meta-analysis established that multi-episode persons with SMI (N=133,470) were significantly more likely to have T2DM than matched controls (N=5,622,664): relative risk, RR=1.85, 95% CI: 1.45-2.37, p<0.001. The T2DM prevalence was consistently elevated in each of the three major diagnostic subgroups compared to matched controls. Higher T2DM prevalences were observed in women with SMI compared to men (RR=1.43, 95% CI: 1.20-1.69, p<0.001). Multi-episode (versus first-episode) status was the only significant predictor for T2DM in a multivariable meta-regression analysis (r(2) =0.52, p<0.001). The T2DM prevalence was higher in patients prescribed antipsychotics, except for aripriprazole and amisulpride. Routine screening and multidisciplinary management of T2DM is needed. T2DM risks of individual antipsychotic medications should be considered when making treatment choices. © 2016 World Psychiatric Association.

A Study of Autoimmune Polyglandular Syndrome (APS) in Patients with Type1 Diabetes Mellitus (T1DM) Followed Up at a Teritiary Care Hospital

PubMed Central

Shaikh, Shaheen Banu; Haji, Ismail M.; Doddamani, Parveen; Rahman, M.

2014-01-01

Background: Type1 diabetes mellitus (T1DM) results from auto- immune destruction of insulin-producing β cells and is characterized by the presence of insulitis and β-cell autoantibodies. Up to one third of patients develop an autoimmune polyglandular syndrome (APS). Presence of other autoimmune disorders in patients with T1DM has been associated with increased morbidity and mortality. Hypoglycemia resulting from concurrent hypothyroidism or adrenal crisis can be dangerous; starting replacement therapy for hypothyroidism may result in adrenal crisis if background hypocortisolism is not recognized. Early detection of antibodies and latent organ-specific dysfunction is advocated to alert physicians to take appropriate action in order to prevent full-blown disease. Aims: The objectives of this study were to assess the concurrence of various autoimmune disorders in patients with T1DM, to review the concept and detect the overt forms of Autoimmune Thyroid Disease (AITD), Addison’s Disease (AD), Vitamin B 12, vitiligo in T1DM and to find their correlation according to age and sex of the patients. Methods: It is a retrospective study where medical records between January 2007-June 2010 of all the patients diagnosed with T1DM, followed up at Department of Endocrinology were reviewed to find out the presence of (AD), AITD, vitiligo, Vitamin B12 deficiency and Primary Gonadal Failure, which were diagnosed clinically with available investigational procedures. Results: A total of 100 cases of T1DM were evaluated during the present study. The age group of patients ranged from 8 to 40 years, with the average being 21.56 years. 64% of the patients were males and the rest were females. 29 % of T1DM subjects had AITD (Hashimoto’s or Graves’disease), 5% were diagnosed with Vitamin B12 deficiency, 4% had AD, and 6% showed Vitiligo. 28 % had family history of autoimmune endocrinopathy. Conclusion: The commonest autoimmune disorder associated with T1DM found in our study was AITD. Because genetic/ autoantibodies testing is not a feasible option, it is important to screen them with best available laboratory facilities and clinical assessment in view of high prevalence of associated autoimmune conditions. PMID:24701486

Comparison of digital color fundus imaging and fluorescein angiographic findings for the early detection of diabetic retinopathy in young type 1 diabetic patients.

PubMed

Kapsala, Z; Anastasakis, A; Mamoulakis, D; Maniadaki, I; Tsilimbaris, M

2018-01-01

To compare the findings from digital 7-field color fundus (CF) photography and fundus fluorescein angiography (FFA) in young patients with diabetes mellitus (DM) type 1 without known diabetic retinopathy. In this prospective, observational cohort study, 54 type 1 diabetic patients were recruited. Participants had been diagnosed with diabetes mellitus (DM) for at least 6 years, had Best Corrected Visual Acuity of 20/25 or better and did not have any known retinal pathology. One hundred and seven eyes were analyzed. All patients underwent a complete ophthalmic examination in the Retina Service of a University Eye Clinic including digital CF imaging and FFA. The mean age of the patients was 18.6 years. Mean duration of DM was 11.3 years, and mean haemoglobin A1c (HbA1c) level was 8.6%. Of the 107 eyes, 8 eyes (7.5%) showed microvascular abnormalities on CF images, while FFA images revealed changes in 26 eyes (24.3%). Hence, 18 of the 26 eyes showing abnormalities on FFA did not show any abnormalities on CF images. Mean DM duration in the patient group with detectable microvascular changes was found to be significantly higher compared to patients without changes, while no difference in HbA1c levels, serum lipid levels or blood pressure was observed. Comparison of digital CF and FFA findings for the detection of diabetic microvascular changes in type 1 diabetic patients showed that FFA reveals more information about retinal vascular pathology for early detection of diabetic retinopathy. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The Fate of Bacterial Cocaine Esterase (CocE): An In Vivo Study of CocE-Mediated Cocaine Hydrolysis, CocE Pharmacokinetics, and CocE EliminationS⃞

PubMed Central

Brim, Remy L.; Noon, Kathleen R.; Collins, Gregory T.; Stein, Aron; Nichols, Joseph; Narasimhan, Diwa; Ko, Mei-Chuan; Woods, James H.

2012-01-01

Cocaine abuse and toxicity remain widespread problems in the United States. Currently cocaine toxicity is treated only symptomatically, because there is no Food and Drug Administration-approved pharmacotherapy for this indication. To address the unmet need, a stabilized mutant of bacterial cocaine esterase [T172R/G173Q-CocE (DM-CocE)], which hydrolyzes cocaine into inactive metabolites and has low immunogenic potential, has been developed and previously tested in animal models of cocaine toxicity. Here, we document the rapid cocaine hydrolysis by low doses of DM-CocE in vitro and in vivo, as well as the pharmacokinetics and distribution of the DM-CocE protein in rats. DM-CocE at 50.5 μg/kg effectively eliminated 4 mg/kg cocaine within 2 min in both male and female rats as measured by mass spectrometry. We expanded on these findings by using a pharmacologically relevant dose of DM-CocE (0.32 mg/kg) in rats and monkeys to hydrolyze convulsant doses of cocaine. DM-CocE reduced cocaine to below detection limits rapidly after injection; however, elimination of DM-CocE resulted in peripheral cocaine redistribution by 30 to 60 min. Elimination of DM-CocE was quantified by using [35S] labeling of the enzyme and was found to have a half-life of 2.1 h in rats. Minor urinary output of DM-CocE was also observed. Immunohistochemistry, Western blotting, and radiography all were used to elucidate the mechanism of DM-CocE elimination, rapid proteolysis, and recycling of amino acids into all tissues. This rapid elimination of DM-CocE is a desirable property of a therapeutic for cocaine toxicity and should reduce the likelihood of immunogenic or adverse reactions as DM-CocE moves toward clinical use. PMID:21990608

Survival of Listeria monocytogenes in Wilted and Additive-Treated Grass Silage

PubMed Central

Pauly, TM; Tham, WA

2003-01-01

Grass was field-dried to 3 different dry matter (DM) levels (200, 430 and 540 g/kg) and inoculated with 106–107 cfu/g of a Listeria monocytogenes strain sharing a phagovar occasionally involved in food-borne outbreaks of listeriosis. Formic acid (3 ml/kg) or lactic acid bacteria (8·105/g) with cellulolytic enzymes were applied only to forages with low and intermediate DM levels. Forages were ensiled in laboratory silos (1700 ml) and were stored at 25°C for 30 or 90 days. After 90 days of storage, L. monocytogenes could not be detected in any silo, except one with the high dry matter grass without additive. After 30 days of storage, between 102 and 106 cfu L. monocytogenes/g silage were isolated from the untreated silages. Increasing the DM content from 200 to 540 g/kg did not reduce listeria counts possibly because of the lower production of fermentation acids (higher pH). In silages treated with additives, counts of L. monocytogenes were always lower than in silages without additive. In wet silages (DM 200 g/kg) both additives were effective, but in the wilted silages (DM 430 g/kg) only the bacterial additive reduced listeria counts below detection level. Listeria counts were highly correlated to silage pH (r = 0.92), the concentration of lactic acid (r = -0.80) and the pooled amount of undissociated acids (r = -0.83). PMID:14650546

Photometry and Blazhko Effect in RR Lyr Type Star DM Cyg

NASA Astrophysics Data System (ADS)

Udovichenko, S. N.; Dubovsky, P. A.; Kudzej, I.

2010-12-01

The photometric CCD observations for RR Lyr type star DM Cyg in Astronomical stations near Odessa(Ukraine) and Kolonica(Slovakia) in 2008 and near Odessa in 2009 have been carried out. The light curves in V system were obtained and the frequency Fourier analyse was performed. From Fourier spectra of the light curves 18 frequencies were identified. The weak Blazhko effect was detected.

Arabidopsis RNA Polymerase V Mediates Enhanced Compaction and Silencing of Geminivirus and Transposon Chromatin during Host Recovery from Infection.

PubMed

Coursey, Tami; Regedanz, Elizabeth; Bisaro, David M

2018-04-01

Plants employ RNA-directed DNA methylation (RdDM) and dimethylation of histone 3 lysine 9 (H3K9me2) to silence geminiviruses and transposable elements (TEs). We previously showed that canonical RdDM (Pol IV-RdDM) involving RNA polymerases IV and V (Pol IV and Pol V) is required for Arabidopsis thaliana to recover from infection with Beet curly top virus lacking a suppressor protein that inhibits methylation (BCTV L2 - ). Recovery, which is characterized by reduced viral DNA levels and symptom remission, allows normal floral development. Here, we used formaldehyde-assisted isolation of regulatory elements (FAIRE) to confirm that >90% of BCTV L2 - chromatin is highly compacted during recovery, and a micrococcal nuclease-chromatin immunoprecipitation assay showed that this is largely due to increased nucleosome occupancy. Physical compaction correlated with augmented cytosine and H3K9 methylation and with reduced viral gene expression. We additionally demonstrated that these phenomena are dependent on Pol V and by extension the Pol IV-RdDM pathway. BCTV L2 - was also used to evaluate the impact of viral infection on host loci, including repressed retrotransposons Ta3 and Athila6A Remarkably, an unexpected Pol V-dependent hypersuppression of these TEs was observed, resulting in transcript levels even lower than those detected in uninfected plants. Hypersuppression is likely to be especially important for natural recovery from wild-type geminiviruses, as viral L2 and AL2 proteins cause ectopic TE expression. Thus, Pol IV-RdDM targets both viral and TE chromatin during recovery, simultaneously silencing the majority of viral genomes and maintaining host genome integrity by enforcing tighter control of TEs in future reproductive tissues. IMPORTANCE In plants, RdDM pathways use small RNAs to target cytosine and H3K9 methylation, thereby silencing DNA virus genomes and transposable elements (TEs). Further, Pol IV-RdDM involving Pol IV and Pol V is a key aspect of host defense that can lead to recovery from geminivirus infection. Recovery is characterized by reduced viral DNA levels and symptom remission and thus allows normal floral development. Studies described here demonstrate that the Pol V-dependent enhanced viral DNA and histone methylation observed during recovery result in increased chromatin compaction and suppressed gene expression. In addition, we show that TE-associated chromatin is also targeted for hypersuppression during recovery, such that TE transcripts are reduced below the already low levels seen in uninfected plants. Thus, Pol IV-RdDM at once silences the majority of viral genomes and enforces a tight control over TEs which might otherwise jeopardize genome integrity in future reproductive tissue. Copyright © 2018 American Society for Microbiology.

Genetic information and the prediction of incident type 2 diabetes in a high-risk multiethnic population: the EpiDREAM genetic study.

PubMed

Anand, Sonia S; Meyre, David; Pare, Guillaume; Bailey, Swneke D; Xie, Changchun; Zhang, Xiaohe; Montpetit, Alexandre; Desai, Dipika; Bosch, Jackie; Mohan, Viswanathan; Diaz, Rafael; McQueen, Matthew J; Cordell, Heather J; Keavney, Bernard; Yusuf, Salim; Gaudet, Daniel; Gerstein, Hertzel; Engert, James C

2013-09-01

To determine if 16 single nucleotide polymorphisms (SNPs) associated with type 2 diabetes (T2DM) in Europeans are also associated with T2DM in South Asians and Latinos and if they can add to the prediction of incident T2DM in a high-risk population. In the EpiDREAM prospective cohort study, physical measures, questionnaires, and blood samples were collected from 25,063 individuals at risk for dysglycemia. Sixteen SNPs that have been robustly associated with T2DM in Europeans were genotyped. Among 15,466 European, South Asian, and Latino subjects, we examined the association of these 16 SNPs alone and combined in a gene score with incident cases of T2DM (n = 1,016) that developed during 3.3 years of follow-up. Nine of the 16 SNPs were significantly associated with T2DM, and their direction of effect was consistent across the three ethnic groups. The gene score was significantly higher among subjects who developed incident T2DM (cases vs. noncases: 16.47 [2.50] vs. 15.99 [2.56]; P = 0.00001). The gene score remained an independent predictor of incident T2DM, with an odds ratio of 1.08 (95% CI 1.05-1.11) per additional risk allele after adjustment for T2DM risk factors. The gene score in those with no family history of T2DM was 16.02, whereas it was 16.19 in those with one parent with T2DM and it was 16.32 in those with two parents with T2DM (P trend = 0.0004). The C statistic of T2DM risk factors was 0.708 (0.691-0.725) and increased only marginally to 0.714 (0.698-0.731) with the addition of the gene score (P for C statistic change = 0.0052). T2DM genetic associations are generally consistent across ethnic groups, and a gene score only adds marginal information to clinical factors for T2DM prediction.

Direct phase selection of initial phases from single-wavelength anomalous dispersion (SAD) for the improvement of electron density and ab initio structure determination.

PubMed

Chen, Chung-De; Huang, Yen-Chieh; Chiang, Hsin-Lin; Hsieh, Yin-Cheng; Guan, Hong-Hsiang; Chuankhayan, Phimonphan; Chen, Chun-Jung

2014-09-01

Optimization of the initial phasing has been a decisive factor in the success of the subsequent electron-density modification, model building and structure determination of biological macromolecules using the single-wavelength anomalous dispersion (SAD) method. Two possible phase solutions (φ1 and φ2) generated from two symmetric phase triangles in the Harker construction for the SAD method cause the well known phase ambiguity. A novel direct phase-selection method utilizing the θ(DS) list as a criterion to select optimized phases φ(am) from φ1 or φ2 of a subset of reflections with a high percentage of correct phases to replace the corresponding initial SAD phases φ(SAD) has been developed. Based on this work, reflections with an angle θ(DS) in the range 35-145° are selected for an optimized improvement, where θ(DS) is the angle between the initial phase φ(SAD) and a preliminary density-modification (DM) phase φ(DM)(NHL). The results show that utilizing the additional direct phase-selection step prior to simple solvent flattening without phase combination using existing DM programs, such as RESOLVE or DM from CCP4, significantly improves the final phases in terms of increased correlation coefficients of electron-density maps and diminished mean phase errors. With the improved phases and density maps from the direct phase-selection method, the completeness of residues of protein molecules built with main chains and side chains is enhanced for efficient structure determination.

Metformin inhibits goitrogenous effects of type 2 diabetes.

PubMed

Ittermann, Till; Markus, Marcello R P; Schipf, Sabine; Derwahl, Michael; Meisinger, Christa; Völzke, Henry

2013-07-01

Data on the association between type 2 diabetes mellitus (T2DM) and thyroid volume are sparse. An experimental study demonstrated an inhibitory effect of metformin on the growth of human thyroid cells. So far no study on humans has investigated potentially modulating effects of metformin on the association between T2DM and thyroid volume. Therefore, we investigated these effects in a population-based cohort study. We used data from the Study of Health in Pomerania and included 2570 individuals for cross-sectional and 1088 individuals for longitudinal analyses. T2DM was defined by physician-diagnosed self-report or intake of antidiabetic medication. In the cross-sectional data, females with T2DM treated with antidiabetic medication other than metformin had a larger thyroid volume (β=4.69; 95% CI 1.87 to 7.50) and a higher odds ratio (OR) for goiter (OR=1.71; 95% CI 1.05 to 2.79) than females without T2DM, whereas in males, no such association was detected. In females or males treated with metformin, T2DM was not associated with thyroid volume or goiter. In longitudinal analyses, incident T2DM not treated with metformin was significantly associated with a higher risk for incident goiter in the total population (incidence rate ratio (IRR)=1.70; 95% CI 1.10 to 2.91). Individuals with T2DM having changed from metformin to other antidiabetic agents during follow-up also had a higher risk for incident goiter than individuals without T2DM (IRR=2.71; 95% CI 1.74 to 4.20). We demonstrate an inhibitory effect of metformin on prevalent and incident goiter. Anti-goitrogenous effects of metformin add to the general benefits of metformin treatment of T2DM.

The FTO variant is associated with chronic complications of diabetes mellitus in Czech population.

PubMed

Hubacek, Jaroslav A; Dlouha, Dana; Klementova, Marta; Lanska, Vera; Neskudla, Tomas; Pelikanova, Terezie

2018-02-05

Genome-wide association studies have resulted in the identification of the FTO gene as an important genetic determinant of diabetes mellitus. The aim of this study was to confirm the role of this gene in the development of DM in the Czech-Slavonic population and to analyse whether this gene is associated with common DM complications. Two groups of patients (814 with T1DM and 848 with T2DM) and a group of healthy controls (2339 individuals) - both of Czech origin - were genotyped for the FTO rs17817449 SNP. ANOVA and logistic regression were used for the statistical evaluations. The frequency of the GG genotype was significantly higher in T2DM (25.4% vs. 16.7%, P<0.0005) but not in T1DM patients (19.3% vs. 16.7%, P=0.20) than in controls. The increased risk of development of diabetic nephropathy was observed both for T1DM patients (GG vs. TT homozygotes, P<0.01) and T2DM patients (G carriers vs. TT homozygotes, P<0.05). FTO genotype predicted the development of diabetic neuropathy (GG vs. TT comparison; P<0.01) in the T2DM patients only. No association between FTO genotype and development of retinopathy was detected. All presented values are after adjustment for age, sex, BMI and duration of diabetes. We confirm the association between the FTO rs17817449 SNP and susceptibility to T2DM in the Czech-Slavonic population. The same variant is associated with a spectrum of chronic complications in both types of diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

Dental and periodontal health, and microbiological and salivary conditions in patients with or without diabetes undergoing haemodialysis.

PubMed

Schmalz, Gerhard; Schiffers, Nora; Schwabe, Sandra; Vasko, Radovan; Müller, Gerhard A; Haak, Rainer; Mausberg, Rainer F; Ziebolz, Dirk

2017-06-01

The aim of this cross-sectional study was to evaluate the dental and periodontal health, as well as the microbiological and salivary conditions, of patients with and without diabetes mellitus (DM) who are receiving haemodialysis. One-hundred and fifty-nine haemodialysis patients were included and divided into groups according to the pre-existing diabetes status: DM or no DM. The oral examination included dental findings and assessment of the periodontal situation. The periodontal condition was classified as healthy/mild, moderate or severe periodontitis. Subgingival biofilm samples were analysed using the polymerase chain reaction. The salivary diagnostics included measurement of unstimulated and stimulated salivary flow, pH and buffer capacity. Statistical analyses used Fisher's test, the t-test and the Mann-Whitney U-test (α = 5%). The dental findings showed no significant difference between patients with and without DM (P = 0.44). The prevalence of periodontitis was high (96% in patients with DM and 97% in patients who did not have DM) and there was no significant difference between the groups (P = 0.71). There was a higher prevalence of Porphyromonas gingivalis, Parvimonas micros, Eubacterium nucleatum and Capnocytophaga spp. in patients without DM (P < 0.05). The salivary pH was significantly higher in patients without DM (P < 0.01). While differences in the prevalence of periodontal pathogenic bacteria and in the salivary pH were detected between the groups, the dental and periodontal status was comparable between patients with and without DM. Accordingly, DM appears to have no decisive influence on the oral health in patients treated with haemodialysis who have well-controlled diabetes. © 2017 FDI World Dental Federation.

Testicular Metabolic Reprogramming in Neonatal Streptozotocin-Induced Type 2 Diabetic Rats Impairs Glycolytic Flux and Promotes Glycogen Synthesis

PubMed Central

Rato, L.; Alves, M. G.; Dias, T. R.; Cavaco, J. E.; Oliveira, Pedro F.

2015-01-01

Defects in testicular metabolism are directly implicated with male infertility, but most of the mechanisms associated with type 2 diabetes- (T2DM) induced male infertility remain unknown. We aimed to evaluate the effects of T2DM on testicular glucose metabolism by using a neonatal-streptozotocin- (n-STZ) T2DM animal model. Plasma and testicular hormonal levels were evaluated using specific kits. mRNA and protein expression levels were assessed by real-time PCR and Western Blot, respectively. Testicular metabolic profile was assessed by 1H-NMR spectroscopy. T2DM rats showed increased glycemic levels, impaired glucose tolerance and hyperinsulinemia. Both testicular and serum testosterone levels were decreased, whereas those of 17β-estradiol were not altered. Testicular glycolytic flux was not favored in testicles of T2DM rats, since, despite the increased expression of both glucose transporters 1 and 3 and the enzyme phosphofructokinase 1, lactate dehydrogenase activity was severely decreased contributing to lower testicular lactate content. However, T2DM enhanced testicular glycogen accumulation, by modulating the availability of the precursors for its synthesis. T2DM also affected the reproductive sperm parameters. Taken together these results indicate that T2DM is able to reprogram testicular metabolism by enhancing alternative metabolic pathways, particularly glycogen synthesis, and such alterations are associated with impaired sperm parameters. PMID:26064993

Sirolimus eluting stent (Cypher) in patients with diabetes mellitus: results from the German Cypher Stent Registry.

PubMed

Weber, Frank D; Schneider, Henrik; Wiemer, Marcus; Pfannebecker, Thomas; Tebbe, Ulrich; Hamm, Christian W; Senges, Jochen; Schneider, Steffen; Nienaber, Christoph A

2008-02-01

Patients with diabetes mellitus (DM) undergoing percutaneous coronary intervention (PCI) are at increased risk for adverse outcomes. The use of sirolimus eluting stents (SES) has been shown to improve outcomes in diabetic patients. Since results from randomized trials were derived from selected patients scientific scrutiny under real world conditions is necessary. 1,948 patients with DM and 4,707 patients without DM were included in the German Cypher Registry, a post-marketing survey of use of SES in Germany. In >99% of entry cases a structured clinical follow-up was completed. By angiographic criteria severity of coronary artery disease was higher in diabetic patients compared to non-diabetics. However, procedural success and in-hospital complication rates were comparable between DM- and non-DM-patients. 6 months MACE rate in the DM group was significantly higher than in the non-DM group (16.4% vs. 13.0%) but lower than expected from historical data with the use of bare metal stents (BMS). The results with SES in diabetics are encouraging but DM remains a risk factor for poor outcome of PCI. No statement is justified whether the treatment of diabetics with SES is at least as safe as bypass surgery. This intriguing question has to be answered in a direct randomized head-to-head comparison with state of the art surgery.

Mass discrepancy-acceleration relation: A universal maximum dark matter acceleration and implications for the ultralight scalar dark matter model

NASA Astrophysics Data System (ADS)

Ureña-López, L. Arturo; Robles, Victor H.; Matos, T.

2017-08-01

Recent analysis of the rotation curves of a large sample of galaxies with very diverse stellar properties reveals a relation between the radial acceleration purely due to the baryonic matter and the one inferred directly from the observed rotation curves. Assuming the dark matter (DM) exists, this acceleration relation is tantamount to an acceleration relation between DM and baryons. This leads us to a universal maximum acceleration for all halos. Using the latter in DM profiles that predict inner cores implies that the central surface density μDM=ρsrs must be a universal constant, as suggested by previous studies of selected galaxies, revealing a strong correlation between the density ρs and scale rs parameters in each profile. We then explore the consequences of the constancy of μDM in the context of the ultralight scalar field dark matter model (SFDM). We find that for this model μDM=648 M⊙ pc-2 and that the so-called WaveDM soliton profile should be a universal feature of the DM halos. Comparing with the data from the Milky Way and Andromeda satellites, we find that they are all consistent with a boson mass of the scalar field particle of the order of 10-21 eV /c2, which puts the SFDM model in agreement with recent cosmological constraints.

Testicular Metabolic Reprogramming in Neonatal Streptozotocin-Induced Type 2 Diabetic Rats Impairs Glycolytic Flux and Promotes Glycogen Synthesis.

PubMed

Rato, L; Alves, M G; Dias, T R; Cavaco, J E; Oliveira, Pedro F

2015-01-01

Defects in testicular metabolism are directly implicated with male infertility, but most of the mechanisms associated with type 2 diabetes- (T2DM) induced male infertility remain unknown. We aimed to evaluate the effects of T2DM on testicular glucose metabolism by using a neonatal-streptozotocin- (n-STZ) T2DM animal model. Plasma and testicular hormonal levels were evaluated using specific kits. mRNA and protein expression levels were assessed by real-time PCR and Western Blot, respectively. Testicular metabolic profile was assessed by (1)H-NMR spectroscopy. T2DM rats showed increased glycemic levels, impaired glucose tolerance and hyperinsulinemia. Both testicular and serum testosterone levels were decreased, whereas those of 17β-estradiol were not altered. Testicular glycolytic flux was not favored in testicles of T2DM rats, since, despite the increased expression of both glucose transporters 1 and 3 and the enzyme phosphofructokinase 1, lactate dehydrogenase activity was severely decreased contributing to lower testicular lactate content. However, T2DM enhanced testicular glycogen accumulation, by modulating the availability of the precursors for its synthesis. T2DM also affected the reproductive sperm parameters. Taken together these results indicate that T2DM is able to reprogram testicular metabolism by enhancing alternative metabolic pathways, particularly glycogen synthesis, and such alterations are associated with impaired sperm parameters.

Prospects for indirect detection of frozen-in dark matter

NASA Astrophysics Data System (ADS)

Heikinheimo, Matti; Tenkanen, Tommi; Tuominen, Kimmo

2018-03-01

We study observational consequences arising from dark matter (DM) of nonthermal origin, produced by dark freeze-out from a hidden sector heat bath. We assume this heat bath was populated by feebly coupled mediator particles, produced via a Higgs portal interaction with the Standard Model (SM). The dark sector then attained internal equilibrium with a characteristic temperature different from the SM photon temperature. We find that even if the coupling between the DM and the SM sectors is very weak, the scenario allows for indirect observational signals. We show how the expected strength of these signals depends on the temperature of the hidden sector at DM freeze-out.

Risk Factors for Diabetes Mellitus in Chronic Pancreatitis: A Cohort of 2011 Patients.

PubMed

Pan, Jun; Xin, Lei; Wang, Dan; Liao, Zhuan; Lin, Jin-Huan; Li, Bai-Rong; Du, Ting-Ting; Ye, Bo; Zou, Wen-Bin; Chen, Hui; Ji, Jun-Tao; Zheng, Zhao-Hong; Hu, Liang-Hao; Li, Zhao-Shen

2016-04-01

Diabetes mellitus (DM) is a common complication of chronic pancreatitis (CP) and increases the mortality. The identification of risk factors for DM development may contribute to the early detection and potential risk reduction of DM in patients with CP.Patients with CP admitted to Changhai Hospital (Shanghai, China) from January 2000 to December 2013 were enrolled. Cumulative rates of DM after the onset of CP were calculated by Kaplan-Meier method. Risk factors for DM development after the diagnosis of CP were identified by Cox proportional hazards regression model.A total of 2011 patients with CP were enrolled. During follow-up (median duration, 22.0 years), 564 patients developed DM. Cumulative rates of DM 20 and 50 years after the onset of CP were 45.8% (95% confidence interval [CI], 41.8%-50.0%) and 90.0% (95% CI, 75.4%-97.7%), respectively. Five risk factors for DM development after the diagnosis of CP were identified: male sex (hazard ratio [HR], 1.51; 95% CI, 1.08-2.11), alcohol abuse (HR, 2.00; 95% CI, 1.43-2.79), steatorrhea (HR, 1.46; 95% CI, 1.01-2.11), biliary stricture (HR, 2.25; 95% CI, 1.43-3.52), and distal pancreatectomy (HR, 3.41; 95% CI, 1.80-6.44).In conclusion, the risk of developing DM in patients with CP is not only influenced by the development of biliary stricture and steatorrhea indicating disease progression, and inherent nature of study subjects such as male sex, but also by modifiable factors including alcohol abuse and distal pancreatectomy .

Risk Factors for Diabetes Mellitus in Chronic Pancreatitis: A Cohort of 2,011 Patients.

PubMed

Pan, Jun; Xin, Lei; Wang, Dan; Liao, Zhuan; Lin, Jin-Huan; Li, Bai-Rong; Du, Ting-Ting; Ye, Bo; Zou, Wen-Bin; Chen, Hui; Ji, Jun-Tao; Zheng, Zhao-Hong; Hu, Liang-Hao; Li, Zhao-Shen

2016-04-01

Diabetes mellitus (DM) is a common complication of chronic pancreatitis (CP) and increases the mortality. The identification of risk factors for DM development may contribute to the early detection and potential risk reduction of DM in patients with CP.Patients with CP admitted to Changhai Hospital (Shanghai, China) from January 2000 to December 2013 were enrolled. Cumulative rates of DM after the onset of CP were calculated by Kaplan-Meier method. Risk factors for DM development after the diagnosis of CP were identified by Cox proportional hazards regression model.A total of 2011 patients with CP were enrolled. During follow-up (median duration, 22.0 years), 564 patients developed DM. Cumulative rates of DM 20 and 50 years after the onset of CP were 45.8% (95% confidence interval [CI], 41.8%-50.0%) and 90.0% (95% CI, 75.4%-97.7%), respectively. Five risk factors for DM development after the diagnosis of CP were identified: male sex (hazard ratio [HR], 1.51; 95% CI, 1.08-2.11), alcohol abuse (HR, 2.00; 95% CI, 1.43-2.79), steatorrhea (HR, 1.46; 95% CI, 1.01-2.11), biliary stricture (HR, 2.25; 95% CI, 1.43-3.52), and distal pancreatectomy (HR, 3.41; 95% CI, 1.80-6.44).In conclusion, the risk of developing DM in patients with CP is not only influenced by the development of biliary stricture and steatorrhea indicating disease progression, and inherent nature of study subjects such as male sex, but also by modifiable factors including alcohol abuse and distal pancreatectomy.

The expression of BAFF in the muscles of patients with dermatomyositis.

PubMed

Baek, Ahmi; Park, Hyung Jun; Na, Sang-Jun; Shim, Dong Suk; Moon, Joon-Shik; Yang, Young; Choi, Young-Chul

2012-08-15

A B-cell activating factor of the tumor necrosis factor (TNF) family (BAFF) plays a crucial role in B-cell survival and maturation. An elevated serum BAFF level has been linked to several autoimmune diseases such as Sjögren syndrome, systemic lupus erythematosus and rheumatoid arthritis. Dermatomyositis (DM), one of autoimmune inflammatory myopathies, is characterized by inflammatory cell infiltration (CD4(+) T cells and B cells) in skeletal muscle. Serum BAFF level was significantly high in DM, but the role of BAFF is not well understood. We investigated the role of BAFF in the immunopathogenesis of DM. To examine the transcriptional increase of BAFF gene expression, we performed RT-PCR analysis with skeletal muscle tissue that contained 4 controls and 9 patients with DM. Next, in order to detect BAFF expression and cellular localization in DM, we executed immunostaining in cryosection of biopsied muscle tissue with 4 controls and 8 patients and we adopted to double immunostaining to find which inflammatory cells expressed BAFF-receptor (BAFF-R). BAFF mRNA level was increased in DM patients compared with normal controls. BAFF expression was markedly increased at muscle fibers in the perifascicular area but not blood vessels. BAFF-R was expressed in inflammatory cells in skeletal muscle tissues of DM patients. We found that BAFF expression in muscle tissue may be associated with an increased number of CD4(+) T cells and CD19(+) B cells in DM. Our study results suggest that BAFF might play an important role in the pathogenesis of DM. Copyright © 2012 Elsevier B.V. All rights reserved.

Transgene expression of Drosophila melanogaster nucleoside kinase reverses mitochondrial thymidine kinase 2 deficiency.

PubMed

Krishnan, Shuba; Zhou, Xiaoshan; Paredes, João A; Kuiper, Raoul V; Curbo, Sophie; Karlsson, Anna

2013-02-15

A strategy to reverse the symptoms of thymidine kinase 2 (TK2) deficiency in a mouse model was investigated. The nucleoside kinase from Drosophila melanogaster (Dm-dNK) was expressed in TK2-deficient mice that have been shown to present with a severe phenotype caused by mitochondrial DNA depletion. The Dm-dNK(+/-) transgenic mice were shown to be able to rescue the TK2-deficient mice. The Dm-dNK(+/-)TK2(-/-) mice were normal as judged by growth and behavior during the observation time of 6 months. The Dm-dNK-expressing mice showed a substantial increase in thymidine-phosphorylating activity in investigated tissues. The Dm-dNK expression also resulted in highly elevated dTTP pools. The dTTP pool alterations did not cause specific mitochondrial DNA mutations or deletions when 6-month-old mice were analyzed. The mitochondrial DNA was also detected at normal levels. In conclusion, the Dm-dNK(+/-)TK2(-/-) mouse model illustrates how dTMP synthesized in the cell nucleus can compensate for loss of intramitochondrial dTMP synthesis in differentiated tissue. The data presented open new possibilities to treat the severe symptoms of TK2 deficiency.

Hot leptogenesis from thermal Dark Matter

DOE PAGES

Bernal, Nicolas; Fong, Chee Sheng

2017-10-26

In this work, we investigate a scenario in which heavy Majorana Right-Handed Neutrinos (RHNs) are in thermal equilibrium with a dark sector with temperature higher than the Standard Model (SM) thermal bath. Specifically, we consider the scenario in which thermal Dark Matter (DM) abundance is fixed from the freeze-out of DM annihilations into RHNs. Due to the inert nature of the RHNs, we show that it is possible for the two sectors to remain thermally decoupled by having more than two generations of the RHNs. The hotter temperature implies higher abundances of DM and RHNs with the following consequences. Formore » leptogenesis, an enhancement in efficiency up to a factor of 51.6 can be obtained, though a resonant enhancement of CP violation is still required due to an upper mass bound of about 4 TeV for the RHNs. For the DM, an enhanced annihilation cross section up to a factor of 51.6 is required to obtain the correct DM abundance. This scenario can be probed via indirect detection of DM annihilating into RHNs, which then decay into hν, Zν and W ± ℓ ∓ with an enhanced annihilation cross section above the typical thermal value.« less

Precessional switching of antiferromagnets by electric field induced Dzyaloshinskii-Moriya torque

NASA Astrophysics Data System (ADS)

Kim, T. H.; Grünberg, P.; Han, S. H.; Cho, B. K.

2018-05-01

Antiferromagnetic insulators (AFIs) have attracted much interest from many researchers as promising candidates for use in ultrafast, ultralow-dissipation spintronic devices. As a fast method of reversing magnetization, precessional switching is realized when antiferromagnetic Néel orders l =(s1+s2 )/2 surmount the magnetic anisotropy or potential barrier in a given magnetic system, which is described well by the antiferromagnetic plane pendulum (APP) model. Here, we report that, as an alternative switching scenario, the direct coupling of an electric field with Dzyaloshinskii-Moriya (DM) interaction, which stems from spin-orbit coupling, is exploited for optimal switching. We derive the pendulum equation of motion of antiferromagnets, where DM torque is induced by a pulsed electric field. The temporal DM interaction is found to not only be in the form of magnetic torques (e.g., spin-orbit torque or magnetic field) but also modifies the magnetic potential that limits l 's activity; as a result, appropriate controls (e.g., direction, magnitude, and pulse shape) of the induced DM vector realize deterministic reversal in APP. The results present an approach for the control of a magnetic storage device by means of an electric field.

Estimation of chromatic errors from broadband images for high contrast imaging

NASA Astrophysics Data System (ADS)

Sirbu, Dan; Belikov, Ruslan

2015-09-01

Usage of an internal coronagraph with an adaptive optical system for wavefront correction for direct imaging of exoplanets is currently being considered for many mission concepts, including as an instrument addition to the WFIRST-AFTA mission to follow the James Web Space Telescope. The main technical challenge associated with direct imaging of exoplanets with an internal coronagraph is to effectively control both the diffraction and scattered light from the star so that the dim planetary companion can be seen. For the deformable mirror (DM) to recover a dark hole region with sufficiently high contrast in the image plane, wavefront errors are usually estimated using probes on the DM. To date, most broadband lab demonstrations use narrowband filters to estimate the chromaticity of the wavefront error, but this reduces the photon flux per filter and requires a filter system. Here, we propose a method to estimate the chromaticity of wavefront errors using only a broadband image. This is achieved by using special DM probes that have sufficient chromatic diversity. As a case example, we simulate the retrieval of the spectrum of the central wavelength from broadband images for a simple shaped- pupil coronagraph with a conjugate DM and compute the resulting estimation error.

Rapid exploration of configuration space with diffusion-map-directed molecular dynamics.

PubMed

Zheng, Wenwei; Rohrdanz, Mary A; Clementi, Cecilia

2013-10-24

The gap between the time scale of interesting behavior in macromolecular systems and that which our computational resources can afford often limits molecular dynamics (MD) from understanding experimental results and predicting what is inaccessible in experiments. In this paper, we introduce a new sampling scheme, named diffusion-map-directed MD (DM-d-MD), to rapidly explore molecular configuration space. The method uses a diffusion map to guide MD on the fly. DM-d-MD can be combined with other methods to reconstruct the equilibrium free energy, and here, we used umbrella sampling as an example. We present results from two systems: alanine dipeptide and alanine-12. In both systems, we gain tremendous speedup with respect to standard MD both in exploring the configuration space and reconstructing the equilibrium distribution. In particular, we obtain 3 orders of magnitude of speedup over standard MD in the exploration of the configurational space of alanine-12 at 300 K with DM-d-MD. The method is reaction coordinate free and minimally dependent on a priori knowledge of the system. We expect wide applications of DM-d-MD to other macromolecular systems in which equilibrium sampling is not affordable by standard MD.

Rapid Exploration of Configuration Space with Diffusion Map-directed-Molecular Dynamics

PubMed Central

Zheng, Wenwei; Rohrdanz, Mary A.; Clementi, Cecilia

2013-01-01

The gap between the timescale of interesting behavior in macromolecular systems and that which our computational resources can afford oftentimes limits Molecular Dynamics (MD) from understanding experimental results and predicting what is inaccessible in experiments. In this paper, we introduce a new sampling scheme, named Diffusion Map-directed-MD (DM-d-MD), to rapidly explore molecular configuration space. The method uses diffusion map to guide MD on the fly. DM-d-MD can be combined with other methods to reconstruct the equilibrium free energy, and here we used umbrella sampling as an example. We present results from two systems: alanine dipeptide and alanine-12. In both systems we gain tremendous speedup with respect to standard MD both in exploring the configuration space and reconstructing the equilibrium distribution. In particular, we obtain 3 orders of magnitude of speedup over standard MD in the exploration of the configurational space of alanine-12 at 300K with DM-d-MD. The method is reaction coordinate free and minimally dependent on a priori knowledge of the system. We expect wide applications of DM-d-MD to other macromolecular systems in which equilibrium sampling is not affordable by standard MD. PMID:23865517

Low irradiances affect abscisic acid, indole-3-acidic acid, and cytokinin levels of wheat (Triticum aestivum L.) tissues

NASA Technical Reports Server (NTRS)

Nan, R.; Carman, J. G.; Salisbury, F. B.

1999-01-01

Wheat (Triticum aestivum L.) plants were grown under four irradiance levels: 1,400, 400, 200, and 100 micromol m-2 s-1. Leaves and roots were sampled before, during, and after the boot stage, and levels of abscisic acid (ABA), indole-3-acetic acid (IAA), zeatin, zeatin riboside, dihydrozeatin, dihydrozeatin riboside, isopentenyl adenine, and isopentenyl adenosine were quantified using noncompetitive indirect ELISA systems. Levels of IAA in leaves and roots of plants exposed to 100 micromol m-2 s-1 of irradiance were 0.7 and 2.9 micromol kg-1 dry mass (DM), respectively. These levels were 0.2 and 1.0 micromol kg-1 DM, respectively, when plants were exposed to 1,400 micromol m-2 s-1. Levels of ABA in leaves and roots of plants exposed to 100 micromol m-2 s-1 were 0.65 and 0.55 micromol kg-1 DM, respectively. They were 0.24 micromol kg-1 DM (both leaves and roots) when plants were exposed to 1,400 micromol m-2 s-1. Levels of isopentenyl adenosine in leaves (24.3 nmol kg-1 DM) and roots (29.9 nmol kg-1 DM) were not affected by differences in the irradiance regime. Similar values were obtained in a second experiment. Other cytokinins could not be detected (<10 nmol kg 1 DM) in either experiment with the sample sizes used (150-600 mg DM for roots and shoots, respectively).

Shot-noise Limited Faraday Rotation Spectroscopy for Detection of Nitric Oxide Isotopes in Breath, Urine, and Blood

PubMed Central

Wang, Yin; Nikodem, Michal; Zhang, Eric; Cikach, Frank; Barnes, Jarrod; Comhair, Suzy; Dweik, Raed A.; Kao, Christina; Wysocki, Gerard

2015-01-01

Measurement of NO and/or its metabolites in the various body compartments has transformed our understanding of biology. The inability of the current NO measurement methods to account for naturally occurring and experimental NO isotopes, however, has prevented the scientific community from fully understating NO metabolism in vivo. Here we present a mid-IR Faraday rotation spectrometer (FRS) for detection of NO isotopes. The instrument utilizes a novel dual modulation/demodulation (DM) FRS method which exhibits noise performance at only 2 times the fundamental quantum shot-noise level and provides the record sensitivity in its class. This is achieved with a system that is fully autonomous, robust, transportable, and does not require cryogenic cooling. The DM-FRS enables continuous monitoring of nitric oxide isotopes with the detection limits of 3.72 ppbv/Hz1/2 to14NO and 0.53 ppbv/Hz1/2 to15NO using only 45 cm active optical path. This DM-FRS measurement method can be used to improve the performance of conventional FRS sensors targeting other radical species. The feasibility of the instrument to perform measurements relevant to studies of NO metabolism in humans is demonstrated. PMID:25767064

Patient engagement in type 2 diabetes mellitus research: what patients want.

PubMed

Simacek, Kristina F; Nelson, Tanya; Miller-Baldi, Mignon; Bolge, Susan C

2018-01-01

As patients are the ultimate stakeholder in their health, their perspectives should be included along with researchers, providers, and funders of research design, execution, and interpretation. Despite the high prevalence of type 2 diabetes mellitus (T2DM), patients are rarely directly included in these decisions. We sought to determine areas of research most important to patients with T2DM, identify ways through which patients with T2DM want to engage in research, and evaluate online patient research networks as a source for obtaining patient perspectives on research engagement. This study used an online patient community forum (PatientsLikeMe) to host two asynchronous moderated discussions, each with three to four prompted discussion posts. A qualitative summary of themes was derived from the posts. Eighty-eight participants with T2DM took part. Participants were mostly white (86%), averaged 58.6 years of age, half were female (50%), and over half (62%) resided in the US. Research priorities included managing T2DM with comorbidities, controlling blood sugar levels, finding a cure, and understanding causes of T2DM. Participants wanted to see direct applications of research to their lives. Clinical research was perceived to have overly restrictive eligibility criteria and to measure outcome sets that do not adequately address patient health concerns. Participants indicated broad interest in partnering in research and a willingness to apply their skills and educational background to specific stages in the research process. Patients with T2DM would like researchers to address outcomes that have meaning in patients' daily lives. Initiatives to involve patients in research should leverage and enable patients to contribute as participants, advisors, or co-investigators, going beyond research topic prioritization to full participation throughout the research process based on their abilities and interest. This study provides support for the use of online patient research network discussions to generate rich qualitative data to engage patients in research.

Heme iron intake and risk of new-onset diabetes in a Mediterranean population at high risk of cardiovascular disease: an observational cohort analysis

PubMed Central

2013-01-01

Background Several epidemiological studies have observed an increased risk of type 2 diabetes mellitus (T2DM) among subjects with a higher consumption of red and processed meat. Heme iron intake has been directly associated with a higher risk of T2DM in healthy adult Chinese and U.S populations. The objective of the present study was to evaluate the association between heme iron intake and the incidence of T2DM in a Mediterranean population at high cardiovascular risk. Methods We assessed a subset of participants in the PREDIMED trial as an observational cohort, followed up for a maximum of eight years. We initially included 1073 non-diabetic subjects (57.1% women) aged 67.3 ± 6.0 years, at high cardiovascular risk. Diet was assessed at the study baseline using a validated, semi-quantitative food frequency questionnaire. Results During the follow-up period 131 diabetics were newly diagnosed. The risk of developing T2DM was assessed using baseline heme iron intake and proportional hazard models, first unadjusted, then adjusted for energy, and finally adjusted for dietary, anthropometric, socio-demographic and lifestyle variables. Significant direct associations with the incidence of T2DM were found for heme iron (Hazard Ratio [HR] 1.30, 95% confidence interval [CI], 1.02 to 1.66). Secondarily, we have also observed that coffee (HR:0.93, 95% CI, 0.89 to 0.98) and alcoholic beverages (HR: 1.02, 95% CI, 1.01 to 1.04) were also found to reduce and increase the risk of T2DM, respectively. Conclusion High dietary intake of heme iron was associated with an increased risk of developing T2DM in a Mediterranean population at high cardiovascular risk. Trial registration Identifier: ISRCTN35739639. PMID:24188615

Is Israel ready for disease management?

PubMed

Linden, Ariel

2006-10-01

Approximately 60% of all worldwide deaths are caused by chronic disease resulting from modifiable health behaviors. In the United States, structured programs tailored to identify and modify health behaviors of patients with chronic illness have grown into a robust industry called disease management. DM is premised upon the basic assumption that health services utilization and morbidity can be reduced for those with chronic illness by augmenting traditional episodic medical care services and support between physician visits. Given that Israel and the U.S. have similar demographics in their chronically ill populations, it would make intuitive sense for Israel to replicate efforts made in the U.S. to incorporate DM strategies. This paper provides a conceptual framework of how DM could be integrated within the current organizational structure of the Israeli healthcare system, which is uniquely conducive to the implementation of DM on a population-wide basis. While ultimately the decision to invest in DM lies with stakeholders at various institutional levels in Israel, this paper is intended to provide direction and support for that decision-making process.

Highlights of DAMA/LIBRA

NASA Astrophysics Data System (ADS)

Bernabei, R.; Belli, P.; d'Angelo, A.; d'Angelo, S.; Di Marco, A.; Montecchia, F.; Incicchitti, A.; Cappella, F.; Caracciolo, V.; Cerulli, R.; Dai, C. J.; He, H. L.; Kuang, H. H.; Ma, X. H.; Sheng, X. D.; Wang, R. G.; Ye, Z. P.

2016-11-01

The DAMA project develops and uses new/improved low background scintillation detectors to investigate the Dark Matter (DM) particle component(s) in the galactic halo and rare processes deep underground at the Gran Sasso National Laboratory (LNGS) of the I.N.F.N.. Here some highlights of DAMA/LIBRA (Large sodium Iodide Bulk for Rare processes) as a unique apparatus in direct DM investigation for its full sensitive mass, target material, intrinsic radio-purity, methodological approach and all the controls performed on the experimental parameters are outlined. The DAMA/LIBRA-phase1 and the former DAMA/NaI data (cumulative exposure 1.33 ton × yr, corresponding to 14 annual cycles) have reached a model-independent evidence at 9.3 σ C.L. for the presence of DM particles in the galactic halo exploiting the DM annual modulation signature with highly radio-pure NaI(Tl) target. Some of the perspectives of the presently running DAMA/LIBRA-phase2 are summarised and the powerful tools offered by a model independent strategy of DM investigation are pointed out.

Are styrene oligomers in coastal sediments of an industrial area aryl hydrocarbon-receptor agonists?

PubMed

Hong, Seongjin; Lee, Junghyun; Lee, Changkeun; Yoon, Seo Joon; Jeon, Seungyeon; Kwon, Bong-Oh; Lee, Jong-Hyeon; Giesy, John P; Khim, Jong Seong

2016-06-01

Effect-directed analysis (EDA) was performed to identify the major aryl hydrocarbon receptor (AhR) agonists in sediments collected from a highly industrialized area (Lake Shihwa, Korea). Great AhR-mediated potencies were found in fractions containing aromatic compounds with log Kow values of 5-8, and relatively great concentrations of styrene oligomers (SOs) and polycyclic aromatic hydrocarbons (PAHs) were detected in those fractions. Until now, there was little information on occurrences and toxic relative potencies (RePs) of SOs in coastal environments. In the present study; i) distributions and compositions, ii) AhR binding affinities, and iii) contributions of SOs to total AhR-mediated potencies were determined in coastal sediments. Elevated concentrations of 10 SOs were detected in sediments of inland creeks ranging from 61 to 740 ng g(-1) dry mass (dm), while lesser concentrations were found in inner (mean = 33 ng g(-1) dm) and outer regions (mean = 25 ng g(-1) dm) of the lake. Concentrations of PAHs in sediments were comparable to those of SOs. 2,4-diphenyl-1-butene (SD3) was the predominant SO analogue in sediments. SOs and PAHs were accumulated in sediments near sources, and could not be transported to remote regions due to their hydrophobicity. RePs of 3 SOs could be derived, which were 1000- to 10,000-fold less than that of one representative potent AhR active PAH, benzo[a]pyrene. Although concentrations of SOs in sediments were comparable to those of PAHs, the collective contribution of SOs to total AhR-mediated potencies were rather small (<1%), primarily due to their smaller RePs. Overall, the present study provides information on distributions and AhR binding affinities for SOs as baseline data for degradation products of polystyrene plastic in the coastal environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Applications of Hadamard transform-gas chromatography/mass spectrometry to the detection of acetone in healthy human and diabetes mellitus patient breath.

PubMed

Fan, Gang-Ting; Yang, Chien-Lin; Lin, Cheng-Huang; Chen, Chien-Chung; Shih, Chung-Hung

2014-03-01

The Hadamard transform-gas chromatography/mass spectrometry (HT-GC/MS) technique was successfully employed to detect acetone, a biomarker for diabetes mellitus (DM) prediction, in human breath. Samples of exhaled breath were collected from four DM patients (one type-I and three type-II) and eight volunteers (nondiabetic healthy subjects), respectively. The gas samples, without any pretreatment, were simultaneously injected into a GC column through a Hadamard-injector based on Hadamard codes. Under optimized conditions, when cyclic S-matrix orders of 255, 1023 and 2047 were used, the S/N ratios of the acetone signals were substantially improved by 8.0-, 16.0- and 22.6-fold, respectively; these improvements are in good agreement with theoretically calculated values. We found that the breath acetone concentration levels in the four DM patients and the eight volunteers ranged from 1 to 10 ppmv and 0.1 to 1 ppmv, respectively. Copyright © 2014 Elsevier B.V. All rights reserved.

ZNF9 Activation of IRES-Mediated Translation of the Human ODC mRNA Is Decreased in Myotonic Dystrophy Type 2

PubMed Central

Sammons, Morgan A.; Antons, Amanda K.; Bendjennat, Mourad; Udd, Bjarne; Krahe, Ralf; Link, Andrew J.

2010-01-01

Myotonic dystrophy types 1 and 2 (DM1 and DM2) are forms of muscular dystrophy that share similar clinical and molecular manifestations, such as myotonia, muscle weakness, cardiac anomalies, cataracts, and the presence of defined RNA-containing foci in muscle nuclei. DM2 is caused by an expansion of the tetranucleotide CCTG repeat within the first intron of ZNF9, although the mechanism by which the expanded nucleotide repeat causes the debilitating symptoms of DM2 is unclear. Conflicting studies have led to two models for the mechanisms leading to the problems associated with DM2. First, a gain-of-function disease model hypothesizes that the repeat expansions in the transcribed RNA do not directly affect ZNF9 function. Instead repeat-containing RNAs are thought to sequester proteins in the nucleus, causing misregulation of normal cellular processes. In the alternative model, the repeat expansions impair ZNF9 function and lead to a decrease in the level of translation. Here we examine the normal in vivo function of ZNF9. We report that ZNF9 associates with actively translating ribosomes and functions as an activator of cap-independent translation of the human ODC mRNA. This activity is mediated by direct binding of ZNF9 to the internal ribosome entry site sequence (IRES) within the 5′UTR of ODC mRNA. ZNF9 can activate IRES-mediated translation of ODC within primary human myoblasts, and this activity is reduced in myoblasts derived from a DM2 patient. These data identify ZNF9 as a regulator of cap-independent translation and indicate that ZNF9 activity may contribute mechanistically to the myotonic dystrophy type 2 phenotype. PMID:20174632

Role of Exercise in the Management of Diabetes Mellitus: the Global Scenario

PubMed Central

Thent, Zar Chi; Das, Srijit; Henry, Leonard Joseph

2013-01-01

Background Exercise training programs have emerged as a useful therapeutic regimen for the management of type 2 diabetes mellitus (T2DM). Majority of the Western studies highlighted the effective role of exercise in T2DM. Therefore, the main aim was to focus on the extent, type of exercise and its clinical significance in T2DM in order to educate the clinicians from developing countries, especially in Asians. Methods Pubmed, Science Direct, Scopus, ISI Web of Knowledge and Google scholar were searched using the terms “type 2 diabetes mellitus,” “type 2 DM,” “exercise,” and/or “physical activity,” and “type 2 diabetes mellitus with exercise.” Only clinical or human studies published in English language between 2000 and 2012 were included. Certain criteria were assigned to achieve appropriate results. Results Twenty five studies met the selected criteria. The majority of the studies were randomized controlled trial study design (65%). Most of the aerobic exercise based studies showed a beneficial effect in T2DM. Resistance exercise also proved to have positive effect on T2DM patients. Minimal studies related to other types of exercises such as yoga classes, joba riding and endurance-type exercise were found. On the other hand, United States of America (USA) showed strong interest of exercise management towards T2DM. Conclusion Aerobic exercise is more common in clinical practice compared to resistance exercise in managing T2DM. Treatment of T2DM with exercise training showed promising role in USA. A large number of researches are mandatory in the developing countries for incorporating exercise in the effective management of T2DM. PMID:24236181

Association of Mannose-Binding Lectin rs1800450 and Tumor Necrotic Factor-α rs1800620 Polymorphism with Helicobacter pylori in Type II Diabetes Mellitus.

PubMed

Mortazavi, Elnaz; Eslami, Behnaz; Aghahosseini, Parisa; Ahron, Fatemeh; Amininejad, Armagan; Mahmoodi, Sepideh; Satarpour, Hadis; Radmanesh, Nilofar; Rassi, Hossein

2017-10-01

Type II diabetes mellitus (T2DM) is the prevalent type of diabetes, including 90% of the cases world-wide. Helicobacter pylori plays a pathogenic role in the development of T2DM. The host genetic factors have a significant impact on the clinical outcome and anatomical distribution of H. pylori infection and polymorphisms in several genes such as tumor necrotic factor (TNF)-α and mannose-binding lectin (MBL) and are considered to increase the risk for the development of T2DM. In this study, we investigate the prevalence rate of H. pylori infection and its relationship to MBL rs1800450 and TNF-α rs1800620 polymorphism in T2DM. In this case-control study, 174 patients with type II diabetes and 185 healthy controls were studied. Also, demographics, physical, and biochemical parameters were performed in all patients. The DNA extracted from blood specimens was amplified by H. pylori cagA-specific primers. The MBL rs1800450 and TNF-α rs1800620 genotyping were detected by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). The results show that H. pylori cagA positivity was detected in 42.82% of the diabetic patients and in 22.16% of the control group, and H. pylori infection was closely correlated with MBL rs1800450 AA genotype and TNF-α rs1800620 GG genotype when compared with healthy controls. Furthermore, these two genotypes were strongly associated with H. pylori cagA(+) samples when compared with cagA(-) samples. In addition, the presence of H. pylori cagA(+) infection was significantly associated with the elevated serum levels of total cholesterol and low-density lipoprotein cholesterol. In general, it can be concluded that molecular analysis of MBL rs1800450 AA genotype and TNF-α rs1800620 AA genotype is important in the early detection and treatment of T2DM with H. pylori cagA(+) infection.

Short communication: Using diurnal patterns of (13)C enrichment of CO2 to evaluate the effects of nitrate and docosahexaenoic acid on fiber degradation in the rumen of lactating dairy cows.

PubMed

Klop, G; Bannink, A; Dieho, K; Gerrits, W J J; Dijkstra, J

2016-09-01

Nitrate decreases enteric CH4 production in ruminants, but may also negatively affect fiber degradation. In this experiment, 28 lactating Holstein dairy cows were grouped into 7 blocks. Within blocks, cows were randomly assigned to 1 of 4 isonitrogenous treatments in a 2×2 factorial arrangement: control (CON); NO3 [21g of nitrate/kg of dry matter (DM)]; DHA [3g of docosahexaenoic acid (DHA)/kg of DM]; or NO3+DHA (21g of nitrate/kg of DM and 3g of DHA/kg of DM). Cows were fed a total mixed ration consisting of 21% grass silage, 49% corn silage, and 30% concentrates on a DM basis. Based on the difference in natural (13)C enrichment and neutral detergent fiber and starch content between grass silage and corn silage, we investigated whether a negative effect on rumen fiber degradation could be detected by evaluating diurnal patterns of (13)C enrichment of exhaled carbon dioxide. A significant nitrate × DHA interaction was found for neutral detergent fiber digestibility, which was reduced on the NO3 treatment to an average of 55%, as compared with 61, 64, and 65% on treatments CON, DHA, and NO3+DHA, respectively. Feeding nitrate, but not DHA, resulted in a pronounced increase in (13)C enrichment of CO2 in the first 3 to 4 h after feeding only. Results support the hypothesis that effects of a feed additive on the rate of fiber degradation in the rumen can be detected by evaluating diurnal patterns of (13)C enrichment of CO2. To be able to detect this, the main ration components have to differ considerably in fiber and nonfiber carbohydrate content as well as in natural (13)C enrichment. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Use of Lactobacillus plantarum fermentation products in bread-making to prevent Bacillus subtilis ropy spoilage.

PubMed

Valerio, Francesca; De Bellis, Palmira; Lonigro, Stella L; Visconti, Angelo; Lavermicocca, Paola

2008-03-20

Four fermentation products (FPs) of the lactic acid bacterium Lactobacillus plantarum ITM21B were screened for their anti-Bacillus activity in vitro and in bread-making trials. Results of the storage tests performed with loaves prepared with an FP or calcium propionate demonstrated that after 3 days at 30 degrees C, gross spoilage was evident in only the control loaves, which contained Bacillus subtilis at numbers of about 10(9) cfu/g. The highest inhibitory activity was shown by DM-FP obtained by growing L. plantarum in a defined medium (DM). Significantly, this medium contained an amino acceptor of the aminoacid transamination, namely alpha-ketoglutaric acid, and an aminoacid pool. With loaves prepared using the DM-acid mixture which simulated the DM-FP composition, the same reduction of ropy spoilage as with DM-FP was obtained after 3 days, while the efficacy of the mixture decreased after 7 days. This result suggests the potential involvement of some unknown metabolites in the inhibitory activity of DM-FP. In baked products made with flour based media (M1-FP, M2-FP, M3-FP), no ropy symptoms were noticeable after 3 days storage although a considerable Bacillus count was detected. DM-FP was as effective as calcium propionate (0.3% w/w, based on flour mass) in prolonging the Bacillus free-shelf life of yeast-leavened bread for 7 days.

Dark matter in the Sun: scattering off electrons vs nucleons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garani, Raghuveer; Palomares-Ruiz, Sergio, E-mail: garani@th.physik.uni-bonn.de, E-mail: sergiopr@ific.uv.es

The annihilation of dark matter (DM) particles accumulated in the Sun could produce a flux of neutrinos, which is potentially detectable with neutrino detectors/telescopes and the DM elastic scattering cross section can be constrained. Although the process of DM capture in astrophysical objects like the Sun is commonly assumed to be due to interactions only with nucleons, there are scenarios in which tree-level DM couplings to quarks are absent, and even if loop-induced interactions with nucleons are allowed, scatterings off electrons could be the dominant capture mechanism. We consider this possibility and study in detail all the ingredients necessary tomore » compute the neutrino production rates from DM annihilations in the Sun (capture, annihilation and evaporation rates) for velocity-independent and isotropic, velocity-dependent and isotropic and momentum-dependent scattering cross sections for DM interactions with electrons and compare them with the results obtained for the case of interactions with nucleons. Moreover, we improve the usual calculations in a number of ways and provide analytical expressions in three appendices. Interestingly, we find that the evaporation mass in the case of interactions with electrons could be below the GeV range, depending on the high-velocity tail of the DM distribution in the Sun, which would open a new mass window for searching for this type of scenarios.« less

Clinical significance of specific autoantibodies in juvenile dermatomyositis.

PubMed

Feldman, B M; Reichlin, M; Laxer, R M; Targoff, I N; Stein, L D; Silverman, E D

1996-10-01

To determine the prevalence and clinical association of myositis specific antibodies in an unselected group of patients with juvenile dermatomyositis (DM). The sera of 42 subjects, representing an unselected group of patients from a single center, with juvenile DM and 7 others with idiopathic inflammatory myopathy (IIM) were examined for the presence of myositis specific antibodies by immunodiffusion against calf thymus extract and immunoprecipitation with HeLa extract. Of the subjects with juvenile DM, only 2 had evidence of antibodies specific to myositis (anti-Mi2). Three other patients with juvenile DM had defined autoantibodies not usually considered to be specific to myositis. Two of the 3 subjects had anti-PM-Scl; both developed features of scleroderma after the juvenile DM remitted. The 5 subjects with defined autoantibodies did not differ clinically from the remainder of the subjects with the exception of the late development of scleroderma features in 2. Fourteen other subjects with juvenile DM had unidentified bands on immunoprecipitation, which may represent as yet undiscovered myositis specific antibodies. No myositis specific antibodies were detected in any of the 7 subjects with other IIM syndromes. Based on our findings, we do not recommend routine clinical testing for these antibodies in children with typical juvenile DM. Further study of the unidentified bands seen in our subjects may lead to better understanding of the clinical groupings and etiopathogenesis of childhood myositis.

SYSTEMATIC AND STOCHASTIC VARIATIONS IN PULSAR DISPERSION MEASURES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lam, M. T.; Cordes, J. M.; Chatterjee, S.

2016-04-10

We analyze deterministic and random temporal variations in the dispersion measure (DM) from the full three-dimensional velocities of pulsars with respect to the solar system, combined with electron-density variations over a wide range of length scales. Previous treatments have largely ignored pulsars’ changing distances while favoring interpretations involving changes in sky position from transverse motion. Linear trends in pulsar DMs observed over 5–10 year timescales may signify sizable DM gradients in the interstellar medium (ISM) sampled by the changing direction of the line of sight to the pulsar. We show that motions parallel to the line of sight can alsomore » account for linear trends, for the apparent excess of DM variance over that extrapolated from scintillation measurements, and for the apparent non-Kolmogorov scalings of DM structure functions inferred in some cases. Pulsar motions through atomic gas may produce bow-shock ionized gas that also contributes to DM variations. We discuss the possible causes of periodic or quasi-periodic changes in DM, including seasonal changes in the ionosphere, annual variations of the solar elongation angle, structure in the heliosphere and ISM boundary, and substructure in the ISM. We assess the solar cycle’s role on the amplitude of ionospheric and solar wind variations. Interstellar refraction can produce cyclic timing variations from the error in transforming arrival times to the solar system barycenter. We apply our methods to DM time series and DM gradient measurements in the literature and assess their consistency with a Kolmogorov medium. Finally, we discuss the implications of DM modeling in precision pulsar timing experiments.« less

Direct detection signatures of self-interacting dark matter with a light mediator

DOE PAGES

Nobile, Eugenio Del; Kaplinghat, Manoj; Yu, Hai-Bo

2015-10-27

Self-interacting dark matter (SIDM) is a simple and well-motivated scenario that could explain long-standing puzzles in structure formation on small scales. If the required self-interaction arises through a light mediator (with mass ~ 10 MeV) in the dark sector, this new particle must be unstable to avoid overclosing the universe. The decay of the light mediator could happen due to a weak coupling of the hidden and visible sectors, providing new signatures for direct detection experiments. The SIDM nuclear recoil spectrum is more peaked towards low energies compared to the usual case of contact interactions, because the mediator mass ismore » comparable to the momentum transfer of nuclear recoils. We show that the SIDM signal could be distinguished from that of DM particles with contact interactions by considering the time-average energy spectrum in experiments employing different target materials, or the average and modulated spectra in a single experiment. Using current limits from LUX and SuperCDMS, we also derive strong bounds on the mixing parameter between hidden and visible sector.« less

Self-consistent Dark Matter simplified models with an s-channel scalar mediator

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bell, Nicole F.; Busoni, Giorgio; Sanderson, Isaac W., E-mail: n.bell@unimelb.edu.au, E-mail: giorgio.busoni@unimelb.edu.au, E-mail: isanderson@student.unimelb.edu.au

We examine Simplified Models in which fermionic DM interacts with Standard Model (SM) fermions via the exchange of an s -channel scalar mediator. The single-mediator version of this model is not gauge invariant, and instead we must consider models with two scalar mediators which mix and interfere. The minimal gauge invariant scenario involves the mixing of a new singlet scalar with the Standard Model Higgs boson, and is tightly constrained. We construct two Higgs doublet model (2HDM) extensions of this scenario, where the singlet mixes with the 2nd Higgs doublet. Compared with the one doublet model, this provides greater freedommore » for the masses and mixing angle of the scalar mediators, and their coupling to SM fermions. We outline constraints on these models, and discuss Yukawa structures that allow enhanced couplings, yet keep potentially dangerous flavour violating processes under control. We examine the direct detection phenomenology of these models, accounting for interference of the scalar mediators, and interference of different quarks in the nucleus. Regions of parameter space consistent with direct detection measurements are determined.« less

Comparison of digital mammography and digital breast tomosynthesis in the detection of architectural distortion.

PubMed

Dibble, Elizabeth H; Lourenco, Ana P; Baird, Grayson L; Ward, Robert C; Maynard, A Stanley; Mainiero, Martha B

2018-01-01

To compare interobserver variability (IOV), reader confidence, and sensitivity/specificity in detecting architectural distortion (AD) on digital mammography (DM) versus digital breast tomosynthesis (DBT). This IRB-approved, HIPAA-compliant reader study used a counterbalanced experimental design. We searched radiology reports for AD on screening mammograms from 5 March 2012-27 November 2013. Cases were consensus-reviewed. Controls were selected from demographically matched non-AD examinations. Two radiologists and two fellows blinded to outcomes independently reviewed images from two patient groups in two sessions. Readers recorded presence/absence of AD and confidence level. Agreement and differences in confidence and sensitivity/specificity between DBT versus DM and attendings versus fellows were examined using weighted Kappa and generalised mixed modeling, respectively. There were 59 AD patients and 59 controls for 1,888 observations (59 × 2 (cases and controls) × 2 breasts × 2 imaging techniques × 4 readers). For all readers, agreement improved with DBT versus DM (0.61 vs. 0.37). Confidence was higher with DBT, p = .001. DBT achieved higher sensitivity (.59 vs. .32), p < .001; specificity remained high (>.90). DBT achieved higher positive likelihood ratio values, smaller negative likelihood ratio values, and larger ROC values. DBT decreases IOV, increases confidence, and improves sensitivity while maintaining high specificity in detecting AD. • Digital breast tomosynthesis decreases interobserver variability in the detection of architectural distortion. • Digital breast tomosynthesis increases reader confidence in the detection of architectural distortion. • Digital breast tomosynthesis improves sensitivity in the detection of architectural distortion.

Hepcidin is directly regulated by insulin and plays an important role in iron overload in streptozotocin-induced diabetic rats.

PubMed

Wang, Heyang; Li, Hongxia; Jiang, Xin; Shi, Wencai; Shen, Zhilei; Li, Min

2014-05-01

Iron overload is frequently observed in type 2 diabetes mellitus (DM2), but the underlying mechanisms remain unclear. We hypothesize that hepcidin may be directly regulated by insulin and play an important role in iron overload in DM2. We therefore examined the hepatic iron content, serum iron parameters, intestinal iron absorption, and liver hepcidin expression in rats treated with streptozotocin (STZ), which was given alone or after insulin resistance induced by a high-fat diet. The direct effect of insulin on hepcidin and its molecular mechanisms were furthermore determined in vitro in HepG2 cells. STZ administration caused a significant reduction in liver hepcidin level and a marked increase in intestinal iron absorption and serum and hepatic iron content. Insulin obviously upregulated hepcidin expression in HepG2 cells and enhanced signal transducer and activator of transcription 3 protein synthesis and DNA binding activity. The effect of insulin on hepcidin disappeared when the signal transducer and activator of transcription 3 pathway was blocked and could be partially inhibited by U0126. In conclusion, the current study suggests that hepcidin can be directly regulated by insulin, and the suppressed liver hepcidin synthesis may be an important reason for the iron overload in DM2.

Characterization of a Fasciola gigantica protein carrying two DM9 domains reveals cellular relocalization property.

PubMed

Phadungsil, Wansika; Smooker, Peter M; Vichasri-Grams, Suksiri; Grams, Rudi

2016-01-01

Even at the present age of whole-organism analysis, e.g., genomics, transcriptomics, and proteomics, the biological roles of many proteins remain unresolved. Classified among the proteins of unknown function is a family of proteins harboring repeats of the DM9 domain, a 60-75 amino acids motif first described in a small number of Drosophila melanogaster proteins. Proteins may carry two or more DM9 domains either in combination with other domains or as their sole constituent. Here we have characterized a 16.8 kDa Fasciola gigantica protein comprising two tandem repeated DM9 domains (FgDM9-1). The protein was located in the parenchyma of the immature and mature parasite and consequently it was not detected in the ES product of the parasite but only in the whole worm extract. Interestingly, extraction with SDS yielded a substantially higher amount of the protein suggesting association with insoluble cell components. In Sf9 insect cells a heterologously expressed EGFP-FgDM9-1 chimera showed cell-wide distribution but relocated to vesicle-like structures in the cytoplasm after stimulating cellular stress by bacteria, heat shock or chloroquine. These structures did not colocalize with the markers of endocytosis/phagocytosis ubiquitin, RAB7, GABARAP. The same behavior was noted for Aedes aegypti PRS1, a homologous mosquito DM9 protein as a positive control while EGFP did not exhibit such relocation in the insect cells. Cross-linking experiments on soluble recombinant FgDM9-1 indicated that the protein can undergo specific oligomerization. It is speculated that proteins carrying the DM9 domain have a role in vesicular transport in flatworms and insects. Copyright © 2016 Elsevier B.V. All rights reserved.

Large-scale population analysis reveals an extremely low threshold for "non-healthy" alanine aminotransferase that predicts diabetes mellitus.

PubMed

Shlomai, Amir; Kariv, Revital; Leshno, Moshe; Beth-or, Anat; Sheinberg, Bracha; Halpern, Zamir

2010-10-01

Serum alanine aminotransferase (ALT) is commonly used to detect liver damage. Recent studies indicate that ALT levels at the upper range of normal limits are predictors of adverse outcomes, especially diabetes mellitus (DM) and the metabolic syndrome. The aim of our study was to define the ALT threshold for both men and women that may predict the onset of DM. We analyzed a large Health Maintenance Organization cohort of 157 308 healthy subjects with no evidence of liver disease and with baseline ALT levels ≤ 120 U/L, and identified those who developed DM within 6 years. Overall, an elevated baseline serum ALT value was significantly associated with the development of DM, with an odds ratio of 3.3 when comparing the higher and the lower quartiles of the whole study population. A subgroup analysis revealed that baseline ALT values higher than 10 U/L among women and 22 U/L among men were already significantly associated with an increased risk for DM for any increment in ALT level. Notably, ALT values higher than ∼55 U/L were associated with increased risk for DM that was relatively constant for any increment in ALT. Higher baseline ALT levels were stronger predictors for DM as compared with age, triglycerides and cholesterol levels. Our study implies that ALT values higher than 10 U/L and 22 U/L for women and men, respectively, may predict DM. We suggest redefining ALT values as either 'normal' or 'healthy', with the later reflecting much lower values, above which an individual is at increased risk for DM. © 2010 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Determination and stereochemistry of proteinogenic and non-proteinogenic amino acids in Saudi Arabian date fruits.

PubMed

Ali, Hatem Salama Mohamed; Alhaj, Omar Amin; Al-Khalifa, Abdulrahman Saleh; Brückner, Hans

2014-09-01

Whereas an abundance of literature is available on the occurrence of common proteinogenic amino acids (AAs) in edible fruits of the date palm (Phoenix dactylifera L.), recent reports on non-proteinogenic (non-coded) AAs and amino components are scarce. With emphasis on these components we have analyzed total hydrolysates of twelve cultivars of date fruits using automated ion-exchange chromatography, HPLC employing a fluorescent aminoquinolyl label, and GC-MS of total hydrolysates using the chiral stationary phases Chirasil(®)-L-Val and Lipodex(®) E. Besides common proteinogenic AAs, relatively large amounts of the following non-proteinogenic amino acids were detected: (2S,5R)-5-hydroxypipecolic acid (1.4-4.0 g/kg dry matter, DM), 1-aminocyclopropane-1-carboxylic acid (1.3-2.6 g/kg DM), γ-amino-n-butyric acid (0.5-1.2 g/kg DM), (2S,4R)-4-hydroxyproline (130-230 mg/kg DM), L-pipecolic acid (40-140 mg/kg DM), and 2-aminoethanol (40-160 mg/kg DM) as well as low or trace amounts (<70 mg/kg DM) of L-ornithine, 5-hydroxylysine, β-alanine, and in some samples (<20 mg/kg DM) of (S)-β-aminoisobutyric acid and (<10 mg/kg DM) L-allo-isoleucine. In one date fruit, traces of α-aminoadipic acid could be determined. Enantiomeric analysis of 6 M DCl/D2O hydrolysates of AAs using chiral capillary gas chromatography-mass spectrometry revealed the presence of very low amounts of D-Ala, D-Asp, D-Glu, D-Ser and D-Phe (1.2-0.4%, relative to the corresponding L-enantiomers), besides traces (0.2-1%) of other D-AAs. The possible relevance of non-proteinogenic amino acids in date fruits is briefly addressed.

Cost-of-Illness Analysis of Type 2 Diabetes Mellitus in Iran

PubMed Central

Javanbakht, Mehdi; Baradaran, Hamid R.; Mashayekhi, Atefeh; Haghdoost, Ali Akbar; Khamseh, Mohammad E.; Kharazmi, Erfan; Sadeghi, Aboozar

2011-01-01

Introduction Diabetes is a worldwide high prevalence chronic progressive disease that poses a significant challenge to healthcare systems. The aim of this study is to provide a detailed economic burden of diagnosed type 2 diabetes mellitus (T2DM) and its complications in Iran in 2009 year. Methods This is a prevalence-based cost-of-illness study focusing on quantifying direct health care costs by bottom-up approach. Data on inpatient hospital services, outpatient clinic visits, physician services, drugs, laboratory test, education and non-medical cost were collected from two national registries. The human capital approach was used to calculate indirect costs separately in male and female and also among different age groups. Results The total national cost of diagnosed T2DM in 2009 is estimated at 3.78 billion USA dollars (USD) including 2.04±0.28 billion direct (medical and non-medical) costs and indirect costs of 1.73 million. Average direct and indirect cost per capita was 842.6±102 and 864.8 USD respectively. Complications (48.9%) and drugs (23.8%) were main components of direct cost. The largest components of medical expenditures attributed to diabetes's complications are cardiovascular disease (42.3% of total Complications cost), nephropathy (23%) and ophthalmic complications (14%). Indirect costs include temporarily disability (335.7 million), permanent disability (452.4 million) and reduced productivity due to premature mortality (950.3 million). Conclusions T2DM is a costly disease in the Iran healthcare system and consume more than 8.69% of total health expenditure. In addition to these quantified costs, T2DM imposes high intangible costs on society in terms of reduced quality of life. Identification of effective new strategies for the control of diabetes and its complications is a public health priority. PMID:22066013

Cardiovascular risk factors and cognitive function in adults 30-59 years of age (NHANES III).

PubMed

Pavlik, Valory N; Hyman, David J; Doody, Rachelle

2005-01-01

In the Third National Health and Nutrition Examination Survey (NHANES III), three measures of cognitive function [Simple Reaction Time Test (SRTT), Symbol Digit Substitution Test (SDST), and Serial Digit Learning Test (SDLT)] were administered to a half-sample of 3,385 adult men and nonpregnant women 30-59 years of age with no history of stroke. We used multiple linear regression analysis to determine whether there was an independent association between performance on each cognitive function measure and defined hypertension (HTN) alone, type 2 diabetes mellitus (DM) alone, and coexistent HTN and DM after adjustment for demographic and socioeconomic variables and selected health behaviors. After adjustment for the sociodemographic variables, the combination of HTN + DM, but not HTN alone or DM alone, was significantly associated with worse performance on the SRTT (p = 0.031) and the SDST (p = 0.011). A similar pattern was observed for SDLT performance, but the relationship did not reach statistical significance (p = 0.101). We conclude that HTN in combination with DM is associated with detectable cognitive decrements in persons under age 60.

Effect of DM Actuator Errors on the WFIRST/AFTA Coronagraph Contrast Performance

NASA Technical Reports Server (NTRS)

Sidick, Erkin; Shi, Fang

2015-01-01

The WFIRST/AFTA 2.4 m space telescope currently under study includes a stellar coronagraph for the imaging and the spectral characterization of extrasolar planets. The coronagraph employs two sequential deformable mirrors (DMs) to compensate for phase and amplitude errors in creating dark holes. DMs are critical elements in high contrast coronagraphs, requiring precision and stability measured in picometers to enable detection of Earth-like exoplanets. Working with a low-order wavefront-sensor the DM that is conjugate to a pupil can also be used to correct low-order wavefront drift during a scientific observation. However, not all actuators in a DM have the same gain. When using such a DM in low-order wavefront sensing and control subsystem, the actuator gain errors introduce high-spatial frequency errors to the DM surface and thus worsen the contrast performance of the coronagraph. We have investigated the effects of actuator gain errors and the actuator command digitization errors on the contrast performance of the coronagraph through modeling and simulations, and will present our results in this paper.

The Lyman-alpha glow of gas falling into the dark matter halo of a z = 3 galaxy.

PubMed

Weidinger, Michael; Møller, Palle; Fynbo, Johan Peter Uldall

2004-08-26

Quasars are the visible signatures of gas falling into the deep potential well of super-massive black holes in the centres of distant galaxies. It has been suggested that quasars are formed when two massive galaxies collide and merge, leading to the prediction that quasars should be found in the centres of regions of largest overdensity in the early Universe. In dark matter (DM)-dominated models of the early Universe, massive DM halos are predicted to attract the surrounding gas, which falls towards their centres. The neutral gas is not detectable in emission by itself, but gas falling into the ionizing cone of such a quasar will glow in the Lyman-alpha line of hydrogen, effectively imaging the DM halo. Here we present a Lyalpha image of a DM halo at redshift z = 3, along with a two-dimensional spectrum of the gaseous halo. Our observations are best understood in the context of the standard model for DM haloes; we infer a mass of (2 - 7) x 10(12) solar masses (M(\\circ)) for the halo.

Telomere Length Attrition, a Marker of Biological Senescence, Is Inversely Correlated with Triglycerides and Cholesterol in South Asian Males with Type 2 Diabetes Mellitus

PubMed Central

Harte, Alison L.; da Silva, Nancy F.; Miller, Michelle A.; Cappuccio, Francesco P.; Kelly, Ann; O'Hare, Joseph P.; Barnett, Anthony H.; Al-Daghri, Nasser M.; Al-Attas, Omar; Alokail, Majed; Sabico, Shaun; Tripathi, Gyanendra; Bellary, Srikanth; Kumar, Sudhesh; McTernan, Philip G.

2012-01-01

South Asians have a higher risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) than white Caucasians, for a given BMI. Premature biological ageing, assessed by reduction in telomere length (TL), may be mediated by factors resulting from altered metabolic profiles associated with obesity. We hypothesise that ethnicity and metabolic status represent detrimental factors contributing to premature biological ageing. Therefore we assessed TL in two South Asian, age and BMI-matched cohorts [T2DM (n = 142) versus non-T2DM (n = 76)] to determine the effects of BMI, gender, lipid and CVD profile on biological ageing. Genomic DNA was obtained from the UKADS cohort; biochemical and anthropometric data was collected and TL was measured by quantitative real-time PCR. Our findings indicated a gender-specific effect with reduced TL in T2DM men compared with non-T2DM men (P = 0.006). Additionally, in T2DM men, TL was inversely correlated with triglycerides and total cholesterol (r = −0.419, P < 0.01; r = −0.443, P < 0.01). In summary, TL was reduced amongst South Asian T2DM men and correlated with triglycerides and total cholesterol. This study highlights enhanced biological ageing among South Asian, T2DM men, which appears to be tracked by changes in lipids and BMI, suggesting that raised lipids and BMI may directly contribute to premature ageing. PMID:22474429

Medical claims-based case-control study of temporal relationship between clinical visits for hand syndromes and subsequent diabetes diagnosis: implications for identifying patients with undiagnosed type 2 diabetes mellitus.

PubMed

Hou, Wen-Hsuan; Li, Chung-Yi; Chen, Lu-Hsuan; Wang, Liang-Yi; Kuo, Li-Chieh; Kuo, Ken N; Shen, Hsiu-Nien; Chiu, Chang-Ta

2016-10-20

To investigate whether a temporal relationship is present between clinical visits for diabetes-related hand syndromes (DHSs) and subsequent type 2 diabetes mellitus (T2DM) diagnosis and, accordingly, whether DHSs can be used for identifying patients with undiagnosed T2DM. This study had a case-control design nested within a cohort of 1 million people from the general population, which was followed from 2005 to 2010. The odds of prior clinical visits for DHSs, namely carpal tunnel syndrome (CTS), flexor tenosynovitis, limited joint mobility and Dupuytren's disease, were estimated for cases and controls. We used a conditional logistic regression model to estimate the OR and 95% CI of T2DM in association with a history of DHSs. The validity and predictive value of using the history of DHSs in predicting T2DM diagnosis were calculated. Taiwan National Health Insurance medical claims. We identified 33 571 patients receiving a new diagnosis of T2DM (cases) between 2005 and 2010. Each T2DM case was matched with 5 controls who had the same sex and birth year and were alive on the date of T2DM diagnosis. The primary outcome measure was T2DM diagnosis. The OR of T2DM in association with prior clinical visits was significantly increased for overall DHS and CTS, being 1.15 (95% CI 1.10 to 1.20) and 1.22 (95% CI 1.16 to 1.29), respectively. Moreover, 11% of patients with T2DM made clinical visits for CTS within 3 months prior to T2DM diagnosis. The history of DHSs had low sensitivity (<0.1% to 5.2%) and a positive predictive value (9.9% to 11.7%) in predicting T2DM. Despite the unsatisfactory validity and performance of DHSs as a clinical tool for detecting patients with undiagnosed T2DM, this study provided evidence that clinical visits for DHSs, particularly for CTS, can be a sign of undiagnosed T2DM. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Risk of Infection in Type 1 and Type 2 Diabetes Compared With the General Population: A Matched Cohort Study.

PubMed

Carey, Iain M; Critchley, Julia A; DeWilde, Stephen; Harris, Tess; Hosking, Fay J; Cook, Derek G

2018-03-01

We describe in detail the burden of infections in adults with diabetes within a large national population cohort. We also compare infection rates between patients with type 1 and type 2 diabetes mellitus (T1DM and T2DM). A retrospective cohort study compared 102,493 English primary care patients aged 40-89 years with a diabetes diagnosis by 2008 ( n = 5,863 T1DM and n = 96,630 T2DM) with 203,518 age-sex-practice-matched control subjects without diabetes. Infection rates during 2008-2015, compiled from primary care and linked hospital and mortality records, were compared across 19 individual infection categories. These were further summarized as any requiring a prescription or hospitalization or as cause of death. Poisson regression was used to estimate incidence rate ratios (IRRs) between 1 ) people with diabetes and control subjects and 2 ) T1DM and T2DM adjusted for age, sex, smoking, BMI, and deprivation. Compared with control subjects without diabetes, patients with diabetes had higher rates for all infections, with the highest IRRs seen for bone and joint infections, sepsis, and cellulitis. IRRs for infection-related hospitalizations were 3.71 (95% CI 3.27-4.21) for T1DM and 1.88 (95% CI 1.83-1.92) for T2DM. A direct comparison of types confirmed higher adjusted risks for T1DM versus T2DM (death from infection IRR 2.19 [95% CI 1.75-2.74]). We estimate that 6% of infection-related hospitalizations and 12% of infection-related deaths were attributable to diabetes. People with diabetes, particularly T1DM, are at increased risk of serious infection, representing an important population burden. Strategies that reduce the risk of developing severe infections and poor treatment outcomes are under-researched and should be explored. © 2018 by the American Diabetes Association.

A genome-wide association search for type 2 diabetes genes in African Americans.

PubMed

Palmer, Nicholette D; McDonough, Caitrin W; Hicks, Pamela J; Roh, Bong H; Wing, Maria R; An, S Sandy; Hester, Jessica M; Cooke, Jessica N; Bostrom, Meredith A; Rudock, Megan E; Talbert, Matthew E; Lewis, Joshua P; Ferrara, Assiamira; Lu, Lingyi; Ziegler, Julie T; Sale, Michele M; Divers, Jasmin; Shriner, Daniel; Adeyemo, Adebowale; Rotimi, Charles N; Ng, Maggie C Y; Langefeld, Carl D; Freedman, Barry I; Bowden, Donald W; Voight, Benjamin F; Scott, Laura J; Steinthorsdottir, Valgerdur; Morris, Andrew P; Dina, Christian; Welch, Ryan P; Zeggini, Eleftheria; Huth, Cornelia; Aulchenko, Yurii S; Thorleifsson, Gudmar; McCulloch, Laura J; Ferreira, Teresa; Grallert, Harald; Amin, Najaf; Wu, Guanming; Willer, Cristen J; Raychaudhuri, Soumya; McCarroll, Steve A; Langenberg, Claudia; Hofmann, Oliver M; Dupuis, Josée; Qi, Lu; Segrè, Ayellet V; van Hoek, Mandy; Navarro, Pau; Ardlie, Kristin; Balkau, Beverley; Benediktsson, Rafn; Bennett, Amanda J; Blagieva, Roza; Boerwinkle, Eric; Bonnycastle, Lori L; Boström, Kristina Bengtsson; Bravenboer, Bert; Bumpstead, Suzannah; Burtt, Noël P; Charpentier, Guillaume; Chines, Peter S; Cornelis, Marilyn; Couper, David J; Crawford, Gabe; Doney, Alex S F; Elliott, Katherine S; Elliott, Amanda L; Erdos, Michael R; Fox, Caroline S; Franklin, Christopher S; Ganser, Martha; Gieger, Christian; Grarup, Niels; Green, Todd; Griffin, Simon; Groves, Christopher J; Guiducci, Candace; Hadjadj, Samy; Hassanali, Neelam; Herder, Christian; Isomaa, Bo; Jackson, Anne U; Johnson, Paul R V; Jørgensen, Torben; Kao, Wen H L; Klopp, Norman; Kong, Augustine; Kraft, Peter; Kuusisto, Johanna; Lauritzen, Torsten; Li, Man; Lieverse, Aloysius; Lindgren, Cecilia M; Lyssenko, Valeriya; Marre, Michel; Meitinger, Thomas; Midthjell, Kristian; Morken, Mario A; Narisu, Narisu; Nilsson, Peter; Owen, Katharine R; Payne, Felicity; Perry, John R B; Petersen, Ann-Kristin; Platou, Carl; Proença, Christine; Prokopenko, Inga; Rathmann, Wolfgang; Rayner, N William; Robertson, Neil R; Rocheleau, Ghislain; Roden, Michael; Sampson, Michael J; Saxena, Richa; Shields, Beverley M; Shrader, Peter; Sigurdsson, Gunnar; Sparsø, Thomas; Strassburger, Klaus; Stringham, Heather M; Sun, Qi; Swift, Amy J; Thorand, Barbara; Tichet, Jean; Tuomi, Tiinamaija; van Dam, Rob M; van Haeften, Timon W; van Herpt, Thijs; van Vliet-Ostaptchouk, Jana V; Walters, G Bragi; Weedon, Michael N; Wijmenga, Cisca; Witteman, Jacqueline; Bergman, Richard N; Cauchi, Stephane; Collins, Francis S; Gloyn, Anna L; Gyllensten, Ulf; Hansen, Torben; Hide, Winston A; Hitman, Graham A; Hofman, Albert; Hunter, David J; Hveem, Kristian; Laakso, Markku; Mohlke, Karen L; Morris, Andrew D; Palmer, Colin N A; Pramstaller, Peter P; Rudan, Igor; Sijbrands, Eric; Stein, Lincoln D; Tuomilehto, Jaakko; Uitterlinden, Andre; Walker, Mark; Wareham, Nicholas J; Watanabe, Richard M; Abecasis, Goncalo R; Boehm, Bernhard O; Campbell, Harry; Daly, Mark J; Hattersley, Andrew T; Hu, Frank B; Meigs, James B; Pankow, James S; Pedersen, Oluf; Wichmann, H-Erich; Barroso, Inês; Florez, Jose C; Frayling, Timothy M; Groop, Leif; Sladek, Rob; Thorsteinsdottir, Unnur; Wilson, James F; Illig, Thomas; Froguel, Philippe; van Duijn, Cornelia M; Stefansson, Kari; Altshuler, David; Boehnke, Michael; McCarthy, Mark I; Soranzo, Nicole; Wheeler, Eleanor; Glazer, Nicole L; Bouatia-Naji, Nabila; Mägi, Reedik; Randall, Joshua; Johnson, Toby; Elliott, Paul; Rybin, Denis; Henneman, Peter; Dehghan, Abbas; Hottenga, Jouke Jan; Song, Kijoung; Goel, Anuj; Egan, Josephine M; Lajunen, Taina; Doney, Alex; Kanoni, Stavroula; Cavalcanti-Proença, Christine; Kumari, Meena; Timpson, Nicholas J; Zabena, Carina; Ingelsson, Erik; An, Ping; O'Connell, Jeffrey; Luan, Jian'an; Elliott, Amanda; McCarroll, Steven A; Roccasecca, Rosa Maria; Pattou, François; Sethupathy, Praveen; Ariyurek, Yavuz; Barter, Philip; Beilby, John P; Ben-Shlomo, Yoav; Bergmann, Sven; Bochud, Murielle; Bonnefond, Amélie; Borch-Johnsen, Knut; Böttcher, Yvonne; Brunner, Eric; Bumpstead, Suzannah J; Chen, Yii-Der Ida; Chines, Peter; Clarke, Robert; Coin, Lachlan J M; Cooper, Matthew N; Crisponi, Laura; Day, Ian N M; de Geus, Eco J C; Delplanque, Jerome; Fedson, Annette C; Fischer-Rosinsky, Antje; Forouhi, Nita G; Frants, Rune; Franzosi, Maria Grazia; Galan, Pilar; Goodarzi, Mark O; Graessler, Jürgen; Grundy, Scott; Gwilliam, Rhian; Hallmans, Göran; Hammond, Naomi; Han, Xijing; Hartikainen, Anna-Liisa; Hayward, Caroline; Heath, Simon C; Hercberg, Serge; Hicks, Andrew A; Hillman, David R; Hingorani, Aroon D; Hui, Jennie; Hung, Joe; Jula, Antti; Kaakinen, Marika; Kaprio, Jaakko; Kesaniemi, Y Antero; Kivimaki, Mika; Knight, Beatrice; Koskinen, Seppo; Kovacs, Peter; Kyvik, Kirsten Ohm; Lathrop, G Mark; Lawlor, Debbie A; Le Bacquer, Olivier; Lecoeur, Cécile; Li, Yun; Mahley, Robert; Mangino, Massimo; Manning, Alisa K; Martínez-Larrad, María Teresa; McAteer, Jarred B; McPherson, Ruth; Meisinger, Christa; Melzer, David; Meyre, David; Mitchell, Braxton D; Mukherjee, Sutapa; Naitza, Silvia; Neville, Matthew J; Oostra, Ben A; Orrù, Marco; Pakyz, Ruth; Paolisso, Giuseppe; Pattaro, Cristian; Pearson, Daniel; Peden, John F; Pedersen, Nancy L; Perola, Markus; Pfeiffer, Andreas F H; Pichler, Irene; Polasek, Ozren; Posthuma, Danielle; Potter, Simon C; Pouta, Anneli; Province, Michael A; Psaty, Bruce M; Rayner, Nigel W; Rice, Kenneth; Ripatti, Samuli; Rivadeneira, Fernando; Rolandsson, Olov; Sandbaek, Annelli; Sandhu, Manjinder; Sanna, Serena; Sayer, Avan Aihie; Scheet, Paul; Seedorf, Udo; Sharp, Stephen J; Shields, Beverley; Sijbrands, Eric J G; Silveira, Angela; Simpson, Laila; Singleton, Andrew; Smith, Nicholas L; Sovio, Ulla; Swift, Amy; Syddall, Holly; Syvänen, Ann-Christine; Tanaka, Toshiko; Tönjes, Anke; Uitterlinden, André G; van Dijk, Ko Willems; Varma, Dhiraj; Visvikis-Siest, Sophie; Vitart, Veronique; Vogelzangs, Nicole; Waeber, Gérard; Wagner, Peter J; Walley, Andrew; Ward, Kim L; Watkins, Hugh; Wild, Sarah H; Willemsen, Gonneke; Witteman, Jaqueline C M; Yarnell, John W G; Zelenika, Diana; Zethelius, Björn; Zhai, Guangju; Zhao, Jing Hua; Zillikens, M Carola; Borecki, Ingrid B; Loos, Ruth J F; Meneton, Pierre; Magnusson, Patrik K E; Nathan, David M; Williams, Gordon H; Silander, Kaisa; Salomaa, Veikko; Smith, George Davey; Bornstein, Stefan R; Schwarz, Peter; Spranger, Joachim; Karpe, Fredrik; Shuldiner, Alan R; Cooper, Cyrus; Dedoussis, George V; Serrano-Ríos, Manuel; Lind, Lars; Palmer, Lyle J; Franks, Paul W; Ebrahim, Shah; Marmot, Michael; Kao, W H Linda; Pramstaller, Peter Paul; Wright, Alan F; Stumvoll, Michael; Hamsten, Anders; Buchanan, Thomas A; Valle, Timo T; Rotter, Jerome I; Siscovick, David S; Penninx, Brenda W J H; Boomsma, Dorret I; Deloukas, Panos; Spector, Timothy D; Ferrucci, Luigi; Cao, Antonio; Scuteri, Angelo; Schlessinger, David; Uda, Manuela; Ruokonen, Aimo; Jarvelin, Marjo-Riitta; Waterworth, Dawn M; Vollenweider, Peter; Peltonen, Leena; Mooser, Vincent; Sladek, Robert

2012-01-01

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.

Prediction and Prevention of Type 1 Diabetes: Update on Success of Prediction and Struggles at Prevention

PubMed Central

Michels, Aaron; Zhang, Li; Khadra, Anmar; Kushner, Jake A.; Redondo, Maria J.; Pietropaolo, Massimo

2015-01-01

Type 1 diabetes mellitus (T1DM) is the archetypal example of a T cell-mediated autoimmune disease characterized by selective destruction of pancreatic β cells. The pathogenic equation for T1DM presents a complex interrelation of genetic and environmental factors, most of which have yet to be identified. Based on the observed familial aggregation of T1DM, it is certain that there is a decided heritable genetic susceptibility for developing T1DM. The well-known association of T1DM with certain human histocompatibility leukocyte antigen (HLA) alleles of the major histocompatibility complex (MHC) was a major step toward understanding the role of inheritance in T1DM. Type 1 diabetes is a polygenic disease with a small number of genes having large effects, (e.g. HLA) and a large number of genes having small effects. Risk of T1DM progression is conferred by specific HLA DR/DQ alleles [e.g., DRB1*03-DQB1*0201 (DR3/DQ2) or DRB1*04-DQB1*0302 (DR4/DQ8)]. In addition, the HLA allele DQB1*0602 is associated with dominant protection from T1DM in multiple populations. A concordance rate lower than 100% between monozygotic twins indicates a potential involvement of environmental factors on disease development. The detection of at least two islet autoantibodies in the blood is virtually pre-diagnostic for T1DM. The majority of children who carry these biomarkers, regardless of whether they have an a priori family history of the disease, will develop insulin-requiring diabetes. Facilitating pre-diagnosis is the timing of seroconversion which is most pronounced in the first two years of life. Unfortunately the significant progress in improving prediction of T1DM has not yet been paralleled by safe and efficacious intervention strategies aimed at preventing the disease. Herein we summarize the chequered history of prediction and prevention of T1DM, describing successes and failures alike, and thereafter examine future trends in the exciting, partially explored field of T1DM prevention. PMID:26202050

A possible cross-talk between autophagy and apoptosis in generating an immune response in melanoma

PubMed Central

Hossain, Azim; Radwan, Faisal F. Y.; Doonan, Bently P.; God, Jason M.; Zhang, Lixia; Bell, Darwin P.; Haque, Azizul

2013-01-01

Melanoma is the most aggressive form of skin cancer, responsible for the majority of skin cancer related deaths. Thus, the search for natural molecules which can effectively destroy tumors while promoting immune activation is essential for designing novel therapies against metastatic melanoma. Here, we report for the first time that a natural triterpenoid, Ganoderic Acid DM (GA-DM), induces an orchestrated autophagic and apoptotic cell death, as well as enhanced immunological responses via increased HLA class II presentation in melanoma cells. Annexin V staining and flow cytometry showed that GA-DM treatment induced apoptosis of melanoma cells, which was supported by a detection of increased Bax proteins, co-localization and elevation of Apaf-1 and cytochrome c, and a subsequent cleavage of caspases 9 and 3. Furthermore, GA-DM treatment initiated a possible cross-talk between autophagy and apoptosis as evidenced by increased levels of Beclin-1 and LC3 proteins, and their timely interplay with apoptotic and/or anti-apoptotic molecules in melanoma cells. Despite GA-DM's moderate cytotoxicity, viable cells expressed high levels of HLA class II proteins with improved antigen presentation and CD4+ T cell recognition. The antitumor efficacy of GA-DM was also investigated in vivo in murine B16 melanoma model, where GA-DM treatment slowed tumor formation with a significant reduction in tumor volume. Taken together, these findings demonstrate the potential of GA-DM as a natural chemo-immunotherapeutic capable of inducing a possible cross-talk between autophagy and apoptosis, as well as improved immune recognition for sustained melanoma tumor clearance. PMID:22847295

Association between Low-density Lipoprotein Receptor-related Protein 5 Polymorphisms and Type 2 Diabetes Mellitus in Han Chinese: a Case-control Study.

PubMed

You, Hai Fei; Zhao, Jing Zhi; Zhai, Yu Jia; Yin, Lei; Pang, Chao; Luo, Xin Ping; Zhang, Ming; Wang, Jin Jin; Li, Lin Lin; Wang, Yan; Wang, Qian; Wang, Bing Yuan; Ren, Yong Cheng; Hu, Dong Sheng

2015-07-01

To investigate the association between low-density lipoprotein receptor-related protein 5 (LRP5) variants (rs12363572 and rs4930588) and type 2 diabetes mellitus (T2DM) in Han Chinese. A total of 1842 T2DM cases (507 newly diagnosed cases and 1335 previously diagnosed cases) and 7777 controls were included in this case-control study. PCR-RFLP was conducted to detect the genotype of the two single nucleotide polymorphisms (SNPs). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to describe the strength of the association by logistic regression. In the study subjects, neither rs12363572 nor rs4930588 was significantly associated with T2DM, even after adjusting for relevant covariates. When stratified by body mass index (BMI), the two SNPs were also not associated with T2DM. Among the 3 common haplotypes, only haplotype TT was associated with reduced risk of T2DM (OR 0.820, 95% CI 0.732-0.919). In addition, rs12363572 was associated with BMI (P<0.001) and rs4930588 was associated with triglyceride levels (P=0.043) in 507 newly diagnosed T2DM cases but not in healthy controls. No LRP5 variant was found to be associated with T2DM in Han Chinese, but haplotype TT was found to be associated with T2DM. Copyright © 2015 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Galactic center gamma-ray excess from dark matter annihilation: is there a black hole spike?

PubMed

Fields, Brian D; Shapiro, Stuart L; Shelton, Jessie

2014-10-10

If the supermassive black hole Sgr A* at the center of the Milky Way grew adiabatically from an initial seed embedded in a Navarro-Frenk-White dark matter (DM) halo, then the DM profile near the hole has steepened into a spike. We calculate the dramatic enhancement to the gamma-ray flux from the Galactic center (GC) from such a spike if the 1-3 GeV excess observed in Fermi data is due to DM annihilations. We find that for the parameter values favored in recent fits, the point-source-like flux from the spike is 35 times greater than the flux from the inner 1° of the halo, far exceeding all Fermi point source detections near the GC. We consider the dependence of the spike signal on astrophysical and particle parameters and conclude that if the GC excess is due to DM, then a canonical adiabatic spike is disfavored by the data. We discuss alternative Galactic histories that predict different spike signals, including (i) the nonadiabatic growth of the black hole, possibly associated with halo and/or black hole mergers, (ii) gravitational interaction of DM with baryons in the dense core, such as heating by stars, or (iii) DM self-interactions. We emphasize that the spike signal is sensitive to a different combination of particle parameters than the halo signal and that the inclusion of a spike component to any DM signal in future analyses would provide novel information about both the history of the GC and the particle physics of DM annihilations.

Predictive value of high-sensitivity troponin-I for future adverse cardiovascular outcome in stable patients with type 2 diabetes mellitus

PubMed Central

2014-01-01

Introduction High-sensitivity cardiac troponin I(hs-TnI) and T levels(hs-TnT) are sensitive biomarkers of cardiomyocyte turnover or necrosis. Prior studies of the predictive role of hs-TnT in type 2 diabetes mellitus(T2DM) patients have yielded conflicting results. This study aimed to determine whether hs-TnI, which is detectable in a higher proportion of normal subjects than hsTnT, is associated with a major adverse cardiovascular event(MACE) in T2DM patients. Methods and results We compared hs-TnI level in stored serum samples from 276 consecutive patients (mean age 65 ± 10 years; 57% male) with T2DM with that of 115 age-and sex-matched controls. All T2DM patients were prospectively followed up for at least 4 years for incidence of MACE including heart failure(HF), myocardial infarction(MI) and cardiovascular mortality. At baseline, 274(99%) patients with T2DM had detectable hs-TnI, and 57(21%) had elevated hs-TnI (male: 8.5 ng/L, female: 7.6 ng/L, above the 99th percentile in healthy controls). A total of 43 MACE occurred: HF(n = 18), MI(n = 11) and cardiovascular mortality(n = 14). Kaplan-Meier analysis showed that an elevated hs-TnI was associated with MACE, HF, MI and cardiovascular mortality. Although multivariate analysis revealed that an elevated hs-TnI independently predicted MACE, it had limited sensitivity(62.7%) and positive predictive value(38.5%). Contrary to this, a normal hs-TnI level had an excellent negative predictive value(92.2%) for future MACE in patients with T2DM. Conclusion The present study demonstrates that elevated hs-TnI in patients with T2DM is associated with increased MACE, HF, MI and cardiovascular mortality. Importantly, a normal hs-TnI level has an excellent negative predictive value for future adverse cardiovascular events during long-term follow-up. PMID:24661773

Transgene Expression of Drosophila melanogaster Nucleoside Kinase Reverses Mitochondrial Thymidine Kinase 2 Deficiency*♦

PubMed Central

Krishnan, Shuba; Zhou, Xiaoshan; Paredes, João A.; Kuiper, Raoul V.; Curbo, Sophie; Karlsson, Anna

2013-01-01

A strategy to reverse the symptoms of thymidine kinase 2 (TK2) deficiency in a mouse model was investigated. The nucleoside kinase from Drosophila melanogaster (Dm-dNK) was expressed in TK2-deficient mice that have been shown to present with a severe phenotype caused by mitochondrial DNA depletion. The Dm-dNK+/− transgenic mice were shown to be able to rescue the TK2-deficient mice. The Dm-dNK+/−TK2−/− mice were normal as judged by growth and behavior during the observation time of 6 months. The Dm-dNK-expressing mice showed a substantial increase in thymidine-phosphorylating activity in investigated tissues. The Dm-dNK expression also resulted in highly elevated dTTP pools. The dTTP pool alterations did not cause specific mitochondrial DNA mutations or deletions when 6-month-old mice were analyzed. The mitochondrial DNA was also detected at normal levels. In conclusion, the Dm-dNK+/−TK2−/− mouse model illustrates how dTMP synthesized in the cell nucleus can compensate for loss of intramitochondrial dTMP synthesis in differentiated tissue. The data presented open new possibilities to treat the severe symptoms of TK2 deficiency. PMID:23288848

Holder pasteurization affects S100B concentrations in human milk.

PubMed

Peila, Chiara; Coscia, Alessandra; Bertino, Enrico; Li Volti, Giovanni; Galvano, Fabio; Visser, Gerard H A; Gazzolo, Diego

2018-02-01

Donor milk (DM) represents an important nutrition source for high-risk newborns. Holder pasteurization (HoP) is the most recommended procedure for DM treatment, providing a good compromise between microbiological safety and biological quality. HoP was previously shown to affect DM cytokines, growth factors and hormones levels, whilst no data concerning the possible effects of HoP on neurobiomarkers (NB) are available. Therefore, our study investigated whether the concentration in DM of a well-known NB involved in brain development/damage, namely S100B, changes due to HoP. We conducted a pretest-test study in 11 mothers, whose DM samples were sub-divided into two parts: the first was immediately frozen (-80 °C); the second was pasteurized with Holder method before freezing. S100B DM levels were measured using a commercially available immunoluminometric assay. S100B protein was detected in all milk samples. Results showed significant differences between groups (p < 0.05) in S100B levels after HoP. Our data provide evidence that S100B is present in preterm milk as well as in term milk during maturation degree. Moreover, the results confirm the susceptibility of this neurotrophic factor to pasteurization stresses and the need to develop new storage techniques to preserve the biological quality of human milk.

Nonalcoholic fatty liver disease - A multisystem disease?

PubMed Central

Mikolasevic, Ivana; Milic, Sandra; Turk Wensveen, Tamara; Grgic, Ivana; Jakopcic, Ivan; Stimac, Davor; Wensveen, Felix; Orlic, Lidija

2016-01-01

Non-alcoholic fatty liver disease (NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome (MetS). Importantly, NAFLD is one of its most dangerous complications because it can lead to severe liver pathologies, including fibrosis, cirrhosis and hepatic cellular carcinoma. Given the increasing worldwide prevalence of obesity, NAFLD has become the most common cause of chronic liver disease and therefore is a major global health problem. Currently, NAFLD is predominantly regarded as a hepatic manifestation of MetS. However, accumulating evidence indicates that the effects of NAFLD extend beyond the liver and are negatively associated with a range of chronic diseases, most notably cardiovascular disease (CVD), diabetes mellitus type 2 (T2DM) and chronic kidney disease (CKD). It is becoming increasingly clear that these diseases are the result of the same underlying pathophysiological processes associated with MetS, such as insulin resistance, chronic systemic inflammation and dyslipidemia. As a result, they have been shown to be independent reciprocal risk factors. In addition, recent data have shown that NAFLD actively contributes to aggravation of the pathophysiology of CVD, T2DM, and CKD, as well as several other pathologies. Thus, NAFLD is a direct cause of many chronic diseases associated with MetS, and better detection and treatment of fatty liver disease is therefore urgently needed. As non-invasive screening methods for liver disease become increasingly available, detection and treatment of NAFLD in patients with MetS should therefore be considered by both (sub-) specialists and primary care physicians. PMID:27920470

The impact of baryons on the direct detection of dark matter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kelso, Chris; Savage, Christopher; Freese, Katherine

2016-08-01

The spatial and velocity distributions of dark matter particles in the Milky Way Halo affect the signals expected to be observed in searches for dark matter. Results from direct detection experiments are often analyzed assuming a simple isothermal distribution of dark matter, the Standard Halo Model (SHM). Yet there has been skepticism regarding the validity of this simple model due to the complicated gravitational collapse and merger history of actual galaxies. In this paper we compare the SHM to the results of cosmological hydrodynamical simulations of galaxy formation to investigate whether or not the SHM is a good representation ofmore » the true WIMP distribution in the analysis of direct detection data. We examine two Milky Way-like galaxies from the MaGICC cosmological simulations (a) with dark matter only and (b) with baryonic physics included. The inclusion of baryons drives the shape of the DM halo to become more spherical and makes the velocity distribution of dark matter particles less anisotropic especially at large heliocentric velocities, thereby making the SHM a better fit. We also note that we do not find a significant disk-like rotating dark matter component in either of the two galaxy halos with baryons that we examine, suggesting that dark disks are not a generic prediction of cosmological hydrodynamical simulations. We conclude that in the Solar neighborhood, the SHM is in fact a good approximation to the true dark matter distribution in these cosmological simulations (with baryons) which are reasonable representations of the Milky Way, and hence can also be used for the purpose of dark matter direct detection calculations.« less

Humanin: A Novel Central Regulator of Peripheral Insulin Action

PubMed Central

Muzumdar, Radhika H.; Huffman, Derek M.; Atzmon, Gil; Buettner, Christoph; Cobb, Laura J.; Fishman, Sigal; Budagov, Temuri; Cui, Lingguang; Einstein, Francine H.; Poduval, Aruna; Hwang, David; Barzilai, Nir; Cohen, Pinchas

2009-01-01

Background Decline in insulin action is a metabolic feature of aging and is involved in the development of age-related diseases including Type 2 Diabetes Mellitus (T2DM) and Alzheimer's disease (AD). A novel mitochondria-associated peptide, Humanin (HN), has a neuroprotective role against AD-related neurotoxicity. Considering the association between insulin resistance and AD, we investigated if HN influences insulin sensitivity. Methods and Findings Using state of the art clamp technology, we examined the role of central and peripheral HN on insulin action. Continuous infusion of HN intra-cerebro-ventricularly significantly improved overall insulin sensitivity. The central effects of HN on insulin action were associated with activation of hypothalamic STAT-3 signaling; effects that were negated by co-inhibition of hypothalamic STAT-3. Peripheral intravenous infusions of novel and potent HN derivatives reproduced the insulin-sensitizing effects of central HN. Inhibition of hypothalamic STAT-3 completely negated the effects of IV HN analog on liver, suggesting that the hepatic actions of HN are centrally mediated. This is consistent with the lack of a direct effect of HN on primary hepatocytes. Furthermore, single treatment with a highly-potent HN analog significantly lowered blood glucose in Zucker diabetic fatty rats. Based upon the link of HN with two age-related diseases, we examined if there were age associated changes in HN levels. Indeed, the amount of detectable HN in hypothalamus, skeletal muscle, and cortex was decreased with age in rodents, and circulating levels of HN were decreased with age in humans and mice. Conclusions We conclude that the decline in HN with age could play a role in the pathogenesis of age-related diseases including AD and T2DM. HN represents a novel link between T2DM and neurodegeneration and along with its analogues offers a potential therapeutic tool to improve insulin action and treat T2DM. PMID:19623253

Prospects for discovering a neutrino line induced by dark matter annihilation

NASA Astrophysics Data System (ADS)

El Aisati, Chaimae; Garcia-Cely, Camilo; Hambye, Thomas; Vanderheyden, Laurent

2017-10-01

In the near future, neutrino telescopes are expected to improve their sensitivity to the flux of monochromatic neutrinos produced by dark matter (DM) in our galaxy. This is illustrated by a new limit on the corresponding cross section that we derive from public IceCube data. In this context, we study which DM models could produce an observable flux of monochromatic neutrinos from DM annihilations. To this end, we proceed in two steps. First, within a set of simple and minimal assumptions concerning the properties of the DM particle, we determine the models that could give rise to a significant annihilation into monochromatic neutrinos at the freeze-out epoch. The list of models turns out to be very limited as a result of various constraints, in particular direct detection and neutrino masses at loop level. Given the fact that, even if largely improved, the sensitivities will be far from reaching the thermal annihilation cross section soon, a signal could only be observed if the annihilation into neutrinos today is boosted with respect to the freeze-out epoch. This is why, in a second step, we analyze the possibility of having such a large enhancement from the Sommerfeld effect. For each scenario, we also compute the cross sections into other annihilation products and confront our results with experimental constraints. We find that, within our simple and minimal assumptions, the expectation to observe monochromatic neutrinos is only possible in very specific scenarios. Some will be confirmed or excluded in the near future because they predict signals slightly below the current experimental sensitivities. We also discuss how these prospects change by relaxing our assumptions as well as by considering other types of sharp spectral features. For the latter, we consider boxed-shaped and bremsstrahlung spectra and provide the corresponding limits from IceCube data.

Prospects for discovering a neutrino line induced by dark matter annihilation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aisati, Chaimae El; Garcia-Cely, Camilo; Hambye, Thomas

In the near future, neutrino telescopes are expected to improve their sensitivity to the flux of monochromatic neutrinos produced by dark matter (DM) in our galaxy. This is illustrated by a new limit on the corresponding cross section that we derive from public IceCube data. In this context, we study which DM models could produce an observable flux of monochromatic neutrinos from DM annihilations. To this end, we proceed in two steps. First, within a set of simple and minimal assumptions concerning the properties of the DM particle, we determine the models that could give rise to a significant annihilationmore » into monochromatic neutrinos at the freeze-out epoch. The list of models turns out to be very limited as a result of various constraints, in particular direct detection and neutrino masses at loop level. Given the fact that, even if largely improved, the sensitivities will be far from reaching the thermal annihilation cross section soon, a signal could only be observed if the annihilation into neutrinos today is boosted with respect to the freeze-out epoch. This is why, in a second step, we analyze the possibility of having such a large enhancement from the Sommerfeld effect. For each scenario, we also compute the cross sections into other annihilation products and confront our results with experimental constraints. We find that, within our simple and minimal assumptions, the expectation to observe monochromatic neutrinos is only possible in very specific scenarios. Some will be confirmed or excluded in the near future because they predict signals slightly below the current experimental sensitivities. We also discuss how these prospects change by relaxing our assumptions as well as by considering other types of sharp spectral features. For the latter, we consider boxed-shaped and bremsstrahlung spectra and provide the corresponding limits from IceCube data.« less

The RNAs of RNA-directed DNA methylation

PubMed Central

Wendte, Jered M.; Pikaard, Craig S.

2016-01-01

Summary RNA-directed chromatin modification that includes cytosine methylation silences transposable elements in both plants and mammals, contributing to genome defense and stability. In Arabidopsis thaliana, most RNA-directed DNA methylation (RdDM) is guided by small RNAs derived from double-stranded precursors synthesized at cytosine-methylated loci by nuclear multisubunit RNA Polymerase IV (Pol IV), in close partnership with the RNA-dependent RNA polymerase, RDR2. These small RNAs help keep transposons transcriptionally inactive. However, if transposons escape silencing, and are transcribed by multisubunit RNA polymerase II (Pol II), their mRNAs can be recognized and degraded, generating small RNAs that can also guide initial DNA methylation, thereby enabling subsequent Pol IV-RDR2 recruitment. In both pathways, the small RNAs find their target sites by interacting with longer noncoding RNAs synthesized by multisubunit RNA Polymerase V (Pol V). Despite a decade of progress, numerous questions remain concerning the initiation, synthesis, processing, size and features of the RNAs that drive RdDM. Here, we review recent insights, questions and controversies concerning RNAs produced by Pols IV and V, and their functions in RdDM. We also provide new data concerning Pol V transcript 5’ and 3’ ends. PMID:27521981

Sex Mediates the Effects of High-Definition Transcranial Direct Current Stimulation on "Mind-Reading".

PubMed

Martin, A K; Huang, J; Hunold, A; Meinzer, M

2017-12-16

Sex differences in social cognitive ability are well established, including measures of Theory of Mind (ToM). The aim of this study was to investigate if sex mediates the effects of high-definition transcranial direct current stimulation (HD-tDCS) administered to a key hub of the social brain (i.e., the dorsomedial prefrontal cortex, dmPFC) on the Reading the Mind in the Eyes Test (RMET). Forty healthy young adults (18-35 years) were randomly allocated to receive either anodal or cathodal HD-tDCS in sham HD-tDCS controlled, double blind designs. In each of the two sessions, subjects completed the RMET. Anodal stimulation to the dmPFC increased accuracy on the RMET in females only. To assure regional specificity we performed a follow-up study stimulating the right temporoparietal junction and found no effect in either sex. The current study is the first to show improved performance on the RMET after tDCS to the dmPFC in females only. The polarity-specific effects and use of focal HD-tDCS provide evidence for sex-dependent differences in dmPFC function in relation to the RMET. Future studies using tDCS to study or improve ToM, need to consider sex. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Dark Matter in B – L supersymmetric Standard Model with inverse seesaw

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abdallah, W.; Khalil, S., E-mail: awaleed@sci.cu.edu.eg, E-mail: s.khalil@zewailcity.edu.eg

We show that the B – L Supersymmetric Standard Model with Inverse Seesaw (BLSSMIS) provides new Dark Matter (DM) candidates (lightest right-handed sneutrino and lightest B – L neutralino) with mass of order few hundreds GeV, while most of other SUSY spectrum can be quite heavy, consistently with the current Large Hadron Collider (LHC) constraints. We emphasize that the thermal relic abundance and direct detection experiments via relic neutralino scattering with nuclei impose stringent constraints on the B – L neutralinos. These constraints can be satisfied by few points in the parameter space where the B – L lightest neutralinomore » is higgsino-like, which cannot explain the observed Galactic Center (GC) gamma-ray excess measured by Fermi-LAT. The lightest right-handed sneutrino DM is analysed. We show that for a wide region of parameter space the lightest right-handed sneutrino, with mass between 80 GeV and 1.2 TeV, can satisfy the limits of the relic abundance and the scattering cross section with nuclei. We also show that the lightest right-handed sneutrino with mass O(100) GeV can account for the observed GC gamma-ray results.« less

Pioglitazone improves the ability of learning and memory via activating ERK1/2 signaling pathway in the hippocampus of T2DM rats.

PubMed

Gao, F; Zang, L; Wu, D Y; Li, Y J; Zhang, Q; Wang, H B; Tian, G L; Mu, Y M

2017-06-09

To explore the correlation between effect of PIO (pioglitazone, PIO) on learning as well as memory and ERK1/2 (extracellular signal regulated kinase 1/2, ERK1/2) pathway in T2DM (type 2 diabetes mellitus, T2DM) rats, further to elucidate the potential mechanism of PIO in improvement of learning and memory. 12-week-old male SD rats (number of 10 per group) were randomly divided into control group (CON), T2DM group (DM) and T2DM +PIO group (DM+PG). Rats in DM and DM+PG groups were given high fat diet for 20 weeks, then treated with Streptozotocin (27mg/kg) by intraperitoneal injection at 21week. After 72h, the FBG (fasting blood glucose, FBG) was greater than 7.0mmol/L can considered T2DM rats. DM+PG group was treated with PIO (10 mg·kg -1 ·d -1 ) by gavage daily. After Hyperinsulinemic-Euglycemic Clamp Study and Morris water maze test at 30-week, all of animals were sacrificed. The expressions of RKIP (Raf-1 kinase inhibitor protein, RKIP) and ERK1/2 in hippocampus were detected using Western Blot and real-time PCR. The FBG level: DM group (7.68±0.54mmol/L) was higher than CON group (5.35±0.63mmol/L) and DM+PG group (6.07±0.84mmol/L), the differences were considered statistically significant (P <0.05). Hyperinsulinemic-Euglycemic Clamp Studies: GIR (glucose infusion rate, GIR) of DM group (21.02±5.10 mg·kg -1 ·d -1 ) was less than CON group (27.64±3.87 mg·kg -1 ·d -1 ) and DM+PG group (26.04 ±5.41 mg·kg -1 ·d -1 ), the differences were considered statistically significant (P <0.05). Morris water maze training: The escape latencies and searching platform performance of DM group (24.54±5.02s) decreased significantly compared with CON group (16.73±4.02s) and DM+PG group (18.05±4.12s) (P <0.05). Changes of RKIP, ERK, p-ERK protein relative content in rat hippocampus: Compared with CON groupand DM+PG group, the relative content of RKIP in DM group remarkably increased (P<0.01); ERK protein levels were not considered statistically significant among the three groups (P>0.05); The relative content of p-ERK1/2 protein in CON group and DM+PG group rats dorsal were higher than those in group DM, the difference was considered statistically significant (P<0.01). Changes in hippocampus of rat RKIP and ERK gene relative content: Compared with CON group and DM+PG group, levels of RKIP mRNA in DM group were significantly increased (P<0.01); ERK mRNA levels were not considered statistically significant among the three groups (P>0.05). Activation of ERK1/2 signal transduction pathway via reducing RKIP in the hippocampus may be one of the mechanisms of PIO to improve the learning and memory of the T2DM rats. Copyright © 2017 Elsevier B.V. All rights reserved.

Existence of dark matter with observed properties of cosmic microwave background radiation substantiates three conservation laws of classical physics and all principles of quantum mechanics as creates the value of Planck’s constant

NASA Astrophysics Data System (ADS)

Boriev, I. A.

2018-03-01

Astronomical data indicate a presence of dark matter (DM) in the space, what is necessary for explanation of observed dynamics of the galaxies within Newtonian mechanics. DM, at its very low density (∼10-26kg/m3), constitutes main part of the matter in the Universe, 10 times the mass of all visible cosmic bodies. No doubt, namely properties of DM, which fills space, must determine its physical properties and fundamental physical laws. Taking into account observed properties of cosmic microwave background radiation (CMBR), whose energy is ∼90% of all cosmic radiation, and understanding that this radiation is produced by DM motion, conservation laws of classical physics and principles of quantum mechanics receive their materialistic substantiation. Thus, CMBR high homogeneity and isotropy (∼10-4), and hence the same properties of DM (and space) justify momentum and angular momentum conservation laws, respectively, according to E. Noether's theorems. CMBR has black body spectrum at ∼2.7K with maximum wavelength ∼1.9·10-3m, what allows calculate the value of mechanical action produced by DM thermal motion (∼7·10-34 J·s). This value corresponds well to the Planck’s constant, which is the mechanical action too, what gives materialistic basis for all principles of quantum mechanics. Obtained results directly confirm the reality of DM existence, and show that CMBR is an observed display of DM thermal motion. Understanding that namely from DM occur known creation of electron-positron pairs as contrarily rotating material vortexes (according to their spins) let substantiate positron nature of ball lightning what first explains all its observed specific properties.

Diabetes Mellitus and Colorectal Neoplasia.

PubMed

Acevedo, Alejandro; Diaz, Yaritza; Perez, Cynthia M; Garau, Maria; Baron, John; Cruz-Correa, Marcia

2012-11-01

Many studies have provided evidence for an association between obesity, physical inactivity, and western diet as risk factors for colorectal cancer (CRC). Few studies directly address the association between type 2 Diabetes Mellitus (DM) and the risk of colorectal lesions at specific anatomic locations. 2,663 subjects with a previous history of adenoma(s) and removal of all current adenomas at study entry were followed for a mean time of three years across three different chemoprevention clinical trials. The primary endpoint was colorectal adenoma recurrence and number of lesions during the treatment phase; the secondary endpoints were presence of advanced colorectal neoplasia (CRN) and location of CRN. Using log linear regression, the effect of DM status on the relative risk (RR) of CRN recurrence, advanced CRN, and location of CRN was assessed. DM status was not significantly associated with incidence of colorectal adenomas, incidence of advanced colorectal lesions, or left-sided colorectal neoplastic lesions. Subjects with DM had a marginally increased risk of right-sided (p= 0.06) colorectal adenomas and a significant increased risk of multiple right-sided adenomas (p=0.03) in the unadjusted model; this association was not significant after adjusting for age and other potential confounders (RR=1.22, 95% CI: 0.85-1.76). We did not observe a statistically significant increased risk in CRN recurrence for overall neoplasia, advanced neoplasia or location of neoplasia in individuals with DM compared to non-DM individuals. However, given the patterns observed in this investigation, future studies with longer follow-up time and longer DM exposure, incorporating objective measurements of type 2 DM might help elucidate the risk of CRN among individuals with DM.

Two-Player 2 × 2 Quantum Game in Spin System

NASA Astrophysics Data System (ADS)

Huang, Zhiming; Situ, Haozhen

2017-05-01

In this work, we study the payoffs of quantum Samaritan's dilemma played with the thermal entangled state of XXZ spin model in the presence of Dzyaloshinskii-Moriya (DM) interaction. We discuss the effect of anisotropy parameter, strength of DM interaction and temperature on quantum Samaritan's dilemma. It is shown that although increasing DM interaction and anisotropy parameter generate entanglement, players payoffs are not simply decided by entanglement and depend on other game components such as strategy and payoff measurement. In general, Entanglement and Alice's payoff evolve to a relatively stable value with anisotropy parameter, and develop to a fixed value with DM interaction strength, while Bob's payoff changes in the reverse direction. It is noted that the augment of Alice's payoff compensates for the loss of Bob's payoff. For different strategies, payoffs have different changes with temperature. Our results and discussions can be analogously generalized to other 2 × 2 quantum static games in various spin models.

Millicharge or decay: a critical take on Minimal Dark Matter

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nobile, Eugenio Del; Dipartimento di Fisica e Astronomia “G. Galilei”, Università di Padova and INFN, Sezione di Padova,Via Marzolo 8, 35131 Padova; Nardecchia, Marco

2016-04-26

Minimal Dark Matter (MDM) is a theoretical framework highly appreciated for its minimality and yet its predictivity. Of the two only viable candidates singled out in the original analysis, the scalar eptaplet has been found to decay too quickly to be around today, while the fermionic quintuplet is now being probed by indirect Dark Matter (DM) searches. It is therefore timely to critically review the MDM paradigm, possibly pointing out generalizations of this framework. We propose and explore two distinct directions. One is to abandon the assumption of DM electric neutrality in favor of absolutely stable, millicharged DM candidates whichmore » are part of SU(2){sub L} multiplets with integer isospin. Another possibility is to lower the cutoff of the model, which was originally fixed at the Planck scale, to allow for DM decays. We find new viable MDM candidates and study their phenomenology in detail.« less

Duobinary pulse shaping for frequency chirp enabled complex modulation.

PubMed

Che, Di; Yuan, Feng; Khodakarami, Hamid; Shieh, William

2016-09-01

The frequency chirp of optical direct modulation (DM) used to be a performance barrier of optical transmission system, because it broadens the signal optical spectrum, which becomes more susceptible to chromatic dispersion induced inter-symbol interference (ISI). However, by considering the chirp as frequency modulation, the single DM simultaneously generates a 2-D signal containing the intensity and phase (namely, the time integral of frequency). This complex modulation concept significantly increases the optical signal to noise ratio (OSNR) sensitivity of DM systems. This Letter studies the duobinary pulse shaping (DB-PS) for chirp enabled DM and its impact on the optical bandwidth and system OSNR sensitivity. DB-PS relieves the bandwidth requirement, at the sacrifice of system OSNR sensitivity. As DB-PS induces a controlled ISI, the receiver requires one more tap for maximum likelihood sequence estimation (MLSE). We verify this modified MLSE with a 10-Gbaud duobinary PAM-4 transmission experiment.

Millicharge or decay: a critical take on Minimal Dark Matter

DOE PAGES

Nobile, Eugenio Del; Nardecchia, Marco; Panci, Paolo

2016-04-26

Minimal Dark Matter (MDM) is a theoretical framework highly appreciated for its minimality and yet its predictivity. Of the two only viable candidates singled out in the original analysis, the scalar eptaplet has been found to decay too quickly to be around today, while the fermionic quintuplet is now being probed by indirect Dark Matter (DM) searches. It is therefore timely to critically review the MDM paradigm, possibly pointing out generalizations of this framework. We propose and explore two distinct directions. One is to abandon the assumption of DM electric neutrality in favor of absolutely stable, millicharged DM candidates whichmore » are part of SU(2)L multiplets with integer isospin. Another possibility is to lower the cutoff of the model, which was originally fixed at the Planck scale, to allow for DM decays. We find new viable MDM candidates and study their phenomenology in detail.« less

Carbonylated plasma proteins as potential biomarkers of obesity induced type 2 diabetes mellitus.

PubMed

Bollineni, Ravi Chand; Fedorova, Maria; Blüher, Matthias; Hoffmann, Ralf

2014-11-07

Protein carbonylation is a common nonenzymatic oxidative post-translational modification, which is often considered as biomarker of oxidative stress. Recent evidence links protein carbonylation also to obesity and type 2 diabetes mellitus (T2DM), though the protein targets of carbonylation in human plasma have not been identified. In this study, we profiled carbonylated proteins in plasma samples obtained from lean individuals and obese patients with or without T2DM. The plasma samples were digested with trypsin, carbonyl groups were derivatized with O-(biotinylcarbazoylmethyl)hydroxylamine, enriched by avidin affinity chromatography, and analyzed by RPC-MS/MS. Signals of potentially modified peptides were targeted in a second LC-MS/MS analysis to retrieve the peptide sequence and the modified residues. A total of 158 unique carbonylated proteins were identified, of which 52 were detected in plasma samples of all three groups. Interestingly, 36 carbonylated proteins were detected only in obese patients with T2DM, whereas 18 were detected in both nondiabetic groups. The carbonylated proteins originated mostly from liver, plasma, platelet, and endothelium. Functionally, they were mainly involved in cell adhesion, signaling, angiogenesis, and cytoskeletal remodeling. Among the identified carbonylated proteins were several candidates, such as VEGFR-2, MMP-1, argin, MKK4, and compliment C5, already connected before to diabetes, obesity and metabolic diseases.

On ultraviolet freeze-in dark matter during reheating

NASA Astrophysics Data System (ADS)

Chen, Shao-Long; Kang, Zhaofeng

2018-05-01

The absence of any confirmative signals from extensive DM searching motivates us to go beyond the conventional WIMPs scenario. The feebly interacting massive particles (FIMPs) paradigm provides a good alternative which, despite of its feebly interaction with the thermal particles, still could correctly produce relic abundance without conventional DM signals. The Infrared-FIMP based on the renormalizable operators is usually suffering the very tiny coupling drawback, which can be overcome in the UltraViolet-FIMP scenario based on high dimensional effective operators. However, it is sensitive to the history of the very early Universe. The previous works terminates this sensitivity at the reheating temperature TRH. We, motivated by its UV-sensitivity, investigate the effects from the even earlier Universe, reheating era. We find that in the usual case with TRHgg mDM, the production rate during reheating is very small as long as the effective operators dimension d <= 8. Besides, we consider the contribution from the mediator, which may be produced during reheating. Moreover, we study the situation when TRH is even lower than mDM and DM can be directly produced during reheating if its mass does not exceed TMAX.

Detection of serpentine in exogenic carbonaceous chondrite material on Vesta from Dawn FC data

NASA Astrophysics Data System (ADS)

Nathues, Andreas; Hoffmann, Martin; Cloutis, Edward A.; Schäfer, Michael; Reddy, Vishnu; Christensen, Ulrich; Sierks, Holger; Thangjam, Guneshwar Singh; Le Corre, Lucille; Mengel, Kurt; Vincent, Jean-Baptist; Russell, Christopher T.; Prettyman, Tom; Schmedemann, Nico; Kneissl, Thomas; Raymond, Carol; Gutierrez-Marques, Pablo; Hall, Ian; Büttner, Irene

2014-09-01

The Dawn mission’s Framing Camera (FC) observed Asteroid (4) Vesta in 2011 and 2012 using seven color filters and one clear filter from different orbits. In the present paper we analyze recalibrated HAMO color cubes (spatial resolution ∼60 m/pixel) with a focus on dark material (DM). We present a definition of highly concentrated DM based on spectral parameters, subsequently map the DM across the Vestan surface, geologically classify DM, study its spectral properties on global and local scales, and finally, compare the FC in-flight color data with laboratory spectra. We have discovered an absorption band centered at 0.72 μm in localities of DM that show the lowest albedo values by using FC data as well as spectral information from Dawn’s imaging spectrometer VIR. Such localities are contained within impact-exposed outcrops on inner crater walls and ejecta material. Comparisons between spectral FC in-flight data, and laboratory spectra of meteorites and mineral mixtures in the wavelength range 0.4-1.0 μm, revealed that the absorption band can be attributed to the mineral serpentine, which is typically present in CM chondrites. Dark material in its purest form is rare on Vesta’s surface and is distributed globally in a non-uniform manner. Our findings confirm the hypothesis of an exogenic origin of the DM by the infall of carbonaceous chondritic material, likely of CM type. It further confirms the hypothesis that most of the DM was deposited by the Veneneia impact.

Efficacy and safety of rivaroxaban in patients with diabetes and nonvalvular atrial fibrillation: the Rivaroxaban Once-daily, Oral, Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF Trial).

PubMed

Bansilal, Sameer; Bloomgarden, Zachary; Halperin, Jonathan L; Hellkamp, Anne S; Lokhnygina, Yuliya; Patel, Manesh R; Becker, Richard C; Breithardt, Günter; Hacke, Werner; Hankey, Graeme J; Nessel, Christopher C; Singer, Daniel E; Berkowitz, Scott D; Piccini, Jonathan P; Mahaffey, Kenneth W; Fox, Keith A A

2015-10-01

The prevalence of both atrial fibrillation (AF) and diabetes mellitus (DM) are rising, and these conditions often occur together. Also, DM is an independent risk factor for stroke in patients with AF. We aimed to examine the safety and efficacy of rivaroxaban vs warfarin in patients with nonvalvular AF and DM in a prespecified secondary analysis of the ROCKET AF trial. We stratified the ROCKET AF population by DM status, assessed associations with risk of outcomes by DM status and randomized treatment using Cox proportional hazards models, and tested for interactions between randomized treatments. For efficacy, primary outcomes were stroke (ischemic or hemorrhagic) or non-central nervous system embolism. For safety, the primary outcome was major or nonmajor clinically relevant bleeding. The 5,695 patients with DM (40%) in ROCKET AF were younger, were more obese, and had more persistent AF, but fewer had previous stroke (the CHADS2 score includes DM and stroke). The relative efficacy of rivaroxaban and warfarin for prevention of stroke and systemic embolism was similar in patients with (1.74 vs 2.14/100 patient-years, hazard ratio [HR] 0.82) and without (2.12 vs 2.32/100 patient-years, HR 0.92) DM (interaction P = .53). The safety of rivaroxaban vs warfarin regarding major bleeding (HRs 1.00 and 1.12 for patients with and without DM, respectively; interaction P = .43), major or nonmajor clinically relevant bleeding (HRs 0.98 and 1.09; interaction P = .17), and intracerebral hemorrhage (HRs 0.62 and 0.72; interaction P = .67) was independent of DM status. Adjusted exploratory analyses suggested 1.3-, 1.5-, and 1.9-fold higher 2-year rates of stroke, vascular mortality, and myocardial infarction in DM patients. The relative efficacy and safety of rivaroxaban vs warfarin was similar in patients with and without DM, supporting use of rivaroxaban as an alternative to warfarin in diabetic patients with AF. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Endothelial Progenitor Cells (EPC) Count by Multicolor Flow Cytometry in Healthy Individuals and Diabetes Mellitus (DM) Patients.

PubMed

Falay, Mesude; Aktas, Server

2016-11-01

The present study aimed to determine circulating Endothelial Progenitor Cell (EPC) counts by multicolor flow cytometry in healthy individuals and diabetic subjects by means of forming an analysis procedure using a combination of monoclonal antibodies (moAbs), which would correctly detect the circulating EPC count. The circulating EPC count was detected in 40 healthy individuals (20 Female, 20 Male; age range: 26 - 50 years) and 30 Diabetes Mellitus (DM) patients (15 Female, 15 Male; age range: 42 - 55) by multicolor flow cytometry (FCM) in a single-tube panel consisting of 5 CD45/CD31/CD34/CD309/ SYTO® and 16 monoclonal antibodies. Circulating EPC count was 11.33 (7.89 - 15.25) cells/µL in the healthy control group and 4.80 (0.70 - 10.85) cells/µL in the DM group. EPC counts were significantly lower in DM cases that developed coronary artery disease (53.3%) as compared to those that did not (p < 0.001). In the present study, we describe a method that identifies circulating EPC counts by multicolor flow cytometry in a single tube and determines the circulating EPC count in healthy individuals. This is the first study conducted on EPC count in Turkish population. We think that the EPC count found in the present study will be a guide for future studies.

Calculated WIMP signals at the ANDES laboratory: comparison with northern and southern located dark matter detectors

NASA Astrophysics Data System (ADS)

Civitarese, O.; Fushimi, K. J.; Mosquera, M. E.

2016-12-01

Weakly interacting massive particles (WIMPs) are possible components of the Universe’s dark matter (DM). The detection of WIMPs is signaled by the recoil of the atomic nuclei which form a detector. CoGeNT at the Soudan Underground Laboratory (SUL) and DAMA at the Laboratori Nazionali del Gran Sasso (LNGS) have reported data on annual modulation of signals attributed to WIMPs. Both experiments are located in laboratories in the Northern Hemisphere. DM detectors are planned to operate (or already operate) in laboratories in the Southern Hemisphere, including SABRE at Stawell Underground Physics Laboratory (SUPL) in Australia, and DM-ICE in Antarctica. In this work we have analyzed the dependence of diurnal and annual modulation of signals, pertaining to the detection of WIMP, on the coordinates of the laboratory, for experiments which may be performed in the planned new Agua Negra Deep Experimental Site (ANDES) underground facility, to be built in San Juan, Argentina. We made predictions for NaI and Ge-type detectors placed in ANDES, to compare with DAMA, CoGeNT, SABRE and DM-ICE arrays, and found that the diurnal modulation of the signals, at the ANDES site, is amplified at its maximum value, both for NaI (Ge)-type detectors, while the annual modulation remains unaffected by the change in coordinates from north to south.

Tool for physics beyond the standard model

NASA Astrophysics Data System (ADS)

Newby, Christopher A.

The standard model (SM) of particle physics is a well studied theory, but there are hints that the SM is not the final story. What the full picture is, no one knows, but this thesis looks into three methods useful for exploring a few of the possibilities. To begin I present a paper by Spencer Chang, Nirmal Raj, Chaowaroj Wanotayaroj, and me, that studies the Higgs boson. The scalar particle first seen in 2012 may be the vanilla SM version, but there is some evidence that its couplings are different than predicted. By means of increasing the Higgs' coupling to vector bosons and fermions, we can be more consistent with the data. Next, in a paper by Spencer Chang, Gabriel Barello, and me, we elaborate on a tool created to study dark matter (DM) direct detection. The original work by Anand. et al. focused on elastic dark matter, whereas we extended this work to include the in elastic case, where different DM mass states enter and leave the collision. We also examine several direct detection experiments with our new framework to see if DAMA's modulation can be explained while avoiding the strong constraints imposed by the other experiments. We find that there are several operators that can do this. Finally, in a paper by Spencer Chang, Gabriel Barello, and me, we study an interesting phenomenon know as kinetic mixing, where two gauge bosons can share interactions with particles even though these particles aren't charged under both gauge groups. This, in and of itself, is not new, but we discuss a different method of obtaining this mixing where instead of mixing between two Abelian groups one of the groups is Nonabelian. Using this we then see that there is an inherent mass scale in the mixing strength; something that is absent in the Abelian-Abelian case. Furthermore, if the Nonabelian symmetry is the SU(2)L of the SM then the mass scale of the physics responsible for the mixing is about 1 TeV, right around the sweet spot for detection at the LHC. This dissertation includes previously published and unpublishedco-authored material.

Should glycated haemoglobin (HbA1c) be used to detect people with type 2 diabetes mellitus and impaired glucose regulation?

PubMed

Mostafa, Samiul A; Davies, Melanie J; Srinivasan, Balasubramanian Thiagarajan; Carey, Marian E; Webb, David; Khunti, Kamlesh

2010-11-01

There is a need to simplify screening tests for type 2 diabetes mellitus (T2DM) so patients can be identified earlier and more efficiently. Glycated haemoglobin (HbA1c) has been recommended by some international organisations as a diagnostic tool for detecting T2DM and impaired glucose regulation (IGR, also termed prediabetes and includes impaired fasting glucose and/or impaired glucose tolerance). The HbA1c cut-point of ≥6.5% (48 mmol/mol) has been selected as diagnostic for T2DM, while the cut-points for IGR are debated by the different international organisations: an International Expert Committee has suggested using HbA1c 6.0-6.4% (42-46 mmol/mol); however, the American Diabetes Association has recommended using HbA1c 5.7-6.4% (39-46 mmol/mol). Some countries will adopt a new method of reporting HbA1c values in millimoles per mole (mmol/mol). Use of HbA1c has some logistical advantages over using an oral glucose tolerance test (OGTT). As patients do not need to fast, appointments do not need to be limited to the morning. The HbA1c result reflects longer term glycaemia and is less affected by recent physical/emotional stress. However, there is some debate as to whether HbA1c should replace fasting plasma glucose or the OGTT. As the two tests detect different people, some individuals with diabetes detected on OGTT will no longer be classified as having T2DM using HbA1c ≥6.5% criteria. Furthermore, some medical conditions can result in HbA1c assay measurements not reflecting glycaemic control over the last 2-3 months; these include haematological disorders, renal failure, and chronic excess alcohol consumption.

Dental Cell Sheet Biomimetic Tooth Bud Model

PubMed Central

Monteiro, Nelson; Smith, Elizabeth E.; Angstadt, Shantel; Zhang, Weibo; Khademhosseini, Ali

2016-01-01

Tissue engineering and regenerative medicine technologies offer promising therapies for both medicine and dentistry. Our long-term goal is to create functional biomimetic tooth buds for eventual tooth replacement in humans. Here, our objective was to create a biomimetic 3D tooth bud model consisting of dental epithelial (DE) – dental mesenchymal (DM) cell sheets (CSs) combined with biomimetic enamel organ and pulp organ layers created using GelMA hydrogels. Pig DE or DM cells seeded on temperature-responsive plates at various cell densities (0.02, 0.114 and 0.228 cells 106/cm2) and cultured for 7, 14 and 21 days were used to generate DE and DM cell sheets, respectively. Dental CSs were combined with GelMA encapsulated DE and DM cell layers to form bioengineered 3D tooth buds. Biomimetic 3D tooth bud constructs were cultured in vitro, or implanted in vivo for 3 weeks. Analyses were performed using micro-CT, H&E staining, polarized light (Pol) microscopy, immunofluorescent (IF) and immunohistochemical (IHC) analyses. H&E, IHC and IF analyses showed that in vitro cultured multilayered DE-DM CSs expressed appropriate tooth marker expression patterns including SHH, BMP2, RUNX2, tenascin and syndecan, which normally direct DE-DM interactions, DM cell condensation, and dental cell differentiation. In vivo implanted 3D tooth bud constructs exhibited mineralized tissue formation of specified size and shape, and SHH, BMP2 and RUNX2and dental cell differentiation marker expression. We propose our biomimetic 3D tooth buds as models to study optimized DE-DM cell interactions leading to functional biomimetic replacement tooth formation. PMID:27565550

The Drosophila melanogaster Homologue of the Xeroderma Pigmentosum D Gene Product Is Located in Euchromatic Regions and Has a Dynamic Response to UV Light-induced Lesions in Polytene Chromosomes

PubMed Central

Reynaud, Enrique; Lomelí, Hilda; Vázquez, Martha; Zurita, Mario

1999-01-01

The XPD/ERCC2/Rad3 gene is required for excision repair of UV-damaged DNA and is an important component of nucleotide excision repair. Mutations in the XPD gene generate the cancer-prone syndrome, xeroderma pigmentosum, Cockayne’s syndrome, and trichothiodystrophy. XPD has a 5′- to 3′-helicase activity and is a component of the TFIIH transcription factor, which is essential for RNA polymerase II elongation. We present here the characterization of the Drosophila melanogaster XPD gene (DmXPD). DmXPD encodes a product that is highly related to its human homologue. The DmXPD protein is ubiquitous during development. In embryos at the syncytial blastoderm stage, DmXPD is cytoplasmic. At the onset of transcription in somatic cells and during gastrulation in germ cells, DmXPD moves to the nuclei. Distribution analysis in polytene chromosomes shows that DmXPD is highly concentrated in the interbands, especially in the highly transcribed regions known as puffs. UV-light irradiation of third-instar larvae induces an increase in the signal intensity and in the number of sites where the DmXPD protein is located in polytene chromosomes, indicating that the DmXPD protein is recruited intensively in the chromosomes as a response to DNA damage. This is the first time that the response to DNA damage by UV-light irradiation can be visualized directly on the chromosomes using one of the TFIIH components. PMID:10198066

Analysis of synthetic derivatives of peptide hormones by capillary zone electrophoresis and micellar electrokinetic chromatography with ultraviolet-absorption and laser-induced fluorescence detection.

PubMed

Solínová, Veronika; Kasicka, Václav; Koval, Dusan; Barth, Tomislav; Ciencialová, Alice; Záková, Lenka

2004-08-25

Capillary zone electrophoresis (CZE) and micellar electrokinetic chromatography (MEKC) were used for the analysis of new synthetic derivatives of hypophysis neurohormones--vasopressin and oxytocin, and pancreatic hormone--human insulin (HI) and its octapeptide fragment, derivatized by fluorescent probe, 4-chloro-7-nitrobenzo[1,2,5]oxadiazol (NBD). The suitable composition of background electrolytes (BGEs) was selected on the basis of calculated pH dependence of effective charge of analyzed peptides. Basic ionogenic peptides were analyzed by CZE in the acidic BGE composed of 100 mM H3PO4, 50 mM Tris, pH 2.25. The ionogenic peptides with fluorescent label, NBD, were analyzed in 0.5 M acetic acid, pH 2.5. The best MEKC separation of non-ionogenic peptides was achieved in alkaline BGE, 20 mM Tris, 5 mM H3PO4, with micellar pseudophase formed by 50 mM sodium dodecylsulfate (SDS), pH 8.8. Selected characteristics (noise, detectability of substance, sensitivity of detector) of the UV-absorption detectors (single wavelength detector, multiple-wavelength photodiode array detector (PDA), both of them operating at constant wavelength 206 nm) and laser-induced fluorescence (LIF) detector (excitation/emission wavelength 488/520 nm) were determined. The detectability of peptides in the single wavelength detector was 1.3-6.0 micromol dm(-3) and in the PDA detector 1.6-3.1 micromol dm(-3). The LIF detection was more sensitive, the applied concentration of NBD derivative of insulin fragment in CZE analysis with LIF detection was three orders lower than in CZE with UV-absorption detector, and the detectability of this peptide was improved to 15.8 nmol dm(-3).

MicroRNA-224 is Readily Detectable in Urine of Individuals with Diabetes Mellitus and is a Potential Indicator of Beta-Cell Demise

PubMed Central

Bacon, Siobhán; Engelbrecht, Britta; Schmid, Jasmin; Pfeiffer, Shona; Gallagher, Ross; McCarthy, Ailbhe; Burke, Marie; Concannon, Caoimhín; Prehn, Jochen H. M.; Byrne, Maria M.

2015-01-01

MicroRNA (miRNA) are a class of non-coding, 19–25 nucleotide RNA critical for network-level regulation of gene expression. miRNA serve as paracrine signaling molecules. Using an unbiased array approach, we previously identified elevated levels of miR-224 and miR-103 to be associated with a monogenic form of diabetes; HNF1A-MODY. miR-224 is a novel miRNA in the field of diabetes. We sought to explore the role of miR-224 as a potential biomarker in diabetes, and whether such diabetes-associated-miRNA can also be detected in the urine of patients. Absolute levels of miR-224 and miR-103 were determined in the urine of n = 144 individuals including carriers of a HNF1A mutation, participants with type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM) and normal controls. Expression levels were correlated with clinical and biochemical parameters. miR-224 was significantly elevated in the urine of carriers of a HNF1A mutation and participants with T1DM. miR-103 was highly expressed in urine across all diabetes cohorts when compared to controls. For both miR-224 and-103, we found a significant correlation between serum and urine levels (p < 0.01). We demonstrate that miRNA can be readily detected in the urine independent of clinical indices of renal dysfunction. We surmise that the differential expression levels of miR-224 in both HNF1A-MODY mutation carriers and T1DM may be an attempt to compensate for beta-cell demise. PMID:26110317

Decaying fermionic dark matter search with CALET

NASA Astrophysics Data System (ADS)

Bhattacharyya, S.; Motz, H.; Torii, S.; Asaoka, Y.

2017-08-01

The ISS-based CALET (CALorimetric Electron Telescope) detector can play an important role in indirect search for Dark Matter (DM), measuring the electron+positron flux in the TeV region for the first time directly. With its fine energy resolution of approximately 2% and good proton rejection ratio (1:105) it has the potential to search for fine structures in the Cosmic Ray (CR) electron spectrum. In this context we discuss the ability of CALET to discern between signals originating from astrophysical sources and DM decay. We fit a parametrization of the local interstellar electron and positron spectra to current measurements, with either a pulsar or 3-body decay of fermionic DM as the extra source causing the positron excess. The expected CALET data for scenarios in which DM decay explains the excess are calculated and analyzed. The signal from this particular 3-body DM decay which can explain the recent measurements from the AMS-02 experiment is shown to be distinguishable from a single pulsar source causing the positron excess by 5 years of observation with CALET, based on the shape of the spectrum. We also study the constraints from diffuse γ-ray data on this DM-only explanation of the positron excess and show that especially for the possibly remaining parameter space a clearly identifiable signature in the CR electron spectrum exists.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhattacharyya, S.; Torii, S.; Motz, H.

The ISS-based CALET (CALorimetric Electron Telescope) detector can play an important role in indirect search for Dark Matter (DM), measuring the electron+positron flux in the TeV region for the first time directly. With its fine energy resolution of approximately 2% and good proton rejection ratio (1:10{sup 5}) it has the potential to search for fine structures in the Cosmic Ray (CR) electron spectrum. In this context we discuss the ability of CALET to discern between signals originating from astrophysical sources and DM decay. We fit a parametrization of the local interstellar electron and positron spectra to current measurements, with eithermore » a pulsar or 3-body decay of fermionic DM as the extra source causing the positron excess. The expected CALET data for scenarios in which DM decay explains the excess are calculated and analyzed. The signal from this particular 3-body DM decay which can explain the recent measurements from the AMS−02 experiment is shown to be distinguishable from a single pulsar source causing the positron excess by 5 years of observation with CALET, based on the shape of the spectrum. We also study the constraints from diffuse γ-ray data on this DM-only explanation of the positron excess and show that especially for the possibly remaining parameter space a clearly identifiable signature in the CR electron spectrum exists.« less

Can dispersion modeling of air pollution be improved by land-use regression? An example from Stockholm, Sweden.

PubMed

Korek, Michal; Johansson, Christer; Svensson, Nina; Lind, Tomas; Beelen, Rob; Hoek, Gerard; Pershagen, Göran; Bellander, Tom

2017-11-01

Both dispersion modeling (DM) and land-use regression modeling (LUR) are often used for assessment of long-term air pollution exposure in epidemiological studies, but seldom in combination. We developed a hybrid DM-LUR model using 93 biweekly observations of NO x at 31 sites in greater Stockholm (Sweden). The DM was based on spatially resolved topographic, physiographic and emission data, and hourly meteorological data from a diagnostic wind model. Other data were from land use, meteorology and routine monitoring of NO x . We built a linear regression model for NO x , using a stepwise forward selection of covariates. The resulting model predicted observed NO x (R 2 =0.89) better than the DM without covariates (R 2 =0.68, P-interaction <0.001) and with minimal apparent bias. The model included (in descending order of importance) DM, traffic intensity on the nearest street, population (number of inhabitants) within 100 m radius, global radiation (direct sunlight plus diffuse or scattered light) and urban contribution to NO x levels (routine urban NO x , less routine rural NO x ). Our results indicate that there is a potential for improving estimates of air pollutant concentrations based on DM, by incorporating further spatial characteristics of the immediate surroundings, possibly accounting for imperfections in the emission data.

Ancient Records and Modern Research on the Mechanisms of Chinese Herbal Medicines in the Treatment of Diabetes Mellitus

PubMed Central

Zhang, Hai-ming; Liang, Feng-xia

2015-01-01

Over the past decades, Chinese herbal medicines (CHM) have been extensively and intensively studied through from both clinical and experimental perspectives and CHM have been proved to be effective in the treatment of diabetes mellitus (DM). This study, by searching ancient records and modern research papers, reviewed CHM in terms of their clinical application and principal mechanism in the treatment of DM. We summarized the use of CHM mentioned in 54 famous ancient materia medica monographs and searched papers on the hypoglycemic effect of several representative CHM. Main mechanisms and limitations of CHM and further research direction for DM were discussed. On the basis of the study, we were led to conclude that TCM, as a main form of complementary and alternative medicine (CAM), was well recorded in ancient literatures and has less adverse effects as shown by modern studies. The mechanisms of CHM treatment of DM are complex, multilink, and multitarget, so we should find main hypoglycemic mechanism through doing research on CHM monomer active constituents. Many CHM monomer constituents possess noteworthy hypoglycemic effects. Therefore, developing a novel natural product for DM and its complications is of much significance. It is strongly significant to pay close attention to CHM for treatment of DM and its complications. PMID:25815039

Metabolite differences in the lenticular nucleus in type 2 diabetes mellitus shown by proton MR spectroscopy.

PubMed

Lin, Y; Zhou, J; Sha, L; Li, Y; Qu, X; Liu, L; Chen, H; An, Z; Wang, Y; Sun, C

2013-09-01

Previous studies by using proton MR spectroscopy found metabolite abnormalities in the cerebral cortex and white matter of patients with type 2 diabetes mellitus. The present study was undertaken to detect metabolite differences in the lenticular nuclei and thalamus in patients with T2DM. Twenty subjects with T2DM and 22 age-matched control subjects underwent single-voxel MR spectroscopy in the left and right lenticular nuclei and left and right thalami. NAA/Cr and Cho/Cr ratios were calculated. Brain lactic acid, fasting blood glucose, and glycosylated hemoglobin levels were also monitored. The NAA/Cr ratio was lower in the left lenticular nuclei of subjects with T2DM (P = .007), whereas the Cho/Cr ratio was increased in both the and right lenticular nuclei (P = .001). The NAA/Cr ratio was negatively correlated with FBG in the left (r = -0.573, P = .008) and right nuclei (r = -0.564, P = .010). It was also negatively correlated to HbA1c in the left (r = -0.560, P = .010) and right (r = -0.453, P = .045) nuclei. The Cho/Cr ratio was positively correlated with these variables (P < .05). No significant differences in NAA/Cr or Cho/Cr ratios were observed in the thalamus of patients with T2DM. Lactic acid was not detected in any of the patients in the study. The different metabolic statuses of the lenticular nuclei and thalamus suggest different effects of T2DM in each of these brain nuclei, with the lenticular nuclei being more vulnerable than the thalamus. The abnormal metabolic status was observed before lesions had appeared in these brain areas.

Cost-effectiveness analysis of trastuzumab emtansine (T-DM1) in human epidermal growth factor receptor 2 (HER2): positive advanced breast cancer.

PubMed

Le, Quang A; Bae, Yuna H; Kang, Jenny H

2016-10-01

The EMILIA trial demonstrated that trastuzumab emtansine (T-DM1) significantly increased the median profession-free and overall survival relative to combination therapy with lapatinib plus capecitabine (LC) in patients with HER2-positive advanced breast cancer (ABC) previously treated with trastuzumab and a taxane. We performed an economic analysis of T-DM1 as a second-line therapy compared to LC and monotherapy with capecitabine (C) from both perspectives of the US payer and society. We developed four possible Markov models for ABC to compare the projected life-time costs and outcomes of T-DM1, LC, and C. Model transition probabilities were estimated from the EMILIA and EGF100151 clinical trials. Direct costs of the therapies, major adverse events, laboratory tests, and disease progression, indirect costs (productivity losses due to morbidity and mortality), and health utilities were obtained from published sources. The models used 3 % discount rate and reported in 2015 US dollars. Probabilistic sensitivity analysis and model averaging were used to account for model parametric and structural uncertainty. When incorporating both model parametric and structural uncertainty, the resulting incremental cost-effectiveness ratios (ICER) comparing T-DM1 to LC and T-DM1 to C were $183,828 per quality-adjusted life year (QALY) and $126,001/QALY from the societal perspective, respectively. From the payer's perspective, the ICERs were $220,385/QALY (T-DM1 vs. LC) and $168,355/QALY (T-DM1 vs. C). From both perspectives of the US payer and society, T-DM1 is not cost-effective when comparing to the LC combination therapy at a willingness-to-pay threshold of $150,000/QALY. T-DM1 might have a better chance to be cost-effective compared to capecitabine monotherapy from the US societal perspective.

The Diabetes Remission Clinical Trial (DiRECT): protocol for a cluster randomised trial.

PubMed

Leslie, Wilma S; Ford, Ian; Sattar, Naveed; Hollingsworth, Kieren G; Adamson, Ashley; Sniehotta, Falko F; McCombie, Louise; Brosnahan, Naomi; Ross, Hazel; Mathers, John C; Peters, Carl; Thom, George; Barnes, Alison; Kean, Sharon; McIlvenna, Yvonne; Rodrigues, Angela; Rehackova, Lucia; Zhyzhneuskaya, Sviatlana; Taylor, Roy; Lean, Mike E J

2016-02-16

Despite improving evidence-based practice following clinical guidelines to optimise drug therapy, Type 2 diabetes (T2DM) still exerts a devastating toll from vascular complications and premature death. Biochemical remission of T2DM has been demonstrated with weight loss around 15kg following bariatric surgery and in several small studies of non-surgical energy-restriction treatments. The non-surgical Counterweight-Plus programme, running in Primary Care where obesity and T2DM are routinely managed, produces >15 kg weight loss in 33% of all enrolled patients. The Diabetes UK-funded Counterpoint study suggested that this should be sufficient to reverse T2DM by removing ectopic fat in liver and pancreas, restoring first-phase insulin secretion. The Diabetes Remission Clinical Trial (DiRECT) was designed to determine whether a structured, intensive, weight management programme, delivered in a routine Primary Care setting, is a viable treatment for achieving durable normoglycaemia. Other aims are to understand the mechanistic basis of remission and to identify psychological predictors of response. Cluster-randomised design with GP practice as the unit of randomisation: 280 participants from around 30 practices in Scotland and England will be allocated either to continue usual guideline-based care or to add the Counterweight-Plus weight management programme, which includes primary care nurse or dietitian delivery of 12-20weeks low calorie diet replacement, food reintroduction, and long-term weight loss maintenance. Main inclusion criteria: men and women aged 20-65 years, all ethnicities, T2DM 0-6years duration, BMI 27-45 kg/m(2). Tyneside participants will undergo Magnetic Resonance (MR) studies of pancreatic and hepatic fat, and metabolic studies to determine mechanisms underlying T2DM remission. Co-primary endpoints: weight reduction ≥ 15 kg and HbA1c <48 mmol/mol at one year. Further follow-up at 2 years. This study will establish whether a structured weight management programme, delivered in Primary Care by practice nurses or dietitians, is a viable treatment to achieve T2DM remission. Results, available from 2018 onwards, will inform future service strategy. Current Controlled Trials ISRCTN03267836 . Date of Registration 20/12/2013.

Clinical presentation and memory function in youth with type 1 diabetes.

PubMed

Semenkovich, Katherine; Bischoff, Allison; Doty, Tasha; Nelson, Suzanne; Siller, Alejandro F; Hershey, Tamara; Arbeláez, Ana Maria

2016-11-01

While cerebral edema and diabetic ketoacidosis (DKA) in type 1 diabetes (T1DM) have well-described acute effects on cognition, little is known about the impact of clinical presentation on longer term cognitive outcomes. We hypothesized that clinical factors (degree of hyperglycemia exposure and DKA) at the time of diagnosis would relate to cognition within 3.5 months later in children with T1DM. Cognitive testing was performed on children 7-17 years old with T1DM (n = 66) within 3.5 months of diagnosis and siblings without T1DM (n = 33). Overall intelligence, processing speed, and memory (including a sensitive long-delay spatial memory test; spatial delayed response or SDR) were assessed. Medical records were reviewed for hemoglobin A1c (HbA1c), DKA status, and other clinical factors at diagnosis. Within the group with T1DM, 17 children presented in DKA and 49 did not. After adjusting for age, gender, and socioeconomic status, the subgroup with T1DM and DKA at diagnosis performed worse on the long-delay SDR task compared to sibling controls (p = 0.006). In addition, within the group with T1DM, higher HbA1c at diagnosis was associated with worse performance on the long-delay SDR task (p = 0.027). Performance on the other cognitive tasks was not different across groups or subgroups. DKA and degree of hyperglycemia exposure at diagnosis have implications for long-delay spatial memory function within 3.5 months of diagnosis. These findings suggest that early detection of T1DM, which decreases risk for prolonged exposure to hyperglycemia and DKA, may avoid negative effects on memory function. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Relationship of dental diseases with coronary artery diseases and diabetes in Bangladesh

PubMed Central

Choudhury, Arup Ratan; Choudhury, Kamrun Nahar

2016-01-01

Background Evidence suggests that dental diseases might have a role in the development and progression of coronary artery diseases (CAD) and diabetes mellitus (DM). The objective of this study was to determine the relationship of dental diseases with CAD and DM in Bangladesh. Methods We conducted a cross-sectional study among 216 consecutive patients admitted in a tertiary hospital between March and July 2011. Data were collected on socio-demographic status, smoking, blood pressure (BP), diet, physical activities, and biochemical measurements of lipid profile, glycated hemoglobin (HbA1c), C-reactive protein (CRP), fibrinogen, creatinine kinase MB (CK-MB), troponin, serum creatinine and serum glutamic-pyruvic transaminase (SGPT). CAD was detected using echocardiographic and coronary angiogram (CAG) reports. All patients underwent oral examination for dental disease. Relationship between dental disease with CAD and DM were explored statistically. Results The mean age of the participants was 57.8±12.5 years and almost two-thirds (67.1%) were male. A great majority of the patients had CAD (90.3%) and type 2 DM (83.8%), and only 44% suffered from dental diseases. Less than one-third patients presented with acute myocardial infarction (MI), 23% with old MI, 11% unstable angina (UA) and 26.4% with non-ST elevation MI. Logistic regression results indicated that patients with DM and CAD had approximately 2.6 and 4.6 times more odds of association with dental diseases than those without DM and CAD (both P value <0.001). Conclusions This study suggests a relationship of dental diseases with CAD and DM among Bangladeshi patients. Further studies are required to confirm these relationships in large clinical studies. Screening for CAD and DM should be considered among those with dental diseases and vice-versa. PMID:27054102

Phalangeal quantitative ultrasound and metabolic control in pre-menopausal women with type 1 diabetes mellitus.

PubMed

Catalano, A; Morabito, N; Di Vieste, G; Pintaudi, B; Cucinotta, D; Lasco, A; Di Benedetto, A

2013-05-01

Several studies have reported increased fracture risk in Type 1 diabetes mellitus (T1DM). Quantitative Ultrasound (QUS) provides information on the structure and elastic properties of bone, which are important determinants of fracture risk, along with bone mineral density. To study phalangeal sites by QUS, examine bone turnover markers and analyze association between these factors with metabolic control in a population of pre-menopausal women with T1DM. Thirty-five T1DM pre-menopausal women (mean age 34.5 ± 6.8 yr) attending the Diabetic Outpatients Clinic in the Department of Internal Medicine, University of Messina, were consecutively enrolled and divided into two groups, taking into account the mean value of glycated hemoglobin in the last three years. Twenty healthy age-matched women served as controls. Phalangeal ultrasound measurements [Amplitude Dependent Speed of Sound (AD-SoS), Ultrasound Bone Profile Index (UBPI), TScore, Z-Score] were performed using a DBM Sonic Bone Profiler. Osteocalcin and deoxypyridinoline served as markers of bone formation and bone resorption, respectively. T1DM women with poor metabolic control showed lower phalangeal QUS values compared to healthy controls (p<0.01) and T1DM women with good metabolic control (p<0.05). No significant differences in QUS measurements were detected between T1DM women with good metabolic control and healthy controls. Lower bone formation and increased bone resorption, although not statistically significant, were observed in patients with poor metabolic control in comparison to patients with good metabolic control. Poor metabolic control may worsen the quality of bone in T1DM. Phalangeal QUS could be considered as a tool to screen T1DM women for osteoporosis in pre-menopausal age.

Repeated Administration of a Mutant Cocaine Esterase: Effects on Plasma Cocaine Levels, Cocaine-Induced Cardiovascular Activity, and Immune Responses in Rhesus Monkeys

PubMed Central

Collins, Gregory T.; Brim, Remy L.; Noon, Kathleen R.; Narasimhan, Diwahar; Lukacs, Nicholas W.; Sunahara, Roger K.; Woods, James H.

2012-01-01

Previous studies have demonstrated the capacity of a long-acting mutant form of a naturally occurring bacterial double mutant cocaine esterase (DM CocE) to antagonize the reinforcing, discriminative, convulsant, and lethal effects of cocaine in rodents and reverse the increases in mean arterial pressure (MAP) and heart rate (HR) produced by cocaine in rhesus monkeys. This study was aimed at characterizing the immunologic responses to repeated dosing with DM CocE and determining whether the development of anti-CocE antibodies altered the capacity of DM CocE to reduce plasma cocaine levels and ameliorate the cardiovascular effects of cocaine in rhesus monkeys. Under control conditions, intravenous administration of cocaine (3 mg/kg) resulted in a rapid increase in the plasma concentration of cocaine (n = 2) and long-lasting increases in MAP and HR (n = 3). Administration of DM CocE (0.32 mg/kg i.v.) 10 min after cocaine resulted in a rapid hydrolysis of cocaine with plasma levels below detection limits within 5 to 8 min. Elevations in MAP and HR were significantly reduced within 25 and 50 min of DM CocE administration, respectively. Although slight (10-fold) increases in anti-CocE antibodies were observed after the fourth administration of DM CocE, these antibodies did not alter the capacity of DM CocE to reduce plasma cocaine levels or ameliorate cocaine's cardiovascular effects. Anti-CocE titers were transient and generally dissipated within 8 weeks. Together, these results suggest that highly efficient cocaine esterases, such as DM CocE, may provide a novel and effective therapeutic for the treatment of acute cocaine intoxication in humans. PMID:22518021

A comparative study of volumetric breast density estimation in digital mammography and magnetic resonance imaging: results from a high-risk population

NASA Astrophysics Data System (ADS)

Kontos, Despina; Xing, Ye; Bakic, Predrag R.; Conant, Emily F.; Maidment, Andrew D. A.

2010-03-01

We performed a study to compare methods for volumetric breast density estimation in digital mammography (DM) and magnetic resonance imaging (MRI) for a high-risk population of women. DM and MRI images of the unaffected breast from 32 women with recently detected abnormalities and/or previously diagnosed breast cancer (age range 31-78 yrs, mean 50.3 yrs) were retrospectively analyzed. DM images were analyzed using QuantraTM (Hologic Inc). The MRI images were analyzed using a fuzzy-C-means segmentation algorithm on the T1 map. Both methods were compared to Cumulus (Univ. Toronto). Volumetric breast density estimates from DM and MRI are highly correlated (r=0.90, p<=0.001). The correlation between the volumetric and the area-based density measures is lower and depends on the training background of the Cumulus software user (r=0.73-84, p<=0.001). In terms of absolute values, MRI provides the lowest volumetric estimates (mean=14.63%), followed by the DM volumetric (mean=22.72%) and area-based measures (mean=29.35%). The MRI estimates of the fibroglandular volume are statistically significantly lower than the DM estimates for women with very low-density breasts (p<=0.001). We attribute these differences to potential partial volume effects in MRI and differences in the computational aspects of the image analysis methods in MRI and DM. The good correlation between the volumetric and the area-based measures, shown to correlate with breast cancer risk, suggests that both DM and MRI volumetric breast density measures can aid in breast cancer risk assessment. Further work is underway to fully-investigate the association between volumetric breast density measures and breast cancer risk.

Combined use of fasting plasma glucose and glycated hemoglobin A1c in a stepwise fashion to detect undiagnosed diabetes mellitus.

PubMed

Nakagami, Tomoko; Tominaga, Makoto; Nishimura, Rimei; Daimon, Makoto; Oizumi, Toshihide; Yoshiike, Nobuo; Tajima, Naoko

2007-09-01

Type 2 diabetes mellitus (DM) is a common and serious condition related with considerable morbidity. Screening for DM is one strategy for reducing this burden. In Japan National Diabetes Screening Program (JNDSP) guideline, the combined use of fasting plasma glucose (FPG) and glycated hemoglobin A1c (HbA1c) in a stepwise fashion has been recommended to identify the group of people needing life-style counseling or medical care. However, the efficacy of this program has not been fully evaluated, as an oral glucose tolerance test (OGTT) is not mandatory in the guideline. The aim of this study was to assess the validity of the screening test scenario, in which an OGTT would be applied to people needing life-style counseling or medical care on this guideline: FPG 110-125 mg/dl and HbA1c over 5.5%. Subjects were 1,726 inhabitants without a previous history of DM in the Funagata study, which is a population-based survey conducted in Yamagata prefecture to clarify the risk factors, related conditions, and consequences of DM. DM was diagnosed according to the 1999 World Health Organization criteria. The prevalence of undiagnosed DM was 6.6%. The tested screening scenario gave a sensitivity of 55.3%, a specificity of 98.4%, a positive predictive value of 70.8%, and a negative predictive value of 96.9% for undiagnosed DM. In conclusion, the screening test scenario, in which an OGTT would be followed by the combined use of FPG and HbA1c in a stepwise fashion according to the JNDSP guideline, was not effective in identifying people with undiagnosed DM.

Hemostasis and Lipoprotein Indices Signify Exacerbated Lung Injury in TB With Diabetes Comorbidity.

PubMed

Dong, Zhengwei; Shi, Jingyun; Dorhoi, Anca; Zhang, Jie; Soodeen-Lalloo, Adiilah K; Tan, WenLing; Yin, Hongyun; Sha, Wei; Li, Weitong; Zheng, Ruijuan; Liu, Zhonghua; Yang, Hua; Qin, Lianhua; Wang, Jie; Huang, Xiaochen; Wu, Chunyan; Kaufmann, Stefan H E; Feng, Yonghong

2018-05-01

Exacerbated immunopathology is a frequent consequence of TB that is complicated by diabetes mellitus (DM); however, the underlying mechanisms are still poorly defined. In the two groups of age- and sex-matched patients with TB and DM (DM-TB) and with TB and without DM, we microscopically evaluated the areas of caseous necrosis and graded the extent of perinecrotic fibrosis in lung biopsies from the sputum smear-negative (SN) patients. We scored acid-fast bacilli in sputum smear-positive (SP) patients and compiled CT scan data from both the SN and SP patients. We compared inflammatory biomarkers and routine hematologic and biochemical parameters. Binary logistic regression analyses were applied to define the indices associated with the extent of lung injury. Enlarged caseous necrotic areas with exacerbated fibrotic encapsulations were found in SN patients with DM-TB, consistent with the higher ratio of thick-walled cavities and more bacilli in the sputum from SP patients with DM-TB. Larger necrotic foci were detected in men compared with women within the SN TB groups. Significantly higher fibrinogen and lower high-density lipoprotein cholesterol (HDL-C) were observed in SN patients with DM-TB. Regression analyses revealed that diabetes, activation of the coagulation pathway (shown by increased platelet distribution width, decreased mean platelet volume, and shortened prothrombin time), and dyslipidemia (shown by decreased low-density lipoprotein cholesterol, HDL-C, and apolipoprotein A) are risk factors for severe lung lesions in both SN and SP patients with TB. Hemostasis and dyslipidemia are associated with granuloma necrosis and fibroplasia leading to exacerbated lung damage in TB, especially in patients with DM-TB. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Detection of relationships between SUDOSCAN with estimated glomerular filtration rate (eGFR) in Chinese patients with type 2 diabetes.

PubMed

Mao, Fei; Zhu, Xiaoming; Lu, Bin; Li, Yiming

2018-04-01

SUDOSCAN (Impeto Medical, Paris, France) has been proved to be a new and non-invasive method in detecting renal dysfunction in type 2 diabetes mellitus (T2DM) patients. In this study, we sought to compare the result of diabetic kidney dysfunction score (DKD-score) of SUDOSCAN with estimated glomerular filtration rate (eGFR) by using quantile regression analysis, which was completely different from previous studies. A total number of 223 Chinese T2DM patients were enrolled in the study. SUDOSCAN, renal function test (including blood urea nitrogen, creatinine and uric acid) and 99 mTc-diethylenetriamine pentaacetic acid ( 99 mTc-DTPA) renal dynamic imaging were performed in all T2DM patients. DKD-score of SUDOSCAN was compared with eGFR detected by 99 mTc-DTPA renal dynamic imaging through quantile regression analysis. Its validation and utility was further determined through bias and precision test. The quantile regression analysis demonstrated the relationship with eGFR was inverse and significant for almost all percentiles of DKD-score. The coefficients decreased as the percentile of DKD-score increased. And in validation data set, both the bias and precision were increased with the eGFR (median difference, -21.2 ml/min/1.73 m 2 for all individuals vs. -4.6 ml/min/1.73 m 2 for eGFR between 0 and 59 ml/min/1.73 m 2 ; interquartile range [IQR] for the difference, -25.4 ml/min/1.73 m 2 vs. -14.7 ml/min/1.73 m 2 ). The eGFR category misclassification rate were 10% in eGFR 0-59 ml/min/1.73 m 2 group, 57.3% in 60-90 group, and 87.2% in eGFR > 90 ml/min/1.73 m 2 group. DKD-score of SUDOSCAN could be used to detect renal dysfunction in T2DM patients. A higher prognostic value of DKD-score was detected when eGFR level was lower. Copyright © 2018 Elsevier B.V. All rights reserved.

Mitochondrial DNA mutations in diabetes mellitus patients in Chinese Han population.

PubMed

Wang, Suijun; Wu, Songhua; Zheng, Taishan; Yang, Zhen; Ma, Xiaojing; Jia, Weiping; Xiang, Kunsan

2013-12-01

Mutations of mitochondrial DNA are associated with diabetes mellitus (DM). The present case-control study aimed to investigate the mutations of mitochondrial DNA in DM patients of Chinese Han ethnicity. A total of 770 DM patients and 309 healthy control individuals were enrolled. The mitochondrial DNA was extracted from blood cells and analyzed by the polymerase chain reaction-restriction fragment length polymorphism assay. In the diabetes group, there were 13 (1.69%) individuals carrying the mt3243 A → G mutation while none of the healthy control had this mutation. Though the 14709, 3316, 3394, and 12026 mutation variants were identified in 9, 17, 18 and 28 in DM patients respectively, there were no significant differences compared with control group. And the 3256, 8296, 8344, 8363, 3426 and 12258 mutations were not detected in either group. In the diabetes group, two double mutations were identified: A3243G+T3394C and A3243G+A12026G. Our data suggested that mitochondrial gene tRNA(Leu(UUR)) 3243 A → G mutation may be one risk of prevalence of DM and associated with worse clinical status in Chinese Han population. © 2013 Elsevier B.V. All rights reserved.

Health policy analysis for prevention and control of cardiovascular diseases and diabetes mellitus in Turkey.

PubMed

Kilic, Bulent; Kalaca, Sibel; Unal, Belgin; Phillimore, Peter; Zaman, Shahaduz

2015-01-01

Current capacity of the Turkish health system is reviewed to evaluate and develop appropriate policies for cardiovascular diseases (CVD), diabetes mellitus (DM) and related risk factors. This paper qualitatively evaluates existing policies; interviews with key informants (KIs); and rapid appraisal fieldwork in clinical settings about CVD-DM through the framework of Walt and Gilson (Health Policy Plan 9:353-370, 1994). Document review shows that prevention and control of CVD-DM were strongly addressed in Turkey, yet no document mentioned country-wide early detection or screening programs. KIs indicated over-fragmented management of CVD-DM by the Ministry of Health (MoH). Coordination among the MoH, organizational structure at provincial level and civil society organizations are poor where mutual trust is a significant problem according to KIs. Clinical setting findings point to a complete lack of a referral structure and a lack of follow-up, compounding the absence of functioning health information systems for patient records. Primary care services for CVD-DM require urgent attention, focusing particularly on the training of staff in public facilities, the integration of patient data, referrals and follow-up across all levels of the health system.

Micro-organization of humic acids in aqueous solutions

NASA Astrophysics Data System (ADS)

Klučáková, Martina; Věžníková, Kateřina

2017-09-01

The methods of dynamic light scattering and micro-rheology were used to investigate the molecular organization of humic acids in solutions. The obtained results were supplemented by ultraviolet/visible spectrometry and measurement of the zeta potential. Particle tracking micro-rheology was used for the first time as a novel method in humic research. Solutions of humic acids were prepared in three different mediums: NaOH, NaCl, and NaOH neutralized by HCl after dissolution of the humic sample. The molecular organization of humic acids was studied over a wide concentration range (0.01-10 g dm-3). Two breaks were detected in the obtained concentration dependencies. The rearrangements were observed at concentrations around 0.02 g dm-3 and 1 g dm-3. Changes in the measured values observed at around 0.02 g dm-3 were less noticeable and were related to the formation of particles between 100 and 1000 nm in size and the strong bimodal character of humic systems diluted by NaCl. The ;switch-over point; at around 1 g dm-3 indicated changes in the secondary structure of humic acids connected with the increase in colloidal stability (decrease of zeta potential), the decrease in polydispersity, and minimal values of viscosity.

Gamma rays from dark matter annihilation in three-loop radiative neutrino mass generation models

NASA Astrophysics Data System (ADS)

Chowdhury, Talal Ahmed; Nasri, Salah

2018-07-01

We present the Sommerfeld enhanced Dark Matter (DM) annihilation into gamma ray for a class of three-loop radiative neutrino mass models with large electroweak multiplets where the DM mass is in O(TeV) range. We show that in this model, the DM annihilation rate becomes more prominent for larger multiplets and it is already within the reach of currently operating Imaging Atmospheric Cherenkov telescopes (IACTs), High Energy Stereoscopic System (H.E.S.S.). Furthermore, Cherenkov Telescope Array (CTA), which will begin operating in 2030, will improve this sensitivity by a factor of O (10) and may exclude a large portion of parameter space of this radiative neutrino mass model with larger electroweak multiplet. This implies that the only viable option is the model with lowest electroweak multiplets i.e. singlets of SU(2)L where the DM annihilation rate is not Sommerfeld enhanced and hence it is not yet constrained by the indirect detection limits from H.E.S.S. or future CTA.

Concentration sensor based on a tilted fiber Bragg grating for anions monitoring

NASA Astrophysics Data System (ADS)

Melo, L. B.; Rodrigues, J. M. M.; Farinha, A. S. F.; Marques, C. A.; Bilro, L.; Alberto, N.; Tomé, J. P. C.; Nogueira, R. N.

2014-08-01

The ubiquity and importance of anions in many crucial roles accounts for the current high interest in the design and preparation of effective sensors for these species. Therefore, a tilted fiber Bragg grating sensor was fabricated to investigate individual detection of different anion concentrations in ethyl acetate, namely acetate, fluoride and chloride. The influence of the refractive index on the transmission spectrum of a tilted fiber Bragg grating was determined by developing a new demodulation method. This is based on the calculation of the standard deviation between the cladding modes of the transmission spectrum and its smoothing function. The standard deviation method was used to monitor concentrations of different anions. The sensor resolution obtained for the anion acetate, fluoride and chloride is 79 × 10-5 mol/dm3, 119 × 10-5 mol/dm3 and 78 × 10-5 mol/dm3, respectively, within the concentration range of (39-396) × 10-5 mol/dm3.

Inoculation of α-synuclein preformed fibrils into the mouse gastrointestinal tract induces Lewy body-like aggregates in the brainstem via the vagus nerve.

PubMed

Uemura, Norihito; Yagi, Hisashi; Uemura, Maiko T; Hatanaka, Yusuke; Yamakado, Hodaka; Takahashi, Ryosuke

2018-05-11

Intraneuronal α-synuclein (α-Syn) aggregates known as Lewy bodies (LBs) and the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) are the pathological hallmarks of Parkinson's disease (PD). Braak's hypothesis based on autopsy studies suggests that Lewy pathology initially occurs in the enteric nervous system (ENS) and then travels retrogradely to the dorsal motor nucleus of the vagus nerve (dmX), proceeding from there in a caudo-rostral direction. Recent evidence that α-Syn aggregates propagate between interconnected neurons supports this hypothesis. However, there is no direct evidence demonstrating this transmission from the ENS to the dmX and then to the SNpc. We inoculated α-Syn preformed fibrils (PFFs) or phosphate-buffered saline (PBS) into the mouse gastric wall and analyzed the progression of the pathology. The mice inoculated with α-Syn PFFs, but not with PBS, developed phosphorylated α-Syn (p-α-Syn)-positive LB-like aggregates in the dmX at 45 days postinoculation. This aggregate formation was completely abolished when vagotomy was performed prior to inoculation of α-Syn PFFs, suggesting that the aggregates in the dmX were retrogradely induced via the vagus nerve. Unexpectedly, the number of neurons containing p-α-Syn-positive aggregates in the dmX decreased over time, and no further caudo-rostral propagation beyond the dmX was observed up to 12 months postinoculation. P-α-Syn-positive aggregates were also present in the myenteric plexus at 12 months postinoculation. However, unlike in patients with PD, there was no cell-type specificity in neurons containing those aggregates in this model. These results indicate that α-Syn PFF inoculation into the mouse gastrointestinal tract can induce α-Syn pathology resembling that of very early PD, but other factors are apparently required if further progression of PD pathology is to be replicated in this animal model.

The current total economic burden of diabetes mellitus in the Netherlands.

PubMed

Peters, M L; Huisman, E L; Schoonen, M; Wolffenbuttel, B H R

2017-09-01

Insight into the total economic burden of diabetes mellitus (DM) is essential for decision makers and payers. Currently available estimates for the Netherlands only include part of the total burden or are no longer up-to-date. Therefore, this study aimed to determine the current total economic burden of DM and its complications in the Netherlands, by including all the relevant cost components. The study combined a systematic literature review to identify all relevant published information and a targeted review to identify relevant information in the grey literature. The identified evidence was then combined to estimate the current total economic burden. In 2016, there were an estimated 1.1 million DM patients in the Netherlands, of whom approximately 10% had type 1 and 90% had type 2 DM. The estimated current total economic burden of DM was € 6.8 billion in 2016. Healthcare costs (excluding costs of complications) were € 1.6 billion, direct costs of complications were € 1.3 billion and indirect costs due to productivity losses, welfare payments and complications were € 4.0 billion. DM and its complications pose a substantial economic burden to the Netherlands, which is expected to rise due to changing demographics and lifestyle. Indirect costs, such as welfare payments, accounted for a large portion of the current total economic burden of DM, while these cost components are often not included in cost estimations. Publicly available data for key cost drivers such as complications were scarce.

The Contribution of Biogeographic Ancestry and Socioeconomic Status to Racial/Ethnic Disparities in Type 2 Diabetes: Results from the Boston Area Community Health (BACH) Survey

PubMed Central

Piccolo, Rebecca S.; Pearce, Neil; Araujo, Andre B.; McKinlay, John B.

2014-01-01

Purpose Racial/ethnic disparities in the incidence of type 2 diabetes (T2DM) are well documented and many researchers have proposed that biogeographical ancestry (BGA) may play a role in these disparities. However, studies examining the role of BGA on T2DM have produced mixed results to date. Therefore, the objective of this research is to quantify the contribution of BGA to racial/ethnic disparities in T2DM incidence controlling for the mediating influences of socioeconomic factors. Methods We analyzed data from the Boston Area Community Health (BACH) Survey, a prospective cohort with approximately equal numbers of Black, Hispanic, and White participants. We used Ancestry Informative Markers to calculate the percentages of West African and Native American ancestry of participants. We used logistic regression with g-computation to analyze the contribution of BGA and socioeconomic factors to racial/ethnic disparities in T2DM incidence. Results We found that socioeconomic factors accounted for 44.7% of the total effect of T2DM attributed to Black race and 54.9% of the effect attributed to Hispanic ethnicity. We found that BGA had almost no direct association with T2DM and was almost entirely mediated by self-identified race/ethnicity and socioeconomic factors. Conclusions It is likely that non-genetic factors, specifically socioeconomic factors, account for much of the reported racial/ethnic disparities in T2DM incidence. PMID:25088753

The association of cytotoxic T-lymphocyte antigen-4 + 49A/G and CT60 polymorphisms with type 1 diabetes and latent autoimmune diabetes in Chinese adults.

PubMed

Jin, P; Xiang, B; Huang, G; Zhou, Z

2015-02-01

The aim of this study was to investigate the association of cytotoxic T-lymphocyte antigen-4 (CTLA-4) + 49A/G and CT60 polymorphisms with latent autoimmune diabetes in adults (LADA) and the genetic differences between LADA, type 1 diabetes (T1DM), and type 2 diabetes (T2DM) in a Chinese population. A total of 231 LADA, 402 T1DM, and 330 T2DM patients as well as 482 nondiabetic controls were recruited in the study. CTLA-4 + 49A/G and CT60 polymorphisms were analyzed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). The level of glutamic acid decarboxylase antibodies (GADAs) was detected by a radioligand binding assay. The CTLA-4 + 49A/G risk genotype GG was most frequent in T1DM patients (45.3%), followed by LADA patients (44.2%) and T2DM patients (38.8%). Significantly higher frequencies of the risk genotype GG were observed in the T1DM (OR = 1.532, 95% CI 1.168-2.010, P = 0.002) and LADA patients (OR = 1.464, 95% CI 1.063-2.017, P = 0.019). The frequencies of the CTLA-4 CT60 risk genotype GG were 65.2, 61.9, 58.5, and 56.4% in the T1DM, LADA, T2DM, and control groups, respectively. The CTLA-4 CT60 GG risk genotypes were only associated with T1DM (OR = 1.445, 95% CI 1.1-1.898, P = 0.008). Compared with controls, patients having a high titer of GADA (GADA ≥ 180 IU/ml) had higher frequencies of the GG risk genotype of CTLA-4 + 49 A/G (49.4% vs. 35.1% OR = 1.807, 95% CI 1.125-2.903, P = 0.014), but there was no difference between patients having a low titer of GADA and controls. The CTLA-4 + 49 A/G polymorphism confers genetic susceptibility to LADA and T1DM, while the CTLA-4 CT60 polymorphism is only associated with T1DM in Chinese population. The CTLA-4 + 49 A/G genotype distribution in LADA is associated with the GADA level.

SIRT6 expression and oxidative DNA damage in individuals with prediabetes and type 2 diabetes mellitus.

PubMed

Çalışkan, Z; Mutlu, T; Güven, M; Tunçdemir, M; Niyazioğlu, M; Hacioglu, Y; Dincer, Y

2018-02-05

Sirtuins (SIRTs) is a family of NAD + dependent histone deacetylases. SIRT6 takes play in glucose homeostasis, genomic stability and DNA repair. Although increased oxidative DNA damage and decreased DNA repair activity were determined in diabetes mellitus, the possible relation between level of oxidative DNA damage and SIRT6 expression has not been investigated so far. We determined SIRT6 expression and urinary 8-hydroxy deoxyguanosine (8-OHdG) levels, marker of oxidative DNA damage, in cases with prediabetes (PreDM) and type 2 diabetes mellitus (T2DM). SIRT6 gene expression was determined in peripheral blood leukocytes of 70 patients with type 2 diabetes, 50 cases in prediabetic stage and 40 healthy subjects. SIRT6 mRNA levels were determined by quantitive real time- polymerase chain reaction. SIRT6 protein was detected by immunocytochemical staining. Urinary 8-hydroxy deoxyguanosine (8-OHdG) levels were measured by ELISA. There was no significant difference between groups for SIRT6 mRNA level. SIRT6 immunopositivity in T2DM group was lower when compared to those in preDM group (P<0.05). SIRT6 positive cell number in T2DM and preDM groups were lower in comparison to control group (P<0.01 for both), however, when study groups were subdivided into two groups according to their age, the difference between preDM and control groups disappeared in both mid-aged and old-aged groups. The urinary 8-OHdG level was found to be higher in the T2DM group in comparison to preDM group (P<0.05). When age is taken into consideration, urinary 8-OHdG level in the T2DM group was found to be higher than those in both preDM and control groups in the old-aged cases but no significant difference was determined between groups in the mid-aged cases. There was no relation between SIRT6 expression and urinary 8-OHDG excretion. It was concluded that SIRT6 may take play in development of T2DM but this effect seems to be independent from repair of oxidative DNA damage. Copyright © 2017 Elsevier B.V. All rights reserved.

Similarity of a 16.5kDa tegumental protein of the human liver fluke Opisthorchis viverrini to nematode cytoplasmic motility protein.

PubMed

Labbunruang, Nipawan; Phadungsil, Wansika; Tesana, Smarn; Smooker, Peter M; Grams, Rudi

2016-05-01

Opisthorchis viverrini is the causative agent of human opisthorchiasis in Thailand and long lasting infection with the parasite has been correlated with the development of cholangiocarcinoma. In this work we have molecularly characterized the first member of a protein family carrying two DM9 repeats in this parasite (OvDM9-1). InterPro and other protein family databases describe the DM9 repeat as a protein domain of unknown function that has been first noted in Drosophila melanogaster. Two paralogous proteins have been partially characterized in the genus Fasciola, Fasciola hepatica TP16.5, a novel tegumental antigen in human fascioliasis and, recently F. gigantica DM9-1, a parenchymal protein with structural similarity to nematode cytoplasmic motility protein (MFP2). In this study, we show further evidence that this family of trematode proteins is related to MFP2 in sequence and structure. Soluble recombinant OvDM9-1 was used for structural analyses and for production of specific antisera. The native protein was detected in soluble and insoluble crude worm extracts and in seemingly various oligomeric forms in the latter. The potential for oligomerization was supported by cross-linking experiments of recombinant OvDM9-1. Structure prediction suggested a β-rich secondary structure of the protein and this was supported by a circular dichroism analysis. Molecular modeling in Phyre2 identified both MFP2 domains as distant homologs of OvDM9-1. The protein was located in tegumental type tissue and the cecal epithelium in the mature parasite. Recombinant OvDM9-1 was used as target in indirect ELISA but sera from infected hamsters showed only marginal reactivity towards it. It is proposed that OvDM9-1 and other members of this protein family have a role in cellular transport through functions on the cytoskeleton. Copyright © 2016 Elsevier B.V. All rights reserved.

Association of polymorphisms at the ADIPOR1 regulatory region with type 2 diabetes and body mass index in a Brazilian population with European or African ancestry.

PubMed

Yeh, E; Kimura, L; Errera, F I V; Angeli, C B; Mingroni-Netto, R C; Silva, M E R; Canani, L H S; Passos-Bueno, M R

2008-06-01

Association studies between ADIPOR1 genetic variants and predisposition to type 2 diabetes (DM2) have provided contradictory results. We determined if two single nucleotide polymorphisms (SNP c.-8503G>A and SNP c.10225C>G) in regulatory regions of ADIPOR1 in 567 Brazilian individuals of European (EA; N = 443) or African (AfA; N = 124) ancestry from rural (quilombo remnants; N = 439) and urban (N = 567) areas. We detected a significant effect of ethnicity on the distribution of the allelic frequencies of both SNPs in these populations (EA: -8503A = 0.27; AfA: -8503A = 0.16; P = 0.001 and EA: 10225G = 0.35; AfA: 10225G = 0.51; P < 0.001). Neither of the polymorphisms were associated with DM2 in the case-control study in EA (SNP c.-8503G>A: DM2 group -8503A = 0.26; control group -8503A = 0.30; P = 0.14/SNP 10225C>G: DM2 group 10225G = 0.37; control group 10225G = 0.32; P = 0.40) and AfA populations (SNP c.-8503G>A: DM2 group -8503A = 0.16; control group -8503A = 0.15; P = 0.34/SNP 10225C>G: DM2 group 10225G = 0.51; control group 10225G = 0.52; P = 0.50). Similarly, none of the polymorphisms were associated with metabolic/anthropometric risk factors for DM2 in any of the three populations, except for HDL cholesterol, which was significantly higher in AfA heterozygotes (GC = 53.75 +/- 17.26 mg/dL) than in homozygotes. We conclude that ADIPOR1 polymorphisms are unlikely to be major risk factors for DM2 or for metabolic/anthropometric measurements that represent risk factors for DM2 in populations of European and African ancestries.

T-DM1, a novel antibody–drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo

PubMed Central

English, Diana P; Bellone, Stefania; Schwab, Carlton L; Bortolomai, Ileana; Bonazzoli, Elena; Cocco, Emiliano; Buza, Natalia; Hui, Pei; Lopez, Salvatore; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Rutherford, Thomas J; Santin, Alessandro D

2014-01-01

Amplification of c-erbB2 has been reported in over 30% of uterine serous carcinoma (USC) and found to confer poor survival because of high proliferation and increased resistance to therapy. In this study, we evaluated for the first time Trastuzumab emtansine (T-DM1), a novel antibody–drug conjugate, against multiple epidermal growth factor receptor-2 (HER2)-positive USC cells in vitro followed by developing a supportive in vivo model. Fifteen primary USC cell lines were assessed by immunohistochemistry (IHC) and flow cytometry for HER2 protein expression. C-erbB2 gene amplification was evaluated using fluorescent in situ hybridization. Sensitivity to T-DM1 and trastuzumab (T)-induced antibody-dependent cell-mediated cytotoxicity was evaluated in 5-h chromium release assays. T-DM1 and T cytostatic and apoptotic activities were evaluated using flow-cytometry-based proliferation assays. In vivo activity of T-DM1 versus T in USC xenografts in SCID mice was also evaluated. High levels of HER2 protein overexpression and HER2 gene amplification were detected in 33% of USC cell lines. T-DM1 was considerably more effective than trastuzumab in inhibiting cell proliferation and in causing apoptosis (P = 0.004) of USC showing HER2 overexpression. Importantly, T-DM1 was highly active at reducing tumor formation in vivo in USC xenografts overexpressing HER2 (P = 0.04) and mice treated with TDM-1 had significantly longer survival when compared to T-treated mice and control mice (P ≤ 0.0001). T-DM1 shows promising antitumor effect in HER2-positive USC cell lines and USC xenografts and its activity is significantly higher when compared to T. T-DM1 may represent a novel treatment option for HER2-positive USC patients with disease refractory to trastuzumab and traditional chemotherapy. PMID:24890382

T-DM1, a novel antibody-drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo.

PubMed

English, Diana P; Bellone, Stefania; Schwab, Carlton L; Bortolomai, Ileana; Bonazzoli, Elena; Cocco, Emiliano; Buza, Natalia; Hui, Pei; Lopez, Salvatore; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Rutherford, Thomas J; Santin, Alessandro D

2014-10-01

Amplification of c-erbB2 has been reported in over 30% of uterine serous carcinoma (USC) and found to confer poor survival because of high proliferation and increased resistance to therapy. In this study, we evaluated for the first time Trastuzumab emtansine (T-DM1), a novel antibody-drug conjugate, against multiple epidermal growth factor receptor-2 (HER2)-positive USC cells in vitro followed by developing a supportive in vivo model. Fifteen primary USC cell lines were assessed by immunohistochemistry (IHC) and flow cytometry for HER2 protein expression. C-erbB2 gene amplification was evaluated using fluorescent in situ hybridization. Sensitivity to T-DM1 and trastuzumab (T)-induced antibody-dependent cell-mediated cytotoxicity was evaluated in 5-h chromium release assays. T-DM1 and T cytostatic and apoptotic activities were evaluated using flow-cytometry-based proliferation assays. In vivo activity of T-DM1 versus T in USC xenografts in SCID mice was also evaluated. High levels of HER2 protein overexpression and HER2 gene amplification were detected in 33% of USC cell lines. T-DM1 was considerably more effective than trastuzumab in inhibiting cell proliferation and in causing apoptosis (P = 0.004) of USC showing HER2 overexpression. Importantly, T-DM1 was highly active at reducing tumor formation in vivo in USC xenografts overexpressing HER2 (P = 0.04) and mice treated with TDM-1 had significantly longer survival when compared to T-treated mice and control mice (P ≤ 0.0001). T-DM1 shows promising antitumor effect in HER2-positive USC cell lines and USC xenografts and its activity is significantly higher when compared to T. T-DM1 may represent a novel treatment option for HER2-positive USC patients with disease refractory to trastuzumab and traditional chemotherapy. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

A Genome-Wide Association Search for Type 2 Diabetes Genes in African Americans

PubMed Central

Palmer, Nicholette D.; McDonough, Caitrin W.; Hicks, Pamela J.; Roh, Bong H.; Wing, Maria R.; An, S. Sandy; Hester, Jessica M.; Cooke, Jessica N.; Bostrom, Meredith A.; Rudock, Megan E.; Talbert, Matthew E.; Lewis, Joshua P.; Ferrara, Assiamira; Lu, Lingyi; Ziegler, Julie T.; Sale, Michele M.; Divers, Jasmin; Shriner, Daniel; Adeyemo, Adebowale; Rotimi, Charles N.; Ng, Maggie C. Y.; Langefeld, Carl D.; Freedman, Barry I.; Bowden, Donald W.

2012-01-01

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10−8). SNP rs7560163 (P = 7.0×10−9, OR (95% CI) = 0.75 (0.67–0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10−5) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations. PMID:22238593

An algorithm to improve diagnostic accuracy in diabetes in computerised problem orientated medical records (POMR) compared with an established algorithm developed in episode orientated records (EOMR).

PubMed

de Lusignan, Simon; Liaw, Siaw-Teng; Dedman, Daniel; Khunti, Kamlesh; Sadek, Khaled; Jones, Simon

2015-06-05

An algorithm that detects errors in diagnosis, classification or coding of diabetes in primary care computerised medial record (CMR) systems is currently available. However, this was developed on CMR systems that are episode orientated medical records (EOMR); and do not force the user to always code a problem or link data to an existing one. More strictly problem orientated medical record (POMR) systems mandate recording a problem and linking consultation data to them. To compare the rates of detection of diagnostic accuracy using an algorithm developed in EOMR with a new POMR specific algorithm. We used data from The Health Improvement Network (THIN) database (N = 2,466,364) to identify a population of 100,513 (4.08%) patients considered likely to have diabetes. We recalibrated algorithms designed to classify cases of diabetes to take account of that POMR enforced coding consistency in the computerised medical record systems [In Practice Systems (InPS) Vision] that contribute data to THIN. We explored the different proportions of people classified as having type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) and with diabetes unclassifiable as either T1DM or T2DM. We compared proportions using chi-square tests and used Tukey's test to compare the characteristics of the people in each group. The prevalence of T1DM using the original EOMR algorithm was 0.38% (9,264/2,466,364), and for T2DM 3.22% (79,417/2,466,364). The prevalence using the new POMR algorithm was 0.31% (7,750/2,466,364) T1DM and 3.65% (89,990/2,466,364) T2DM. The EOMR algorithms also left more people unclassified 11,439 (12%), as to their type of diabetes compared with 2,380 (2.4%), for the new algorithm. Those people who were only classified by the EOMR system differed in terms of older age, and apparently better glycaemic control, despite not being prescribed medication for their diabetes (p < 0.005). Increasing the degree of problem orientation of the medical record system can improve the accuracy of recording of diagnoses and, therefore, the accuracy of using routinely collected data from CMRs to determine the prevalence of diabetes mellitus; data processing strategies should reflect the degree of problem orientation.

Plant Insecticide L-Canavanine Repels Drosophila via the Insect Orphan GPCR DmX

PubMed Central

Framery, Bérénice; Bockaert, Joël; Parmentier, Marie-Laure; Grau, Yves

2009-01-01

For all animals, the taste sense is crucial to detect and avoid ingesting toxic molecules. Many toxins are synthesized by plants as a defense mechanism against insect predation. One example of such a natural toxic molecule is l-canavanine, a nonprotein amino acid found in the seeds of many legumes. Whether and how insects are informed that some plants contain l-canavanine remains to be elucidated. In insects, the taste sense relies on gustatory receptors forming the gustatory receptor (Gr) family. Gr proteins display highly divergent sequences, suggesting that they could cover the entire range of tastants. However, one cannot exclude the possibility of evolutionarily independent taste receptors. Here, we show that l-canavanine is not only toxic, but is also a repellent for Drosophila. Using a pharmacogenetic approach, we find that flies sense food containing this poison by the DmX receptor. DmXR is an insect orphan G-protein–coupled receptor that has partially diverged in its ligand binding pocket from the metabotropic glutamate receptor family. Blockade of DmXR function with an antagonist lowers the repulsive effect of l-canavanine. In addition, disruption of the DmXR encoding gene, called mangetout (mtt), suppresses the l-canavanine repellent effect. To avoid the ingestion of l-canavanine, DmXR expression is required in bitter-sensitive gustatory receptor neurons, where it triggers the premature retraction of the proboscis, thus leading to the end of food searching. These findings show that the DmX receptor, which does not belong to the Gr family, fulfills a gustatory function necessary to avoid eating a natural toxin. PMID:19564899

Identifying cognitive impairment in type 2 diabetes with functional connectivity: a multivariate pattern analysis of resting state fMRI data

NASA Astrophysics Data System (ADS)

Liu, Zhenyu; Cui, Xingwei; Tang, Zhenchao; Dong, Di; Zang, Yali; Tian, Jie

2017-03-01

Previous researches have shown that type 2 diabetes mellitus (T2DM) is associated with an increased risk of cognitive impairment. Early detection of brain abnormalities at the preclinical stage can be useful for developing preventive interventions to abate cognitive decline. We aimed to investigate the whole-brain resting-state functional connectivity (RSFC) patterns of T2DM patients between 90 regions of interest (ROIs) based on the RS-fMRI data, which can be used to test the feasibility of identifying T2DM patients with cognitive impairment from other T2DM patients. 74 patients were recruited in this study and multivariate pattern analysis was utilized to assess the prediction performance. Elastic net was firstly used to select the key features for prediction, and then a linear discrimination model was constructed. 23 RSFCs were selected and it achieved the performance with classification accuracy of 90.54% and areas under the receiver operating characteristic curve (AUC) of 0.944 using ten-fold cross-validation. The results provide strong evidence that functional interactions of brain regions undergo notable alterations between T2DM patients with cognitive impairment or not. By analyzing the RSFCs that were selected as key features, we found that most of them involved the frontal or temporal. We speculated that cognitive impairment in T2DM patients mainly impacted these two lobes. Overall, the present study indicated that RSFCs undergo notable alterations associated with the cognitive impairment in T2DM patients, and it is possible to predicted cognitive impairment early with RSFCs.

Interactions between genetic polymorphisms of glucose metabolizing genes and smoking and alcohol consumption in the risk of type 2 diabetes mellitus.

PubMed

Gao, Kaiping; Ren, Yongcheng; Wang, Jinjin; Liu, Zichen; Li, Jianna; Li, Linlin; Wang, Bingyuan; Li, Hong; Wang, Yaxi; Cao, Yunkai; Ohno, Kinji; Zhai, Rihong; Liang, Zhen

2017-12-01

The impact of gene-environment interaction on diabetes remains largely unknown. We aimed to investigate if interaction between glucose metabolizing genes and lifestyle factors is associated with type 2 diabetes mellitus (T2DM). Interactions between genotypes of 4 glucose metabolizing genes (MTNR1B, KCNQ1, KLF14, and GCKR) and lifestyle factors were estimated in 722 T2DM patients and 759 controls, using multiple logistic regression. No significant associations with T2DM were detected for the single nucleotide polymorphisms of MTNR1B, KLF14 and GCKR. However, rs151290 (KCNQ1) polymorphisms were found to be associated with risk of T2DM. Compared with AA, the odds ratios (ORs) of AC or CC genotypes for developing T2DM were 1.545 (P = 0.0489) and 1.603 (P = 0.0383), respectively. In stratified analyses, the associations were stronger in smokers with CC than smokers with AA (OR = 3.668, P = 0.013); drinkers with AC (OR = 5.518, P = 0.036), CC (OR = 8.691, P = 0.0095), and AC+CC (OR = 6.764, P = 0.016) than drinkers with AA. Compared with nondrinkers with AA, drinkers who carry AC and CC had 12.072-fold (P = 0.0007) and 8.147-fold (P = 0.0052) higher risk of developing T2DM. In conclusions, rs151290 (KCNQ1) polymorphisms are associated with increased risk of T2DM, alone and especially in interaction with smoking and alcohol.

Cytogenetic and molecular identification of a wheat-Leymus mollis alien multiple substitution line from octoploid Tritileymus x Triticum durum.

PubMed

Pang, Y H; Zhao, J X; Du, W L; Li, Y L; Wang, J; Wang, L M; Wu, J; Cheng, X N; Yang, Q H; Chen, X H

2014-05-23

Leymus mollis (Trin.) Pilger (NsNsXmXm, 2n = 28), a wild relative of common wheat, possesses many traits that are potentially valuable for wheat improvement. In order to exploit and utilize the useful genes of L. mollis, we developed a multiple alien substitution line, 10DM50, from the progenies of octoploid Tritileymus M842-16 x Triticum durum cv. D4286. Genomic in situ hybridization analysis of mitosis and meiosis (metaphase I), using labeled total DNA of Psathyrostachys huashanica as probe, showed that the substitution line 10DM50 was a cytogenetically stable alien substitution line with 36 chromosomes from wheat and three pairs of Ns genome chromosomes from L. mollis. Simple sequence repeat analysis showed that the chromosomes 3D, 6D, and 7D were absent in 10DM50. Expressed sequence tag-sequence tagged sites analysis showed that new chromatin from 3Ns, 6Ns, and 7Ns of L. mollis were detected in 10DM50. We deduced that the substitution line 10DM50 was a multiple alien substitution line with the 3D, 6D, and 7D chromosomes replaced by 3Ns, 6Ns, and 7Ns from L. mollis. 10DM50 showed high resistance to leaf rust and significantly improved spike length, spikes per plant, and kernels per spike, which are correlated with higher wheat yield. These results suggest that line 10DM50 could be used as intermediate material for transferring desirable traits from L. mollis into common wheat in breeding programs.

Cultivation and partial characterization of spiroplasmas in cell cultures.

PubMed Central

Steiner, T; McGarrity, G J; Phillips, D M

1982-01-01

Spiroplasmas were propagated in the Drosophila melanogaster cell line Dm-1. Spiroplasma citri and unidentified strains (corn shunt organism, 277F [tick isolate], powder puff, BNR-1, honey bee, and OBMG) grew to 10(8) to 10(9) colony-forming units per ml and could be passaged. Cytopathic effect (CPE) varied with the infecting spiroplasma. The honey bee isolate killed Dm-1 within 2 to 4 days and produced CPE in four mammalian cells tested. At 25 degrees C, suckling mouse cataract agent produced no CPE in Dm-1 cells. Dm-1 cells did not support growth of the spiroplasmal sex ratio organism. Spiroplasmas could be detected in the cell cultures by agar inoculation, dark-field microscopy, scanning electron microscopy, and DNA fluorescent staining. The uridine phosphorylase test showed significant levels of conversion of [14C]uridine to [14C]uracil for all but some plant isolates: S. citri, corn shunt organism, lettuce, cactus, and powder puff strains, the first mycoplasmas to lack the enzyme. Primary isolations of corn shunt organism from infected corn plants were made in Dm-1 and I-XII cultures. The course of corn stunt organism infection of Dm-1 was monitored for three passages. The use of agarose and Dienes staining of the colonies improved growth and colony counting of corn stunt organism. The number of viable infected DM-1 cells decreased from 1.2 x 10(7) at passage 1 to 7.0 x 10(6) at passage 2 and 3 x 10(5) at passage 3. Images PMID:6797950

Association between IGF2BP2 Polymorphisms and Type 2 Diabetes Mellitus: A Case–Control Study and Meta-Analysis

PubMed Central

Rao, Ping; Wang, Hao; Fang, Honghong; Gao, Qing; Zhang, Jie; Song, Manshu; Zhou, Yong; Wang, Youxin; Wang, Wei

2016-01-01

Background: Genome-wide association studies (GWAS) found that IGF2BP2 rs4402960 and rs1470579 polymorphisms were associated with type 2 diabetes mellitus (T2DM) risk. Many studies have replicated this association, but yielded inconsistent results. Materials and Methods: A case-control study consisting of 461 T2DM patients and 434 health controls was conducted to detect the genetic susceptibility of IGF2BP2 in a northern Han Chinese population. A meta-analysis was to evaluate the association more precisely in Asians. Results: In the case-control study, the carriers of TT genotype at rs4402960 had a higher T2DM risk than the G carriers (TG + GG) (adjusted odd ratio (AOR) = 1.962, 95% confidence interval (95% CI) = 1.065–3.612, p = 0.031]; CC carriers at rs1470579 were more susceptible to T2DM than A carriers (CA + AA) (AOR = 2.014, 95% CI = 1.114–3.642, p = 0.021). The meta-analysis containing 36 studies demonstrated that the two polymorphisms were associated with T2DM under the allele comparison, genetic models of dominant and recessive in Asians (p < 0.05). The rs4402960 polymorphisms were significantly associated with the T2DM risk after stratification by diagnostic criterion, size of sample and average age and BMI of cases, while there’re no consistent results for rs1470579. Conclusions: Our data suggests that IGF2BP2 polymorphisms are associated with T2DM in Asian populations. PMID:27294943

Diabetes mellitus mortality in Spanish cities: Trends and geographical inequalities.

PubMed

Aguilar-Palacio, I; Martinez-Beneito, M A; Rabanaque, M J; Borrell, C; Cirera, L; Daponte, A; Domínguez-Berjón, M F; Gandarillas, A; Gotsens, M; Lorenzo-Ruano, P; Marí-Dell'Olmo, M; Nolasco, A; Saez, M; Sánchez-Villegas, P; Saurina, C; Martos, C

2017-10-01

To analyze the geographical pattern of diabetes mellitus (DM) mortality and its association with socioeconomic factors in 26 Spanish cities. We conducted an ecological study of DM mortality trends with two cross-sectional cuts (1996-2001; 2002-2007) using census tract (CT) as the unit of analysis. Smoothed standardized mortality rates (sSMR) were calculated using Bayesian models, and a socioeconomic deprivation score was calculated for each CT. In total, 27,757 deaths by DM were recorded, with higher mortality rates observed in men and in the period 1996-2001. For men, a significant association between CT deprivation score and DM mortality was observed in 6 cities in the first study period and in 7 cities in the second period. The highest relative risk was observed in Pamplona (RR, 5.13; 95% credible interval (95%CI), 1.32-15.16). For women, a significant association between CT deprivation score and DM mortality was observed in 13 cities in the first period and 8 in the second. The strongest association was observed in San Sebastián (RR, 3.44; 95%CI, 1.25-7.36). DM mortality remained stable in the majority of cities, although a marked decrease was observed in some cities, including Madrid (RR, 0.67 and 0.64 for men and women, respectively). Our findings demonstrate clear inequalities in DM mortality in Spain. These inequalities remained constant over time are were more marked in women. Detection of high-risk areas is crucial for the implementation of specific interventions. Copyright © 2017 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

A Pol V–Mediated Silencing, Independent of RNA–Directed DNA Methylation, Applies to 5S rDNA

PubMed Central

Douet, Julien; Tutois, Sylvie; Tourmente, Sylvette

2009-01-01

The plant-specific RNA polymerases Pol IV and Pol V are essential to RNA–directed DNA methylation (RdDM), which also requires activities from RDR2 (RNA–Dependent RNA Polymerase 2), DCL3 (Dicer-Like 3), AGO4 (Argonaute), and DRM2 (Domains Rearranged Methyltransferase 2). RdDM is dedicated to the methylation of target sequences which include transposable elements, regulatory regions of several protein-coding genes, and 5S rRNA–encoding DNA (rDNA) arrays. In this paper, we have studied the expression of the 5S-210 transcript, a marker of silencing release at 5S RNA genes, to show a differential impact of RNA polymerases IV and V on 5S rDNA arrays during early development of the plant. Using a combination of molecular and cytological assays, we show that Pol IV, RDR2, DRM2, and Pol V, actors of the RdDM, are required to maintain a transcriptional silencing of 5S RNA genes at chromosomes 4 and 5. Moreover, we have shown a derepression associated to chromatin decondensation specific to the 5S array from chromosome 4 and restricted to the Pol V–loss of function. In conclusion, our results highlight a new role for Pol V on 5S rDNA, which is RdDM–independent and comes specifically at chromosome 4, in addition to the RdDM pathway. PMID:19834541

Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy on Intact Dried Leaves of Sage (Salvia officinalis L.): Accelerated Chemotaxonomic Discrimination and Analysis of Essential Oil Composition.

PubMed

Gudi, Gennadi; Krähmer, Andrea; Krüger, Hans; Schulz, Hartwig

2015-10-07

Sage (Salvia officinalis L.) is cultivated worldwide for its aromatic leaves, which are used as herbal spice, and for phytopharmaceutical applications. Fast analytical strategies for essential oil analysis, performed directly on plant material, would reduce the delay between sampling and analytical results. This would enhance product quality by improving technical control of cultivation. The attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) method described here provides a reliable calibration model for quantification of essential oil components [EOCs; R(2) = 0.96; root-mean-square error of cross-validation (RMSECV) = 0.249 mL 100 g(-1) of dry matter (DM); and range = 1.115-5.280 mL 100 g(-1) of DM] and main constituents [e.g., α-thujone/β-thujone; R(2) = 0.97/0.86; RMSECV = 0.0581/0.0856 mL 100 g(-1) of DM; and range = 0.010-1.252/0.005-0.893 mL 100 g(-1) of DM] directly on dried intact leaves of sage. Except for drying, no further sample preparation is required for ATR-FTIR, and the measurement time of less than 5 min per sample contrasts with the most common alternative of hydrodistillation followed by gas chromatography analysis, which can take several hours per sample.

[Electronic versus paper-based patient records: a cost-benefit analysis].

PubMed

Neubauer, A S; Priglinger, S; Ehrt, O

2001-11-01

The aim of this study is to compare the costs and benefits of electronic, paperless patient records with the conventional paper-based charts. Costs and benefits of planned electronic patient records are calculated for a University eye hospital with 140 beds. Benefit is determined by direct costs saved by electronic records. In the example shown, the additional benefits of electronic patient records, as far as they can be quantified total 192,000 DM per year. The costs of the necessary investments are 234,000 DM per year when using a linear depreciation over 4 years. In total, there are additional annual costs for electronic patient records of 42,000 DM. Different scenarios were analyzed. By increasing the time of depreciation to 6 years, the cost deficit reduces to only approximately 9,000 DM. Increased wages reduce the deficit further while the deficit increases with a loss of functions of the electronic patient record. However, several benefits of electronic records regarding research, teaching, quality control and better data access cannot be easily quantified and would greatly increase the benefit to cost ratio. Only part of the advantages of electronic patient records can easily be quantified in terms of directly saved costs. The small cost deficit calculated in this example is overcompensated by several benefits, which can only be enumerated qualitatively due to problems in quantification.